Sample records for relevant factors involved

  1. Mycobacterium biofilms: factors involved in development, dispersal, and therapeutic strategies against biofilm-relevant pathogens.

    Xiang, Xiaohong; Deng, Wanyan; Liu, Minqiang; Xie, Jianping


    Many bacteria can develop biofilm (BF), a multicellular structure largely combining bacteria and their extracellular polymeric substances (EPS). The formation of biofilm results in an alternative existence in which microbes ensure their survival in adverse environments. Biofilm-relevant infections are more persistent, resistant to most antibiotics, and more recalcitrant to host immunity. Mycobacterium tuberculosis, the causative agent of tuberculosis, can develop biofilm, though whether M. tuberculosis can form biofilm within tuberculosis patients has yet to be determined. Here, we summarize the factors involved in the development and dispersal of mycobacterial biofilms, as well as underlying regulatory factors and inhibitors against biofilm to deepen our understanding of their development and to elucidate potential novel modes of action for future antibiotics. Key factors in biofilm formation identified as drug targets represent a novel and promising avenue for developing better antibiotics.

  2. Relevant Factors in the Process of Socialization, Involvement and Belonging of Descendants in Family Businesses

    Melquicedec Lozano-Posso


    Full Text Available This research works toward the identification of the factors that comprise the process of socialization, involvement and initial belonging of descendants in family businesses and the key relationships between them. By means of a qualitative detailed study of four cases, complemented by a quantitative survey of 274 Colombian family businesses, the authors generate a new model that takes into account both factors explored in previous research as well as others identified in this study. Findings confirm the specific dependency of each stage on the subsequent ones; socialization influences involvement, which in turn influences the belonging of the descendants to the family business, with a strong presence of factors such as knowledge, leadership, mode, timing, and motivation. Those responsible for the orientation of potential successors may examine these findings in order to optimize their preparation efforts and support of family human resources for the continuity of the business.

  3. Functional dyspepsia: Are psychosocial factors of relevance?

    Sandra Barry; Timothy G Dinan


    The pathogenesis of Functional Dyspepsia (FD) remains unclear, appears diverse and is thus inadequately understood. Akin to other functional gastrointestinal disorders, research has demonstrated an association between this common diagnosis and psychosocial factors and psychiatric morbidity. Conceptualising the relevance of these factors within the syndrome of FD requires application of the biopsychosocial model of disease.Using this paradigm, dysregulation of the reciprocal communication between the brain and the gut is central to symptom generation, interpretation and exacerbation.Appreciation and understanding of the neurobiological correlates of various psychological states is also relevant.The view that psychosocial factors exert their influence in FD predominantly through motivation of health care seeking also persists. This appears too one-dimensional an assertion in light of the evidence available supporting a more intrinsic aetiological link. Evolving understanding of pathogenic mechanisms and the heterogeneous nature of the syndrome will facilitate effective management.Co-morbid psychiatric illness warrants treatment with conventional therapies. Acknowledging the relevance of psychosocial variables in FD, the degree of which is subject to variation, has implications for assessment and management. Available evidence suggests psychological therapies may benefit FD patients particularly those with chronic symptoms. The rationale for use of psychotropic medications in FD is apparent but the evidence base to support the use of antidepressant pharmacotherapy is to date limited.

  4. Environmental Factors Impacting Bone-Relevant Chemokines

    Smith, Justin T.; Schneider, Andrew D.; Katchko, Karina M.; Yun, Chawon; Hsu, Erin L.


    Chemokines play an important role in normal bone physiology and the pathophysiology of many bone diseases. The recent increased focus on the individual roles of this class of proteins in the context of bone has shown that members of the two major chemokine subfamilies—CC and CXC—support or promote the formation of new bone and the remodeling of existing bone in response to a myriad of stimuli. These chemotactic molecules are crucial in orchestrating appropriate cellular homing, osteoblastogenesis, and osteoclastogenesis during normal bone repair. Bone healing is a complex cascade of carefully regulated processes, including inflammation, progenitor cell recruitment, differentiation, and remodeling. The extensive role of chemokines in these processes and the known links between environmental contaminants and chemokine expression/activity leaves ample opportunity for disruption of bone healing by environmental factors. However, despite increased clinical awareness, the potential impact of many of these environmental factors on bone-related chemokines is still ill defined. A great deal of focus has been placed on environmental exposure to various endocrine disruptors (bisphenol A, phthalate esters, etc.), volatile organic compounds, dioxins, and heavy metals, though mainly in other tissues. Awareness of the impact of other less well-studied bone toxicants, such as fluoride, mold and fungal toxins, asbestos, and chlorine, is also reviewed. In many cases, the literature on these toxins in osteogenic models is lacking. However, research focused on their effects in other tissues and cell lines provides clues for where future resources could be best utilized. This review aims to serve as a current and exhaustive resource detailing the known links between several classes of high-interest environmental pollutants and their interaction with the chemokines relevant to bone healing. PMID:28261155

  5. 28 CFR 51.57 - Relevant factors.


    ... THE VOTING RIGHTS ACT OF 1965, AS AMENDED Determinations by the Attorney General § 51.57 Relevant... afforded members of racial and language minority groups an opportunity to participate in the decision to... language minority groups into account in making the change....

  6. Mycobacterial factors relevant for transmission of tuberculosis

    Verhagen, L.M.; Hof, S. van den; Deutekom, H. van; Hermans, P.W.M.; Kremer, K.; Borgdorff, M.W.; Soolingen, D. van


    BACKGROUND: Tuberculosis (TB) transmission is associated with patient-related risk factors. However, DNA fingerprint analysis has provided anecdotal evidence suggesting a role for bacteriological factors. METHODS: To examine the importance of the bacteriological component in TB transmission, we inve

  7. Definitions of relevent efficiency and stress factors

    Wahlgren, U.


    A general efficiency function and related stress factors are defined from energy flow considerations. The efficiency function, or index, is related to maximum energy utilization, and stress is defined as total derivatives of the efficiency function. The efficiency function can be expressed, for an aquatic ecosystem, in terms of incident radiation, total production, total growth and the outflow at the highest trophical level. It is shown that the efficiency in principle can be measured for a lake from oxygen balance and hydrological conciderations. Changes in the efficiency are intimately connected with the activity at the primary level, which contributes most of the biomass and the production in the system. Perturbations on other levels effects the total system more indirectly, and this is the reason for using total rather than partial derivatives in the stress definitions. The behaviour of the efficiency function is demonstrated for a three-level Lotka-Volterra-type model with competition.(author).

  8. Factors Affecting the Value Relevance of Accounting Information

    Mahmoud Dehghan Nayeri; Ali Faal Ghayoumi; Mohammad Ali Bidari


    The present study examines the factors affecting the value relevance of accounting information for investors in the Tehran Stock Exchange over the period of six years. In this study, the effect of four factors; being profitable or loss generating, company size, earnings stability and company growth on the value relevance of accounting information have been studied. For this purpose Ohlson model and the cumulative regression analysis is used in order to examine the hypotheses and as the basis ...

  9. Lupus pleuritis: a relevant risk factor for pulmonary tuberculosis.

    Pasoto, S G; Borba, E F; Bonfa, E; Shinjo, S K


    The objective of the study was to evaluate risk factors for pulmonary tuberculosis in systemic lupus erythematosus (SLE). Clinical/laboratorial features of 1283 SLE patients (ACR criteria) followed at the Lupus Clinic were obtained from the electronic register database from 2001 to 2009. Pulmonary tuberculosis was diagnosed in 20 patients (1.6%) (TB+ group). As control group (TB-), 40 patients without tuberculosis matched for age, gender, ethnicity, age at SLE diagnosis, and disease duration were arbitrarily selected. All 20 patients of the TB+ group presented confirmed pulmonary tuberculosis from 1 to 23 years after SLE diagnosis (7.6 ± 8.1 years). Frequencies of previous SLE involvements (cutaneous, articular, hematological, renal, pericarditis, pneumonitis, and central nervous system) were alike in TB+ and TB- groups (p > 0.05). In contrast, prior pleuritis was more frequent in the TB+ group (40% vs. 5%, p = 0.001). In fact, pulmonary tuberculosis was diagnosed in 8/10 patients with previous pleuritis. Immunosuppressive and corticosteroid therapies at the moment of tuberculosis diagnosis were also similar in both groups (p > 0.05). We have identified pleuritis as a relevant risk factor for pulmonary tuberculosis, suggesting that previous pleural injury is a critical part of the complex interplay between altered immune system, socio-economic conditions, and increased susceptibility to this mycobacterial infection.


    Yu-Jia Hu


    Full Text Available Although literature review supported the concept that customer loyalty, brand equity and perceived risk are significant factors to affect customer involvement, very limited studies have extensively examined the relationship among those variables. This research applied quantitative study to comprehensively explore the relationship between customer loyalty, brand equity, perceived risk and customer involvement for consumers. The population for this research was identified as consumers having the shopping experience for digital camera. The findings supported the hypothesis that customer loyalty, brand equity and perceived risk have significant and positive relationship to customer involvement. The findings identified the predictors of customer loyalty, brand equity and perceived risk on the customer involvement and generated the recommendations for corporate operations and future scholar studies.

  11. Classifying transcription factor targets and discovering relevant biological features

    DeLisi Charles


    Full Text Available Abstract Background An important goal in post-genomic research is discovering the network of interactions between transcription factors (TFs and the genes they regulate. We have previously reported the development of a supervised-learning approach to TF target identification, and used it to predict targets of 104 transcription factors in yeast. We now include a new sequence conservation measure, expand our predictions to include 59 new TFs, introduce a web-server, and implement an improved ranking method to reveal the biological features contributing to regulation. The classifiers combine 8 genomic datasets covering a broad range of measurements including sequence conservation, sequence overrepresentation, gene expression, and DNA structural properties. Principal Findings (1 Application of the method yields an amplification of information about yeast regulators. The ratio of total targets to previously known targets is greater than 2 for 11 TFs, with several having larger gains: Ash1(4, Ino2(2.6, Yaf1(2.4, and Yap6(2.4. (2 Many predicted targets for TFs match well with the known biology of their regulators. As a case study we discuss the regulator Swi6, presenting evidence that it may be important in the DNA damage response, and that the previously uncharacterized gene YMR279C plays a role in DNA damage response and perhaps in cell-cycle progression. (3 A procedure based on recursive-feature-elimination is able to uncover from the large initial data sets those features that best distinguish targets for any TF, providing clues relevant to its biology. An analysis of Swi6 suggests a possible role in lipid metabolism, and more specifically in metabolism of ceramide, a bioactive lipid currently being investigated for anti-cancer properties. (4 An analysis of global network properties highlights the transcriptional network hubs; the factors which control the most genes and the genes which are bound by the largest set of regulators. Cell-cycle and

  12. Major congenital defects. Relevant risk factors. Cienfuegos. 2000-2005.

    Vivian Vázquez Martínez


    Full Text Available Background: Major congenital defects have an impact on perinatal mortality and morbidity with economic and social consequences. Objective: To determine the relevant risk factors linked to the occurrence of congenital defects in Cienfuegos between 2000 and 2005. Methods: A case-control study was carried out. Women with fetus or newborns with major congenital defects formed the case group (255 while the control group consisted of a similar number of healthy children selected each year by a randomized simple sample. The variables gathered by the Cuban Congenital Defects Records were studied. Chi-Square method was used with 95% of accuracy and a reliance rate of 95%; logistic regression was used with the Wald test. Results: There was a predominance of Central Nervous System defects (28, 6%. The most relevant risk factors were a history of congenital defects, smoking habits, and acute infection during the first three months, as well as belong to the third birth on. Conclusion: The most clinical relevant risks factors were the congenital defect history and the acute infection during the firs three months.

  13. [Relevance of Personality Factors for Successful Vocational Rehabilitation].

    Arling, V; Slavchova, V; Knispel, J; Spijkers, W


    The Main purpose of vocational rehabilitation is occupational reintegration of clients into the job market who have lost their job or whose job is threatened because of a handicap or chronicl illness. With regard to existing evidence for the relevance of personality factors for work performance and job achievement, the present study investigated the influence of participants' personality factors on a successful reintegration after a retraining program in a vocational training center over 2 years. A central research objective was to identify prognostic personality factors for successful vocational integration. In this longitudinal study 15 vocational training centers participated at 3 time points of measurement (T1, T2 and T3). Data gathering was based on rehabilitants' self-reports (standardized questionnaires: SVF, BSW, SPR, CSES) about personality aspects. First data collection started at the beginning (T1) and a second survey was conducted at the end of the training 2 years later (T2). Based on the data at measurement points T1 and T2, 4 prognostic models were computed (binary logistic regression analysis) and evaluated, examining the differenzial influence of several scales and items on direct reintegration after completing the vocational retraining and reintegration status 6 months later (T3). As expected, different variables turned out to be relevant for occupational integration at the end of the training program and 6 months later. Correspondingly other variables appeared to be relevant for occupational reintegration at T1 and at T2. At the end of the vocational training program, approximately 24% of the participants had a job. With respect to direct reintegration, regression analysis revealed that vocational self-efficacy (R(2)=0,175) and self-evaluation were relevant (R(2)=0,383). Approximately 70% of the participants had gotten a job 6 months later. Several stress coping strategies (R(2)=0,170), estimation of the own reintegration prognosis and aspects

  14. Analysis of the Relevant Factors of Retaining Women in Judo

    Joško Sindik


    Full Text Available This study aimed to determine the latent dimensions of all relevant factors about engagement of women in judo, to determine the intercorrelations among these latent dimensions, as well as the correlations with three relevant variables. Final goal was to determine the differences in revealed latent dimensions, in relation to several independent variables: educational level, marital status, impulses to engage in judo, then depending are the women athletes (competitors or not, members of the Board or not, trainers or not. A total of 50 female judokas from a larger number of Croatian clubs were examined, by specially composed the survey. The results showed that all seven questionnaires showed medium to high satisfactory reliability, together with good con¬struct validity, in 15 latent dimensions that are revealed. It can be noticed that relatively older women have more obligations and more barriers that oppose to their engagement in judo. Only small number of differences are found among women engaged in judo, mainly among participants who are members of the Board in the club or Croatian Judo Federation, as compared with those who are not. Small number of statistically significant differences (as well as the correlations can be also observed as the fact that all women partially share similar problems, while the media strategies are perceived as the most powerful to increase women’s persistence in judo, in any type of engagement.

  15. Relevant factors of stability of the financial sector

    Oleg Lunyakov


    Full Text Available The cause and effect of relevant factors in the development of the financial sector and the level of macroeconomic stability are researched. Key indicators of financial imbalances, the stability of the financial sector, with GDP per capita by application to 29 countries, including Ukraine, are analyzed. It is shown that the declining of per capita GDP in 2009, in the context of the financial crisis, to a large extent has been caused by accumulated imbalances in the financial sector. Moreover, indicators of financial stability for all countries signaled the impending crisis. The models that can use by the monetary authorities (central banks for the forecast impact of the financial sector imbalances on macroeconomic stability are developed

  16. [Analyses prognostic factors relevant to sudden sensorineural hearing loss].

    Wang, Jun; Xiao, Shuifang; Zeng, Zhengang; Zhen, Zhen; Zhang, Xuexi; Lin, Feng; Dong, Mingmin; Lu, Wei; Qin, Zhaobing; Zuo, Bin; Bai, Xianfeng


    To investigate the prognostic factors relevant to sudden sensorineural hearing loss. The internationally accepted standardized clinical research methods, unified design, and unified program were adopted to conduct the prospective clinical multi-center study. The sudden deafness patients between 18 to 65 years old, with the course of this disorder less than two weeks, and without any medical treatments were collected, and then, divided into four types according to the hearing curve: type A, acute sensorineural hearing loss in low tone frequencies; type B, acute sensorineural hearing loss in high tone frequencies; type C, acute sensorineural hearing loss in all frequencies; and type D, total deafness. The factors, in terms of age, gender, type of initial audiogram, time delay before the first visit, and severity of hearing loss, were included in the analyses. A total of 1 024 cases with single side sudden deafness were collected in the study from 33 hospitals in China from August 2007 to October 2011, inclusive of for 492 males (48.05%) and 532 females (51.95%). The average age was (41.2 ± 12.8) years old. There were 553 cases (54.00%) in left ear, and 471 cases (46.00%) in right ear. The curative effects of different types were shown as follows: the type in low tone frequencies had the highest rate of 90.73%, the type in all frequencies was 82.59%; the type of total deafness was 70.29%; and the type in high tone frequencies had the lowest rate of 65.96%. It had significant difference of the effective rate between different types (χ(2) = 231.58, P = 0.000). Age, time delay before first visit, and severity of initial hearing loss were significantly correlated with hearing improvement. Initial audiogram of SSNHL might predict hearing recovery. The young in age and a short time delay before starting treatment are positive prognostic factors for hearing recovery in SSNHL. The initial severity of hearing loss is negative prognostic factor of hearing recovery.

  17. 49 CFR 1150.32 - Procedures and relevant dates-transactions that involve creation of Class III carriers.


    ... 49 Transportation 8 2010-10-01 2010-10-01 false Procedures and relevant dates-transactions that involve creation of Class III carriers. 1150.32 Section 1150.32 Transportation Other Regulations Relating.... 10901 § 1150.32 Procedures and relevant dates—transactions that involve creation of Class III...

  18. Relevant Factors in The Post-Merger Systems Integration and Information Technology in Brazilian Banks

    Marcel Ginotti Pires


    Full Text Available This article discusses the factors present in post-merger integration of Systems and Information Technology (SIT that lead to positive and negative results in mergers and acquisitions (M & A. The research comprised three of the largest acquiring banks in Brazil. We adopted two methods of research, qualitative, to operationalize the theoretical concepts and quantitative, to test the hypotheses. We interviewed six executives of banks that held relevant experience in M & A processes. Subsequently, we applied questionnaires to IT professionals who were involved in the SIT integration processes. The results showed that the quality and expertise of the integration teams and managing the integration were the most relevant factors in the processes, with positive results for increased efficiency and the increased capacity of SIT. Negative results were due to failures in exploiting learning opportunities, the loss of employees and the inexpressive record of integration procedures.

  19. User and stakeholder involvement for relevant, reliable and robust local-scale climate projections in Norway

    Neby, Simon; Sobolowski, Stefan


    How can users and stakeholders be actively involved with providing input to and using output from local-scale climate projections? How can the scientific community better understand the needs of local actors? And how should communication and cooperation efforts be organized? These are critical questions we aim to answer in a climate services project funded by the Norwegian Research Council (R3: Relevant, Reliable and Robust local-scale climate projections for Norway). The project takes into consideration not only the scientific issues in establishing useful local-scale climate projections, but also addresses the "usability gap" between climate information and decision-making. The lack of effective communication between scientists and user communities often result in outputs and products that are not matched with decision-relevant climate information. In the R3 project, the scientific participants actively engage with a range of users that have quite different information needs: municipalities, infrastructure developers, agriculture, energy producers, insurance companies, and more. In this particular presentation, we present our experiences concerning three specific issues that relate to the stakeholder-science interface: 1) Preferences are not clear-cut and pre-defined. In practice, this means that stakeholders often do not have precise information about their needs, nor precise information about how, where and whether their needs can be voiced. Similarly, science communities tend to presuppose that stakeholders are interested and have well-articulated needs, which is hardly the case. Collectively, that means that there is a need for an approach that guides the articulation and prioritization of preferences in a manner that integrates both scientific and stakeholder perspectives and takes the integrity of both perspectives seriously. 2) Technologies are unclear. Although information may be produced and used, past experiences, trial and error processes and pragmatic

  20. Key factors relevant to In-service teacher training



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

  1. Relevant Networks involving the p53 Signalling Pathway in Renal Cell Carcinoma

    Villaamil, V. Medina; Gallego, G. Aparicio; Caínzos, I. Santamarina; Ruvira, L. Valbuena; Valladares-Ayerbes, M.; Aparicio, L. M. Antón


    Introduction: Renal cell carcinoma is the most common type of kidney cancer. A better understanding of the critical pathways and interactions associated with alterations in renal function and renal tumour properties is required. Our final goal is to combine the knowledge provided by a regulatory network with experimental observations provided by the dataset. Methods: In this study, a systems biology approach was used, integrating immunohistochemistry protein expression profiles and protein interaction information with the STRING and MeV bioinformatics tools. A group consisting of 80 patients with renal cell carcinoma was studied. The expression of selected markers was assessed using tissue microarray technology on immunohistochemically stained slides. The immunohistochemical data of the molecular factors studied were analysed using a parametric statistical test, Pearson’s correlation coefficient test. Results: Bioinformatics analysis of tumour samples resulted in 2 protein networks. The first network consists of proteins involved in the angiogenesis pathway and the apoptosis suppressor, BCL2, and includes both positive and negative correlations. The second network shows a negative interaction between the p53 tumour suppressor protein and the glucose transporter type 4. Conclusion: The comprehensive pathway network will help us to realise the cooperative behaviours among pathways. Regulation of metabolic pathways is an important role of p53. The pathway involving the tumour suppressor gene p53 could regulate tumour angiogenesis. Further investigation of the proteins that interact with this pathway in this type of tumour may provide new strategies for cancer therapies to specifically inhibit the molecules that play crucial roles in tumour progression. PMID:23675247

  2. Relevant Affect Factors of Smartphone Mobile Data Traffic

    Siniša Husnjak


    Full Text Available Smartphones are used to access a wide range of different information and communication services and perform functions based on data transfer. A number of subscription contracts for smartphones is rapidly increasing, and the development of mobile communications network provides higher speed of data transfer. The continuous increase in the average amount of data traffic per one subscriber contract leads to an increase in the total Mobile Data Traffic (MDT, globally. This research represents a summary of factors that affect the amount of smartphone MDT. Previous literature shows only a few of the factors individually that affect the realization of smartphone MDT. The results of the research clarify the ways which influence the amount of MDT generated by a smartphone. This paper increases the awareness of the users of the methods of generating smartphone MDT. The research also allows users to specify parameters that affect the prediction of generated MDT of a smartphone.

  3. Pathologically Relevant Prelamin A Interactions with Transcription Factors.

    Infante, Arantza; Rodríguez, Clara I


    LMNA-linked laminopathies are a group of rare human diseases caused by mutations in LMNA or by disrupted posttranslational processing of its largest encoded isoform, prelamin A. The accumulation of mutated or immature forms of farnesylated prelamin A, named progerin or prelamin A, respectively, dominantly disrupts nuclear lamina structure with toxic effects in cells. One hypothesis is that aberrant lamin filament networks disrupt or "trap" proteins such as transcription factors, thereby interfering with their normal activity. Since laminopathies mainly affect tissues of mesenchymal origin, we tested this hypothesis by generating an experimental model of laminopathy by inducing prelamin A accumulation in human mesenchymal stem cells (hMSCs). We provide detailed protocols for inducing and detecting prelamin A accumulation in hMSCs, and describe the bioinformatic analysis and in vitro assays of transcription factors potentially affected by prelamin A accumulation.

  4. Identification of Immune-Relevant Factors Conferring Sarcoidosis Genetic Risk

    Fischer, Annegret; Ellinghaus, David; Nutsua, Marcel; Hofmann, Sylvia; Montgomery, Courtney G.; Iannuzzi, Michael C.; Rybicki, Benjamin A.; Petrek, Martin; Mrazek, Frantisek; Pabst, Stefan; Grohé, Christian; Grunewald, Johan; Ronninger, Marcus; Eklund, Anders; Padyukov, Leonid; Mihailovic-Vucinic, Violeta; Jovanovic, Dragana; Sterclova, Martina; Homolka, Jiri; Nöthen, Markus M.; Herms, Stefan; Gieger, Christian; Strauch, Konstantin; Winkelmann, Juliane; Boehm, Bernhard O.; Brand, Stephan; Büning, Carsten; Schürmann, Manfred; Ellinghaus, Eva; Baurecht, Hansjörg; Lieb, Wolfgang; Nebel, Almut; Müller-Quernheim, Joachim; Franke, Andre


    Rationale: Genetic variation plays a significant role in the etiology of sarcoidosis. However, only a small fraction of its heritability has been explained so far. Objectives: To define further genetic risk loci for sarcoidosis, we used the Immunochip for a candidate gene association study of immune-associated loci. Methods: Altogether the study population comprised over 19,000 individuals. In a two-stage design, 1,726 German sarcoidosis cases and 5,482 control subjects were genotyped for 128,705 single-nucleotide polymorphisms using the Illumina Immunochip for the screening step. The remaining 3,955 cases, 7,514 control subjects, and 684 parents of affected offspring were used for validation and replication of 44 candidate and two established risk single-nucleotide polymorphisms. Measurements and Main Results: Four novel susceptibility loci were identified with genome-wide significance in the European case-control populations, located on chromosomes 12q24.12 (rs653178; ATXN2/SH2B3), 5q33.3 (rs4921492; IL12B), 4q24 (rs223498; MANBA/NFKB1), and 2q33.2 (rs6748088; FAM117B). We further defined three independent association signals in the HLA region with genome-wide significance, peaking in the BTNL2 promoter region (rs5007259), at HLA-B (rs4143332/HLA-B*0801) and at HLA-DPB1 (rs9277542), and found another novel independent signal near IL23R (rs12069782) on chromosome 1p31.3. Conclusions: Functional predictions and protein network analyses suggest a prominent role of the drug-targetable IL23/Th17 signaling pathway in the genetic etiology of sarcoidosis. Our findings reveal a substantial genetic overlap of sarcoidosis with diverse immune-mediated inflammatory disorders, which could be of relevance for the clinical application of modern therapeutics PMID:26051272

  5. 13 Factors Limiting Women's Involvement in Development: Lesson ...

    Nekky Umera

    the persistent and increasing burdens of poverty, malnutrition, poor health ... This paper investigates factors limiting an active involvement of rural women in .... and children, but decisions on economic and political issues are solely undertaken ...

  6. Relevant principal factors affecting the reproducibility of insect primary culture.

    Ogata, Norichika; Iwabuchi, Kikuo


    The primary culture of insect cells often suffers from problems with poor reproducibility in the quality of the final cell preparations. The cellular composition of the explants (cell number and cell types), surgical methods (surgical duration and surgical isolation), and physiological and genetic differences between donors may be critical factors affecting the reproducibility of culture. However, little is known about where biological variation (interindividual differences between donors) ends and technical variation (variance in replication of culture conditions) begins. In this study, we cultured larval fat bodies from the Japanese rhinoceros beetle, Allomyrina dichotoma, and evaluated, using linear mixed models, the effect of interindividual variation between donors on the reproducibility of the culture. We also performed transcriptome analysis of the hemocyte-like cells mainly seen in the cultures using RNA sequencing and ultrastructural analyses of hemocytes using a transmission electron microscope, revealing that the cultured cells have many characteristics of insect hemocytes.

  7. Relevance of Educational Factors in the Treatment of Pancreatic Cancer

    Dan Silviu VERZEA


    Full Text Available Introduction: radical pancreatic resections are the only chance to cure a pancreatic cancer, if the tumor is in an early stage of development. The results of the surgical teams have constantly improved in time, in terms of survival and a good quality of life. Unfortunately, only a small part of the patients benefit from surgical interventions. The causes of this phenomenon are complex, educational factors playing an important role. Material and Methods: 44 patients with pancreatoduodenectomy, operated between 2005 and 2008 were divided in 2 groups. Several parameters were recorded, including age, sex, level of education and place of origin, associated diabetes mellitus, these being studied in relation with the postoperative morbidity and mortality. Results: the morbidity after operation was 65,90%, and the mortality – 6,81%. The level of education, age, socioeconomic status, the presence of diabetes mellitus did not significantly influence the morbidity and the mortality after pancreatoduodenectomy. Conclusions: the postoperative morbidity and mortality are more incidental in small medical centers, but their values are acceptable, if compared with the data from the literature. Excluding the potential patients candidates for radical surgery because they are old or they have poor economic status is not a justified attitude. Education of the patients, medical stuff and surgeons is very important and it can raise the number of healed cases and could change the perception on pancreatic cancer.

  8. Complementary feeding: clinically relevant factors affecting timing and composition.

    Krebs, Nancy F; Hambidge, K Michael


    Exclusive breastfeeding for the first 6 mo of life followed by optimal complementary feeding are critical public health measures for reducing and preventing morbidity and mortality in young children. Clinical factors, such as birth weight, prematurity, and illness, that affect the iron and zinc requirements of younger infants are discussed. Maternal diet and nutritional status do not have a strong effect on the mineral content of human milk, but physiologic changes in milk and the infants' status determine the dependence of the infant on complementary foods in addition to human milk to meet iron and zinc requirements after 6 mo. The nature of zinc absorption, which is suitably characterized by saturation response modeling, dictates that plant-based diets, which are low in zinc, are associated with low absolute daily absorbed zinc, which is inadequate to meet requirements. Foods with a higher zinc content, such as meats, are much more likely to be sufficient to meet dietary requirements. Current plant-based complementary feeding patterns for older fully breastfed infants in both developed and developing countries pose a risk of zinc deficiency. The strong rationale for the potential benefits of providing meat as an early complementary food, and the examples of successful intervention programs, provide potent incentives to pursue broader implementation programs, with concurrent rigorous evaluation of both efficacy and effectiveness.

  9. Identifying the Relevant Factors in Newspaper Advertising Effectiveness

    Cristóbal Benavides


    Full Text Available Este estudio explora varios factores con el fin de establecer cuáles son losmás importantes en motivar a los lectores de periódicos locales a comprar,visitar tiendas y buscar información adicional acerca de los productos oservicios promovidos en los anuncios. El comportamiento durante el pro-ceso de compra es consecuencia de una compleja interacción de dimen-siones culturales, sociales, personales y psicológicas. Este proceso –el cualse produce antes de la acción– tiene implicaciones relevantes y los depar-tamentos de mercadeo deben prestar atención a ello. Una serie de hipóte-sis basadas en la forma como la publicidad atrae a los consumidores y encómo afecta la toma de decisiones al momento de la compra fueron puestasa prueba usando una encuesta que fue administrada a una muestra de 1.333personas encuestadas en Chile. También se realizó un análisis discriminan-te para averiguar por qué algunos lectores de periódicos se ven motivadosa comprar bienes o servicios, visitar una tienda o buscar más información.Los resultados muestran que el atractivo de la oferta anunciada es el factormás importante para explicar el comportamiento posterior del consumidor.

  10. Polymicrobial infections involving clinically relevant Gram-negative bacteria and fungi.

    Dhamgaye, Sanjiveeni; Qu, Yue; Peleg, Anton Y


    Interactions between fungi and bacteria and their relevance to human health and disease have recently attracted increased attention in biomedical fields. Emerging evidence shows that bacteria and fungi can have synergistic or antagonistic interactions, each with important implications for human colonization and disease. It is now appreciated that some of these interactions may be strategic and helps promote the survival of one or both microorganisms within the host. This review will shed light on clinically relevant interactions between fungi and Gram-negative bacteria. Mechanism of interaction, host immune responses, and preventive measures will also be reviewed. © 2016 John Wiley & Sons Ltd.

  11. Predictors of healthcare professionals' attitudes towards family involvement in safety-relevant behaviours: a cross-sectional factorial survey study.

    Davis, Rachel; Savvopoulou, M; Shergill, R; Shergill, S; Schwappach, David


    OBJECTIVES To investigate predictors of healthcare professionals' (HCPs) attitudes towards family involvement in safety-relevant behaviours. DESIGN A cross-sectional fractional factorial survey that assessed HCPs' attitudes towards family involvement in two error scenarios relating to hand hygiene and medication safety. Each survey comprised two randomised vignettes that described the potential error, how the family member communicated with the HCP about the error and how the HCP ...

  12. Relevant Factors of Estrogen Changes of Myopia in Adolescent Females

    Juan-Fen Gong; Hong-Li Xie; Xin-Jie Mao; Xue-Bo Zhu; Zuo-Kai Xie; Hai-Hong Yang; Yang Gao


    Background:Gender is one of the risk factors accounting for the high prevalence of adolescent myopia.Considerable research results have shown that myopia incidence of female is higher than that of male.This study aimed to analyze the correlation between ocular parameters and serum estrogen level and to investigate the vision changes along with estrogen change in menstrual cycle of adolescent females.Methods:A total of 120 young females aged between 15 and 16 years,diagnosed with myopia were recruited.Spherical lens,cylindrical lens,axis,interpupillary distance (IPD),and vision in each tested eye of the same subject were measured by automatic optometry and comprehensive optometry,with repetition of all measurements in the menstrual cycle of the 2nd or 3rd days,14th days,and 282 days,respectively.Serum estradiol (E2) levels were assayed by chemiluminescence immunoassay at the same three times points of the menstrual cycle mentioned above.Results:In young females with myopia,the spherical lens showed a statistically significant difference among all different time in menstrual cycle (all P < 0.0001).The cylindrical lens,axis,and IPD were changed significantly during the menstrual cycle (P < 0.05).The vision of the three different time points in menstrual cycle had a significant difference (x2 =6.35,P =0.042).The vision during the 14th and 28th day was higher compared to that on the 2nd or 3rd days (P =0.021).Serum E2 levels were significantly different at different time points in menstrual cycle (P < 0.05).E2 levels reached its maximum value on the 142 day and the minimum value on the 2nd or 3rd day.Conclusions:In adolescent females,the spherical lens and other related ocular parameters vary sensitively with different levels of E2 in menstrual cycle.Vision in late menstrual stage is significantly higher than that in premenstrual stage.

  13. The Relevance of Parents' Beliefs for Their Involvement in Children's School Life

    Bubic, Andreja; Tošic, Antonela


    Parents play a very important role in all aspects of children's experiences, and parental involvement in children's school lives is associated with numerous educational outcomes. Therefore, the present study investigated the role of several parents' demographic characteristics, parental self-efficacy, as well as beliefs regarding the value of…

  14. Lymphvascular space involvement : an independent prognostic factor in endometrial cancer

    Briet, JM; Hollema, H; Reesink, N; Aalders, Jan; Mourits, MJE; ten Hoor, KA; Pras, Elisabeth; Boezen, HM; van der Zee, AGJ; Nijman, HW


    Purpose of investigation. To evaluate whether lymphvascular space involvement (LVSI) is a risk factor for relapse of disease and lymph node metastasis in endometrial cancer. Methods. From 1978 till 2003, 609 patients with epithelial endometrial cancer were treated at the Groningen University Medical

  15. Factors Affecting Teen Involvement in Pennsylvania 4-H Programming

    Gill, Bart E.; Ewing, John C.; Bruce, Jacklyn A.


    The study reported here determined the factors that affect teen involvement in 4-H programming. The design of the study was descriptive and correlational in nature. Using a purposive sampling procedure, a survey questionnaire was distributed to all (N=214) 4-H members attending the 4-H State Leadership Conference. The major findings of the study…

  16. Participatory Evaluation: Factors to Consider when Involving Youth

    Fox, Janet; Cater, Melissa


    This article provides a critical perspective on the increasing involvement of young people in participatory evaluation as well as identifies the factors to consider when designing a youth-led evaluation project. Through this avenue, young people will increase their participation in organizational development and community change. Youth-led…

  17. Analysis of factors associated with injury severity in crashes involving young New Zealand drivers

    Weiss, Harold B.; Kaplan, Sigal; Prato, Carlo Giacomo


    Young people are a risk to themselves and other road users, as motor vehicle crashes are the leading cause of their death. A thorough understanding of the most important factors associated with injury severity in crashes involving young drivers is important for designing well-targeted restrictive...... measures within youth-oriented road safety programs. The current study estimates discrete choice models of injury severity of crashes involving young drivers conditional on these crashes having occurred. The analysis examined a comprehensive set of single-vehicle and two-vehicle crashes involving at least...... fit than a binary and a generalized ordered logit. Results show that the young drivers’ behavior, the presence of passengers and the involvement of vulnerable road users were the most relevant factors associated with higher injury severity in both single-vehicle and two-vehicle crashes. Seatbelt non...

  18. Photophysics and electrochemistry relevant to photocatalytic water splitting involved at solid–electrolyte interfaces

    Shinagawa, Tatsuya


    Direct photon to chemical energy conversion using semiconductor-electrocatalyst-electrolyte interfaces has been extensively investigated for more than a half century. Many studies have focused on screening materials for efficient photocatalysis. Photocatalytic efficiency has been improved during this period but is not sufficient for industrial commercialization. Detailed elucidation on the photocatalytic water splitting process leads to consecutive six reaction steps with the fundamental parameters involved: The photocatalysis is initiated involving photophysics derived from various semiconductor properties (1: photon absorption, 2: exciton separation). The generated charge carriers need to be transferred to surfaces effectively utilizing the interfaces (3: carrier diffusion, 4: carrier transport). Consequently, electrocatalysis finishes the process by producing products on the surface (5: catalytic efficiency, 6: mass transfer of reactants and products). Successful photocatalytic water splitting requires the enhancement of efficiency at each stage. Most critically, a fundamental understanding of the interfacial phenomena is highly desired for establishing "photocatalysis by design" concepts, where the kinetic bottleneck within a process is identified by further improving the specific properties of photocatalytic materials as opposed to blind material screening. Theoretical modeling using the identified quantitative parameters can effectively predict the theoretically attainable photon-conversion yields. This article provides an overview of the state-of-the-art theoretical understanding of interfacial problems mainly developed in our laboratory. Photocatalytic water splitting (especially hydrogen evolution on metal surfaces) was selected as a topic, and the photophysical and electrochemical processes that occur at semiconductor-metal, semiconductor-electrolyte and metal-electrolyte interfaces are discussed.

  19. Grandmother Involvement as a Protective Factor for Early Childhood Social Adjustment

    Barnett, Melissa A.; Scaramella, Laura V.; Neppl, Tricia K.; Ontai, Lenna L.; Conger, Rand D.


    Despite high rates of grandmother involvement with young grandchildren, very little research has examined the associations between non-residential grandmother involvement and grandchild social adjustment. The present study draws 127 families enrolled in the Family Transitions Project to consider the degree to which mother-reported maternal grandmother involvement buffers 3- and 4-year old grandchildren from economic, parenting, and child temperamental risks for reduced social competence and elevated externalizing behaviors. Findings indicate that higher levels of mother-reported grandmother involvement reduced the negative association between observed grandchild negative emotional reactivity and social competence. Further, high levels of mother-reported grandmother involvement protected grandchildren from the positive association between observed harsh mother parenting and grandchild externalizing behaviors. These findings underscore the relevance of moving beyond the nuclear family to understand factors linked to social adjustment during early childhood. PMID:20954774

  20. Factors Relevant to Recruitment/Retention of Minorities in Science Professions.

    Rowe, Mary Budd

    This paper discusses some of the factors that may be relevant to recruitment/retention of minorities into professions. It is based on two assumptions: (1) the job potential in science professions is especially good for minorities; and (2) parity with respect to minorities in science professions is an acceptable goal. Certain factors influencing…

  1. A review of the electrophilic reaction chemistry involved in covalent protein binding relevant to toxicity.

    Enoch, S J; Ellison, C M; Schultz, T W; Cronin, M T D


    Several pieces of legislation have led to an increased interest in the use of in silico methods, specifically the formation of chemical categories for the assessment of toxicological endpoints. For a number of endpoints, this requires a detailed knowledge of the electrophilic reaction chemistry that governs the ability of an exogenous chemical to form a covalent adduct. Historically, this chemistry has been defined as compilations of structural alerts without documenting the associated electrophilic chemistry mechanisms. To address this, this article has reviewed the literature defining the structural alerts associated with covalent protein binding and detailed the associated electrophilic reaction chemistry. This information is useful to both toxicologists and regulators when using the chemical category approach to fill data gaps for endpoints involving covalent protein binding. The structural alerts and associated electrophilic reaction chemistry outlined in this review have been incorporated into the OECD (Q)SAR Toolbox, a freely available software tool designed to fill data gaps in a regulatory environment without the need for further animal testing.


    Masyantie Mohamad


    Full Text Available Sarawak multilayered cake among Sarawak product signature famous among the local as well as international tourist visiting Sarawak. In fact, Sarawak Malay women entrepreneurs have become very necessary players in the entrepreneurial field specifically in this cottage industries from the early introduction of this business, they have facing various problem in this businesses. Thus, this research aims to build an understanding of motivational factor that encourage Sarawak Malay women entrepreneurial experiences especially in multilayered cake businesses. Using qualitative methods, this research aims to identify the entrepreneurial motivations factors; with regards to start-up motivation by Sarawak Malay women. The finding shows that the motivations that influence Malay women within Kuching, Sarawak areas to start and grow their business are involve self-driven and context driven that motivate them involve in multilayered cakes businesses.

  3. NAC Transcription Factors of Barley (Hordeum vulgare L.) and their Involvement in Leaf Senescence

    Wagner, Michael

    yielding cereal crops are generated. In cereals, the process of leaf senescence is of utmost relevance when discussing yield. It is during the senescence process that all nutrients are transported from the withering leaf to the developing grains. Furthermore, the timing of senescence determines...... parts of the senescence process. The specific aims of this study were therefore (1) to establish and characterise the NAC transcription factors of the model cereal crop barley (Hordeum vulgare L.) (2) to identify and study putative barley NAC transcription factors involved in the regulation of leaf...

  4. Overview of Macrophage Migration Inhibitory Factor (MIF as a Potential Biomarker Relevant to Adiposity

    Jun Nishihira


    Full Text Available The cytokine “macrophage migration inhibitory factor (MIF” is generally recognized as a proinflammatory cytokine, and MIF is involved in broad range of acute and chronic inflammatory states. With regard to glucose metabolism and insulin secretion, MIF is produced by pancreatic β cells and acts as a positive regulator of insulin secretion. In contrast, it is evident that MIF expressed in adipose tissues causes insulin resistance. Concerning MIF gene analysis, we found four alleles: 5-, 6-, 7-and 8-CATT at position −794 of MIF gene in a Japanese population. Genotypes without the 5-CATT allele were more common in the obese subjects than in the lean or overweight groups. It is conceivable that promoter polymorphism in the MIF gene is profoundly linked with obesity relevant to lifestyle diseases, such as diabetes. Obesity has become a serious social issue due to the inappropriate nutritional balance, and the consumption of functional foods (including functional foods to reduce fat mass is expected to overcome this issue. In this context, MIF would be a reliable quantitative biomarker to evaluate the effects of functional foods on adiposity.

  5. Evidence for the involvement of ZNF804A in cognitive processes of relevance to reading and spelling.

    Becker, J; Czamara, D; Hoffmann, P; Landerl, K; Blomert, L; Brandeis, D; Vaessen, A; Maurer, U; Moll, K; Ludwig, K U; Müller-Myhsok, B; Nöthen, M M; Schulte-Körne, G; Schumacher, J


    Previous studies have shown that individuals with schizophrenia and dyslexia display common neurocognitive abnormalities. The aim of the present study was to determine whether known schizophrenia-risk genes contribute to dyslexia risk or to disease-relevant cognitive functions. For this purpose, we genotyped the schizophrenia-associated risk variants within zinc-finger protein 804A (ZNF804A), transcription-factor 4 and neurogranin in a large dyslexia case-control sample. We tested all variants for association with dyslexia (927 cases, 1096 controls), and with eight language-relevant cognitive processes (1552 individuals). We observed six significant associations between language-relevant traits and the ZNF804A-variant rs1344706. Interestingly, the ZNF804A schizophrenia risk variant was associated with a better cognitive performance in our data set. This finding might be consistent with a previously reported ZNF804A association in schizophrenia, in which patients carrying the schizophrenia-risk allele at rs1344706 showed a better performance in two memory tests. In conclusion, the present study provides evidence that ZNF804A might have a role in cognitive traits of relevance to reading and spelling, and underlines the phenotypic complexity that might be associated with ZNF804A.

  6. Mechanisms, Cofactors, and Augmenting Factors Involved in Anaphylaxis

    Rosa Muñoz-Cano


    Full Text Available Anaphylaxis is an acute and life-threatening systemic reaction. Many triggers have been described, including food, drug, and hymenoptera allergens, which are the most frequently involved. The mechanisms described in anaphylactic reactions are complex and implicate a diversity of pathways. Some of these mechanisms may be key to the development of the anaphylactic reaction, while others may only modify its severity. Although specific IgE, mast cells, and basophils are considered the principal players in anaphylaxis, alternative mechanisms have been proposed in non-IgE anaphylactic reactions. Neutrophils, macrophages, as well as basophils, have been involved, as have IgG-dependent, complement and contact system activation. A range of cationic substances can induce antibody-independent mast cells activation through MRGPRX2 receptor. Cofactors and augmenting factors may explain why, in some patients, food allergen exposure can cause anaphylaxis, while in other clinical scenario it can be tolerated or elicits a mild reaction. With the influence of these factors, food allergic reactions may be induced at lower doses of allergen and/or become more severe. Exercise, alcohol, estrogens, and some drugs such as Non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, β-blockers, and lipid-lowering drugs are the main factors described, though their mechanisms and signaling pathways are poorly understood.

  7. Factors Associated with Involvement in Bullying: A Study in Nicaragua

    Eva M. Romera


    Full Text Available School bullying is one of the main problems affecting the quality of peer relationships in schools and in general the coexistence. At European level, there are scientific findings that indicate its nature, characteristics and factors related to its involvement. However, in poor and developing countries, where the problem is more serious, there is a high degree of awareness on this matter. The present study aimed to identify what factors may be influencing the occurrence of bullying in a representative sample of primary schools in the Nicaraguan capital. For this propose, 3042 students from Managua and its metropolitan area were explored with instruments comparable to those used in Europe. A multinomial logistic regression analysis indicated that being a boy, to show antisocial behaviors and attitudes and contact with drugs were the three factors most related with the role of aggressor, as well as negative relationships had a significant influence on involvement in this phenomenon, either as a victim, aggressor or victimized aggressor. Results are discussed in relation to the profiles of aggressor and victim of bullying in international studies focusing on differences in developed countries.

  8. Factors involved in mechanical fatigue degradation of dental resin composites.

    Lohbauer, U; Belli, R; Ferracane, J L


    The design of clinical trials allows for limited insights into the fatigue processes occurring in resin composites and the factors involved therein. In vitro studies, in contrast, can fundamentally narrow study interests to focus on particular degradation mechanisms and, to date, represent the major contributors to the state of knowledge on the subject. These studies show that microstructural features are important in determining strength and fracture toughness, whereas fatigue resistance is mainly related to the susceptibility of the matrix and the filler/matrix interface to mechanical and chemical degradation. In this review, we focus on fracture mechanisms occurring during fatigue, on the methods used to assess them, and on additional phenomena involved in the degradation of initial mechanical properties of resin composites.

  9. Growth factor involvement in tension-induced skeletal muscle growth

    Vandenburgh, Herman H.


    Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

  10. The incidence of aspirin resistance and relevant influencing factors in patients on maintenance hemodialysis



    Objective To explore aspirin resistance(AR)and its relevant influencing factors in patients on maintenance hemodialysis(MHD).Methods Patients on MHD who visited Beijing Chaoyang Hospital from June 1 to 30,2011 were enrolled in this study.A total of 150 age and gender matched individuals with normal renal function were taken as control group.Anthropometric data,bio-

  11. A review of potential factors relevant to coping in patients with advanced cancer

    Thomsen, Thora Grothe; Hansen, Susan Rydahl; Wagner, Lis


    The aim was to identify characteristics that are considered to describe coping in patients with advanced cancer, as seen from a patient perspective. Based on the identified characteristics, the second aim was to identify potential factors that are relevant to coping in patients with advanced cancer....

  12. Factors associated with male involvement in reproductive care in Bangladesh.

    Bishwajit, Ghose; Tang, Shangfeng; Yaya, Sanni; Ide, Seydou; Fu, Hang; Wang, Manli; He, Zhifei; Da, Feng; Feng, Zhanchun


    Men's active involvement in reproductive healthcare has shown to be positively associated with maternal and child health outcomes. Bangladesh has made appreciable progress in its pursuance of maternal mortality related goals in the framework of the MDGs. However, there remains a lot to be accomplished to realise the long-term goals for which active participation of male counterparts in reproductive care is crucial. Therefore, the objective of the present study was to investigate factors associated with male involvement in reproductive health among Bangladeshi men. We used data from Bangladesh Demographic and Health Survey (BDHS) conducted in 2011. Study participants were 1196 married men, aged between 15 and 69 years and living in both urban and rural households. Level of male involvement (outcome variable) was measured based on the responses on knowledge, awareness and practice regarding reproductive health. Chi-square tests and multivariable logistic regression models were performed for data analysis. Out of 1196 participants, only 40% were found to be active about partners' reproductive healthcare. Chi-square test showed significant association between active involvement and ever hearing about family planning (FP) in television, learning about FP through community health events, community health workers and poster/billboard. Results from logistic regression analysis revealed that type of residency [p = 0.004, AOR = 0.666, 95% CI = 0.504-0.879], literacy [secondary/higher education- p = 0.006. AOR = 0.579, 95% CI = 0.165-0.509], learning about family planning from Newspaper [p < 0.001. AOR = 1.952, 95% CI = 1.429-2.664], and television [p = 0.017. AOR = 1.514 95% CI = 1.298-1.886], and having been communicated about family planning by community health workers [p = 0.017. AOR = 1.946, 95% CI = 1.129-3.356] were significantly associated with active involvement of men in reproductive health issues. Level

  13. Hypersensitivity reactions to fluoroquinolones: analysis of the factors involved.

    Blanca-López, N; Ariza, A; Doña, I; Mayorga, C; Montañez, M I; Garcia-Campos, J; Gomez, F; Rondón, C; Blanca, M; Torres, M J


    Hypersensitivity reactions to fluoroquinolones seem to be on the increase, especially immediate type reactions. The aim of this study was to determine whether several conditions, including gender, age, type of reaction, time interval between the reaction and the study, type of symptoms, the specific fluoroquinolone involved in the reaction and previous confirmed hypersensitivity to betalactams or to other drugs were factors contributing to the development of hypersensitivity to fluoroquinolones. We analysed retrospectively all patients attending our allergy department between January 2005 and December 2010 because of a reaction associated with fluoroquinolone administration. The diagnosis was confirmed by basophil activation test or drug provocation tests. In accordance with the results, patients were then classified as having hypersensitivity or non-hypersensitivity to fluoroquinolones. A group of 218 patients was evaluated; 69 were confirmed as having hypersensitivity, 146 as non-hypersensitivity and 3 were excluded. Comparisons between groups showed that the allergic patients more often had a previous confirmed hypersensitivity to betalactams (P = 0.029), immediate reactions (P = 0.001) and anaphylaxis (P = 0.000), and moxifloxacin was the fluoroquinolone most frequently involved (P = 0.027). The logistic regression analysis showed three factors associated with the diagnosis of hypersensitivity reactions to fluoroquinolones: previous hypersensitivity to betalactams (OR: 4.571; 95% CI: 0.987-21.171; adjusted OR: 23.654; 95% CI: 1.529-365.853), immediate reactions (OR: 17.333; 95% CI: 4.374-68.691; adjusted OR: 52.493; 95% CI: 6.621-416.200) and reactions induced by moxifloxacin (OR: 3.091; 95% CI: 1.160-8.239; adjusted OR: 13.610; 95% CI: 2.419-76.565). In patients who develop reactions to fluoroquinolones, hypersensitivity is more often confirmed in those with immediate reactions and when moxifloxacin is involved. Moreover, patients with hypersensitivity to

  14. Delayed onset muscle soreness: Involvement of neurotrophic factors.

    Mizumura, Kazue; Taguchi, Toru


    Delayed-onset muscle soreness (DOMS) is quite a common consequence of unaccustomed strenuous exercise, especially exercise containing eccentric contraction (lengthening contraction, LC). Its typical sign is mechanical hyperalgesia (tenderness and movement related pain). Its cause has been commonly believed to be micro-damage of the muscle and subsequent inflammation. Here we present a brief historical overview of the damage-inflammation theory followed by a discussion of our new findings. Different from previous observations, we have observed mechanical hyperalgesia in rats 1-3 days after LC without any apparent microscopic damage of the muscle or signs of inflammation. With our model we have found that two pathways are involved in inducing mechanical hyperalgesia after LC: activation of the B2 bradykinin receptor-nerve growth factor (NGF) pathway and activation of the COX-2-glial cell line-derived neurotrophic factor (GDNF) pathway. These neurotrophic factors were produced by muscle fibers and/or satellite cells. This means that muscle fiber damage is not essential, although it is sufficient, for induction of DOMS, instead, NGF and GDNF produced by muscle fibers/satellite cells play crucial roles in DOMS.

  15. Involvement of Oct-1 in the regulation of CDKN1A in response to clinically relevant doses of ionizing radiation.

    Nenoi, Mitsuru; Daino, Kazuhiro; Nakajima, Tetsuo; Wang, Bing; Taki, Keiko; Kakimoto, Ayana


    CDKN1A is a cyclin-dependent kinase inhibitor that plays a critical role in cell cycle checkpoint regulation. It is transcriptionally induced by TP53 (p53) following exposure to ionizing radiation (IR). Induction of CDKN1A after irradiation is closely related to IR-sensitivity of tumor cells, but the underlying mechanisms remain obscure because conventional reporter gene systems respond poorly to IR unless hyperlethal doses are used. Here, we performed a promoter analysis of the CDKN1A gene following irradiation with clinically relevant doses of IR using the adeno-associated virus-mediated reporter system which we have recently shown to be highly responsive to IR. We demonstrate that there are regulatory elements at -1.1 kb, -1.4 kb, and -1.8 kb, and deletion of these elements attenuate induction of the CDKN1A gene promoter in response to 0.2-2.0 Gy of IR. EMSA and ChIP assays showed that Oct-1 binds constitutively to the elements at -1.1 kb and -1.8 kb. Functional involvement of Oct-1 was confirmed by RNA interference targeting the Oct-1 gene, which suppressed both the basal and IR-inducible components of the CDKN1A expression. Thus, our results reveal that Oct-1 is crucial to the TP53-mediated regulation of the CDKN1A gene promoter following exposure to clinically relevant doses of IR.

  16. Involvement of Oct-1 in the regulation of CDKN1A in response to clinically relevant doses of ionizing radiation

    Nenoi, M.; Nakajima, T.; Wang, B.; Taki, K.; Kakimoto, A. [Radiation Effect Mechanisms Research Group, National Institute of Radiological Sciences, 9-1, Anagawa-4-chome, Inage-ku, Chiba 263-8555 (Japan); Daino, K. [Laboratoire de Cancerologie Experimentale, Departement de Radiobiologie et Radiopathologie, Commissariat a l' Energie Atomique, 92265 Fontenay-aux-Roses Cedex (France)


    CDKN1A is a cyclin-dependent kinase inhibitor that plays a critical role in cell cycle checkpoint regulation. It is transcriptionally induced by TP53 (p53) following exposure to ionizing radiation (IR). Induction of CDKN1A after irradiation is closely related to IR-sensitivity of tumor cells, but the underlying mechanisms remain obscure because conventional reporter gene systems respond poorly to IR unless hyper-lethal doses are used. Here, we performed a promoter analysis of the CDKN1A gene following irradiation with clinically relevant doses of IR using the adeno-associated virus-mediated reporter system which we have recently shown to be highly responsive to IR. We demonstrate that there are regulatory elements at -1.1 kb, -1.4 kb, and -1.8 kb, and deletion of these elements attenuate induction of the CDKN1A gene promoter in response to 0.2-2.0 Gy of IR. EMSA and ChIP assays showed that Oct-1 binds constitutively to the elements at -1.1 kb and -1.8 kb. Functional involvement of Oct-1 was confirmed by RNA interference targeting the Oct-1 gene, which suppressed both the basal and IR-inducible components of the CDKN1A expression. Thus, our results reveal that Oct-1 is crucial to the TP53-mediated regulation of the CDKN1A gene promoter following exposure to clinically relevant doses of IR. (authors)

  17. Predictors of healthcare professionals’ attitudes towards family involvement in safety-relevant behaviours: a cross-sectional factorial survey study

    Davis, Rachel; Savvopoulou, M; Shergill, R; Shergill, S; Schwappach, D


    Objectives To investigate predictors of healthcare professionals’ (HCPs) attitudes towards family involvement in safety-relevant behaviours. Design A cross-sectional fractional factorial survey that assessed HCPs’ attitudes towards family involvement in two error scenarios relating to hand hygiene and medication safety. Each survey comprised two randomised vignettes that described the potential error, how the family member communicated with the HCP about the error and how the HCP responded to the family member’s question. Setting 5 teaching hospitals in London, the Midlands and York. HCPs were approached on a range of medical and surgical wards. Participants 160 HCPs (73 doctors; 87 nurses) aged between 21 and 65 years (mean 37) 102 were female. Outcome measures HCP approval of family member’s behaviour; HCP reaction to the family member; anticipated effects on the family member–HCP relationship; HCP support for being questioned about hand hygiene/medication; affective rating responses. Results HCPs supported family member's intervening (88%) but only 41% agreed this would have positive effects on the family member/HCP relationship. Across vignettes and error scenarios the strongest predictors of attitudes were how the HCP (in the scenario) responded to the family member and whether an error actually occurred. Doctors (vs nurses) provided systematically more positive affective ratings to the vignettes. Conclusions Important predictors of HCPs’ attitudes towards family members’ involvement in patient safety have been highlighted. In particular, a discouraging response from HCP’s decreased support for family members being involved and had strong perceived negative effects on the family member/HCP relationship. PMID:25186154

  18. Some relevant risk factors and causal mechanisms to understand crime in Romania

    Alassane Diaw; Oana-Ramona Lobont; Nicoleta Claudia Moldovan


    The objective of this paper is to provide some empirical evidence of relevant risk factors and causal mechanisms to understand criminal behavior in Romania. In order to achieve this goal, some socio-economic variables are considered: long-term unemployment rate and people at risk of poverty or social exclusion and, as crime variables we use four different types of crimes: domestic burglary, homicide, motor vehicle theft and robbery. At the regional level, the results of our panel data analysi...

  19. Clinical Relevant Fatigue in Women with Breast Cancer: Prevalence and Associated Factors

    Lamino, Daniela de Araujo; Sra Cibele, Cibele Andruciolli de Mattos Pimenta; Sra Patricia, Patricia Emilia Braga; Sra Dalete, Dalete Delalibera Corrêa de Faria Mota


    Introduction: Fatigue is a common symptom in patients with cancer. Objective: Toexamine the prevalence and independent predictors of fatigue in women with breastcancer. Material and Method: A cross-sectional study with a nonrandom sample of163 patients in outpatient follow-up. Fatigue was assessed by the Piper Fatigue Scale.Results: Clinical relevant fatigue (score ≥ 4) was present in 31.9% of the sample andthe average intensity was 6 (SD = 1.3).Pain and depression were factors independentlya...

  20. Effectiveness and relevant factors of 2% rebamipide ophthalmic suspension treatment in dry eye.

    Ueda, Kaori; Matsumiya, Wataru; Otsuka, Keiko; Maeda, Yoshifumi; Nagai, Takayuki; Nakamura, Makoto


    Rebamipide with mucin secretagogue activity was recently approved for the treatment of dry eye. The efficacy and safety in the treatment of rebamipide were shown in two pivotal clinical trials. It was the aim of this study to evaluate the effect of 2% rebamipide ophthalmic suspension in patients with dry eye and analyze relevant factors for favorable effects of rebamipide in clinical practice. This was a retrospective cohort study of 48 eyes from 24 patients with dry eye treated with 2% rebamipide ophthalmic suspension. Dry eye-related symptom score, tear film break-up time (TBUT), fluorescein ocular surface staining score (FOS) and the Schirmer test were used to collect the data from patients at baseline, and at 2, 4, 8, and 12 week visits. To determine the relevant factors, multiple regression analyses were then performed. Mean dry eye-related symptom score showed a significant improvement from the baseline (14.5 points) at 2, 4, 8 and 12 weeks (9.80, 7.04, 7.04 and 7.83 points, corrected P value rebamipide ophthalmic suspension was an effective therapy for dry eye patients. Moreover the fluorescein conjunctiva staining score and dry eye-related symptom score might be good relevant factors for favorable effects of rebamipide.

  1. Identification of relevant factors and diversified portfolio selection in brazilian stock market

    Alysson Ramos Artuso


    Full Text Available Starting from fundamental variables, this research aims to construct unobservable factors to explain the most part of the accounting data’s variability of listed companies on Bovespa. So, it was applied the multivariate statistical technique factor analysis by means principal components, in which eight factors were relevant. Based on the scores of these factors, the assets were ranked and annual portfolios with twelve actions were selected. This strategy had positive abnormal returns at 5% of significance level in the period 1999 to 2009, bringing evidence of inefficiencies in the Brazilian stock market. Thus, the techniques provide an option for understanding the stock market and the portfolios’ selection through the analysis of multiple variables.

  2. Factors and Strategies That Influence Faculty Involvement in Public Service

    Holland, Barbara A.


    Data from several national research and evaluation projects involving 32 diverse institutions offer insights into what motivates college-faculty involvement in public service and outreach efforts, what faculty find to be obstacles to involvement, and what institutions can do to facilitate involvement. One salient policy supporting faculty…

  3. Familial and social factors of involving teenagers into alcohol use

    Andreeva, Tatiana


    Full Text Available BACKGROUND: Many authors discuss factors which influence involving adolescence into alcohol use. This study was aimed to assess contribution of factors related to alcohol use in the family, getting into situations of alcohol use as well as preventive work in teenage establishments.MATERIAL AND METHODS: Survey of 373 adolescents attending teenage clubs was conducted in Kazan, Russia, with questions related to alcohol use in the family and among peers, age and circumstances of first alcohol use. The outcome measure was whether respondents were current alcohol users. Associations were explored through logistic regression models.RESULTS: Alcohol use by teenagers did not differ by gender. Odds of using alcohol increased with age (OR=1.46 95%CI 1.19-1.80 per year. Risk of alcohol use was lower if no family members used alcohol (OR=0.3 95%CI 0.2-0.5 compared to those teenagers who have any family members who used alcohol. After adding to the model variables related to the first alcohol use, most significant was association with the response that no one has ever proposed to drink alcohol (OR=0.014 95%CI 0.005-0.041 compared to any situations of alcohol use, while the association with familial factors was attenuated. This shows that impact of familial factors could be mediated through the occasions of alcohol use. Teenagers whose parents do not use alcohol less likely get into situations where they are proposed to drink in a peer group (12% vs. 24% or at a party (18% vs. 25%.Adolescents who expressed negative attitude to alcohol-related work in youth clubs more likely were alcohol users themselves (OR=21.1 95%CI 2.6-170.3, which is better applicable for diagnostics than for program evaluation.CONCLUSION: Absence of alcohol in the family predetermines alcohol use by adolescents. Teenagers whose parents do not use alcohol less likely get into situations where they are suggested to drink alcohol.

  4. Relevant Etiological Factors Involved in Human Trafficking in order to Practice Prostitution

    Alexandru Boroi


    Full Text Available Human trafficking (especially women and young girls, though men count equally among the victims are recently developed worldwide. The situation in certain regions of Central and Eastern Europe (with the opening of borders, increasing unemployment and poverty, dislocations and reducing state control structures tend to favour the development of all forms of trafficking, especially of human trafficking forsexual exploitation. To adopt appropriate measures to prevent and combat we have to know first the causes and conditions that generate human beings trafficking. Analysis of case studies and police statistics allowed the structuring of categories of causes and conditions that generate and sustain the phenomenon of traffickingin order to practice prostitution.

  5. Relevant Etiological Factors Involved in Human Trafficking in order to Practice Prostitution

    Alexandru Boroi


    Human trafficking (especially women and young girls, though men count equally among the victims) are recently developed worldwide. The situation in certain regions of Central and Eastern Europe (with the opening of borders, increasing unemployment and poverty, dislocations and reducing state control structures) tend to favour the development of all forms of trafficking, especially of human trafficking forsexual exploitation. To adopt appropriate measures to prevent and combat we have to know ...

  6. Exploratory Factor Analysis of SCL90-R Symptoms Relevant to Psychosis

    Javad Amini


    Full Text Available "nObjective: Inconsistent results have been reported regarding the symptom dimensions relevant to psychosis in symptoms check list revised (SCL90-R, i.e., "psychoticism" and "paranoid ideation". Therefore, some studies have suggested different factor structures for questions of these two dimensions, and proposed two newly defined dimensions of "schizotypal signs" and "schizophrenia nuclear symptoms". We conducted an exploratory factor analysis on the items of these two dimensions in a general population sample in Iran. "nMethod: A total of 2158 subjects residing in Southern Tehran (capital of Iran were interviewed using the psychoticism and paranoid ideation questions in SCL90-R to assess severity of these symptom dimensions. Factor analysis was done through SAS 9.1.3 PROC FACTOR using Promax rotation (power=3 on the matrix of "polychoric correlations among variables" as the input data. "nResults: Two factors were retained by the proportion criterion. Considering loadings >= 0.5 as minimum criteria for factor loadings, 7 out of 10 questions  from psychoticism ,and 3 out of 6 questions from paranoid ideation were retained, and others were eliminated. The factor labels proposed by the questionnaire suited the extracted factors and were retained. Internal consistency for each of the dimensions was acceptable (Cronbach's alpha 0.7 and 0.74 for paranoid ideation and psychoticism respectively. Composite scores showed a half-normal distribution for both dimensions which is predictable for instruments that detect psychotic symptoms. "nConclusion: Results were in contrast with similar studies, and questioned them by suggesting a different factor structure obtained from a statistically large population. The population in a developing nation (Iran in this study and the socio-cultural differences in developed settings are the potential sources for discrepancies between this analysis and previous reports.

  7. Upper GI endoscopy in elderly patients: predictive factors of relevant endoscopic findings.

    Buri, Luigi; Zullo, Angelo; Hassan, Cesare; Bersani, Gianluca; Anti, Marcello; Bianco, Maria A; Cipolletta, Livio; Giulio, Emilio Di; Matteo, Giovanni Di; Familiari, Luigi; Ficano, Leonardo; Loriga, Piero; Morini, Sergio; Pietropaolo, Vincenzo; Zambelli, Alessandro; Grossi, Enzo; Tessari, Francesco; Intraligi, Marco; Buscema, Massimo


    Elderly patients are at increased risk for peptic ulcer and cancer. Predictive factors of relevant endoscopic findings at upper endoscopy in the elderly are unknown. This was a post hoc analysis of a nationwide, endoscopic study. A total of 3,147 elderly patients were selected. Demographic, clinical, and endoscopic data were systematically collected. Relevant findings and new diagnoses of peptic ulcer and malignancy were computed. Both univariate and multivariate analyses were performed. A total of 1,559 (49.5%), 213 (6.8%), 93 (3%) relevant findings, peptic ulcers, and malignancies were detected. Peptic ulcers and malignancies were more frequent in >85-year-old patients (OR 3.1, 95% CI = 2.0-4.7, p = 0.001). The presence of dysphagia (OR = 5.15), weight loss (OR = 4.77), persistent vomiting (OR = 3.68), anaemia (OR = 1.83), and male gender (OR = 1.9) were significantly associated with a malignancy, whilst overt bleeding (OR = 6.66), NSAIDs use (OR = 2.23), and epigastric pain (OR = 1.90) were associated with the presence of peptic ulcer. Peptic ulcer or malignancies were detected in 10% of elderly patients, supporting the use of endoscopy in this age group. Very elderly patients appear to be at higher risk of such lesions.

  8. Relevant Factors for Establishing Inter-firm Cooperation Networks in Rio Grande do Sul

    Jorge Renato Verschoore


    Full Text Available The cooperation among firms in a network form has been stressed as an alternative organizational configuration in response to recent economic transformation. The increased number of initiatives and the empirical research scarcity on the network formation in Brazil motivated the present study. The main objective of this paper is to comprehend the factors which effect the establishment of network cooperation in the Southern Brazilian context. In order to achieve this objective a quantitative research was carried out with 443 enterprise representatives, associated to 120 cooperation networks. The empirical data were collected by the researchers in 2005 and statistically processed through a conjoint analysis. The results confirmed the theoretical propositions built by the researchers,appointing the relevance of factors, such as learning and innovation, increased scale and market power, and access to solutions.


    Olimpia OANCEA


    Full Text Available Today, organizations must adapt to the new realities of the environment in which they operate, and their efforts must be increasingly more oriented towards identifying the factors that influence consumer behavior, in particular economic, social and psychological aspects. When consumers are acting on incomplete information base, they assume automatically a risk for each purchasing decision. The size of the risk decreases depending on the quantity and relevance of information transmitted through communicational messages. Therefore, the aim of this paper is to highlight the factors that should be taken into account when designing a communicational message, so that this has to have the ability to change consumer attitudes and to keep constant interest to the products and / or services of a company.

  10. [Relevance of personal contextual factors of the ICF for use in practical social medicine and rehabilitation].

    Grotkamp, S; Cibis, W; Bahemann, A; Baldus, A; Behrens, J; Nyffeler, I D; Echterhoff, W; Fialka-Moser, V; Fries, W; Fuchs, H; Gmünder, H P; Gutenbrunner, C; Keller, K; Nüchtern, E; Pöthig, D; Queri, S; Rentsch, H P; Rink, M; Schian, H-M; Schian, M; Schmitt, K; Schwarze, M; Ulrich, P; von Mittelstaedt, G; Seger, W


    Personal contextual factors play an essential part in the model of the International Classification of Functioning, Disability and Health (ICF). The WHO has not yet classified personal factors for global use although they impact on the functioning of persons positively or negatively. In 2010, the ICF working group of the German Society of Social Medicine and Prevention (DGSMP) presented a proposal for the classification of personal factors into 72 categories previously arranged in 6 chapters. Now a positioning paper has been added in order to stimulate a discussion about the fourth component of the ICF, to contribute towards a broader and common understanding about the nature of personal factors and to incite a dialogue among all those involved in health care as well as those people with or with-out health problems in order to gain a comprehensive perspective about a person's condition.

  11. Pediculosis capitis and relevant factors in secondary school students of Hamadan, west of Iran.

    Omidi, Afsar; Khodaveisi, Masoud; Moghimbeigi, Abas; Mohammadi, Nahid; Amini, Roya


    Pediculosis capitis is a problem in children and has worldwide distribution. The aim of the present study was to determine the prevalence of pediculosis degree and its relevant factors in the secondary schools in Hamadan west of Iran. The study was carried out in two phases. A cross-sectional procedure was used to determine the prevalence of pediculosis, and the case study was done to identify the relevant factors to the infestation. Totally, 10841 secondary students were chosen and classified in accordance with the clustering sample. The prevalence of pediculosis was 1.05%. It was 1.27% among the urban student; whereas 0.05% among the rural students. About 2.3% belonged to female students, and 0.11% was pertained to the male students. The greatest amount of infestation prevalence was reported from the schools of urban areas particularly in the public schools of suburbia. Furthermore, the prevalence of infestation was more where some individuals had pediculosis previous history and suffered from head inching. It turned out to be a significant relationship between pediculosis, head itching (Ppediculosis (Ppediculosis in Hamadan is low, but is more in the areas which are deprived of the access to health facilities. Therefore, there is a need for educational campaigns about danger of infection and regular mass screening at school.

  12. Relevant factors to consider prior to an investor-owned acquisition of a nonprofit healthcare entity.

    Ault, Kelvin; Childs, Brad; Wainright, Charles F; Young, Marilyn


    The purpose of this article is to explore the factors that affect the negotiations for an acquisition of a nonprofit system by an investor-owned entity. The recent economic downturn, accompanying credit crisis, and healthcare reform legislation will likely encourage and accelerate the pace of merger and acquisition (M&A) transactions between investor-owned entities and nonprofit hospitals. As many nonprofits are smaller, more financially vulnerable, and more limited in their access to capital than their investor-owned counterparts, nonprofits could be prime targets for investor-owned acquirers during the healthcare reform implementation period. In M&A transactions of this type, the investor-owned acquirer typically is motivated to pursue an acquisition when the deal promises an acceptable return on investment and decreased operating costs from economies of scale. Alternatively, the nonprofit target is typically seeking funding for upgrades to facilities and information technology systems as well as a continued commitment to charity care and managed-care contracting leverage. A successful acquisition of a nonprofit hospital by an investor-owned company requires a careful analysis of relevant tax, economic, and strategic factors prior to closing the deal. This article lists the most significant factors to consider in these deals and explains how these factors should influence the purchase price and postacquisition cash flow.

  13. Factors that Influence Male Involvement in Sexual and Reproductive ...


    a local nongovernmental organization, Kisumu Medical and Education Trust ... status of male involvement in reproductive health services in western Kenya and ..... vulnerabilities and expose any reproductive health secrets, exposures that ...

  14. Relevant Obstetric Factors for Cerebral Palsy: From the Nationwide Obstetric Compensation System in Japan.

    Junichi Hasegawa

    Full Text Available The aim of this study was to identify the relevant obstetric factors for cerebral palsy (CP after 33 weeks' gestation in Japan.This retrospective case cohort study (1:100 cases and controls used a Japanese national CP registry. Obstetric characteristics and clinical course were compared between CP cases in the Japan Obstetric Compensation System for Cerebral Palsy database and controls in the perinatal database of the Japan Society of Obstetrics and Gynecology born as live singleton infants between 2009 and 2011 with a birth weight ≥ 2,000 g and gestation ≥ 33 weeks.One hundred and seventy-five CP cases and 17,475 controls were assessed. Major relevant single factors for CP were placental abnormalities (31%, umbilical cord abnormalities (15%, maternal complications (10%, and neonatal complications (1%. A multivariate regression model demonstrated that obstetric variables associated with CP were acute delivery due to non-reassuring fetal status (relative risk [RR]: 37.182, 95% confidence interval [CI]: 20.028-69.032, uterine rupture (RR: 24.770, 95% CI: 6.006-102.160, placental abruption (RR: 20.891, 95% CI: 11.817-36.934, and preterm labor (RR: 3.153, 95% CI: 2.024-4.911, whereas protective factors were head presentation (RR: 0.199, 95% CI: 0.088-0.450 and elective cesarean section (RR: 0.236, 95% CI: 0.067-0.828.CP after 33 weeks' gestation in the recently reported cases in Japan was strongly associated with acute delivery due to non-reassuring fetal status, uterine rupture, and placental abruption.

  15. Therapy-relevant factors in adult ADHD from a cognitive behavioural perspective.

    Newark, Patricia Elizabeth; Stieglitz, Rolf-Dieter


    Adult individuals with attention-deficit hyperactivity disorder (ADHD) have been suffering from this neurobiological and highly heritable disorder chronically since childhood. Resulting from their longstanding neuropsychological impairments, such as attentional problems, emotional instability, and disinhibition, they are familiar to a multiplicity of negative life outcomes and underachievement. Furthermore, a large part of this population suffers from psychiatric comorbidity. This accumulation of negative experiences has an impact on therapy-relevant factors such as the individual's self-esteem, self-efficacy, development of core beliefs/schemas, and coping strategies. Based on negative beliefs about the self, individuals confronted with difficult situations develop maladaptive coping strategies, for instance avoidance and procrastination. These strategies lead to maintenance and reinforcement of maladaptive beliefs, and as such they acquit themselves as schema-confirming. Captured in this vicious cycle, the individual sees her negative view of the self confirmed. The purpose of this paper is to illuminate these interactive factors that influence the aforementioned cycle in order to emphasize the cognitive behavioural interventions tailored to those factors on the basis of latest research. Furthermore, the authors want to attract notice to the resources people with ADHD are said to have, namely creativity and resilience. These postulated resources could be therapy-relevant by creating positive beliefs about the self, hence improving coping skills and breaking the vicious circle of negative appraisal. Taking into account personal resources and their fostering may be an important fundament for the treatment plan of adult ADHD. Information on the current state of research and theoretical approaches concerning the below-mentioned key words was gathered through MEDLINE, PsycINFO, PSYNDEXplus, and PubMed databases.

  16. Relevant Obstetric Factors for Cerebral Palsy: From the Nationwide Obstetric Compensation System in Japan

    Hasegawa, Junichi; Toyokawa, Satoshi; Ikenoue, Tsuyomu; Asano, Yuri; Satoh, Shoji; Ikeda, Tomoaki; Ichizuka, Kiyotake; Tamiya, Nanako; Nakai, Akihito; Fujimori, Keiya; Maeda, Tsugio; Masuzaki, Hideaki; Suzuki, Hideaki; Ueda, Shigeru


    Objective The aim of this study was to identify the relevant obstetric factors for cerebral palsy (CP) after 33 weeks’ gestation in Japan. Study design This retrospective case cohort study (1:100 cases and controls) used a Japanese national CP registry. Obstetric characteristics and clinical course were compared between CP cases in the Japan Obstetric Compensation System for Cerebral Palsy database and controls in the perinatal database of the Japan Society of Obstetrics and Gynecology born as live singleton infants between 2009 and 2011 with a birth weight ≥ 2,000 g and gestation ≥ 33 weeks. Results One hundred and seventy-five CP cases and 17,475 controls were assessed. Major relevant single factors for CP were placental abnormalities (31%), umbilical cord abnormalities (15%), maternal complications (10%), and neonatal complications (1%). A multivariate regression model demonstrated that obstetric variables associated with CP were acute delivery due to non-reassuring fetal status (relative risk [RR]: 37.182, 95% confidence interval [CI]: 20.028–69.032), uterine rupture (RR: 24.770, 95% CI: 6.006–102.160), placental abruption (RR: 20.891, 95% CI: 11.817–36.934), and preterm labor (RR: 3.153, 95% CI: 2.024–4.911), whereas protective factors were head presentation (RR: 0.199, 95% CI: 0.088–0.450) and elective cesarean section (RR: 0.236, 95% CI: 0.067–0.828). Conclusion CP after 33 weeks’ gestation in the recently reported cases in Japan was strongly associated with acute delivery due to non-reassuring fetal status, uterine rupture, and placental abruption. PMID:26821386

  17. A Multidimensional Study of School-Family-Community Partnership Involvement: School, School Counselor, and Training Factors

    Bryan, Julia A.; Griffin, Dana


    A multidimensional study examines both the dimensions of school counselors' involvement in school-family-community partnerships and the factors related to their involvement in partnerships. The School Counselor Involvement in Partnerships Survey was revised and its factor structure examined. Principal factor analyses revealed three dimensions of…

  18. Complement Factor B Mutations in Atypical Hemolytic Uremic Syndrome—Disease-Relevant or Benign?

    Marinozzi, Maria Chiara; Vergoz, Laura; Rybkine, Tania; Ngo, Stephanie; Bettoni, Serena; Pashov, Anastas; Cayla, Mathieu; Tabarin, Fanny; Jablonski, Mathieu; Hue, Christophe; Smith, Richard J.; Noris, Marina; Halbwachs-Mecarelli, Lise; Donadelli, Roberta; Fremeaux-Bacchi, Veronique


    Atypical hemolytic uremic syndrome (aHUS) is a genetic ultrarare renal disease associated with overactivation of the alternative pathway of complement. Four gain-of-function mutations that form a hyperactive or deregulated C3 convertase have been identified in Factor B (FB) ligand binding sites. Here, we studied the functional consequences of 10 FB genetic changes recently identified from different aHUS cohorts. Using several tests for alternative C3 and C5 convertase formation and regulation, we identified two gain-of-function and potentially disease-relevant mutations that formed either an overactive convertase (M433I) or a convertase resistant to decay by FH (K298Q). One mutation (R178Q) produced a partially cleaved protein with no ligand binding or functional activity. Seven genetic changes led to near-normal or only slightly reduced ligand binding and functional activity compared with the most common polymorphism at position 7, R7. Notably, none of the algorithms used to predict the disease relevance of FB mutations agreed completely with the experimental data, suggesting that in silico approaches should be undertaken with caution. These data, combined with previously published results, suggest that 9 of 15 FB genetic changes identified in patients with aHUS are unrelated to disease pathogenesis. This study highlights that functional assessment of identified nucleotide changes in FB is mandatory to confirm disease association. PMID:24652797

  19. Genetic factors involves in intracranial aneurysms--actualities

    Mohan, D; Munteanu, V; Coman, T; Ciurea, A V


    ...% of all IAs in the population. Cerebral aneurysm disease is related to hemodynamic and genetic factors, associated with structural weakness in the arterial wall, which was acquired by a specific, often unknown, event...

  20. Option Pricing Method in a Market Involving Interval Number Factors


    The method for pricing the option in a market with interval number factors is proposed. The no-arbitrage principle in the interval number valued market and the rule to judge the reasonability of a price interval are given. Using the method, the price interval where the riskless interest and the volatility under B-S setting is given. The price interval from binomial tree model when the key factors u, d, R are all interval numbers is also discussed.

  1. Some factors involved in microprojectile-mediated indica rice transformation

    XUERui; QIUXiaohui; YANMeixian; HUANGDanian; CAOShouyun; TIANWenzhong


    Immature embryos and calli derived from immature or mature embryos of the 16 indica rice varieties have been transformed by using particle bombardment. To improve growth state of subcultured calli, we set up a variety of parameters to optimize the important tactors involved in Biolistic system, and added various hormones, mannitol, and MES to CC or NB medium.

  2. Analysis of the Relevant Factors for the Engaging Women in Various Sports in Croatia

    Joško Sindik


    Full Text Available Goals of this research were to determine the correlations among the dimensions of relevant factors about engagement of women in sports, as well as to determine the differences in the dimensions of relevant factors about engagement of women in sports, according to several independent variables: type of sport, educational level, marital status and place of living. A total of 342 female athletes and other sport practitioners are examined, with the average age of 31.53±13.92 years (M±SD from several Croatian sport federations: judo, badminton, gymnastics, bowling, acrobatic rock’n roll, handball, sport fishing, Association of the deaf athletes, archery, chess and basketball. The results revealed that according to the type of sport, the differences are statistically significant for: negative environment, relaxation/fun and ambition/self-esteem motives; environmental, obligation and financial/traffic/rules barriers; indirect strategies and already present initiatives for including women in sports. According to the education level, the differences are statistically significant for: positive personal, negative environmental motives and ambition/self-esteem motives; obligations as the barriers; organization out-of-sport commitments and specific strategies for media. The differences in the marital status of participants are statistically significant for the variables: positive personal, negative environmental and ambition/self-esteem motives; environmental and obligation barriers; organization of out-of-sport commitments. At last, only two statistically significant differences are found according to the place of living: for indirect strategies for including women in sports and for the programs created only for women. The results provide the platform for developing programs and strategies for retaining and engaging women in particular sports in Croatia.

  3. Clinically relevant risk factors for suicide: Comparison between clinical group with passive suicidal ideation, active suicidal ideation and without suicidal ideation

    Miloseva, Lence; Cuijpers, Pim; Stojcev, Saso; Niklewski, Gunter; Richter, Kneginja; Jovevska, Svetlana; Arsova, Roza; Serafimov, Aleksandar


    Introduction: In recent years, researchers and clinicians do not treat passive suicidal ideation as a clinically relevant risk factor for suicide, while underestimating the strength of this desire to die, compared with making a plan for suicide in individuals having active suicidal ideation. This research study is clinically prospective, cross-sequential, but also partly retrospective because it involves also variables from the past, such as patients’ history data (number of suicidal attempts...

  4. Munchausen Syndrome by proxy: Definition, context, and psychological factors involved

    Thomas Gomes Gonçalves


    Full Text Available The Munchausen syndrome by proxy refers to a pathology characterized by physical and emotional abuse in which the simulation or production of symptoms is directed towards a child, which involves taking him or her to health treatments and unnecessary surgeries. The difficulties in the diagnosis of this form of abuse and the emotional aspects involved highlight the destructive effects in the infancy subjectivity due to the lack of loving capacity protecting and prioritizing the child demands. Psychoanalysis offers a differentiated view, comprehending that the mother attempts to elaborate her own psychic conflicts by the repetition of traumatic experience. There is a necessity of comprehension of the instinct destructivity presented in the maternal unconscious dynamics revealed in the modality of caring which is reflected in violence.

  5. Clinical incidents involving students on placement: an analysis of incident reports to identify potential risk factors.

    Gaida, J E; Maloney, S; Lo, K; Morgan, P


    Students are sometimes involved in incidents during clinical training. To the authors' knowledge, no quantitative studies of incidents specifically involving physiotherapy students on clinical placement are available in the literature. A retrospective audit (2008 to 2011) of incident reports involving physiotherapy students was conducted to identify the nature and features of incidents. The study aimed to determine if injuries to a student or patient were more or less likely when the supervisor was in close proximity, and whether students with lower academic performance in their preclinical semester were more likely to be involved in an incident. There were 19 care-delivery-related and three equipment-related incidents. There were no incidents of violent, aggressive or demeaning behaviour towards students. The incident rate was 9.0/100,000 student-hours for third-year students and 6.8/100,000 student-hours for fourth-year students. The majority of incidents (55%) occurred from 11 am to 12-noon and from 3 pm to 3.30 pm. Incidents more often resulted in patient or student injury when the supervisor was not in close proximity (approximately 50% vs approximately 20%), although the difference was not significant (P=0.336). The academic results of students involved in incidents were equivalent to the whole cohort in their preclinical semester {mean 75 [standard deviation (SD) 6] vs 76 (SD 7); P=0.488}. The unexpected temporal clustering of incidents warrants further investigation. Student fatigue may warrant attention as a potential contributor; however, contextual factors, such as staff workload, along with organisational systems, structures and procedures may be more relevant. The potential relationship between supervisor proximity and injury also warrants further exploration. The findings of the present study should be integrated into clinical education curricula and communicated to clinical educators. Copyright © 2014 Chartered Society of Physiotherapy. Published by

  6. Exosomes: A Promising Factor Involved in Cancer Hypoxic Microenvironments.

    Yang, Y; Yang, X; Yang, Y; Zhu, H; Chen, X; Zhang, H; Wang, F; Qin, Q; Cheng, H; Sun, X


    As a significant tumor feature, hypoxia can trigger cancer adaptive processes, induce malignant phenotype development, and promote drug resistance. Previous studies demonstrated that exosomes are critical during these procedures. Exosomes are small vesicles formed in vesicular bodies in the endosomal network. These small vesicles are mainly involved in the transport of bioactive molecules between cells. Exosomes are also involved in the mediation of some cellular communications depending on derived donor cells; thus, recipient cells undergo phenotypic changes. Furthermore, hypoxia can remarkably stimulate exosomal secretion; for instance, nucleic acids and proteins as transmission signals in exosomes in a tumor microenvironment are involved in various functions, such as inducing intratumoral heterogeneity, altering immunological responses, producing cancer-associated fibroblasts, and promoting angiogenesis and metastasis. Moreover, exosome contents resemble those of a donor cell; this finding indicates that exosomes may also be regarded as suitable biomarkers of hypoxia status. Therefore, exosomes can be used to facilitate diagnosis and prognosis with minimal invasive procedures. Further studies on exosomes in cancer may provide new therapeutic strategies.

  7. Susceptibility Factors Relevant for the Association Between Long-Term Air Pollution Exposure and Incident Asthma.

    Burte, Emilie; Nadif, Rachel; Jacquemin, Bénédicte


    In this review, we identified 15 studies in children and 10 studies in adults that assessed the association between long-term exposure to air pollution and incident asthma and that conducted stratified analyses to explore potential susceptibility factors. Overall, adult never-/former smokers seem to be at higher risk of incident asthma due to air pollution. Children without atopy and children from low socioeconomic status families also seem to be at higher risk of incident asthma due to air pollution. While interaction between air pollution and genes involved in the response to oxidative stress pathways have been explored, results are somewhat inconsistent and in need of replication. To evaluate interactions, large sample sizes are necessary, and much more research, including data pooling from existing studies, is needed to further explore susceptibility factors for asthma incidence due to long-term air pollution exposure.

  8. Zagreb and Tenerife: Airline Accidents Involving Linguistic Factors

    Cookson, Simon


    The International Civil Aviation Organization (ICAO) is currently implementing a program to improve the language proficiency of pilots and air traffic controllers worldwide. In justifying the program, ICAO has cited a number of airline accidents that were at least partly caused by language factors. Two accidents cited by ICAO are analysed in this…

  9. Factors Involved in Extracellular Matrix Turnover in Human Derived Cardiomyocytes

    Gregori Casals


    Full Text Available Background: The molecular mechanisms by which myocardial ischemia translates into ventricular remodeling remain unclear. Methods: We investigated whether hypoxia and proinflammatory cytokines are specific inducers of remodeling signals in an in vitro model of cultured adult human ventricular myocytes (AC16 cells. Results:Hypoxia modified the ratio of matrix remodeling factors by increasing the aminoterminal propeptide of type III procollagen (PIIINP and reducing tissue inhibitor of matrix metalloproteinase type 1 (TIMP-1 secretion in AC16 cells. These effects, however, were not associated with either modifications in expression of matrix metalloproteinase type 2, collagen-I or metalloproteinase activity. Hypoxia does, actually increase the production of the cardiac antifibrogenic growth factors, Apelin and VEGF, through an Hypoxia Inducible Factor type 1-dependent mechanism. Concerning proinflammatory signaling pathways, IL1β emerged as a powerful inducer of matrix turnover, since it significantly enhanced PIIINP, TIMP-1 and hyaluronic acid production and increased metalloproteinase activity. In contrast, TNFα did not modify matrix turnover but markedly induced the production of Apelin and VEGF. Conclusion: Hypoxia and increased TNFα activity likely exert cardioprotective actions by activating the cardiac antifibrogenic factors Apelin and VEGF. In contrast, IL1β is a strong promoter of interstitial collagen remodeling that may contribute to ventricular dilation and heart failure in the ischemic myocardium.

  10. Zagreb and Tenerife: Airline Accidents Involving Linguistic Factors

    Cookson, Simon


    The International Civil Aviation Organization (ICAO) is currently implementing a program to improve the language proficiency of pilots and air traffic controllers worldwide. In justifying the program, ICAO has cited a number of airline accidents that were at least partly caused by language factors. Two accidents cited by ICAO are analysed in this…

  11. Analysis of Clinically Relevant Factors for Pulmonary Hypertension in Maintenance Hemodialysis Patients

    Shen, Shen; Sun, Qianmei


    Background Pulmonary hypertension (PH) is common in patients with maintenance hemodialysis (MHD) and is associated with high mortality. This study analyzed clinically relevant factors for pulmonary hypertension in MHD patients and the effect of serum pentraxin3 (PTX3) in the pathogenesis of PH to provide the basis for early diagnosis and treatment of MHD patients with PH. Material/Methods This study included 60 MHD patients (group A) and 30 healthy controls (group B). Group A was further divided into PH and non-PH groups. Clinical characteristics, auxiliary examination results and serum PTX3 level of the PH and non-PH groups were compared. Binary logistic regression was used to assess the risk factors for PH in MHD patients. ROC curve was applied to evaluate the diagnostic value of PTX3 in PH. Results The incidence rate of PH in MHD patients was 50%, and most presented as mild to moderate. Compared with the non-PH group, patients in PH group presented significantly longer atrial diameter, right ventricular diameter and main pulmonary artery diameter (PMHD patients. AUC of PTX3 was 0.721 (95%CI: 0.590–0.851, P=0.003). Conclusions The prevalence of PH was higher in MHD patients and mostly presented as mild to moderate. Such patients often developed heart structural changes and cardiac ultrasound was highly recommended. Serum PTX3 level was significantly elevated and could be used as a marker of PH in MHD patients. PMID:26706606

  12. Relationships Among Factors Relevant to Abdominal Fat and Age-Related Hearing Loss.

    Lee, Young; Park, Mina


    Metabolic syndrome is related with abdominal fat and with age-related hearing loss (ARHL). In this study, we evaluated the association between a variety of factors relevant to abdominal fat (FRAs) and hearing thresholds. We reviewed retrospectively the medical records of 2,602 subjects aged over 40 years with symmetrical sensorineural hearing loss who underwent abdominal fat computed tomography (CT) scans. Univariate and multivariate linear regression analyses were used to demonstrate the association between each FRA and hearing thresholds at low and high frequencies. Four of 5 FRAs were associated with hearing thresholds at high frequencies in males. All FRAs examined showed a relationship with hearing thresholds at low frequencies in females. Diabetes mellitus (DM) among clinical factors and visceral adipose tissue (VAT) among the 5 FRAs were the most reflective of hearing thresholds in both males and females. We found that FRAs were associated with hearing loss with frequency specific characteristics according to sex and reinforced that DM and VAT is particularly an important role for hearing.

  13. How pharmacist-patient communication determines pharmacy loyalty? Modeling relevant factors.

    Patrícia Antunes, Liliana; Gomes, João José; Cavaco, Afonso Miguel


    Portuguese community pharmacies provide pharmaceutical services, such as therapeutic outcomes follow-up, supplemented by relevant point-of-care testing that require continuity of provision to be effective. To identify factors of technical and communication nature that during a patient interview contribute to patients' loyalty. A cross-sectional descriptive study, with a purposive sample of community pharmacies providing pharmaceutical care, was conducted. Patient interviews were taped and transcribed verbatim. Duration, segments and utterances were identified and time stamped, using a previously validated coding scheme. To identify predictors of loyalty, logistic regression analyses were performed. From 59 interviews, participants' average age was 65.7 years and 42 (71.2%) were female; 45 (76.3%) interviews were classified as outcomes measurements and 14 (23.7%) as pharmaceutical consultations, with 33.2% of the patients booking a following appointment. The significant items to explain loyalty were associated with lifestyle and psychosocial exchange, age of the patient, and the presence of all interview segments (i.e. a complete consultation). Contrary to common professional beliefs and practice orientation it would appear that pharmacists' technical skills are not the essential factors that promote patients' loyalty needed for continuity of care, at least in the same extent as the social and lifestyle-related content of the exchange. Pharmaceutical care education should focus on relational skills as much as on medication-related competencies. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Path-factors involving paths of order seven and nine

    EGAWA, Yoshimi; Furuya, Michitaka


    In this paper, we show the following two theorems (here $c_{i}(G-X)$ is the number of components $C$ of $G-X$ with $|V(C)|=i$): (i)~If a graph $G$ satisfies $c_{1}(G-X)+\\frac{1}{3}c_{3}(G-X)+\\frac{1}{3}c_{5}(G-X)\\leq \\frac{2}{3}|X|$ for all $X\\subseteq V(G)$, then $G$ has a $\\{P_{2},P_{7}\\}$-factor. (ii)~If a graph $G$ satisfies $c_{1}(G-X)+c_{3}(G-X)+\\frac{2}{3}c_{5}(G-X)+\\frac{1}{3}c_{7}(G-X)\\leq \\frac{2}{3}|X|$ for all $X\\subseteq V(G)$, then $G$ has a $\\{P_{2},P_{9}\\}$-factor.

  15. Multiple Factors Involved in the Pathogenesis of White Matter Lesions

    Lin, Jing; Wang, Dilong; Lan, Linfang


    White matter lesions (WMLs), also known as leukoaraiosis (LA) or white matter hyperintensities (WMHs), are characterized mainly by hyperintensities on T2-weighted or fluid-attenuated inversion recovery (FLAIR) images. With the aging of the population and the development of imaging technology, the morbidity and diagnostic rates of WMLs are increasing annually. WMLs are not a benign process. They clinically manifest as cognitive decline and the subsequent development of dementia. Although WMLs are important, their pathogenesis is still unclear. This review elaborates on the advances in the understanding of the pathogenesis of WMLs, focusing on anatomy, cerebral blood flow autoregulation, venous collagenosis, blood brain barrier disruption, and genetic factors. In particular, the attribution of WMLs to chronic ischemia secondary to venous collagenosis and cerebral blood flow autoregulation disruption seems reasonable. With the development of gene technology, the effect of genetic factors on the pathogenesis of WMLs is gaining gradual attention. PMID:28316994

  16. Expression, regulation and clinical relevance of the ATPase inhibitory factor 1 in human cancers

    Sánchez-Aragó, M; Formentini, L; Martínez-Reyes, I; García-Bermudez, J; Santacatterina, F; Sánchez-Cenizo, L; Willers, I M; Aldea, M; Nájera, L; Juarránz, Á; López, E C; Clofent, J; Navarro, C; Espinosa, E; Cuezva, J M


    Recent findings in colon cancer cells indicate that inhibition of the mitochondrial H+-adenosine triphosphate (ATP) synthase by the ATPase inhibitory factor 1 (IF1) promotes aerobic glycolysis and a reactive oxygen species (ROS)-mediated signal that enhances proliferation and cell survival. Herein, we have studied the expression, biological relevance, mechanism of regulation and potential clinical impact of IF1 in some prevalent human carcinomas. We show that IF1 is highly overexpressed in most (>90%) of the colon (n=64), lung (n=30), breast (n=129) and ovarian (n=10) carcinomas studied as assessed by different approaches in independent cohorts of cancer patients. The expression of IF1 in the corresponding normal tissues is negligible. By contrast, the endometrium, stomach and kidney show high expression of IF1 in the normal tissue revealing subtle differences by carcinogenesis. The overexpression of IF1 also promotes the activation of aerobic glycolysis and a concurrent ROS signal in mitochondria of the lung, breast and ovarian cancer cells mimicking the activity of oligomycin. IF1-mediated ROS signaling activates cell-type specific adaptive responses aimed at preventing death in these cell lines. Remarkably, regulation of IF1 expression in the colon, lung, breast and ovarian carcinomas is exerted at post-transcriptional levels. We demonstrate that IF1 is a short-lived protein (t1/2 ∼100 min) strongly implicating translation and/or protein stabilization as main drivers of metabolic reprogramming and cell survival in these human cancers. Analysis of tumor expression of IF1 in cohorts of breast and colon cancer patients revealed its relevance as a predictive marker for clinical outcome, emphasizing the high potential of IF1 as therapeutic target. PMID:23608753

  17. Proteomic Assessment of the Relevant Factors Affecting Pork Meat Quality Associated with Muscles in Duroc Pigs

    Jin Hyoung Cho


    Full Text Available Meat quality is a complex trait influenced by many factors, including genetics, nutrition, feeding environment, animal handling, and their interactions. To elucidate relevant factors affecting pork quality associated with oxidative stress and muscle development, we analyzed protein expression in high quality longissimus dorsi muscles (HQLD and low quality longissimus dorsi muscles (LQLD from Duroc pigs by liquid chromatographytandem mass spectrometry (LC-MS/MS–based proteomic analysis. Between HQLD (n = 20 and LQLD (n = 20 Duroc pigs, 24 differentially expressed proteins were identified by LC-MS/MS. A total of 10 and 14 proteins were highly expressed in HQLD and LQLD, respectively. The 24 proteins have putative functions in the following seven categories: catalytic activity (31%, ATPase activity (19%, oxidoreductase activity (13%, cytoskeletal protein binding (13%, actin binding (12%, calcium ion binding (6%, and structural constituent of muscle (6%. Silver-stained image analysis revealed significant differential expression of lactate dehydrogenase A (LDHA between HQLD and LQLD Duroc pigs. LDHA was subjected to in vitro study of myogenesis under oxidative stress conditions and LDH activity assay to verification its role in oxidative stress. No significant difference of mRNA expression level of LDHA was found between normal and oxidative stress condition. However, LDH activity was significantly higher under oxidative stress condition than at normal condition using in vitro model of myogenesis. The highly expressed LDHA was positively correlated with LQLD. Moreover, LDHA activity increased by oxidative stress was reduced by antioxidant resveratrol. This paper emphasizes the importance of differential expression patterns of proteins and their interaction for the development of meat quality traits. Our proteome data provides valuable information on important factors which might aid in the regulation of muscle development and the improvement of

  18. Psychological factors involved in prurigo nodularis: A pilot study.

    Dazzi, Carla; Erma, Daniela; Piccinno, Roberta; Veraldi, Stefano; Caccialanza, Massimo


    Emotional stresses and psychological disorders seem to be concurrent factors in some cases of prurigo nodularis (PN), a chronic skin condition with a difficult therapeutic approach. In order to improve the therapeutic strategies, we performed a psychometric study on 20 patients affected by generalized and histological proven PN. Specific questionnaires were employed to examine the hypotheses (General Health Questionnaire, State Trait Anxiety Inventory - form Y, Beck Depression Inventory-II, and Eysenck Personality Questionnaire). The results show that symptoms of anxiety and depression associated with PN are more severe than in the control group and that some specific traits of personality are more frequently represented in such subjects. The results of our study represent a first attempt to analyze the psychological problems and the personality dimensions which seem to characterize PN patients. Such evidence supports the importance of a psychological approach in the clinical management of PN, which should always include psychological assessment and treatment together with the other therapeutic options.

  19. Underlying causal factors associated with construction worker fatalities involving stepladders

    Aneurin Thomas James Grant


    Full Text Available Stepladders are frequently utilized on construction projects as a means of access to elevation. Stepladder heights commonly range from 4 feet (1.2 m to 14 feet (4.3 m. Since these heights are not extreme, there is a common misperception that stepladder use presents a low risk. On the contrary, extreme care must be exercised to ensure that work on stepladders is performed safely, as described in the conspicuously located recommendations and brightly-colored warnings that adorn virtually all newly-purchased equipment. Despite this, accidents involving stepladders occur on a regular basis.  This study was conducted to better understand the underlying causes of these accidents. The narrative descriptions of 180 stepladder-related fatalities were obtained from the U.S. Occupational Safety and Health Administration and were analyzed to identify the at-risk behaviors that preceded the fatality incidents. The results showed that most of the incidents should have been anticipated and could have been avoided. Unsafe practices such as improper lockout-tagout of electrical equipment, loss of balance, working on a folded stepladder, over-reaching, straddling the ladder, “walking” the ladder, poor footing, and unstable/shifting ladders, among others were identified. Virtually all of these fatalities could have been avoided by adhering to the guidelines posted on the stepladders and by complying with basic safe construction practices.

  20. Underlying causal factors associated with construction worker fatalities involving stepladders

    Aneurin Thomas James Grant


    Full Text Available Stepladders are frequently utilized on construction projects as a means of access to elevation. Stepladder heights commonly range from 4 feet (1.2 m to 14 feet (4.3 m. Since these heights are not extreme, there is a common misperception that stepladder use presents a low risk. On the contrary, extreme care must be exercised to ensure that work on stepladders is performed safely, as described in the conspicuously located recommendations and brightly-colored warnings that adorn virtually all newly-purchased equipment. Despite this, accidents involving stepladders occur on a regular basis.  This study was conducted to better understand the underlying causes of these accidents. The narrative descriptions of 180 stepladder-related fatalities were obtained from the U.S. Occupational Safety and Health Administration and were analyzed to identify the at-risk behaviors that preceded the fatality incidents. The results showed that most of the incidents should have been anticipated and could have been avoided. Unsafe practices such as improper lockout-tagout of electrical equipment, loss of balance, working on a folded stepladder, over-reaching, straddling the ladder, “walking” the ladder, poor footing, and unstable/shifting ladders, among others were identified. Virtually all of these fatalities could have been avoided by adhering to the guidelines posted on the stepladders and by complying with basic safe construction practices. 

  1. Social and clinically-relevant cardiovascular risk factors in Asian Americans adults: NHANES 2011-2014.

    Echeverria, Sandra E; Mustafa, Mehnaz; Pentakota, Sir Ram; Kim, Soyeon; Hastings, Katherine; Amadi, Chioma; Palaniappan, Latha


    Little evidence exists examining cardiovascular risk factors among Asian Americans and how social determinants such as nativity status and education pattern risk in the United States (U.S.) context. We used the 2011-2014 National Health and Nutrition Examination Survey, which purposely oversampled Asian Americans from 2011 to 2014, and examined prevalence of Type II diabetes, smoking and obesity for Asian Americans (n=1363) and non-Latino Whites (n=4121). We classified Asian Americans as U.S. or foreign-born and by years in the U.S. Obesity status was based on standard body mass index (BMI) cut points of ≥30kg/m(2) and Asian-specific cut points (BMI≥25kg/m(2)) that may be more clinically relevant for this population. We fit separate logistic regression models for each outcome using complex survey design methods and tested for the joint effect of race, nativity and education on each outcome.Diabetes and obesity prevalence (applying Asian-specific BMI cut points) were higher among Asian Americans when compared to non-Latino Whites but smoking prevalence was lower. These patterns remained in fully adjusted models and showed small increases with longer duration in the U.S. Joint effects models showed higher odds of prevalent Type II diabetes and obesity (Asian-specific) for foreign-born Asians, regardless of years in the U.S. and education, when compared to non-Latino Whites with high education. Smoking models showed significant interaction effects between race and education for non-Latino Whites only. Our study supports the premise that social as well as clinical factors should be considered when developing health initiatives for Asian Americans.

  2. FTO is a relevant factor for the development of the metabolic syndrome in mice.

    Kathrin Ikels

    Full Text Available The metabolic syndrome is a worldwide problem mainly caused by obesity. FTO was found to be a obesity-risk gene in humans and FTO deficiency in mice led to reduction in adipose tissue. Thus, FTO is an important factor for the development of obesity. Leptin-deficient mice are a well characterized model for analysing the metabolic syndrome. To determine the relevance of FTO for the development of the metabolic syndrome we analysed different parameters in combined homozygous deficient mice (Lep(ob/ob;Fto(-/-. Lep(ob/ob;Fto(-/- mice showed an improvement in analysed hallmarks of the metabolic syndrome in comparison to leptin-deficient mice wild type or heterozygous for Fto. Lep(ob/ob;Fto(-/- mice did not develop hyperglycaemia and showed an improved glucose tolerance. Furthermore, extension of beta-cell mass was prevented in Lep(ob/ob;Fto(-/-mice and accumulation of ectopic fat in the liver was reduced. In conclusion this study demonstrates that FTO deficiency has a protective effect not only on the development of obesity but also on the metabolic syndrome. Thus, FTO plays an important role in the development of metabolic disorders and is an interesting target for therapeutic agents.

  3. The relevance of coagulation factor X protection of adenoviruses in human sera.

    Duffy, M R; Doszpoly, A; Turner, G; Nicklin, S A; Baker, A H


    Intravenous delivery of adenoviruses is the optimal route for many gene therapy applications. Once in the blood, coagulation factor X (FX) binds to the adenovirus capsid and protects the virion from natural antibody and classical complement-mediated neutralisation in mice. However, to date, no studies have examined the relevance of this FX/viral immune protective mechanism in human samples. In this study, we assessed the effects of blocking FX on adenovirus type 5 (Ad5) activity in the presence of human serum. FX prevented human IgM binding directly to the virus. In individual human sera samples (n=25), approximately half of those screened inhibited adenovirus transduction only when the Ad5-FX interaction was blocked, demonstrating that FX protected the virus from neutralising components in a large proportion of human sera. In contrast, the remainder of sera tested had no inhibitory effects on Ad5 transduction and FX armament was not required for effective gene transfer. In human sera in which FX had a protective role, Ad5 induced lower levels of complement activation in the presence of FX. We therefore demonstrate for the first time the importance of Ad-FX protection in human samples and highlight subject variability and species-specific differences as key considerations for adenoviral gene therapy.

  4. Which Type of Risk Information to Use for Whom? Moderating Role of Outcome-Relevant Involvement in the Effects of Statistical and Exemplified Risk Information on Risk Perceptions.

    So, Jiyeon; Jeong, Se-Hoon; Hwang, Yoori


    The extant empirical research examining the effectiveness of statistical and exemplar-based health information is largely inconsistent. Under the premise that the inconsistency may be due to an unacknowledged moderator (O'Keefe, 2002), this study examined a moderating role of outcome-relevant involvement (Johnson & Eagly, 1989) in the effects of statistical and exemplified risk information on risk perception. Consistent with predictions based on elaboration likelihood model (Petty & Cacioppo, 1984), findings from an experiment (N = 237) concerning alcohol consumption risks showed that statistical risk information predicted risk perceptions of individuals with high, rather than low, involvement, while exemplified risk information predicted risk perceptions of those with low, rather than high, involvement. Moreover, statistical risk information contributed to negative attitude toward drinking via increased risk perception only for highly involved individuals, while exemplified risk information influenced the attitude through the same mechanism only for individuals with low involvement. Theoretical and practical implications for health risk communication are discussed.

  5. [May Medically Assisted Procreation (MAP) be relevant for homosexual women? Study among 147 gynaeco-logists involved in MAP techniques].

    Sintes, R; Darves-Bornoz, J-M


    The second part of the twentieth century has seen societal modifications as well as evolution of medical techniques allowing now thinking human procreation in terms of choices or even rights. Certain voices require sometimes Medically Assisted Procreation (MAP) for lesbians. Even though society did not allow such a possibility in France, it seemed interesting to question about it professionals actively involved in the use of MAP techniques. Through systematic internet queries, we obtained a list of one hundred private or public french medical institutions with a unit for the treatment of sterility. A telephone call to their secretary allowed us to individualize those doctors who did practice MAP. A sample of 147 medical doctors practicing MAP was then drawn. They were questioned with a clinical instrument including 20 ended-questions in order to assess their opinions on: homosexual women with a desire of a child; possibility for these clinicians to intervene with a donor insemination in such situations; developmental risk for such children. One hundred twenty five (85%) accepted to answer. Nine percent of these gynaecologists still consider homosexuality as pathological, and 10% as deviant - contrary to international classifications of mental disorders - and 5% deny good maternal abilities to homosexual women. Before the so-called french laws of bioethics in 1994, none of them had practiced a donor insemination for a lesbian couple, though 4% had realized some for single homosexual women. Two third of them do not agree opening donor insemination to homosexual women though for half of them, the anonymity of a donor is not perceived as prejudicial to the child. Eighty-seven percent of these gynaecologists think that a child brought up by homosexual parents is at risk for developmental disorder, the configuration supposed the most pathogenic being when the birth results from a donor insemination. The supposedly most important risk factors are thought to be the

  6. Chlamydial entry involves TARP binding of guanine nucleotide exchange factors.

    B Josh Lane


    Full Text Available Chlamydia trachomatis attachment to cells induces the secretion of the elementary body-associated protein TARP (Translocated Actin Recruiting Protein. TARP crosses the plasma membrane where it is immediately phosphorylated at tyrosine residues by unknown host kinases. The Rac GTPase is also activated, resulting in WAVE2 and Arp2/3-dependent recruitment of actin to the sites of chlamydia attachment. We show that TARP participates directly in chlamydial invasion activating the Rac-dependent signaling cascade to recruit actin. TARP functions by binding two distinct Rac guanine nucleotide exchange factors (GEFs, Sos1 and Vav2, in a phosphotyrosine-dependent manner. The tyrosine phosphorylation profile of the sequence YEPISTENIYESI within TARP, as well as the transient activation of the phosphatidylinositol 3-kinase (PI3-K, appears to determine which GEF is utilized to activate Rac. The first and second tyrosine residues, when phosphorylated, are utilized by the Sos1/Abi1/Eps8 and Vav2, respectively, with the latter requiring the lipid phosphatidylinositol 3,4,5-triphosphate. Depletion of these critical signaling molecules by siRNA resulted in inhibition of chlamydial invasion to varying degrees, owing to a possible functional redundancy of the two pathways. Collectively, these data implicate TARP in signaling to the actin cytoskeleton remodeling machinery, demonstrating a mechanism by which C.trachomatis invades non-phagocytic cells.

  7. Nerve growth factor involvement in liver cirrhosis and hepatocellular carcinoma


    AIM: To define NGF (nerve growth factor) and its highaffinity receptor trkANGF presence and distribution in fibrotic liver and in HCC, and to verify if NGF might have a role in fibrosis and HCC.METHODS: Intracellular distribution of NGF and trkANGF were assessed by immunohistochemistry and immunoelectron microscopy in liver specimens from HCC,cirrhosis or both. ELISA was used to measure circulating NGF levels.RESULTS: NGF and trkANGF were highly expressed in HCC tissue, mainly localized in hepatocytes, endothelial and some Kupffer cells. In the cirrhotic part of the liver they were also markedly expressed in bile ducts epithelial and spindle-shaped cells. Surprisingly, in cirrhotic tissue from patients without HCC, both NGF and trkANGF were negative. NGF serum levels in cirrhotic and/or HCC patient were up to 25-fold higher than in controls.CONCLUSION: NGF was only detected in liver tissue with HCC present. Intracellular distribution suggests paracrine and autocrine mechanisms of action. Better definition of mechanisms may allow for therapeutic and diagnostic/prognostic use of NGF.

  8. 24. The transcription factors and the relevant signaling pathways activated by low concentration MNNG


    Aims: To explore the transcription factors and related signal transduction pathways activated in the alkylating agents N-methyl-N'-nitro-N-nitrosoguanindine (MNNG) exposed cells which may involved in the mechanism of MNNG induced changes of gene expression, especially the elevation of DNA polymerase β expression and also the consequence of JNK kinase activation which were reported previously in this lab. Methods: Clontech Mercury pathway profiling system containing 8 different vectors in which a specific response element is located upstream from the SEAP-reporter gene were employed to detect the transcription factor activation in Vero cells treated with 0.2 μmol/L MNNG for 2 hours. Thoroughly, CREB phosphorylation, protein kinase A (PKA) and the cellular cAMP content were also assayed with PhosphoPlus CREB (ser-133) antibody kit, protein kinase assay kit and cAMP RIA kit respectively. Results: Among 8 different response elements, the expression of the reporter gene governed by the transcription factors CREB (cAMP response element binding protein), AP1 (activator protein 1), NF-κB (nuclear factor κ B) were elevated by 1.3, 1.4 and 1.3 times higber than control respectively. The level of activated CREB by Ser-133 phosphorylation was 2.08 times higher than control in cells treated with MNNG for 60 min, as measured by immunoblotting. The activity of CREB upstream kinase protein kinase A (PKA), which can phosphorylate CREB on ser-133 was also activated, and the activation peaked at 60 min (11.03±2.80 arbitrary units vs 0.86±0.43 of control). Also, cAMP levels were significantly raised after 60-minute-treatment, 1.52 times higher vs those in solvent control. Conclusion: In addition of previously reported JNK activation, we show here that low concentration alkylating agent MNNG can also activate the cAMP-PKA and NF-κB pathway. These in consequence induce the activation of transcription factors APl, CREB and NF-κB, which may related to the MNNG induced changes in

  9. Ring-Shaped Potential and a Class of Relevant Integrals Involved Universal Associated Legendre Polynomials with Complicated Arguments

    Wei Li


    Full Text Available We find that the solution of the polar angular differential equation can be written as the universal associated Legendre polynomials. Its generating function is applied to obtain an analytical result for a class of interesting integrals involving complicated argument, that is, ∫-11Pl′m′xt-1/1+t2-2xtPk′m′(x/(1+t2-2tx(l′+1/2dx, where t∈(0,1. The present method can in principle be generalizable to the integrals involving other special functions. As an illustration we also study a typical Bessel integral with a complicated argument ∫0∞Jn(αx2+z2/(x2+z2nx2m+1dx.

  10. Meandering main pancreatic duct as a relevant factor to the onset of idiopathic recurrent acute pancreatitis.

    Wataru Gonoi

    Full Text Available BACKGROUND: Meandering main pancreatic duct (MMPD, which comprises loop type and reverse-Z type main pancreatic duct (MPD, has long been discussed its relation to pancreatitis. However, no previous study has investigated its clinical significance. We aimed to determine the non-biased prevalence and the effect of MMPD on idiopathic pancreatitis using non-invasive magnetic resonance (MR technique. METHODS AND FINDINGS: A cross-sectional study performed in a tertiary referral center. The study enrolled 504 subjects from the community and 30 patients with idiopathic pancreatitis (7 acute, 13 chronic, and 10 recurrent acute. All subjects underwent MR scanning and medical examination. MMPD was diagnosed when the MPD in the head of pancreas formed two or more extrema in the horizontal direction on coronal images of MR cholangiopancreatography, making a loop or a reverse-Z shaped hairpin curves and not accompanied by other pancreatic ductal anomaly. Statistical comparison was made among groups on the rate of MMPD including loop and reverse-Z subtypes, MR findings, and clinical features. The rate of MMPD was significantly higher for all idiopathic pancreatitis/idiopathic recurrent acute pancreatitis (RAP (20%/40%; P<0.001/0.0001; odds ratio (OR, 11.1/29.0 than in the community (2.2% but was not higher for acute/chronic pancreatitis (14%/8%; P = 0.154/0.266. Multiple logistic regression analysis revealed MMPD to be a significant factor that induces pancreatitis/RAP (P<0.0001/0.0001; OR, 4.01/26.2. Loop/reverse-Z subtypes were found more frequently in idiopathic RAP subgroup (20%/20%; P = 0.009/0.007; OR, 20.2/24.2 than in the community (1.2%/1.0%. The other clinical and radiographic features were shown not associated with the onset of pancreatitis. CONCLUSIONS: MMPD is a common anatomical variant and might be a relevant factor to the onset of idiopathic RAP.

  11. Predicting involvement in prison gang activity: street gang membership, social and psychological factors.

    Wood, Jane L; Alleyne, Emma; Mozova, Katarina; James, Mark


    The aim of this study was to examine whether street gang membership, psychological factors, and social factors such as preprison experiences could predict young offenders' involvement in prison gang activity. Data were collected via individual interviews with 188 young offenders held in a Young Offenders Institution in the United Kingdom. Results showed that psychological factors such as the value individuals attached to social status, a social dominance orientation, and antiauthority attitudes were important in predicting young offenders' involvement in prison gang activity. Further important predictors included preimprisonment events such as levels of threat, levels of individual delinquency, and levels of involvement in group crime. Longer current sentences also predicted involvement in prison gang activity. However, street gang membership was not an important predictor of involvement in prison gang activity. These findings have implications for identifying prisoners involved in prison gang activity and for considering the role of psychological factors and group processes in gang research.

  12. Tissue factor pathway inhibitor-2: a novel gene involved in zebrafish central nervous system development.

    Zhang, Yanli; Wang, Lina; Zhou, Wenhao; Wang, Huijun; Zhang, Jin; Deng, Shanshan; Li, Weihua; Li, Huawei; Mao, Zuohua; Ma, Duan


    Tissue factor pathway inhibitor-2 (Tfpi-2) is an important serine protease inhibitor in the extracellular matrix (ECM), but its precise physiological significance remains unknown. This work is part of a series of studies intended to investigate functional roles of Tfpi-2 and explore the underlying molecular mechanisms. First, we cloned and identified zebrafish Tfpi-2 (zTfpi-2) as an evolutionarily conserved protein essential for zebrafish development. We also demonstrated that ztfpi-2 is mainly expressed in the central nervous system (CNS) of zebrafish, and embryonic depletion of ztfpi-2 caused severe CNS defects. In addition, changes of neural markers, including pax2a, egr2b, huC, ngn1, gfap and olig2, confirmed the presence of developmental abnormalities in the relevant regions of ztfpi-2 morphants. Using microarray analysis, we found that members of the Notch pathway, especially her4 and mib, which mediate lateral inhibition in CNS development, were also downregulated. Intriguingly, both her4 and mib were able to partially rescue the ztfpi-2 morphant phenotype. Furthermore, Morpholino knockdown of ztfpi-2 resulted in upregulation of neuronal markers while downregulation of glial markers, providing evidence that the Notch pathway is probably involved in ztfpi-2-mediated CNS development.

  13. The relevance of cultural factors in predicting condom-use intentions among immigrants from the Netherlands Antilles

    Kocken, P.L.; Dorst, A.G. van; Schaalma, H.


    A study into the relevance of cultural factors in predicting condom-use intentions among Antillean migrants in the Netherlands is described in this article. The association between the intention to use condoms with a new sexual partner and a perceived taboo on discussing sex, beliefs about sex educa

  14. The Relevance of Cultural Factors in Predicting Condom-Use Intentions among Immigrants from the Netherlands Antilles

    Kocken, P. L.; van Dorst, A. G.; Schaalma, H.


    A study into the relevance of cultural factors in predicting condom-use intentions among Antillean migrants in the Netherlands is described in this article. The association between the intention to use condoms with a new sexual partner and a perceived taboo on discussing sex, beliefs about sex education and machismo beliefs on gender and power…

  15. The relevance of cultural factors in predicting condom-use intentions among immigrants from the Netherlands Antilles

    Kocken, P.L.; Dorst, A.G. van; Schaalma, H.


    A study into the relevance of cultural factors in predicting condom-use intentions among Antillean migrants in the Netherlands is described in this article. The association between the intention to use condoms with a new sexual partner and a perceived taboo on discussing sex, beliefs about sex

  16. Potential causative agents of acute gastroenteritis in households with preschool children : prevalence, risk factors, clinical relevance and household transmission

    Heusinkveld, M.; Mughini-Gras, L.; Pijnacker, R.; Vennema, H.; Scholts, R.; van Huisstede-Vlaanderen, K. W.; Kortbeek, T.; Kooistra-Smid, M.; van Pelt, W.


    Acute gastroenteritis (AGE) morbidity remains high amongst preschool children, posing a significant societal burden. Empirical data on AGE-causing agents is needed to gauge their clinical relevance and identify agent-specific targets for control. We assessed the prevalence, risk factors and associat

  17. Factors that Influence the Perceived Advantages and Relevance of Facebook as a Learning Tool: An Extension of the UTAUT

    Escobar-Rodríguez, Tomás; Carvajal-Trujillo, Elena; Monge-Lozano, Pedro


    Social media technologies are becoming a fundamental component of education. This study extends the Unified Theory of Acceptance and Use of Technology (UTAUT) to identify factors that influence the perceived advantages and relevance of Facebook as a learning tool. The proposed model is based on previous models of UTAUT. Constructs from previous…

  18. Potential causative agents of acute gastroenteritis in households with preschool children : prevalence, risk factors, clinical relevance and household transmission

    Heusinkveld, M.; Mughini-Gras, L.; Pijnacker, R.; Vennema, H.; Scholts, R.; van Huisstede-Vlaanderen, K. W.; Kortbeek, T.; Kooistra-Smid, M.; van Pelt, W.


    Acute gastroenteritis (AGE) morbidity remains high amongst preschool children, posing a significant societal burden. Empirical data on AGE-causing agents is needed to gauge their clinical relevance and identify agent-specific targets for control. We assessed the prevalence, risk factors and

  19. Potential causative agents of acute gastroenteritis in households with preschool children : prevalence, risk factors, clinical relevance and household transmission

    Heusinkveld, M.; Mughini-Gras, L.; Pijnacker, R.; Vennema, H.; Scholts, R.; van Huisstede-Vlaanderen, K. W.; Kortbeek, T.; Kooistra-Smid, M.; van Pelt, W.


    Acute gastroenteritis (AGE) morbidity remains high amongst preschool children, posing a significant societal burden. Empirical data on AGE-causing agents is needed to gauge their clinical relevance and identify agent-specific targets for control. We assessed the prevalence, risk factors and associat

  20. The relevance of cultural factors in predicting condom-use intentions among immigrants from the Netherlands Antilles

    Kocken, P.L.; Dorst, A.G. van; Schaalma, H.


    A study into the relevance of cultural factors in predicting condom-use intentions among Antillean migrants in the Netherlands is described in this article. The association between the intention to use condoms with a new sexual partner and a perceived taboo on discussing sex, beliefs about sex educa

  1. The Relevance of Cultural Factors in Predicting Condom-Use Intentions among Immigrants from the Netherlands Antilles

    Kocken, P. L.; van Dorst, A. G.; Schaalma, H.


    A study into the relevance of cultural factors in predicting condom-use intentions among Antillean migrants in the Netherlands is described in this article. The association between the intention to use condoms with a new sexual partner and a perceived taboo on discussing sex, beliefs about sex education and machismo beliefs on gender and power…

  2. The Context of Military Environments: An Agenda for Basic Research on Social and Organizational Factors Relevant to Small Units


    currently in play ( Samuelson and Zeckhauser, 1988). A related notion is regret avoidance: since people experience greater regret for action than for...for Basic Research on Social and Organizational Factors Relevant to Small Units 56 THE CONTEXT OF MILITARY ENVIRONMENTS Samuelson , W., and R. Zeckhauser

  3. The main but not the accessory olfactory system is involved in the processing of socially relevant chemosignals in ungulates.

    Matthieu eKELLER


    Full Text Available Ungulates like sheep and goats have, like many other mammalian species, two complementary olfactory systems. The relative role played by these two systems has long been of interest regarding the sensory control of social behavior. The study of ungulate social behavior could represent a complimentary alternative to rodent studies because they live in a more natural environment and their social behaviors depend heavily on olfaction. In addition, the relative size of the main olfactory bulb (in comparison to the accessory olfactory bulb is more developped than in many other lissencephalic species like rodents. In this review, we present data showing a clear involvement of the main olfactory system in two well-characterized social situations under olfactory control in ungulates, namely maternal behavior and offspring recognition at birth and the reactivation of the gonadotropic axis of females exposed to males during the anestrous season. In conclusion, we discuss the apparent discrepancy between the absence of evidence for a role of the vomeronasal system in ungulate social behavior and the existence of a developed accessory olfactory system in these species.

  4. Kinetic magnetic-field effect involving the small biologically relevant inorganic radicals NO and O2(·-).

    Karogodina, Tatiana Y; Dranov, Igor G; Sergeeva, Svetlana V; Stass, Dmitry V; Steiner, Ulrich E


    Oxidation of dihydrorhodamine 123 (DHR) to rhodamine 123 (RH) by oxoperoxonitrite (ONOO(-)), formed through recombination of NO and O(2)(·-) radicals resulting from thermal decomposition of 3-morpholinosydnonimine (SIN-1) in buffered aerated aqueous solution at pH 7.6, represents a kinetic model system of the reactivity of NO and O(2)(·-) in biochemical systems. A magnetic-field effect (MFE) on the yield of RH detected in this system is explored in the full range of fields between 0 and 18 T. It is found to increase in a nearly linear fashion up to a value of 5.5±1.6 % at 18 T and 23 °C (3.1±0.7 % at 40 °C). A theoretical framework to analyze the MFE in terms of the magnetic-field-enhanced recombination rate constant k(rec) of NO and O(2)(·-) due to magnetic mixing of T(0) and S spin states of the radical pair by the Δg mechanism is developed, including estimation of magnetic properties (g tensor and spin relaxation times) of NO and O(2)(·-) in aqueous solution, and calculation of the MFE on k(rec) using the theoretical formalism of Gorelik at al. The factor with which the MFE on k(rec) is translated to the MFE on the yield of ONOO(-) and RH is derived for various kinetic scenarios representing possible sink channels for NO and O(2)(·-). With reasonable assumptions for the values of some unknown kinetic parameters, the theoretical predictions account well for the observed MFE.

  5. To be involved or not: factors that influence nurses' involvement in providing treatment decisional support in advanced cancer.

    Barthow, Christine; Moss, Cheryle; McKinlay, Eileen; McCullough, Leslie; Wise, Debbie


    Decisional support is a multifaceted process of facilitating patients' decision making regarding treatment choices. Effective decisional support practices of nurses in relation to the use of anticancer therapies in patients with advanced disease are central to quality cancer care. A recent qualitative descriptive study (n=21) exploring the decision making practices of doctors and nurses in one tertiary cancer centre in New Zealand identified many complexities associated with nurses and their participation in decisional support. The study revealed that cancer nurses had varied opinions about the meaning and importance of their roles in treatment related decision making. This variation was significant and led the researchers to undertake a detailed secondary exploration of factors that impacted on the nurses' involvement in the provision of decisional support. Four key groups of factors were identified. These were factors relating to degree of knowledge, level of experience, beliefs and understandings about nursing roles and cancer therapies, and structural interfaces in the work setting. Understanding these factors is important because it allows modification of the conditions which impact on the ability to provide effective decisional care. It also provides some understanding of clinical drivers associated with nurses' decisional support work with patients who have advanced cancer.

  6. Relevant factors affecting the outcome of ultrasound guided foam sclerotherapy of the great saphenous vein

    Giorgio Falaschi


    Full Text Available Ultrasound guided foam sclerotherapy (UGFS constitutes a valid ablative treatment for superficial vein diseases for the great saphenous vein (GSV, but no standardized protocol for its execution has yet been defined. Different variable factors involved in this procedure influence the final outcome and clinical results. The aim of our study was to analyze the respective influence on efficacy and side effects of three variable factors (foam volume, foam concentration, and contact time between the foam and the endothelium for UGFS procedures for GSV insufficiency in order to select the best protocol for treatment. A retrospective analysis was made of UGFS procedures (190 patients, 201 legs performed for GSV insufficiency in our institute from January 2007 to January 2010. All great saphenous veins included in our study exhibited a trans-ostial reflux and caliber range was 7-11 mm. In all cases, foam was prepared according to the Tessari method, using polidocanol (POL and a gas mixture of CO2 (70% and filtered room air (30%, in a proportion of 1:4. A single injection procedure in the GSV was performed under Doppler ultrasound guidance at mid to lower third of the thigh. Legs were randomly assigned to one of three different treatment protocols: - Group A (71 legs: POL 3%, mean foam volume 4.5 cc, intermittent groin pressure 5 min, supine bed rest 10 min; - Group B (61 legs: POL 2%, mean foam volume 9 cc, intermittent groin pressure 5 min, supine bed rest 10 min; - Group C (69 legs: POL 2%, mean foam volume 9 cc, continuous groin pressure 5 min followed by intermittent groin pressure 5 min, continuous leg compression 5 min, supine bed rest 10 min. Efficacy of treatment and occurrence of side effects were evaluated in each group at two weeks and again at two years after the procedure and the cumulative results compared. Analysis of outcomes did not show any significant difference between the complete obliteration rate (P=0.825 or occurrence of local


    M.A. Nurul Haikal


    Full Text Available This research is conducted to know what factors that influence the students’ involvement in speaking activity in order to practice their speaking skill and what strategies that the teacher used to encourage those external factors. This research uses descriptive qualitative method. There are two instruments used for this research, namely, class observation and interview. Based on the results of class observation and interview, the researcher concludes that teacher factor gives the greatest impact on students’ involvement and the appropriate strategies can support those external factors.

  8. 22. Proteomic Analysis of Differential Protein Expression in vero Cell with Antisense Blocking of Relevant Gene Involved in inhibition of Nontargeted Mutagenesis


    Objective: Recent studies have demonstrated that cells exposed to ionizing radiation or alkylating agents can develop prolonged genetic instability. But its mechanism is still unknown. A cDNA fragment (fragment 9) has been isolated in MNNG-exposed vero cell by mRNA differential display in this lab. After antisense blocking the expression of its relevant gene (fragment 9 related gene, FNR gene), we found that nontargeted mutation frequency induced by MNNG was enhanced significantly. which implicated that the product of the blocked gene may be involved in the inhibition of nontargeted mutation. In order to elucidate the functional mechanism of the FNR gene, we try to separate the proteins from the established cell line expressing antisense fragment 9 to find out the FNR gene-coded protein. Method: The total cellular proteins of MNNG-exposed vero cell transfected with antisense RNA expression plasmid (vero-pM-amp--9-) and those with vector DNA (vero-pM-amp-) were separated by two-dimensional gel electrophoresis, and the resulting maps were analyzed with 2-D analysis software packages to find out the differentially expressed protein spots. Then the related 2-D PAGE database ( was searched according to the protein spots information obtained from 2-DE including the position in the gel, isoelectric point (pl) and molecular weight (Mr). Result: Twelve proteins were specifically expressed only in vero-pM-amp-, and 2 proteins in vero-pM-amp--9-. In addition, there were 24 proteins expressed in higher level in vero-pM-amp--9- as compared with vero-pM-amp- (P<0.05), among them the expression of 7 proteins were enhanced by greater than 5 folds. On the other hand, no sequence similarity was found by homology analysis in GenBank through comparing the fragment 9 with the cDNA sequences of those proteins found in this study. Conclusion: Gene expression alterations bave occurred after antisense blocking of the FNR gene expression as demonstrated by

  9. Generalized Identities Involving Common Factors of Generalized Fibonacci, Jacobsthal and Jacobsthal-Lucas Numbers

    Yashwant K. Panwar


    Full Text Available In this paper, we present generalized identities involving common factors of generalized Fibonacci, Jacobsthal and jacobsthal-Lucas numbers. Binet’s formula will employ to obtain the identities.

  10. School, Neighborhood, and Family Factors Are Associated with Children's Bullying Involvement: A Nationally Representative Longitudinal Study

    Bowes, Lucy; Arseneault, Louise; Maughan, Barbara; Taylor, Alan; Caspi, Ashalom; Moffitt, Terrie E.


    School size and problems with neighbors is associated with a greater risk of being a bullying victim while family factors such as maltreatment and domestic violence are associated with involvement in bullying. The findings are based on the Environmental Risk Longitudinal Twin Study that involves 2,232 children.

  11. Perceptions of Risk Factors for Female Gang Involvement among African American and Hispanic Women.

    Walker-Barnes, Chanequa J.; Mason, Craig A.


    Female minority students at an urban alternative high school completed interviews regarding perceptions of risk factors for female gang involvement. Peer pressure was the largest influence on female gang involvement. Respondents believed girls might turn to gangs for protection from neighborhood crime, abusive families, and other gangs. Lack of…

  12. Factors involved in the etiology of temporomandibular disorders - a literature review



    Background and aim This review aims at presenting a current view on the most frequent factors involved in the mechanisms causing temporomandibular disorders (TMD). Method We conducted a critical review of the literature for the period January 2000 to December 2014 to identify factors related to TMD development and persistence. Results The etiology of TMD is multidimensional: biomechanical, neuromuscular, bio-psychosocial and biological factors may contribute to the disorder. Occlusal overloading and parafunctions (bruxism) are frequently involved as biomechanical factors; increased levels of estrogen hormones are considered biological factors affecting the temporo-mandibular-joint. Among bio-psychosocial factors, stress, anxiety or depression, were frequently encountered. Conclusions The etiopathogenesis of this condition is poorly understood, therefore TMDs are difficult to diagnose and manage. Early and correct identification of the possible etiologic factors will enable the appropriate treatment scheme application in order to reduce or eliminate TMDs debilitating signs and symptoms. PMID:26732121

  13. Relevance of risk factors of breast cancer in women: An Eastern Indian scenario

    Ranen Kanti Aich


    Conclusion: Risk factors for breast cancer do not differ significantly between developed and developing countries. Hence appropriate time has come for developing countries to incorporate breast cancer risk factors in health education and to consider pharmacological interventions in high risk women.

  14. [Stationary thromboprophylaxis in casualty surgery. Relevance of postoperative mobility and preexisting risk factors].

    Eisele, R; Maier, E; Kinzl, L; Gude, U


    The presented thromboprophylactic concept includes weight bearing and ankle motion as well as breathing therapy and drug prophylaxis (antiphlogistics, analgesic drugs, heparin). Routinely performed ultrasound screening of the deep veins (legs and pelvis) before release showed a low DVT incidence of 2.5% in a prospective clinical observation of 841 inpatients. Obesity, venous insufficiency, and a history of previous thromboembolic events were associated with a significantly increased risk of thrombosis (relative risk 4.1, 4,9, and 5.8, respectively) The duration of immobilization also had a relevant influence indicating that early postoperative physiotherapy in traumatology and orthopedic surgery has a widely underestimated thromboprophylactic effect.

  15. Factors influencing the degree and pattern of parental involvement in play therapy for sexually abused children.

    Hill, Andrew


    Although much has been written about the role of therapists in children's recovery from child sexual abuse, relatively little attention has been paid to the role of nonoffending parents. This study investigated the work of a team of therapists who sometimes included such parents in therapy sessions with children. The study sought to understand what factors were influencing the degree and pattern of parental involvement and to understand what effect these patterns of parental involvement were having on the process and outcomes of therapy. The study successfully identified a range of factors influencing the patterns of parental involvement, but more research will be needed to understand the effect on outcomes.

  16. Qualitative analysis of factors that increase and reduce involvement in gambling



    Full Text Available During the rapid development of gambling business, the number of pathological gamblers is increasing as well. The problem of pathological gambling is just as important as alcoholism or drug addiction. However, there is a lack of information and research of this topicin Lithuania. The aim of work: to investigate and analyse the factors that increase or reduce involvement in gambling. Research questions: 1 What factors increase involvement in gambling? 2 What factors reduce involvement in gambling? Critical case sampling was used for selection of the participants. Subjects were required to a have experience of involvement in gambling for at least one year; b have experience of negative impact of gambling on quality of life; c have at least 6 months of gambling abstinence. Five individuals participated in the research; all of them were males who live in Vilnius. Age of the participants varied from 19 to 45. Semi-structured interviews were used to collect data. Interviews were recorded and transcribed verbatim. The matic analysis of the data led to the identification of four major the matic categories: psychological factors; social relations; material well being; quality of life. There search results show that negatyve childhood experience, gambling friends, escaping from various troubles, disputes in family and high financial needs can increase involvement in gambling. Factors that reduce involvement in gambling are: feeling support of social environment, proper evaluation of financial position, awareness of one‘s own addiction to gambling and desire to change life.

  17. Factors associated with involvement in nonmetropolitan LGBTQ organizations: Proximity? Generativity? Minority stress? Social location?

    Paceley, Megan S; Oswald, Ramona Faith; Hardesty, Jennifer L


    Little is known about involvement in LGBTQ organizations. Factors associated with involvement in nonmetropolitan LGBTQ organizations were examined using logistic regression and survey data from 426 LGBTQ individuals residing in a nonmetropolitan region. Involvement was examined in five types of organizations (professional, social/recreational, religious, political, and community center/charity). The same model testing proximity, generativity, minority stress, and social location hypotheses was repeated for each organization type. Results demonstrate that the generativity hypothesis is most strongly supported. Indeed, emotional attachment to the LGBTQ community significantly increased the odds of involvement in every type of organization. However, the factors associated with involvement otherwise differed by organization type. Implications for organizational leaders are discussed.

  18. Factors Involved in Iranian Women Heads of Household's Health Promotion Activities: A Grounded Theory Study.

    Rafii, Forough; Seyedfatemi, Naima; Rezaei, Mahboubeh


    We aimed to explore and describe the factors involved in Iranian women heads of household's health promotion activities. Grounded theory was used as the method. Sixteen women heads of household were recruited. Data were generated by semi structured interviews. Our findings indicated that remainder of resources (money, time and energy) alongside perceived severity of health risk were two main factors whereas women's personal and socio-economic characteristics were two contextual factors involved in these women's health promotion activities. To help these women improve their health status, we recommended that the government, non-governmental organizations and health care professionals provide them with required resources and increase their knowledge by holding training sessions.

  19. Factors involved in the etiology of temporomandibular disorders - a literature review



    Background and aim This review aims at presenting a current view on the most frequent factors involved in the mechanisms causing temporomandibular disorders (TMD). Method We conducted a critical review of the literature for the period January 2000 to December 2014 to identify factors related to TMD development and persistence. Results The etiology of TMD is multidimensional: biomechanical, neuromuscular, bio-psychosocial and biological factors may contribute to the disorder. Occlusal overload...

  20. [Occurrence and diagnostic relevance of virulence-associated factors in Streptococcus suis].

    Baums, C G; Da Silva, L M; Goethe, R; Valentin-Weigand, P


    Streptococcus suis (Sc. suis) can cause very different clinical entities. In contrast to Sc. suis-associated pneumonia, the induction of meningitis, septicemia, and polyarthritis by certain Sc. suis strains requires the expression of virulence factors that contribute to the invasiveness of the pathogen. In the presented study, we examined the occurrence of known virulence-associated factors in Sc. suis isolates from samples sent to the Institute of Microbiology, School of Veterinary Medicine Hannover, in order to evaluate their significance as potential virulence factors in different disease complexes in Northern Germany. The results show that (i) MRP + EF + serotype 2 and MRP* EF-serotype 9 strains are statistically significant associated with the disease complex meningitis/septicemia/arthritis and, thus, have to be considered invasive strains, (ii) serotyping alone is not sufficient for identification of virulent strains, (iii) there is a remarkable heterogeneity among pneumonia-associated Sc. suis strains and (iv) activity of haemolysin or suilysin appears to be not appropriate as virulence marker. Finally, it has to be noted that at present only half of the Sc. suis isolates from pigs with meningitis/septicemia/poyarthritis can be characterised by the detection of virulence-associated factors. Thus, the identification and characterisation of additional, serotype independent virulence factors of Sc. suis is a very important issue in future studies.

  1. On the relevance of assumptions associated with classical factor analytic approaches.

    Kasper, Daniel; Unlü, Ali


    A personal trait, for example a person's cognitive ability, represents a theoretical concept postulated to explain behavior. Interesting constructs are latent, that is, they cannot be observed. Latent variable modeling constitutes a methodology to deal with hypothetical constructs. Constructs are modeled as random variables and become components of a statistical model. As random variables, they possess a probability distribution in the population of reference. In applications, this distribution is typically assumed to be the normal distribution. The normality assumption may be reasonable in many cases, but there are situations where it cannot be justified. For example, this is true for criterion-referenced tests or for background characteristics of students in large scale assessment studies. Nevertheless, the normal procedures in combination with the classical factor analytic methods are frequently pursued, despite the effects of violating this "implicit" assumption are not clear in general. In a simulation study, we investigate whether classical factor analytic approaches can be instrumental in estimating the factorial structure and properties of the population distribution of a latent personal trait from educational test data, when violations of classical assumptions as the aforementioned are present. The results indicate that having a latent non-normal distribution clearly affects the estimation of the distribution of the factor scores and properties thereof. Thus, when the population distribution of a personal trait is assumed to be non-symmetric, we recommend avoiding those factor analytic approaches for estimation of a person's factor score, even though the number of extracted factors and the estimated loading matrix may not be strongly affected. An application to the Progress in International Reading Literacy Study (PIRLS) is given. Comments on possible implications for the Programme for International Student Assessment (PISA) complete the presentation.

  2. Clusters of Factors Identify A High Prevalence of Pregnancy Involvement Among US Adolescent Males.

    Lau, May; Lin, Hua; Flores, Glenn


    The study purpose was to use recursive partitioning analysis (RPA) to identify factors that, when clustered, are associated with a high prevalence of pregnancy involvement among US adolescent males. The National Survey of Family Growth is a nationally representative survey of individuals 15-44 years old. RPA was done for the 2002 and 2006-2010 cycles to identify factors which, when combined, identify adolescent males with the highest prevalence of pregnancy involvement. Pregnancy-involvement prevalence among adolescent males was 6 %. Two clusters of adolescent males have the highest pregnancy-involvement prevalence, at 84-87 %. In RPA, the highest pregnancy-involvement prevalence (87 %) was seen in adolescent males who ever HIV tested, had >4 lifetime sexual partners, reported less than an almost certain chance of feeling less physical pleasure with condom use, had an educational attainment of 4 lifetime sexual partners, reported less than an almost certain chance of feeling less physical pleasure with condom use, had an educational attainment ≥11th grade, were >17 years old, and had their first contraceptive education ≥10th grade, had a pregnancy-involvement prevalence of 84 %. Pregnancy-prevention efforts among adolescent males who have been involved in a pregnancy may need to target risk factors identified in clusters with the highest pregnancy prevalence to prevent subsequent pregnancies in these adolescent males and improve their future outcomes.

  3. Research on relevant factors affecting results of extubation of trachea cannula in neurocritical care patients



    Objective To explore the relative factors which caused the extubation failure in neurological intensive care unit(NICU). Methods It was a retrospective study. 40 cases of patients who met the criteria,were brought into statistical analysis. They were admitted in NICU in

  4. Physical interactions among plant MADS-box transcription factors and their biological relevance

    Nougalli Tonaco, I.A.


    The biological interpretation of the genome starts from transcription, and many different signaling pathways are integrated at this level. Transcription factors play a central role in the transcription process, because they select the down-stream genes and determine their spatial and temporal

  5. Physical interactions among plant MADS-box transcription factors and their biological relevance

    Nougalli Tonaco, I.A.


    The biological interpretation of the genome starts from transcription, and many different signaling pathways are integrated at this level. Transcription factors play a central role in the transcription process, because they select the down-stream genes and determine their spatial and temporal expres

  6. The Assessment of the Likelihood of Mammography Usage with Relevant Factors among Women with Disabilities

    Kung, Pei-Tseng; Tsai, Wen-Chen; Chiou, Shang-Jyh


    Research that identifies the determinants of low mammography use among disabled people is scant. This study examines the determining factors related to the low usage of mammography among women with disabilities. To identify the barriers that prevent women with disabilities from participating in mammography screening can help authorities conceive…


    The goal of this U.S. Environmental Protection Agency (EPA) study is to characterize activity patterns, physiological changes, and environmental exposures for the aging population. Meta analysis was performed on more than 2000 reviewed articles to evaluate the lifestyle factors ...

  8. De novo characterization of the spleen transcriptome of the large yellow croaker (Pseudosciaena crocea) and analysis of the immune relevant genes and pathways involved in the antiviral response

    Mu, Yinnan


    The large yellow croaker (Pseudosciaena crocea) is an economically important marine fish in China. To understand the molecular basis for antiviral defense in this species, we used Illumia paired-end sequencing to characterize the spleen transcriptome of polyriboinosinic:polyribocytidylic acid [poly(I:C)]-induced large yellow croakers. The library produced 56,355,728 reads and assembled into 108,237 contigs. As a result, 15,192 unigenes were found from this transcriptome. Gene ontology analysis showed that 4,759 genes were involved in three major functional categories: biological process, cellular component, and molecular function. We further ascertained that numerous consensus sequences were homologous to known immune-relevant genes. Kyoto Encyclopedia of Genes and Genomes orthology mapping annotated 5,389 unigenes and identified numerous immune-relevant pathways. These immune-relevant genes and pathways revealed major antiviral immunity effectors, including but not limited to: pattern recognition receptors, adaptors and signal transducers, the interferons and interferon-stimulated genes, inflammatory cytokines and receptors, complement components, and B-cell and T-cell antigen activation molecules. Moreover, the partial genes of Toll-like receptor signaling pathway, RIG-I-like receptors signaling pathway, Janus kinase-Signal Transducer and Activator of Transcription (JAK-STAT) signaling pathway, and T-cell receptor (TCR) signaling pathway were found to be changed after poly(I:C) induction by real-time polymerase chain reaction (PCR) analysis, suggesting that these signaling pathways may be regulated by poly(I:C), a viral mimic. Overall, the antivirus-related genes and signaling pathways that were identified in response to poly(I:C) challenge provide valuable leads for further investigation of the antiviral defense mechanism in the large yellow croaker. © 2014 Mu et al.

  9. Molecular genetic analysis of activation-tagged transcription factors thought to be involved in photomorphogenesis

    Neff, Michael M.


    This is a final report for Department of Energy Grant No. DE-FG02-08ER15927 entitled “Molecular Genetic Analysis of Activation-Tagged Transcription Factors Thought to be Involved in Photomorphogenesis”. Based on our preliminary photobiological and genetic analysis of the sob1-D mutant, we hypothesized that OBP3 is a transcription factor involved in both phytochrome and cryptochrome-mediated signal transduction. In addition, we hypothesized that OBP3 is involved in auxin signaling and root development. Based on our preliminary photobiological and genetic analysis of the sob2-D mutant, we also hypothesized that a related gene, LEP, is involved in hormone signaling and seedling development.

  10. Mechanistic basis and clinical relevance of the role of transforming growth factor-βin cancer

    Run-Long Lin; Lu-Jun Zhao


    Transforming growth factor-β(TGF-β) is a key factor in cancer development and progression. TGF-βcan suppress tumorigenesis by inhibiting cell cycle progression and stimulating apoptosis in early stages of cancer progression. However, TGF-βcan modulate cancer-related processes, such as cell invasion, distant metastasis, and microenvironment modiifcation that may be used by cancer cells to their advantage in late stages. Corresponding mechanisms include angiogenesis promotion, anti-tumor immunity suppression, and epithelial-to-mesenchymal transition (EMT) induction. hTe correlation between TGF-βexpression and cancer prognosis has also been extensively investigated. Results suggest that TGF-βpathway can be targeted to treat cancer;as such, the feasibility of this treatment is investigated in clinical trials.

  11. Microbial Relevant Fouling in Membrane Bioreactors: Influencing Factors, Characterization, and Fouling Control

    Anthony G. Fane; Bing Wu


    Microorganisms in membrane bioreactors (MBRs) play important roles on degradation of organic/inorganic substances in wastewaters, while microbial deposition/growth and microbial product accumulation on membranes potentially induce membrane fouling. Generally, there is a need to characterize membrane foulants and to determine their relations to the evolution of membrane fouling in order to identify a suitable fouling control approach in MBRs. This review summarized the factors in MBRs that inf...

  12. Relevance of hemostatic risk factors on coronary morphology in patients with diabetes mellitus type 2

    Peters Ansgar J


    Full Text Available Abstract Objective The influence hemostatitc parameters on the morphological extent and severity of coronary artery disease were studied in patients with and without DM type 2. Background It is known that patients with diabetes (DM have abnormal metabolic and hemostatic parameters Methods Of 150 consecutive patients with angiographically proven coronary artery disease 29 presented with DM. Additionally to parameters of lipid-metabolism fibrinogen, tissue-plasminogenactivator (t-PA, plasminogen-activator-inhibitor (PAI, plasmin-a-antiplasmin (PAP, prothrombin-fragment 1+2 (F1+2, thrombin-antithrombin (TAT, von-willebrand-factor (vWF, platelet factor 4 (PF4, glykomembranproteine 140 (GMP140 and the rheologic parameters plasma viscosity and red blood cell aggregation were evaluated. The extent and severity of CAD was evaluated according to the criteria of the American Heart Association. Results Patients with DM presented with a higher number of conventional risk factors as compared to non-diabetic patients. Additionally there were significant differences for F1+2, red blood cell aggregation and PAI. Diabetic patients showed a more severe extent of coronary arteriosclerosis, which also could be found more distally. A significant relationship between blood-glucose, thrombocyte-activation (vWF, endogenous fibrinolysis (PAI and the severity of CAD and a more distal location of stenoses could be found (r = 0.6, p Conclusion Patients with coronary artery disease and DM type 2 showed marked alterations of metabolic, hemostatic, fibrinolytic and rheologic parameters, which can produce a prothrombogenic state. A direct association of thrombogenic factors on coronary morphology could be shown. This can be the pathophysiologic mechanism of more severe and distal pronounced coronary atherosclerosis in these patients.

  13. A teacher-centered exploration of the relevance of social factors to theory of mind development.

    Wright, Barlow C; Mahfoud, Janina


    Many accounts of children's Theory of Mind (ToM) development favor a cognitive explanation, for example, in terms of mental representational improvements at or before 4 years. Here, we investigated whether social factors as rated by a child's teacher, are related to ToM development. We tested 82 children of 3-6 years on each of four ToM tasks, and their class teacher completed a social questionnaire about each child's playing behavior, sharing, talkativeness, confidence, aggressiveness and outgoingness. A measure of task memory and the child's gender were also recorded. Here, children generally passed ToM tasks after 5 years-old, but no one gender performed reliably better than the other. Teacher-rated confidence and playing behavior were correlated to ToM. But in a regression analysis, these were replaced by teacher-rated talkativeness; with age and memory given primacy in both sets of analyses. It is concluded that maturation and cognitive factors may well have primacy but social factors, facilitated during early primary education, must also be given a role in ToM development.

  14. Clinical Relevance of Environmental Factors in the Pathogenesis of Autoimmune Thyroid Disease

    Wilmar M. Wiersinga


    Full Text Available Genetic factors contribute for about 70% to 80% and environmental factors for about 20% to 30% to the pathogenesis of autoimmune thyroid disease (AITD. Relatives of AITD patients carry a risk to contract AITD themselves. The 5-year risk can be quantified by the so-called Thyroid Events Amsterdam-score, based on serum thyroid-stimulating hormone, thyroid peroxidase (TPO-antibodies and family history. Subjects at risk may ask what they can do to prevent development of AITD. This review summarizes what is known about modulation of exposure to environmental factors in terms of AITD prevention. To stop smoking decreases the risk on Graves disease but increases the risk on Hashimoto disease. Moderate alcohol intake provides some protection against both Graves and Hashimoto disease. Low selenium intake is associated with a higher prevalence of thyroid autoimmunity, but evidence that selenium supplementation may lower TPO antibodies and prevent subclinical hypothyroidism remains inconclusive. Low serum vitamin D levels are associated with a higher prevalence of TPO antibodies, but intervention studies with extra vitamin D have not been done yet. Stress may provoke Graves hyperthyroidism but not Hashimoto thyroiditis. Estrogen use have been linked to a lower prevalence of Graves disease. The postpartum period is associated with an increased risk of AITD. Taking together, preventive interventions to diminish the risk of AITD are few, not always feasible, and probably of limited efficacy.

  15. Factors associated with sex work involvement among transgender women in Jamaica: a cross-sectional study

    Carmen H Logie


    Conclusions: Findings reveal high HIV infection rates among transgender women in Jamaica. Sex work-involved participants experience social and structural drivers of HIV, including violence, stigma, and unemployment. Transgender women involved in transactional sex also experience high rates of incarceration, forced sex and homelessness in comparison with non-sex workers. Taken together, these findings suggest that social ecological factors elevate HIV exposure among sex work-involved transgender women in Jamaica. Findings can inform interventions to advance human rights and HIV prevention and care cascades with transgender women in Jamaica.

  16. Distinctive Risk Factors and Phenotype of Younger Patients With Resistant Hypertension: Age Is Relevant.

    Ghazi, Lama; Oparil, Suzanne; Calhoun, David A; Lin, Chee Paul; Dudenbostel, Tanja


    Resistant hypertension, defined as blood pressure >140/90 mm Hg despite using ≥3 antihypertensive medications, is a well-recognized clinical entity. Patients with resistant hypertension are at an increased risk of cardiovascular disease compared with those with more easily controlled hypertension. Coronary heart disease mortality rates of younger adults are stagnating or on the rise. The purpose of our study was to characterize the phenotype and risk factors of younger patients with resistant hypertension, given the dearth of data on cardiovascular risk profile in this cohort. We conducted a cross-sectional analysis with predefined age groups of a large, ethnically diverse cohort of 2170 patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. Patients (n=2068) met the inclusion criteria and were classified by age groups, that is, ≤40 years (12.7% of total cohort), 41 to 55 years (32.1%), 56 to 70 years (36.1%), and ≥71 years (19.1%). Patients aged ≤40 years compared with those aged ≥71 years had significantly earlier onset of hypertension (24.7±7.4 versus 55.0±14.1 years; Phypertension, younger individuals have a distinct phenotype characterized by overlapping risk factors and comorbidities, including obesity, high aldosterone, and high dietary sodium intake compared with elderly. © 2017 American Heart Association, Inc.

  17. Some relevant factors in the consumption and non consumption of nicotine in adolescence

    Alfonso Palmer


    Full Text Available Tobacco is the second most consumed substance among Spanish adolescents and its effects on health are well known. The aim of this study is to analyze the predictor value of different personal, family and environmental factors on tobacco consumption in the adolescent population using appropriate modelling techniques and strategies included in Data Mining. The total sample is made up of 9,300 students aged between 14 and 18 years. The adolescents anonymously answered a questionnaire which asked about the frequency of use of addictive substances as well as a series of psychosocial variables. Tobacco consumption by friends, frequency of nights out, age, production of prohibited, impulsive behaviour and the control exerted by parents bear a statistically significant influence on the number of cigarettes consumed per week and constitute risk factors for initiating consumption. Future studies should analyze, using the techniques proposed in this work and longitudinal studies, whether the tougher anti-smoking laws have been transformed into a decrease in tobacco consumption in adolescents.

  18. [Analysis of the relevant factors for recurrent sudden sensorineural hearing loss].

    Liang, H; Zhong, S X


    Objective: To investigate the possible factors related to recurrence and prognosis of sudden sensorineural hearing loss(SSNHL). Methods: Four hundred and ninety-five patients with unilateral sudden sensorineural hearing loss between January 2013 to April 2014 were analyzed retrospectively(34 patients lost to follow-up with a dropout rate of 6.87%). Twenty of the 495 patients were diagnosed as recurrent SSNHL and treated again in the same hospital. The data of the patients were summarized to analyze the related factors which might influence the recurrence and prognosis of SSNHL. Results: In the 20 patients with recurrent SSNHL, 19 had the second attack in same ear as the first attack, and the other one had in both ears. There were seven male patients, and thirteen female patients. Patients ranged in age from 24 to 77years, with a median age of 39.5 years. Types of hearing loss: low frequency in eight patients, high frequency in two patients, flat frequency in eight patients, total deafness in two patients, the types of the second attack in 17 patients were same as the first attack, only one patient was changed from total deafness to flat frequency, one case was changed from flat frequency to high frequency, one case changed from flat frequency to total deafness. The intervals between of the first attack time and the second attack time were 1-36 months with the median time of 3.5 months. After systemic oral and (or) transtympanic steroid treatment, recovered in three cases, effective in three cases and 14 cases invalid, the cure rate was 15%, and the total effective rate was 30%. There were statistically significant differences in the recovery rate(χ(2)=8.640, Phearing loss except low frequency type, the treatment effect was invalid. The patients with hearing loss at low frequency had the best outcomes. The total effective rates were significant different between patients younger and old than 34 years old(P0.05). The recurrence rates of patients with various types

  19. First recurrence of Clostridium difficile infection: clinical relevance, risk factors, and prognosis.

    Larrainzar-Coghen, T; Rodriguez-Pardo, D; Puig-Asensio, M; Rodríguez, V; Ferrer, C; Bartolomé, R; Pigrau, C; Fernández-Hidalgo, N; Pumarola, T; Almirante, B


    Therapy for recurrent Clostridium difficile-associated diarrhea (CDAD) is challenging. We evaluated the frequency, associated risk factors, and prognosis of first CDAD recurrences. Prospective cohort study of all consecutive cases of primary CDAD diagnosed in a university hospital from January 2006 to June 2013. Recurrent infection was defined as reappearance of symptoms within 8 weeks of the primary diagnosis, provided that CDAD symptoms had previously resolved and a new toxin test was positive. Predictors of a first episode of recurrent CDAD were determined by logistic regression analysis. In total, 502 patients (51.6 % men) with a mean age of 62.3 years (SD 18.5) had CDAD; 379 (76 %) were cured, 61 (12 %) had a first recurrence, 52 (10 %) died within 30 days of the CDAD diagnosis, nine (2 %) required colectomy, and one was lost to follow-up. Among the 61 patients with a first recurrence, 36 (59.3 %) were cured, 15 (23.7 %) had a second recurrence, nine (15.3 %) died, and one (1.7 %) required colectomy. On multivariate analysis, age older than 65 years (OR 2.04; 95 % CI, 1.14-3.68; P predictors of a first recurrence. A risk score was developed for first CDAD recurrence using the predictive factors and selected biological variables. In our CDAD cohort, 12 % of patients had a first recurrence of this disease, in which the prognosis was less favorable than that of the primary episode, as it heralded a higher risk of additional recurrences. Patient age and enteral nutrition were predictors of a first recurrence.

  20. On the selection of relevant environmental factors to predict microbial dynamics in solidified media.

    Theys, T E; Geeraerd, A H; Devlieghere, F; Van Impe, J F


    Several studies have shown that food structure causes slower growth rates and narrower growth boundaries of bacteria compared to laboratory media. In predictive microbiology, both a(w) or corresponding solute concentration (mainly NaCl) have been used as a growth influencing factor for kinetic models or growth/no growth interface models. The majority of these models have been based on data generated in liquid broth media with NaCl as the predominant a(w) influencing solute. However, in complex food systems, other a(w) influencing components might be present, next to NaCl. In this study, the growth rate of Salmonella typhimurium was studied in the growth region and the growth/no growth response was tested in Tryptic Soy Broth at 20 degrees C at varying gelatin concentration (0, 10, 50 g L(-1) gelatin), pH (3.25-5.5) and water activity (a(w)) (0.929-0.996). From the viewpoint of water activity, the results suggest that NaCl is the main a(w) affecting compound. However, gelatin seemed to have an effect on medium a(w) too. Moreover, there is also an interaction effect between NaCl and gelatin. From the microbial viewpoint, the results confirmed that the a(w) decreasing effect of gelatin is less harmful to cells than the effect of Na(+) ions. The unexpected shift of the growth/no growth interface to more severe conditions when going from a liquid medium to a medium with 10 g L(-1) gelatin is more pronounced when formulating the models in terms of a(w) than in terms of NaCl concentrations. At 50 g L(-1) gelatin, the model factored with NaCl concentration shifts to milder conditions (concordant to literature results) while the model with a(w) indicates a further shift to more severe conditions, which is due to the water activity lowering effect of gelatin and the interaction between gelatin and NaCl. The results suggest that solute concentration should be used instead of a(w), both for kinetic models in the growth region and for growth/no growth interface models, if the

  1. Temporomandibular joint involvement as a positive clinical prognostic factor in necrotising external otitis.

    Yeheskeli, E; Eta, R Abu; Gavriel, H; Kleid, S; Eviatar, E


    Necrotising otitis externa is associated with high morbidity and mortality rates. This study investigated whether temporomandibular joint involvement had any prognostic effect on the course of necrotising otitis externa in patients who had undergone hyperbaric oxygen therapy after failed medical and sometimes surgical therapy. A retrospective case series was conducted of patients in whom antibiotic treatment and surgery had failed, who had been hospitalised for further treatment and hyperbaric oxygen therapy. Twenty-three patients with necrotising otitis externa were identified. The temporomandibular joint was involved in four patients (17 per cent); these patients showed a constant gradual improvement in C-reactive protein and were eventually discharged free of disease, except one patient who was lost to follow up. Four patients (16 per cent) without temporomandibular joint involvement died within 90 days of discharge, while all patients with temporomandibular joint involvement were alive. Three patients (13 per cent) without temporomandibular joint involvement needed recurrent hospitalisation including further hyperbaric oxygen therapy; no patients with temporomandibular joint involvement required such treatment. Patients with temporomandibular joint involvement had lower rates of recurrent disease and no mortality. Therefore, we suggest considering temporomandibular joint involvement as a positive prognostic factor in necrotising otitis externa management.

  2. socio-cultural factors influencing male involvement in home-based ...


    Aug 8, 2011 ... East African Medical Journal Vol. 88 No. 8 August ... Objective: To investigate socio-cultural factors that influence male involvement in ... 59.7% of the respondents had not received formal training on home-based care. Those.

  3. Socio-cultural factors influencing male involvement in home-based ...

    Socio-cultural factors influencing male involvement in home-based care for people living with HIV and ... East African Medical Journal ... of close relatives and 59.7% of the respondents had not received formal training on home-based care.

  4. School, neighborhood, and family factors are associated with children's bullying involvement: a nationally representative longitudinal study.

    Bowes, Lucy; Arseneault, Louise; Maughan, Barbara; Taylor, Alan; Caspi, Avshalom; Moffitt, Terrie E


    To test whether school, neighborhood, and family factors are independently associated with children's involvement in bullying, over and above their own behaviors that may increase their risk for becoming involved in bullying. We examined bullying in the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative 1994-1995 birth cohort of 2,232 children. We used mother and teacher reports to identify children who experienced bullying between the ages of 5 and 7 years either as victims, bullies, or bully-victims. We collected information about school characteristics from the Department for Children, Schools and Families. We collected reports from mothers about children's neighborhood and home environments and reports from mothers and teachers about children's internalizing and externalizing problems when they were 5 years old. Multinomial logistic regressions showed that over and above other socioenvironmental factors and children's behavior problems, school size was associated with an increased risk for being a victim of bullying, problems with neighbors was associated with an increased risk for being a bully-victim, and family factors (e.g., child maltreatment, domestic violence) were associated with all groups of children involved in bullying. Socioenvironmental factors are associated with children's risk for becoming involved in bullying over and above their own behaviors. Intervention programs aimed at reducing bullying should extend their focus beyond schools to include local communities and families.

  5. Factors Affecting the Involvement of Teachers in Guidance and Counselling as a Whole-School Approach

    Lam, Sarah K. Y.; Hui, Eadaoin K. P.


    This study explores factors affecting the involvement of regular secondary school teachers in the whole-school approach to guidance and counselling by interviewing 12 secondary school teachers in Hong Kong. Emerging themes include teachers' ownership of their role in student guidance and counselling, the alignment of their disposition with…

  6. Molecular characterization of Candida in the oral cavity and factors involved in biofilm formation and virulence

    Kraneveld, E.A.


    The research described in this thesis addresses current issues related to oral Candida infections. Interactions of Candida with the oral microbiome were characterized and factors involved in biofilm formation and virulence were studied. All in all, the work described in this thesis contributes

  7. Analysis of the Internal and External Factors Involved in Second Language Acquisition



    Materialist dialectics holds that internal causes are the basis of change and the external causes are the condition of change, and that external causes become operative through internal causes. This law can be applied into SLA. The internal causes and external causes influence SLA gready. This paper mainly discusses the factors involved in SLA process.

  8. Personal and Situational Factors Affecting Exercise Involvement: The Importance of Enjoyment.

    Wankel, Leonard M.


    Interviews were conducted with participants and dropouts of a male employee fitness program in order to investigate factors affecting involvement. A combination of items pertaining to reactions to the program, initial goals for joining, and social support for the program could effectively discriminate between participants and dropouts. (Author/MT)

  9. Risk Factors Associated with Renal Involvement in Childhood Henoch-Schönlein Purpura: A Meta-Analysis

    Chan, Han; Tang, Yan-Ling; Lv, Xiao-Hang; Zhang, Gao-Fu; Wang, Mo; Yang, Hai-Ping; Li, Qiu


    Background and objective Henoch-Schönlein purpura (HSP) is an important cause of chronic kidney disease in children. This meta-analysis identified risk factors associated with renal involvement in childhood HSP. Methods PubMed, Embase, and Web of Science were searched. The quality of all eligible studies was assessed using the Newcastle-Ottawa scale criteria. An analysis of possible risk factors was conducted to report the odds ratio (OR) and weighted mean difference (WMD). Results Thirteen studies (2398 children) revealed 20 possible and 13 significant risk factors associated with renal involvement in HSP, with the following meta-analysis estimates of OR and WMD, with 95% confidence intervals: older age (0.90, 0.61–1.19); age > 10 y (3.13, 1.39–7.07); male gender (1.36, 1.07–1.74); abdominal pain (1.94,1.24–3.04); gastrointestinal bleeding (1.86, 1.30–2.65); severe bowel angina (3.38, 1.17–9.80); persistent purpura (4.02, 1.22–13.25); relapse (4.70, 2.42–9.14); WBC > 15 × 109/L (2.42, 1.39–4.22); platelets > 500 × 109/L (2.98, 1.22–7.25); elevated antistreptolysin O (ASO) (2.17, 1.29–3.64); and decreased complement component 3 (C3) (3.13, 1.62–6.05). Factors not significantly associated with renal involvement were: blood pressure; orchitis; elevated C-reactive protein; elevated erythrocyte sedimentation rate (ESR); and elevated serum IgA/IgE or IgG. Arthritis/arthralgia may be a risk factor according to the criteria of the American College of Rheumatology (1.41, 1.01–1.96). Conclusion The following are associated with renal involvement in pediatric HSP: male gender; > 10 y old; severe gastrointestinal symptoms (abdominal pain, gastrointestinal bleeding, and severe bowel angina); arthritis/arthralgia; persistent purpura or relapse; WBC > 15 × 109/L; platelets > 500 × 109/L; elevated ASO; and low C3. Relevant clinical interventions for these risk factors may exert positive effects on the prevention of kidney disease during the early

  10. Glucocorticoid regulation of brain-derived neurotrophic factor: relevance to hippocampal structural and functional plasticity.

    Suri, D; Vaidya, V A


    Glucocorticoids serve as key stress response hormones that facilitate stress coping. However, sustained glucocorticoid exposure is associated with adverse consequences on the brain, in particular within the hippocampus. Chronic glucocorticoid exposure evokes neuronal cell damage and dendritic atrophy, reduces hippocampal neurogenesis and impairs synaptic plasticity. Glucocorticoids also alter expression and signaling of the neurotrophin, brain-derived neurotrophic factor (BDNF). Since BDNF is known to promote neuroplasticity, enhance cell survival, increase hippocampal neurogenesis and cellular excitability, it has been hypothesized that specific adverse effects of glucocorticoids may be mediated by attenuating BDNF expression and signaling. The purpose of this review is to summarize the current state of literature examining the influence of glucocorticoids on BDNF, and to address whether specific effects of glucocorticoids arise through perturbation of BDNF signaling. We integrate evidence of glucocorticoid regulation of BDNF at multiple levels, spanning from the well-documented glucocorticoid-induced changes in BDNF mRNA to studies examining alterations in BDNF receptor-mediated signaling. Further, we delineate potential lines of future investigation to address hitherto unexplored aspects of the influence of glucocorticoids on BDNF. Finally, we discuss the current understanding of the contribution of BDNF to the modulation of structural and functional plasticity by glucocorticoids, in particular in the context of the hippocampus. Understanding the mechanistic crosstalk between glucocorticoids and BDNF holds promise for the identification of potential therapeutic targets for disorders associated with the dysfunction of stress hormone pathways.

  11. Determining success factors for effective strategic change: Role of middle managers' strategic involvement

    Minhajul Islam Ukil


    Full Text Available Middle managers are believed to play most crucial part in strategic change that in consequence leads to organizational success. The present study seeks to identify the underlying success factors for effective strategic change and, to investigate the relationship between middle management strategic involvement and effective strategic change. Data were collected following a survey administered among a group of mid-level managers (N=144 serving in twenty different private commercial banks in Bangladesh, and analyzed using various statistical tests including descriptive analysis, Pearson correlation, and simple and multiple regressions in STATA. Results uncovers that factors like relation with top management, strategy, role and skills are essential for effective strategic change. This study also reveals significant relationship between middle management strategic involvement and effective strategic change. Findings of this research suggest that organizations shall involve mid-level managers to formulate and implement strategy since middle mangers work as a bridge between top management and ground level workers.

  12. The Potential Risk Factors Relevant to Lateral Epicondylitis by Wrist Coupling Posture.

    Su-Ya Lee

    Full Text Available The use of awkward wrist postures and unskilled techniques might induce lateral epicondylitis. This study thus investigated the effects of wrist deviation combined with extension and movement velocity on the dynamic performances of the wrist muscles during the coupling posture via a custom-made bi-planar isokinetic dynamometer. Thirty subjects were recruited to perform the isokinetic testing. We measured the muscle strengths and activities for the wrist extensors and flexors during concentric and eccentric contractions at three movement velocities, 30°s-1, 90°s-1, and 180°s-1, combined with three wrist postures, neutral position (NP, radial deviation (RD, and ulnar deviation (UD. The root mean square (RMS of the electromyographic signal in the extensor digitorum communis (EDC, normalized peak torque of extensors, and ratio of normalized peak torque between wrist extensors and flexors, were all greater in the NP than RD and UD in both contractions. The ratio of RMS between EDC and flexor digitorum superficialis (FDS had a significantly greater value in RD than UD during the concentric contraction. The EDC showed significantly higher activity at the fast velocity in both contractions. Nevertheless, a significantly higher RMS of the electromyographic signal between EDC and FDS and the ratio of strength between wrist extensors and flexors were found at slow velocity in both contractions. The wrist deviation combined with extension and movement velocity of the wrist joint should thus be considered as influential factors which might alter the dynamic performances, and may result in further injury of the elbow joint.

  13. The Potential Risk Factors Relevant to Lateral Epicondylitis by Wrist Coupling Posture

    Lee, Su-Ya; Chieh, Hsiao-Feng; Lin, Chien-Ju; Jou, I-Ming; Kuo, Li-Chieh; Su, Fong-Chin


    The use of awkward wrist postures and unskilled techniques might induce lateral epicondylitis. This study thus investigated the effects of wrist deviation combined with extension and movement velocity on the dynamic performances of the wrist muscles during the coupling posture via a custom-made bi-planar isokinetic dynamometer. Thirty subjects were recruited to perform the isokinetic testing. We measured the muscle strengths and activities for the wrist extensors and flexors during concentric and eccentric contractions at three movement velocities, 30°s-1, 90°s-1, and 180°s-1, combined with three wrist postures, neutral position (NP), radial deviation (RD), and ulnar deviation (UD). The root mean square (RMS) of the electromyographic signal in the extensor digitorum communis (EDC), normalized peak torque of extensors, and ratio of normalized peak torque between wrist extensors and flexors, were all greater in the NP than RD and UD in both contractions. The ratio of RMS between EDC and flexor digitorum superficialis (FDS) had a significantly greater value in RD than UD during the concentric contraction. The EDC showed significantly higher activity at the fast velocity in both contractions. Nevertheless, a significantly higher RMS of the electromyographic signal between EDC and FDS and the ratio of strength between wrist extensors and flexors were found at slow velocity in both contractions. The wrist deviation combined with extension and movement velocity of the wrist joint should thus be considered as influential factors which might alter the dynamic performances, and may result in further injury of the elbow joint. PMID:27171198

  14. The MnSOD Ala16Val SNP: relevance to human diseases and interaction with environmental factors.

    Bresciani, G; Cruz, I B M; de Paz, J A; Cuevas, M J; González-Gallego, J


    The relevance of reactive oxygen species (ROS) production relies on the dual role shown by these molecules in aerobes. ROS are known to modulate several physiological phenomena, such as immune response and cell growth and differentiation; on the other hand, uncontrolled ROS production may cause important tissue and cell damage, such as deoxyribonucleic acid oxidation, lipid peroxidation, and protein carbonylation. The manganese superoxide dismutase (MnSOD) antioxidant enzyme affords the major defense against ROS within the mitochondria, which is considered the main ROS production locus in aerobes. Structural and/or functional single nucleotide polymorphisms (SNP) within the MnSOD encoding gene may be relevant for ROS detoxification. Specifically, the MnSOD Ala16Val SNP has been shown to alter the enzyme localization and mitochondrial transportation, affecting the redox status balance. Oxidative stress may contribute to the development of type 2 diabetes, cardiovascular diseases, various inflammatory conditions, or cancer. The Ala16Val MnSOD SNP has been associated with these and other chronic diseases; however, inconsistent findings between studies have made difficult drawing definitive conclusions. Environmental factors, such as dietary antioxidant intake and exercise have been shown to affect ROS metabolism through antioxidant enzyme regulation and may contribute to explain inconsistencies in the literature. Nevertheless, whether environmental factors may be associated to the Ala16Val genotypes in human diseases still needs to be clarified.

  15. Identification and Characterization of Soluble Factors Involved in Delayed Effects of Low Dose Radiation. Final report

    Baulch, Janet


    This is a 'glue grant' that was part of a DOE Low Dose project entitled 'Identification and Characterization of Soluble Factors Involved in Delayed Effects of Low Dose Radiation'. This collaborative program has involved Drs. David L. Springer from Pacific Northwest National Laboratory (PNNL), John H. Miller from Washington State University, Tri-cities (WSU) and William F. Morgan then from the University of Maryland, Baltimore (UMB). In July 2008, Dr. Morgan moved to PNNL and Dr. Janet E. Baulch became PI for this project at University of Maryland. In November of 2008, a one year extension with no new funds was requested to complete the proteomic analyses. The project stemmed from studies in the Morgan laboratory demonstrating that genomically unstable cells secret a soluble factor or factors into the culture medium, that cause cytogenetic aberrations and apoptosis in normal parental GM10115 cells. The purpose of this project was to identify the death inducing effect (DIE) factor or factors, estimate their relative abundance, identify the cell signaling pathways involved and finally recapitulate DIE in normal cells by exogenous manipulation of putative DIE factors in culture medium. As reported in detail in the previous progress report, analysis of culture medium from the parental cell line, and stable and unstable clones demonstrated inconsistent proteomic profiles as relate to candidate DIE factors. While the proposed proteomic analyses did not provide information that would allow DIE factors to be identified, the analyses provided another important set of observations. Proteomic analysis suggested that proteins associated with the cellular response to oxidative stress and mitochondrial function were elevated in the medium from unstable clones in a manner consistent with mitochondrial dysfunction. These findings correlate with previous studies of these clones that demonstrated functional differences between the mitochondria of stable and

  16. Identification and Characterization of Soluble Factors Involved in Delayed Effects of Low Dose Radiation. Final report

    Baulch, Janet


    This is a 'glue grant' that was part of a DOE Low Dose project entitled 'Identification and Characterization of Soluble Factors Involved in Delayed Effects of Low Dose Radiation'. This collaborative program has involved Drs. David L. Springer from Pacific Northwest National Laboratory (PNNL), John H. Miller from Washington State University, Tri-cities (WSU) and William F. Morgan then from the University of Maryland, Baltimore (UMB). In July 2008, Dr. Morgan moved to PNNL and Dr. Janet E. Baulch became PI for this project at University of Maryland. In November of 2008, a one year extension with no new funds was requested to complete the proteomic analyses. The project stemmed from studies in the Morgan laboratory demonstrating that genomically unstable cells secret a soluble factor or factors into the culture medium, that cause cytogenetic aberrations and apoptosis in normal parental GM10115 cells. The purpose of this project was to identify the death inducing effect (DIE) factor or factors, estimate their relative abundance, identify the cell signaling pathways involved and finally recapitulate DIE in normal cells by exogenous manipulation of putative DIE factors in culture medium. As reported in detail in the previous progress report, analysis of culture medium from the parental cell line, and stable and unstable clones demonstrated inconsistent proteomic profiles as relate to candidate DIE factors. While the proposed proteomic analyses did not provide information that would allow DIE factors to be identified, the analyses provided another important set of observations. Proteomic analysis suggested that proteins associated with the cellular response to oxidative stress and mitochondrial function were elevated in the medium from unstable clones in a manner consistent with mitochondrial dysfunction. These findings correlate with previous studies of these clones that demonstrated functional differences between the mitochondria of stable and

  17. Vascular endothelial growth factor in the circulation in cancer patients may not be a relevant biomarker.

    Tatjana M H Niers

    Full Text Available BACKGROUND: Levels of circulating vascular endothelial growth factor (VEGF have widely been used as biomarker for angiogenic activity in cancer. For this purpose, non-standardized measurements in plasma and serum were used, without correction for artificial VEGF release by platelets activated ex vivo. We hypothesize that "true" circulating (cVEGF levels in most cancer patients are low and unrelated to cancer load or tumour angiogenesis. METHODOLOGY: We determined VEGF levels in PECT, a medium that contains platelet activation inhibitors, in citrate plasma, and in isolated platelets in 16 healthy subjects, 18 patients with metastatic non-renal cancer (non-RCC and 12 patients with renal cell carcinoma (RCC. In non-RCC patients, circulating plasma VEGF levels were low and similar to VEGF levels in controls if platelet activation was minimized during the harvest procedure by PECT medium. In citrate plasma, VEGF levels were elevated in non-RCC patients, but this could be explained by a combination of increased platelet activation during blood harvesting, and by a two-fold increase in VEGF content of individual platelets (controls: 3.4 IU/10(6, non-RCC: 6.2 IU/10(6 platelets, p = 0.001. In contrast, cVEGF levels in RCC patients were elevated (PECT plasma: 64 pg/ml vs. 21 pg/ml, RCC vs. non-RCC, p<0.0001, and not related to platelet VEGF concentration. CONCLUSIONS: Our findings suggest that "true" freely cVEGF levels are not elevated in the majority of cancer patients. Previously reported elevated plasma VEGF levels in cancer appear to be due to artificial release from activated platelets, which in cancer have an increased VEGF content, during the blood harvest procedure. Only in patients with RCC, which is characterized by excessive VEGF production due to a specific genetic defect, were cVEGF levels elevated. This observation may be related to limited and selective success of anti-VEGF agents, such as bevacizumab and sorafenib, as monotherapy in

  18. Quality of Life among Family Caregivers of Patients on Hemodialysis and its Relevant Factors: A Systematic Review

    Seyedeh Azam Sajadi


    Full Text Available Background: Family caregivers are considered as hidden patients experiencing physical and mental disorders. This affects the quality of not only their lives but also the health care provided to patients.This study aimed to investigate the quality of life (QOL and its related factors among the caregivers of patients undergoing hemodialysis. Methods: This systematic review was conducted based on the eight-step guidelines presented by the York University. The databases relevant to the medical field including Nursing and Allied Health, Web of Science, Scopus, Pubmed, Embase, PsycINFO and Psychology Library were used. Finally, 12 articles observing the inclusion criteria and with regard to the research questions were found. The data obtained from these articles were summarized, classified, and analyzed. Results: QOL among Family Caregivers of Patients on Hemodialysis is low, compared to the general population; however, their QOL is higher than the patients under their care. Factors relevant to the QOL for caregivers including age, gender, perceived social support, perceived burden of care, affliction with other diseases (lupus, hypertension, hypothyroidism and depression, intellectual understanding of the limitations of the patient’s disease in their daily life, employment of adaptation strategies, better marital relationships, accepting self and family relationship with the patient (mother and wife. Furthermore, the factors associated with care takers affecting the quality of caregivers’ lives were age, QOL and the type of treatment. Conclusions: Caregivers of patients undergoing hemodialysis enjoyed low QOL. Since there is a direct relationship between family caregivers’ quality and patients’ QOL, health care system and health policy makers should pay more attention to family caregivers.

  19. Factors associated with sex work involvement among transgender women in Jamaica: a cross-sectional study.

    Logie, Carmen H; Wang, Ying; Lacombe-Duncan, Ashley; Jones, Nicolette; Ahmed, Uzma; Levermore, Kandasi; Neil, Ava; Ellis, Tyrone; Bryan, Nicolette; Marshall, Annecka; Newman, Peter A


    Transgender women are disproportionately impacted by HIV. Transgender women involved in sex work may experience exacerbated violence, social exclusion, and HIV vulnerabilities, in comparison with non-sex work-involved transgender women. Scant research has investigated sex work among transgender women in the Caribbean, including Jamaica, where transgender women report pervasive violence. The study objective was to examine factors associated with sex work involvement among transgender women in Jamaica. In 2015, we implemented a cross-sectional survey using modified peer-driven recruitment with transgender women in Kingston and Ocho Rios, Jamaica, in collaboration with a local community-based AIDS service organization. We conducted multivariable logistic regression analyses to identify factors associated with paid sex and transactional sex. Exchanging oral, anal or vaginal sex for money only was categorized as paid sex. Exchanging sex for survival needs (food, accommodation, transportation), drugs or alcohol, or for money along with survival needs and/or drugs/alcohol, was categorized as transactional sex. Among 137 transgender women (mean age: 24.0 [SD: 4.5]), two-thirds reported living in the Kingston area. Overall, 25.2% reported being HIV-positive. Approximately half (n = 71; 51.82%) reported any sex work involvement, this included sex in exchange for: money (n = 64; 47.06%); survival needs (n = 27; 19.85%); and drugs/alcohol (n = 6; 4.41%). In multivariable analyses, paid sex and transactional sex were both associated with: intrapersonal (depression), interpersonal (lower social support, forced sex, childhood sexual abuse, intimate partner violence, multiple partners/polyamory), and structural (transgender stigma, unemployment) factors. Participants reporting transactional sex also reported increased odds of incarceration perceived to be due to transgender identity, forced sex, homelessness, and lower resilience, in comparison with participants reporting

  20. Effects of (-)-Epigallocatechin gallate on some protein factors involved in the epidermal growth factor receptor signaling pathway

    Yinjiu Huang; Ruiqing Xu; Baoan Song; Song Yang; Li Zhao; Shouwei Wua


    (-)-Epigallocatechin gallate (EGCG), a major polyphenolic constituent of green tea, can inhibit activity of specific receptor tyrosine kinases (RTKs) and related downstream signal transduction pathways, resulting in the control of unwanted cell proliferation. The epidermal growth factor receptor (EGFR) signaling pathway is one of the most important pathways that regulates growth, survival, proliferation and differentiation in mammalian cells. This review addresses the effects of EGCG on some protein factors involved in the EGFR signaling pathway in a direct or indirect manner. Based on our understanding of the interaction between EGCG and these factors, and based on their structures, EGCG could be used as a lead compound for designing and synthesizing novel drugs with significant biological activity.

  1. Factors Affecting Adolescents' Involvement in Cyberbullying: What Divides the 20% from the 80%?

    Shin, Namin; Ahn, Hwasil


    Despite some variations among cyberbullying studies, about 20% of the youth population surveyed appears to be involved in cyberbullying. Coincidentally, the current study found that exactly 20% of the students surveyed were involved in cyberbullying as bullies (7.8%), victims (7.5%), and bully/victims (4.7%). What divides those 20% from the 80% of noninvolved students? This study aimed to produce a parsimonious and accurate model that can predict the occurrence of involvement in cyberbullying among youth. Data were collected from a questionnaire survey administered to 1,036 students enrolled in secondary schools in South Korea. Stepwise logistic regression (SLR) was carried out to predict the dichotomous dependent variable (involved/noninvolved) with 10 independent variables grouped into three categories: (a) demographic, (b) media-related, and (c) school and psychology factors. The result of the SLR analysis yielded a four-step model including the variables of cyber-confidence, weekday game time, mobile activities, and age as being significant in explaining the 20/80 division (model χ(2)=34.306, df=4, pcyberbullying than other students. In particular, the construct of cyber-confidence calls for further elaboration and research, given its controversial function with respect to adolescents' involvement in cyberbullying. Also, this study may bring about insights into practical considerations needed for concerned researchers, teachers, and parents to identify who is inside the group involved in cyberbullying so as to help the participating adolescents escape from the circle of cyberbullying.

  2. Influence of independent risk factors on health status of persons involved in the process of education

    Guriev A.V.


    Full Text Available The research goal is to increase efficiency of health education for subjects involved in the process of education. Materials: 498 questionnaires have been worked out for respondents. Methods: They have included supervision, questioning, free interviewing and methods for statistical processing of results of research. Results: The following factors have been revealed: peculiarity of leisure-time; bad quality of interaction between subjects of educational system and health care system. The characteristic of extra-curriculum risk factors has been done. Conclusion: It is stressed that the survey has determined the basic directions of training for teachers and adults to form healthy way of life.

  3. The relevance of cultural factors in predicting condom-use intentions among immigrants from the Netherlands Antilles.

    Kocken, Pl; van Dorst, Ag; Schaalma, H


    A study into the relevance of cultural factors in predicting condom-use intentions among Antillean migrants in the Netherlands is described in this article. The association between the intention to use condoms with a new sexual partner and a perceived taboo on discussing sex, beliefs about sex education and machismo beliefs on gender and power relationships is addressed. The study was conducted among 346 Dutch Antilleans from a random sample of an Antillean population aged 15-50 years. The response rate was 37.8%. The results showed that condom-use intentions were primarily determined by perceived subjective norms, the perceived taboo on discussing sex, machismo attitudes, gender, age and educational background. Moreover, the respondent's opinion regarding machismo was an effect modificator for the association between condom-use intentions and subjective social norm. It is concluded that, in predicting condom-use intentions, factors specific to the culture of a population contribute significantly to the determinants drawn from the general social-cognition models. It is recommended that future research should use measurement instruments that are adapted to culture-specific beliefs, and should explore the influence of cultural factors on actual condom use. Moreover, interventions promoting condom use among migrant populations should target the cultural correlates of condom use.

  4. Characteristics and risk factors of major and clinically relevant non-major bleeding in cancer patients receiving anticoagulant treatment for acute venous thromboembolism-the CATCH study

    Kamphuisen, P.W.; Lee, A.Y.Y.; Meyer, Guy; Bauersachs, R.; Janas, M.S.; Jarner, M.F.; Khorana, A.A.


    Background: Cancer patients with acute venous thromboembolism (VTE) receiving anticoagulant treatment have a substantial risk of bleeding complications. Aims: To assess the rate, site and risk factors of clinically relevant bleeding (CRB; major or clinically relevant non-major bleeding) in cancer pa

  5. Identifying contributing factors to fatal and serious injury motorcycle collisions involving children in Malaysia.

    Oxley, Jennifer; Ravi, Mano Deepa; Yuen, Jeremy; Hoareau, Effie; Hashim, Hizal Hanis


    In Malaysia, motorcycle crashes constitute approximately 60 percent of all road trauma, and a substantial proportion involve children 16 years and younger. There are, however, many gaps in our knowledge on contributing factors to crashes and injury patterns amongst children killed and seriously injured in motorcycle crashes. The aim of this study was to examine fatal and serious injury motorcycle-related collisions to identify contributing factors and injury patterns amongst child motorcyclists. All identified motorcyclist fatal crashes between 2007 and 2011 (inclusive) were extracted from the national Police-reported crash database (M-ROADS) and a range of variables were selected for examination. A total of 17,677 crashes were extracted where a rider or pillion was killed and of these crashes 2,038 involved children, equating to 12 percent. Examination of crashes involving children revealed that some crashes involved more than two children on the motorcycle, therefore, overall children constituted 9.5% of fatal and 18.4% of serious injury collisions. A high proportion of child fatal or serious injury collisions involved the child as the rider (62%), and this was most common for children aged between 10 and 16 years. The majority of collisions occurred on rural roads, in speed limit zones of 50-70km/h, and approximately one-third occurred at an intersection. Collisions involving another motorcycle or a passenger vehicle contributed to 41% and 53% of the total fatalities and severe injuries, respectively. A high proportion (43.9%) of the children (25.5% riders and 18.8% pillion) sustained head injuries with 37.7% being in the 10-16 age group. Furthermore, 52.4% of the children sustaining head injuries did not wear a helmet. The implications of these findings for countermeasures within a Safe System framework, particularly interventions aimed at reducing the rate of unlicensed riding and helmet wearing, and infrastructure countermeasures are discussed.

  6. Incidence and risk factors of bone marrow involvement by non-Hodgkin lymphoma.

    Kittivorapart, Janejira; Chinthammitr, Yingyong


    Since trephine bone marrow biopsy is an invasive procedure, the identification of a subgroup of patients with Non-Hodgkin lymphoma (NHL) who have a minimal risk of bone marrow involvement would be helpful. This study is aimed to determine the incidence of bone marrow involvement (BMI) by NHL and the predictors of no BMI to not only avoid this invasive procedure but also decrease the cost of investigation. Data from 320 patients with NHL at division of hematology between January 2008 and June 2009 were reviewed and analyzed. The cell types of NHL were classified as B-cell in 283 patients (88.4%), T-cell in 37 patients (11.6%) and incidence of BMI is 24.4% and 18.9% in B- and T-cell, respectively. Factors significantly associated with BMI in univariate analysis were the hepatic and splenic involvement (p = 0.03 and low percent of blood neutrophil (p high percent of blood lymphocyte (p low absolute neutrophil count (p = 0.002), high absolute lymphocyte count (p = 0.045), low platelet count (p high LDH (p = 0.026), and high alkaline phosphatase (p = 0.020). On the multivariate analysis, factors associated with BMI included LN below diaphragm, anemia, low percent of blood neutrophil and low platelet count. Excluding Burkitt lymphoma and mantle cell lymphoma, NHL patients with no LN below diaphragm, no hepatic & splenic involvement, no significant weight loss, hemoglobin (Hb) >11 g/dL and platelet > 150,000/uL had BMI in 3/78 (3.8%). The incidence of bone marrow involvement in NHL is 23.8%. Excluding Burkitt lymphoma and mantle cell lymphoma, NHL patients with no LN below diaphragm, no hepatic & splenic involvement, no significant weight loss, Hb > 11 g/dL and platelet > 150,000/uL had low risk of BMI.

  7. Diurnal rhythmicity in biological processes involved in bioavailability of functional food factors.

    Tsurusaki, Takashi; Sakakibara, Hiroyuki; Aoshima, Yoshiki; Yamazaki, Shunsuke; Sakono, Masanobu; Shimoi, Kayoko


    In the past few decades, many types of functional factors have been identified in dietary foods; for example, flavonoids are major groups widely distributed in the plant kingdom. However, the absorption rates of the functional food factors are usually low, and many of these are difficult to be absorbed in the intact forms because of metabolization by biological processes during absorption. To gain adequate beneficial effects, it is therefore mandatory to know whether functional food factors are absorbed in sufficient quantity, and then reach target organs while maintaining beneficial effects. These are the reasons why the bioavailability of functional food factors has been well investigated using rodent models. Recently, many of the biological processes have been reported to follow diurnal rhythms recurring every 24 h. Therefore, absorption and metabolism of functional food factors influenced by the biological processes may vary with time of day. Consequently, the evaluation of the bioavailability of functional food factors using rodent models should take into consideration the timing of consumption. In this review, we provide a perspective overview of the diurnal rhythm of biological processes involved in the bioavailability of functional food factors, particularly flavonoids.

  8. Analysis of molecular markers as predictive factors of lymph node involvement in breast carcinoma.

    Paula, Luciana Marques; De Moraes, Luis Henrique Ferreira; Do Canto, Abaeté Leite; Dos Santos, Laurita; Martin, Airton Abrahão; Rogatto, Silvia Regina; De Azevedo Canevari, Renata


    Nodal status is the most significant independent prognostic factor in breast cancer. Identification of molecular markers would allow stratification of patients who require surgical assessment of lymph nodes from the large numbers of patients for whom this surgical procedure is unnecessary, thus leading to a more accurate prognosis. However, up to now, the reported studies are preliminary and controversial, and although hundreds of markers have been assessed, few of them have been used in clinical practice for treatment or prognosis in breast cancer. The purpose of the present study was to determine whether protein phosphatase Mg2+/Mn2+ dependent 1D, β-1,3-N-acetylglucosaminyltransferase, neural precursor cell expressed, developmentally down-regulated 9, prohibitin, phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5), phosphatidylinositol-5-phosphate 4-kinase type IIα, TRF1-interacting ankyrin-related ADP-ribose polymerase 2, BCL2 associated agonist of cell death, G2 and S-phase expressed 1 and PAX interacting protein 1 genes, described as prognostic markers in breast cancer in a previous microarray study, are also predictors of lymph node involvement in breast carcinoma Reverse transcription-quantitative polymerase chain reaction analysis was performed on primary breast tumor tissues from women with negative lymph node involvement (n=27) compared with primary tumor tissues from women with positive lymph node involvement (n=23), and was also performed on primary tumors and paired lymph node metastases (n=11). For all genes analyzed, only the PIK3R5 gene exhibited differential expression in samples of primary tumors with positive lymph node involvement compared with primary tumors with negative lymph node involvement (P=0.0347). These results demonstrate that the PIK3R5 gene may be considered predictive of lymph node involvement in breast carcinoma. Although the other genes evaluated in the present study have been previously characterized to be involved with

  9. Analysis of molecular markers as predictive factors of lymph node involvement in breast carcinoma

    Paula, Luciana Marques; De Moraes, Luis Henrique Ferreira; Do Canto, Abaeté Leite; Dos Santos, Laurita; Martin, Airton Abrahão; Rogatto, Silvia Regina; De Azevedo Canevari, Renata


    Nodal status is the most significant independent prognostic factor in breast cancer. Identification of molecular markers would allow stratification of patients who require surgical assessment of lymph nodes from the large numbers of patients for whom this surgical procedure is unnecessary, thus leading to a more accurate prognosis. However, up to now, the reported studies are preliminary and controversial, and although hundreds of markers have been assessed, few of them have been used in clinical practice for treatment or prognosis in breast cancer. The purpose of the present study was to determine whether protein phosphatase Mg2+/Mn2+ dependent 1D, β-1,3-N-acetylglucosaminyltransferase, neural precursor cell expressed, developmentally down-regulated 9, prohibitin, phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5), phosphatidylinositol-5-phosphate 4-kinase type IIα, TRF1-interacting ankyrin-related ADP-ribose polymerase 2, BCL2 associated agonist of cell death, G2 and S-phase expressed 1 and PAX interacting protein 1 genes, described as prognostic markers in breast cancer in a previous microarray study, are also predictors of lymph node involvement in breast carcinoma Reverse transcription-quantitative polymerase chain reaction analysis was performed on primary breast tumor tissues from women with negative lymph node involvement (n=27) compared with primary tumor tissues from women with positive lymph node involvement (n=23), and was also performed on primary tumors and paired lymph node metastases (n=11). For all genes analyzed, only the PIK3R5 gene exhibited differential expression in samples of primary tumors with positive lymph node involvement compared with primary tumors with negative lymph node involvement (P=0.0347). These results demonstrate that the PIK3R5 gene may be considered predictive of lymph node involvement in breast carcinoma. Although the other genes evaluated in the present study have been previously characterized to be involved with

  10. Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy

    Nalla, Amarnadh; Ringholm, Lene; Søstrup, Birgitte


    is able to stimulate proliferation of rat beta cells. We have identified several circulating factors that may contribute to beta cell adaptation to pregnancy. Further studies are needed to elucidate their possible role in glucose homeostasis in the mother and her offspring.......OBJECTIVE: Several studies have shown an increase in beta cell mass during pregnancy. Somatolactogenic hormones are known to stimulate the proliferation of existing beta cells in rodents whereas the mechanism in humans is still unclear. We hypothesize that in addition to somatolactogenic hormones...... there are other circulating factors involved in beta cell adaptation to pregnancy. This study aimed at screening for potential pregnancy-associated circulating beta cell growth factors. SAMPLES: Serum samples from nonpregnant and pregnant women. METHODS: The effect of serum from pregnant women...

  11. Model correction factor method for reliability problems involving integrals of non-Gaussian random fields

    Franchin, P.; Ditlevsen, Ove Dalager; Kiureghian, Armen Der


    The model correction factor method (MCFM) is used in conjunction with the first-order reliability method (FORM) to solve structural reliability problems involving integrals of non-Gaussian random fields. The approach replaces the limit-state function with an idealized one, in which the integrals...... are considered to be Gaussian. Conventional FORM analysis yields the linearization point of the idealized limit-state surface. A model correction factor is then introduced to push the idealized limit-state surface onto the actual limit-state surface. A few iterations yield a good approximation of the reliability...... reliability method; Model correction factor method; Nataf field integration; Non-Gaussion random field; Random field integration; Structural reliability; Pile foundation reliability...

  12. Fusion of Cytothrophoblast with Syncytiotrophoblast in the Human Placenta: Factors Involved in Syncytialization

    Gauster M


    Full Text Available Human placental villi are covered by a characteristic epithelial-like layer. It consists of mononucleated cytotrophoblasts and an overlyingsyncytiotrophoblast layer both in contact to the trophoblastic basement membrane. The syncytiotrophoblast mostly lacks DNA replication andseems to transcribe only barely mRNA. Therefore, the syncytiotrophoblast depends on cell compounds delivered by fusing cytotrophoblasts. Delivery of fresh cytoplasmic contents into the syncytiotrophoblast is achieved by continuous fusion with cytotrophoblasts throughout gesta-tion. Fusion between cytotrophoblasts and the syncytiotrophoblast is driven by multiple factors, including environmental growth factors andcytokines, which turn on a specific cascade of fusogenic proteins in cytotrophoblasts destined for fusion. The cascade includes protein kinasesand transcription factors, as well as induced expression of fusion-promoting proteins associated with the cell membrane. Additionally, specificproteases are activated, which cleave and remodel structural proteins to prepare the cell for fusion. However, not only fusogenic proteins, butalso plasma membrane architecture and physicochemical factors such as calcium and oxygen affect intertrophoblastic fusion. Coordinatedaction of all factors involved is crucial for proper cytotrophoblast – syncytiotrophoblast fusion. Deregulation of a single factor might cause aninadequate fusion rate and could lead to pregnancy complications such as preeclampsia or even spontaneous abortion.

  13. Factors Influencing the Private Involvement in Urban Rail Public-Private Partnership Projects in China

    Yongjian Ke


    Full Text Available Private investors have been encouraged to participate in the development and operation of urban rail projects in China through Public-Private Partnerships (PPPs, given the fact that subnational governments are suffering from urgent development demands and severe fiscal pressure. However, there is no formal assessment to determine the private involvement in a PPP project. This problem is particularly critical in the sector of urban rail, in which the huge investment cannot rely on the private sector alone. This study hence aimed to uncover and identify the influencing factors. Multiple research methods, including content analysis, case study and focus group discussion were adopted to achieve the research purpose. Seven types of influencing factors were identified, including project financial model, government fiscal commitment, risk allocation, public accountability, efficiency considerations, policy and regulations, and organisational marketing strategies. The findings add to the current knowledge base by uncovering the drivers behind private involvement in a PPP project. They are also beneficial for industry practitioners as a basis/checklist to determine the private involvement.

  14. Adolescent gang involvement: The role of individual, family, peer, and school factors in a multilevel perspective.

    Lenzi, Michela; Sharkey, Jill; Vieno, Alessio; Mayworm, Ashley; Dougherty, Danielle; Nylund-Gibson, Karen


    Youth gang involvement is a serious public health challenge as adolescents involved in gangs are more likely than others to engage in violence and aggression. To better understand gang involvement, we examined the role of protective (empathy and parental support) and risk (peer deviance and lack of safety at school) factors, as well as their interactions, in predicting adolescent gang affiliation. The study involved a sample of 26,232 students (53.4% females; mean age = 14.62, SD = 1.69) participating in the California Healthy Kids Survey (CHKS), a survey investigating a wide range of youth health and risk behaviors administered in all California schools every 2 years. Using hierarchical linear modeling (HLM), findings indicated that high levels of empathy and parental support were associated with a lower likelihood of affiliating with a gang. Associating with deviant peers and perceiving the school as unsafe were positively correlated with gang membership. At the school level, lack of safety and type of school (special education, vocational, or alternative school vs. comprehensive schools) were associated with greater probability of gang membership. Empathy mitigated the association between deviant peers and gang membership.

  15. Class I ADP-ribosylation factors are involved in enterovirus 71 replication.

    Jianmin Wang

    Full Text Available Enterovirus 71 is one of the major causative agents of hand, foot, and mouth disease in infants and children. Replication of enterovirus 71 depends on host cellular factors. The viral replication complex is formed in novel, cytoplasmic, vesicular compartments. It has not been elucidated which cellular pathways are hijacked by the virus to create these vesicles. Here, we investigated whether proteins associated with the cellular secretory pathway were involved in enterovirus 71 replication. We used a loss-of-function assay, based on small interfering RNA. We showed that enterovirus 71 RNA replication was dependent on the activity of Class I ADP-ribosylation factors. Simultaneous depletion of ADP-ribosylation factors 1 and 3, but not three others, inhibited viral replication in cells. We also demonstrated with various techniques that the brefeldin-A-sensitive guanidine nucleotide exchange factor, GBF1, was critically important for enterovirus 71 replication. Our results suggested that enterovirus 71 replication depended on GBF1-mediated activation of Class I ADP-ribosylation factors. These results revealed a connection between enterovirus 71 replication and the cellular secretory pathway; this pathway may represent a novel target for antiviral therapies.

  16. Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico.

    Ramos-Lopez, Omar; Martinez-Lopez, Erika; Roman, Sonia; Fierro, Nora A; Panduro, Arturo


    Liver cirrhosis (LC) is a chronic illness caused by inflammatory responses and progressive fibrosis. Globally, the most common causes of chronic liver disease include persistent alcohol abuse, followed by viral hepatitis infections and nonalcoholic fatty liver disease. However, regardless of the etiological factors, the susceptibility and degree of liver damage may be influenced by genetic polymorphisms that are associated with distinct ethnic and cultural backgrounds. Consequently, metabolic genes are influenced by variable environmental lifestyle factors, such as diet, physical inactivity, and emotional stress, which are associated with regional differences among populations. This Topic Highlight will focus on the genetic and environmental factors that may influence the metabolism of alcohol and nutrients in the setting of distinct etiologies of liver disease. The interaction between genes and environment in the current-day admixed population, Mestizo and Native Mexican, will be described. Additionally, genes involved in immune regulation, insulin sensitivity, oxidative stress and extracellular matrix deposition may modulate the degree of severity. In conclusion, LC is a complex disease. The onset, progression, and clinical outcome of LC among the Mexican population are influenced by specific genetic and environmental factors. Among these are an admixed genome with a heterogenic distribution of European, Amerindian and African ancestry; a high score of alcohol consumption; viral infections; a hepatopathogenic diet; and a high prevalence of obesity. The variance in risk factors among populations suggests that intervention strategies directed towards the prevention and management of LC should be tailored according to such population-based features.

  17. Proteomic Assessment of the Relevant Factors Affecting Pork Meat Quality Associated with Longissimus dorsi Muscles in Duroc Pigs

    Cho, Jin Hyoung; Lee, Ra Ham; Jeon, Young-Joo; Park, Seon-Min; Shin, Jae-Cheon; Kim, Seok-Ho; Jeong, Jin Young; Kang, Hyun-sung; Choi, Nag-Jin; Seo, Kang Seok; Cho, Young Sik; Kim, MinSeok S.; Ko, Sungho; Seo, Jae-Min; Lee, Seung-Youp; Shim, Jung-Hyun; Chae, Jung-Il


    Meat quality is a complex trait influenced by many factors, including genetics, nutrition, feeding environment, animal handling, and their interactions. To elucidate relevant factors affecting pork quality associated with oxidative stress and muscle development, we analyzed protein expression in high quality longissimus dorsi muscles (HQLD) and low quality longissimus dorsi muscles (LQLD) from Duroc pigs by liquid chromatographytandem mass spectrometry (LC-MS/MS)–based proteomic analysis. Between HQLD (n = 20) and LQLD (n = 20) Duroc pigs, 24 differentially expressed proteins were identified by LC-MS/MS. A total of 10 and 14 proteins were highly expressed in HQLD and LQLD, respectively. The 24 proteins have putative functions in the following seven categories: catalytic activity (31%), ATPase activity (19%), oxidoreductase activity (13%), cytoskeletal protein binding (13%), actin binding (12%), calcium ion binding (6%), and structural constituent of muscle (6%). Silver-stained image analysis revealed significant differential expression of lactate dehydrogenase A (LDHA) between HQLD and LQLD Duroc pigs. LDHA was subjected to in vitro study of myogenesis under oxidative stress conditions and LDH activity assay to verification its role in oxidative stress. No significant difference of mRNA expression level of LDHA was found between normal and oxidative stress condition. However, LDH activity was significantly higher under oxidative stress condition than at normal condition using in vitro model of myogenesis. The highly expressed LDHA was positively correlated with LQLD. Moreover, LDHA activity increased by oxidative stress was reduced by antioxidant resveratrol. This paper emphasizes the importance of differential expression patterns of proteins and their interaction for the development of meat quality traits. Our proteome data provides valuable information on important factors which might aid in the regulation of muscle development and the improvement of meat

  18. New Calculations for Phase Space Factors Involved in Double Beta Decay

    Stoica, Sabin


    We present new results for the phase space factors involved in double beta decay for beta-beta- transitions to ground states and excited 0+1 states, for isotopes of experimental interest. The Coulomb distortion of the electron wave functions is treated by solving numerically the Dirac equation with inclusion of the finite nuclear size and electron screening effects, and using a Coulomb potential derived from a realistic proton density distribution in the daughter nucleus. Our results are compared with other results from literature, obtained in different approximations, and possible causes that can give differences are discussed.

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

    Martha Elia Luevano


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

  20. Resident interest and factors involved in entering a pediatric pulmonary fellowship

    Gershan William M


    Full Text Available Abstract Background Relatively little is known about interest in pediatric pulmonology among pediatric residents. The purpose of this study, therefore, was to determine at this institution: 1 the level of pediatric resident interest in pursuing a pulmonary fellowship, 2 potential factors involved in development of such interest, 3 whether the presence of a pulmonary fellowship program affects such interest. Methods A questionnaire was distributed to all 52 pediatric residents at this institution in 1992 and to all 59 pediatric residents and 14 combined internal medicine/pediatrics residents in 2002, following development of a pulmonary fellowship program. Results Response rates were 79% in 1992 and 86% in 2002. Eight of the 43 responders in 1992 (19% had considered doing a pulmonary fellowship compared to 7 of 63 (11% in 2002. The highest ranked factors given by the residents who had considered a fellowship included wanting to continue one's education after residency, enjoying caring for pulmonary patients, and liking pulmonary physiology and the pulmonary faculty. Major factors listed by residents who had not considered a pulmonary fellowship included not enjoying the tracheostomy/ventilator population and chronic pulmonary patients in general, and a desire to enter general pediatrics or another fellowship. Most residents during both survey periods believed that they would be in non-academic or academic general pediatrics in 5 years. Only 1 of the 106 responding residents (~1% anticipated becoming a pediatric pulmonologist. Conclusions Although many pediatric residents consider enrolling in a pulmonary fellowship (~10–20% here, few (~1% here will actually pursue a career in pediatric pulmonology. The presence of a pulmonary fellowship program did not significantly alter resident interest, though other confounding factors may be involved.

  1. Major congenital defects. Relevant risk factors. Cienfuegos. 2000-2005. Malformaciones congénitas mayores. Factores de riesgo relevantes. Cienfuegos. 2000-2005.

    Gladis Barberis Pérez


    Full Text Available

    Background: Major congenital defects have an impact on perinatal mortality and morbidity with economic and social consequences. Objective: To determine the relevant risk factors linked to the occurrence of congenital defects in Cienfuegos between 2000 and 2005. Methods: A case-control study was carried out. Women with fetus or newborns with major congenital defects formed the case group (255 while the control group consisted of a similar number of healthy children selected each year by a randomized simple sample. The variables gathered by the Cuban Congenital Defects Records were studied. Chi-Square method was used with 95% of accuracy and a reliance rate of 95%; logistic regression was used with the Wald test. Results: There was a predominance of Central Nervous System defects (28, 6%. The most relevant risk factors were a history of congenital defects, smoking habits, and acute infection during the first three months, as well as belong to the third birth on. Conclusion: The most clinical relevant risks factors were the congenital defect history and the acute infection during the firs three months.

    Fundamento: Las malformaciones congénitas mayores influyen en la morbimortalidad perinatal, lo que tiene implicaciones sociales y económicas. Objetivo: Determinar los factores de riesgo relevantes, asociados a la aparición de malformaciones congénitas mayores, en la provincia Cienfuegos en el período 2000-2005. Métodos: Se realizó un estudio de casos y controles no pareados. Las mujeres registradas con fetos o recién nacidos con malformaciones congénitas mayores, constituyeron el grupo de casos (255, mientras que el grupo control estuvo conformado por un número similar de niños sanos, seleccionados en cada año, por un muestreo aleatorio simple. Se estudiaron las variables recogidas en el modelo

  2. Soluble ST2 associates with diabetes but not established cardiovascular risk factors: a new inflammatory pathway of relevance to diabetes?

    Ashley M Miller

    Full Text Available Preliminary data mostly from animal models suggest the sST2/IL-33 pathway may have causal relevance for vascular disease and diabetes and thus point to a potential novel inflammatory link to cardiometabolic disease. However, the characterisation of sST2 levels in terms of metabolic or vascular risk in man is completely lacking. We sought to address this gap via a comprehensive analysis of risk factor and vascular correlates of sST2 in a cross-sectional study (pSoBid. We measured sST2 in plasma in 639 subjects and comprehensively related it to cardiovascular and diabetes risk factors and imaged atherosclerosis measures. Circulating sST2 levels increased with age, were lower in women and in highest earners. After adjusting for age and gender, sST2 levels associated strongly with markers of diabetes, including triglycerides [effect estimate (EE per 1 standard deviation increase in sST2:1.05 [95%CI 1.01,1.10], liver function (alanine aminotransaminase [ALT] and γ-glutamyl transferase [GGT]: EE 1.05 [1.01,1.09] and 1.13 [1.07,1.19] respectively, glucose (1.02 [1.00,1.03] and sICAM-1 (1.05 [1.02,1.07]. However, sST2 levels were not related to smoking, cholesterol, blood pressure, or atheroma (carotid intima media thickness, plaque presence. These results suggest that sST2 levels, in individuals largely without vascular disease, are related principally to markers associated with diabetes and ectopic fat and add support for a role of sST2 in diabetes. Further mechanistic studies determining how sST2 is linked to diabetes pathways may offer new insights into the inflammatory paradigm for type 2 diabetes.

  3. Effectiveness and relevant factors of platelet-rich plasma treatment in managing plantar fasciitis:A systematic review

    Seet Khing Chiew


    Full Text Available Background: Plantar fasciitis (PF is a common foot complaint, affects both active sportsmen and physically inactive middle age group. It is believed that PF results from degenerative changes rather than inflammation. Platelet-rich plasma (PRP therapy has been introduced as an alternative therapy for PF. This study is aimed to systematically review to the effectiveness and relevant factors of PRP treatment in managing PF. Materials and Methods: A search was conducted in electronic databases, including PubMed, Scopus, and Google Scholar using different keywords. Publications in English-language from 2010 to 2015 were included. Two reviewers extracted data from selected articles after the quality assessment was done. Results: A total of 1126 articles were retrieved, but only 12 articles met inclusion and exclusion criteria. With a total of 455 patients, a number of potentially influencing factors on the effectiveness of PRP for PF was identified. In all these studies, PRP had been injected directly into the plantar fascia, with or without ultrasound guidance. Steps from preparation to injection were found equally crucial. Amount of collected blood, types of blood anti-coagulant, methods in preparing PRP, speed, and numbers of time the blood samples were centrifuged, activating agent added to the PRP and techniques of injection, were varied between different studies. Regardless of these variations, superiority of PRP treatment compared to steroid was reported in all studies. Conclusion: In conclusion, PRP therapy might provide an effective alternative to conservative management of PF with no obvious side effect or complication. The onset of action after PRP injection also greatly depended on the degree of degeneration.

  4. Involvement of vascular endothelial growth factor in nasal obstruction in patients with nasal allergy

    Tetsuji Yamashita


    Full Text Available It has recently been shown that vascular endothelial growth factor (VEGF enhances vascular permeability and that mast cells produce VEGF, suggesting the involvement of VEGF in allergic diseases. In the present study we quantitatively analyzed VEGF in the nasal lavage fluid of patients with nasal allergy. We performed nasal antigen challenge with Japanese cedar pollen antigen in 10 healthy adult volunteers and in 10 cedar pollen IgE-positive patients with nasal allergy. In all patients with nasal allergy, VEGF and histamine levels in the nasal lavage fluid reached a peak 30 min after antigen challenge, then returned to prechallenge values 2 h after antigen challenge. In these patients, the histamine level increased three-fold, while the VEGF level increased 10-fold. However, in all healthy adult volunteers, VEGF and histamine levels did not increase. A stronger correlation was noted between the ratio of decreased nasal cavity volume and the ratio of increased VEGF levels (R = 0.823; P < 0.001 than between the ratio of nasal cavity volume and the ratio of increased histamine levels (R = 0.660; P < 0.01. These results suggest that VEGF may contribute to the pathogenesis of nasal obstruction in the early phase of nasal allergy as a new factor involved in increasing vascular permeability.

  5. A pilot study on factors involved with work participation in the early stages of multiple sclerosis.

    Karin Van der Hiele

    Full Text Available Up to 30% of recently diagnosed MS patients lose their jobs in the first four years after diagnosis. Taking into account the personal and socio-economic importance of sustaining employment, it is of the utmost importance to examine factors involved with work participation.To investigate differences in self-reported functioning in recently diagnosed MS patients with and without a paid job.Self-reports of physical and cognitive functioning, depression, anxiety and fatigue were gathered from 44 relapsing-remitting MS patients diagnosed within 3 years.Patients with a paid job (57% reported better physical functioning (p<0.001, better memory functioning (p = 0.01 and a lower physical impact of fatigue (p = 0.018 than patients without a paid job. Physical functioning was the main predictor of employment status in a logistic regression model. In those with a paid job better memory functioning (r = 0.54, p = 0.005 and a lower social impact of fatigue (r =  -0.46, p = 0.029 correlated with an increased number of working hours.Better physical functioning is the primary factor involved with increased work participation in early MS. Better self-reported memory functioning and less social fatigue were associated with increased working hours. These findings highlight the importance of battling these symptoms in the early stages of MS.

  6. The influence of contextual factors on patient involvement during follow-up consultations after colorectal cancer surgery

    Thomsen, Thora G; Soelver, Lisbeth; Hølge-Hazelton, Bibi


    AIMS AND OBJECTIVES: To identify the contextual factors that influence individual patient involvement during colorectal cancer surgical follow-up consultations. BACKGROUND: The healthcare system is subject to the requirement and expectation of greater involvement of patients and relatives...... the identification of current contextual factors. RESULTS: The results showed five contextual factors that seemed to have an impact on patient involvement. The first, 'Two dimensions of patient involvement: treatment-oriented and person-oriented' highlighted a dual interpretation of patient involvement...... in the consultation situation. The two dimensions seemed to be influenced by four additional factors: 'Doctors leading the agenda', 'Traditional health professional roles', 'Unclear responsibilities' and 'Guidance primarily focused on treatment'. CONCLUSION: The results showed how patient involvement in clinical...

  7. Identification of transcription factors potentially involved in the juvenile to adult phase transition in Citrus.

    Castillo, Mari-Cruz; Forment, Javier; Gadea, José; Carrasco, Jose Luis; Juarez, José; Navarro, Luís; Ancillo, Gema


    The juvenile to adult transition (JAT) in higher plants is required for them to reach reproductive competence. However, it is a poorly understood process in woody plants, where only a few genes have been definitely identified as being involved in this transition. This work aims at increasing our understanding of the mechanisms regulating the JAT in citrus. Juvenile and adult plants from Pineapple sweet orange (Citrus sinensis) and Rough lemon (C. jambhiri) were used to screen for differentially expressed transcription factors (TFs) using a 1·15K microarray developed on the basis of the CitrusTF database. Murcott tangor (C. reticulata × C. sinensis) and Duncan grapefruit (C. paradisi) were incorporated into the quantitative real-time reverse transcription-PCR validation in order to select those genes whose phase-specific regulation was common to the four species. A browsable web database has been created with information about the structural and functional annotation related to 1152 unigenes of putative citrus TFs (CTFs). This database constitutes a valuable resource for research on transcriptional regulation and comparative genomics. Moreover, a microarray has been developed and used that contains these putative CTFs, in order to identify eight genes that showed differential expression in juvenile and adult meristems of four different species of citrus. Those genes have been characterized, and their expression pattern in vegetative and reproductive tissues has been analysed. Four of them are MADS-box genes, a family of TFs involved in developmental processes, whereas another one resembles MADS-box genes but lacks the MADS box itself. The other three showed high partial sequence similarity restricted to specific Arabidopsis protein domains but negligible outside those domains. The work presented here indicates that the JAT in citrus could be controlled by mechanisms that are in part common to those of Arabidopsis, but also somehow different, since specific factors

  8. Prenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: evidence from MRI in a mouse model.

    Qi Li

    Full Text Available OBJECTIVES: Maternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood. METHOD: We used an established mouse model of maternal immune activation (MIA by the viral mimic PolyI:C administered in early (day 9 or late (day 17 gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities. RESULTS: PolyI:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4(th ventricle volume but did not disrupt sensorimotor gating. CONCLUSIONS: Our results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life.

  9. Investigation of critical inter-related factors affecting the efficacy of pulsed light for inactivating clinically relevant bacterial pathogens.

    Farrell, H P; Garvey, M; Cormican, M; Laffey, J G; Rowan, N J


    To investigate critical electrical and biological factors governing the efficacy of pulsed light (PL) for the in vitro inactivation of bacteria isolated from the clinical environment. Development of this alternative PL decontamination approach is timely, as the incidence of health care-related infections remains unacceptably high. Predetermined cell numbers of clinically relevant Gram-positive and Gram-negative bacteria were inoculated separately on agar plates and were flashed with pulses of broad-spectrum light under varying operating conditions, and their inactivation measured. Significant differences in inactivation largely occurred depending on the level of the applied lamp discharge energy (range 3.2-20 J per pulse), the amount of pulsing applied (range 0-60 pulses) and the distance between light source and treatment surface (range 8-20 cm) used. Greater decontamination levels were achieved using a combination of higher lamp discharge energies, increased number of pulses and shorter distances between treatment surface and the xenon light source. Levels of microbial sensitivity also varied depending on the population type, size and age of cultures treated. Production of pigment pyocynanin and alginate slime in mucoid strains of Pseudomonas aeruginosa afforded some protection against lethal action of PL; however, this was evident only by using a combination of reduced amount of pulsing at the lower lamp discharge energies tested. A clear pattern was observed where Gram-positive bacterial pathogens were more resistant to cidal effects of PL compared to Gram negatives. While negligible photoreactivation of PL-treated bacterial strains occurred after full pulsing regimes at the different lamp discharge energies tested, some repair was evident when using a combination of reduced pulsing at the lower lamp discharge energies. Strains harbouring genes for multiple resistances to antibiotics were not significantly more resistant to PL treatments. Slight temperature

  10. Association of ABO Blood Types With Atherosclerosis Risk Factors and Number of Involved Coronary Arteries

    Golmohammadi Ali


    Full Text Available Objective: Cardiovascular disease (CVD is a common cause of morbidity and mortality. The relationship between ABO blood groups and main risk factors of CVD is unknown. So this study was designed to investigate whether there is an association between ABO blood groups and cardiovascular risk factors in otherwise healthy people. Materials and Methods: In this cross-sectional study, risk factors for CVD were screened in 300 patients with coronary artery disease (CAD who were hospitalized in Madani hospital (biggest heart center in Tabriz in 2013-2014 and evaluated by a questionnaire that aimed to extract information about age, sex, smoking, blood group type, weight, height, blood pressure, diabetes mellitus and family history of CVD. Data were analyzed with SPSS 17. Results: Of the total selected 300 patients, 69.3% were male, 35.3% were smoker, 61% were hypertensive, 30.3% were diabetic mellitus, 31% had hyperlipidemia, 70.97% were obese and 17.3% had family history of CVD. The mean age was 62.06 ± 11.40 years. Blood groups O (28%, A (43.3%, B (19% and AB (7.3% were the most frequent ones, respectively. According to our results, we found that the rate of CAD in individuals with the blood group A was higher than the other blood groups. Regarding the risk factors, however, no significant difference was observed between the blood groups. Conclusion: A correlation was found between blood group A and the incidence of CAD and there was no significant difference between the blood groups and cardiovascular risk factors and number of involved coronary arteries.

  11. Transcription factor CP2 is involved in activating mBMP4 in mouse mesenchymal stem cells.

    Kang, Ho Chul; Chae, Ji Hyung; Kim, Beom Sue; Han, Su Youne; Kim, Sung-Hyun; Auh, Chung-Kyoon; Yang, Sung-Il; Kim, Chul Geun


    CP2 is a member of a family of transcription factors that regulate genes involved in events from early development to terminal differentiation. In an effort to understand how it selects its target genes we carried out a database search, and located several CP2 binding motifs in the promoter region of bone morphogenetic protein-4 (BMP4). BMP4 is a key regulator of cell fate and body patterning throughout development. For the CP2 binding motifs in BMP4 promoter region to be relevant in vivo, CP2 and BMP4 should be expressed together. We found that CP2b and CP2c, two potent transcriptional activators, are expressed in a manner similar to BMP4 during osteoblast differentiation of C3H10T1/2 cells. In in vitro assays, the CP2 proteins bound to two CP2 binding motifs (-715 to -676 and -147 to -118) in the BMP4 promoter, and luciferase reporter assays indicated that this binding was essential for transcription of BMP4 during osteoblast differentiation. Taken together, our data indicate that CP2b and CP2c play important roles during bone development by activating BMP4 transcription.

  12. Secretome analysis identifies potential virulence factors of Diplodia corticola, a fungal pathogen involved in cork oak (Quercus suber) decline.

    Fernandes, Isabel; Alves, Artur; Correia, António; Devreese, Bart; Esteves, Ana Cristina


    The characterisation of the secretome of phytopathogenic fungi may contribute to elucidate the molecular mechanisms of pathogenesis. This is particularly relevant for Diplodia corticola, a fungal plant pathogen belonging to the family Botryosphaeriaceae, whose genome remains unsequenced. This phytopathogenic fungus is recognised as one of the most important pathogens of cork oak, being related to the decline of cork oak forests in the Iberian Peninsula. Unfortunately, secretome analysis of filamentous fungi is limited by the low protein concentration and by the presence of many interfering substances, such as polysaccharides, which affect the separation and analysis by 1D and 2D gel electrophoresis. We compared six protein extraction protocols concerning their suitability for further application with proteomic workflows. The protocols involving protein precipitation were the most efficient, with emphasis on TCA-acetone protocol, allowing us to identify the most abundant proteins on the secretome of this plant pathogen. Approximately 60% of the spots detected were identified, all corresponding to extracellular proteins. Most proteins identified were carbohydrate degrading enzymes and proteases that may be related to D. corticola pathogenicity. Although the secretome was assessed in a noninfection environment, potential virulence factors such as the putative glucan-β-glucosidase, neuraminidase, and the putative ferulic acid esterase were identified. The data obtained forms a useful basis for a deeper understanding of the pathogenicity and infection biology of D. corticola. Moreover, it will contribute to the development of proteomics studies on other members of the Botryosphaeriaceae.

  13. Involvement of inflammatory factors in pancreatic carcinogenesis and preventive effects of anti-inflammatory agents.

    Takahashi, Mami; Mutoh, Michihiro; Ishigamori, Rikako; Fujii, Gen; Imai, Toshio


    Chronic inflammation is known to be a risk for many cancers, including pancreatic cancer. Heavy alcohol drinking and cigarette smoking are major causes of pancreatitis, and epidemiological studies have shown that smoking and chronic pancreatitis are risk factors for pancreatic cancer. Meanwhile, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are elevated in pancreatitis and pancreatic cancer tissues in humans and in animal models. Selective inhibitors of iNOS and COX-2 suppress pancreatic cancer development in a chemical carcinogenesis model of hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). In addition, hyperlipidemia, obesity, and type II diabetes are also suggested to be associated with chronic inflammation in the pancreas and involved in pancreatic cancer development. We have shown that a high-fat diet increased pancreatic cancer development in BOP-treated hamsters, along with aggravation of hyperlipidemia, severe fatty infiltration, and increased expression of adipokines and inflammatory factors in the pancreas. Of note, fatty pancreas has been observed in obese and/or diabetic cases in humans. Preventive effects of anti-hyperlipidemic/anti-diabetic agents on pancreatic cancer have also been shown in humans and animals. Taking this evidence into consideration, modulation of inflammatory factors by anti-inflammatory agents will provide useful data for prevention of pancreatic cancer.

  14. Mechanisms involved in alleviation of intestinal inflammation by bifidobacterium breve soluble factors.

    Elise Heuvelin

    Full Text Available OBJECTIVES: Soluble factors released by Bifidobacterium breve C50 (Bb alleviate the secretion of pro-inflammatory cytokines by immune cells, but their effect on intestinal epithelium remains elusive. To decipher the mechanisms accounting for the cross-talk between bacteria/soluble factors and intestinal epithelium, we measured the capacity of the bacteria, its conditioned medium (Bb-CM and other Gram(+ commensal bacteria to dampen inflammatory chemokine secretion. METHODS: TNFalpha-induced chemokine (CXCL8 secretion and alteration of NF-kappaB and AP-1 signalling pathways by Bb were studied by EMSA, confocal microscopy and western blotting. Anti-inflammatory capacity was also tested in vivo in a model of TNBS-induced colitis in mice. RESULTS: Bb and Bb-CM, but not other commensal bacteria, induced a time and dose-dependent inhibition of CXCL8 secretion by epithelial cells driven by both AP-1 and NF-kappaB transcription pathways and implying decreased phosphorylation of p38-MAPK and IkappaB-alpha molecules. In TNBS-induced colitis in mice, Bb-CM decreased the colitis score and inflammatory cytokine expression, an effect reproduced by dendritic cell conditioning with Bb-CM. CONCLUSIONS: Bb and secreted soluble factors contribute positively to intestinal homeostasis by attenuating chemokine production. The results indicate that Bb down regulate inflammation at the epithelial level by inhibiting phosphorylations involved in inflammatory processes and by protective conditioning of dendritic cells.

  15. [Rbf1 (RPG-box binding factor), a transcription factor involved in yeast-hyphal transition of Candida albicans].

    Aoki, Y; Ishii, N; Watanabe, M; Yoshihara, F; Arisawa, M


    The major fungal pathogen for fungal diseases which have become a major medical problem in the last few years is Candida albicans, which can grow both in yeast and hyphae forms. This ability of C. albicans is thought to contribute to its colonization and dissemination within host tissues. In a recent few years, accompanying the introduction of molecular biological tools into C. albicans organism, several factors involved in the signal transduction pathway for yeast-hyphal transition have been identified. One MAP kinase pathway in C. albicans, similar to that leading to STE12 activation in Saccharomyces cerevisiae, has been reported. C. albicans strains mutant in these genes show retarded filamentous growth on a solid media but no impairment of filamentous growth in mice. These results suggest two scenarios that a kinase signaling cascade plays a part in stimulating the morphological transition in C. albicans, and that there would be another signaling pathway effective in animals. In this latter true hyphal pathway, although some candidate proteins, such as Efg1 (transcription factor), Int1 (integrin-like membrane protein), or Phr1 (pH-regulated membrane protein), have been identified, it is still too early to say that we understand the whole picture of that cascade. We have cloned a C. albicans gene encoding a novel DNA binding protein, Rbf1, that predominantly localizes in the nucleus, and shows transcriptional activation capability. Disruption of the functional RBF1 genes of C. albicans induced the filamentous growth on all solid and liquid media tested, suggesting that Rbf1 might be another candidate for the true hyphal pathway. Relationships with other factors described above, and the target (regulated) genes of Rbf1 is under investigation.

  16. How to Cope with the Rare Human Error Events Involved with organizational Factors in Nuclear Power Plants

    Kim, Sa Kil; Luo, Meiling; Lee, Yong Hee [Korea Atomic Research Institute, Daejeon (Korea, Republic of)


    The current human error guidelines (e.g. US DOD handbooks, US NRC Guidelines) are representative tools to prevent human errors. These tools, however, have limits that they do not adapt all operating situations and circumstances such as design base events. In other words, these tools are only adapted foreseeable standardized operating situations and circumstances. In this study, our research team proposed an evidence-based approach such as UK's safety case to coping with the rare human error events such as TMI, Chernobyl, Fukushima accidents. These accidents are representative events involved with rare human errors. Our research team defined the 'rare human errors' as the follow three characterized events; Extremely low frequency Extremely high complicated structure Extremely serious damage of human life and property A safety case is a structured argument, supported by evidence, intended to justify that a system is acceptably safe. The definition by UK defense standard 00-56 issue 4 states that such an evidence-based approach can be contrast with a prescriptive approach to safety certification, which require safety to be justified using a prescribed process. Safety managements and safety regulatory activities based on safety case are effective to control organizational factors in terms of integrated safety management. Especially safety issues relevant with public acceptance are useful to provide practical evidences to the public reasonably. European Union including UK has developed the concept of engineered safety management system to deal with public acceptance using the safety case. In Korea nuclear industry, the Korean Atomic Research Institute has firstly performed a basic research to adapt the safety case in the field of radioactive waste according to the IAEA SSG-23(KAERI/TR-4497, 4531). Excepting the radioactive waste, there is no try to adapt the safety case yet. Most incidents and accidents involved human during operating NPPs have a tendency

  17. What factors are most relevant to the assessment of work ability of employees on long-term sick leave? The physicians' perspective.

    Dekkers-Sánchez, Patricia M; Wind, Haije; Sluiter, Judith K; Frings-Dresen, Monique H W


    To reach insurance physician (IPs) consensus on factors that must be taken into account in the assessment of the work ability of employees who are sick-listed for 2 years. A Delphi study using online questionnaires was conducted from October 2010 to March 2011. One hundred and two insurance physicians reached a consensus on important factors for return to work (RTW) of employees on long-term sick leave; from those factors, the most relevant for the assessment of work ability was determined. From a total of 22 relevant factors considered for the return to work of long-term sick-listed employees, consensus was reached on nine relevant factors that need to be taken into account in the assessment of the work ability of employees on long-term sick leave. Relevant factors that support return to work are motivation, attitude towards RTW, assessment of cognitions and behaviour, vocational rehabilitation in an early stage and instruction for the sick-listed employee to cope with his disabilities. Relevant factors that hinder RTW are secondary gain from illness, negative perceptions of illness, inefficient coping style and incorrect advice of treating physicians regarding RTW. Non-medical personal and environmental factors may either hinder or promote RTW and must be considered in the assessment of the work ability of long-term sick-listed employees. Assessment of work ability should start early during the sick leave period. These factors may be used by IPs to improve the quality of the assessment of the work ability of employees on long-term sick leave.

  18. The associated factors to endometrial cavity fluid and the relevant impact on the IVF-ET outcome

    Li Ya-Qiong


    Full Text Available Abstract Background Endometrial cavity fluid (ECF is a fluid accumulation within the endometrial cavity. The significance of ECF remains unclear during the program of in vitro fertilization-embryo transfer (IVF-ET. The aim of the present study was to investigate the associated factors to ECF, visualized through ultrasound at the day of oocyte retrieval, and the relevant impact on the outcome of IVF-ET. Methods From the clinical data of 1557 infertility patients for IVF-ET program, 46 ECF patients were retrospectively selected as the ECF group; and another 134 patients with a bilateral salpingectomy and without ECF, selected as the control group. The demographics and the outcome of IVF-ET were compared between the two groups. Results The incidence of ECF was 2.95% (46/1557. Over half (28/46, 60.87% of ECF patients had tubal infertility. Only 12 Of 46 ECF patients (26.09% had visible hydrosalpinx on ultrasonography before ovarian stimulation. The cycle cancellation rate (4/46, 8.69% of ECF group was not significantly higher than that of the control group (6/134, 4.48%; P > 0.05. Reasons for cycle cancellation in both groups were all the high risk of ovarian hyperstimulation syndrome (OHSS. No significant difference was found in clinical pregnancy rate between the patients with their ECF 0.05. No clinical pregnancy was found among those patients with their ECF equal or higher 3.5 mm in APD. Conclusions It was tubal infertility, not hydrosalpinx, which was related to the development of ECF. Excessive ECF (equal or higher 3.5 mm in APD at the day of oocyte retrieval would have a negative impact on the outcome of IVF-ET.

  19. Are the risk and protective factors similar for gang-involved, pressured-to-join, and non-gang-involved youth? A social-ecological analysis.

    Merrin, Gabriel J; Hong, Jun Sung; Espelage, Dorothy L


    This study examines the risk and protective factors for gang involvement among subgroups of youth (i.e., current or former gang members, youth who resisted gang membership, and non-gang-involved youth) using the social-ecological framework. Middle and high school students (N = 17,366) from school districts in a large Midwestern county participated. Results indicated that males were more likely than females to be involved in gangs. For the individual context, our findings indicate that racial and ethnic minorities, females, and youth with depression/suicidal ideation are likely to be at risk for gang involvement. For the family context, we found that having gang-involved family members and family dysfunction are related to youth gang involvement. For the peer context, peers' alcohol and drug use and bullying were significantly associated with gang involvement. For the school context, as our results demonstrate, youth who perceived fair treatment from teachers and other adults in school and those with a sense of belonging in school are more likely to avoid gang membership. For the neighborhood context, we found that presence of adult support in the neighborhood and perceived neighborhood safety are negatively associated with gang membership. Findings suggest that gang prevention efforts need to target multiple ecologies that surround and influence youth. (PsycINFO Database Record

  20. Studying Factors Involved in Biogenesis of Lysobacter sp. XL1 Outer Membrane Vesicles.

    Kudryakova, I V; Suzina, N E; Vinokurova, N G; Shishkova, N A; Vasilyeva, N V


    The Gram-negative bacterium Lysobacter sp. XL1 produces outer membrane vesicles that are heterogeneous in size, density, and protein composition. One of the subpopulations is secretory vesicles for lytic protease L5 of Lysobacter sp. XL1 (Kudryakova et al. (2015) FEMS Microbiol. Lett., 362, fnv137). Protein L5 was assumed to influence biogenesis of these secretory vesicles that contain it. Using a Pseudomonas fluorescens Q2-87/B expression system, it was shown that the recombinant L5 protein may act as a factor of vesicle biogenesis. This points to a possible involvement of L5 protein in Lysobacter sp. XL1 vesicle biogenesis. Furthermore, it was established that the main phospholipid of Lysobacter sp. XL1 vesicles is cardiolipin, and vesicles are formed predominantly of outer membrane regions enriched with this phospholipid. This indicates that cardiolipin participates in biogenesis of all vesicle subpopulations in Lysobacter sp. XL1.

  1. Analysis of molecular markers as predictive factors of lymph node involvement in breast carcinoma

    Paula, Luciana Marques; De Moraes, Luis Henrique Ferreira; Do Canto, Abaeté Leite


    Nodal status is the most significant independent prognostic factor in breast cancer. Identification of molecular markers would allow stratification of patients who require surgical assessment of lymph nodes from the large numbers of patients for whom this surgical procedure is unnecessary, thus...... leading to a more accurate prognosis. However, up to now, the reported studies are preliminary and controversial, and although hundreds of markers have been assessed, few of them have been used in clinical practice for treatment or prognosis in breast cancer. The purpose of the present study...... ankyrin-related ADP-ribose polymerase 2, BCL2 associated agonist of cell death, G2 and S-phase expressed 1 and PAX interacting protein 1 genes, described as prognostic markers in breast cancer in a previous microarray study, are also predictors of lymph node involvement in breast carcinoma Reverse...

  2. Consistent analysis of one-nucleon spectroscopic factors involving weakly- and strongly-bound nucleons

    Okołowicz, J.; Lam, Y. H.; Płoszajczak, M.; Macchiavelli, A. O.; Smirnova, N. A.


    There is a considerable interest in understanding the dependence of one-nucleon removal cross sections on the asymmetry of the neutron Sn and proton Sp separation energies, following a large amount of experimental data and theoretical analyses in a framework of sudden and eikonal approximations of the reaction dynamics. These theoretical calculations involve both the single-particle cross section and the shell-model description of the projectile initial state and final states of the reaction residues. The configuration mixing in shell-model description of nuclear states depends on the proximity of one-nucleon decay threshold but does it depend sensitively on Sn -Sp? To answer this question, we use the shell model embedded in the continuum to investigate the dependence of one-nucleon spectroscopic factors on the asymmetry of Sn and Sp for mirror nuclei 24Si, 24Ne and 28S, 28Mg and for a series of neon isotopes (20 ≤ A ≤ 28).

  3. Platelet-derived growth factor involvement in myocardial remodeling following infarction.

    Zhao, Wenyuan; Zhao, Tieqiang; Huang, Valerie; Chen, Yuanjian; Ahokas, Robert A; Sun, Yao


    Cardiac remodeling occurs in the infarcted heart (MI). The underlying regulatory mechanisms are under investigation. Platelet-derived growth factor (PDGF) is a family of growth factors that stimulates cell growth, differentiation and migration. Herein, we sought to determine whether PDGF is involved in cardiac repair/remodeling following MI. The temporal and spatial expressions of PDGF isoforms (A, B, C and D) and PDGF receptor (PDGFR)-α and β as well as cell types expressing PDGF were examined in the infarcted rat heart. Sham-operated rats served as controls. We found that the normal myocardium expressed all PDGF isoforms, and cell types expressing PDGF were primarily interstitial cells. Following MI, PDGF-A and D were significantly increased in the infarcted myocardium during 6 weeks of the observation period and cells expressing PDGF-A and D were primarily endothelial cells, macrophages and myofibroblasts (myoFb). PDGF-B and C expressions were, however, reduced in the infarcted heart. In the noninfarcted myocardium, PDGF-D expression was increased in the late stage of MI and cells expressing PDGF-D were predominantly fibroblasts. Both PDGFR-α and β were significantly increased in the infarcted myocardium in the early and late stages of MI and in the noninfarcted myocardium in the late stage of MI. Enhanced PDGF-A, PDGF-D and PDGFR are coincident with angiogenesis, and inflammatory and fibrogenic responses in the infarcted myocardium, suggesting their regulation on cardiac repair. Elevated PDGF-D in the noninfarcted myocardium suggests its involvement in the development of interstitial fibrosis that appears in the late stage of MI.

  4. Hypothalamic corticotropin-releasing factor is centrally involved in learning under moderate stress.

    Lucas, Morgan; Chen, Alon; Richter-Levin, Gal


    The corticotropin-releasing factor (CRF) neuropeptide is found to have a pivotal role in the regulation of the behavioral and neuroendocrine responses to stressful challenges. Here, we studied the involvement of the hypothalamic CRF in learning under stressful conditions. We have used a site-specific viral approach to knockdown (KD) CRF expression in the paraventricular nucleus of the hypothalamus (PVN). The two-way shuttle avoidance (TWSA) task was chosen to assess learning and memory under stressful conditions. Control animals learned to shuttle from one side to the other to avoid electrical foot shock by responding to a tone. Novel object and social recognition tasks were used to assess memory under less stressful conditions. KD of PVN-CRF expression decreased the number of avoidance responses in a TWSA session under moderate (0.8 mA), but not strong (1.5 mA), stimulus intensity compared to control rats. On the other hand, KD of PVN-CRF had no effect on memory performance in the less stressful novel object or social recognition tasks. Interestingly, basal or stress-induced corticosterone levels in CRF KD rats were not significantly different from controls. Taken together, the data suggest that the observed impairment was not a result of alteration in HPA axis activity, but rather due to reduced PVN-CRF activity on other brain areas. We propose that hypothalamic CRF is centrally involved in learning under moderate stressful challenge. Under 'basal' (less stressful) conditions or when the intensity of the stress is more demanding, central CRF ceases to be the determinant factor, as was indicated by performances in the TWSA with higher stimulus intensity or in the less stressful tasks of object and social recognition.

  5. Trophic factor-induced excitatory synaptogenesis involves postsynaptic modulation of nicotinic acetylcholine receptors.

    Woodin, Melanie A; Munno, David W; Syed, Naweed I


    Neurotrophic factors have well established roles in neuronal development, although their precise involvement in synapse formation and plasticity is yet to be fully determined. Using soma-soma synapses between identified Lymnaea neurons, we have shown recently that trophic factors are required for excitatory but not inhibitory synapse formation. However, neither the precise site (presynaptic versus postsynaptic cell) nor the underlying mechanisms have yet been defined. In the present study, synapse formation between the presynaptic cell visceral dorsal 4 (VD4) and its postsynaptic partner right pedal dorsal 1 (RPeD1) was examined to define the cellular mechanisms mediating trophic factor-induced excitatory synaptogenesis in cell culture. When paired in a soma-soma configuration in the presence of defined media (DM, nonproteinacious), mutually inhibitory synapses were appropriately reconstructed between VD4 and RPeD1. However, when cells were paired in the presence of increasing concentrations of Lymnaea brain-conditioned medium (CM), a biphasic synapse (initial excitatory synaptic component followed by inhibition) developed. The CM-induced excitatory synapse formation required trophic factor-mediated activation of receptor tyrosine kinases in the postsynaptic cell, RPeD1, and a concomitant modulation of existing postsynaptic nicotinic acetylcholine receptors (nAChRs). Specifically, when RPeD1 was isolated in DM, exogenously applied ACh induced a hyperpolarizing response that was sensitive to the AChR antagonist methyllycaconitine (MLA). In contrast, a single RPeD1 isolated in CM exhibited a biphasic response to exogenously applied ACh. The initial depolarizing phase of the biphasic response was sensitive to both mecamylamine and hexamethonium chloride, whereas the hyperpolarizing phase was blocked by MLA. In soma-soma-paired neurons, the VD4-induced synaptic responses in RPeD1 were sensitive to the cholinergic antagonists in a concentration range similar to that

  6. Endothelial cell permeability during hantavirus infection involves factor XII-dependent increased activation of the kallikrein-kinin system.

    Shannon L Taylor

    Full Text Available Hemorrhagic fever with renal syndrome (HFRS and hantavirus pulmonary syndrome (HPS are diseases caused by hantavirus infections and are characterized by vascular leakage due to alterations of the endothelial barrier. Hantavirus-infected endothelial cells (EC display no overt cytopathology; consequently, pathogenesis models have focused either on the influx of immune cells and release of cytokines or on increased degradation of the adherens junction protein, vascular endothelial (VE-cadherin, due to hantavirus-mediated hypersensitization of EC to vascular endothelial growth factor (VEGF. To examine endothelial leakage in a relevant in vitro system, we co-cultured endothelial and vascular smooth muscle cells (vSMC to generate capillary blood vessel-like structures. In contrast to results obtained in monolayers of cultured EC, we found that despite viral replication in both cell types as well as the presence of VEGF, infected in vitro vessels neither lost integrity nor displayed evidence of VE-cadherin degradation. Here, we present evidence for a novel mechanism of hantavirus-induced vascular leakage involving activation of the plasma kallikrein-kinin system (KKS. We show that incubation of factor XII (FXII, prekallikrein (PK, and high molecular weight kininogen (HK plasma proteins with hantavirus-infected EC results in increased cleavage of HK, higher enzymatic activities of FXIIa/kallikrein (KAL and increased liberation of bradykinin (BK. Measuring cell permeability in real-time using electric cell-substrate impedance sensing (ECIS, we identified dramatic increases in endothelial cell permeability after KKS activation and liberation of BK. Furthermore, the alterations in permeability could be prevented using inhibitors that directly block BK binding, the activity of FXIIa, or the activity of KAL. Lastly, FXII binding and autoactivation is increased on the surface of hantavirus-infected EC. These data are the first to demonstrate KKS activation

  7. Study of signal transduction factors involved in mycoparasitic response of Trichoderma atroviride

    Lorito M; Zeilinger S; Ambrosino P; Brunner K; Reithner B; Mach R L; Woo S L; Cristilli M; Scala F


    @@ Numerous Trichoderma spp. are mycoparasites and commercially applied as biological control agents against a large number of plant pathogenic fungi. The mycoparasitic interaction is host-specific and several research strategies have been applied to identify the main genes and compounds involved in the antagonist-plant-pathogen three-way interaction. During mycoparasitism, signals from the host fungus are recognised by Trichoderma, stimulating antifungal activities that are accompanied by morphological changes and the secretion of hydrolytic enzymes and antibiotics. Interestingly some morphological changes appeared highly conserved in the strategy of pathogenicity within the fungal world, i.e. the formation of appressoria as well as the secretion of hydrolytic enzymes seem to be general mechanisms of attack both for plant pathogens and mycoparasitic antagonists. This knowledge is being used to identify receptors and key components of signalling pathways involved in fungus-fungus interaction. For this purpose we have cloned the first genes (tmk1 , tga1 , tga3) from T. atroviride showing a high similarity to MAP kinase and G protein subunits (see abstract by Zeilinger et al.),which have been found to have an important role in pathogenicity by Magnaporthe grisea. To identify the function and involvement of these factors in mycoparasitism by T. atroviride, tmk1, tga1, tga3disruptant strains were produced. The knock-out mutants were tested by in vivo biocontrol assays for their ability to inhibit soil and foliar plant pathogens such as Rhizoctonia solani, Pythium ultimum and Botrytis cinerea . Disruption of these genes corresponded to a complete loss of biocontrol ability,suggesting a significant role in mycoparasitism. In particular, it has been suggested that tga3 regulates the expression of chitinase-encoding genes, the secretion of the corresponding enzymes and the process of conidiation. Comparative proteome analysis of wild type and disruptants supported this

  8. Perpetual factors involved in performance of air traffic controllers using a microwave landing system

    Gershzohn, G.


    The task involved the control of two simulated aircraft targets per trial, in a 37.0 -km radius terminal area, by means of conventional radar vectoring and/or speed control. The goal was to insure that the two targets crossed the Missed Approach Point (MAP) at the runway threshold exactly 60 sec apart. The effects on controller performance of the MLS configuration under wind and no-wind conditions were examined. The data for mean separation time between targets at the MAP and the range about that mean were analyzed by appropriate analyses of variance. Significant effects were found for mean separation times as a result of the configuration of the MLS and for interaction between the configuration and wind conditions. The analysis of variance for range indicated significantly poorer performance under the wind condition. These findings are believed to be a result of certain perceptual factors involved in radar air traffic control (ATC) using the MLS with separation of targets in time.

  9. Adiponectin stimulates Wnt inhibitory factor-1 expression through epigenetic regulations involving the transcription factor specificity protein 1.

    Liu, Jing; Lam, Janice B B; Chow, Kim H M; Xu, Aimin; Lam, Karen S L; Moon, Randall T; Wang, Yu


    Adiponectin (ADN) is an adipokine possessing growth inhibitory activities against various types of cancer cells. Our previous results demonstrated that ADN could impede Wnt/beta-catenin-signaling pathways in MDA-MB-231 human breast carcinoma cells [Wang,Y. et al. (2006) Adiponectin modulates the glycogen synthase kinase-3 beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. Cancer Res., 66, 11462-11470]. Here, we extended our studies to elucidate the effects of ADN on regulating the expressions of Wnt inhibitory factor-1 (WIF1), a Wnt antagonist frequently silenced in human breast tumors. Our results showed that ADN time dependently stimulated WIF1 gene and protein expressions in MDA-MB-231 cells. Overexpression of WIF1 exerted similar inhibitory effects to those of ADN on cell proliferations, nuclear beta-catenin activities, cyclin D1 expressions and serum-induced phosphorylations of Akt and glycogen synthase kinase-3 beta. Blockage of WIF1 activities significantly attenuated the suppressive effects of ADN on MDA-MB-231 cell growth. Furthermore, our in vivo studies showed that both supplementation of recombinant ADN and adenovirus-mediated overexpression of this adipokine substantially enhanced WIF1 expressions in MDA-MB-231 tumors implanted in nude mice. More interestingly, we found that ADN could alleviate methylation of CpG islands located within the proximal promoter region of WIF1, possibly involving the specificity protein 1 (Sp1) transcription factor and its downstream target DNA methyltransferase 1 (DNMT1). Upon ADN treatment, the protein levels of both Sp1 and DNMT1 were significantly decreased. Using silencing RNA approaches, we confirmed that downregulation of Sp1 resulted in an increased expression of WIF1 and decreased methylation of WIF1 promoter. Taken together, these data suggest that ADN might elicit its antitumor activities at least partially through promoting WIF1 expressions.

  10. Human factors involvement in bringing the power of AI to a heterogeneous user population

    Czerwinski, Mary; Nguyen, Trung


    The Human Factors involvement in developing COMPAQ QuickSolve, an electronic problem-solving and information system for Compaq's line of networked printers, is described. Empowering customers with expert system technology so they could solve advanced networked printer problems on their own was a major goal in designing this system. This process would minimize customer down-time, reduce the number of phone calls to the Compaq Customer Support Center, improve customer satisfaction, and, most importantly, differentiate Compaq printers in the marketplace by providing the best, and most technologically advanced, customer support. This represents a re-engineering of Compaq's customer support strategy and implementation. In its first generation system, SMART, the objective was to provide expert knowledge to Compaq's help desk operation to more quickly and correctly answer customer questions and problems. QuickSolve is a second generation system in that customer support is put directly in the hands of the consumers. As a result, the design of QuickSolve presented a number of challenging issues. Because the produce would be used by a diverse and heterogeneous set of users, a significant amount of human factors research and analysis was required while designing and implementing the system. Research that shaped the organization and design of the expert system component as well.

  11. Identification of pathogenic factors potentially involved in Staphylococcus aureus keratitis using proteomics.

    Khan, Shamila; Cole, Nerida; Hume, Emma B H; Garthwaite, Linda L; Nguyen-Khuong, Terry; Walsh, Bradley J; Willcox, Mark D P


    Staphylococcus is a leading cause of microbial keratitis, characterized by destruction of the cornea by bacterial exoproteins and host-associated factors. The aim of this study was to compare extracellular and cell-associated proteins produced by two different isolates of S. aureus, a virulent clinical isolate (Staph 38) and a laboratory strain (Staphylococcus aureus 8325-4) of weaker virulence in the mouse keratitis model. Proteins were analyzed using 2D polyacrylamide gel electrophoresis and identified by subsequent mass spectrometry. Activity of staphylococcal adhesins was assessed by allowing strains to bind to various proteins adsorbed onto polymethylmethacrylate squares. Thirteen proteins in the extracellular fraction and eight proteins in the cell-associated fractions after bacterial growth were produced in increased amounts in the clinical isolate Staph 38. Four of these proteins were S. aureus virulence factor adhesins, fibronectin binding protein A, staphopain, glyceraldehyde-3-phosphate dehydrogenase 2 and extracellular adherence protein. The clinical isolate Staph 38 adhered to a greater extent to all mammalian proteins tested, indicating the potential of the adhesins to be active on its surface. Other proteins with increased expression in Staph 38 included potential moonlighting proteins and proteins involved in transcription or translation. This is the first demonstration of the proteome of S. aureus isolates from keratitis. These results indicate that the virulent clinical isolate produces more potentially important virulence factors compared to the less virulent laboratory strain and these may be associated with the ability of a S. aureus strain to cause more severe keratitis.

  12. ROP6 is involved in root hair deformation induced by Nod factors in Lotus japonicus.

    Ke, Danxia; Li, Xiangyong; Han, Yapeng; Cheng, Lin; Yuan, Hongyu; Wang, Lei


    Roots of leguminous plants perceive Nod factor signals, and then root hair deformation responses such as swelling and curling are activated. However, very little is known about the molecular mechanisms of such root hair deformation. We have previously shown that LjROP6, a member of the Rho family of small GTPases, was identified as an NFR5 (Nod Factor Receptor 5)-interacting protein and participated in symbiotic nodulation in Lotus japonicus. In this study, we identified ten LjROP GTPases including LjROP6, and they were distributed into groups II, III, IV but not group I by phylogenetic analysis. The expression profiles of ten LjROP genes during nodulation were examined. LjROP6 belonged to group IV and interacted with NFR5 in a GTP-dependent manner. Overexpression of either wild-type ROP6 or a constitutively active mutant (ROP6-CA) generated root hair tip growth depolarization, while overexpression of a dominant negative mutant (ROP6-DN) exhibited normal root hair growth. After inoculating with Mesorhizobium loti or adding Nod factors to hairy roots, overexpression of ROP6 and ROP6-CA exhibited extensive root hair deformation, while overexpression of ROP6-DN inhibited root hair deformation. The infection event and nodule number were increased in ROP6 and ROP6-CA overexpressing transgenic plants; but decreased in ROP6-DN overexpressing transgenic plants. These studies provide strong evidence that ROP6 GTPase, which binds NFR5 in a GTP-dependent manner, is involved in root hair development as well as root hair deformation responses induced by NFs in the early stage of symbiotic interaction in L. japonicus.

  13. Risk and Protective Factors of Suicidal Ideation and Attempt among Adolescents with Different Types of School Bullying Involvement.

    Yen, Cheng-Fang; Liu, Tai-Ling; Yang, Pinchen; Hu, Huei-Fan


    Suicide has been found to be prevalent among adolescents involved in bullying; however, there has been a lack of research examining whether the risk and protective factors of suicidal ideation and attempt are different among adolescents with different types of bullying involvement. The aims of this study were to examine the risk and protective factors of suicidal ideation and attempt among adolescents with different experiences of bullying involvement, victimization, and perpetration. A total of 4,533 adolescents participated in this study. Different groups of bullying involvement, victimization, and perpetration were determined through use of the Chinese version of the School Bullying Experience Questionnaire. The associations of suicidal ideation and attempt with possible risk factors (domestic violence, overweight, depression, anxiety, and alcohol abuse) and protective factors (family support and self-esteem) were examined using logistic regression analysis. Pure victims, pure perpetrators, and victim-perpetrators were more likely to report suicidal ideation and attempt than the neutral group. The risk and protective factors of suicidal ideation and attempt were different across adolescents with different experiences of bullying involvement, victimization, and perpetrators. The risk of suicide should be monitored among adolescents who are involved in any type of bullying. The risk and protective factors of suicide identified in this study should be taken into consideration in prevention and intervention programs for suicide in adolescents involved in bullying.

  14. Variability and reduced performance of preschool- and early school-aged children on psychoacoustic tasks: What are the relevant factors?

    Allen, Prudence


    Young children typically perform more poorly on psychoacoustic tasks than do adults, with large individual differences. When performance is averaged across children within age groups, the data suggest a gradual change in performance with increasing age. However, an examination of individual data suggests that the performance matures more rapidly, although at different times for different children. The mechanisms of development responsible for these changes are likely very complex, involving both sensory and cognitive processes. This paper will discuss some previously suggested mechanisms including attention and cue weighting, as well as possibilities suggested from more recent studies in which learning effects were examined. In one task, a simple frequency discrimination was required, while in another the listener was required to extract regularities in complex sequences of sounds that varied from trial to trial. Results suggested that the ability to select and consistently employ an effective listening strategy was especially important in the performance of the more complex task, while simple stimulus exposure and motivation contributed to the simpler task. These factors are important for understanding the perceptual development and for the subsequent application of psychoacoustic findings to clinical populations. [Work supported by the NSERC and the Canadian Language and Literacy Research Network.

  15. Examining Socio-Cultural and Neighborhood Factors Associated with Trajectories of Mexican-Origin Mothers' Education-Related Involvement.

    Bhargava, Sakshi; Bámaca-Colbert, Mayra Y; Witherspoon, Dawn P; Pomerantz, Eva M; Robins, Richard W


    Parental involvement in education is an important determinant of youth's academic success. Yet, there is limited knowledge on how Latino parents' education-related involvement changes over time. Using data from a longitudinal study of 674 Mexican-origin families (mother-adolescent dyad; M age of child at Wave 1=10.4, SD = 0.60), we examined trajectories of parental involvement from 5(th) to 11(th) grade and the effects of socio-cultural (e.g., family SES and acculturation) and contextual (e.g., neighborhood) factors on these trajectories. Results showed that mothers reduced two aspects of the educational involvement: home-based involvement and academic aspirations, but increased on a third aspect of involvement, resource seeking. Furthermore, family SES, acculturation, and neighborhood context were differentially associated with mothers' involvement at 5(th) grade and predicted changes in involvement across elementary and high school.

  16. The Multiple Factors and Multiple Stages Involved in Sedimentary Ore Genesis

    叶连俊; 陈其英


    Sedimentary mineral deposits cannot be formed by any kind of simple chemical reactions,but are products of a complex multi-episodic process depending on multiple factors,The whole process is governed by a combination of sedimentary,geochemical,biogeochemical,organic geochemical,paleoclimatical,mechanical agents as well as by the properties of relevant earth crust segment and its structural making up and tectonic mobility A Sedimentary ore deposit is nothing but a special kind of sedimentary facies,characterized by definite sedimentary assemblages,Different genetic types of ore deposit and different ore associations characterize different sedimentary assemblages in different ore-forming belts.Crustal movement,including orogenic,epeirogenic and,oparticularly eustatic events,controls the formation and distribution of all kinds of sedimentary mineral deposits,most of which occur within the transgression front in the lower part of marine transpressive series.Mineral deposits of economic importance cannot be precipitated directly from sea water,but are products of terrestrial imbibition,biological enrichment and pore water concentration instead,Deposits formed above the wave base in the inner continental shelf under strong dynamic condition of sea water are often large and predominantly clastic in texture with commercial grade.Below the wave base in the outer continental shelf environment,where it is more or less dynamically stagnant and oxygen-deficient,the resulted in dustrial ore deposits are mostly of diagenetic or strata-bound type,formed through deep-burying diagenesis.The theory of multi-factor and multi-episodic metallogenesis includes three major aspects:the ore-forming process,the sedimentary environment and the geological background.The study of the forma tion process itself and the sources of ore-forming elements would provide useful clues to further prospectiong Whereas,invstigations of the sedimentary environments should shed light on the spacial

  17. Factores relevantes en complicaciones de fracturas mandibulares: Relato de 5 años Factors relevant to mandibular fracture complications: A 5-year experience

    E. Serena Gómez


    Full Text Available Objetivo: Este estudio ayudará a comprender factores relevantes y su relación con complicaciones post-operatorias en pacientes con tratamiento de fracturas mandibulares. Diseño de estudio: Para el estudio fueron obtenidos datos de pacientes atendidos en un periodo de cinco años por el Área de Cirugía y Traumatología Buco-Maxilofacial de la Facultad de Odontología de Piracicaba, UNICAMP, Brasil. Los datos relevantes de los pacientes en esta investigación fueron; edad, género, actividad económica, consumo de sustancias, etiología del trauma, demora de tratamiento de fractura, tipo de fractura mandibular, complicación post-operatoria y tratamiento a la complicación. Resultados: Un total de 472 pacientes presentaron fracturas mandibulares, de los cuales 54 pacientes (11,4% desarrollaron alguna complicación postoperatoria al tratamiento. En el grupo de pacientes con complicaciones postoperatorias, el género masculino predominó con 44 pacientes y la media de edad fue de 29,3 años de edad. En este grupo se presentaron sin actividad económica 35,2% de los pacientes y 33 (61% relataron abuso en sustancias nocivas a la salud. La agresión física fue la causa mas común (35,1%. Fracturas mandibulares múltiples fueron relatadas en 34 pacientes (62,9%. Infección se presento en 32 pacientes (59,2%. Tratamiento hospitalario para las complicaciones fue necesario para 30 pacientes (55,5%. Conclusiones: Actividad económica y demora en el tratamiento de fracturas mandibulares no fueron significantes en el desarrollo de complicaciones post-operatorias. Por otra parte, la severidad del trauma y el tipo de fractura, consideradamente pueden influir, así como el consumo de sustancias, que presentó una fuerte relación en la presencia de complicaciones.Objective: This study was made to determine the factors relevant to postoperative complications in patients treated for mandibular fracture. Study design: The study was based on the medical

  18. Transcription factors of Schizophyllum commune involved in mushroom formation and modulation of vegetative growth.

    Pelkmans, Jordi F; Patil, Mohini B; Gehrmann, Thies; Reinders, Marcel J T; Wösten, Han A B; Lugones, Luis G


    Mushrooms are the most conspicuous fungal structures. Transcription factors (TFs) Bri1 and Hom1 of the model fungus Schizophyllum commune are involved in late stages of mushroom development, while Wc-2, Hom2, and Fst4 function early in development. Here, it is shown that Bri1 and Hom1 also stimulate vegetative growth, while biomass formation is repressed by Wc-2, Hom2, and Fst4. The Δbri1Δbri1 and the Δhom1Δhom1 strains formed up to 0.6 fold less biomass when compared to wild-type, while Δwc-2Δwc-2, Δhom2Δhom2, and Δfst4Δfst4 strains formed up to 2.8 fold more biomass. Inactivation of TF gene tea1, which was downregulated in the Δwc-2Δwc-2, Δhom2Δhom2, and Δfst4Δfst4 strains, resulted in a strain that was severely affected in mushroom development and that produced 1.3 fold more biomass than the wild-type. In contrast, introducing a constitutive active version of hom2 that had 4 predicted phosphorylation motifs eliminated resulted in radial growth inhibition and prompt fructification in both Δhom2 and wild-type strains, even in sterile monokaryons. Together, it is concluded that TFs involved in mushroom formation also modulate vegetative growth. Among these TFs is the homeodomain protein Hom2, being the first time that this class of regulatory proteins is implicated in repression of vegetative growth in a eukaryote.

  19. Mothers' and Fathers' Involvement in Home Activities with Their Children: Psychosocial Factors and the Role of Parental Self-Efficacy

    Giallo, Rebecca; Treyvaud, Karli; Cooklin, Amanda; Wade, Catherine


    Parent involvement in play, learning, and everyday home activities is important for promoting children's cognitive and language development. The aims of the study were to (a) examine differences between mothers' and fathers' self-reported involvement with their children, (b) explore the relationship between child, parent and family factors, and…

  20. Factors involved in selection of a career in surgery and orthopedics for medical students in Malawi.

    Kollias, C; Banza, L; Mkandawire, N


    There is a critical shortage of Orthopedic Surgeons in Malawi as well as all countries in sub-Saharan Africa. To date, there is no published literature that has investigated surgical or Orthopedic career selection amongst African medical trainees. With the goal of facilitating recruitment into Surgery and Orthopedics in Malawi, we explored the key aspects of Malawian Medical Students' choice of careers in surgical disciplines. An on-line survey of all students in clinical years at the College of Medicine in Blantyre, Malawi was performed. The survey was anonymous and constructed de novo by a stringent process including Item Generation, Item reduction, Survey composition, Pre-testing, Assessment of Validity by a recognized survey expert, Pilot testing in on-line format by several Malawian Medical Students, and then formal survey testing. Surgery was the most popular specialty choice among the medical trainees (46%). General Surgery was the popular surgical specialty (27%), followed by Neurosurgery (22%) and Orthopedics (19%). The majority of students (67%) feared occupational exposure to HIV but this did not appear to be a factor in specialty choice (p = 0.9). Students with Orthopedic mentors were significantly more likely to choose Orthopedics as their first choice surgical specialty (p = 0.01). Despite limited resources and surgeons in sub-Saharan Africa, surgical specialties are desirable career choices. This is the first evaluation of factors involved in surgical or Orthopedic career selection in any African context. Future initiatives to improve exposure and mentorship in Orthopedics are fundamental to recruitment into the specialty.

  1. Identification of Heat Shock Transcription Factor Genes Involved in Thermotolerance of Octoploid Cultivated Strawberry

    Liao, Wan-Yu; Lin, Lee-Fong; Jheng, Jing-Lian; Wang, Chun-Chung; Yang, Jui-Hung; Chou, Ming-Lun


    Heat shock transcription factors (HSFs) are mainly involved in the activation of genes in response to heat stress as well as other abiotic and biotic stresses. The growth, development, reproduction, and yield of strawberry are strongly limited by extreme temperatures and droughts. In this study, we used Illumina sequencing and obtained transcriptome data set from Fragaria × ananassa Duchessne cv. Toyonoka. Six contigs and three unigenes were confirmed to encode HSF proteins (FaTHSFs). Subsequently, we characterized the biological functions of two particularly selected unigenes, FaTHSFA2a and FaTHSFB1a, which were classified into class A2 and B HSFs, respectively. Expression assays revealed that FaTHSFA2a and FaTHSFB1a expression was induced by heat shock and correlated well with elevated ambient temperatures. Overexpression of FaTHSFA2a and FaTHSFB1a resulted in the activation of their downstream stress-associated genes, and notably enhanced the thermotolerance of transgenic Arabidopsis plants. Besides, both FaTHSFA2a and FaTHSFB1a fusion proteins localized in the nucleus, indicating their similar subcellular distributions as transcription factors. Our yeast one-hybrid assay suggested that FaTHSFA2a has trans-activation activity, whereas FaTHSFB1a expresses trans-repression function. Altogether, our annotated transcriptome sequences provide a beneficial resource for identifying most genes expressed in octoploid strawberry. Furthermore, HSF studies revealed the possible insights into the molecular mechanisms of thermotolerance, thus rendering valuable molecular breeding to improve the tolerance of strawberry in response to high-temperature stress. PMID:27999304

  2. [Factors involved in the burden of the primary caregiver of cancer patients].

    Valencia, M C; Meza-Osnaya, G; Pérez-Cruz, I; Cortes-Campero, N; Hernández-Ovalle, J; Hernández-Paredes, P; Juárez-Romero, K; Chino-Hernández, B; Romero-Figueroa, M S

    The aim of the study was to identify the factors involved between burden in the primary caregiver of cancer patients and their quality of life. A cross-sectional study was conducted in a secondary level hospital on 100 primary caregivers of cancer patients. The level of burden was determined using the Zarit scale and the perception of quality of life using the World Health Organisation Quality of Life questionnaire. Quality of life was categorised as high or low and compared between groups according to their level of burden. Descriptive statistics were performed on the study variables, and differences between groups were analysed according to their level of burden. In assessing the overload, it was found that 31% of caregivers had burden. A good quality of life was perceived by 76% of caregivers, while the remaining 24% perceived it as poor. To identify association between these two variables Chi squared (X2) was used to determine whether there was any association between quality of life and overloading of the primary caregiver, giving a P≤.05. A Spearman correlation was also performed, obtaining an r-value of .321 with a P≤.05, finding a slightly positive correlation. The factors that have a bearing on a good quality of life despite having burden were: being married, dedicated to the home, and kinship (to be immediate family: spouse, parents and children). Conversely, the type of cancer, sleep hours, and hours of care influence the perception of a poor quality of life. Copyright © 2017 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Factors involved in alleviating water stress by partial crop removal in pear trees.

    Marsal, Jordi; Mata, Merce; Arbones, Amadeu; Del Campo, Jesus; Girona, Joan; Lopez, Gerardo


    We studied the relief of water stress associated with fruit thinning in pear (Pyrus communis L.) trees during drought to determine what mechanisms, other than stomatal adjustment, were involved. Combinations of control irrigation (equal to crop water use less effective rainfall) and deficit irrigation (equal to 20% of control irrigation), fruit load (unthinned and thinned to 40 fruits per tree) and root pruning (pruned and unpruned) treatments were applied to pear (cv. 'Conference') trees during Stage II of fruit development. Daily patterns of midday stem water potential (Psi(stem)) and leaf conductance to water vapor (g(l)) of deficit-irrigated trees differed after fruit thinning. In response to fruit thinning, gl progressively declined with water stress until 30 days after fruit thinning and then leveled off, whereas the effects of decreased fruit load on Psi(stem) peaked 30-40 days after fruit thinning and then tended to decline. Soil water depletion was significantly correlated with fruit load during drought. Our results indicate that stomatal adjustment and the resulting soil water conservation were the factors determining the Psi(stem) response to fruit thinning. However, these factors could not explain differences in daily patterns between g(l) and Psi(stem) after fruit thinning. In all cases, effects of root pruning treatments on Psi(stem) in deficit-irrigated trees were transitory (Psi(stem) recovered from root pruning in less than 30 days), but the recovery of Psi(stem) after root pruning was faster in trees with low fruit loads. This behavior is compatible with the concept that the water balance (reflected by Psi(stem) values) was better in trees with low fruit loads compared with unthinned trees, perhaps because more carbon was available for root growth. Thus, a root growth component is hypothesized as a mechanism to explain the bimodal Psi(stem) response to fruit thinning during drought.

  4. AP2/ERF Transcription Factors Involved in Response to Tomato Yellow Leaf Curly Virus in Tomato

    Ying Huang


    Full Text Available Tomato yellow leaf curly virus (TYLCV, transmitted by the whitefly (, causes leaf curling and yellowing, plant dwarfism, and growth inhibition in tomato ( L.. The APETALA2 (AP2 and ethylene response factor (ERF transcription factor (TF family, the largest plant-specific TF family, was identified to function in plant development and pathogen defense. Our study aimed to analyze the mechanism underlying the function of ERF (SlERF TFs in response to TYLCV infection and improve useful information to increase the resistance to TYLCV in tomato. A total of 22 tomato AP2/ERF TFs in response to TYLCV were identified according to transcriptome database. Five ERF-B3 TFs were identified in cultivars Hongbeibei (highly resistant, Zheza-301, Zhefen-702 (both resistant, Jinpeng-1, and Xianke-6 (both susceptible. Interaction network indicated that SlERF TFs could interact with mitogen-activated protein kinase (MAPK. Expression profiles of five ERF-B3 genes (, , , , and were detected by quantitative real-time–polymerase chain reaction (qRT-PCR after TYLCV infection in five tomato cultivars. expression was upregulated in five tomato cultivars. The expressions of three genes (, , and were upregulated in Zheza-301 and Zhefen-702. and expressions were downregulated in Hongbeibei and Xianke-6, respectively. Yeast one-hybrid showed that the GCC-box binding ability of ERF-B3 TFs differed in resistant and susceptible tomato cultivars. Expression profiles were related to the GCC-box binding ability of SlERF TFs in resistant and susceptible tomato cultivars. The defense mechanism underlying the tomato’s response to TYLCV involved a complicated network, which provided important information for us in breeding and genetic analysis.

  5. Moral Responsibility and Confidence as Factors that Influence Teacher Involvement in Educational Change

    López Cecilio


    Full Text Available Various factors that are not easily observed have a strong impact on educational change. In this paper, I examine some of the issues that emerged from the data collected while exploring my informants’ perceptions and attitudes towards their changing roles when confronted with curriculum innovation. This research demonstrates that the experience teachers acquire during their career may often enable them to participate in the design of a new study plan. However, this experience does not always justify their role as curriculum-designers in either the eyes of their colleagues or in their own eyes, particularly when coerced into playing this or other roles. The results indicate that teachers, depending on their levels of moral responsibility and confidence, become involved in different roles during their teaching career. Key words: Change, confidence, curriculum, innovation, moral responsibility Existen diversos factores que tienen un fuerte impacto en el cambio educativo y que no se observan fácilmente. En este artículo examino algunos de los temas que emergieron de los datos recogidos mientras exploraba las opiniones y las actitudes de mis informantes hacia sus roles siempre cambiantes cuando se enfrentan a la innovación curricular. Esta investigación demuestra que los profesores, con la experiencia que adquieren durante su carrera, pueden permitirse a menudo participar en el diseño de un nuevo plan de estudios. Sin embargo, para sus colegas o para ellos mismos, esta experiencia no justifica siempre su papel como diseñadores de un plan de estudios particularmente cuando están obligados a jugar éste u otros roles. Los resultados indican que los profesores se involucran en diversos roles durante su carrera como profesores, dependiendo de sus niveles de responsabilidad moral y de confianza. Palabras clave: cambio, confianza, currículo, innovación, responsabilidad moral

  6. Thalamic involvement in a spinocerebellar ataxia type 2 (SCA2) and a spinocerebellar ataxia type 3 (SCA3) patient, and its clinical relevance

    Rub, U; Del Turco, D; Del Tredici, K; de Vos, RAI; Brunt, ER; Reifenberger, G; Seifried, C; Schultz, C; Auburger, G; Braak, H


    In spite of the considerable progress in clinical and molecular research, knowledge regarding brain damage in spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3) still is limited and the extent to which the thalamus is involved in both diseases is uncertain. Accordingly, we performed a pathoanato

  7. Factors involved in the identification of stuttering severity in a foreign language.

    Cosyns, Marjan; Einarsdóttir, Jóhanna T; Van Borsel, John


    Speech-language pathologists nowadays are more and more confronted with clients who speak a language different from their own mother tongue. The assessment of persons who speak a foreign language poses particular challenges. The present study investigated the possible role and interplay of factors involved in the identification of stuttering severity in a foreign language. Nineteen speech-language pathologists from five different countries (i.e. Iceland, Sweden, Norway, Finland, and Belgium) rated stuttering severity of speech samples featuring persons who stutter speaking Icelandic, Swedish, Norwegian, or Dutch. Additionally, they were asked to score how easy they found it to rate the samples. Accuracy of rating stuttering severity in another language appeared to be foremost determined by the client's stuttering severity, while experienced ease of rating stuttering severity was essentially related to closeness of the language of the clinician to that of the client and familiarity of the clinician with the client's language. Stuttering measurement training programmes in different languages are needed.

  8. Molecular flexibility of Mycobacterium tuberculosis ribosome recycling factor and its functional consequences: An exploration involving mutants

    M Selvaraj; A Govindan; A Seshadri; B Dubey; U Varshney; M Vijayan


    Internal mobility of the two domain molecule of ribosome recycling factor (RRF) is known to be important for its action. Mycobacterium tuberculosis RRF does not complement E. coli for its deficiency of RRF (in the presence of E. coli EF-G alone). Crystal structure had revealed higher rigidity of the M. tuberculosis RRF due to the presence of additional salt bridges between domains. Two inter-domain salt bridges and one between the linker region and the domain containing C-terminal residues were disrupted by appropriate mutations. Except for a C-terminal deletion mutant, all mutants showed RRF activity in E. coli when M. tuberculosis EF-G was also co-expressed. The crystal structures of the point mutants, that of the C-terminal deletion mutant and that of the protein grown in the presence of a detergent, were determined. The increased mobility resulting from the disruption of the salt bridge involving the hinge region allows the appropriate mutant to weakly complement E. coli for its deficiency of RRF even in the absence of simultaneous expression of the mycobacterial EF-G. The loss of activity of the C-terminal deletion mutant appears to be partly due to the rigidification of the molecule consequent to changes in the hinge region.

  9. Consistent analysis of one-nucleon spectroscopic factors involving weakly- and strongly-bound nucleons

    Okołowicz, J; Płoszajczak, M; Macchiavelli, A O; Smirnova, N A


    There is a considerable interest in understanding the dependence of one-nucleon removal cross sections on the asymmetry of the neutron $S_n$ and proton $S_p$ separation energies, following a large amount of experimental data and theoretical analyses in a framework of sudden and eikonal approximations of the reaction dynamics. These theoretical calculations involve both the single-particle cross section and the shell-model description of the projectile initial state and final states of the reaction residues. The configuration mixing in shell-model description of nuclear states depends on the proximity of one-nucleon decay threshold but does it depend sensitively on $S_n - S_p$? To answer this question, we use the shell model embedded in the continuum to investigate the dependence of one-nucleon spectroscopic factors on the asymmetry of $S_n$ and $S_p$ for mirror nuclei $^{24}$Si, $^{24}$Ne and $^{28}$S, $^{28}$Mg and for a series of neon isotopes ($20 \\leq A \\leq 28$).

  10. Religious factors associated with alcohol involvement: results from the Mauritian Joint Child Health Project.

    Luczak, Susan E; Prescott, Carol A; Dalais, Cyril; Raine, Adrian; Venables, Peter H; Mednick, Sarnoff A


    The purpose of this study was to examine religious factors associated with alcohol involvement in Mauritius. The three main religions on the island, Hinduism, Catholicism, and Islam, promote different views of the appropriate use of alcohol. Based on reference group theory, we hypothesized that both the content of a religion's alcohol norms and an individual's religious commitment would relate to alcohol use behavior. Participants were from the Joint Child Health Project, a longitudinal study that has followed a birth cohort of 1.795 individuals since 1972 when they were 3 years old. All available participants (67%; 55% male) were assessed in mid-adulthood on religious variables, lifetime drinking, and lifetime alcohol use disorders. Across religions, individuals who viewed their religion as promoting abstinence were less likely to be drinkers. Religious commitment was associated with reduced probability of drinking only in those who viewed their religion as promoting abstinence. Among drinkers, abstention norms and religious commitment were not associated with lower likelihood of alcohol use disorders. In Catholics who viewed their religion as promoting abstinence and still were drinkers, high religious commitment was associated with increased risk for alcohol use disorders. Predictions based on reference group theory were largely supported, with religious norms and commitment differentially related to alcohol use and problems both across religions and among individuals within religions. Findings highlight the importance of examining multiple aspects of religion to better understand the relationship of religion with alcohol behaviors. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Involvement of nuclear factor {kappa}B in platelet CD40 signaling

    Hachem, Ahmed [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Yacoub, Daniel [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Zaid, Younes [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Mourad, Walid [Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Merhi, Yahye, E-mail: [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada)


    Highlights: Black-Right-Pointing-Pointer sCD40L induces TRAF2 association to CD40 and NF-{kappa}B activation in platelets. Black-Right-Pointing-Pointer I{kappa}B{alpha} phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. Black-Right-Pointing-Pointer I{kappa}B{alpha} is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-{kappa}B). Given that platelets contain NF-{kappa}B, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of I{kappa}B{alpha}, which are abolished by CD40L blockade. Inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced I{kappa}B{alpha} phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on I{kappa}B{alpha} phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-{kappa}B activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against thrombo

  12. Survey of Parents in a Predominately Latino Elementary School to Determine Factors that Affect Parental Involvement

    Bodenstab, Tracy


    Present research has shown that parental involvement has a large effect on student achievement. The current study utilized both casual-comparative and correlation methodology and identified variables that influence parental involvement. A review of literature with respect to parental involvement was presented. The study utilized survey data from…

  13. The Influence of Psychosocial Factors on Bullying Involvement of Students with Disabilities

    Rose, Chad A.; Forber-Pratt, Anjali J.; Espelage, Dorothy L.; Aragon, Steven R.


    The involvement of students with disabilities within the bullying dynamic has been recognized as a pressing issue within the nation's schools. Unfortunately, few studies have examined the psychosocial outcomes related to the bullying involvement of students with disabilities. However, involvement in bullying has been linked to negative short-…

  14. Evaluation and comparison of benchmark QSAR models to predict a relevant REACH endpoint: The bioconcentration factor (BCF)

    Gissi, Andrea [Laboratory of Environmental Chemistry and Toxicology, IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano (Italy); Dipartimento di Farmacia – Scienze del Farmaco, Università degli Studi di Bari “Aldo Moro”, Via E. Orabona 4, 70125 Bari (Italy); Lombardo, Anna; Roncaglioni, Alessandra [Laboratory of Environmental Chemistry and Toxicology, IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano (Italy); Gadaleta, Domenico [Laboratory of Environmental Chemistry and Toxicology, IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano (Italy); Dipartimento di Farmacia – Scienze del Farmaco, Università degli Studi di Bari “Aldo Moro”, Via E. Orabona 4, 70125 Bari (Italy); Mangiatordi, Giuseppe Felice; Nicolotti, Orazio [Dipartimento di Farmacia – Scienze del Farmaco, Università degli Studi di Bari “Aldo Moro”, Via E. Orabona 4, 70125 Bari (Italy); Benfenati, Emilio, E-mail: [Laboratory of Environmental Chemistry and Toxicology, IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano (Italy)


    The bioconcentration factor (BCF) is an important bioaccumulation hazard assessment metric in many regulatory contexts. Its assessment is required by the REACH regulation (Registration, Evaluation, Authorization and Restriction of Chemicals) and by CLP (Classification, Labeling and Packaging). We challenged nine well-known and widely used BCF QSAR models against 851 compounds stored in an ad-hoc created database. The goodness of the regression analysis was assessed by considering the determination coefficient (R{sup 2}) and the Root Mean Square Error (RMSE); Cooper's statistics and Matthew's Correlation Coefficient (MCC) were calculated for all the thresholds relevant for regulatory purposes (i.e. 100 L/kg for Chemical Safety Assessment; 500 L/kg for Classification and Labeling; 2000 and 5000 L/kg for Persistent, Bioaccumulative and Toxic (PBT) and very Persistent, very Bioaccumulative (vPvB) assessment) to assess the classification, with particular attention to the models' ability to control the occurrence of false negatives. As a first step, statistical analysis was performed for the predictions of the entire dataset; R{sup 2}>0.70 was obtained using CORAL, T.E.S.T. and EPISuite Arnot–Gobas models. As classifiers, ACD and log P-based equations were the best in terms of sensitivity, ranging from 0.75 to 0.94. External compound predictions were carried out for the models that had their own training sets. CORAL model returned the best performance (R{sup 2}{sub ext}=0.59), followed by the EPISuite Meylan model (R{sup 2}{sub ext}=0.58). The latter gave also the highest sensitivity on external compounds with values from 0.55 to 0.85, depending on the thresholds. Statistics were also compiled for compounds falling into the models Applicability Domain (AD), giving better performances. In this respect, VEGA CAESAR was the best model in terms of regression (R{sup 2}=0.94) and classification (average sensitivity>0.80). This model also showed the best

  15. Regulatory Mechanisms Involved in the Expression of Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor


    Growth Factor Nerve growth factor (NGF), the prototypical neurotrophin, originally isolated by Levi -Montalcini and colleagues ( Levi -Montalcini, 1987; see...inclusion of NGF antibodies ( Levi -Montalcini, 1987). In addition, these neurons exhibit enhanced differentiation, as evidenced by extensive neurite...the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron 6: 845-858, 1991. Hefti, F. Nerve growth factor

  16. Relevance Theory in Translation

    Shao Jun; Jiang Min


    In perspective of relevance theory, translation is regarded as communication. According to relevance theory, communication not only requires encoding, transfer and decoding processes, but also involves inference in addition. As communication, translation decision-making is also based on the human beings' inferential mental faculty. Concentrating on relevance theory, this paper tries to analyze and explain some translation phenomena in two English versions of Cai Gen Tan-My Crude Philosophy of Life.

  17. 进展性卒中的相关因素研究%Relevent Factors stroke in progression Patients

    刘俊艳; 董玉娟; 李娜; 任士卿; 李育臣; 王建茹; 刘好文; 王冰


    Objective: In order to prophylactic treat stroke in progression (SIP), we analysed risk factors and imagery characters of SIP patients. Methods: retrospectively study 58 cases SIP patients, and analysis relevent factors of SIP, which includ blood pressure(systolic pressure and diastolic pressure), blood glucose and blood lipid level, the changes of magnetic resonance angiography and transcranial Dopple. All data were analysed by chi-test. Results: 1. Results showed that 46 patients of 58 SIP were accompanied with hypertension. among them, 18 patients` systolic prssure were less than 150 mmHg and 13 cases with a decrement of pulse pressure (P<0.001). and patients with a long course history and informal treatment hypertension, especially those patients accompanied by low systolic pressure, were easy suffer from SIP. 2. In SIP group, 31 pateints were accompanied wiht DM, the morbidity was obviously higher than that of control (P<0.000). 3. Among 21 SIP patients examined by MRA or/and TCD, 14 patients showed intracranial of/and extracraial vascular stenosis of occlusion. there were only 4 cases in control group. In thosse patients, low perfusion pressure that resulting from artery trunk stenosis or occlusion and decrement of pulse pressure was main cause of SIP. 4. On image, most common infarction site of SIP were in body of lateral ventricles and water-shed territoy, which is usually suggesting large vessel disease. Conclusion: HT, especially the hypertension whth lower systolic pressure, DM, intra-or extracranial vascular stenosis/occlusion and severely function defciency in neurologic system are associated whth SIP. The latter ply a main role in progressive of late phase in first week. About treatment therapy of SIP patients, we emphasize not to reduce blood pressure, excessively meanwhile giving anticoagulation, we should apply for a MRA or TCD exam and early find vascular change, further prevent relapse with cerebral vascular diseases.%目的:寻找引起进

  18. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.

    Yee Suan Poo


    Full Text Available The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA.

  19. Cellular intrinsic factors involved in the resistance of squamous cell carcinoma to photodynamic therapy.

    Gilaberte, Yolanda; Milla, Laura; Salazar, Nerea; Vera-Alvarez, Jesús; Kourani, Omar; Damian, Alejandra; Rivarola, Viviana; Roca, Maria José; Espada, Jesús; González, Salvador; Juarranz, Angeles


    Photodynamic therapy (PDT) is widely used to treat non-melanoma skin cancer. However, some patients affected with squamous cell carcinoma (SCC) do not respond adequately to PDT with methyl-δ-aminolevulinic acid (MAL-PDT) and the tumors acquire an infiltrative phenotype and became histologically more aggressive, less differentiated, and more fibroblastic. To search for potential factors implicated in SCC resistance to PDT, we have used the SCC-13 cell line (parental) and resistant SCC-13 cells obtained by repeated MAL-PDT treatments (5th and 10th PDT-resistant generations). Xenografts assays in immunodeficient mice showed that the tumors generated by resistant cells were bigger than those induced by parental cells. Comparative genomic hybridization array (aCGH) showed that the three cell types presented amplicons in 3p12.1 CADM2, 7p11.2 EFGR, and 11q13.3 CCND1 genes. The 5th and 10th PDT-resistant cells showed an amplicon in 5q11.2 MAP3K1, which was not present in parental cells. The changes detected by aCGH on CCND1, EFGR, and MAP3K1 were confirmed in extracts of SCC-13 cells by reverse-transcriptase PCR and by western blot, and by immunohistochemistry in human biopsies from persistent tumors after MAL-PDT. Our data suggest that genomic imbalances related to CCND1, EFGR, and particularly MAP3K1 seem to be involved in the development of the resistance of SCC to PDT.

  20. Attention-deficit hyperactivity disorder medication use: factors involved in prescribing, safety aspects and outcomes

    Martinez-Raga, Jose; Ferreros, Amparo; Knecht, Carlos; de Alvaro, Raquel; Carabal, Eloisa


    While treatment of patients with attention-deficit hyperactivity disorder (ADHD) is based on a multimodal approach that combines medication with specific psychological interventions, pharmacotherapy alone is generally considered an essential and cost-effective element. This paper aims to comprehensively and critically review factors involved in prescribing and medication use in individuals diagnosed with ADHD, focusing on the difficulties facing patients with ADHD seeking treatment, as well as the safety and tolerability aspects of ADHD pharmacotherapies, with particular attention on the cardiovascular adverse events and the potential risk of misuse or diversion of ADHD medications. A comprehensive and systematic literature search of PubMed/MEDLINE database was conducted to identify studies published in peer-reviewed journals until 1 August 2016. Children, adolescents and adults often encounter significant difficulties in the process of accessing specialist assessment and treatment for ADHD as a consequence of disparities in service organization and available treatment provision. Despite the well-established efficacy and overall safety profile, ADHD medications are not exempt from adverse events. The cardiovascular safety of pharmacotherapies used for treating individuals with ADHD has raised particular concerns; however there is little evidence of serious cardiovascular adverse events, including no serious corrected QT (QTc) abnormalities associated with stimulants, atomoxetine or α2-adrenergic receptor agonists. Although the abuse of prescription stimulant drugs, particularly, short-acting stimulants is a prevalent and growing problem, nonmedical use of prescription stimulants within the clinical context is very limited. In addition, nonstimulant ADHD medications lack any reinforcing effects and consequently any abuse potential.

  1. Role of a circadian-relevant gene NR1D1 in brain development: possible involvement in the pathophysiology of autism spectrum disorders

    Goto, Masahide; Mizuno, Makoto; Matsumoto, Ayumi; Yang, Zhiliang; Jimbo, Eriko F.; Tabata, Hidenori; Yamagata, Takanori; Nagata, Koh-ichi


    In our previous study, we screened autism spectrum disorder (ASD) patients with and without sleep disorders for mutations in the coding regions of circadian-relevant genes, and detected mutations in several clock genes including NR1D1. Here, we further screened ASD patients for NR1D1 mutations and identified three novel mutations including a de novo heterozygous one c.1499 G > A (p.R500H). We then analyzed the role of Nr1d1 in the development of the cerebral cortex in mice. Acute knockdown of mouse Nr1d1 with in utero electroporation caused abnormal positioning of cortical neurons during corticogenesis. This aberrant phenotype was rescued by wild type Nr1d1, but not by the c.1499 G > A mutant. Time-lapse imaging revealed characteristic abnormal migration phenotypes in Nr1d1-deficient cortical neurons. When Nr1d1 was knocked down, axon extension and dendritic arbor formation of cortical neurons were also suppressed while proliferation of neuronal progenitors and stem cells at the ventricular zone was not affected. Taken together, Nr1d1 was found to play a pivotal role in corticogenesis via regulation of excitatory neuron migration and synaptic network formation. These results suggest that functional defects in NR1D1 may be related to ASD etiology and pathophysiology. PMID:28262759

  2. MicroRNAs are involved in the development of morphine-induced analgesic tolerance and regulate functionally relevant changes in Serpini1

    Jenica D. Tapocik


    Full Text Available Long-term opioid treatment results in reduced therapeutic efficacy and in turn leads to an increase in the dose required to produce equivalent pain relief and alleviate break-through or insurmountable pain. Altered gene expression is a likely means for inducing long-term neuroadaptations responsible for tolerance. Studies conducted by our laboratory (Tapocik et al., 2009 revealed a network of gene expression changes occurring in canonical pathways involved in neuroplasticity, and uncovered miRNA processing as a potential mechanism. In particular, the mRNA coding the protein responsible for processing miRNAs, Dicer1, was positively correlated with the development of analgesic tolerance. The purpose of the present study was to test the hypothesis that miRNAs play a significant role in the development of analgesic tolerance as measured by thermal nociception. Dicer1 knockdown, miRNA profiling, bioinformatics and confirmation of high value targets were used to test the proposition.Regionally targeted Dicer1 knockdown (via shRNA had the anticipated consequence of eliminating the development of tolerance in C57BL/6J (B6 mice, thus supporting the involvement of miRNAs in the development of tolerance. MiRNA expression profiling identified a core set of chronic morphine-regulated miRNAs (miR’s 27a, 9, 483, 505, 146b, 202. Bioinformatics approaches were implemented to identify and prioritize their predicted target mRNAs. We focused our attention on miR27a and its predicted target serpin peptidase inhibitor clade I (Serpini1 mRNA, a transcript known to be intricately involved in dendritic spine density regulation in a manner consistent with chronic morphine’s consequences and previously found to be correlated with the development of analgesic tolerance. In vitro reporter assay confirmed the targeting of the Serpini1 3’-untranslated region by miR27a. Interestingly miR27a was found to positively regulate Serpini1 mRNA and protein levels in multiple

  3. Parental Involvement as a Protective Factor during the Transition to High School

    Chen, Wei-Bing; Gregory, Anne


    The authors investigated whether student-perceived parental involvement predicts improvement in academic, behavioral, and relational outcomes for low-achieving adolescents. With a sample of 59 racially diverse 9th-grade students, the authors measured 3 dimensions of parental involvement: direct participation, academic encouragement, and…

  4. Viewing Generativity and Social Capital as Underlying Factors of Parent Involvement

    Stevens, Sharon; Patel, Nimisha


    Parent involvement in education is a multifaceted support that has many well-documented benefits for students of all ages. Parent involvement is also a common expression of generativity as defined in Erik Erikson's theory of psychosocial development. The activities parents engage in during their children's educational pursuits, as well as their…

  5. Understanding Teachers' Perspectives of Factors That Influence Parental Involvement Practices in Special Education in Barbados

    Blackman, Stacey; Mahon, Erin


    Parental involvement has been defined in various ways by researchers and is reported to have many advantages for children's education. The research utilises a case study strategy to investigate teachers' perspectives of parental involvement at four case sites in Barbados. In-depth interviews were done with teachers and analysis utilised content…

  6. Practicing Professional Values: Factors Influencing Involvement in Social Work Student Organizations

    Martindale, Dorothy; Olate, René; Anderson, Keith A.


    One of the most promising avenues for the development of professional values is involvement in professional student organizations. A convenience sample of baccalaureate social work students (n = 482) was drawn from 15 institutions. Regression analyses revealed several predictors of involvement in social work student organizations, including…

  7. A Study on Characteristics and Relevant Factors of Adaptive Behaviours in Schizophrenic Children%精神分裂症儿童适应行为及影响因素的分析

    袁水平; 赖淑珍; 江礼华; 魏永超; 涂飞龙; 梁琛; 熊富先


    Objective: To examine characteristics and relevant factors of adaptive behaviours in childhood schizophrenia. Methods: The adaptive behaviors of schizophrenic children were rated by Child Adaptive Behavior Scale. Data on relevant factors were collected by a specifically developed scale. Results: Relationship with parents, schooling, family education, parental culture, and family configuration were related to development of adaptive behaviors in schizophrenic children. Conclusion: The study of adaptive behaviours and their relevant factors was valuable in predicting prognosis of childhood schizophrenia.

  8. Factors predicting survival in patients with proximal gastric carcinoma involving the esophagus

    Yi-Fen Zhang; Jiong Shi; Hui-Ping Yu; An-Ning Feng; Xiang-Shan Fan; Gregory Y Lauwers; Hiroshi Mashimo


    AIM:To investigate the clinicopathologic features which predict surgical overall survival in patients with proximal gastric carcinoma involving the esophagus (PGCE).METHODS:Electronic pathology database established in the Department of Pathology of the Nanjing Drum Tower Hospital was searched for consecutive resection cases of proximal gastric carcinoma over the period from May 2004 through July 2009.Each retrieved pathology report was reviewed and the cases with tumors crossing the gastroesophageal junction line were selected as PGCE.Each tumor was re-staged,following the guidelines on esophageal adenocarcinoma,according to the 7th edition of the American Joint Commission on Cancer Staging Manual.All histology slides were studied along with the pathology report for a retrospective analysis of 13 clinicopathologic features,i.e.,age,gender,Helicobacter pylori (H.pylori) infection,surgical modality,Siewert type,tumor Bormann's type,size,differentiation,histology type,surgical margin,lymphovascular and perineural invasion,and pathologic stage in relation to survival after surgical resection.Prognostic factors for overall survival were assessed with uniand multi-variate analyses.RESULTS:Patients' mean age was 65 years (range:47-90 years).The male:female ratio was 3.3.The 1-,3-and 5-year overall survival rates were 87%,61% and 32%,respectively.By univariate analysis,age,male gender,H,pylori,tumor Bormann's type,size,histology type,surgical modality,positive surgical margin,lymphovascular invasion,and pT stage were not predictivefor overall survival; in contrast,perineural invasion (P =0.003),poor differentiation (P =0.0003),> 15 total lymph nodes retrieved (P =0.008),positive lymphnodes (P =0.001),and distant metastasis (P =0.005)predicted poor post-operative overall survival.Celiac axis nodal metastasis was associated with significantly worse overall survival (P =0.007).By multivariate analysis,≥ 16 positive nodes (P =0.018),lymph node ratio > 0.2 (P =0

  9. Endothelin Receptors Expressed by Immune Cells Are Involved in Modulation of Inflammation and in Fibrosis: Relevance to the Pathogenesis of Systemic Sclerosis.

    Elisa, Tinazzi; Antonio, Puccetti; Giuseppe, Patuzzo; Alessandro, Barbieri; Giuseppe, Argentino; Federico, Confente; Marzia, Dolcino; Ruggero, Beri; Giacomo, Marchi; Andrea, Ottria; Daniela, Righetti; Mariaelisa, Rampudda; Claudio, Lunardi


    Endothelin-1 (ET-1) plays a pivotal role in vasoconstriction, fibrosis, and inflammation, the key features of systemic sclerosis (SSc). ET-1 receptors (ETA and ET(B)) are expressed on endothelial cells, smooth muscle cells, and fibroblasts, but their presence on immune cells has not been deeply investigated so far. Endothelin receptors antagonists such as bosentan have beneficial effects on vasoconstriction and fibrosis, but less is known about their potential anti-inflammatory effects. We studied the expression of ET-1 receptors on immune cells (T and B lymphocytes, monocytes, and neutrophils) and the link between ET-1 and inflammation in patients with SSc. We show here that ET-1 exerts a proinflammatory effect in CD4+ T cells, since it induces an increased IFN-γ production; preincubation with antagonists of both receptors reduces IFN-γ production. Moreover, following ET-1 stimulation, neutrophils produce proinflammatory mediators, thus amplifying the effects of activated CD4+ T cells. Our data indicate that ET-1 system is involved in the pathogenesis of inflammation and fibrosis typical of SSc, through the activation of T lymphocytes and neutrophils and the consequent release of proinflammatory and profibrotic cytokines. These findings suggest that dual ET-1 receptors antagonist therapy, besides its effect on vasculopathy, has a profound impact on the immune system favouring antiinflammatory and antifibrogenic effects.

  10. Should Students Have a Gap Year? Motivation and Performance Factors Relevant to Time Out after Completing School

    Martin, Andrew J.


    Increasingly, school leavers are taking time out from study or formal work after completing high school--often referred to as a "gap year" (involving structured activities such as "volunteer tourism" and unstructured activities such as leisure). Although much opinion exists about the merits--or otherwise--of taking time out after completing…

  11. Should Students Have a Gap Year? Motivation and Performance Factors Relevant to Time Out after Completing School

    Martin, Andrew J.


    Increasingly, school leavers are taking time out from study or formal work after completing high school--often referred to as a "gap year" (involving structured activities such as "volunteer tourism" and unstructured activities such as leisure). Although much opinion exists about the merits--or otherwise--of taking time out after completing…

  12. Food rejections in children: Cognitive and social/environmental factors involved in food neophobia and picky/fussy eating behavior.

    Lafraire, Jérémie; Rioux, Camille; Giboreau, Agnès; Picard, Delphine


    Food neophobia and picky/fussy eating behavior are presented as the two main forms of children's food rejections which are responsible for a reduction of their dietary repertoire. We review the key factors, presented in the literature, that are involved in food rejections during childhood. We first consider a range of "cognitive factors", such as food perception, mental representations, categorization of food items, and emotions and feelings toward food. Next we focus on "social and environmental factors", as these might also significantly influence and modulate children's food rejections. We then summarize the findings to provide a comprehensive view of the factors involved in children's food rejections. Finally, we discuss the need for future studies on food rejections, regarding (i) the distinction between food neophobia and picky/fussy eating, and (ii) the potential link between food categorization abilities and children's food neophobia and pickiness.

  13. Factors associated with sex work involvement among transgender women in Jamaica: a cross‐sectional study

    Logie, Carmen H; Wang, Ying; Lacombe‐Duncan, Ashley; Jones, Nicolette; Ahmed, Uzma; Levermore, Kandasi; Neil, Ava; Ellis, Tyrone; Bryan, Nicolette; Marshall, Annecka; Newman, Peter A


    Introduction : Transgender women are disproportionately impacted by HIV. Transgender women involved in sex work may experience exacerbated violence, social exclusion, and HIV vulnerabilities, in comparison with non‐sex work...

  14. Teacher Involvement as a Protective Factor from the Association between Race-Based Bullying and Smoking Initiation

    Earnshaw, Valerie A.; Rosenthal, Lisa; Carroll-Scott, Amy; Peters, Susan M.; McCaslin, Catherine; ICKOVICS, Jeannette R.


    Experiencing bullying as a victim is associated with negative health and health behavior outcomes, including substance use, among adolescents. However, understandings of protective factorsfactors that enhance adolescents’ resilience to the negative consequences of bullying – remain limited. The current study investigates whether teacher involvement protects adolescent students from the association between being bullied due to race and smoking initiation. Students were recruited from 12 Kin...

  15. Are Outness and Community Involvement Risk or Protective Factors for Alcohol and Drug Abuse Among Sexual Minority Women?

    Feinstein, Brian A; Dyar, Christina; London, Bonita


    Sexual minority women (SMW) are at increased risk for substance abuse compared to heterosexual women. Two psychosocial factors that have been implicated in SMW's substance abuse are outness and LGBT community involvement, but findings have been mixed as to whether these are risk or protective factors. One possible explanation is that they may have different consequences for subgroups of SMW (lesbians, bisexual women, and queer women). While being open about one's sexual orientation and involved in the community may be protective for lesbians, discrimination against bisexual women may lead these same factors to contribute to substance abuse for bisexual women. It is unclear how these associations will operate for queer women, given limited research on this subpopulation. The current study examined whether sexual identity moderated the associations between outness and community involvement with alcohol and drug abuse. We also examined whether perceived discrimination would help explain why these associations may be different for subgroups of SMW. A sample of 288 self-identified SMW (113 lesbians, 106 bisexual women, and 69 queer women) completed an online survey. Higher outness was associated with higher alcohol and drug abuse for bisexual women, but not for lesbians or queer women. Similarly, higher community involvement was associated with higher drug abuse for bisexual women, but not for lesbians or queer women. Among bisexual women, the association between community involvement and drug abuse was mediated by perceived discrimination. Further, the association between outness and drug abuse was mediated by both community involvement and perceived discrimination. Findings demonstrate that outness and community involvement function as risk factors for substance abuse for bisexual women, in part due to their associations with discrimination.

  16. Genes involved in the transforming growth factor beta signalling pathway and the risk of intracranial aneurysms

    Ruigrok, Y. M.; Tan, S.; Medic, J.; Rinkel, G. J. E.; Wijmenga, C.


    Background and purpose: The 19q13.3 locus for intracranial aneurysms (IA) partly overlaps with the 19q13 locus for abdominal aortic aneurysms (AAA). A common genetic risk factor located in this locus for the two aneurysm types seems plausible. The transforming growth factor beta (TGF-beta) signallin

  17. Organotypic Cultures of Intervertebral Disc Cells: Responses to Growth Factors and Signaling Pathways Involved

    Harris Pratsinis


    Full Text Available Intervertebral disc (IVD degeneration is strongly associated with low back pain, a major cause of disability worldwide. An in-depth understanding of IVD cell physiology is required for the design of novel regenerative therapies. Accordingly, aim of this work was the study of IVD cell responses to mitogenic growth factors in a three-dimensional (3D organotypic milieu, comprising characteristic molecules of IVD’s extracellular matrix. In particular, annulus fibrosus (AF cells were cultured inside collagen type-I gels, while nucleus pulposus (NP cells in chondroitin sulfate A (CSA supplemented collagen gels, and the effects of Platelet-Derived Growth Factor (PDGF, basic Fibroblast Growth Factor (bFGF, and Insulin-Like Growth Factor-I (IGF-I were assessed. All three growth factors stimulated DNA synthesis in both AF and NP 3D cell cultures, with potencies similar to those observed previously in monolayers. CSA supplementation inhibited basal DNA synthesis rates, without affecting the response to growth factors. ERK and Akt were found to be phosphorylated following growth factor stimulation. Blockade of these two signaling pathways using pharmacologic inhibitors significantly, though not completely, inhibited growth factor-induced DNA synthesis. The proposed culture systems may prove useful for further in vitro studies aiming at future interventions for IVD regeneration.

  18. Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation: corticotrophin-releasing factor and nerve growth factor interplay


    Neonatal maternal deprivation (NMD) increases gut paracellular permeability (GPP) through mast cells and nerve growth factor (NGF), and modifies corticotrophin-releasing factor (CRF) and corticosterone levels. CRF, corticosterone and mast cells are involved in stress-induced mucosal barrier impairment. Consequently, this study aimed to specify whether corticosteronaemia and colonic expression of both preproCRF and CRF are modified by NMD, and to determine if altered expression may participate...

  19. Energy absorption buildup factors of human organs and tissues at energies and penetration depths relevant for radiotherapy and diagnostics.

    Manohara, S R; Hanagodimath, S M; Gerward, L


    Energy absorption geometric progression (GP) fitting parameters and the corresponding buildup factors have been computed for human organs and tissues, such as adipose tissue, blood (whole), cortical bone, brain (grey/white matter), breast tissue, eye lens, lung tissue, skeletal muscle, ovary, testis, soft tissue, and soft tissue (4-component), for the photon energy range 0.015-15 MeV and for penetration depths up to 40 mfp (mean free path). The chemical composition of human organs and tissues is seen to influence the energy absorption buildup factors. It is also found that the buildup factor of human organs and tissues changes significantly with the change of incident photon energy and effective atomic number, Z(eff). These changes are due to the dominance of different photon interaction processes in different energy regions and different chemical compositions of human organs and tissues. With the proper knowledge of buildup factors of human organs and tissues, energy absorption in the human body can be carefully controlled. The present results will help in estimating safe dose levels for radiotherapy patients and also useful in diagnostics and dosimetry. The tissue-equivalent materials for skeletal muscle, adipose tissue, cortical bone, and lung tissue are also discussed. It is observed that water and MS20 are good tissue equivalent materials for skeletal muscle in the extended energy range.

  20. Energy absorption buildup factors of human organs and tissues at energies and penetration depths relevant for radiotherapy and diagnostics

    Manohara, S. R.; Hanagodimath, S. M.; Gerward, Leif


    Energy absorption geometric progression (GP) fitting parameters and the corresponding buildup factors have been computed for human organs and tissues, such as adipose tissue, blood (whole), cortical bone, brain (grey/white matter), breast tissue, eye lens, lung tissue, skeletal muscle, ovary...

  1. The relevance of uniform reporting in oral leukoplakia: Definition, certainty factor and staging based on experience with 275 patients

    Brouns, E.R.E.A.; Baart, J.A.; Bloemena, E.; Karagozoglu, H.; van der Waal, I.


    The aim of the present study was to evaluate the definition of oral leukoplakia, proposed by the WHO in 2005 and taking into account a previously reported classification and staging system, including the use of a Certainty factor of four levels with which the diagnosis of leukoplakia can be

  2. The relevance of uniform reporting in oral leukoplakia: Definition, certainty factor and staging based on experience with 275 patients

    Brouns, E.R.E.A.; Baart, J.A.; Bloemena, E.; Karagozoglu, H.; van der Waal, I.


    The aim of the present study was to evaluate the definition of oral leukoplakia, proposed by the WHO in 2005 and taking into account a previously reported classification and staging system, including the use of a Certainty factor of four levels with which the diagnosis of leukoplakia can be establis

  3. The relevance of uniform reporting in oral leukoplakia: Definition, certainty factor and staging based on experience with 275 patients

    Brouns, E.R.E.A.; Baart, J.A.; Bloemena, E.; Karagozoglu, H.; van der Waal, I.


    The aim of the present study was to evaluate the definition of oral leukoplakia, proposed by the WHO in 2005 and taking into account a previously reported classification and staging system, including the use of a Certainty factor of four levels with which the diagnosis of leukoplakia can be establis

  4. Family Engagement in Education in Uttar Pradesh, India: Factors Associated with the Involvement of Families in Their Children's Education

    Sanchez, Amanda Joy


    The purpose of this study was to examine the extent to which families within the Shravasti district of Uttar Pradesh, India are engaged in their children's education, as well as to examine the child, family, school, and community factors that are potentially associated with families' involvement in their children's education. Additionally,…

  5. Socio-Economic Factors Affecting Parents' Involvement in Homework: Practices and Perceptions from Eight Johannesburg Public Primary Schools

    Ndebele, Misheck


    This paper examines socio-economic factors influencing parental involvement in homework at the Foundation Phase in eight Johannesburg public primary schools. The research was conducted among over 600 parents from schools in different geographical and socio-economic areas such as the inner city, suburban and township. Two primary schools were…

  6. Predictive Factors in Undergraduates' Involvement in Campus Secret Cults in Public Universities in Edo State of Nigeria

    Azetta Arhedo, Philip; Aluede, Oyaziwo; Adomeh, Ilu O. C.


    This study examined the predictive factors in undergraduates' involvement in campus secret cults in public universities in Edo State of Nigeria. The study employed the descriptive method, specifically the survey format. A random sample of three hundred and eighty (380) undergraduates was drawn from the two public universities. Data were elicited…

  7. Toward Digital Citizenship: Examining Factors Affecting Participation and Involvement in the Internet Society among Higher Education Students

    Al-Zahrani, Abdulrahman


    The current study aims to understand digital citizenship, based on the assumptions of Ribble (2014), by examining factors affecting participation and involvement in the Internet virtual societies among higher education students. A quantitative approach using a survey questionnaire was implemented. The participants were 174 students from the…

  8. Socio-Economic Factors Affecting Parents' Involvement in Homework: Practices and Perceptions from Eight Johannesburg Public Primary Schools

    Ndebele, Misheck


    This paper examines socio-economic factors influencing parental involvement in homework at the Foundation Phase in eight Johannesburg public primary schools. The research was conducted among over 600 parents from schools in different geographical and socio-economic areas such as the inner city, suburban and township. Two primary schools were…

  9. [Family perceptions and moderating factors of involvement in non-residential fathers].

    Della Casa, André; Spillner, Murielle; Winkler-Metzke, Christa; Steinhausen, Hans-Christoph


    The involvement of non-resident fathers with their child was analysed by use of a questionnaire in a sample of 74 divorced or separated families living in the city of Ziurich, Switzerland. Fathers, mothers, and one child separately rated the involvement of the father. The three perspectives were compared and showed significant differences in the dimensions of educational responsibility, cognitive and social support, and the quality of the emotional relationship. The temporal availability and leisure time activities did not show significant differences. The different family perspectives should be considered when assessing a father's involvement with his child. The quality of the relationship of the children to their fathers was primarily fostered by the emotional engagement of the father.

  10. Deriving amplification factors from simple site parameters using generalized regression neural networks: implications for relevant site proxies

    Boudghene Stambouli, Ahmed; Zendagui, Djawad; Bard, Pierre-Yves; Derras, Boumédiène


    Most modern seismic codes account for site effects using an amplification factor (AF) that modifies the rock acceleration response spectra in relation to a "site condition proxy," i.e., a parameter related to the velocity profile at the site under consideration. Therefore, for practical purposes, it is interesting to identify the site parameters that best control the frequency-dependent shape of the AF. The goal of the present study is to provide a quantitative assessment of the performance of various site condition proxies to predict the main AF features, including the often used short- and mid-period amplification factors, Fa and Fv, proposed by Borcherdt (in Earthq Spectra 10:617-653, 1994). In this context, the linear, viscoelastic responses of a set of 858 actual soil columns from Japan, the USA, and Europe are computed for a set of 14 real accelerograms with varying frequency contents. The correlation between the corresponding site-specific average amplification factors and several site proxies (considered alone or as multiple combinations) is analyzed using the generalized regression neural network (GRNN). The performance of each site proxy combination is assessed through the variance reduction with respect to the initial amplification factor variability of the 858 profiles. Both the whole period range and specific short- and mid-period ranges associated with the Borcherdt factors Fa and Fv are considered. The actual amplification factor of an arbitrary soil profile is found to be satisfactorily approximated with a limited number of site proxies (4-6). As the usual code practice implies a lower number of site proxies (generally one, sometimes two), a sensitivity analysis is conducted to identify the "best performing" site parameters. The best one is the overall velocity contrast between underlying bedrock and minimum velocity in the soil column. Because these are the most difficult and expensive parameters to measure, especially for thick deposits, other

  11. The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein

    Larsen, L F; Marckmann, P; Bladbjerg, Else-Marie


    Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood samples...... that triglyceride-rich lipoproteins may activate prokallikrein. Neither plasma triglycerides nor kallikrein and activated FVII were statistically associated. This may suggest that additional factors are involved in the postprandial FVII activation. No clear evidence for a role of tissue factor expression...

  12. Virulence factors of Actinobacillus pleuropneumoniae involved in colonization, persistence and induction of lesions in its porcine host

    Chiers, Koen; De Waele, Tine; Pasmans, Frank; Ducatelle, Richard; Haesebrouck, Freddy


    Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia. The virulence factors of this microorganism involved in colonization and the induction of lung lesions have been thoroughly studied and some have been well characterized. A. pleuropneumoniae binds preferentially to cells of the lower respiratory tract in a process involving different adhesins and probably biofilm formation. Apx toxins and lipopolysaccharides exert pathogenic effects on several host cells, resulting in typical lung lesions. Lysis of host cells is essential for the bacterium to obtain nutrients from the environment and A. pleuropneumoniae has developed several uptake mechanisms for these nutrients. In addition to persistence in lung lesions, colonization of the upper respiratory tract – and of the tonsils in particular – may also be important for long-term persistent asymptomatic infection. Information on virulence factors involved in tonsillar and nasal cavity colonization and persistence is scarce, but it can be speculated that similar features as demonstrated for the lung may play a role. PMID:20546697

  13. Relevant Organizational Factors for Social Efficiency in the Road Transport Sector; Procesos Organizativos Clave para la Eficiencia Social en el Transporte por Carretera

    Silla, I.; Gamero, N.


    Previous research has emphasized the need to consider the social dimension featuring organizations in order to maximize organizational efficiency (Rasmussen, 1997). In the road transport sector, previous research has focused on the relationship between human factor, stress, fatigue, and other relevant issues, and professional drivers health and safety (p.e., De Croon et al, 2004). However, research on relevant organizational factors is scarce. This study aims to examine the association between leadership and supportive climate, and employees health and safety. Moreover, the impact of stress (time pressure) was also examined because previous research has stressed its importance. This study used a sample of 486 employees from 35 different Spanish companies pertaining to the road transport sector. Findings showed time pressure to be negatively associated to employees health, job satisfaction and satisfaction with safety. Additionally, leadership was positively associated employees health, job satisfaction and satisfaction with safety. Finally, co-workers and supervisors supportive climate was positively associated with job satisfaction and negatively associated to illness. These findings have relevant practical implications for the competitiveness of road transport companies. (Author) 21 refs.

  14. Misexpression Screen in Drosophila melanogaster Aiming to Reveal Novel Factors Involved in Formation of Body Parts

    Grieder, N.; Charlafti, I.; Kloter, U.; Jaeckle, H.; Schaefer, U.; Gehring, W


    To identify novel factors that lead a fly imaginal disc to adopt its developmental fate, we carried out a modular dominant misexpression screen in imaginal discs. We have identified two factors that appear to change the fate of the respective body structure and appear to lead to the transformation of a body part. In one mutant line, notum tissue, normally derived from wing imaginal tissue, formed close to the site of the sternopleural bristles, which are leg disc derivatives. In the other lin...

  15. 76 FR 36092 - Antidumping Methodologies in Proceedings Involving Non-Market Economies: Valuing the Factor of...


    ... International Trade Administration Antidumping Methodologies in Proceedings Involving Non-Market Economies... methodology used by the Department of Commerce (``the Department'') to value the cost of labor in non- market... wage rates.\\3\\ \\2\\ See Certain Woven Electric Blankets From the People's Republic of China:...

  16. Characterization of RACK7 as a Novel Factor Involved in BRCA1 Mutation Mediated Breast Cancer


    control for the restriction digestion. Fig. 2. Library screening and cloning of the gene(s) involved in BRCA-1 mediated DNA damage...hypersensitivity. A. A diagram of the library screening procedure. B. Isolation of the gene candidates that confer the resistance to DNA damage HCC1937 cells. Fig 3. Effect of BRCA1, Noc-4, PKCBP and H3.3 on protection from irradiation hypersensitivity. A. . A diagram of the library

  17. Identification of a novel pathway involving a GATA transcription factor in yeast and possibly in plant Zn uptake and homeostasis

    Matthew J. Milner; Nicole S. Pence; Jiping Liu; Leon V. Kochian


    To gain a better understanding of the regulation of Zn homeostasis in plants and the degree of conservation of Zn homeostasis between plants and yeast, a cDNA library from the Zn/Cd hyperaccumulating plant species, Noccaea caerules-cens, was screened for its ability to restore growth under Zn limiting conditions in the yeast mutant zap1D. ZAP1 is a transcription factor that activates the Zn dependent transcrip-tion of yeast genes involved in Zn uptake, including ZRT1, the yeast high affinity Zn transporter. From this screen two members of the E2F family of transcription factors were found to activate ZRT1 expression in a Zn independent manner. The activation of ZRT1 by the plant E2F proteins involves E2F-mediated activation of a yeast GATA transcription factor which in turn activates ZRT1 expression. A ZRT1 promoter region necessary for activation by E2F and GATA proteins is upstream of two zinc responsive elements previously shown to bind ZAP1 in ZRT1. This activation may not involve direct binding of E2F to the ZRT1 promoter. The expression of E2F genes in yeast does not replace function of ZAP1; instead it appears to activate a novel GATA regulatory pathway involved in Zn uptake and homeostasis that is not Zn responsive.

  18. Comparative Analysis of the Factors Necessitating Commercial Banks and Manufacturing Firms’ Involvement in Corporate Social Responsibility in Nigeria

    Abiola Idowu


    Full Text Available This research investigates the factors necessitating commercial banks and manufacturing firms’ involvement in Corporate Social Responsibility (CSR in Nigeria comparatively. The research took place in Lagos State in South-west geo-political zone in Nigeria. The survey research design was used in this research. Moreover, the purposive sampling was used in selecting five commercial banks and five manufacturing firms. Primary data were gathered with the aid of questionnaire from 216 respondents out of 250 selected respondents from bank and 205 respondents out of 250 selected respondents from manufacturing firms. Fifty copies of the questionnaires were distributed to each company. All respondents selected were involved in CSR activities of their companies. Factors necessitating companies’ involvement in CSR were examined with Analysis of Variance. The research reveals that t-test value is -0.39 and p-value is 0.8, which shows that there is no significant difference between factors necessitating of the commercial banks and manufacturing firms’ involvement in CSR. The research recommends that corporate organizations should give attention to CSR initiatives as these lead to improvement of customers loyalty, improvement of the positive image of the organization, improved relationship with local communities,   and enhances shareholders values as well as improved relations with public authorities amongst others.

  19. Misexpression screen in Drosophila melanogaster aiming to reveal novel factors involved in formation of body parts.

    Grieder, Nicole C; Charlafti, Ilias; Kloter, Urs; Jäckle, Herbert; Schäfer, Ulrich; Gehring, Walter J


    To identify novel factors that lead a fly imaginal disc to adopt its developmental fate, we carried out a modular dominant misexpression screen in imaginal discs. We have identified two factors that appear to change the fate of the respective body structure and appear to lead to the transformation of a body part. In one mutant line, notum tissue, normally derived from wing imaginal tissue, formed close to the site of the sternopleural bristles, which are leg disc derivatives. In the other line, the arista is transformed into a tubular structure, resembling an abnormal leg. We found that ectopic expression of abrupt was responsible for this potential transformation of the arista.

  20. The relevance of uniform reporting in oral leukoplakia: definition, certainty factor and staging based on experience with 275 patients.

    Brouns, Elisabeth-R E A; Baart, Jacques-A; Bloemena, Elisabeth; Karagozoglu, Hakki; van der Waal, Isaäc


    The aim of the present study was to evaluate the definition of oral leukoplakia, proposed by the WHO in 2005 and taking into account a previously reported classification and staging system, including the use of a Certainty factor of four levels with which the diagnosis of leukoplakia can be established. In the period 1997-2012 a hospital-based population of 275 consecutive patients with a provisional diagnosis of oral leukoplakia has been examined. In only 176 patients of these 275 patients a firm diagnosis of leukoplakia has been established based on strict clinicopathological criteria. The 176 patients have subsequently been staged using a classification and staging system based on size and histopathologic features. For use in epidemiological studies it seems acceptable to accept a diagnosis of leukoplakia based on a single oral examination (Certainty level 1). For studies on management and malignant transformation rate the recommendation is made to include the requirement of histopathologic examination of an incisional or excisional biopsy, representing Certainty level 3 and 4, respectively. This recommendation results in the following definition of oral leukoplakia: "A predominantly white lesion or plaque of questionable behaviour having excluded, clinically and histopathologically, any other definable white disease or disorder". Furthermore, we recommend the use of strict diagnostic criteria for predominantly white lesions for which a causative factor has been identified, e.g. smokers' lesion, frictional lesion and dental restoration associated lesion.

  1. Mammography usage with relevant factors among women with mental disabilities in Taiwan: a nationwide population-based study.

    Yen, Suh-May; Kung, Pei-Tseng; Tsai, Wen-Chen


    Women with mental illness are at increased risk of developing and dying from breast cancer and are thus in urgent need of breast cancer preventive care. This study examined the use of screening mammography by Taiwanese women with mental disabilities and analyzed factors affecting this use. 17,243 Taiwanese women with mental disabilities aged 50-69 years were retrospectively included as study subjects. Linked patient data were obtained from three national databases in Taiwan (the 2008 database of physically and mentally disabled persons, the Health Promotion Administration's 2007-2008 mammography screening data, and claims data from the National Health Insurance Research Database). Besides descriptive statistics and bivariate analysis, logistic regression analysis was also performed to examine factors affecting screening mammography use. The 2007-2008 mammography screening rate for Taiwanese women with mental disabilities was 8.79% (n=1515). Variables that significantly influenced screening use were income, education, presence of catastrophic illness/injury, severity of mental disability, and usage of other preventive care services. Screening was positively correlated with income and education. Those with catastrophic illness/injury were more likely to be screened (odds ratio [OR], 1.40; 95% CI=1.15-1.72). Severity of disability was negatively correlated with screening, with very severe, severe, and moderate disability being associated with 0.34-0.69 times the odds of screening as mild disability. In Taiwan, women with mental disabilities receive far less mammography screening than women in general.

  2. Analysis of nodulation kinetics in Frankia-Discaria trinervis symbiosis reveals different factors involved in the nodulation process.

    Gabbarini, Luciano Andrés; Wall, Luis Gabriel


    The induction of root nodule development in actinorhizal symbiosis would depend on the concentration of factors produced by the bacteria and the plant. A detailed analysis of nodulation description parameters revealed different factors related to the nodulation process. The initial time for nodulation (t(0)), the initial nodulation rate (v(0)) and the total time of nodule development (t(NOD)) were defined and consequently quantified in different experimental conditions: co-inoculation of Discaria trinervis with increasing concentrations of different non-infective bacteria together with the full compatible infective Frankia strain (the indicator strain) used at a limiting concentration or by changing plant factor(s) concentration. All the above nodulation parameters were modified by changing doses of full compatibility infective strain Frankia BCU110501; v(0) appears to be an expression of symbiotic recognition between partners as only fully symbiotic indicator Frankia BCU110501 was able to change it; t(0) seems not to reflect symbiotic recognition because it can also be modified by non-infective Frankia but suggest the existence of a basic level of plant microbe recognition. The initial time for nodulation t(0), reflecting the time required for the early interactions toward nodulation, is an inverse measure of the ability to establish early interactions toward nodulation. The increase in plant factors concentration also reduces t(0) values, suggesting that a plant factor is involved and favors very early interactions. Increases in plant factors concentration also modify the final number of nodules per plant and the nodule cluster profile along the taproot as an expression of the autoregulation phenomenon. Meanwhile, Frankia inoculums' concentration, either infective or not, modified t(NOD) in an opposite way plant factors did. In conclusion, the analysis of nodulation kinetics appears to be an appropriate tool to investigate factors involved in the symbiotic

  3. The neuroprotection of cannabidiol against MPP⁺-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson's disease.

    Santos, Neife Aparecida Guinaim; Martins, Nádia Maria; Sisti, Flávia Malvestio; Fernandes, Laís Silva; Ferreira, Rafaela Scalco; Queiroz, Regina Helena Costa; Santos, Antônio Cardozo


    Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis sativa with potential to treat neurodegenerative diseases. Its neuroprotection has been mainly associated with anti-inflammatory and antioxidant events; however, other mechanisms might be involved. We investigated the involvement of neuritogenesis, NGF receptors (trkA), NGF, and neuronal proteins in the mechanism of neuroprotection of CBD against MPP(+) toxicity in PC12 cells. CBD increased cell viability, differentiation, and the expression of axonal (GAP-43) and synaptic (synaptophysin and synapsin I) proteins. Its neuritogenic effect was not dependent or additive to NGF, but it was inhibited by K252a (trkA inhibitor). CBD did not increase the expression of NGF, but protected against its decrease induced by MPP(+), probably by an indirect mechanism. We also evaluated the neuritogenesis in SH-SY5Y cells, which do not express trkA receptors. CBD did not induce neuritogenesis in this cellular model, which supports the involvement of trkA receptors. This is the first study to report the involvement of neuronal proteins and trkA in the neuroprotection of CBD. Our findings suggest that CBD has a neurorestorative potential independent of NGF that might contribute to its neuroprotection against MPP(+), a neurotoxin relevant to Parkinson's disease.

  4. Cognitive Factors Involved in the First Stage of Programming Skill Acquisition.


    70j .71 - P3y .71/ Figure 7. One-factor model (Model 7) of the algebra word problem solving test. PS = word problem solving skill . TABLE 2. GOODNESS...14, 389-433. Kyllonen, P.C., & Soule, C. (1988, April). The role of working memory and general problem solving skill in acquiring computer

  5. Membrane association of the Arabidopsis ARF exchange factor GNOM involves interaction of conserved domains

    Anders, Nadine; Nielsen, Michael M.; Keicher, Jutta;


    The GNOM protein plays a fundamental role in Arabidopsis thaliana development by regulating endosome-to-plasma membrane trafficking required for polar localization of the auxin efflux carrier PIN1. GNOM is a family member of large ARF guanine nucleotide exchange factors (ARF-GEFs), which regulate...

  6. Background Noise Acceptance and Personality Factors Involved in Library Environment Choices by College Students

    Gordon-Hickey, Susan; Lemley, Trey


    For decades, academic libraries made efforts to provide study environments differing in acoustic environment. The present study aimed to provide an evidence basis for this practice by comparing background noise acceptance and personality factors of two groups of college-aged students self identified as preferring quiet or background noise when…

  7. Mapping Escherichia coli elongation factor Tu residues involved in binding of aminoacyl-tRNA

    Wiborg, Ove; Andersen, C; Knudsen, Charlotte Rohde


    were characterized with respect to thermal and chemical stability, GTPase activity, tRNA affinity, and activity in an in vitro translation assay. Most conspicuously tRNA affinities were reduced for all mutants. The results verify our structural analysis of elongation factor Tu in complex with aminoacyl...

  8. Mapping Escherichia coli elongation factor Tu residues involved in binding of aminoacyl-tRNA

    Wiborg, Ove; Andersen, C; Knudsen, Charlotte Rohde


    -tRNA, which suggested an important role of Lys-89 and Asn-90 in tRNA binding. Furthermore, our results indicate helix B to be an important target site for nucleotide exchange factor EF-Ts. Also the mutants His-66 to Ala and His-118 to either Ala or Glu were characterized in an in vitro translation assay...

  9. Mass spectrometric characterization of a biotechnologically produced full-length mechano growth factor (MGF) relevant for doping controls.

    Thevis, Mario; Thomas, Andreas; Geyer, Hans; Schänzer, Wilhelm


    Since Goldspink and colleagues identified the expression of the mRNA of an insulin-like growth factor 1 (IGF-1) isoform in response to mechanical stress in 1996, substantial research into the so-called mechano growth factor and its modus operandi followed until today. Promising preclinical results were obtained by using the synthetic, 24-amino acid residues spanning peptide translated from the exons 4-6 of IGF-1Ec (which was later referred to as the mechano growth factor (MGF) peptide), particularly with regard to increased muscle myoblast proliferation. Consequently, the MGF peptide represented a promising drug candidate for the treatment of neuromuscular disorders; however, its misuse potential in sport was also identified shortly thereafter, and the substance (or class of substances) has been considered prohibited according to the regulations of the World Anti-Doping Agency (WADA) since 2005. While various MGF peptide versions have been known to sports drug testing authorities, the occurrence of a 'full-length MGF' as offered via illicit channels to athletes or athletes' managers was reported in 2014, arguably being undetectable in doping controls. An aliquot of the product was obtained and the content characterized by state-of-the-art analytical approaches including gel electrophoretic and mass spectrometric (top-down and bottom-up) sequencing approaches. Upon full characterization, its implementation into modified routine doping controls using ultrafiltration, immunoaffinity-based isolation, and nanoliquid chromatography-high resolution/high accuracy mass spectrometry was established. A protein with a monoisotopic molecular mass of 12264.9 Da and a sequence closely related to IGF-1Ec (lacking the signal- and propeptide moiety) was identified. The C-terminus was found to be modified by the elimination of the terminal lysine and a R109H substitution. With the knowledge of the compound's composition, existing doping control assays targeting peptide hormones such

  10. Roles of heat shock factor 1 in neuronal response to fetal environmental risks and its relevance to brain disorders.

    Hashimoto-Torii, Kazue; Torii, Masaaki; Fujimoto, Mitsuaki; Nakai, Akira; El Fatimy, Rachid; Mezger, Valerie; Ju, Min J; Ishii, Seiji; Chao, Shih-Hui; Brennand, Kristen J; Gage, Fred H; Rakic, Pasko


    Prenatal exposure of the developing brain to various environmental challenges increases susceptibility to late onset of neuropsychiatric dysfunction; still, the underlying mechanisms remain obscure. Here we show that exposure of embryos to a variety of environmental factors such as alcohol, methylmercury, and maternal seizure activates HSF1 in cerebral cortical cells. Furthermore, Hsf1 deficiency in the mouse cortex exposed in utero to subthreshold levels of these challenges causes structural abnormalities and increases seizure susceptibility after birth. In addition, we found that human neural progenitor cells differentiated from induced pluripotent stem cells derived from schizophrenia patients show higher variability in the levels of HSF1 activation induced by environmental challenges compared to controls. We propose that HSF1 plays a crucial role in the response of brain cells to prenatal environmental insults and may be a key component in the pathogenesis of late-onset neuropsychiatric disorders.

  11. The relevance of childhood developmental factors to the efficacy of acupuncture on the affective component of back pain.

    Straiton, Nicholas


    There is substantial evidence to support the use of acupuncture in the treatment of low back pain. The main predictors of chronic low back pain are non-medical and psychosocial. The understanding of how acupuncture can modulate the pain experience has recently been enhanced by the elucidation of the role of C fibre afferents on the limbic system. C fibre deactivation of the limbic system can only occur in the presence of intact corticosubcortical neuronal pathways. The normal development of these pathways is determined by social factors in the early years of life. The effect of acupuncture treatment for low back pain may be determined by successful relationships between the mother and child in the first 18 months of life.

  12. Measurement of the pion form factor at BESIII in the rho-peak region relevant for (g — 2)μ

    Redmer, C. F.; BESIII Collaboration


    Measurements of hadronic cross sections in e+e- collisions are an important input for the Standard Model calculations of the hadronic contribution to the anomalous magnetic moment of the muon, (g — 2)μ. We present a new measurement of the cross section e+e- → π+π-, the pion form factor, which dominates the hadronic contribution. Using the method of initial state radiation, 2.93 fb-1 of data taken with the BESIII detector at the ψ (3770) peak have been evaluated to determine the cross section in the energy range between 600 and 900 MeV with a systematic uncertainty of 0.9%. The new BESIII data are compared to previous measurements by KLOE and BaBar, and their impact on (g — 2)μ is discussed.

  13. Identifying SME mortality factors in the life cycle stages: an empirical approach of relevant factors for small business owner-managers in Brazil

    Filho, Edmundo Escrivão; Albuquerque, Alexandre Farias; Nagano, Marcelo Seido; Junior, Luiz Adalberto Philippsen; de Oliveira, Jair


    .... This paper discusses the relation between the SME mortality factors and the small business owner-manager, based on the life cycle stage as an essential part for a better understanding of their closure moment...

  14. Acute strength exercise and the involvement of small or large muscle mass on plasma brain-derived neurotrophic factor levels

    Paulo Roberto Correia


    Full Text Available OBJECTIVE: Blood neurotrophins, such as the brain-derived neurotrophic factor, are considered to be of great importance in mediating the benefits of physical exercise. In this study, the effect of acute strength exercise and the involvement of small versus large muscle mass on the levels of plasma brain-derived neurotrophic factor were evaluated in healthy individuals. METHODS: The concentric strengths of knee (large and elbow (small flexor and extensor muscles were measured on two separate days. Venous blood samples were obtained from 16 healthy subjects before and after exercise. RESULTS: The levels of brain-derived neurotrophic factor in the plasma did not significantly increase after both arm and leg exercise. There was no significant difference in the plasma levels of the brain-derived neurotrophic factor in the arms and legs. CONCLUSION: The present results demonstrate that acute strength exercise does not induce significant alterations in the levels of brain-derived neurotrophic factor plasma concentrations in healthy individuals. Considering that its levels may be affected by various factors, such as exercise, these findings suggest that the type of exercise program may be a decisive factor in altering peripheral brain-derived neurotrophic factor.

  15. Characterization of a transcription factor involved in mother cell specific transcription of the yeast HO gene.

    Stillman, D J; Bankier, A T; Seddon, A; Groenhout, E G; Nasmyth, K A


    The yeast HO gene, which encodes an endonuclease involved in initiating mating type interconversion, is expressed in mother cells but not in daughters. It has been demonstrated that the SWI5 gene, which is an activator of HO expression, plays a critical role in this differential mother/daughter expression of HO. In this paper we describe the cloning and sequencing of the SWI5 gene. The predicted amino acid sequence derived from the cloned SWI5 gene shows homology with the repeated DNA-binding...

  16. Evolution of the interaction between Runx2 and VDR, two transcription factors involved in osteoblastogenesis

    Barriga Elias H


    Full Text Available Abstract Background The mineralized skeleton is a major evolutionary novelty that has contributed to the impressive morphological diversifications of the vertebrates. Essential to bone biology is the solidified extracellular matrix secreted by highly specialized cells, the osteoblasts. We now have a rather complete view of the events underlying osteogenesis, from a cellular, molecular, genetic, and epigenetic perspective. Because this knowledge is still largely restricted to mammals, it is difficult, if not impossible, to deduce the evolutionary history of the regulatory network involved in osteoblasts specification and differentiation. In this study, we focused on the transcriptional regulators Runx2 and VDR (the Vitamin D Receptor that, in mammals, directly interact together and stabilize complexes of co-activators and chromatin remodellers, thereby allowing the transcriptional activation of target genes involved in extracellular matrix mineralization. Using a combination of functional, biochemical, and histological approaches, we have asked if the interaction observed between Runx2 and VDR represents a recent mammalian innovation, or if it results from more ancient changes that have occurred deep in the vertebrate lineage. Results Using immunohistochemistry and in situ hybridization in developing embryos of chick, frog and teleost fishes, we have revealed that the co-expression of Runx2 and VDR in skeletal elements has been particularly strengthened in the lineage leading to amniotes. We show that the teleost Runx2 orthologue as well as the three mammalian Runx1, Runx2 and Runx3 paralogues are able to co-immunoprecipitate with the VDR protein present in nuclear extracts of rat osteoblasts stimulated with 1α,25-dihydroxyvitamin D3. In addition, the teleost Runx2 can activate the transcription of the mammalian osteocalcin promoter in transfection experiments, and this response can be further enhanced by 1α,25-dihydroxyvitamin D3. Finally

  17. Involvement of pro- and antinociceptive factors in minocycline analgesia in rat neuropathic pain model.

    Rojewska, Ewelina; Popiolek-Barczyk, Katarzyna; Jurga, Agnieszka M; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna


    In neuropathic pain the repeated minocycline treatment inhibited the mRNA and protein expression of the microglial markers and metalloproteinase-9 (MMP-9). The minocycline diminished the pronociceptive (IL-6, IL-18), but not antinociceptive (IL-1alpha, IL-4, IL-10) cytokines at the spinal cord level. In vitro primary cell culture studies have shown that MMP-9, TIMP-1, IL-1beta, IL-1alpha, IL-6, IL-10, and IL-18 are of microglial origin. Minocycline reduces the production of pronociceptive factors, resulting in a more potent antinociceptive effect. This change in the ratio between pro- and antinociceptive factors, in favour of the latter may be the mechanism of minocycline analgesia in neuropathy.

  18. [Factors family background of mothers involved in having a premature baby].

    Kamburova, M; Hristova, I


    Level of prematurity is an objective criterion for determining the health welfare of the population. Several family background factors of the mother increases the risk of preterm birth child - family status, unwanted pregnancy, etc. Pregnancy among unmarried women and unwanted pregnancy are associated with a higher risk of giving premature baby. Aim of this study is a survey and analysis of factors of family background of the mother (family status and unplanned pregnancy) and their influence on the birth of a premature baby. The survey found nearly three times higher risk OR = 2,83 95 % CI (1,7-4,7) for the birth of a premature baby among unmarried mothers compared to married women, and twice as high proportion of unplanned pregnancy mothers of preterm infants - 20.7% compared to terminfants-10.4%.

  19. Selective factors involved in oil flotation isolation of black yeasts from the environment.

    Satow, M M; Attili-Angelis, D; de Hoog, G S; Angelis, D F; Vicente, V A


    The oil flotation isolation technique has been successfully applied to recover chaetothyrialean black yeasts and relatives from the environment. The selective mechanisms playing a role in isolation are unknown. The fungi concerned are supposed to occupy specialized microniches in nature, taking advantage of (1) oligotrophism. Mineral oil as a main selective agent may be based on (2) hydrophobicity or on (3) assimilation. All three hypotheses are tested in this paper. Results show that cell wall hydrophobicity is unlikely to be a selective factor. Incubation under poor nutrient conditions provides competitive advantage for black yeasts, especially for Exophiala strains, which are subsequently enriched by mineral oil which enhances growth in this group of fungi. Incubation under mineral media and mineral oil can be used as selective factor.

  20. Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.

    Gaut, Carrie; Sugaya, Kiminobu


    Articular cartilage defects often progress to osteoarthritis, which negatively impacts quality of life for millions of people worldwide and leads to high healthcare expenditures. Tissue engineering approaches to osteoarthritis have concentrated on proliferation and differentiation of stem cells by activation and suppression of signaling pathways, and by using a variety of scaffolding techniques. Recent studies indicate a key role of environmental factors in the differentiation of mesenchymal stem cells to mature cartilage-producing chondrocytes. Therapeutic approaches that consider environmental regulation could optimize chondrogenesis protocols for regeneration of articular cartilage. This review focuses on the effect of scaffold structure and composition, mechanical stress and hypoxia in modulating mesenchymal stem cell fate and the current use of these environmental factors in tissue engineering research.

  1. Extrinsic Factors Involved in the Differentiation of Stem Cells into Insulin-Producing Cells: An Overview

    Rebecca S. Y. Wong


    Full Text Available Diabetes mellitus is a chronic disease with many debilitating complications. Treatment of diabetes mellitus mainly revolves around conventional oral hypoglycaemic agents and insulin replacement therapy. Recently, scientists have turned their attention to the generation of insulin-producing cells (IPCs from stem cells of various sources. To date, many types of stem cells of human and animal origins have been successfully turned into IPCs in vitro and have been shown to exert glucose-lowering effect in vivo. However, scientists are still faced with the challenge of producing a sufficient number of IPCs that can in turn produce sufficient insulin for clinical use. A careful choice of stem cells, methods, and extrinsic factors for induction may all be contributing factors to successful production of functional beta-islet like IPCs. It is also important that the mechanism of differentiation and mechanism by which IPCs correct hyperglycaemia are carefully studied before they are used in human subjects.

  2. Catheter-related infections caused by Pseudomonas aeruginosa: virulence factors involved and their relationships.

    Olejnickova, Katerina; Hola, Veronika; Ruzicka, Filip


    The nosocomial pathogen Pseudomonas aeruginosa is equipped with a large arsenal of cell-associated and secreted virulence factors which enhance its invasive potential. The complex relationships among virulence determinants have hitherto not been fully elucidated. In the present study, 175 catheter-related isolates were observed for the presence of selected virulence factors, namely extracellular enzymes and siderophore production, biofilm formation, resistance to antibiotics, and motility. A high percentage of the strains produced most of the tested virulence factors. A positive correlation was identified between the production of several exoproducts, and also between the formation of both types of biofilm. An opposite trend was observed between the two types of biofilm and the production of siderophores. Whereas the relationship between the submerged biofilm production (i.e. the biofilm formed on the solid surface below the water level) and the siderophore secretion was negative, the production of air-liquid interface (A-L) biofilm (i.e. the biofilm floating on the surface of the cultivation medium) and the siderophore secretion were positively correlated. All correlations were statistically significant at the level P = 0.05 with the correlation coefficient γ ≥ 0.50. Our results suggest that: (1) the co-production of the lytic enzymes and siderophores can play an important role in the pathogenesis of the catheter-related infections and should be taken into account when the virulence potential is assessed; (2) biofilm-positive strains are capable of forming both submerged and non-attached A-L biofilms; and (3) the different micro-environment in the submerged biofilm and A-L biofilm layers have opposite consequences for the production of other virulence factors.

  3. Examining factors involved in stress-related working memory impairments: Independent or conditional effects?

    Banks, Jonathan B; Tartar, Jaime L; Tamayo, Brittney A


    A large and growing body of research demonstrates the impact of psychological stress on working memory. However, the typical study approach tests the effects of a single biological or psychological factor on changes in working memory. The current study attempted to move beyond the standard single-factor assessment by examining the impact of 2 possible factors in stress-related working memory impairments. To this end, 60 participants completed a working memory task before and after either a psychological stressor writing task or a control writing task and completed measures of both cortisol and mind wandering. We also included a measure of state anxiety to examine the direct and indirect effect on working memory. We found that mind wandering mediated the relationship between state anxiety and working memory at the baseline measurement. This indirect relationship was moderated by cortisol, such that the impact of mind wandering on working memory increased as cortisol levels increased. No overall working memory impairment was observed following the stress manipulation, but increases in state anxiety and mind wandering were observed. State anxiety and mind wandering independently mediated the relationship between change in working memory and threat perception. The indirect paths resulted in opposing effects on working memory. Combined, the findings from this study suggest that cortisol enhances the impact of mind wandering on working memory, that state anxiety may not always result in stress-related working memory impairments, and that high working memory performance can protect against mind wandering.

  4. State of the art: psychotherapeutic interventions targeting the psychological factors involved in IBD.

    Leone, Daniela; Menichetti, Julia; Fiorino, Gionata; Vegni, Elena


    The present article aims to review the literature on the relationship between psychology and inflammatory bowel disease (IBD). In particular, the first section is dedicated to explore the role of psychological factors in the etiopathology of the disease, its development and the efficacy of treatments, while the second analyzes existing literature on the role of psychological interventions in the care of IBD patients. Although the role of psychological factors in IBD appears controversial, literature seems to distinguish between antecedents of the disease (stress and lifestyle behavior), potential mediators of disease course (family functioning, attachment style, coping strategies, and illness perception), outcomes of IBD and concurrent factors (anxiety, depression and quality of life). Four types of psychological interventions are described: Stress management, Psychodynamic, Cognitive behavioral and Hypnosis based. Data on the role and efficacy of psychological interventions in IBD patients show little evidence both on reduction of the disease activity and benefits on psychological variables. Psychological interventions seem to be beneficial in the short term especially for adolescents. The importance of considering the connections between psychology and IBD from a broader perspective reflecting the complexity of the phenomenon at multiple levels is discussed.

  5. Factors Involved in the In Vitro Fermentability of Short Carbohydrates in Static Faecal Batch Cultures

    Eva Gietl


    Full Text Available In recent years, research has focused on the positive effects of prebiotics on intestinal health and gut microbiota. The relationship between their chemical structure and their fermentation pattern by human intestinal microbiota is still not well understood. The aim of this study was to improve understanding of this relationship and identify factors that may be used to design galactooligosaccharides that reach more distal regions than commercial prebiotics which mainly target the proximal colon. The following factors were investigated: monomer type, linkage, substitution, and degree of polymerisation. Total organic acid production from sugars by faecal bacteria was fitted to a model which allowed an estimate of the time when half of the maximal organic acid concentration was reached (T50 in static faecal batch cultures. The different factors can be grouped by their effectiveness at prolonging fermentation time as follows: substitution is most effective, with methylgalactose, β-galactose-pentaacetate, D-fucose, and galactitol fermented more slowly than D-galactose. Monomers and linkage also influence fermentation time, with L rhamnose, arabinose, melezitose, and xylose being fermented significantly slower than D-glucose (P<0.05, maltose, isomaltose, cellobiose, and gentiobiose showing that Glcα1-6Glc and Glcβ1-4Glc were utilised slowest. Chain length had the smallest effect on fermentation time.

  6. Characterization of a novel Medicago sativa NAC transcription factor gene involved in response to drought stress.

    Wang, Yong Xin


    Relying on the regulation of transcription factors, plants resist to various abiotic and biotic stresses. NAC (NAM, ATAF1/2, CUC2) are one of the largest families of plant-specific transcription factors and known to play important roles in plant development and response to environmental stresses. A new NAC gene was cloned on the basis of 503 bp EST fragment from the SSH cDNA library of Medicago sativa. It was 1,115 bp including an 816 bp ORF and encodes 271 amino acids. A highly conserved region is located from the 7th amino acid to the 315th amino acid in its N-terminal domain. The NAC protein is subcellularly localized in the nucleus of onion epidemical cells and possible functions as a transcription factor. The relative quantitative real-time RT-PCR was performed at different stress time. The results revealed that the transcription expression of NAC gene could be induced by drought, high salinity and ABA. The transgenic Arabidopsis with NAC gene has the drought tolerance better than the wild-type.

  7. Vision and Relevant Risk Factor Interventions for Preventing Falls among Older People: A Network Meta-analysis.

    Zhang, Xin-Yi; Shuai, Jian; Li, Li-Ping


    Our study objective was to determine the effect of vision intervention and combinations of different intervention components on preventing falls and fall-related injuries among older people. Six electronic databases were searched to identify seven articles published before May, 2014. We conducted a systematic review of data from seven randomized controlled trails and identified eight regimens: vision intervention alone (V), vision plus exercise (referred to as physical exercise) interventions (V + E), vision plus home hazard interventions (V + HH), vision plus exercise plus home hazard interventions (V + E + HH), vision plus exercise plus sensation interventions (V + E + S), vision plus hearing interventions (V + H), vision plus various risk factor assessment and interventions (V + VRF), and the control group (C, no intervention group). The main outcome was the incidence of falls during the follow-up period. Seven papers included 2723 participants. Network meta-analysis of seven trials, using pairwise comparisons between each intervention, indicated there was no significant difference. However, there was a trend in which intervention incorporating V + VRF had more advantages than any other combination of interventions. In conclusion, V + VRF proves to be more effective than other V combination interventions in preventing falls in older people (≥65 years of age). V alone appears less effective in our network meta-analysis.

  8. Relevance of psychosocial factors to quality of life in oral cancer and oral lichen planus: a prospective comparative study.

    Rana, Madiha; Kanatas, Anastasios; Herzberg, Philipp Y; Gellrich, Nils-Claudius; Rana, Majeed


    We can improve our understanding of how patients cope with oral squamous cell carcinoma (SCC) by making a comparison with their processes of coping and those used in other conditions. We have therefore compared quality of life (QoL), severity of symptoms, coping strategies, and factors that influence coping between patients with oral SCC and those with oral lichen planus. We asked 104 patients with oral SCC and 51 with oral lichen planus to complete questionnaires about their coping strategies, social support, locus of control, spirituality, QoL, and severity of symptoms. The outcome was that patients with oral SCC were far more likely to resort to coping strategies such as depressive coping, distraction, and self-motivation. The groups also differed regarding QoL and severity of symptoms. Patients with oral SCC had a poorer QoL and higher depression scores, whereas patients with oral lichen planus had better scores in the social support and spirituality categories. Patients with oral SCC generally had more distress than those with oral lichen planus. Not only did the former resort to depressive coping strategies, but they also had poorer QoL and higher values for depression. For the patients with oral lichen planus, social support and spirituality were protective, whereas they were associated with distress by patients with oral SCC.

  9. The impact factor of a journal is a poor measure of the clinical relevance of its papers.

    Kodumuri, P; Ollivere, B; Holley, J; Moran, C G


    We evaluated the top 13 journals in trauma and orthopaedics by impact factor and looked at the longer-term effect regarding citations of their papers. All 4951 papers published in these journals during 2007 and 2008 were reviewed and categorised by their type, subspecialty and super-specialty. All citations indexed through Google Scholar were reviewed to establish the rate of citation per paper at two, four and five years post-publication. The top five journals published a total of 1986 papers. Only three (0.15%) were on operative orthopaedic surgery and none were on trauma. Most (n = 1084, 54.5%) were about experimental basic science. Surgical papers had a lower rate of citation (2.18) at two years than basic science or clinical medical papers (4.68). However, by four years the rates were similar (26.57 for surgery, 30.35 for basic science/medical), which suggests that there is a considerable time lag before clinical surgical research has an impact. We conclude that high impact journals do not address clinical research in surgery and when they do, there is a delay before such papers are cited. We suggest that a rate of citation at five years post-publication might be a more appropriate indicator of importance for papers in our specialty.

  10. Combined incineration of industrial wastes with in-plant residues in fluidized-bed utility boilers--decision relevant factors.

    Ragossnig, Arne M; Lorber, Karl E


    In Austria more than 50% of the high-calorific industrial residues and wastes generated are utilized for energy recovery in industrial utility boilers. This study investigated full-scale trials of combined incineration of in-plant residues with various industrial wastes. These trials were carried out in order to learn how the alternatively used fuel influences the incineration process itself as well as the quantity and quality of the various incineration products. The currently used fuel, which consisted of in-plant residues as well as externally acquired waste wood and the refuse-derived fuel (RDF) mixtures used during the full-scale trials are characterized in terms of material composition as well as chemical and physical parameters. An input-output mass balance for the incineration plant (two fluidized bed combustion units, 20 and 30 MW, respectively) has been established, based on the data collected during the full-scale incineration trials. Furthermore, pollutant concentrations in the off-gas as well as the solid incineration residue are reported. It is not only the pollutant content but also a variety of other internal as well as external factors that have to be considered if a company is to decide whether or not to thermally utilize specific waste types. Therefore a strengths and weaknesses profile for several types of waste and the specific industrial boiler is also presented.

  11. The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia

    Stühmer Walter


    Full Text Available Abstract Background The voltage-gated potassium channel hEag1 (KV10.1 has been related to cancer biology. The physiological expression of the human channel is restricted to the brain but it is frequently and abundantly expressed in many solid tumors, thereby making it a promising target for a specific diagnosis and therapy. Because chronic lymphatic leukemia has been described not to express hEag1, it has been assumed that the channel is not expressed in hematopoietic neoplasms in general. Results Here we show that this assumption is not correct, because the channel is up-regulated in myelodysplastic syndromes, chronic myeloid leukemia and almost half of the tested acute myeloid leukemias in a subtype-dependent fashion. Most interestingly, channel expression strongly correlated with increasing age, higher relapse rates and a significantly shorter overall survival. Multivariate Cox regression analysis revealed hEag1 expression levels in AML as an independent predictive factor for reduced disease-free and overall survival; such an association had not been reported before. As a functional correlate, specific hEag1 blockade inhibited the proliferation and migration of several AML cell lines and primary cultured AML cells in vitro. Conclusion Our observations implicate hEag1 as novel target for diagnostic, prognostic and/or therapeutic approaches in AML.

  12. Factors associated with crashes involving taxi owners and non-owners: A case of moral hazard and adverse selection?

    Tay, Richard; Choi, Jaisung


    Taxis experience a higher risk of a motor vehicle crash partly because of their much higher levels of exposure on the roads. Although several studies have been conducted to examine the factors associated with the frequency and severity of taxi collisions, little research has been conducted to examine the differences in the factors associated with owner taxis and non-owner taxis. This study finds that collisions involving non-owners are more likely to be associated with poor or risky driving behaviors than collisions involving taxi vehicle owners. This result is consistent with the economic principles of moral hazard and adverse selection. Hence, policy makers responsible for traffic safety, taxi regulation or taxi operations should consider measures to reduce these market inefficiencies and improve the safety of not only taxi drivers but all road users.

  13. An investigation of cognitive factors involved in the development of problem-solving strategies by young children

    Whitebread, David


    There is much current interest in children's problem-solving, both within education, and within psychology. The present study explores the development of young children's problem-solving abilities, and the cognitive factors which might be related to this. Such development is conceptualised in terms of the emergence of increasingly sophisticated and powerful cognitive strategies. In a previous study (Whitebread, 1983), which involved 20 children aged 5 and 6 years, a strong interact...

  14. Parenting factors, social skills, and value commitments as precursors to school failure, involvement with deviant peers, and delinquent behavior.

    Simons, R L; Whitbeck, L B; Conger, R D; Conger, K J


    Elements of social control theory were combined with social learning theory to construct a model of delinquency which specifies the manner in which parenting factors, social skills, value commitments, and problems in school contribute to association with deviant peers and involvement in delinquent behavior. The model was tested using a sample of 61 families, each of which included a seventh grader. Questionnaire responses and coded videotaped family interaction were employed as measures of study constructs. The results largely supported the proposed model.

  15. Why are women so intelligent? The effect of maternal IQ on childhood mortality may be a relevant evolutionary factor.

    Charlton, Bruce G


    Humans are an unusual species because they exhibit an economic division of labour. Most theories concerning the evolution of specifically human intelligence have focused either on economic problems or sexual selection mechanisms, both of which apply more to men than women. Yet while there is evidence for men having a slightly higher average IQ, the sexual dimorphism of intelligence is not obvious (except at unusually high and low levels). However, a more female-specific selection mechanism concerns the distinctive maternal role in child care during the offspring's early years. It has been reported that increasing maternal intelligence is associated with reducing child mortality. This would lead to a greater level of reproductive success for intelligent women, and since intelligence is substantially heritable, this is a plausible mechanism by which natural selection might tend to increase female intelligence in humans. Any effect of maternal intelligence on improving child survival would likely be amplified by assortative mating for IQ by which people tend to marry others of similar intelligence - combining female maternal and male economic or sexual selection factors. Furthermore, since general intelligence seems to have the functional attribute of general purpose problem-solving and more rapid learning, the advantages of maternal IQ are likely to be greater as the environment for child-rearing is more different from the African hunter-gatherer society and savannah environment in which ancestral humans probably evolved. However, the effect of maternal IQ on child mortality would probably only be of major evolutionary significance in environments where childhood mortality rates were high. The modern situation is that population growth is determined mostly by birth rates; so in modern conditions, maternal intelligence may no longer have a significant effect on reproductive success; the effect of female IQ on reproductive success is often negative. Nonetheless, in the

  16. Yeast genetic analysis reveals the involvement of chromatin reassembly factors in repressing HIV-1 basal transcription.

    Manuela Vanti


    Full Text Available Rebound of HIV viremia after interruption of anti-retroviral therapy is due to the small population of CD4+ T cells that remain latently infected. HIV-1 transcription is the main process controlling post-integration latency. Regulation of HIV-1 transcription takes place at both initiation and elongation levels. Pausing of RNA polymerase II at the 5' end of HIV-1 transcribed region (5'HIV-TR, which is immediately downstream of the transcription start site, plays an important role in the regulation of viral expression. The activation of HIV-1 transcription correlates with the rearrangement of a positioned nucleosome located at this region. These two facts suggest that the 5'HIV-TR contributes to inhibit basal transcription of those HIV-1 proviruses that remain latently inactive. However, little is known about the cell elements mediating the repressive role of the 5'HIV-TR. We performed a genetic analysis of this phenomenon in Saccharomyces cerevisiae after reconstructing a minimal HIV-1 transcriptional system in this yeast. Unexpectedly, we found that the critical role played by the 5'HIV-TR in maintaining low levels of basal transcription in yeast is mediated by FACT, Spt6, and Chd1, proteins so far associated with chromatin assembly and disassembly during ongoing transcription. We confirmed that this group of factors plays a role in HIV-1 postintegration latency in human cells by depleting the corresponding human orthologs with shRNAs, both in HIV latently infected cell populations and in particular single-integration clones, including a latent clone with a provirus integrated in a highly transcribed gene. Our results indicate that chromatin reassembly factors participate in the establishment of the equilibrium between activation and repression of HIV-1 when it integrates into the human genome, and they open the possibility of considering these factors as therapeutic targets of HIV-1 latency.

  17. Factors involved in the inflammatory events of cervical ripening in humans

    Wang Hong


    Full Text Available Abstract Background Cervical ripening is an inflammatory reaction. The glucocorticoid receptor (GR mediates glucocorticoid anti-inflammatory reactions, whereas nuclear factor (NFkappaB is a key pro-inflammatory transcription factor. Prostaglandins as well as platelet activating factor (PAF are inflammatory mediators. Inducible nitric oxide synthase (iNOS regulates the level of nitric oxide (NO in response to various inflammatory stimuli. We hypothesize that a changed biological response to glucocorticoids could be a mechanism regulating the inflammatory events resulting in cervical ripening. Methods We monitored GR and NFkappaB, prostaglandin synthases cyclooxygenase (COX-1 and -2, iNOS, as well as the PAF-receptor (PAF-R in the uterine cervix from term pregnant women (with unripe cervices before the onset of labor (TP, immediately after parturition (PP, as compared to non-pregnant (NP, using immunohistochemistry and RT-PCR. Results The GR protein was detected by immunohistochemistry in the nuclei of stroma and squamous epithelium (SQ. Stromal GR staining was increased in TP as compared to the NP group and decreased again after parturition. GR staining in SQ was decreased after parturition as compared to term. NFkappaB was present in SQ and glandular epithelium (GE, stroma and vascular endothelium. Increased nuclear NFkappaB staining was observed postpartum as compared to term pregnancy in stroma and GE. Stromal immunostaining for COX-1 as well as COX-2 was increased in the TP and PP groups as compared to the NP, and GE displayed an intensely increased COX-2 immunostaining at term and postpartum. Stromal PAF-R immunostaining was highest at term, while it was greatly increased in GE postpartum. No difference in the immunostaining for iNOS was found between the groups. RT-PCR showed a predominance of GRalpha to GRbeta mRNA in cervical tissue. The COX-2 mRNA level was increased in the PP group as compared to the TP group. Conclusions There is a

  18. 住院乳腺癌患者心理痛苦及其相关因素调查%Psychological distress and its relevant factors among inpatients with breast cancer

    陈静; 刘均娥; 苏娅丽; 王会颖


    Objective To investigate the prevalence of psychological distress and analyze its relevant factors among breast cancer inpatients. Methods A total of 320 inpatiente were recruited. The Distress Management Screening Measure( DMSM ) and a demographic information material form were employed through purpose sampling method. Results Among the involved patients,48.13% patients got 4 points or above in distress scale. Poor communication with spouse,fatigue, insurance/financial situation and constipation were risk factors, while age and the course of disease were protective factors. Conclusion Medical staff should pay attention to the relevant factors of psychological distress in breast cancer patients and develop targeted intervention.%目的 调查住院乳腺癌患者心理痛苦发生状况并探索其相关因素.方法 采用描述性研究,通过目的抽样法抽取住院乳腺癌患者320例,采用一般资料问卷和心理痛苦管理筛查工具进行问卷调查.结果 48.13%的住院乳腺癌患者心理痛苦评分≥4分;心理痛苦相关因素有6项,即与丈夫沟通差、疲乏、保险/经济、便秘是危险因素,年龄和病程是保护性因素.结论 医护人员应当关注乳腺癌患者引起心理痛苦的相关因素,并制订具有针对性的干预措施.

  19. Function and regulation of transcription factors involved in root apical meristem and stem cell maintenance

    Rebecca Corinna Drisch


    Full Text Available Plant roots are essential for overall plant development, growth and performance by providing anchorage in the soil and uptake of nutrients and water. The primary root of higher plants derives from a group of pluripotent, mitotically active stem cells residing in the root apical meristem (RAM which provides the basis for growth, development and regeneration of the root. The stem cells in the Arabidopsis thaliana RAM are surrounding the quiescent center (QC, which consists of a group of rarely dividing cells. The QC maintains the stem cells in a non-cell-autonomous manner and prevents them from differentiation. The necessary dynamic but also tight regulation of the transition from stem cell fate to differentiation most likely requires complex regulatory mechanisms to integrate external and internal cues. Transcription factors play a central role in root development and are regulated by phytohormones, small signaling molecules and miRNAs. In this review we give a comprehensive overview about the function and regulation of specific transcription factors controlling stem cell fate and root apical meristem maintenance and discuss the possibility of TF complex formation, subcellular translocations and cell-to-cell movement functioning as another level of regulation.

  20. Status of Taenia solium cysticercosis and predisposing factors in developing countries involved in pig farming

    Joseph M. Kungu


    Full Text Available Taenia solium cysticercosis is a disease of pigs and humans populations considered endemic in many developing countries of Latin America, Africa, and South East Asia having serious impact on public health and agriculture. We conducted an in-depth comparative analysis of literature on the disease situation and predisposing factors in selected countries known to be at the interface of poverty-emerging livestock systems-zoonoses and with a growing small holder pig industry. Transmission, methods of diagnosis and employed control strategies of T. solium infection in pig and human populations in these countries are also discussed. Limited knowledge on porcine cysticercosis (PC by various stakeholders expected to be key players in its control has undermined efforts for eliminating this potentially eradicable condition. Poor pig production practices, poor hygiene, and sanitation habits have also been important in the maintenance of the T. solium life-cycle. The major gaps identified in this review include scanty current information on PC prevalence in pigs with hardly any reports on the condition in humans in most developing countries. Factors affecting pattern of the infection and how they interact at the different levels of the pig value chain have not been exhaustively studied. Information on socioeconomic and public health impact is inadequate and not current.

  1. A novel metalloproteinase virulence factor is involved in Bacillus thuringiensis pathogenesis in nematodes and insects.

    Peng, Donghai; Lin, Jian; Huang, Qiong; Zheng, Wen; Liu, Guoqiang; Zheng, Jinshui; Zhu, Lei; Sun, Ming


    The Gram-positive soil bacterium Bacillus thuringiensis has been developed as the leading microbial insecticide for years. The pathogenesis of B. thuringiensis requires common extracellular factors that depend on the PlcR regulon, which regulates a large number of virulence factors; however, the precise role of many of these proteins is not known. In this study, we describe the complete lifecycle of a nematicidal B. thuringiensis strain in the free living nematode Caenorhabditis elegans using in vitro and in vivo molecular techniques to follow host and bacterial effectors during the infection process. We then focus on the metalloproteinase ColB, a collagenase, which was found highly important for destruction of the intestine thereby facilitates the adaptation and colonization of B. thuringiensis in C. elegans. In vivo green fluorescent protein (GFP) reporter-gene studies showed that ColB expression is highly induced and regulated by the global activator PlcR. Finally, we demonstrated that ColB also takes part in B. thuringiensis virulence in an insect model following injection and oral infection. Indeed, addition of purified ColB accelerates the action of Cry toxin proteins in insects, too. These results give novel insights into host adaptation for B. thuringiensis and other B. cereus group bacteria and highlight the role of collagenase metalloproteases to synergize infection process.

  2. How not to do kinetics: examples involving GTPases and guanine nucleotide exchange factors.

    Goody, Roger S


    Guanine nucleotide exchange factors (GEFs) are crucial regulators of the action of GTPases in signal transduction and cellular regulation. Although their basic mechanism of action has been apparent for almost 20 years, there are still misconceptions concerning their properties, and these are confounded by superficial or incorrect interpretation of experimental results in individual cases. Here, an example is described in which an incorrect mechanism was derived because of an inadequate analysis of kinetic results. In a second example, a case is discussed where certain GTP analogs were erroneously described as being able to function as low molecular mass GEFs. In both cases, a lack of distinction between rates, rate constants, and apparent rate constants, together with a disregard of relative signal amplitudes, led to the misinterpretations. In a final example, it is shown how the lack of an appropriate kinetic investigation led to the false conclusion that a secreted protein from Legionella pneumophila can act not only as a GEF towards eukaryotic Rab1 but also as a factor that is able to actively dissociate the stable complex between Rab1 and GDP dissociation inhibitor.

  3. Identification of three LRR-RKs involved in perception of root meristem growth factor in Arabidopsis.

    Shinohara, Hidefumi; Mori, Ayaka; Yasue, Naoko; Sumida, Kumiko; Matsubayashi, Yoshikatsu


    A peptide hormone, root meristem growth factor (RGF), regulates root meristem development through the PLETHORA (PLT) stem cell transcription factor pathway, but it remains to be uncovered how extracellular RGF signals are transduced to the nucleus. Here we identified, using a combination of a custom-made receptor kinase (RK) expression library and exhaustive photoaffinity labeling, three leucine-rich repeat RKs (LRR-RKs) that directly interact with RGF peptides in Arabidopsis These three LRR-RKs, which we named RGFR1, RGFR2, and RGFR3, are expressed in root tissues including the proximal meristem, the elongation zone, and the differentiation zone. The triple rgfr mutant was insensitive to externally applied RGF peptide and displayed a short root phenotype accompanied by a considerable decrease in meristematic cell number. In addition, PLT1 and PLT2 protein gradients, observed as a gradual gradient decreasing toward the elongation zone from the stem cell area in wild type, steeply declined at the root tip in the triple mutant. Because RGF peptides have been shown to create a diffusion-based concentration gradient extending from the stem cell area, our results strongly suggest that RGFRs mediate the transformation of an RGF peptide gradient into a PLT protein gradient in the proximal meristem, thereby acting as key regulators of root meristem development.

  4. Breaking the gender digital divide. Involved factors in the choice of a technological career

    Naira Sánchez Vadillo


    Full Text Available In Spain, only 17% of computer science students are women, a dramatically low tax, yet similar to the ones in the other western countries. This research analyses how some girls manage to overcome the gender digital divide, participating actively in a strongly masculinized world. To understand this process three young computer students girls technological life stories are analyzed. This research method allowed identifying the social practices surrounding the exceptional technological trajectories of these women. The results indicate that these girls have a high sense of technological competence; use self-learning strategies, scorning ICT formal education; and, have a developed taste for mathematics and logical processes. These factors may come from: a a favorable family environment, in which the absence of brothers which could compete for computers and consoles use appears as a one striking factor; and, b a fondness for videogames, that are, as literature signals, an important gateway to new technologies, which increase educational and professional opportunities. Finally, the research puts in evidence that, if a family environment favorable to technology exists, formal education processes can generate counteractive effects when comparing to fostering vocations capacity of informal learning.

  5. [Research progress of the bHLH transcription factors involved in genic male sterility in plants].

    Yongming, Liu; Ling, Zhang; Jianyu, Zhou; Moju, Cao


    Male sterility exists widely in the spermatophytes. It contributes to the study of plant reproductive development and can be used as an effective tool for hybrid seed production in heterosis utilization. Therefore, the study on male sterility is of great value in both theory and application. As one of the largest transcription factor families in plants, basic helix-loop-helix proteins (bHLHs) play a crucial role in regulating plant growth and development. This paper introduces the mechanism of bHLH regulating stamen development in several important model plants. Furthermore, we discuss the molecular mechanisms of genic male sterility resulting from bHLH dysfunction to provide references for crop breeding and theoretical studies.

  6. Factors involved in patient choice of oral or vaginal treatment for vulvovaginal candidiasis

    Sobel JD


    Full Text Available Jack D SobelDivision of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI, USAAbstract: Vulvovaginal candidiasis (VVC is an extremely common cause of vaginal symptoms in women. Multiple antifungal products are available by either the oral or vaginal route, although no new drugs have become available for two decades. Given the therapeutic equivalence of the antimycotic agents and their routes of administration, the specific drug and formulation selected is entirely arbitrary in relation to final treatment outcome. Nevertheless, multiple factors affecting preference, both practitioner-dependent and patient-dependent, impact on selection of a specific drug and route of administration.Keywords: antifungal drugs, antimycotics, Candida vaginitis, vulvovaginal candidiasis

  7. A cell-free system for studying a priming factor involved in repair of bleomycin-damaged DNA.



    Full Text Available A simple cell-free system for studying a priming factor involved in the repair of bleomycin-damaged DNA was established. The template-primer used for the repair DNA synthesis was prepared by treating the closed circular, superhelical form of pUC19 plasmid DNA with 2.2 microM bleomycin and 20 microM ferrous ions. Single-strand breaks were introduced into pUC19 DNA by the bleomycin treatment, and the DNA was consequently converted largely into the open circular form. A system for repair of this bleomycin-damaged DNA was constructed with a priming factor, DNA polymerase (DNA polymerase beta or Klenow fragment of DNA polymerase I, ATP, T4 DNA ligase and four deoxynucleoside triphosphates. After incubation, the conformation of the DNA was analyzed by agarose gel electrophoresis and electron microscopy. The open circular DNA was largely converted to the closed circular DNA, indicating that the single-strand breaks of DNA were repaired. When the priming factor was omitted, DNA repair did not occur. The present system seemed to be applicable to the study of priming factors involved in the repair of DNA with single-strand breaks caused not only by bleomycin but also by ionizing radiation or active oxygen.

  8. The Fish Pathogen Vibrio vulnificus Biotype 2: Epidemiology, Phylogeny, and Virulence Factors Involved in Warm-Water Vibriosis.

    Amaro, Carmen; Sanjuán, Eva; Fouz, Belén; Pajuelo, David; Lee, Chung-Te; Hor, Lien-I; Barrera, Rodolfo


    Vibrio vulnificus biotype 2 is the etiological agent of warm-water vibriosis, a disease that affects eels and other teleosts, especially in fish farms. Biotype 2 is polyphyletic and probably emerged from aquatic bacteria by acquisition of a transferable virulence plasmid that encodes resistance to innate immunity of eels and other teleosts. Interestingly, biotype 2 comprises a zoonotic clonal complex designated as serovar E that has extended worldwide. One of the most interesting virulence factors produced by serovar E is RtxA13, a multifunctional protein that acts as a lethal factor for fish, an invasion factor for mice, and a survival factor outside the host. Two practically identical copies of rtxA13 are present in all biotype 2 strains regardless of the serovar, one in the virulence plasmid and the other in chromosome II. The plasmid also contains other genes involved in survival and growth in eel blood: vep07, a gene for an outer membrane (OM) lipoprotein involved in resistance to eel serum and vep20, a gene for an OM receptor specific for eel-transferrin and, probably, other related fish transferrins. All the three genes are highly conserved within biotype 2, which suggests that they are under a strong selective pressure. Interestingly, the three genes are related with transferable plasmids, which emphasizes the role of horizontal gene transfer in the evolution of V. vulnificus in nutrient-enriched aquatic environments, such as fish farms.

  9. Dissection of genetic and environmental factors involved in tomato organoleptic quality

    Frusciante Luigi


    Full Text Available Abstract Background One of the main tomato breeding objectives is to improve fruit organoleptic quality. However, this task is made somewhat challenging by the complex nature of sensory traits and the lack of efficient selection criteria. Sensory quality depends on numerous factors, including fruit colour, texture, aroma, and composition in primary and secondary metabolites. It is also influenced by genotypic differences, the nutritional regime of plants, stage of ripening at harvest and environmental conditions. In this study, agronomic, biochemical and sensory characterization was performed on six Italian heirlooms grown in different environmental conditions. Result We identified a number of links among traits contributing to fruit organoleptic quality and to the perception of sensory attributes. PCA analysis was used to highlight some biochemical, sensory and agronomic discriminating traits: this statistical test allowed us to identify which sensory attributes are more closely linked to environmental conditions and those, instead, linked to the genetic constitution of tomato. Sweetness, sourness, saltiness and tomato flavour are not only grouped in the same PCA factor, but also result in a clear discrimination of tomato ecotypes in the three different fields. The three different traditional varieties cluster on the basis of attributes like juiciness, granulosity, hardness and equatorial diameter, and are therefore more closely related to the genetic background of the cultivar. Conclusion This finding suggests that a different method should be undertaken to improve sensory traits related to taste perception and texture. Our results might be used to ascertain in what direction to steer breeding in order to improve the flavour characteristics of tomato ecotypes.

  10. Factors involved in nurses' responses to burnout: a grounded theory study

    Nikravesh Mansoure


    Full Text Available Abstract Background Intense and long-standing problems in burn centers in Tehran have led nurses to burnout. This phenomenon has provoked serious responses and has put the nurses, patients and the organization under pressure. The challenge for managers and nurse executives is to understand the factors which would reduce or increase the nurses' responses to burnout and develop delivery systems that promote positive adaptation and facilitate quality care. This study, as a part of more extensive research, aims to explore and describe the nurses' perceptions of the factors affecting their responses to burnout. Methods Grounded theory was used as the method. Thirty- eight participants were recruited. Data were generated by unstructured interviews and 21 sessions of participant observations. Constant comparison was used for data analysis. Results Nurses' and patients' personal characteristics and social support influenced nurses' responses to burnout. Personal characteristics of the nurses and patients, especially when interacting, had a more powerful effect. They altered emotional, attitudinal, behavioral and organizational responses to burnout and determined the kind of caring behavior. Social support had a palliative effect and altered emotional responses and some aspects of attitudinal responses. Conclusions The powerful effect of positive personal characteristics and its sensitivity to long standing and intense organizational pressures suggests approaches to executing stress reduction programs and refreshing the nurses' morale by giving more importance to ethical aspects of caring. Moreover, regarding palliative effect of social support and its importance for the nurses' wellbeing, nurse executives are responsible for promoting a work environment that supports nurses and motivates them.

  11. Control of angiogenesis by galectins involves the release of platelet-derived proangiogenic factors.

    Julia Etulain

    Full Text Available Platelets contribute to vessel formation through the release of angiogenesis-modulating factors stored in their α-granules. Galectins, a family of lectins that bind β-galactoside residues, are up-regulated in inflammatory and cancerous tissues, trigger platelet activation and mediate vascularization processes. Here we aimed to elucidate whether the release of platelet-derived proangiogenic molecules could represent an alternative mechanism through which galectins promote neovascularization. We show that different members of the galectin family can selectively regulate the release of angiogenic molecules by human platelets. Whereas Galectin (Gal-1, -3, and -8 triggered vascular endothelial growth factor (VEGF release, only Gal-8 induced endostatin secretion. Release of VEGF induced by Gal-8 was partially prevented by COX-1, PKC, p38 and Src kinases inhibitors, whereas Gal-1-induced VEGF secretion was inhibited by PKC and ERK blockade, and Gal-3 triggered VEGF release selectively through a PKC-dependent pathway. Regarding endostatin, Gal-8 failed to stimulate its release in the presence of PKC, Src and ERK inhibitors, whereas aspirin or p38 inhibitor had no effect on endostatin release. Despite VEGF or endostatin secretion, platelet releasates generated by stimulation with each galectin stimulated angiogenic responses in vitro including endothelial cell proliferation and tubulogenesis. The platelet angiogenic activity was independent of VEGF and was attributed to the concerted action of other proangiogenic molecules distinctly released by each galectin. Thus, secretion of platelet-derived angiogenic molecules may represent an alternative mechanism by which galectins promote angiogenic responses and its selective blockade may lead to the development of therapeutic strategies for angiogenesis-related diseases.

  12. Comparison of the Pharmacological Effects of Paricalcitol and Doxercalciferol on the Factors Involved in Mineral Homeostasis

    J. Ruth Wu-Wong


    Full Text Available Vitamin D receptor agonists (VDRAs directly suppress parathyroid hormone (PTH mRNA expression. Different VDRAs are known to have differential effects on serum calcium (Ca, which may also affect serum PTH levels since serum Ca regulates PTH secretion mediated by the Ca-sensing receptor (CaSR. In this study, we compared the effects of paricalcitol and doxercalciferol on regulating serum Ca and PTH, and also the expression of PTH, VDR, and CaSR mRNA. The 5/6 nephrectomized (NX Sprague-Dawley rats on a normal or hyperphosphatemia-inducing diet were treated with vehicle, paricalcitol, or doxercalciferol for two weeks. Both drugs at the tested doses (0.042–0.33 g/kg suppressed PTH mRNA expression and serum PTH effectively in the 5/6 NX rats, but paricalcitol was less potent in raising serum Ca than doxercalciferol. In pig parathyroid cells, paricalcitol and the active form of doxercalciferol induced VDR translocation from the cytoplasm into the nucleus, suppressed PTH mRNA expression and inhibited cell proliferation in a similar manner, although paricalcitol induced the expression of CaSR mRNA more effectively. The multiple effects of VDRAs on modulating serum Ca, parathyroid cell proliferation, and the expression of CaSR and PTH mRNA reflect the complex involvement of the vitamin D axis in regulating the mineral homeostasis system.

  13. Factors associated with substance use among Spanish military personnel involved in "Bosnia-Herzegovina".

    Vargas Pecino, Cristina; Castellano, Enrique; Trujillo, Humberto


    The use of both legal and illegal drugs has rarely been investigated among the Spanish military population involved in multinational military operations. The aim of the current study was to examine the consumption of drugs by Spanish military personnel in Bosnia-Herzegovina, and the variables associated with such substance use. A total of 605 military personnel participated in the cross-sectional study. The participants' mean age was 25.9 years (SD = 5.9), and 93.9% of the sample was male. The majority of the participants were enlisted personnel (83.5%). The most widely used drugs were tobacco (54.2%), and alcohol (39.9%). With respect to illegal drugs, the results showed that the drug with the highest prevalence of "use at some point during a lifetime" was cannabis (36.2%), followed by cocaine (14.9%) and amphetamines (12.1%). The most important variable associated with a decrease in the consumption of illegal drugs was social support. Conversely, participants with friends who have used illegal drugs had an increased likelihood of drug consumption. Given that the use of drugs can adversely affect soldiers' performance, preventive measures should be applied in multinational military operations.

  14. Activation of Rac1 and the exchange factor Vav3 are involved in NPM-ALK signaling in anaplastic large cell lymphomas.

    Colomba, A; Courilleau, D; Ramel, D; Billadeau, D D; Espinos, E; Delsol, G; Payrastre, B; Gaits-Iacovoni, F


    The majority of anaplastic large cell lymphomas (ALCLs) express the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) fusion protein, which is oncogenic due to its constitutive tyrosine kinase activity. Transformation by NPM-ALK not only increases proliferation, but also modifies cell shape and motility in both lymphoid and fibroblastic cells. We report that the Rac1 GTPase, a known cytoskeletal regulator, is activated by NPM-ALK in ALCL cell lines (Karpas 299 and Cost) and transfected cells (lymphoid Ba/F3 cells, NIH-3T3 fibroblasts). We have identified Vav3 as one of the exchange factors involved in Rac1 activation. Stimulation of Vav3 and Rac1 by NPM-ALK is under the control of Src kinases. It involves formation of a signaling complex between NPM-ALK, pp60(c-src), Lyn and Vav3, in which Vav3 associates with tyrosine 343 of NPM-ALK via its SH2 domain. Moreover, Vav3 is phosphorylated in NPM-ALK positive biopsies from patients suffering from ALCL, demonstrating the pathological relevance of this observation. The use of Vav3-specific shRNA and a dominant negative Rac1 mutant demonstrates the central role of GTPases in NPM-ALK elicited motility and invasion.

  15. Analysis of risk factors of involvement of seminal vesicles in patients with prostate cancer undergoing radical prostatectomy

    Marcos F. Dall'Oglio


    Full Text Available OBJECTIVE: To determine through preoperative serum PSA level, Gleason score on biopsy and percentage of fragments affected by tumor on biopsy, the probability of involvement of the seminal vesicles. MATERIALS AND METHODS: During the period between March 1991 to December 2002, we selected 899 patients undergoing radical prostatectomy for treatment of localized prostate adenocarcinoma. The analyzed preoperative variables were PSA, percentage of positive fragments and Gleason score on the biopsy. Pre-operative PSA was divided in scales from 0 to 4.0 ng/mL, 4.1 to 10 ng/mL, 10.1 to 20 ng/mL and > 20 ng/mL, Gleason score was categorized in scales from 2 to 6. 7 and 8 to 10, and the percentage of affected fragments was divided in 0 to 25%, 25.1% to 50%, 50.1% to 75%, and 75.1% to 100%. All these variables were correlated with the involvement of seminal vesicles in the surgical specimen. RESULTS: Of the 899 patients under study, approximately 11% (95% CI, [9% - 13%] had involvement of seminal vesicles. On the multivariate analysis, when PSA was < 4, the Gleason score was 2 to 6, and less than 25% of fragments were involved on the biopsy, only 3.6%, 7.6% and 6.2% of patients respectively, had involvement of seminal vesicles. On the multivariate analysis, we observed that PSA, Gleason score and the percentage of involved fragments were independent prognostic factors for invasion of seminal vesicles. CONCLUSION: The preoperative variables used in the present study allow the identification of men with minimal risk (lower than 5% if involvement of seminal vesicles.

  16. Relevance of Helicobacter pylori virulence factors for vaccine development Relevancia de los factores de virulencia de helicobacter pylori para el desarrollo de vacunas

    Luz del Carmen Hernández-Hernández


    Full Text Available Helicobacter pylori infection increases the risk for a wide spectrum of clinical outcomes, ranging from peptic ulcer disease to gastric cancer. However, the infection induces gastric and duodenal ulceration or gastric cancer in only a minority of infected subjects because H. pylori strains are genetically diverse and express different virulence factors. Individuals infected with strains that express these virulence factors probably develop severe diseases such as gastric cancer. Nevertheless, the ancient relationship between H. pylori and humans suggests that some strains could be beneficial to human health, which means that generalized administration of antibiotic therapy could eventually cause problems. The development of vaccines based on virulence factors that provide long-term protection is the best strategy for control and/or elimination of pathogenic strains. The different immunization schemes and formulations designed to evaluate the vaccines based on virulence factors in animal models have offered promising results. However, it is necessary to determine whether or not these results can be reproduced in humans. This article reviews recent vaccination studies that explore this possibility: oral vaccines using urease or inactivated whole cells plus LT as adjuvant and urease expressed in Salmonella spp. vectors, as well as a parenteral multicomponent vaccine plus aluminum hydroxide as adjuvant. Although these studies have achieved limited success, they have established support for the development of an effective vaccine against this infection.La infección por Helicobacter pylori incrementa el riesgo de un amplio espectro de cuadros clínicos, que van de la úlcera péptica al cáncer gástrico. Sin embargo, la infección sólo induce ulceración gástrica y duodenal o cáncer gástrico en la minoría de los sujetos infectados debido que las cepas de H. pylori son genéticamente diversas y expresan diferentes factores de virulencia. As

  17. Genetic Factors Involved in Fumonisin Accumulation in Maize Kernels and Their Implications in Maize Agronomic Management and Breeding

    Santiago, Rogelio; Cao, Ana; Butrón, Ana


    Contamination of maize with fumonisins depends on the environmental conditions; the maize resistance to contamination and the interaction between both factors. Although the effect of environmental factors is a determinant for establishing the risk of kernel contamination in a region, there is sufficient genetic variability among maize to develop resistance to fumonisin contamination and to breed varieties with contamination at safe levels. In addition, ascertaining which environmental factors are the most important in a region will allow the implementation of risk monitoring programs and suitable cultural practices to reduce the impact of such environmental variables. The current paper reviews all works done to address the influence of environmental variables on fumonisin accumulation, the genetics of maize resistance to fumonisin accumulation, and the search for the biochemical and/or structural mechanisms of the maize plant that could be involved in resistance to fumonisin contamination. We also explore the outcomes of breeding programs and risk monitoring of undertaken projects. PMID:26308050

  18. Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor

    Han, Na; Kim, You Jeong; Park, Su Min; Kim, Seung Man; Lee, Ji Suk; Jung, Hye Sook; Lee, Eun Ju; Kim, Tae Kyoon; Kim, Tae Nyun; Kwon, Min Jeong; Lee, Soon Hee; Rhee, Byoung Doo


    Background Cognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more neuronal cell death than glucose deprivation itself. The forkhead box O (FOXO) transcription factors are implicated in the regulation of cell apoptosis and survival, but their role in neuronal cells remains unclear. We examined the role of FOXO transcription factors and the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt and apoptosis-related signaling pathways in PC-12 cells exposed to repeated glucose deprivation/reperfusion. Methods PC-12 cells were exposed to control (Dulbecco's Modified Eagle Medium [DMEM] containing 25 mM glucose) or glucose deprivation/reperfusion (DMEM with 0 mM glucose for 6 hours and then DMEM with 25 mM glucose for 18 hours) for 5 days. MTT assay and Western blot analysis were performed for cell viability, apoptosis, and the expression of survival signaling pathways. FOXO3/4',6-diamidino-2-phenylindole staining was done to ascertain the involvement of FOXO transcription factors in glucose deprivation/reperfusion conditions. Results Compared to PC-12 cells not exposed to hypoglycemia, cells exposed to glucose deprivation/reperfusion showed a reduction of cell viability, decreased expression of phosphorylated Akt and Bcl-2, and an increase of cleaved caspase-3 expression. Of note, FOXO3 protein was localized in the nuclei of glucose deprivation/reperfusion cells but not in the control cells. Conclusion Repeated glucose deprivation/reperfusion caused the neuronal cell death. Activated FOXO3 via the PI3K/Akt pathway in repeated glucose deprivation/reperfusion was involved in genes related to apoptosis.

  19. Analysis of epidermal growth factor signaling in nasal mucosa epithelial cell proliferation involved in chronic rhinosinusitis

    Li Yunchuan; Li Lijuan; Wang Tong; Zang Hongrui; An Yunsong; Li Lifeng; Zhang Junyi


    Background Aberrant epithelial repair has been observed in chronic rhinosinusitis (CRS) patients; however,the mechanism of epithelial cell repair regulation is unclear.Epidermal growth factor (EGF) plays an important role in regulating epithelial cell repair in lower airway and may be a critical factor in the remodeling processes of CRS.The objective of our research is to evaluate the differences between CRS and normal subjects and between chronic rhinosinusitis without nasal polys (CRSsNP) and chronic rhinosinusitis with nasal polys (CRSwNP) in the regulation of EGF pathways and the regulating proliferative position of classic Ras/Raf/MEK/ERK pathways.Methods We evaluated the proliferation rates of ethmoidal mucosal cells before and after stimulation with EGF,epidermal growth factor receptor (EGFR) kinase inhibitor AG1478,and extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 using MTT assays.We also analyzed the sinonasal epithelial cells collected from control subjects and patients with CRS subtypes CRSsNP and CRSwNP for the expression of ERK1/2,phosphorylated ERK1/2,P21,P15,and P27 using western blotting analyses.Results The proliferation rates of sinonasal epithelial cells before and after EGF stimulation were lower in CRS patients than in the controls.AG1478 or PD98059 inhibitor treatment of control epithelial cells did not result in a significant difference in proliferation.Although,AG1478 and PD98059 inhibited the proliferation of CRS cells,the degree of proliferation inhibition was markedly different in CRSsNP.AG 1478 suppressed the proliferation of CRSwNP epithelial cells,whereas PD98059 had no effect.The ratio of ERK1/2 phosphorylation in CRS cells was lower than that of the control cells.Cyclin-dependent kinase inhibitors were highly expressed in CRS cells compared with that of control cells.ERK1/2 and P27 showed differential expression in CRSsNP and CRSwNP.Conclusions Differences existed in EGF pathways in CRS patients and normal

  20. The predictive and prognostic values of factors associated with visceral pleural involvement in resected lung adenocarcinomas

    Zhang HB


    Full Text Available Huibiao Zhang,1 Chen Lu,2 Yingjie Lu,1 Bo Yu,2 Fanzhen Lv,1 Zhenghong Zhu1 1Department of Thoracic Surgery, 2Department of Pathology, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China Background: The predictive and prognostic impact of factors associated with visceral pleural invasion (VPI on survival and recurrence in patients with resected lung adenocarcinomas is not clearly defined.Patients and methods: A total of 505 consecutive patients with stage Ia–IIIa lung adenocarcinomas treated with radical resection were included. The predominant growth pattern was classified according to the new classification system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society. The correlations of VPI with clinical and pathologic parameters were analyzed.Results: The incidence of VPI was significantly lower in lepidic predominant group (15.5% vs 4.5%, P<0.001 and higher in solid and micropapillary predominant group (28.6% vs 17.6%, P=0.004 and 14.7% vs 4.2%, P<0.001, respectively. VPI correlated with higher risk in regional postoperative recurrence (hazard ratio, 2.341; 95% confidence interval, 1.564–3.504 and distant recurrence (hazard ratio, 2.193; 95% confidence interval, 1.665–2.89 in surgically resected lung adenocarcinomas. However, when growth patterns of adenocarcinoma were lumped into multivariate analysis, VPI was not a significant independent predictive factor for survival (P=0.854 for overall survival [OS] and P=0.575 for disease-free survival [DFS] and recurrence (P=0.38 for regional recurrence and P=0.089 for distant recurrence. Of the 95 patients with stage Ib, those who received adjuvant chemotherapy had longer DFS and OS than the patients who received no chemotherapy after surgery. However, these differences in DFS and OS did not reach statistical significance (P=0.063 for DFS, P=0.85 for OS

  1. Improved Variable Selection Algorithm Using a LASSO-Type Penalty, with an Application to Assessing Hepatitis B Infection Relevant Factors in Community Residents.

    Pi Guo

    Full Text Available In epidemiological studies, it is important to identify independent associations between collective exposures and a health outcome. The current stepwise selection technique ignores stochastic errors and suffers from a lack of stability. The alternative LASSO-penalized regression model can be applied to detect significant predictors from a pool of candidate variables. However, this technique is prone to false positives and tends to create excessive biases. It remains challenging to develop robust variable selection methods and enhance predictability.Two improved algorithms denoted the two-stage hybrid and bootstrap ranking procedures, both using a LASSO-type penalty, were developed for epidemiological association analysis. The performance of the proposed procedures and other methods including conventional LASSO, Bolasso, stepwise and stability selection models were evaluated using intensive simulation. In addition, methods were compared by using an empirical analysis based on large-scale survey data of hepatitis B infection-relevant factors among Guangdong residents.The proposed procedures produced comparable or less biased selection results when compared to conventional variable selection models. In total, the two newly proposed procedures were stable with respect to various scenarios of simulation, demonstrating a higher power and a lower false positive rate during variable selection than the compared methods. In empirical analysis, the proposed procedures yielding a sparse set of hepatitis B infection-relevant factors gave the best predictive performance and showed that the procedures were able to select a more stringent set of factors. The individual history of hepatitis B vaccination, family and individual history of hepatitis B infection were associated with hepatitis B infection in the studied residents according to the proposed procedures.The newly proposed procedures improve the identification of significant variables and enable us to

  2. Involvement of Fibroblast Growth Factor Receptor Genes in Benign Prostate Hyperplasia in a Korean Population

    Hae Jeong Park


    Full Text Available Fibroblast growth factors (FGFs and their receptors (FGFRs have been implicated in prostate growth and are overexpressed in benign prostatic hyperplasia (BPH. In this study, we investigated whether single nucleotide polymorphisms (SNPs of the FGFR genes (FGFR1 and FGFR2 were associated with BPH and its clinical phenotypes in a population of Korean men. We genotyped four SNPs in the exons of FGFR1 and FGFR2 (rs13317 in FGFR1; rs755793, rs1047100, and rs3135831 in FGFR2 using direct sequencing in 218 BPH patients and 213 control subjects. No SNPs of FGFR1 or FGFR2 genes were associated with BPH. However, analysis according to clinical phenotypes showed that rs1047100 of FGFR2 was associated with prostate volume in BPH in the dominant model (GA/AA versus GG, P = 0.010. In addition, a significant association was observed between rs13317 of FGFR1 and international prostate symptom score (IPSS in the additive (TC versus CC versus TT, P = 0.0022 and dominant models (TC/CC versus TT, P = 0.005. Allele frequency analysis also showed significant association between rs13317 and IPSS (P = 0.005. These results suggested that FGFR genes could be related to progression of BPH.

  3. DEWAX Transcription Factor Is Involved in Resistance to Botrytis cinerea in Arabidopsis thaliana and Camelina sativa

    Seulgi Ju


    Full Text Available The cuticle of land plants is the first physical barrier to protect their aerial parts from biotic and abiotic stresses. DEWAX, an AP2/ERF-type transcription factor, negatively regulates cuticular wax biosynthesis. In this study, we investigated the resistance to Botrytis cinerea in Arabidopsis thaliana and Camelina sativa overexpressing DEWAX and in Arabidopsis dewax mutant. Compared to wild type (WT leaves, Arabidopsis DEWAX OX and dewax leaves were more and less permeable to toluidine blue dye, respectively. The ROS levels increased in DEWAX OX leaves, but decreased in dewax relative to WT leaves. Compared to WT, DEWAX OX was more resistant, while dewax was more sensitive to B. cinerea; however, defense responses to Pseudomonas syringae pv. tomato DC3000:GFP were inversely modulated. Microarray and RT-PCR analyses indicated that the expression of defense-related genes was upregulated in DEWAX OX, but downregulated in dewax relative to WT. Transactivation assay showed that DEWAX upregulated the expression of PDF1.2a, IGMT1, and PRX37. Chromatin immunoprecipitation assay revealed that DEWAX directly interacts with the GCC-box motifs of PDF1.2a promoter. In addition, ectopic expression of DEWAX increased the tolerance to B. cinerea in C. sativa. Taken together, we suggest that increased ROS accumulation and DEWAX-mediated upregulation of defense-related genes are closely associated with enhanced resistance to B. cinerea in Arabidopsis and C. sativa.

  4. Autocrine growth factors are involved in branching morphogenesis of mouse lung epithelium.

    Okada, Kimiko; Noda, Masatsugu; Nogawa, Hiroyuki


    The current model for branching morphogenesis of mouse lung proposes that the epithelium bifurcates as cells pursue separate sources of fibroblast growth factor (FGF) 10, secreted from mesenchymal tissue through interactions with epithelial tissue. If so, it may be assumed that the lung epithelium will grow into a uniform, expanding ball (without branching) when uniformly exposed to a constant concentration of FGF10. To test this hypothesis, we cultured Matrigel-embedded lung epithelium explants in FGF10-supplemented medium while shaking the culture dishes. Shaking cultures with FGF10 resulted in inferior epithelial branching compared to control cultures at rest. However, this effect was unexpectedly accompanied by poor growth rather than by ball-like expansion. When using FGF1, epithelial cultures grew and branched similarly well under either culture condition. Thus, we hypothesized that FGF10 signaling must be mediated by autocrine FGFs, such as FGF1, which might easily diffuse through the culture medium in the shaking culture. Reverse transcription-polymerase chain reaction analyses showed that FGF9 as well as FGF1 were expressed in the epithelium in vivo and in FGF10-stimulated epithelium in vitro, and FGF9 induced epithelial branching at a much lower concentration than FGF10. These results suggest that FGF1 and FGF9 may mediate FGF10 signaling and induce branching in the lung epithelium via autocrine signaling.

  5. Assessment of Various Factors Involved in the Tissue Culture System of Rice

    Shaukat ALI; XUE Qing-zhong; ZHANG Xian-yin


    To optimize conditions for an efficient embryogenic callus induction and plant regeneration from mature seeds of japonica rice cultivar Xiushui 11 and indica cultivar XC95, different factors such as plant growth regulators, casein hydrolysate,carbohydrate source and concentration, and various gelation conditions including gel type for callus induction and phyta gel concentration for shoot regeneration were studied in detail to determine their role in the system. Overall, induction of embryogenic callus in case of Xiushui 11 was the most efficient (67.2%) in the media supplemented with 2 mg/L 2,4-D, 3% sucrose and 0.8%agar while in case of XC95, 2 mg/L of 2,4-D combined with 0.5 mg/L of BAP and NAA generated the best result (61.2%). Inclusion of 0.3% agarose (pure form) or phyta gel further enhanced the callus induction efficiency (80%) in Xiusui 11. Higher concentration (300-500 mg/L) of casein hydrolysate was found to significantly inhibit the browning of calli in XC95. Role of cytokinin and phyta gel concentration was critical for shoot regeneration in both classes of rice. Increased strength of phyta gel was observed to enhance the shoot regeneration frequency. The optimal concentration of 2 mg/L and 3 mg/L for KT was necessary for higher differentiation frequency supplemented with 0.5% and 0.6% phyta gel in case of japonica and indica rice, respectively.

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

    Eric Baranowski

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

  7. Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1.

    Christopher Terranova

    Full Text Available Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development.

  8. Factors involved in making post-performance judgments in mathematics problem-solving.

    García Fernández, Trinidad; Kroesbergen, Evelyn; Rodríguez Pérez, Celestino; González-Castro, Paloma; González-Pienda, Julio A


    This study examines the impact of executive functions, affective-motivational variables related to mathematics, mathematics achievement and task characteristics on fifth and sixth graders’ calibration accuracy after completing two mathematical problems. A sample of 188 students took part in the study. They were divided into two groups as function of their judgment accuracy after completing the two tasks (accurate= 79, inaccurate= 109). Differences between these groups were examined. The discriminative value of these variables to predict group membership was analyzed, as well as the effect of age, gender, and grade level. The results indicated that accurate students showed better levels of executive functioning, and more positive feelings, beliefs, and motivation related to mathematics. They also spent more time on the tasks. Mathematics achievement, perceived usefulness of mathematics, and time spent on Task 1 significantly predicted group membership, classifying 71.3% of the sample correctly. These results support the relationship between academic achievement and calibration accuracy, suggesting the need to consider a wide range of factors when explaining performance judgments.

  9. Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1).

    Terranova, Christopher; Narla, Sridhar T; Lee, Yu-Wei; Bard, Jonathan; Parikh, Abhirath; Stachowiak, Ewa K; Tzanakakis, Emmanuel S; Buck, Michael J; Birkaya, Barbara; Stachowiak, Michal K


    Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development.

  10. Structure, Function and Networks of Transcription Factors Involved in Abiotic Stress Responses

    Karen Skriver


    Full Text Available Transcription factors (TFs are master regulators of abiotic stress responses in plants. This review focuses on TFs from seven major TF families, known to play functional roles in response to abiotic stresses, including drought, high salinity, high osmolarity, temperature extremes and the phytohormone ABA. Although ectopic expression of several TFs has improved abiotic stress tolerance in plants, fine-tuning of TF expression and protein levels remains a challenge to avoid crop yield loss. To further our understanding of TFs in abiotic stress responses, emerging gene regulatory networks based on TFs and their direct targets genes are presented. These revealed components shared between ABA-dependent and independent signaling as well as abiotic and biotic stress signaling. Protein structure analysis suggested that TFs hubs of large interactomes have extended regions with protein intrinsic disorder (ID, referring to their lack of fixed tertiary structures. ID is now an emerging topic in plant science. Furthermore, the importance of the ubiquitin-proteasome protein degradation systems and modification by sumoylation is also apparent from the interactomes. Therefore; TF interaction partners such as E3 ubiquitin ligases and TF regions with ID represent future targets for engineering improved abiotic stress tolerance in crops.

  11. Temporal SILAC-based quantitative proteomics identifies host factors involved in chikungunya virus replication.

    Treffers, Emmely E; Tas, Ali; Scholte, Florine E M; Van, Myrthe N; Heemskerk, Matthias T; de Ru, Arnoud H; Snijder, Eric J; van Hemert, Martijn J; van Veelen, Peter A


    Chikungunya virus (CHIKV) is an arthropod-borne reemerging human pathogen that generally causes a severe persisting arthritis. Since 2005, the virus has infected millions of people during outbreaks in Africa, Indian Ocean Islands, Asia, and South/Central America. Many steps of the replication and expression of CHIKV's 12-kb RNA genome are highly dependent on cellular factors, which thus constitute potential therapeutic targets. SILAC and LC-MS/MS were used to define the temporal dynamics of the cellular response to infection. Using samples harvested at 8, 10, and 12 h postinfection, over 4700 proteins were identified and per time point 2800-3500 proteins could be quantified in both biological replicates. At 8, 10, and 12 h postinfection, 13, 38, and 106 proteins, respectively, were differentially expressed. The majority of these proteins showed decreased abundance. Most subunits of the RNA polymerase II complex were progressively degraded, which likely contributes to the transcriptional host shut-off observed during CHIKV infection. Overexpression of four proteins that were significantly downregulated (Rho family GTPase 3 (Rnd3), DEAD box helicase 56 (DDX56), polo-like kinase 1 (Plk1), and ubiquitin-conjugating enzyme E2C (UbcH10) reduced susceptibility of cells to CHIKV infection, suggesting that infection-induced downregulation of these proteins is beneficial for CHIKV replication. All MS data have been deposited in the ProteomeXchange with identifier PXD001330 (

  12. Stem cells and related factors involved in facial nerve function regeneration

    Kamil H. Nelke


    Full Text Available The facial nerve (VII is one of the most important cranial nerves for head and neck surgeons. Its function is closely related to facial expressions that are individual for every person. After its injury or palsy, its functions can be either impaired or absent. Because of the presence of motor, sensory and parasympathetic fibers, the biology of its repair and function restoration depends on many factors. In order to achieve good outcome, many different therapies can be performed in order to restore as much of the nerve function as possible. When rehabilitation and physiotherapy are not sufficient, additional surgical procedures and therapies are taken into serious consideration. The final outcome of many of them is discussable, depending on nerve damage etiology. Stem cells in facial nerve repair are used, but long-term outcomes and results are still not fully known. In order to understand this therapeutic approach, clinicians and surgeons should understand the immunobiology of nerve repair and regeneration. In this review, potential stem cell usage in facial nerve regeneration procedures is discussed.


    M. Rahmani


    Full Text Available Intracranial hemorrhage is one of the major causes of neonatal mortality and morbidity. It is the most severe cranial problem in that period. Those who survive would be affected by hydrocephalus, encephalomalacia, and finally brain atrophy. With accurate knowledge of risk factors, hemorrhage may be diagnosed earlier and the complications managed earlier. This study was performed in Neonatal Intensive Care Unit of Imam Khomeini Hospital. All the neonates less than 34 weeks of gestation were undergone intracranial sonography from Feb 2005 to Feb 2006. Sonography was performed via anterior fontanel with proper probe according to neonatal age. 113 neonates less than 34 weeks of gestation have been studied. Mean gestational age was 32 weeks. Mean neonatal weight were 1566 ± 734 grams. Intracranial hemorrhage was evident in 21% of them; 16.8% was grade 1, 0.9% grade 2, 2.7% grade 3, 0.9% grade 4. The mean weight of neonates with hemorrhage was 1504.11 grams. Intracranial hemorrhage had correlation with respiratory acidosis and pneumothorax. The latter was also correlated with hemorrhage grade. Supposing the safety and non-invasiveness of intacranial sonography, we suggest performing sonography in all premature neonates with low birth weight, and also in those neonates with pneumothorax and respiratory acidosis.


    Gabriela Geletu


    Full Text Available Biphosphonates are used in the treatment of bone metastases of some cancer forms, such as multiple myeloma, Paget disease, osteoporosis, fibrous displasia, etc. A significant consequence of the utilization of such drugs is osteonecrosis of the maxillary bones. The aim of the study was to evaluate the risk factors provoking osteonecrosis of the maxillary bones after the treatment with biphosphonates, in the patients who addressed the Clinics of Oral and Maxillo-Facial Surgery between 2006-2011. Materials and method: 33 patients suffering from this pathology were registered, their files including information on age, sex, social background, the disease for which the drug had been recommended and the prescribed dose, the manner of its administration and the duration, the cause of the maxillary lesion, the symptomatology demonstrated during the first consultation, additional examinations, treatment and evolution. Results: most cases of osteo-necrosis had been caused by dental extractions, especially at the mandible. The higher risk was faced by women who were administered the drug intravenously. Conclusions: Post-surgical evolution was favourably influenced when the surgery had in view the value of the carboxy-terminal group from the structure of serum colagen.

  15. CitI, a Transcription Factor Involved in Regulation of Citrate Metabolism in Lactic Acid Bacteria†

    Martin, Mauricio G.; Magni, Christian; de Mendoza, Diego; López, Paloma


    A large variety of lactic acid bacteria (LAB) can utilize citrate under fermentative conditions. Although much information concerning the metabolic pathways leading to citrate utilization by LAB has been gathered, the mechanisms regulating these pathways are obscure. In Weissella paramesenteroides (formerly called Leuconostoc paramesenteroides), transcription of the citMDEFCGRP citrate operon and the upstream divergent gene citI is induced by the presence of citrate in the medium. Although genetic experiments have suggested that CitI is a transcriptional activator whose activity can be modulated in response to citrate availability, specific details of the interaction between CitI and DNA remained unknown. In this study, we show that CitI recognizes two A+T-rich operator sites located between citI and citM and that the DNA-binding affinity of CitI is increased by citrate. Subsequently, this citrate signal propagation leads to the activation of the cit operon through an enhanced recruitment of RNA polymerase to its promoters. Our results indicate that the control of CitI by the cellular pools of citrate provides a mechanism for sensing the availability of citrate and adjusting the expression of the cit operon accordingly. In addition, this is the first reported example of a transcription factor directly functioning as a citrate-activated switch allowing the cell to optimize the generation of metabolic energy. PMID:16030208

  16. Involvement of brain-derived neurotrophic factor (BDNF) in MP4-induced autoimmune encephalomyelitis.

    Javeri, Sita; Rodi, Michael; Tary-Lehmann, Magdalena; Lehmann, Paul V; Addicks, Klaus; Kuerten, Stefanie


    The role of brain-derived neurotrophic factor (BDNF) in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) is still unclear. Here we investigate the clinical course, CNS histopathology and peripheral antigen-specific immunity in MP4-induced EAE of BDNF (-/+) mice. We demonstrate that these mice displayed less severe disease compared to BDNF (+/+) mice, reflected by decreased inflammation and demyelination. In correspondence to diminished frequencies of T and B cells in CNS infiltrates, the peripheral MP4-specific T(H)1/T(H)17 response was attenuated in BDNF (-/+), but not in wild-type animals. In contrast, immunization with ovalbumin triggered similar frequencies of IFN-γ- and IL-17-secreting T cells in both groups. The cytokine secretion and proliferative activity upon mitogen stimulation did not reveal any global defect of T cell function in BDNF (-/+) mice. By influencing the antigen-specific immune response in autoimmune encephalomyelitis, BDNF may support and maintain the disease in ways that go beyond its alleged neuroprotective role.

  17. Class I BASIC PENTACYSTEINE factors regulate HOMEOBOX genes involved in meristem size maintenance.

    Simonini, Sara; Kater, Martin M


    The BASIC PENTACYSTEINE (BCP) family is a poorly characterized plant transcription factor family of GAGA BINDING PROTEINS. In Arabidopsis, there are seven members (BPC1-7) that are broadly expressed, and they can potentially bind more than 3000 Arabidopsis GAGA-repeat-containing genes. To date, BPCs are known to be direct regulators of the INNER NO OUTER (INO), SEEDSTICK (STK), and LEAFY COTYLEDON 2 (LEC2) genes. Because of the high functional redundancy, neither single knockout nor double bpc mutant combinations cause aberrant phenotypes. The bpc1-2 bpc2 bpc3 triple mutant shows several pleiotropic developmental defects, including enlargement of the inflorescence meristem and flowers with supernumerary floral organs. Here, we demonstrated through expression analysis and chromatin immunoprecipitation assays that this phenotype is probably due to deregulation of the expression of the SHOOTMERISTEMLESS (STM) and BREVIPEDICELLUS/KNAT1 (BP) genes, which are both direct targets of BPCs. Moreover, we assigned a role to BPCs in the fine regulation of the cytokinin content in the meristem, as both ISOPENTENYLTRANSFERASE 7 (IPT7) and ARABIDOPSIS RESPONSE REGULATOR 7 (ARR7) genes were shown to be overexpressed in the bpc1-2 bpc2 bpc3 triple mutant.


    SI Yi-ling; HAN Wei-dong; ZhAO Ya-li; LI Qi; HAO Hao-jie; SONG Hai-jing; MU Yi-ming; YU Li


    Objective: To investigate the role of Sp1 as transcription factor required for transactivation of LRP16 gene by estrogen. Methods: Specific antibodies of Erα and Sp1 were used to precipitate the target DNA/protein complexes of MCF-7 cells at different time points after estrogen treatment (Chromatin immunoprecipitation assay), the promoter region of LRP16 gene was amplified by semi-nested polymerase chain reaction (snPCR). Small interfering RNA (siRNA) against Sp1 was transiently cotransfected with LRP16-Luc (containing the region from -213bp to -126bp of LRP16 gene promoter) in MCF-7 cells. The luciferase activities were measured by dual-luciferase assay. Results: The results of chromatin immunoprecipitation assay showed that Sp1 protein directly bound to the -213bp to -126bp region of LRP16 gene, and Erα could enhance the affinity of Sp1 to DNA. Sp1-siRNA specifically decreased the transactivation of LRP16-Luc by 17β-estradiol to 70-80%. Conclusion: The estrogen-induced transactivation of the human LRP16 gene was mediated by Sp1 protein. Moreover, the interactions of ER(/Sp1 functional complex with LRP16 promoter DNA were required for enhanced LRP16 gene transactivation.

  19. Family and individual factors associated with substance involvement and PTS symptoms among adolescents in greater New Orleans after Hurricane Katrina.

    Rowe, Cynthia L; La Greca, Annette M; Alexandersson, Anders


    This study examined the influence of hurricane impact as well as family and individual risk factors on posttraumatic stress (PTS) symptoms and substance involvement among clinically referred adolescents affected by Hurricane Katrina. A total of 80 adolescents (87% male; 13-17 years old; mean age = 15.6 years; 38% minorities) and their parents were interviewed at the adolescent's intake into substance abuse treatment, 16 to 46 months postdisaster. Independent measures included hurricane impact variables (initial loss/disruption and perceived life threat); demographic and predisaster variables (family income, gender, predisaster adolescent substance use, predisaster trauma exposure, and parental substance abuse); postdisaster family factors (parental psychopathology, family cohesion, and parental monitoring); and postdisaster adolescent delinquency. Hierarchical multivariate regression analyses showed that adolescent substance involvement was associated with higher family income, lower parental monitoring (adolescent report), and more adolescent delinquency. Adolescent-reported PTS symptoms were associated with greater hurricane-related initial loss/disruption, lower family cohesion (adolescent report), and more adolescent delinquency, whereas parent-reported adolescent PTS symptoms were associated with greater parental psychopathology, lower parental monitoring (adolescent report), and lower family cohesion (parent report). The results suggest that hurricane impact was related only to adolescent-reported PTS. However, certain postdisaster family and individual risk factors (low family cohesion and parental monitoring, more adolescent delinquency) were associated both with adolescent substance involvement and with PTS symptoms. Identification of these factors suggests directions for future research as well as potential target areas for screening and intervention with substance-abusing adolescents after disasters. (c) 2010 APA, all rights reserved.

  20. Structural factors associated with an increased risk of HIV and sexually transmitted infection transmission among street-involved youth

    Shoveller Jean A


    Full Text Available Abstract Background The prevalence of HIV and sexually transmitted infections (STIs among street-involved youth greatly exceed that of the general adolescent population; however, little is known regarding the structural factors that influence disease transmission risk among this population. Methods Between September 2005 and October 2006, 529 street-involved youth were enroled in a prospective cohort known as the At Risk Youth Study (ARYS. We examined structural factors associated with number of sex partners using quasi-Poisson regression and consistent condom use using logistic regression. Results At baseline, 415 (78.4% were sexually active, of whom 253 (61.0% reported multiple sex partners and 288 (69.4% reported inconsistent condom use in the past six months. In multivariate analysis, self-reported barriers to health services were inversely associated with consistent condom use (adjusted odds ratio [aOR] = 0.52, 95%CI: 0.25 – 1.07. Structural factors that were associated with greater numbers of sex partners included homelessness (adjusted incidence rate ratio [aIRR] = 1.54, 95%CI: 1.11 – 2.14 and having an area restriction that affects access to services (aIRR = 2.32, 95%CI: 1.28 – 4.18. Being searched or detained by the police was significant for males (aIRR = 1.36, 95%CI: 1.02 – 1.81. Conclusion Although limited by its cross-sectional design, our study found several structural factors amenable to policy-level interventions independently associated with sexual risk behaviours. These findings imply that the criminalization and displacement of street-involved youth may increase the likelihood that youth will engage in sexual risk behaviours and exacerbate the negative impact of resultant health outcomes. Moreover, our findings indicate that environmental-structural interventions may help to reduce the burden of these diseases among street youth in urban settings.

  1. The Relevance of Literature.

    Dunham, L. L.


    The "legacy" of the humanities is discussed in terms of relevance, involvement, and other philosophical considerations. Reasons for studying foreign literature in language classes are developed in the article. Comment is also made on attitudes and ideas culled from the writings of Clifton Fadiman, Jean Paul Sartre, and James Baldwin. (RL)

  2. Assessment of Hematological Factors Involved in Development and Prognosis of Idiopathic Sudden Sensorineural Hearing Loss.

    Durmuş, Kasim; Terzi, Hatice; Karataş, Tuba Doğan; Doğan, Mansur; Uysal, Ismail Önder; Şencan, Mehmet; Altuntaş, Emine Elif


    The aim of this study was to investigate the possible effects of routine hematological parameters on the development and prognosis of idiopathic sudden sensorineural hearing loss in patients applying to our clinic. A retrospective clinical study. One academic health center from 2008 to 2014. One hundred forty patients with sudden hearing loss and 132 healthy controls were included in the present study. Patients having idiopathic sudden sensorineural hearing loss were divided into 2 subgroups based on whether they recovered (complete, partial, and slight recovery) (Group 1; n = 83, 59.3%) or not (Group 2; n = 57, 40.7%) during the follow-up term. Group 1, Group 2, and the controls differed statistically significantly in terms of neutrophil-to-lymphocyte ratio (P = 0.001), platelet-to-lymphocyte ratio (P = 0.001), lymphocytes % (P = 0.001), mean corpuscular hemoglobin (P = 0.019), mean corpuscular hemoglobin concentration (P = 0.015), platelet (P  = 0.001), mean platelet volume (P = 0.001), platelet distribution width (P = 0.009), and glucose (P = 0.001). The study groups and the controls did not have any significant difference in terms of other laboratory parameters affecting the prognosis of Idiopathic sudden sensorineural hearing loss. The results the authors obtained showed that laboratory parameters such as lymphocyte, lymphocyte%, platelet, mean platelet volume, platelet distribution width, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration may be indicative for prognosis and treatment success in groups of patients suffering idiopathic sudden sensorineural hearing loss in whose etiology many factors play a role.

  3. A Genome-Wide RNAi Screen for Factors Involved in Neuronal Specification in Caenorhabditis elegans.

    Richard J Poole


    Full Text Available One of the central goals of developmental neurobiology is to describe and understand the multi-tiered molecular events that control the progression of a fertilized egg to a terminally differentiated neuron. In the nematode Caenorhabditis elegans, the progression from egg to terminally differentiated neuron has been visually traced by lineage analysis. For example, the two gustatory neurons ASEL and ASER, a bilaterally symmetric neuron pair that is functionally lateralized, are generated from a fertilized egg through an invariant sequence of 11 cellular cleavages that occur stereotypically along specific cleavage planes. Molecular events that occur along this developmental pathway are only superficially understood. We take here an unbiased, genome-wide approach to identify genes that may act at any stage to ensure the correct differentiation of ASEL. Screening a genome-wide RNAi library that knocks-down 18,179 genes (94% of the genome, we identified 245 genes that affect the development of the ASEL neuron, such that the neuron is either not generated, its fate is converted to that of another cell, or cells from other lineage branches now adopt ASEL fate. We analyze in detail two factors that we identify from this screen: (1 the proneural gene hlh-14, which we find to be bilaterally expressed in the ASEL/R lineages despite their asymmetric lineage origins and which we find is required to generate neurons from several lineage branches including the ASE neurons, and (2 the COMPASS histone methyltransferase complex, which we find to be a critical embryonic inducer of ASEL/R asymmetry, acting upstream of the previously identified miRNA lsy-6. Our study represents the first comprehensive, genome-wide analysis of a single neuronal cell fate decision. The results of this analysis provide a starting point for future studies that will eventually lead to a more complete understanding of how individual neuronal cell types are generated from a single

  4. Human rhinovirus 2 2Apro recognition of eukaryotic initiation factor 4GI. Involvement of an exosite.

    Foeger, Nicole; Schmid, Eva M; Skern, Tim


    The 2A proteinase (2Apro) of human rhinovirus 2 is a cysteine proteinase with a unique chymotrypsin-like fold. During viral replication, 2Apro performs self-processing by cleaving between its own N terminus and the C terminus of the preceding protein, VP1. Subsequently, 2Apro cleaves the two isoforms of the cellular protein, eukaryotic initiation factor (eIF) 4G. We have previously shown that HRV2 2Apro can directly bind to eIF4G isoforms. Here we demonstrate using deletion mutants of eIF4GI that HRV2 2Apro requires eIF4GI amino acids 600-674 for binding; however, the amino acids at the cleavage site, Arg681 downward arrow Gly, are not required. The HRV2 2Apro binding domain for eIF4GI was identified by site-directed mutagenesis. Specifically, mutations Leu17 --> Arg and Asp35 --> Glu severely impaired HRV2 2Apro binding and thus processing of eIF4GI in rabbit reticulocyte lysates; self-processing, however, was not affected. Alanine scanning analysis further identified the loop containing residues Tyr32, Ser33, and Ser34 as important for eIF4GI binding. Although Asp35 is part of the catalytic triad, most of the eIF4GI binding domain lies in a unique exosite structure absent from other chymotrypsin-like enzymes and is distinct from the substrate binding cleft. The exosite represents a novel virulence determinant that may allow the development of specific inhibitors for HRV2 2Apro.

  5. Signaling pathways involved in the inhibition of epidermal growth factor receptor by erlotinib in hepatocellular cancer

    Alexander Huether; Michael H(o)pfner; Andreas P Sutter; Viola Baradari; Detlef Schuppan; Hans Scherübl


    AIM: To examine the underlying mechanisms of erlotinib-induced growth inhibition in hepatocellular carcinoma (HCC).METHODS: Erlotinib-induced alterations in gene expression were evaluated using cDNA array technology;changes in protein expression and/or protein activation due to erlotinib treatment as well as IGF-1-induced EGFR transactivation were investigated using Western blotting. RESULTS: Erlotinib treatment inhibited the mitogen activated protein (MAP)-kinase pathway and signal transducer of activation and transcription (STAT)mediated signaling which led to an altered expression of apoptosis and cell cycle regulating genes as demonstrated by cDNA array technology. Overexpression of proapoptotic factors like caspases and gadds associated with a down-regulation of antiapoptoticfactors like Bcl-2, Bcl-XL or jun D accounted for erlotinib's potency to induce apoptosis. Downregulation of cell cycle regulators promoting the G1/S-transition and overexpression of cyclin-dependent kinase inhibitors and gadds contributed to the induction of a G1/Go-arrest in response to erlotinib. Furthermore, we displayed the transactivation of EGFR-mediated signaling by the IGF-1-receptor and showed erlotinib's inhibitory effects on the receptor-receptor cross talk. CONCLUSION: Our study sheds light on the understanding of the mechanisms of action of EGFR-TKinhibition in HCC-cells and thus might facilitate the design of combination therapies that act additively or synergistically. Moreover, our data on the pathways responding to erlotinib treatment could be helpful in predicting the responsiveness of tumors to EGFR-TKIs in the future.

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

    Ling Wang

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

  7. 3D Cinema and Headache: The First Evidential Relation and Analysis of Involved Factors.

    Braschinsky, Mark; Raidvee, Aire; Sabre, Liis; Zmachinskaja, Nadezhda; Zukovskaja, Olga; Karask, Anti; Saar, Bruno; Rakitin, Aleksei


    A possible link between 3D movies and headache (HA) has never been a target of specific and systematic investigations. The aim of this study was to investigate the relationship between 3D cinema and HA and to evaluate possible risk factors of developing HA during or after watching a 3D movie. This was a prospective, non-randomized, observational study. Six thousand specifically designed questionnaires were distributed to consecutive cinema visitors. Relative HA risks for 2D- vs. 3D-movie visitors and the effects of background variables were analyzed. The questionnaire was filled and returned by 1293 persons. The mean age of responders was 33.0 ± 11.3 years. Individuals who viewed 3D movies reported HA during or after the movie 1.61 times more often than 2D-movie viewers (11.1% in 3D vs. 7.2% in 2D movies, p = 0.017). The risk was higher in women: 2.65 times for 2D (p = 0.019) and 1.85 times for 3D movies (p = 0.06), and decreased with age by 4.6% with each year for 2D (p = 0.0035) and by 3.2% for 3D movies (p = 0.0098). Among 3D-movie visitors, those with previous HAs were 4.17 times more prone to get a cinema-induced HA (p = 0.02). The risk was the highest for persons with migraine (OR = 3.37, p = 0.001). For the first time, it was evidentially shown that 3D movies can provoke HA. Persons at risk are mostly younger women and/or migraineurs. Based on our results, for those belonging to the aforementioned risk groups, it can be mainly recommended to choose passive 3D technology and to view movies from the farthest possible distance.

  8. Small bowel involvement is a prognostic factor in colorectal carcinomatosis treated with complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy

    Benizri Emmanuel I


    Full Text Available Abstract Background Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC is a promising treatment for patients with peritoneal carcinomatosis (PC. Our objective was to identify new prognostic factors in patients with PC from colorectal cancer treated with this procedure. Methods All patients with PC from colorectal cancer treated by HIPEC from January 2000 to December 2007 were prospectively included. The tumor extension was assessed by the Peritoneal Cancer Index (PCI and the residual disease was recorded using the completeness cytoreductive score (CCs. All clinical and treatment data were computed in univariate and multivariable analyses using survival as primary end point. Results We carried out 51 complete procedures in 49 consecutive patients. The mean PCI was 10. The allocation of CCs was: CC-0 = 37, CC-1 = 14. The five-year overall and progression-free survival rate were 40% and 20%, respectively. Several prognostic factors for survival were identified by univariate analysis: PCI P P P = 0.06, area 5 (P = 0.031, area 7 (P = 0.014, area 8 (P = 0.022, area 10 (P P = 0.02. Only the involvement of the distal jejunum (area 10 was significant in the multivariable analysis (P = 0.027. Conclusions We demonstrated that the involvement of area 10 (distal jejunum of the PCI score was an independent factor associated with poor prognosis.

  9. A review of foot-and-mouth disease with special consideration for the clinical and epidemiological factors relevant to predictive modelling of the disease.

    Kitching, R P; Hutber, A M; Thrusfield, M V


    Modelling the epidemiology of foot-and-mouth disease (FMD) has been undertaken since the early 1970s. We review here clinical factors and modelling procedures that have been used in the past, differentiating between those that have proved to be more relevant in controlling FMD epidemics, and those that have showed less significance. During the 2001 UK FMD epidemic, many previously developed FMD models were available for consideration and use. Accurate epidemiological models can become useful tools for determining relevant control policies for different scenarios and, conversely, inaccurate models may become an abuse for disease control. Inaccuracy presents two opposing difficulties. Firstly, too much control (in terms of animal slaughter for 2001) would negatively impact the farming community for many subsequent years, whilst too little control would permit an epidemic to persist. Accuracy however, presents the optimal permutation of control measures that could be implemented for a given set of conditions, and is a prerequisite to boosting public confidence in the use of epidemiological models for future epidemics.

  10. Romance, recovery & community re-entry for criminal justice involved women: Conceptualizing and measuring intimate relationship factors and power.

    Walt, Lisa C; Hunter, Bronwyn; Salina, Doreen; Jason, Leonard

    Researchers have suggested that interpersonal relationships, particularly romantic relationships, may influence women's attempts at substance abuse recovery and community re-entry after criminal justice system involvement. The present paper evaluates relational and power theories to conceptualize the influence of romantic partner and romantic relationship qualities on pathways in and out of substance abuse and crime. The paper then combines these conceptualizations with a complementary empirical analysis to describe an ongoing research project that longitudinally investigates these relational and power driven factors on women's substance abuse recovery and community re-entry success among former substance abusing, recently criminally involved women. This paper is designed to encourage the integration of theory and empirical analysis by detailing how each of these concepts are operationalized and measured. Future research and clinical implications are also discussed.

  11. Parental Involvement

    Ezra S Simon


    This study was conducted in Ghana to investigate, (1) factors that predict parental involvement, (2) the relationship between parental home and school involvement and the educational achievement of adolescents, (3) the relationship between parental authoritativeness and the educational achievement of adolescent students, (4) parental involvement serving as a mediator between their authoritativeness and the educational achievement of the students, and (5) whether parental involvement decreases...

  12. Krüppel-like factors 4 and 5 expression and their involvement in differentiation of oral carcinomas.

    Shibata, Masaki; Chiba, Tadashige; Matsuoka, Takanori; Mihara, Nozomi; Kawashiri, Shuichi; Imai, Kazushi


    Proliferation-differentiation balance of epithelial cells is regulated by Krüppel-like factors (KLF) 4 and 5, and the unbalanced expression relates to carcinoma progression. However, little is known about the expression and role in oral carcinomas. This study examined expression of KLF4 and KLF 5 in the carcinomas by immunohistochemistry (n = 67) and the involvement in proliferation and differentiation of carcinoma cells. KLF4 was detected in keratinizing carcinoma cells and KLF5 in non-keratinizing cells. KLF4 staining declined in the patient with lymph node metastasis (P carcinoma progression through the dedifferentiation of carcinoma cells.

  13. Identification of neuronal and angiogenic growth factors in an in vitro blood-brain barrier model system: Relevance in barrier integrity and tight junction formation and complexity.

    Freese, Christian; Hanada, Sanshiro; Fallier-Becker, Petra; Kirkpatrick, C James; Unger, Ronald E


    We previously demonstrated that the co-cultivation of endothelial cells with neural cells resulted in an improved integrity of the in vitro blood-brain barrier (BBB), and that this model could be useful to evaluate the transport properties of potential central nervous system disease drugs through the microvascular brain endothelial. In this study we have used real-time PCR, fluorescent microscopy, protein arrays and enzyme-linked immunosorbent assays to determine which neural- and endothelial cell-derived factors are produced in the co-culture and improve the integrity of the BBB. In addition, a further improvement of the BBB integrity was achieved by adjusting serum concentrations and growth factors or by the addition of brain pericytes. Under specific conditions expression of angiogenic, angiostatic and neurotrophic factors such as endostatin, pigment epithelium derived factor (PEDF/serpins-F1), tissue inhibitor of metalloproteinases (TIMP-1), and vascular endothelial cell growth factor (VEGF) closely mimicked the in vivo situation. Freeze-fracture analysis of these cultures demonstrated the quality and organization of the endothelial tight junction structures and their association to the two different lipidic leaflets of the membrane. Finally, a multi-cell culture model of the BBB with a transendothelial electrical resistance up to 371 (±15) Ω×cm(2) was developed, which may be useful for preliminary screening of drug transport across the BBB and to evaluate cellular crosstalk of cells involved in the neurovascular unit.

  14. The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory.

    Yoshida, Keisuke; Maekawa, Toshio; Zhu, Yujuan; Renard-Guillet, Claire; Chatton, Bruno; Inoue, Kentaro; Uchiyama, Takeru; Ishibashi, Ken-ichi; Yamada, Takuji; Ohno, Naohito; Shirahige, Katsuhiko; Okada-Hatakeyama, Mariko; Ishii, Shunsuke


    Immunological memory is thought to be mediated exclusively by lymphocytes. However, enhanced innate immune responses caused by a previous infection increase protection against reinfection, which suggests the presence of innate immunological memory. Here we identified an important role for the stress-response transcription factor ATF7 in innate immunological memory. ATF7 suppressed a group of genes encoding factors involved in innate immunity in macrophages by recruiting the histone H3K9 dimethyltransferase G9a. Treatment with lipopolysaccharide, which mimics bacterial infection, induced phosphorylation of ATF7 via the kinase p38, which led to the release of ATF7 from chromatin and a decrease in repressive histone H3K9me2 marks. A partially disrupted chromatin structure and increased basal expression of target genes were maintained for long periods, which enhanced resistance to pathogens. ATF7 might therefore be important in controlling memory in cells of the innate immune system.

  15. The Many Organisational Factors Relevant to Planning Change in Emergency Care Departments: A Qualitative Study to Inform a Cluster Randomised Controlled Trial Aiming to Improve the Management of Patients with Mild Traumatic Brain Injuries

    Bosch, Marije; Tavender, Emma J.; Brennan, Sue E.; Knott, Jonathan; Gruen, Russell L.; Green, Sally E.


    commitment, but relatively low change efficacy). Regarding implementation processes, the importance of (visible) senior leadership for all professions involved was identified as a critical factor. An unpredictable and hectic environment brings challenges in creating an environment in which team-based and organisational learning can thrive (system antecedents for innovation). In addition, the position of the ED as the entry-point of the hospital points to the relevance of securing buy-in from other units. Conclusions We identified several organisational factors relevant to realising change in ED management of patients who present with mild head injuries. These factors will inform the intervention design and process evaluation in a trial evaluating the effectiveness of our implementation intervention. PMID:26845772

  16. The Many Organisational Factors Relevant to Planning Change in Emergency Care Departments: A Qualitative Study to Inform a Cluster Randomised Controlled Trial Aiming to Improve the Management of Patients with Mild Traumatic Brain Injuries.

    Bosch, Marije; Tavender, Emma J; Brennan, Sue E; Knott, Jonathan; Gruen, Russell L; Green, Sally E


    change efficacy). Regarding implementation processes, the importance of (visible) senior leadership for all professions involved was identified as a critical factor. An unpredictable and hectic environment brings challenges in creating an environment in which team-based and organisational learning can thrive (system antecedents for innovation). In addition, the position of the ED as the entry-point of the hospital points to the relevance of securing buy-in from other units. We identified several organisational factors relevant to realising change in ED management of patients who present with mild head injuries. These factors will inform the intervention design and process evaluation in a trial evaluating the effectiveness of our implementation intervention.

  17. The Many Organisational Factors Relevant to Planning Change in Emergency Care Departments: A Qualitative Study to Inform a Cluster Randomised Controlled Trial Aiming to Improve the Management of Patients with Mild Traumatic Brain Injuries.

    Marije Bosch

    relatively low change efficacy. Regarding implementation processes, the importance of (visible senior leadership for all professions involved was identified as a critical factor. An unpredictable and hectic environment brings challenges in creating an environment in which team-based and organisational learning can thrive (system antecedents for innovation. In addition, the position of the ED as the entry-point of the hospital points to the relevance of securing buy-in from other units.We identified several organisational factors relevant to realising change in ED management of patients who present with mild head injuries. These factors will inform the intervention design and process evaluation in a trial evaluating the effectiveness of our implementation intervention.

  18. Altered Expression Pattern of Molecular Factors Involved in Colonic Smooth Muscle Functions: An Immunohistochemical Study in Patients with Diverticular Disease

    Mattii, Letizia; Ippolito, Chiara; Segnani, Cristina; Battolla, Barbara; Colucci, Rocchina; Dolfi, Amelio; Bassotti, Gabrio; Blandizzi, Corrado; Bernardini, Nunzia


    Background The pathogenesis of diverticular disease (DD) is thought to result from complex interactions among dietary habits, genetic factors and coexistence of other bowel abnormalities. These conditions lead to alterations in colonic pressure and motility, facilitating the formation of diverticula. Although electrophysiological studies on smooth muscle cells (SMCs) have investigated colonic motor dysfunctions, scarce attention has been paid to their molecular abnormalities, and data on SMCs in DD are lacking. Accordingly, the main purpose of this study was to evaluate the expression patterns of molecular factors involved in the contractile functions of SMCs in the tunica muscularis of colonic specimens from patients with DD. Methods and Findings By means of immunohistochemistry and image analysis, we examined the expression of Cx26 and Cx43, which are prominent components of gap junctions in human colonic SMCs, as well as pS368-Cx43, PKCps, RhoA and αSMA, all known to regulate the functions of gap junctions and the contractile activity of SMCs. The immunohistochemical analysis revealed significant abnormalities in DD samples, concerning both the expression and distribution patterns of most of the investigated molecular factors. Conclusion This study demonstrates, for the first time, that an altered pattern of factors involved in SMC contractility is present at level of the tunica muscularis of DD patients. Moreover, considering that our analysis was conducted on colonic tissues not directly affected by diverticular lesions or inflammatory reactions, it is conceivable that these molecular alterations may precede and predispose to the formation of diverticula, rather than being mere consequences of the disease. PMID:23437299

  19. Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development.

    Halima Rakhila

    Full Text Available Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2, cell adhesion (αv and β3 integrins, survival (B-cell lymphoma-2 and angiogenic (vascular endothelial cell growth factors relevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis.

  20. Preferential response of acute myeloid leukemias with translocation involving chromosome 17 to human recombinant granulocyte colony-stimulating factor.

    Pébusque, M J; Lafage, M; Lopez, M; Mannoni, P


    Induction of proliferation and differentiation in response to the addition of recombinant human granulocyte colony-stimulating factor (G-CSF) was studied by both suspension and semisolid cultures in a series of acute myeloid leukemias (AML). Induction of proliferation by G-CSF alone was observed in six of 27 cases of AML. All acute promyelocytic leukemias with the specific chromosomal translocation t(15;17) and one case of myelomonocytic leukemia with balanced chromosomal translocation involving chromosome 17 at band q12q21 were induced to proliferate strongly by the G-CSF. However, contrary to the long-term proliferative effect observed with granulocyte/macrophage colony-stimulating factor (GM-CSF), G-CSF activity can be characterized by its capability to initiate and promote the growth of responding AML cells but not to sustain long-term proliferation. Finally, no terminal differentiation was found, as assessed by morphology, cytochemistry, and cell surface marker analysis. These results indicate that G-CSF may be sufficient to provide a specific signal for induction of a transient proliferation in AML without induction of terminal differentiation. The cells with the highest response are clonal leukemia cells, all bearing a translocation involving the chromosome region 17q12q21 in which the G-CSF gene has been recently located.

  1. Transcription factor 7-like 1 is involved in hypothalamo–pituitary axis development in mice and humans

    Gaston-Massuet, Carles; McCabe, Mark J.; Scagliotti, Valeria; Young, Rodrigo M.; Carreno, Gabriela; Gregory, Louise C.; Jayakody, Sujatha A.; Pozzi, Sara; Gualtieri, Angelica; Basu, Basudha; Koniordou, Markela; Wu, Chun-I; Bancalari, Rodrigo E.; Rahikkala, Elisa; Veijola, Riitta; Lopponen, Tuija; Graziola, Federica; Turton, James; Signore, Massimo; Mousavy Gharavy, Seyedeh Neda; Charolidi, Nicoletta; Sokol, Sergei Y.; Merrill, Bradley J.; Dattani, Mehul T.; Martinez-Barbera, Juan Pedro


    Aberrant embryonic development of the hypothalamus and/or pituitary gland in humans results in congenital hypopituitarism (CH). Transcription factor 7-like 1 (TCF7L1), an important regulator of the WNT/β-catenin signaling pathway, is expressed in the developing forebrain and pituitary gland, but its role during hypothalamo–pituitary (HP) axis formation or involvement in human CH remains elusive. Using a conditional genetic approach in the mouse, we first demonstrate that TCF7L1 is required in the prospective hypothalamus to maintain normal expression of the hypothalamic signals involved in the induction and subsequent expansion of Rathke’s pouch progenitors. Next, we reveal that the function of TCF7L1 during HP axis development depends exclusively on the repressing activity of TCF7L1 and does not require its interaction with β-catenin. Finally, we report the identification of two independent missense variants in human TCF7L1, p.R92P and p.R400Q, in a cohort of patients with forebrain and/or pituitary defects. We demonstrate that these variants exhibit reduced repressing activity in vitro and in vivo relative to wild-type TCF7L1. Together, our data provide support for a conserved molecular function of TCF7L1 as a transcriptional repressor during HP axis development in mammals and identify variants in this transcription factor that are likely to contribute to the etiology of CH. PMID:26764381

  2. Activating transcription factor 4 is involved in endoplasmic reticulum stress-mediated apoptosis contributing to vascular calcification.

    Duan, Xiao-Hui; Chang, Jin-Rui; Zhang, Jing; Zhang, Bao-Hong; Li, Yu-Lin; Teng, Xu; Zhu, Yi; Du, Jie; Tang, Chao-Shu; Qi, Yong-Fen


    Our previous work reported that endoplasmic reticulum stress (ERS)-mediated apoptosis was activated during vascular calcification (VC). Activating transcription factor 4 (ATF4) is a critical transcription factor in osteoblastogenesis and ERS-induced apoptosis. However, whether ATF4 is involved in ERS-mediated apoptosis contributing to VC remains unclear. In the present study, in vivo VC was induced in rats by administering vitamin D3 plus nicotine. Vascular smooth muscle cell (VSMC) calcification in vitro was induced by incubation in calcifying media containing β-glycerophosphate and CaCl2. ERS inhibitors taurine or 4-phenylbutyric acid attenuated ERS and VSMC apoptosis in calcified rat arteries, reduced calcification and retarded the VSMC contractile phenotype transforming into an osteoblast-like phenotype in vivo. Inhibition of ERS retarded the VSMC phenotypic transition into an osteoblast-like cell phenotype and reduced VSMC calcification and apoptosis in vitro. Interestingly, ATF4 was activated in calcified aortas and calcified VSMCs in vitro. ATF4 knockdown attenuated ERS-induced apoptosis in calcified VSMCs. ATF4 deficiency blocked VSMC calcification and negatively regulated the osteoblast phenotypic transition of VSMCs in vitro. Our results demonstrate that ATF4 was involved at least in part in the process of ERS-mediated apoptosis contributing to VC.

  3. Let's stay together? Intrinsic and extrinsic factors involved in pair bond dissolution in a recolonizing wolf population.

    Milleret, Cyril; Wabakken, Petter; Liberg, Olof; Åkesson, Mikael; Flagstad, Øystein; Andreassen, Harry Peter; Sand, Håkan


    For socially monogamous species, breeder bond dissolution has important consequences for population dynamics, but the extent to which extrinsic or intrinsic population factors causes pair dissolution remain poorly understood, especially among carnivores. Using an extensive life-history data set, a survival analysis and competing risks framework, we examined the fate of 153 different wolf (Canis lupus) pairs in the recolonizing Scandinavian wolf population, during 14 winters of snow tracking and DNA monitoring. Wolf pair dissolution was generally linked to a mortality event and was strongly affected by extrinsic (i.e. anthropogenic) causes. No divorce was observed, and among the pair dissolution where causes have been identified, death of one or both wolves was always involved. Median time from pair formation to pair dissolution was three consecutive winters (i.e. approximately 2 years). Pair dissolution was mostly human-related, primarily caused by legal control actions (36·7%), verified poaching (9·2%) and traffic-related causes (2·1%). Intrinsic factors, such as disease and age, accounted for only 7·7% of pair dissolutions. The remaining 44·3% of dissolution events were from unknown causes, but we argue that a large portion could be explained by an additional source of human-caused mortality, cryptic poaching. Extrinsic population factors, such as variables describing the geographical location of the pair, had a stronger effect on risk of pair dissolution compared to anthropogenic landscape characteristics. Population intrinsic factors, such as the inbreeding coefficient of the male pair member, had a negative effect on pair bond duration. The mechanism behind this result remains unknown, but might be explained by lower survival of inbred males or more complex inbreeding effects mediated by behaviour. Our study provides quantitative estimates of breeder bond duration in a social carnivore and highlights the effect of extrinsic (i.e. anthropogenic) and

  4. Pedestrian- and driver-related factors associated with the risk of causing collisions involving pedestrians in Spain.

    Jiménez-Mejías, Eladio; Martínez-Ruiz, Virginia; Amezcua-Prieto, Carmen; Olmedo-Requena, Rocío; Luna-Del-Castillo, Juan de Dios; Lardelli-Claret, Pablo


    This study aimed to quantify the association between pedestrian- and driver-related factors and the risk of causing road crashes involving pedestrians in urban areas in Spain between 1993 and 2011. From the nationwide police-based registry of road crashes with victims in Spain, we analyzed all 63,205 pairs of pedestrians and drivers involved in crashes in urban areas in which only the pedestrian or only the driver was at fault. Logistic regression models were used to obtain adjusted odds ratios to assess the strength of association between each individual-related variable and the pedestrian's odds of being at fault for the crash (and conversely, the driver's odds of not being at fault). The subgroups of road users at high risk of causing a road crash with a pedestrian in urban areas were young and male pedestrians, pedestrians with psychophysical conditions or health problems, the youngest and the oldest drivers, and drivers with markers of high-risk behaviors (alcohol use, nonuse of safety devices, and driving without a valid license). These subgroups should be targeted by preventive strategies intended to decrease the rate of urban road crashes involving pedestrians in Spain.

  5. Factors associated with family-centered involvement in family practice--a cross-sectional multivariate analysis.

    Deutsch, Tobias; Frese, Thomas; Sandholzer, Hagen


    The importance of a family-centered approach in family practice has been emphasized. Knowledge about factors associated with higher family-centered involvement seems beneficial to stimulate its realization. German office-based family physicians completed a questionnaire addressing several aspects of family-centered care. Logistic regression was used to identify associations with the involvement overall and in different domains: routine inquiry and documentation of family-related information, family orientation regarding diagnosis and treatment, family-oriented dialogues, family conferences, and case-related collaboration with marriage and family therapists. We found significant associations between physicians' family-centered involvement and expected patient receptiveness, perceived impact of the family's influence on health, self-perceived psychosocial family-care competences (overall and concerning concepts for family orientation, psychosocial intervention in family conferences, and the communication of the idea of family counseling), advanced training in psychosocial primary care (PPC), personal acquaintance with family therapists (regarding case-related collaboration), and rural office environment. Increased emphasis on the family's influence on health in medical education and training, the provision of concepts for a family-centered perspective, and versatile skills for psychosocial intervention and inquiry of patient preferences, as well as the strengthening of networking between family physicians and family therapists, might promote the family-centered approach in family practice.


    also indicate that the initial treatment given to a patient influences mortality at the A&E .... Cardiovascular complication of obesity _ 3 0.9. Total 135. 40.1 ... our A&E where doctors are in the rank of Senior House Officers without any special ...

  7. A systematic review of motivational interviewing in healthcare: the potential of motivational interviewing to address the lifestyle factors relevant to multimorbidity

    Kylie McKenzie


    Full Text Available Internationally, health systems face an increasing demand for services from people living with multimorbidity. Multimorbidity is often associated with high levels of treatment burden. Targeting lifestyle factors that impact across multiple conditions may promote quality of life and better health outcomes for people with multimorbidity. Motivational interviewing (MI has been studied as one approach to supporting lifestyle behaviour change. A systematic review was conducted to assess the effectiveness of MI in healthcare settings and to consider its relevance for multimorbidity. Twelve meta-analyses pertinent to multimorbidity lifestyle factors were identified. As an intervention, MI has been found to have a small-to-medium statistically significant effect across a wide variety of single diseases and for a range of behavioural outcomes. This review highlights the need for specific research into the application of MI to determine if the benefits of MI seen with single diseases are also present in the context of multimorbidity. Journal of Comorbidity 2015;5:162–174

  8. Suppressed Expression of T-Box Transcription Factors is Involved in Senescence in Chronic Obstructive Pulmonary Disease

    Acquaah-Mensah, George; Malhotra, Deepti; Vulimiri, Madhulika; McDermott, Jason E.; Biswal, Shyam


    Chronic obstructive pulmonary disease (COPD) is a major global health problem. The etiology of COPD has been associated with apoptosis, oxidative stress, and inflammation. However, understanding of the molecular interactions that modulate COPD pathogenesis remains only partly resolved. We conducted an exploratory study on COPD etiology to identify the key molecular participants. We used information-theoretic algorithms including Context Likelihood of Relatedness (CLR), Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNE), and Inferelator. We captured direct functional associations among genes, given a compendium of gene expression profiles of human lung epithelial cells. A set of genes differentially expressed in COPD, as reported in a previous study were superposed with the resulting transcriptional regulatory networks. After factoring in the properties of the networks, an established COPD susceptibility locus and domain-domain interactions involving protein products of genes in the generated networks, several molecular candidates were predicted to be involved in the etiology of COPD. These include COL4A3, CFLAR, GULP1, PDCD1, CASP10, PAX3, BOK, HSPD1, PITX2, and PML. Furthermore, T-box (TBX) genes and cyclin-dependent kinase inhibitor 2A (CDKN2A), which are in a direct transcriptional regulatory relationship, emerged as preeminent participants in the etiology of COPD by means of senescence. Contrary to observations in neoplasms, our study reveals that the expression of genes and proteins in the lung samples from patients with COPD indicate an increased tendency towards cellular senescence. The expression of the anti-senescence mediators TBX transcription factors, chromatin modifiers histone deacetylases, and sirtuins was suppressed; while the expression of TBX-regulated cellular senescence markers such as CDKN2A, CDKN1A, and CAV1 was elevated in the peripheral lung tissue samples from patients with COPD. The critical balance between senescence

  9. Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5

    Takashi Ashino


    Full Text Available Cytochrome P450 gene expression is altered by various chemical compounds. In this study, we used nuclear factor erythroid 2-related factor 2 (Nrf2–deficient (Nrf2−⧸− mice to investigate the involvement of Nrf2 in Cyp2b10 and Cyp2a5 gene expression. Phorone, an Nrf2 activator, strongly increased Cyp2b10 and Cyp2a5 mRNA as well as Nrf2 target genes, including NAD(PH-quinone oxidoreductase-1 and heme oxygenase-1, in wild-type mouse livers 8 h after treatment. The phorone-induced mRNA levels in Nrf2−⧸− mouse livers were lower than that in wild-type mouse livers. Nrf2−⧸− mice showed attenuated Cyp2b10 and Cyp2a5 induction by phenobarbital, a classical Cyp2b inducer. These findings suggest that the Nrf2 pathway is involved in Cyp2b10 and Cyp2a5 gene expression.

  10. How Much Should We Involve Genetic and Environmental Factors in the Risk Assessment of Mycotoxins in Humans?

    Maria Rosaria Carratu


    Full Text Available Despite consented efforts in prevention, mycotoxins remain a problem of human health concern in several parts of the world including developed countries. Within the same range of toxins concentrations in the blood some people develop a disease while others do not. Could this inequality in front of mycotoxins effects be explained by environment factors and/or genetic predisposition? Among recent advances in environmental health research Correlation between chronic diseases and mycotoxins in humans deserves attention through several questions: Are genetic factors involved in disease causation of mycotoxins? How much are these factors currently taken into account for mycotoxins risk assessment and how much should we involve them? Answers are still to come. Genetic and environment factors deserve therefore more attention when dealing with regulatory limits, since among the general population, those who are at risk and will develop specific diseases are likely those bearing genetic predispositions. We have addressed these questions for the specific case of ochratoxin A in humans by investigating in Tunisia, county of Jelma, in four rural families forming a household of 21 persons all exposed to ochratoxin A in diet. Our results confirm that ochratoxin A induces chronic tubular nephropathy in humans and mainly point at those having the HLA haplotype A3, B27/35, DR7 to be more sensitive to the disease for quantitatively similar or lower exposure. Persons with such haplotype were found to bear chronic interstitial nephropathy with tubular karyomegalic cells while others were apparently healthy. Godin et al. (1996 in France have also found in sibling (a sister and her brother from urban area that have similar HLA haplotype B35-patern, OTA-related renal tubulopathy with mild proteinuria including β2-microglobulinuria. Several mechanisms are discussed that could be put ahead to explain how the HLA haplotype could lead to tubular cells lyses and

  11. Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation: corticotrophin-releasing factor and nerve growth factor interplay.

    Barreau, Frederick; Cartier, Christel; Leveque, Mathilde; Ferrier, Laurent; Moriez, Raphael; Laroute, Valerie; Rosztoczy, Andras; Fioramonti, Jean; Bueno, Lionel


    Neonatal maternal deprivation (NMD) increases gut paracellular permeability (GPP) through mast cells and nerve growth factor (NGF), and modifies corticotrophin-releasing factor (CRF) and corticosterone levels. CRF, corticosterone and mast cells are involved in stress-induced mucosal barrier impairment. Consequently, this study aimed to specify whether corticosteronaemia and colonic expression of both preproCRF and CRF are modified by NMD, and to determine if altered expression may participate in the elevated GPP in connection with NGF and mast cells. Male Wistar rat pups were either separated from postnatal days 2-14, or left undisturbed with their dam. At 12 weeks of age, adult rats were treated with mifepristone (an antagonist of corticoid receptors), alpha-helical CRF((9-41)) (a non-specific CRF receptor antagonist), or SSR-125543 (CRF-R(1) receptor antagonist). We also determined corticosteronaemia and both colonic preproCRF and CRF expression. Then, control rats were treated by CRF, doxantrazole (mast cell stabilizer), BRX-537A (a mast cell activator) and anti-NGF antibody. NMD did not modify colonic CRF level but increased colonic preproCRF expression and corticosteronaemia. Peripheral CRF, via CRF-R(1) receptor, but not corticosterone, was involved in the elevated GPP observed in these rats, through a mast-cell-mediated mechanism, since the increase of GPP induced by exogenous CRF was abolished by doxantrazole. Anti-NGF antibody treatment also reduced the elevated GPP induced by CRF or BRX-537A. CRF acts through CRF-R(1) receptors to stimulate NGF release from mast cells, which participates in the elevated GPP observed in NMD adult rats. This suggests that early traumatic experience induced neuro-endocrine dysfunction, involved in alterations of gut mucosal barrier.

  12. Changes in the number of CD31(-)CD45(-)Sca-1(+) cells and Shh signaling pathway involvement in the lungs of mice with emphysema and relevant effects of acute adenovirus infection.

    Deng, Minhua; Li, Jinhua; Gan, Ye; Chen, Yan; Chen, Ping


    COPD is a leading cause of mortality worldwide, and cigarette smoke is a pivotal risk factor. Adenovirus is a common cause of acute exacerbations of COPD and expedites COPD progression. Lung stem/progenitor cells play an important role in the development of COPD, while the relevant mechanism remains elusive. Here, we investigated the number of lung CD31(-)CD45(-)Sca-1(+) cells and sonic hedgehog (Shh) signaling pathway expression levels in cigarette smoke extract (CSE)-induced emphysema mice, as well as the relevant effects of acute adenovirus infection (AAI). BALB/c mice were treated with CSE by intraperitoneal injection and/or adenovirus endotracheal instillation at different time points for 28 days. Lung function, lung histomorphology, CD31(-)CD45(-)Sca-1(+) cell count, and expression levels of major components in the Shh signaling pathway in the lungs were measured. CSE intraperitoneal injection and adenovirus endotracheal instillation successfully induced emphysema and AAI in mice, respectively. In the lungs of emphysema mice, both the number of CD31(-)CD45(-)Sca-1(+) cells and expression levels of Shh signaling pathway molecules were reduced. However, AAI increased the number of inhibited CD31(-)CD45(-)Sca-1(+) cells and activated the suppression of the Shh signaling pathway. Both CD31(-)CD45(-)Sca-1(+) cell numbers and Shh signaling pathway expression levels were downregulated in the lungs of emphysema mice induced by CSE intraperitoneal injection, which likely contributes to the pathogenesis of emphysema. Additionally, these inhibited lung CD31(-)CD45(-)Sca-1(+) cells and Shh signaling pathway molecules were upregulated during AAI, indicating that they play a protective role in the epithelial repair process after AAI injury.

  13. PI3K/Akt is involved in brown adipogenesis mediated by growth differentiation factor-5 in association with activation of the Smad pathway

    Hinoi, Eiichi; Iezaki, Takashi; Fujita, Hiroyuki; Watanabe, Takumi; Odaka, Yoshiaki; Ozaki, Kakeru; Yoneda, Yukio, E-mail:


    Highlights: • Akt is preferentially phosphorylated in BAT and sWAT of aP2-GDF5 mice. • PI3K/Akt signaling is involved in GDF5-induced brown adipogenesis. • PI3K/Akt signaling regulates GDF5-induced Smad5 phosphorylation. - Abstract: We have previously demonstrated promotion by growth differentiation factor-5 (GDF5) of brown adipogenesis for systemic energy expenditure through a mechanism relevant to activating the bone morphological protein (BMP) receptor/mothers against decapentaplegic homolog (Smad)/peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) pathway. Here, we show the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in brown adipogenesis mediated by GDF5. Overexpression of GDF5 in cells expressing adipocyte protein-2 markedly accelerated the phosphorylation of Smad1/5/8 and Akt in white and brown adipose tissues. In brown adipose tissue from heterozygous GDF5{sup Rgsc451} mutant mice expressing a dominant-negative (DN) GDF5 under obesogenic conditions, the basal phosphorylation of Smad1/5/8 and Akt was significantly attenuated. Exposure to GDF5 not only promoted the phosphorylation of both Smad1/5/8 and Akt in cultured brown pre-adipocytes, but also up-regulated Pgc1a and uncoupling protein-1 expression in a manner sensitive to the PI3K/Akt inhibitor Ly294002 as well as retroviral infection with DN-Akt. GDF5 drastically promoted BMP-responsive luciferase reporter activity in a Ly294002-sensitive fashion. Both Ly294002 and DN-Akt markedly inhibited phosphorylation of Smad5 in the nuclei of brown pre-adipocytes. These results suggest that PI3K/Akt signals play a role in the GDF5-mediated brown adipogenesis through a mechanism related to activation of the Smad pathway.

  14. Combinatorial Signal Integration by APETALA2/Ethylene Response Factor (ERF-Transcription Factors and the Involvement of AP2-2 in Starvation Response

    Karl-Josef Dietz


    Full Text Available Transcription factors of the APETALA 2/Ethylene Response Factor (AP2/ERF-family have been implicated in diverse processes during development, stress acclimation and retrograde signaling. Fifty-three leaf-expressed AP2/ERFs were screened for their transcriptional response to abscisic acid (ABA, 3-(3,4-dichlorophenyl-1,1-dimethylurea (DCMU, methylviologen (MV, sucrose and high or low light, respectively, and revealed high reactivity to these effectors. Six of them (AP2-2, ARF14, CEJ1, ERF8, ERF11, RAP2.5 were selected for combinatorial response analysis to ABA, DCMU and high light. Additive, synergistic and antagonistic effects demonstrated that these transcription factors are components of multiple signaling pathways. AP2-2 (At1g79700 was subjected to an in depth study. AP2-2 transcripts were high under conditions linked to limited carbohydrate availability and stress and down-regulated in extended light phase, high light or in the presence of sugar. ap2-2 knock out plants had unchanged metabolite profiles and transcript levels of co-expressed genes in extended darkness. However, ap2-2 revealed more efficient germination and faster early growth under high sugar, osmotic or salinity stress, but the difference was abolished in the absence of sugar or during subsequent growth. It is suggested that AP2-2 is involved in mediating starvation-related and hormonal signals.

  15. Heat shock transcription factors involved in seed desiccation tolerance and longevity retard vegetative senescence in transgenic tobacco.

    Almoguera, Concepción; Personat, José-María; Prieto-Dapena, Pilar; Jordano, Juan


    Transcription factors normally expressed in sunflower seeds delayed vegetative senescence induced by severe stress in transgenic tobacco. This revealed a novel connection between seed heat shock factors, desiccation tolerance and vegetative longevity. HaHSFA9 and HaHSFA4a coactivate a genetic program that, in sunflower (Helianthus annuus L.), contributes to seed longevity and desiccation tolerance. We have shown that overexpression of HaHSFA9 in transgenic tobacco seedlings resulted in tolerance to drastic dehydration and oxidative stress. Overexpression of HaHSFA9 alone was linked to a remarkable protection of the photosynthetic apparatus. In addition, the combined overexpression of HaHSFA9 and HaHSFA4a enhanced all these stress-resistance phenotypes. Here, we find that HaHSFA9 confers protection against damage induced by different stress conditions that accelerate vegetative senescence during different stages of development. Seedlings and plants that overexpress HaHSFA9 survived lethal treatments of dark-induced senescence. HaHSFA9 overexpression induced resistance to effects of culture under darkness for several weeks. Only some homoiochlorophyllous resurrection plants are able to withstand this experimental severe stress condition. The combined overexpression of HaHSFA9 and HaHSFA4a did not result in further slowing of dark-induced seedling senescence. However, combined expression of the two transcription factors caused improved recovery of the photosynthetic organs of seedlings after lethal dark treatments. At later stages of vegetative development, HaHSFA9 delayed the appearance of senescence symptoms in leaves of plants grown under normal illumination. This delay was observed under either control or stress treatments. Thus, HaHSFA9 delayed both natural and stress-induced leaf senesce. These novel observations connect transcription factors involved in desiccation tolerance with leaf longevity.

  16. Da redução da incerteza estratégica à perpetuação da exclusão: a relevância dos fatores ideacionais na análise de política externa From the reduction of strategic uncertainty to the consolidation of exclusion: the relevance of ideational factors in foreign policy analysis

    Diego Santos Vieira de Jesus


    Full Text Available O objetivo do artigo é discutir a relevância dos fatores ideacionais nos debates da subárea de análise de política externa. O argumento central aponta que os fatores ideacionais assumem relevância crescente nos debates de política externa, porque um número cada vez maior de especialistas da subárea de análise de política externa - predominantemente autores neoinstitucionalistas, construtivistas "moderados" e pós-estruturalistas envolvidos nessas discussões - concebeu que as ideias podem ter impacto sobre o conteúdo e os rumos de políticas externas ao oferecer mapas que ampliam a clareza dos atores sobre objetivos ou a relação entre meios e fins em condições de incerteza, afetar resultados de situações estratégicas em que não há um único equilíbrio e generalizar padrões de comportamento quando incorporadas em instituições (enfoque neoinstitucionalista. Podem também regular o comportamento político dos Estados e construir suas identidades e interesses de política externa, de forma que tais fatores ideacionais podem ser vistos como endógenos à interação. Os ambientes em que os atores estão envolvidos podem ser concebidos como ideacionais em vez de apenas materiais e constituir as propriedades básicas desses atores. O significado de forças materiais também pode depender de ideias compartilhadas (enfoque construtivista. As ideias podem ainda ser entendidas como construções de práticas discursivas relacionadas à formulação e à execução da política externa e, assim, legitimar o poder e a soberania e perpetuar a marginalização e a exclusão da diferença (enfoque pós-estruturalista.The main purpose of this article is to discuss the relevance of ideational factors in Foreign Policy Analysis. The main idea indicates that ideational factors are gradually relevant in foreign policy debates, because a growing number of foreign policy analysts - mainly neo-institutionalists, "moderate" constructivists and

  17. Preoperatively Assessable Clinical and Pathological Risk Factors for Parametrial Involvement in Surgically Treated FIGO Stage IB-IIA Cervical Cancer.

    Canaz, Emel; Ozyurek, Eser Sefik; Erdem, Baki; Aldikactioglu Talmac, Merve; Yildiz Ozaydin, Ipek; Akbayir, Ozgur; Numanoglu, Ceyhun; Ulker, Volkan


    Determining the risk factors associated with parametrial involvement (PMI) is of paramount importance to decrease the multimodality treatment in early-stage cervical cancer. We investigated the preoperatively assessable clinical and pathological risk factors associated with PMI in surgically treated stage IB1-IIA2 cervical cancer. A retrospective cohort study of women underwent Querleu-Morrow type C hysterectomy for cervical cancer stage IB1-IIA2 from 2001 to 2015. All patients underwent clinical staging examination under anesthesia by the same gynecological oncologists during the study period. Evaluated variables were age, menopausal status, body mass index, smoking status, FIGO (International Federation of Obstetrics and Gynecology) stage, clinically measured maximal tumor diameter, clinical presentation (exophytic or endophytic tumor), histological type, tumor grade, lymphovascular space invasion, clinical and pathological vaginal invasion, and uterine body involvement. Endophytic clinical presentation was defined for ulcerative tumors and barrel-shaped morphology. Two-dimensional transvaginal ultrasonography was used to measure tumor dimensions. Of 127 eligible women, 37 (29.1%) had PMI. On univariate analysis, endophytic clinical presentation (P = 0.01), larger tumor size (P PMI. In multivariate analysis endophytic clinical presentation (odds ratio, 11.34; 95% confidence interval, 1.34-95.85; P = 0.02) and larger tumor size (odds ratio, 32.31; 95% confidence interval, 2.46-423.83; P = 0.008) were the independent risk factors for PMI. Threshold of 31 mm in tumor size predicted PMI with 71% sensitivity and 75% specificity. We identified 18 patients with tumor size of more than 30 mm and endophytic presentation; 14 (77.7%) of these had PMI. Endophytic clinical presentation and larger clinical tumor size (>3 cm) are independent risk factors for PMI in stage IB-IIA cervical cancer. Approximately 78% of the patients with a tumor size of more than 3 cm and endophytic

  18. Nuclear factor-κB is involved in the phenotype loss of parvalbumin-interneurons in vitro.

    Wang, Xian; Zhou, Zhiqiang; Yang, Chun; Xu, Jianguo; Yang, Jianjun


    The phenotype loss of parvalbumin-containing interneurons, characterized by decreased parvalbumin expression, has been observed in schizophrenic patients. Overproduction of intraneuronal reactive oxygen species leads to such a phenotype loss. Nuclear factor-κB (NF-κB) activation is both a target and a regulator of intracellular oxidative stress response, suggesting its involvement in the parvalbumin regulation. This study was carried out to investigate the role of the NF-κB activation in the ketamine-induced phenotype loss of parvalbumin-interneurons in vitro. Ketamine was applied to primary neuronal cultures to successfully evoke the production of increased reactive oxygen species and decreased parvalbumin expression in parvalbumin-interneurons, which was invalid in the presence of a NF-κB inhibitor, SN50 or Bay11-7082. These results suggest potential links among NF-κB activation, oxidative stress, and parvalbumin-interneurons in vitro.

  19. Sex determination. foxl3 is a germ cell-intrinsic factor involved in sperm-egg fate decision in medaka.

    Nishimura, Toshiya; Sato, Tetsuya; Yamamoto, Yasuhiro; Watakabe, Ikuko; Ohkawa, Yasuyuki; Suyama, Mikita; Kobayashi, Satoru; Tanaka, Minoru


    Sex determination is an essential step in the commitment of a germ cell to a sperm or egg. However, the intrinsic factors that determine the sexual fate of vertebrate germ cells are unknown. Here, we show that foxl3, which is expressed in germ cells but not somatic cells in the gonad, is involved in sperm-egg fate decision in medaka fish. Adult XX medaka with disrupted foxl3 developed functional sperm in the expanded germinal epithelium of a histologically functional ovary. In chimeric medaka, mutant germ cells initiated spermatogenesis in female wild-type gonad. These results indicate that a germ cell-intrinsic cue for the sperm-egg fate decision is present in medaka and that spermatogenesis can proceed in a female gonadal environment.

  20. Genome wide expression profiling of the mesodiencephalic region identifies novel factors involved in early and late dopaminergic development

    Koushik Chakrabarty


    Meso-diencephalic dopaminergic (mdDA neurons are critical for motor control and cognitive functioning and their loss or dysfunction is associated with disorders such as Parkinson's disease (PD, schizophrenia and addiction. However, relatively little is known about the molecular mechanisms underlying mdDA neuron development and maintenance. Here, we determined the spatiotemporal map of genes involved in the development of mdDA neurons to gain further insight into their molecular programming. Genome-wide gene expression profiles of the developing ventral mesencephalon (VM were compared at different developmental stages leading to the identification of novel regulatory roles of neuronal signaling through nicotinic acthylcholine receptors (Chrna6 and Chrnb3 subunits and the identification of novel transcription factors (Oc2 and 3 involved in the generation of the mdDA neuronal field. We show here that Pitx3, in cooperation with Nurr1, is the critical component in the activation of the Chrna6 and Chrnb3 subunits in mdDA neurons. Furthermore, we provide evidence of two divergent regulatory pathways resulting in the expression of Chrna6 and Chrnb3 respectively.

  1. Genome-wide Identification of TCP Family Transcription Factors from Populus euphratica and Their Involvement in Leaf Shape Regulation.

    Ma, Xiaodong; Ma, Jianchao; Fan, Di; Li, Chaofeng; Jiang, Yuanzhong; Luo, Keming


    Higher plants have been shown to experience a juvenile vegetative phase, an adult vegetative phase, and a reproductive phase during its postembryonic development and distinct lateral organ morphologies have been observed at the different development stages. Populus euphratica, commonly known as a desert poplar, has developed heteromorphic leaves during its development. The TCP family genes encode a group of plant-specific transcription factors involved in several aspects of plant development. In particular, TCPs have been shown to influence leaf size and shape in many herbaceous plants. However, whether these functions are conserved in woody plants remains unknown. In the present study, we carried out genome-wide identification of TCP genes in P. euphratica and P. trichocarpa, and 33 and 36 genes encoding putative TCP proteins were found, respectively. Phylogenetic analysis of the poplar TCPs together with Arabidopsis TCPs indicated a biased expansion of the TCP gene family via segmental duplications. In addition, our results have also shown a correlation between different expression patterns of several P. euphratica TCP genes and leaf shape variations, indicating their involvement in the regulation of leaf shape development.

  2. Transcriptomic analysis reveals numerous diverse protein kinases and transcription factors involved in desiccation tolerance in the resurrection plant Myrothamnus flabellifolia.

    Ma, Chao; Wang, Hong; Macnish, Andrew J; Estrada-Melo, Alejandro C; Lin, Jing; Chang, Youhong; Reid, Michael S; Jiang, Cai-Zhong


    The woody resurrection plant Myrothamnus flabellifolia has remarkable tolerance to desiccation. Pyro-sequencing technology permitted us to analyze the transcriptome of M. flabellifolia during both dehydration and rehydration. We identified a total of 8287 and 8542 differentially transcribed genes during dehydration and rehydration treatments respectively. Approximately 295 transcription factors (TFs) and 484 protein kinases (PKs) were up- or down-regulated in response to desiccation stress. Among these, the transcript levels of 53 TFs and 91 PKs increased rapidly and peaked early during dehydration. These regulators transduce signal cascades of molecular pathways, including the up-regulation of ABA-dependent and independent drought stress pathways and the activation of protective mechanisms for coping with oxidative damage. Antioxidant systems are up-regulated, and the photosynthetic system is modified to reduce ROS generation. Secondary metabolism may participate in the desiccation tolerance of M. flabellifolia as indicated by increases in transcript abundance of genes involved in isopentenyl diphosphate biosynthesis. Up-regulation of genes encoding late embryogenesis abundant proteins and sucrose phosphate synthase is also associated with increased tolerance to desiccation. During rehydration, the transcriptome is also enriched in transcripts of genes encoding TFs and PKs, as well as genes involved in photosynthesis, and protein synthesis. The data reported here contribute comprehensive insights into the molecular mechanisms of desiccation tolerance in M. flabellifolia.

  3. Involvement of leukotriene B4 receptor 1 signaling in platelet-activating factor-mediated neutrophil degranulation and chemotaxis.

    Gaudreault, Eric; Stankova, Jana; Rola-Pleszczynski, Marek


    Platelet-activating factor (PAF) is a potent lipid mediator of inflammation that can act on human neutrophils. When neutrophils are stimulated with PAF at concentrations greater than 10 nM, a double peak of intracellular calcium mobilization is observed. The second calcium peak observed in PAF-treated neutrophils has already been suggested to come from the production of endogenous leukotriene B4 (LTB4). Here we demonstrate the involvement of endogenous LTB4 production and subsequent activation of the high affinity LTB4 receptor (BLT1) in this second calcium mobilization peak observed after stimulation with PAF. We also show that the second, but not the first peak, could be desensitized by prior exposure to LTB4. Moreover, when neutrophils were pre-treated with pharmacological inhibitors of LTB4 production or with the specific BLT1 antagonist, U75302, PAF-mediated neutrophil degranulation was inhibited by more than 50%. On the other hand, pre-treating neutrophils with the PAF receptor specific antagonist (WEB2086) did not prevent any LTB4-induced degranulation. Also, when human neutrophils were pre-treated with U75302, PAF-mediated chemotaxis was reduced by more than 60%. These data indicate the involvement of BLT1 signaling in PAF-mediated neutrophil activities.

  4. Factors involved in early polarization of the anterior-posterior axis in the milkweed bug Oncopeltus fasciatus.

    Ginzburg, Neta; Cohen, Mira; Chipman, Ariel D


    The axes of insect embryos are defined early in the blastoderm stage. Genes involved in this polarization are well known in Drosophila, but less so in other insects, such as the milkweed bug Oncopeltus fasciatus. Using quantitative PCR, we looked at differential expression of several candidate genes for early anterior-posterior patterning and found that none of them are expressed asymmetrically in the early blastoderm. We then used an RNA-Seq approach to identify novel candidate genes that might be involved in early polarization in Oncopeltus. We focused on transcription factors (TFs) as these are likely to be central players in developmental processes. Using both homology and domain based identification approaches, we were unable to find any TF encoding transcripts that are expressed asymmetrically along the anterior-posterior axis at early stages. Using a GO-term analysis of all asymmetrically expressed mRNAs, we found an enrichment of genes relating to mitochondrial function in the posterior at the earliest studied time-point. We also found a gradual enrichment of transcription related activities, giving us a putative time frame for the maternal to zygotic transition. Our dataset provides us with a list of new candidate genes in early development, which can be followed up experimentally. © 2017 Wiley Periodicals, Inc.

  5. Involvement of the leucine response transcription factor LeuO in regulation of the genes for sulfa drug efflux.

    Shimada, Tomohiro; Yamamoto, Kaneyoshi; Ishihama, Akira


    LeuO, a LysR family transcription factor, exists in a wide variety of bacteria of the family Enterobacteriaceae and is involved in the regulation of as yet unidentified genes affecting the stress response and pathogenesis expression. Using genomic screening by systematic evolution of ligands by exponential enrichment (SELEX) in vitro, a total of 106 DNA sequences were isolated from 12 different regions of the Escherichia coli genome. All of the SELEX fragments formed complexes in vitro with purified LeuO. After Northern blot analysis of the putative target genes located downstream of the respective LeuO-binding sequence, a total of nine genes were found to be activated by LeuO, while three genes were repressed by LeuO. The LeuO target gene collection included several multidrug resistance genes. A phenotype microarray assay was conducted to identify the gene(s) responsible for drug resistance and the drug species that are under the control of the LeuO target gene(s). The results described herein indicate that the yjcRQP operon, one of the LeuO targets, is involved in sensitivity control against sulfa drugs. We propose to rename the yjcRQP genes the sdsRQP genes (sulfa drug sensitivity determinant).

  6. GAMETOPHYTIC FACTOR 1, Involved in Pre-mRNA Splicing, Is Essential for Megagametogenesis and Embryogenesis in Arabidopsis

    Man Liu; Li Yuan; Nai-You Liu; Dong-Qiao Shi; Jie Liu; Wei-Cai Yang


    RNA biogenesis is essential and vital for accurate expression of genes. It is obvious that cells cannot continue normal metabolism when RNA splicing is interfered with. sgt13018 is such a mutant, with partial loss of function of GAMETOPHYTIC FACTOR 1 (GFA1); a gene likely involved in RNA biogenesis in Arabidopsis. The mutant is featured in the phenotype of diminished female gametophyte development at stage FG5 and is associated with the arrest of early embryo development in Arabidopsis. Bioinformatics data showed that homoiogs of gene GFA1 in yeast and human encode putative U5 snRNPspecific proteins required for pre-mRNA splicing. Furthermore, the result of yeast two-hybrid assay indicated that GFA1 physically interacted with AtBrr2 and AtPrp8, the putative U5 snRNP components, of Arabidopsis. This investigation suggests that GFA1 is involved in mRNA biogenesis through interaction with AtBrr2 and AtPrp8 and functions in megagametogeneeis and embryogenesis in plant.

  7. Identification of haplotype tag single nucleotide polymorphisms within the nuclear factor-κB family genes and their clinical relevance in patients with major trauma.

    Pan, Wei; Zhang, An Qiang; Gu, Wei; Gao, Jun Wei; Du, Ding Yuan; Zhang, Lian Yang; Zeng, Ling; Du, Juan; Wang, Hai Yan; Jiang, Jian Xin


    Nuclear factor-κB (NF-κB) family plays an important role in the development of sepsis in critically ill patients. Although several single nucleotide polymorphisms (SNPs) have been identified in the NF-κB family genes, only a few SNPs have been studied. A total of 753 patients with major blunt trauma were included in this study. Tag SNPs (tSNPs) were selected from the NF-κB family genes (NFKB1, NFKB2, RELA, RELB and REL) through construction of haplotype blocks. The SNPs selected from genes within the canonical NF-κB pathway (including NFKB1, RELA and REL), which played a critical role in innate immune responses were genotyped using pyrosequencing method and analyzed in relation to the risk of development of sepsis and multiple organ dysfunction (MOD) syndrome. Moreover, the rs842647 polymorphism was analyzed in relation to tumor necrosis factor α (TNF-α) production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Eight SNPs (rs28362491, rs3774932, rs4648068, rs7119750, rs4803789, rs12609547, rs1560725 and rs842647) were selected from the NF-κB family genes. All of them were shown to be high-frequency SNPs in this study cohort. Four SNPs (rs28362491, rs4648068, rs7119750 and rs842647) within the canonical NF-κB pathway were genotyped, and rs842647 was associated with sepsis morbidity rate and MOD scores. An association was also observed between the rs842647 A allele and lower TNF-α production. rs842647 polymorphism might be used as relevant risk estimate for the development of sepsis and MOD syndrome in patients with major trauma.

  8. Interethnic differences in the relevance of CYP2C9 genotype and environmental factors for diclofenac metabolism in Hispanics from Cuba and Spain.

    Llerena, A; Alvarez, M; Dorado, P; González, I; Peñas-LLedó, E; Pérez, B; Cobaleda, J; Calzadilla, L R


    The aims of this study were to evaluate the diclofenac metabolism in Hispanics from Cuba and Spain and its relation to ethnicity, CYP2C9 genotypes and environmental factors. Diclofenac hydroxylation capacity (concentration ratios of diclofenac/metabolites in 8-h urine) was studied in 160 Cuban (classified as 76 Cuban-Whites-CWs and 84 Cuban-Mestizos-CMs) and 148 Spaniard (SPs) healthy volunteers. Diclofenac and its main metabolites, 4'-hydroxy (OH), 3'-OH and 5-OH diclofenac, and CYP2C9*2 to *6 and *8 alleles were also determined in 132 and 128 CWs and CMs, respectively. Gender, tobacco, caffeine and ethanol consumption were also evaluated. The mean diclofenac/4'-OH diclofenac ratio was higher in CMs (0.72±0.25) than in CWs (0.64±0.20; P<0.05) and SPs (0.57±0.26; P<0.001). The mean diclofenac/4'-OH diclofenac ratio was higher (P<0.05) in subjects with CYP2C9*1/*3 (0.77±0.19; n=22) and CYP2C9*1/*8 (0.93±0.33; n=4) genotypes than with CYP2C9*1/*1 (0.65±0.24; n=90). Environmental factors did not seem to influence the diclofenac metabolism in these populations. The present findings show for the first time interethnic differences between Hispanic groups in urinary diclofenac/4'-OH diclofenac ratios, and the relevance of CYP2C9*3 and CYP2C9*8 alleles.

  9. Transforming growth factor-β1 involved in urotensin Ⅱ-induced phenotypic differentiation of adventitial fibroblasts from rat aorta

    ZHANG Yong-gang; HU Yan-chao; MAO Yan-yan; WEI Rui-hong; BAO Shi-lin; WU Li-biao; KUANG Ze-jian


    Background Urotensin Ⅱ (UⅡ) is a new vasoconstrictive peptide that may activate the adventitial fibroblasts.Transforming growth factor-β1 (TGF-β1) is an important factor that could induce the phenotypical transdifferentiation of adventitial fibroblasts. This study aimed to explore whether TGF-β1 is involved in UⅡ-induced phenotypic differentiation of adventitial fibroblasts from rat aorta.Methods Adventitial fibroblasts were prepared by the explant culture method. TGF-β1 protein secretion from the cells was determined by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression of α-smooth nuscle actin (α-SM-actin), the marker of phenotypic differentiation from fibroblasts to myofibroblasts, were determined using real-time quantitative RT-PCR (real-time RT-PCR) and Western blotting, respectively.Results UⅡ stimulated the secretion of TGF-β1 in cultured adventitial fibroblasts in a time-dependent manner. The secretion reached a peak at 24 hours, was higher by 69.8% (P <0.01), than the control group. This effect was also concentration dependent. Maximal stimulation was reached at 10-8 mol/L of UⅡ (P <0.01), which was increased by 59.9%,compared with in the control group (P <0.01). The secretion of TGF-β1 induced by UⅡ was significantly blocked by SB-710411 (10-7 mol/L), a specific antagonist of UⅡ receptor. In addition, both UⅡ (10-8 mol/L) and TGF-β1 significantly stimulated α-SM-actin mRNA and protein expression. Moreover, the α-SM-actin induced by UⅡ was inhibited by the specific neutralizing antibody (20 μg/ml) of TGF-β1, while the α-SM-actin expression stimulated by TGF-β1 (20 ng/ml)was inhibited by SB-710411 (10-7 mol/L), the UⅡ receptor antagonist.Conclusion This study suggests that UⅡ could induce TGF-β1 secretion in adventitial fibroblasts via UT activation, and TGF-β1 might be involved in phenotypic differentiation from adventitial fibroblasts into myofibroblasts induced by UⅡ, and TGF-β1

  10. Identification of cis-acting elements and splicing factors involved in the regulation of BIM Pre-mRNA splicing.

    Juan, Wen Chun; Roca, Xavier; Ong, S Tiong


    Aberrant changes in the expression of the pro-apoptotic protein, BCL-2-like 11 (BIM), can result in either impaired or excessive apoptosis, which can contribute to tumorigenesis and degenerative disorders, respectively. Altering BIM pre-mRNA splicing is an attractive approach to modulate apoptosis because BIM activity is partly determined by the alternative splicing of exons 3 or 4, whereby exon 3-containing transcripts are not apoptotic. Here we identified several cis-acting elements and splicing factors involved in BIM alternative splicing, as a step to better understand the regulation of BIM expression. We analyzed a recently discovered 2,903-bp deletion polymorphism within BIM intron 2 that biased splicing towards exon 3, and which also impaired BIM-dependent apoptosis. We found that this region harbors multiple redundant cis-acting elements that repress exon 3 inclusion. Furthermore, we have isolated a 23-nt intronic splicing silencer at the 3' end of the deletion that is important for excluding exon 3. We also show that PTBP1 and hnRNP C repress exon 3 inclusion, and that downregulation of PTBP1 inhibited BIM-mediated apoptosis. Collectively, these findings start building our understanding of the cis-acting elements and splicing factors that regulate BIM alternative splicing, and also suggest potential approaches to alter BIM splicing for therapeutic purposes.

  11. Maternal Gene Polymorphisms Involved in Folate Metabolism as Risk Factors for Down Syndrome Offspring in Southern Brazil

    Ana Paula Carneiro Brandalize


    Full Text Available This study aimed to investigate the role of maternal polymorphisms, as well as their risk genotypes combinations of MTR A2756G, MTRR A66G, CBS 844ins68, and RFC A80G, involved in folate/homocysteine metabolism, as possible risk factors for Down syndrome (DS in Southern Brazil. A case-control study was conducted with 239~mothers of DS children and 197 control mothers. The investigation of polymorphisms was performed by PCR and PCR-RFLP. The distribution of genotypic variants was similar in both groups when they were analyzed separately. An investigation of combined risk genotypes showed that the risk of having a DS child for one, two or three risk genotypes was 6.23, 6.96 and 5.84 (95%CI 1.48–26.26; 1.69–28.66; 1.37–24.86, respectively. The combined MTRR 66G and MTHFR 677T alleles were significantly more common among mothers of children with DS than among control mothers (OR 1.55; IC 95% 1.03–2.35. The results show that individual polymorphisms studied in this work are not associated with DS; however, the effects of the combined risk genotypes among MTR, MTRR, CBS and RFC genes are considered maternal risk factors for DS offspring in our population.

  12. The FlbA-regulated predicted transcription factor Fum21 of Aspergillus niger is involved in fumonisin production.

    Aerts, David; Hauer, Esther E; Ohm, Robin A; Arentshorst, Mark; Teertstra, Wieke R; Phippen, Christopher; Ram, Arthur F J; Frisvad, Jens C; Wösten, Han A B


    Aspergillus niger secretes proteins throughout the colony except for the zone that forms asexual spores called conidia. Inactivation of flbA that encodes a regulator of G-protein signaling results in colonies that are unable to reproduce asexually and that secrete proteins throughout the mycelium. In addition, the ΔflbA strain shows cell lysis and has thinner cell walls. Expression analysis showed that 38 predicted transcription factor genes are differentially expressed in strain ΔflbA. Here, the most down-regulated predicted transcription factor gene, called fum21, was inactivated. Growth, conidiation, and protein secretion were not affected in strain Δfum21. Whole genome expression analysis revealed that 63 and 11 genes were down- and up-regulated in Δfum21, respectively, when compared to the wild-type strain. Notably, 24 genes predicted to be involved in secondary metabolism were down-regulated in Δfum21, including 10 out of 12 genes of the fumonisin cluster. This was accompanied by absence of fumonisin production in the deletion strain and a 25% reduction in production of pyranonigrin A. Together, these results link FlbA-mediated sporulation-inhibited secretion with mycotoxin production.

  13. Neuroprotective effects of salidroside on focal cerebral ischemia/reperfusion injury involves the nuclear erythroid 2-related factor 2 pathway

    Jing Han


    Full Text Available Salidroside, the main active ingredient extracted from Rhodiola crenulata, has been shown to be neuroprotective in ischemic cerebral injury, but the underlying mechanism for this neuroprotection is poorly understood. In the current study, the neuroprotective effect of salidroside on cerebral ischemia-induced oxidative stress and the role of the nuclear factor erythroid 2-related factor 2 (Nrf2 pathway was investigated in a rat model of middle cerebral artery occlusion. Salidroside (30 mg/kg reduced infarct size, improved neurological function and histological changes, increased activity of superoxide dismutase and glutathione-S-transferase, and reduced malon-dialdehyde levels after cerebral ischemia and reperfusion. Furthermore, salidroside apparently increased Nrf2 and heme oxygenase-1 expression. These results suggest that salidroside exerts its neuroprotective effect against cerebral ischemia through anti-oxidant mechanisms and that activation of the Nrf2 pathway is involved. The Nrf2/antioxidant response element pathway may become a new therapeutic target for the treatment of ischemic stroke.

  14. A regulatory pathway, ecdysone-transcription factor relish-cathepsin L, is involved in insect fat body dissociation.

    Yao Zhang

    Full Text Available Insect fat body is the organ for intermediary metabolism, comparable to vertebrate liver and adipose tissue. Larval fat body is disintegrated to individual fat body cells and then adult fat body is remodeled at the pupal stage. However, little is known about the dissociation mechanism. We find that the moth Helicoverpa armigera cathepsin L (Har-CL is expressed heavily in the fat body and is released from fat body cells into the extracellular matrix. The inhibitor and RNAi experiments demonstrate that Har-CL functions in the fat body dissociation in H. armigera. Further, a nuclear protein is identified to be transcription factor Har-Relish, which was found in insect immune response and specifically binds to the promoter of Har-CL gene to regulate its activity. Har-Relish also responds to the steroid hormone ecdysone. Thus, the dissociation of the larval fat body is involved in the hormone (ecdysone-transcription factor (Relish-target gene (cathepsin L regulatory pathway.

  15. CF2 transcription factor is involved in the regulation of Mef2 RNA levels, nuclei number and muscle fiber size.

    Arredondo, Juan J; Vivar, Jorge; Laine-Menéndez, Sara; Martínez-Morentin, Leticia; Cervera, Margarita


    CF2 and Mef2 influence a variety of developmental muscle processes at distinct stages of development. Nevertheless, the exact nature of the CF2-Mef2 relationship and its effects on muscle building remain yet to be resolved. Here, we explored the regulatory role of CF2 in the Drosophila embryo muscle formation. To address this question and not having proper null CF2 mutants we exploited loss or gain of function strategies to study the contribution of CF2 to Mef2 transcription regulation and to muscle formation. Our data point to CF2 as a factor involved in the regulation of muscle final size and/or the number of nuclei present in each muscle. This function is independent of its role as a Mef2 collaborative factor in the transcriptional regulation of muscle-structural genes. Although Mef2 expression patterns do not change, reductions or increases in parallel in CF2 and Mef2 transcript abundance were observed in interfered and overexpressed CF2 embryos. Since CF2 expression variations yield altered Mef2 expression levels but with correct spatio-temporal Mef2 expression patterns, it can be concluded that only the mechanism controlling expression levels is de-regulated. Here, it is proposed that CF2 regulates Mef2 expression through a Feedforward Loop circuit.

  16. Identification of transcription factors ZmMYB111and ZmMYB148 involved in phenylpropanoid metabolism

    Junjie eZhang


    Full Text Available Maize is the leading crop worldwide in terms of both planting area and total yields, but environmental stresses cause significant losses in productivity. Phenylpropanoid compounds play an important role in plant stress resistance; however, the mechanism of their synthesis is not fully understood, especially in regard to the expression and regulation of key genes. Phenylalanine ammonia-lyase (PAL is the first key enzyme involved in phenylpropanoid metabolism, and it has a significant effect on the synthesis of important phenylpropanoid compounds. According to the results of sequence alignments and functional prediction, we selected two conserved R2R3-MYB transcription factors as candidate genes for the regulation of phenylpropanoid metabolism. The two candidate R2R3-MYB genes, which we named ZmMYB111and ZmMYB148, were cloned, and then their structural characteristics and phylogenetic placement were predicted and analyzed. In addition, a series of evaluations were performed, including expression profiles, subcellular localization, transcription activation, protein-DNA interaction, and transient expression in maize endosperm. Our results indicated that both ZmMYB111 and ZmMYB148 are indeed R2R3-MYB transcription factors and that they may play a regulatory role in PAL gene expression.

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

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


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

  18. Factors involved in sustained use of point-of-use water disinfection methods: a field study from Flores Island, Indonesia.

    Roma, E; Bond, T; Jeffrey, P


    Many scientific studies have suggested that point-of-use water treatment can improve water quality and reduce the risk of infectious diseases. Despite the ease of use and relatively low cost of such methods, experience shows the potential benefits derived from provision of such systems depend on recipients' acceptance of the technology and its sustained use. To date, few contributions have addressed the problem of user experience in the post-implementation phase. This can diagnose challenges, which undermine system longevity and its sustained use. A qualitative evaluation of two household water treatment systems, solar disinfection (SODIS) and chlorine tablets (Aquatabs), in three villages was conducted by using a diagnostic tool focusing on technology performance and experience. Cross-sectional surveys and in-depth interviews were used to investigate perceptions of involved stakeholders (users, implementers and local government). Results prove that economic and functional factors were significant in using SODIS, whilst perceptions of economic, taste and odour components were important in Aquatabs use. Conclusions relate to closing the gap between factors that technology implementers and users perceive as key to the sustained deployment of point-of-use disinfection technologies.

  19. A novel invertebrate trophic factor related to invertebrate neurotrophins is involved in planarian body regional survival and asexual reproduction.

    Bueno, David; Fernàndez-Rodríguez, Juana; Cardona, Albert; Hernàndez-Hernàndez, Victor; Romero, Rafael


    Trophic factors are a heterogeneous group of molecules that promote cell growth and survival. In freshwater planarians, the small secreted protein TCEN49 is linked to the regional maintenance of the planarian central body region. To investigate its function in vivo, we performed loss-of-function and gain-of-function experiments by RNA interference and by the implantation of microbeads soaked in TCEN49, respectively. We show that TCEN49 behaves as a trophic factor involved in central body region neuron survival. In planarian tail regenerates, tcen49 expression inhibition by double-stranded RNA interference causes extensive apoptosis in various cell types, including nerve cells. This phenotype is rescued by the implantation of microbeads soaked in TCEN49 after RNA interference. On the other hand, in organisms committed to asexual reproduction, both tcen49 mRNA and its protein are detected not only in the central body region but also in the posterior region, expanding from cells close to the ventral nerve chords. In some cases, the implantation of microbeads soaked in TCEN49 in the posterior body region drives organisms to reproduce asexually, and the inhibition of tcen49 expression obstructs this process, suggesting a link between the central nervous system, TCEN49, regional induction, and asexual reproduction. Finally, the distribution of TCEN49 cysteine and tyrosine residues also points to a common evolutionary origin for TCEN49 and molluscan neurotrophins.

  20. Th17 response and autophagy - main pathways implicated in the development of inflammatory bowel disease by genome-wide association studies: new factors involved in inflammatory bowel disease susceptibility

    Roberto Díaz-Peña


    Full Text Available Inflammatory bowel disease (IBD is an entity that mainly includes ulcerative colitis (UC and Crohn's disease (CD. Improved health care, diet changes, and higher industrialization are associated with an increase in IBD prevalence. This supports the central role of environmental factors in the pathology of this disease. However, IBD also shows a relevant genetic component as shown by high heritability. Classic genetic studies showed relevant associations between IBD susceptibility and genes involved in the immune response. This is consistent with prior theories about IBD development. According to these, contact of the immune system with a high number of harmless antigens from the diet and the bacterial flora should originate tolerance while preserving response against pathogens. Failure to achieve this balance may originate the typical inflammatory response associated with IBD. Recently, genome-wide association studies (GWASs have confirmed the implication of the immune system, particularly the Th17 immune response, previously associated to other autoimmune diseases, and of autophagy. In this paper, the mechanisms involved in these two relevant pathways and their potential role in the pathogenesis of IBD are reviewed.

  1. Factors involved in the discontinuation of oral intake in elderly patients with recurrent aspiration pneumonia: a multicenter study

    Kenzaka, Tsuneaki; Takeshima, Taro; Kosami, Koki; Kumabe, Ayako; Ueda, Yuki; Takahashi, Takeshi; Yamamoto, Yuya; Hayashi, Yurika; Kitao, Akihito; Okayama, Masanobu


    Purpose To assess the factors involved in oral intake discontinuation in elderly patients with recurrent aspiration pneumonia. Patients and methods This study included patients with pneumonia who were treated at Jichi Medical University Hospital between 2007 and 2013, at Toyooka Public Hospital between 2011 and 2013 and at Yuzawa Community Medical Center between 2010 and 2012. We consecutively enrolled patients with aspiration pneumonia. The primary study point was oral intake discontinuation after the initiation of oral intake during hospitalization in cases of recurrent aspiration. Various parameters were recorded at admission, at the initiation of intake, and during hospitalization; these parameters were statistically evaluated. Results A total of 390 patients were assigned to either a “no reaspiration of intake” group (n=310) or a “reaspiration of intake” group (n=80), depending on whether intake was discontinued owing to aspiration during hospitalization. At admission, the following items significantly differed between the groups: level of consciousness, respiratory rate, oxygen saturation, CURB-65 score, extent of infiltration/opacity on chest radiography, albumin levels, blood urea nitrogen levels, and application of swallowing function assessment. At the initiation of intake, level of consciousness, pulse rate, and albumin levels significantly differed between the groups. The following items did not significantly differ between groups: systolic blood pressure, pulse rate, C-reactive protein, bacteremia, use of ventilator at admission, oxygen administration, respiratory rate, and systolic blood pressure at initiation of intake. Multivariate analysis revealed that application of swallowing function assessment, level of consciousness at the initiation of intake, and extent of infiltration/opacity on chest radiography were significant predictive variables for discontinuation of intake. Conclusion A low level of consciousness at the initiation of intake

  2. An activating transcription factor of Litopenaeus vannamei involved in WSSV genes Wsv059 and Wsv166 regulation.

    Li, Xiao-Yun; Yue, Hai-Tao; Zhang, Ze-Zhi; Bi, Hai-Tao; Chen, Yong-Gui; Weng, Shao-Ping; Chan, Siuming; He, Jian-Guo; Chen, Yi-Hong


    Members of activating transcription factor/cyclic adenosine 3', 5'-monophosphate response element binding protein (ATF/CREB) family are induced by various stress signals and function as effector molecules. Consequently, cellular changes occur in response to discrete sets of instructions. In this work, we found an ATF transcription factor in Litopenaeus vannamei designated as LvATFβ. The full-length cDNA of LvATFβ was 1388 bp long with an open reading frame of 939 bp that encoded a putative 313 amino acid protein. The protein contained a basic region-leucine zipper (bZip) domain that was a common feature among ATF/CREB transcription factors. LvATFβ was highly expressed in intestines, gills, and heart. LvATFβ expression was dramatically upregulated by white spot syndrome virus (WSSV) infection. Pull-down assay revealed that LvATFβ had strong affinity to promoters of WSSV genes, namely, wsv059 and wsv166. Dual-luciferase reporter assay showed that LvATFβ could upregulate the expression of wsv059 and wsv166. Knocked down LvATFβ resulted in decreased expression of wsv059 and wsv166 in WSSV-challenged L. vannamei. Knocked down expression of wsv059 and wsv166 by RNA interference inhibited the replication and reduce the mortality of L. vannamei during WSSV challenge inoculation. The copy numbers of WSSV in wsv059 and wsv166 knocked down group were significant lower than in the control. These results suggested that LvATFβ may be involved in WSSV replication by regulating the expression of wsv059 and wsv166.

  3. Density-dependent interference of aphids with caterpillar-induced defenses in Arabidopsis: involvement of phytohormones and transcription factors.

    Kroes, Anneke; van Loon, Joop J A; Dicke, Marcel


    In nature, plants are exposed to attacks by multiple herbivore species at the same time. To cope with these attacks, plants regulate defenses with the production of hormones such as salicylic acid (SA) and jasmonic acid (JA). Because herbivore densities are dynamic in time, this may affect plant-mediated interactions between different herbivores attacking at the same time. In Arabidopsis thaliana, feeding by Brevicoryne brassicae aphids interferes with induced defenses against Plutella xylostella caterpillars. This is density dependent: at a low aphid density, the growth rate of P. xylostella was increased, whereas caterpillars feeding on plants colonized by aphids at a high density have a reduced growth rate. Growth of P. xylostella larvae was unaffected on sid2-1 or on dde2-2 mutant plants when feeding simultaneously with a low or high aphid density. This shows that aphid interference with caterpillar-induced defenses requires both SA and JA signal transduction pathways. Transcriptional analysis revealed that simultaneous feeding by caterpillars and aphids at a low density induced the expression of the SA transcription factor gene WRKY70 whereas expression of WRKY70 was lower in plants induced with both caterpillars and a high aphid density. Interestingly, the expression of the JA transcription factor gene MYC2 was significantly higher in plants simultaneously attacked by aphids at a high density and caterpillars. These results indicate that a lower expression level of WRKY70 leads to significantly higher MYC2 expression through SA-JA cross-talk. Thus, plant-mediated interactions between aphids and caterpillars are density dependent and involve phytohormonal cross-talk and differential activation of transcription factors.

  4. Diabetes, cardiac disorders and asthma as risk factors for severe organ involvement among adult dengue patients: A matched case-control study

    Pang, Junxiong; Hsu, Jung Pu; Yeo, Tsin Wen; Leo, Yee Sin; Lye, David C.


    Progression to severe organ involvement due to dengue infection has been associated with severe dengue disease, intensive care treatment, and mortality. However, there is a lack of understanding of the impact of pre-existing comorbidities and other risk factors of severe organ involvement among dengue adults. The aim of this retrospective case-control study is to characterize and identify risk factors that predispose dengue adults at risk of progression with severe organ involvement. This study involved 174 dengue patients who had progressed with severe organ involvement and 865 dengue patients without severe organ involvement, matched by the year of presentation of the cases, who were admitted to Tan Tock Seng Hospital between year 2005 and 2008. Age group of 60 years or older, diabetes, cardiac disorders, asthma, and having two or more pre-existing comorbidities were independent risk factors of severe organ involvement. Abdominal pain, clinical fluid accumulation, and hematocrit rise and rapid platelet count drop at presentation were significantly associated with severe organ involvement. These risk factors, when validated in a larger study, will be useful for triage by clinicians for prompt monitoring and clinical management at first presentation, to minimize the risk of severe organ involvement and hence, disease severity. PMID:28045096

  5. Stability of the transthyretin molecule as a key factor in the interaction with a-beta peptide--relevance in Alzheimer's disease.

    Carlos A Ribeiro

    Full Text Available Transthyretin (TTR protects against A-Beta toxicity by binding the peptide thus inhibiting its aggregation. Previous work showed different TTR mutations interact differently with A-Beta, with increasing affinities correlating with decreasing amyloidogenecity of the TTR mutant; this did not impact on the levels of inhibition of A-Beta aggregation, as assessed by transmission electron microscopy. Our work aimed at probing differences in binding to A-Beta by WT, T119M and L55P TTR using quantitative assays, and at identifying factors affecting this interaction. We addressed the impact of such factors in TTR ability to degrade A-Beta. Using a dot blot approach with the anti-oligomeric antibody A11, we showed that A-Beta formed oligomers transiently, indicating aggregation and fibril formation, whereas in the presence of WT and T119M TTR the oligomers persisted longer, indicative that these variants avoided further aggregation into fibrils. In contrast, L55PTTR was not able to inhibit oligomerization or to prevent evolution to aggregates and fibrils. Furthermore, apoptosis assessment showed WT and T119M TTR were able to protect against A-Beta toxicity. Because the amyloidogenic potential of TTR is inversely correlated with its stability, the use of drugs able to stabilize TTR tetrameric fold could result in increased TTR/A-Beta binding. Here we showed that iododiflunisal, 3-dinitrophenol, resveratrol, [2-(3,5-dichlorophenylamino] (DCPA and [4-(3,5-difluorophenyl] (DFPB were able to increase TTR binding to A-Beta; however only DCPA and DFPB improved TTR proteolytic activity. Thyroxine, a TTR ligand, did not influence TTR/A-Beta interaction and A-Beta degradation by TTR, whereas RBP, another TTR ligand, not only obstructed the interaction but also inhibited TTR proteolytic activity. Our results showed differences between WT and T119M TTR, and L55PTTR mutant regarding their interaction with A-Beta and prompt the stability of TTR as a key factor in this

  6. Transcriptome analysis of Neisseria meningitidis in human whole blood and mutagenesis studies identify virulence factors involved in blood survival.

    Hebert Echenique-Rivera


    Full Text Available During infection Neisseria meningitidis (Nm encounters multiple environments within the host, which makes rapid adaptation a crucial factor for meningococcal survival. Despite the importance of invasion into the bloodstream in the meningococcal disease process, little is known about how Nm adapts to permit survival and growth in blood. To address this, we performed a time-course transcriptome analysis using an ex vivo model of human whole blood infection. We observed that Nm alters the expression of ≈30% of ORFs of the genome and major dynamic changes were observed in the expression of transcriptional regulators, transport and binding proteins, energy metabolism, and surface-exposed virulence factors. In particular, we found that the gene encoding the regulator Fur, as well as all genes encoding iron uptake systems, were significantly up-regulated. Analysis of regulated genes encoding for surface-exposed proteins involved in Nm pathogenesis allowed us to better understand mechanisms used to circumvent host defenses. During blood infection, Nm activates genes encoding for the factor H binding proteins, fHbp and NspA, genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as several less characterized surface-exposed proteins that might have a role in blood survival. Through mutagenesis studies of a subset of up-regulated genes we were able to identify new proteins important for survival in human blood and also to identify additional roles of previously known virulence factors in aiding survival in blood. Nm mutant strains lacking the genes encoding the hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate permease LctP were sensitive to killing by human blood. This increased knowledge of how Nm responds to adaptation in blood could also be helpful to develop diagnostic and therapeutic strategies to control the devastating

  7. The small ethylene response factor ERF96 is involved in the regulation of the abscisic acid response in Arabidopsis

    Xiaoping eWang


    Full Text Available Ethylene regulates many aspects of plant growth and development including seed germination, leaf senescence, and fruit ripening, and of plant responses to environmental stimuli including both biotic and abiotic stresses. Ethylene Response Factors (ERFs are plant-specific transcription factors and are a subfamily of the AP2 (APETALA2/ERF transcription factor family. The function of many members in this large gene family remains largely unknown. ERF96, a member of the Group IX ERF family transcription factors, has recently been shown to be a transcriptional activator that is involved in plant defense response in Arabidopsis. Here we provide evidence that ERF96 is a positive regulator of abscisic acid (ABA responses. Bioinformatics analysis indicated that there are a total four small ERFs in Arabidopsis including ERF95, ERF96, ERF97 and ERF98, and that ERF96 forms a cluster with ERF95 and ERF97. By using quantitative RT-PCR, we found that ERF96 is expressed in all tissues and organs examined except roots, with relatively high expression in flowers and seeds. Results from the protoplast transfection assay results indicated that the EDLL motif-containing C-terminal domain is responsible for ERF96’s transcriptional activity. Although loss-of-function mutant of ERF96 was morphologically similar to wild type plants, transgenic plants overexpressing ERF96 had smaller rosette size and were delayed in flowering time. In ABA sensitivity assays, we found that ERF96 overexpression plants were hypersensitive to ABA in terms of ABA inhibition of seed germination, early seedling development and root elongation. Consistent with these observations, elevated transcript levels of some ABA-responsive genes including RD29A, ABI5, ABF3, ABF4, P5CS and COR15A were observed in the transgenic plants in the presence of ABA. However, in the absence of ABA treatment, the transcript levels of these ABA-responsive genes remained largely unchanged. Our experiments also showed

  8. Involvement of transcription factor activator protein-2α in doxazosin-induced HeLa cell apoptosis

    Lu GAN; Dong-xing ZHU; Li-ping YANG; Ru-shi LIU; Feng YAN; Jian ZHANG


    Aim:To investigate the pro-apoptotic effects of α- 1-adrenergic inhibitor doxazosin in HeLa cells and the potential involvement of transcription factor activator pro-tein-2α (AP-2α) in doxazosin-indueed apoptosis. Methods:The HeLa cells were exposed to various concentrations of doxazosin for 16 h. Apoptosis was detected using a DNA fragmentation assay, Hoechst 33258 staining, and flow cytometric analysis. The expression of AP-2α and caspase-3 was detected by relative quan-titative RT-PCR and Western blot assays, respectively. After the respective trans-fections of the HeLa cells with AP-2α overexpressing constructs and an antisense oligonucleotide against AP-2α, apoptosis was assessed by flow cytometric analysis, and the expression of AP-2α and easpase-3 was detected by relative quantitative RT-PCR and Western blot assays. The colorimetric assay was per-formed to detect the caspase-3 activity. Results:Treatment with various concen-trations of doxazosin for 16 h increased the apoptotic rate and total cell death rate of the HeLa cells in a dose-dependent manner and upregulated the expression of AP-2α and caspase-3 in a dose-dependent manner. A dose-dependent increase was observed in the caspase-3 activity. Overexpressing AP-2α led to the in-creased rate of doxazosin-induced apoptosis and the total cell death, whereas doxazosin-induced apoptosis and the total cell death in HeLa cells decreased by antisense AP-2α. Furthermore, overexpressing AP-2α increased the expression and activity of caspase-3, whereas antisense AP-2α in part abolished the increased effects of doxazosin on caspase-3 expression and activity. Conclusion:Doxazosin induces apoptosis in HeLa cells in a dose-dependent manner, and transcription factor AP-2α is functionally involved in doxazosin-induced HeLa cell apoptosis.

  9. Involvement of retinoblastoma (Rb) and E2F transcription factors during photodynamic therapy of human epidermoid carcinoma cells A431.

    Ahmad, N; Gupta, S; Mukhtar, H


    Photodynamic therapy (PDT), a promising new therapeutic modality for the management of a variety of solid malignancies and many non-malignant diseases, is a bimodal therapy using a porphyrin based photosensitizing chemical and visible light. The proper understanding of the mechanism of PDT-mediated cancer cell-kill may result in improving the efficacy of this treatment modality. Earlier we have shown (Proc. Natl. Acad. Sci. USA; 95: 6977-6982, 1998) that silicon phthalocyanine (Pc4)-PDT results in an induction of the cyclin kinase inhibitor WAF1/CIP1/p21 which, by inhibiting cyclins (E and D1) and cyclin dependent kinases (cdk2 and cdk6), results in a G0/G1-phase arrest followed by apoptosis in human epidermoid carcinoma cells A431. We have also demonstrated the generation of nitric oxide during PDT-mediated apoptosis (Cancer Res.; 58: 1785-1788, 1998). Retinoblastoma (pRb) and E2F family transcription factors are important proteins, which regulate the G1-->S transition in the cell cycle. Here, we provide evidence for the involvement of pRb-E2F/DP machinery as an important contributor of PDT-mediated cell cycle arrest and apoptosis. Western blot analysis demonstrated a decrease in the hyper-phosphorylated form of pRb at 3, 6 and 12 h post-PDT with a relative increase in hypo-phosphorylated pRb. Western blot analysis also revealed that PDT-caused decrease in phosphorylation of pRb occurs at serine-780. The ELISA data demonstrated a time dependent accumulation of hypo-phosphorylated pRb by PDT. This response was accompanied with down-regulation in the protein expression of all five E2F (1-5) family transcription factors, and their heterodimeric partners DP1 and DP2. These results suggest that Pc4-PDT of A431 cells results in a down regulation of hyper-phosphorylated pRb protein with a relative increase in hypo-phosphorylated pRb that, in turn, compromises with the availability of free E2F. We suggest that these events result in a stoppage of the cell cycle

  10. Extent of liver resection modulates the activation of transcription factors and the production of cytokines involved in liver regeneration


    AIM: To investigate the molecular events involved in liver regeneration following subtotal hepatectomy (SH) as previous studies have largely focused on partial hepatectomy (PH).METHODS: Male Wistar rats were subjected to 70% PH or 90% SH, respectively, and sacrificed at different times after surgery. Untreated and sham-operated animals served as controls. Serum and liver samples were obtained to investigate liver function, apoptosis (TUNEL assay) and transcription factors (NF-κB, Stat3; ELISA) or cytokines (HGF, TNF-α, IL-6, TGF-α, TGF-β; quantitative RT-PCR) involved in liver regeneration. RESULTS: Serum levels of ALT and AST in animals with 70% PH differed significantly from sham-operated and control animals. We found that the peak concentration 12 h after surgery returned to control levels 7 d after surgery. LDH was increased only at 12 h after 70% PH compared to sham. Bilirubin showed no differences between the sham and 70% resection. After PH, early NF-κB activation was detected 12 h after surgery (313.21 ± 17.22 ng/mL), while there was no activation after SH (125.22 ± 44.36 ng/mL) compared to controls (111.43 ± 32.68 ng/mL) at this time point. In SH, however, NF-κB activation was delayed until 24 h (475.56 ± 144.29 ng/mL). Star3 activation was similar in both groups. These findings correlated with suppressed and delayed induction of regenerative genes after SH (i.e. TNF-α 24 h postoperatively: 2375 ± 1220 in 70% and 88±31 in 90%; IL-6 12 h postoperatively: 2547 ± 441 in 70% and 173 ± 82 in 90%). TUNEL staining revealed elevated apoptosis rates in SH (0.44% at 24 h; 0.63% at 7 d) compared to PH (0.27% at 24 h; 0.15% at 7 d). CONCLUSION: The molecular events involved in liver regeneration are significantly influenced by the extent of resection as SH leads to suppression and delay of liver regeneration compared to PH, which is associated with delayed activation of NF-κB and suppression of proregenerative cytokines.

  11. Evaluation of ocular defects and its relevant factors in patients with beta thalassemia major in Sari Boo Ali Sina hospital, (2006-2008

    hosein Karami


    Full Text Available Background: As There is not accurate information about ocular defects in Thalassemia Major (TM patients in Mazandaran province ,this study was designed to assess the prevalence of ophtalmopathies in thalassemic patients and also recognize its relevant factors in Sari Boo Ali Sina hospital. Sari. Materials and Methods: This descriptive Cross-sectional was Carried out on 60 TM patients in Thalassemia center at Sari Boo Ali Sina hospital. Subjects were selected by systematic sampling. After gathering demographic data , patients were evaluated about their illness and its complications from their medical records. Their visual acuity was assessed using Snell chart by an optometrist. Evaluation of retina was done by our ophthalmologist colleague. Visual evoked potential (VEP was assessed by TOENEES instrument made in Italy which had the ability to assess both VEP and P300 . Findings were analyzed by SPSS13 software and Chi square and Mann-whitney tests. Results: 60 patients underwen this study that 33 of them (55% were male. 4 of them (6.6% had problems in visual acuity . 3 of these became normal after refractive correction. 3 patients (5% had Inferior Posterior Cortical Cataract. 2 of them (3.3% had punctuate lens cortical opacity and one (1.7% had mild nuclear sclerosis. 4 patients( 6.7% had macular pigmentation and one (1.7% had left optic nerve head pit. No abnormal finding was detected in VEP, such as latency in voltage. Conclusion: Totally 20 patients had ocular complications. These defects can be a result of desferal toxicity or Iron toxicity and drug effects on binding to cupper and zinc and removing them from retinal cells or extramedulary hematopoesis. So based on the results, ophthalmologic evaluation of TM patients and tight desferal dose adjustment in these patients seems necessary.

  12. IAA8 involved in lateral root formation interacts with the TIR1 auxin receptor and ARF transcription factors in Arabidopsis.

    Fumi Arase

    Full Text Available The expression of auxin-responsive genes is regulated by the TIR1/AFB auxin receptor-dependent degradation of Aux/IAA transcriptional repressors, which interact with auxin-responsive factors (ARFs. Most of the 29 Aux/IAA genes present in Arabidopsis have not been functionally characterized to date. IAA8 appears to have a distinct function from the other Aux/IAA genes, due to its unique transcriptional response to auxin and the stability of its encoded protein. In this study, we characterized the function of Arabidopsis IAA8 in various developmental processes governed by auxin and in the transcriptional regulation of the auxin response. Transgenic plants expressing estrogen-inducible IAA8 (XVE::IAA8 exhibited significantly fewer lateral roots than the wild type, and an IAA8 loss-of-function mutant exhibited significantly more. Ectopic overexpression of IAA8 resulted in abnormal gravitropism. The strong induction of early auxin-responsive marker genes by auxin treatment was delayed by IAA8 overexpression. GFP-fusion analysis revealed that IAA8 localized not only to the nucleus, but, in contrast to other Aux/IAAs, also to the cytosol. Furthermore, we demonstrated that IAA8 interacts with TIR1, in an auxin-dependent fashion, and with ARF proteins, both in yeast and in planta. Taken together, our results show that IAA8 is involved in lateral root formation, and that this process is regulated through the interaction with the TIR1 auxin receptor and ARF transcription factors in the nucleus.

  13. Granulocyte Colony Stimulating Factor and MT1-MMP Involved in Development of Atherosclerosis in Apolipoprotein E-Deficient Mice

    Su-zhen GUO; Andres J. Espinoza; Christian A. Espinoza; Terence M. Doherty; Xiao WANG


    Objectives Genetic deficiency of macrophage colony stimulating factor (M-CSF) in atherosclerosis-prone (apoE-/-) mice markedly reduces formation of atheroma. But Little is known about the potential effects of other colony stimulating factors(CSF), such as granulocyte CSF(G-CSF), on atherosclerosis. This study tested the hypothesis that G-CSF would be involved in development of atherosclerotic plaque. Methods apoE-/- mice fed with a Western-style diet (0.15% cholesterol) were injected subcutaneously with recombinant human G-CSF(10 mg/day) daily for 9 weeks then sacrificed. The matrix metalloproteinase(MMP)2 and MMP9 in serum of mice were measured by Gelatin Zymography analysis and c-kit and membrane type1-MMP(MT1-MMP) antigens were detected using fluorescence activated cell sorting (FACS). Meanwhile, complete blood counts (CBC) and serum cholesterol, relative fractions of VLDL,LDL, and HDL were evaluated by spectrophotometric techniques and high performance liquid chromatography (HPLC)respectively. Atherosclerotic Lesions of the aorta were also analyzed by histological methods. Results G-CSF treatment resulted in increased proportions of circulating monocytes (6.9±2.2% vs.3.8±0.3%;P<0.05), and decreased serum levels of total cholesterol (1225±594 vs.1991±1009;P<0.005) compared to control mice. A greater proportion of bone marrow cells from G-CSF treated mice expressed MT1-MMP (14.5±5.5% vs.6.2±5.0%, P<0.05) compared to bone marrow cells from vehicle treated mice. G-CSF treatment was also associated with smaller atheromatous plaque, and decreased oil red O staining. Conclusions G-CSF lowers serum cholesterol, increases circulating monocytes, increases bone marrow cell expression of MT1-MMP, inhibits plaque development, and decreases lipid and macrophage infiltration into developing plaque.

  14. Extracytoplasmic function (ECF sigma factor σF is involved in Caulobacter crescentus response to heavy metal stress

    Kohler Christian


    Full Text Available Abstract Background The α-proteobacterium Caulobacter crescentus inhabits low-nutrient environments and can tolerate certain levels of heavy metals in these sites. It has been reported that C. crescentus responds to exposure to various heavy metals by altering the expression of a large number of genes. Results In this work, we show that the ECF sigma factor σF is one of the regulatory proteins involved in the control of the transcriptional response to chromium and cadmium. Microarray experiments indicate that σF controls eight genes during chromium stress, most of which were previously described as induced by heavy metals. Surprisingly, σF itself is not strongly auto-regulated under metal stress conditions. Interestingly, σF-dependent genes are not induced in the presence of agents that generate reactive oxygen species. Promoter analyses revealed that a conserved σF-dependent sequence is located upstream of all genes of the σF regulon. In addition, we show that the second gene in the sigF operon acts as a negative regulator of σF function, and the encoded protein has been named NrsF (Negative regulator of sigma F. Substitution of two conserved cysteine residues (C131 and C181 in NrsF affects its ability to maintain the expression of σF-dependent genes at basal levels. Furthermore, we show that σF is released into the cytoplasm during chromium stress and in cells carrying point mutations in both conserved cysteines of the protein NrsF. Conclusion A possible mechanism for induction of the σF-dependent genes by chromium and cadmium is the inactivation of the putative anti-sigma factor NrsF, leading to the release of σF to bind RNA polymerase core and drive transcription of its regulon.

  15. Microscopy-based Assays for High-throughput Screening of Host Factors Involved in Brucella Infection of Hela Cells.

    Casanova, Alain; Low, Shyan H; Emmenlauer, Mario; Conde-Alvarez, Raquel; Salcedo, Suzana P; Gorvel, Jean-Pierre; Dehio, Christoph


    Brucella species are facultative intracellular pathogens that infect animals as their natural hosts. Transmission to humans is most commonly caused by direct contact with infected animals or by ingestion of contaminated food and can lead to severe chronic infections. Brucella can invade professional and non-professional phagocytic cells and replicates within endoplasmic reticulum (ER)-derived vacuoles. The host factors required for Brucella entry into host cells, avoidance of lysosomal degradation, and replication in the ER-like compartment remain largely unknown. Here we describe two assays to identify host factors involved in Brucella entry and replication in HeLa cells. The protocols describe the use of RNA interference, while alternative screening methods could be applied. The assays are based on the detection of fluorescently labeled bacteria in fluorescently labeled host cells using automated wide-field microscopy. The fluorescent images are analyzed using a standardized image analysis pipeline in CellProfiler which allows single cell-based infection scoring. In the endpoint assay, intracellular replication is measured two days after infection. This allows bacteria to traffic to their replicative niche where proliferation is initiated around 12 hr after bacterial entry. Brucella which have successfully established an intracellular niche will thus have strongly proliferated inside host cells. Since intracellular bacteria will greatly outnumber individual extracellular or intracellular non-replicative bacteria, a strain constitutively expressing GFP can be used. The strong GFP signal is then used to identify infected cells. In contrast, for the entry assay it is essential to differentiate between intracellular and extracellular bacteria. Here, a strain encoding for a tetracycline-inducible GFP is used. Induction of GFP with simultaneous inactivation of extracellular bacteria by gentamicin enables the differentiation between intracellular and extracellular

  16. Skeletal involvement in Gaucher disease: An observational multicenter study of prognostic factors in the Argentine Gaucher disease patients.

    Drelichman, Guillermo; Fernández Escobar, Nicolás; Basack, Nora; Aversa, Luis; Larroude, María Silvia; Aguilar, Gabriela; Szlago, Marina; Schenone, Andrea; Fynn, Alcyra; Cuello, María Fernanda; Aznar, Marcela; Fernández, Ramiro; Ruiz, Alba; Reichel, Paola; Guelbert, Norberto; Robledo, Hugo; Watman, Nora; Bolesina, Moira; Elena, Graciela; Veber, S Ernesto; Pujal, Graciela; Galván, Graciela; Chain, Juan José; Arizo, Adriana; Bietti, Julieta; Bar, Daniel; Dragosky, Marta; Marquez, Marisa; Feldman, Leonardo; Muller, Katja; Zirone, Sandra; Buchovsky, Greogorio; Lanza, Victoria; Sanabria, Alba; Fernández, Ignacio; Jaureguiberry, Rossana; Contte, Marcelo; Barbieri María, Angie; Maro, Alejandra; Zárate, Graciela; Fernández, Gabriel; Rapetti, María Cristina; Donato, Hugo; Degano, Adriana; Kantor, Gustavo; Albina, Roberto; Á Lvarez Bollea, María; Brun, María; Bacciedoni, Viviana; Del Río, Francis; Soberón, Bárbara; Boido, Nazario; Schweri, Maya; Borchichi, Sandra; Welsh, Victoria; Corrales, Marcela; Cedola, Alejandra; Carvani, Analía; Diez, Blanca; Richard, Lucía; Baduel, Ccecilia; Nuñez, Gabriela; Colimodio, Rubén; Barazzutti, Lucía; Medici, Hugo; Meschengieser, Susana; Damiani, Germán; Nucifora, María; Girardi, Beatriz; Gómez, Sergio; Papucci, Maura; Verón, David; Quiroga, Luis; Carro, Gustavo; De Ambrosio, Patricia; Ferro, José; Pujol, Marcelo; Castella, Cristina Cabral; Franco, Liliana; Nisnovich, Gisela; Veloso, María; Pacheco, Isabel; Savarino, Mario; Marino, Andrés; Saavedra, José Luis


    Patients with Gaucher type 1 (GD1) throughout Argentina were enrolled in the Argentine bone project to evaluate bone disease and its determinants. We focused on presence and predictors of bone lesions (BL) and their relationship to therapeutic goals (TG) with timing and dose of enzyme replacement therapy (ERT). A total of 124 patients on ERT were enrolled in a multi-center study. All six TG were achieved by 82% of patients: 70.1% for bone pain and 91.1% for bone crisis. However, despite the fact that bone TGs were achieved, residual bone disease was present in 108 patients on ERT (87%) at time 0. 16% of patients showed new irreversible BL (bone infarcts and avascular osteonecrosis) despite ERT, suggesting that they appeared during ERT or were not detected at the moment of diagnosis. We observed 5 prognostic factors that predicted a higher probability of being free of bone disease: optimal ERT compliance; early diagnosis; timely initiation of therapy; ERT initiation dose ≥45 UI/kg/EOW; and the absence of history of splenectomy. Skeletal involvement was classified into 4 major phenotypic groups according to BL: group 1 (12.9%) without BL; group 2 (28.2%) with reversible BL; group 3 (41.9%) with reversible BL and irreversible chronic BL; and group 4 (16.9%) with acute irreversible BL. Our study identifies prognostic factors for achieving best therapeutic outcomes, introduces new risk stratification for patients and suggests the need for a redefinition of bone TG. Am. J. Hematol. 91:E448-E453, 2016. © 2016 Wiley Periodicals, Inc.

  17. Logistic regression analysis of relevant factors on the prognosis of sudden deafness%突发性耳聋预后影响因素分析

    余娇艳; 杨柏球


    目的:探讨影响突发性耳聋预后转归的相关因素。方法回顾性分析89例突聋患者的临床资料,对性别、年龄、初诊时间,是否合并高血压、糖尿病,有无眩晕,发病耳别,听力损伤类型及分级等可能与突发性耳聋预后相关的因素进行观察和分析。结果初诊时间越短、听力损伤程度越轻、不伴有眩晕和听力曲线分型为上升型者预后较好。结论应根据突发性耳聋患者的发病时间、耳聋程度、听力曲线类型及是否伴有眩晕分析患者的预后并做到早发现、早治疗。%Objective To investigate the relevant factors on the prognosis of sudden deafness.Methods The clinical data of 89 patients with sudden deafness were analyzed retrospectively.The factors may be associated with the prognosis of sudden deaf-ness such as gender,age,the time from onset to treatment,complicated by hypertension,diabetes,vertigo or not,the type and grade of hearing impairment were observed and analysed.Results The patients who got the better prognosis were those with shorter time from onset to treatment,lighter degree of hearing damage,the ascending curve hearing type and those who were not complicated by dizziness.Conclusion The prognosis of sudden deafness should be analysed according to the time from onset to treatment,complicated by vertigo or not,and the type and grade of hearing impairment,it is necessary to achieve early detection and early treatment.

  18. Clinical Relevance of Adipokines

    Matthias Blüher


    Full Text Available The incidence of obesity has increased dramatically during recent decades. Obesity increases the risk for metabolic and cardiovascular diseases and may therefore contribute to premature death. With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines changes towards a pro-inflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity, chronic inflammation and have the potential for future pharmacological treatment strategies for obesity and its related diseases. This review focuses on the clinical relevance of selected adipokines as markers or predictors of obesity related diseases and as potential therapeutic tools or targets in metabolic and cardiovascular diseases.

  19. Transcription factor Ctip2 controls epidermal lipid metabolism and regulates expression of genes involved in sphingolipid biosynthesis during skin development

    Wang, Zhixing; Kirkwood, Jay S.; Taylor, Alan W.; Stevens, Jan F.; Leid, Mark; Ganguli-Indra, Gitali; Indra, Arup K.


    The stratum corneum is composed of protein-enriched corneocytes embedded in an intercellular matrix of nonpolar lipids organized as lamellar layers and give rise to epidermal permeability barrier (EPB). EPB defects play an important role in the pathophysiology of skin diseases such as eczema. The transcriptional control of skin lipid metabolism is poorly understood. We have discovered that mouse lacking a transcription factor COUP-TF interacting protein 2 (Ctip2) exhibit EPB defects including altered keratinocyte terminal differentiation, delayed skin barrier development and interrupted neutral lipid distribution in the epidermis. We adapted herein a targeted lipidomic approach using mass spectrometry, and have determined that Ctip2−/− mice (germline deletion of Ctip2 gene) display altered composition of major epidermal lipids such as ceramides and sphingomyelins compared to wildtype at different stages of skin development. Interestingly, expressions of several genes involved in skin sphingolipid biosynthesis and metabolism were altered in mutant skin. Ctip2 was found to be recruited to the promoter region of a subset of those genes, suggesting their possible direct regulation by Ctip2. Our results confirm an important role of Ctip2 in regulating skin lipid metabolism and indicate that profiling of epidermal sphingolipid could be useful for designing effective strategies to improve barrier dysfunctions. PMID:23096701

  20. Stromal Derived Factor-1/CXCR4 Axis Involved in Bone Marrow Mesenchymal Stem Cells Recruitment to Injured Liver

    Kuai Xiao Ling


    Full Text Available The molecular mechanism of bone marrow mesenchymal stromal stem cells (BMSCs mobilization and migration to the liver was poorly understood. Stromal cell-derived factor-1 (SDF-1 participates in BMSCs homing and migration into injury organs. We try to investigate the role of SDF-1 signaling in BMSCs migration towards injured liver. The expression of CXCR4 in BMSCs at mRNA level and protein level was confirmed by RT-PCR, flow cytometry, and immunocytochemistry. The SDF-1 or liver lysates induced BMSCs migration was detected by transwell inserts. CXCR4 antagonist, AMD3100, and anti-CXCR4 antibody were used to inhibit the migration. The Sprague-Dawley rat liver injury model was established by intraperitoneal injection of thioacetamide. The concentration of SDF-1 increased as modeling time extended, which was determined by ELISA method. The Dir-labeled BMSCs were injected into the liver of the rats through portal vein. The cell migration in the liver was tracked by in vivo imaging system and the fluorescent intensity was measured. In vivo, BMSCs migrated into injured liver which was partially blocked by AMD3100 or anti-CXCR4 antibody. Taken together, the results demonstrated that the migration of BMSCs was regulated by SDF-1/CXCR4 signaling which involved in BMSCs recruitment to injured liver.

  1. Possible Involvement of a Mitochondrial Translation Initiation Factor 3 Variant Causing Decreased mRNA Levels in Parkinson's Disease

    Anna Anvret


    Full Text Available Genes important for mitochondrial function have been implicated in Parkinson's disease (PD. Mitochondrial translation initiation factor 3 (MTIF3 is a nuclear encoded protein required for the initiation of complex formation on mitochondrial ribosomes. Dysfunction of MTIF3 may impair mitochondrial function and dopamine neurons appear to be particularly vulnerable to oxidative stress, which may relate to their degeneration in PD. An association was recently reported between the synonymous rs7669(C>T in MTIF3 and PD in a German case-control material. We investigated rs7669 in a Swedish Parkinson case-control material. The study revealed no significant association of the individual genotypes or alleles with PD. When comparing the combined TT/CT-genotypes versus the CC-genotype, we observed a significant association (P=.0473 with PD. We also demonstrated that the TT-genotype causes a significant decrease in MTIF3 mRNA expression compared to the CC-genotype (P=.0163. Our findings support the hypothesis that MTIF3 may be involved in the etiology of PD.

  2. Endothelium-derived hyperpolarizing factor mediated relaxations in pig coronary arteries do not involve Gi/o proteins

    Kwok Fu Jacobus NG; Susan Wai Sum LEUNG; Picky Ying Keung MAN; Paul M VANHOUTTE


    Aim: Endothelium-dependent relaxations to certain neurohumoral substances are mediated by pertussis toxin-sensitive Gi/o protein. Our experiments were designed to determine the role, if any, of pertussis toxin-sensitive G-proteins in relaxations attributed to endothelium-derived hyperpolarizing factor (EDHF). Methods: Pig coronary arterial rings with endothelia were suspended in organ chambers filled with Krebs-Ringer bicarbonate solution maintained at 37℃ and continuously aerated with 95%O2 and 5% CO2. Isometric tension was measured during contractions to prostaglandin F2, in the presence of indomethacin and Nω-nitro-L-arginine methyl ester (L-NAME). Results: Thrombin, the thrombin re-ceptor-activating peptide SFLLRN, bradykinin, substance P, and calcimycin pro-duced dose-dependent relaxations. These relaxations were not inhibited by prior incubation with pertussis toxin, but were abolished upon the addition of charyb-dotoxin plus apamin. Relaxations to the α2-adrenergic agonist UK14304 and those to serotonin were abolished in the presence of indomethacin and L-NAME. Conclusion: Unlike nitric oxide-mediated relaxations, EDHF-mediated relax-ations of pig coronary arteries do not involve pertussis toxin-sensitive pathways and are Gi/o protein independent.

  3. Involvement of aquaporin-3 in epidermal growth factor receptor signaling via hydrogen peroxide transport in cancer cells.

    Hara-Chikuma, Mariko; Watanabe, Sachiko; Satooka, Hiroki


    Aquaporin 3 (AQP3), a water/glycerol channel protein, is capable of transporting hydrogen peroxide (H2O2). Here, we show that AQP3-mediated intracellular H2O2 is involved in epidermal growth factor (EGF)-induced cell signaling and its dependent cell function in the EGF receptor (EGFR)-positive cancer cell lines A431 and H1666. AQP3 knockdown suppressed the transport into the cells of extracellular H2O2 produced in response to EGF in A431 and H1666 cells. EGF-induced Erk and Akt activation, which occurred through SHP2 and/or PTEN modulation, was impaired by AQP3 knockdown. Cell growth and migration induced by EGF stimulation were attenuated in AQP3 knockdown cells compared with those in control cells. Coincidentally, tumor growth of A431 cell xenografts in immunodeficient mice was decreased by AQP3 knockdown. Accordingly, a xenograft with AQP3 knockdown A431 cells significantly enhanced the survival of recipient mice compared with the transplantation with control cells. In addition, AQP3 associated with EGFR and NADPH oxidase 2, which we propose is linked to AQP3 producing a localized increase in intracellular H2O2 to function as a second messenger during EGFR cell signaling. Therefore, our findings suggest that AQP3 is required for EGF-EGFR cell signaling in cancer cells and is a therapeutic target for cancer progression.

  4. Complex molecular genetic abnormalities involving three or more genetic mutations are important prognostic factors for acute myeloid leukemia.

    Wakita, S; Yamaguchi, H; Ueki, T; Usuki, K; Kurosawa, S; Kobayashi, Y; Kawata, E; Tajika, K; Gomi, S; Koizumi, M; Fujiwara, Y; Yui, S; Fukunaga, K; Ryotokuji, T; Hirakawa, T; Arai, K; Kitano, T; Kosaka, F; Tamai, H; Nakayama, K; Fukuda, T; Inokuchi, K


    We conducted a comprehensive analysis of 28 recurrently mutated genes in acute myeloid leukemia (AML) in 271 patients with de novo AML. Co-mutations were frequently detected in the intermediate cytogenetic risk group, at an average of 2.76 co-mutations per patient. When assessing the prognostic impact of these co-mutations in the intermediate cytogenetic risk group, overall survival (OS) was found to be significantly shorter (P=0.0006) and cumulative incidence of relapse (CIR) significantly higher (P=0.0052) in patients with complex molecular genetic abnormalities (CMGAs) involving three or more mutations. This trend was marked even among patients aged ⩽65 years who were also FLT3-ITD (FMS-like tyrosine kinase 3 internal tandem duplications)-negative (OS: P=0.0010; CIR: P=0.1800). Moreover, the multivariate analysis revealed that CMGA positivity was an independent prognostic factor associated with OS (P=0.0007). In stratification based on FLT3-ITD and CEBPA status and 'simplified analysis of co-mutations' using seven genes that featured frequently in CMGAs, CMGA positivity retained its prognostic value in transplantation-aged patients of the intermediate cytogenetic risk group (OS: P=0.0002. CIR: Pmutation analysis to have clinical usefulness and applicability.

  5. Vimentin-Mediated Steroidogenesis Induced by Phthalate Esters: Involvement of DNA Demethylation and Nuclear Factor κB.

    Li, Yuan; Hu, Yanhui; Dong, Congcong; Lu, Hongchao; Zhang, Chang; Hu, Qi; Li, Shifeng; Qin, Heng; Li, Zhong; Wang, Yubang


    Di-n-butyl phthalate (DBP) and its active metabolite, monobutyl phthalate (MBP) are the most common endocrine disrupting chemicals. Many studies indicate that high-doses of DBP and/or MBP exhibit toxicity on testicular function, however, little attention have been paid to the effects of low levels of DBP/MBP on steroidogenesis. As we all know, the steroidogenic acute regulatory protein (StAR) is a key regulator involved in the steroidogenesis. Here we found that, in addition to StAR, MBP/DBP increased the steroidogenesis by a cytoskeletal protein, vimentin. Briefly, in murine adrenocortical tumor (Y1) and the mouse Leydig tumor (MLTC-1) cells, vimentin regulated the secretion of progesterone. When these two cells were exposure to MBP, the DNA demethylation in the vimentin promoter was observed. In addition, MBP also induced the activation of nuclear factor kappa B (NF-κB, a transcriptional regulator of vimentin). These two processes improved the transcriptional elevation of vimentin. Knockdown of NF-κB/vimentin signaling blocked the DBP/MBP-induced steroidogenesis. These in vitro results were also confirmed via an in vivo model. By identifying a mechanism whereby DBP/MBP regulates vimentin, our results expand the understanding of the endocrine disrupting potential of phthalate esters.

  6. The thumb subdomain of yeast mitochondrial RNA polymerase is involved in processivity, transcript fidelity and mitochondrial transcription factor binding.

    Velazquez, Gilberto; Sousa, Rui; Brieba, Luis G


    Single subunit RNA polymerases have evolved 2 mechanisms to synthesize long transcripts without falling off a DNA template: binding of nascent RNA and interactions with an RNA:DNA hybrid. Mitochondrial RNA polymerases share a common ancestor with T-odd bacteriophage single subunit RNA polymerases. Herein we characterized the role of the thumb subdomain of the yeast mtRNA polymerase gene (RPO41) in complex stability, processivity, and fidelity. We found that deletion and point mutants of the thumb subdomain of yeast mtRNA polymerase increase the synthesis of abortive transcripts and the probability that the polymerase will disengage from the template during the formation of the late initial transcription and elongation complexes. Mutations in the thumb subdomain increase the amount of slippage products from a homopolymeric template and, unexpectedly, thumb subdomain deletions decrease the binding affinity for mitochondrial transcription factor (Mtf1). The latter suggests that the thumb subdomain is part of an extended binding surface area involved in binding Mtf1.

  7. The involvement of hypoxia-inducible factor 1 alpha in Toll-like receptor 7/8-mediated inflammatory response

    Sally A Nicholas; Vadim V Sumbayev


    Toll-like receptors (TLRs) 7 and 8 are crucial in host defence against single-stranded RNA (ssRNA) viruses. Such viruses cause severe illnesses, which remain a serious medical burden in both industrialised and developing countries. TLR7/8 downstream signaling leads to a dramatic cellular stress associated with energy consumption. However, the molecular mechanisms of cell survival and adaptation to TLR7/8-induced stress, which give the cells an opportunity to initiate proper inflammatory reactions, are not clear at all. Here we report for the first time that ligand-induced ac-tivation of TLR7/8 leads to the accumulation of hypoxia-inducible factor 1 alpha (HIF-1α) protein in THP-1 human myeloid macrophages via redox-and reactive nitrogen species-dependent mechanisms. MAP kinases and phosphoi-nositol-3K are not involved in TLR7/8-mediated HIF-1α accumulation. Experiments with HIF-la knockdown THP-1 cells have clearly demonstrated that HIF-1α is important for the protection of these cells against TLR7/8-induced depletion of ATP. Thus, HIF-1α might support both cell survival and the production of pro-inflammatory cytokines upon TLR7/8 activation.

  8. Involvement of Nuclear Factor κB, not Pregnane X Receptor, in Inflammation-Mediated Regulation of Hepatic Transporters.

    Abualsunun, Walaa A; Piquette-Miller, Micheline


    Endotoxin-induced inflammation decreases the hepatic expression of several drug transporters, metabolizing enzymes, and nuclear transcription factors, including pregnane X receptor (PXR). As the nuclear factor κB (NF-κB) is a major mediator of inflammation, and reciprocal repression between NF-κB and PXR signaling has been reported, the objective of this study was to examine whether NF-κB directly regulates the expression of transporters or exerts its effect indirectly via PXR. PXR-deficient (-/-) or wild-type (+/+) male mice were dosed with the selective NF-κB inhibitor PHA408 (40 mg/kg i.p.) or vehicle (n = 5-8/group), followed by endotoxin (5 mg/kg) or saline 30 minutes later. Animals were sacrificed at 6 hours; samples were analyzed using quantitative reverse-transcription polymerase chain reaction and Western blots. Endotoxin induced tumor necrosis factor-α, interleukin (IL)-6, IL-1β, and inducible nitric oxide synthase in PXR (+/+) and (-/-) mice. As compared with saline controls, endotoxin administration imposed 30%-70% significant decreases in the expression of Abcb1a, Abcb11, Abcc2, Abcc3, Abcg2, Slc10a1, Slco2b1, and Slco1a4 in PXR (+/+) and (-/-) mice to a similar extent. Preadministration of PHA408 attenuated endotoxin-mediated changes in both PXR (+/+) and (-/-) mice (P < 0.05). Our findings demonstrate that endotoxin activates NF-κB and imposes a downregulation of numerous ATP-binding cassette and solute carrier transporters through NF-κB in liver and is independent of PXR. Moreover, inhibition of NF-κB attenuates the impact of endotoxin on transporter expression. As NF-κB activation is involved in many acute and chronic disease states, disease-induced changes in transporter function may be an important source of variability in drug response. This information may be useful in predicting potential drug-disease interactions. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  9. Ankylosing spondylitis diagnosis in US patients with back pain: identifying providers involved and factors associated with rheumatology referral delay.

    Deodhar, Atul; Mittal, Manish; Reilly, Patrick; Bao, Yanjun; Manthena, Shivaji; Anderson, Jaclyn; Joshi, Avani


    This study aimed to identify providers involved in diagnosing ankylosing spondylitis (AS) following back pain diagnosis in the USA and to identify factors leading to the delay in rheumatology referrals. The Truven Health MarketScan® US Commercial Database was searched for patients aged 18-64 years with back pain diagnosis in a non-rheumatology setting followed by AS diagnosis in any setting during January 2000-December 2012. Patients with a rheumatologist visit on or before AS diagnosis were considered referred. Cox regression was used to determine factors associated with referral time after adjusting for age, sex, comorbidities, physician specialty, drug therapy, and imaging procedures. Of 3336 patients included, 1244 (37 %) were referred to and diagnosed by rheumatologists; the others were diagnosed in primary care (25.7 %), chiropractic/physical therapy (7 %), orthopedic surgery (3.8 %), pain clinic (3.6 %), acute care (3.4 %), and other (19.2 %) settings. Median time from back pain diagnosis to rheumatology referral was 307 days and from first rheumatologist visit to AS diagnosis was 28 days. Referred patients were more likely to be younger (hazard ratio [HR] = 0.986; p < 0.0001), male (HR = 1.15; p = 0.0163), diagnosed with uveitis (HR = 1.49; p = 0.0050), referred by primary care physicians (HR = 1.96; p < 0.0001), prescribed non-steroidal anti-inflammatory drugs (HR = 1.55; p < 0.0001), disease-modifying antirheumatic drugs (HR = 1.33; p < 0.0001), and tumor necrosis factor inhibitors (HR = 1.40; p = 0.0036), and to have had spinal/pelvic X-ray prior to referral (HR = 1.28; p = 0.0003). During 2000-2012, most patients with AS were diagnosed outside of rheumatology practices. The delay before referral to rheumatology was 10 months; AS diagnosis generally followed within a month. Earlier referral of patients with AS signs and symptoms may lead to more timely diagnosis and appropriate

  10. Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.

    Biaoru Li

    Full Text Available Fetal stem cells isolated from umbilical cord blood (UCB possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of therapies for β-hemoglobinopathies. Transcriptome data are available for erythroid progenitors derived from adult stem cells, however studies to define molecular mechanisms controlling globin gene regulation during fetal erythropoiesis are limited. Here, we utilize UCB-CD34+ stem cells induced to undergo erythroid differentiation to characterize the transcriptome and transcription factor networks (TFNs associated with the γ/β-globin switch during fetal erythropoiesis. UCB-CD34+ stem cells grown in the one-phase liquid culture system displayed a higher proliferative capacity than adult CD34+ stem cells. The γ/β-globin switch was observed after day 42 during fetal erythropoiesis in contrast to adult progenitors where the switch occurred around day 21. To gain insights into transcription factors involved in globin gene regulation, microarray analysis was performed on RNA isolated from UCB-CD34+ cell-derived erythroid progenitors harvested on day 21, 42, 49 and 56 using the HumanHT-12 Expression BeadChip. After data normalization, Gene Set Enrichment Analysis identified transcription factors (TFs with significant changes in expression during the γ/β-globin switch. Forty-five TFs were silenced by day 56 (Profile-1 and 30 TFs were activated by day 56 (Profile-2. Both GSEA datasets were analyzed using the MIMI Cytoscape platform, which discovered TFNs centered on KLF4 and GATA2 (Profile-1 and KLF1 and GATA1 for Profile-2 genes. Subsequent shRNA studies in KU812 leukemia cells and human erythroid progenitors generated from UCB-CD34+ cells supported a negative role of MAFB in γ-globin regulation. The characteristics of erythroblasts derived from UCB-CD34

  11. Lipoxin A4 and platelet activating factor are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice.

    Haiya Wu

    Full Text Available CFTR (cystic fibrosis transmembrane conductance regulator is expressed by both neutrophils and platelets. Lack of functional CFTR could lead to severe lung infection and inflammation. Here, we found that mutation of CFTR (F508del or inhibition of CFTR in mice led to more severe thrombocytopenia, alveolar neutrocytosis and bacteriosis, and lower lipoxin A4/MIP-2 (macrophage inhibitory protein-2 or lipoxin A4/neutrophil ratios in the BAL (bronchoalveolar lavage during acute E. coli pneumonia. In vitro, inhibition of CFTR promotes MIP-2 production in LPS-stimulated neutrophils; however, lipoxin A4 could dose-dependently suppress this effect. In LPS-induced acute lung inflammation, blockade of PSGL-1 (P-selectin glycoprotein ligand-1 or P-selectin, antagonism of PAF by WEB2086, or correction of mutated CFTR trafficking by KM11060 could significantly increase plasma lipoxin A4 levels in F508del relevant to wildtype mice. Concurrently, F508del mice had higher plasma platelet activating factor (PAF levels and PAF-AH activity compared to wildtype under LPS challenge. Inhibiting hydrolysis of PAF by a specific PAF-AH (PAF-acetylhydrolase inhibitor, MAFP, could worsen LPS-induced lung inflammation in F508del mice compared to vehicle treated F508del group. Particularly, depletion of platelets in F508del mice could significantly decrease plasma lipoxin A4 and PAF-AH activity and deteriorate LPS-induced lung inflammation compared to control F508del mice. Taken together, lipoxin A4 and PAF are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice, suggesting that lipoxin A4 and PAF might be therapeutic targets for ameliorating CFTR-deficiency deteriorated lung inflammation.

  12. Effect of Creosote Bush-Derived NDGA on Expression of Genes Involved in Lipid Metabolism in Liver of High-Fructose Fed Rats: Relevance to NDGA Amelioration of Hypertriglyceridemia and Hepatic Steatosis.

    Haiyan Zhang

    Full Text Available Nordihydroguaiaretic acid (NDGA, the main metabolite of Creosote bush, has been shown to have profound effects on the core components of the metabolic syndrome (MetS, lowering blood glucose, free fatty acids (FFA and triglyceride (TG levels in several models of dyslipidemia, as well as improving body weight (obesity, insulin resistance, diabetes and hypertension, and ameliorating hepatic steatosis. In the present study, a high-fructose diet (HFrD fed rat model of hypertriglyceridemia was employed to further delineate the underlying mechanism by which NDGA exerts its anti-hypertriglyceridemic action. In the HFrD treatment group, NDGA administration by oral gavage decreased plasma levels of TG, glucose, FFA, and insulin, increased hepatic mitochondrial fatty acid oxidation and attenuated hepatic TG accumulation. qRT-PCR measurements indicated that NDGA treatment increased the mRNA expression of key fatty acid transport (L-FABP, CD36, and fatty acid oxidation (ACOX1, CPT-2, and PPARα transcription factor genes and decreased the gene expression of enzymes involved in lipogenesis (FASN, ACC1, SCD1, L-PK and ChREBP and SREBP-1c transcription factors. Western blot analysis indicated that NDGA administration upregulated hepatic insulin signaling (P-Akt, AMPK activity (P-AMPK, MLYCD, and PPARα protein levels, but decreased SCD1, ACC1 and ACC2 protein content and also inactivated ACC1 activity (increased P-ACC1. These findings suggest that NDGA ameliorates hypertriglyceridemia and hepatic steatosis primarily by interfering with lipogenesis and promoting increased channeling of fatty acids towards their oxidation.

  13. Effect of Creosote Bush-Derived NDGA on Expression of Genes Involved in Lipid Metabolism in Liver of High-Fructose Fed Rats: Relevance to NDGA Amelioration of Hypertriglyceridemia and Hepatic Steatosis.

    Zhang, Haiyan; Li, Yihang; Hu, Jie; Shen, Wen-Jun; Singh, Madhurima; Hou, Xiaoming; Bittner, Alex; Bittner, Stefanie; Cortez, Yuan; Tabassum, Juveria; Kraemer, Fredric B; Azhar, Salman


    Nordihydroguaiaretic acid (NDGA), the main metabolite of Creosote bush, has been shown to have profound effects on the core components of the metabolic syndrome (MetS), lowering blood glucose, free fatty acids (FFA) and triglyceride (TG) levels in several models of dyslipidemia, as well as improving body weight (obesity), insulin resistance, diabetes and hypertension, and ameliorating hepatic steatosis. In the present study, a high-fructose diet (HFrD) fed rat model of hypertriglyceridemia was employed to further delineate the underlying mechanism by which NDGA exerts its anti-hypertriglyceridemic action. In the HFrD treatment group, NDGA administration by oral gavage decreased plasma levels of TG, glucose, FFA, and insulin, increased hepatic mitochondrial fatty acid oxidation and attenuated hepatic TG accumulation. qRT-PCR measurements indicated that NDGA treatment increased the mRNA expression of key fatty acid transport (L-FABP, CD36), and fatty acid oxidation (ACOX1, CPT-2, and PPARα transcription factor) genes and decreased the gene expression of enzymes involved in lipogenesis (FASN, ACC1, SCD1, L-PK and ChREBP and SREBP-1c transcription factors). Western blot analysis indicated that NDGA administration upregulated hepatic insulin signaling (P-Akt), AMPK activity (P-AMPK), MLYCD, and PPARα protein levels, but decreased SCD1, ACC1 and ACC2 protein content and also inactivated ACC1 activity (increased P-ACC1). These findings suggest that NDGA ameliorates hypertriglyceridemia and hepatic steatosis primarily by interfering with lipogenesis and promoting increased channeling of fatty acids towards their oxidation.

  14. Finding biomarkers in non-model species: literature mining of transcription factors involved in bovine embryo development

    Turenne Nicolas


    Full Text Available Abstract Background Since processes in well-known model organisms have specific features different from those in Bos taurus, the organism under study, a good way to describe gene regulation in ruminant embryos would be a species-specific consideration of closely related species to cattle, sheep and pig. However, as highlighted by a recent report, gene dictionaries in pig are smaller than in cattle, bringing a risk to reduce the gene resources to be mined (and so for sheep dictionaries. Bioinformatics approaches that allow an integration of available information on gene function in model organisms, taking into account their specificity, are thus needed. Besides these closely related and biologically relevant species, there is indeed much more knowledge of (i trophoblast proliferation and differentiation or (ii embryogenesis in human and mouse species, which provides opportunities for reconstructing proliferation and/or differentiation processes in other mammalian embryos, including ruminants. The necessary knowledge can be obtained partly from (i stem cell or cancer research to supply useful information on molecular agents or molecular interactions at work in cell proliferation and (ii mouse embryogenesis to supply useful information on embryo differentiation. However, the total number of publications for all these topics and species is great and their manual processing would be tedious and time consuming. This is why we used text mining for automated text analysis and automated knowledge extraction. To evaluate the quality of this “mining”, we took advantage of studies that reported gene expression profiles during the elongation of bovine embryos and defined a list of transcription factors (or TF, n = 64 that we used as biological “gold standard”. When successful, the “mining” approach would identify them all, as well as novel ones. Methods To gain knowledge on molecular-genetic regulations in a non model organism, we offer an

  15. Expression of mature micro-RNA involved in the functioning of p53-dependent system of maintaining the genome stability of the individuals exposed to radiation at clinically relevant doses

    Shulenina L.V.


    Full Text Available Purpose: to explore the content of mature micro-RNA involved in the functioning of p53-dependent system of maintaining the genome stability in the blood of patients in distant time after irradiation at clinically relevant doses and to compare these micro-RNA with the development of malignant tumors in the period of late consequences of radiation injury. Materials and methods. We used the blood samples of patients with acute radiation syndrome (ARS, acute radiation syndrome with the development of local radiation injury (ARS+LRI and local radiation injury (LRI obtained through 1-51 year after radiation injury. The mature mir34a, mir21, mir145, mir16, mir125b, Iet7a which contained in the common fractions of RNA were reverse transcribed by using specific "stem-loop" — primers. The relative amount of micro-RNA in blood of patients by real-time PCR. Statistical analysis of the results was carried out using the non-parametric Mann —Whitney test. Data are presented as median and quartiles, normalized to median of control group accepted for 1. Results. We found a significant reduction of content of mir34a, mir21 in the blood of patients with a diagnosis ARS and the increase of content of mir145 in patients with LRI. Analysis of the individual values of micro-RNA expression in the blood of patients whose cancer was detected, except for patients with a bazalioma, showed consistency of changes with risk of carcinogenesis. Conclusion. For the first time was investigated the functional activity of p53-dependent system of maintaining the genome stability by measuring of micro-RNA in the blood of patients after many years post radiation injury. We found a significant reduction of content of mir34a, mir21 in blood of patients with ARS, and increased mir145 in patients with LRI. Our results suggest that further research with groups of patients, and analysis the dynamics of micro-RNA content would allow for use the micro-RNA as indicators of risk of late

  16. A two-component system, an anti-sigma factor and two paralogous ECF sigma factors are involved in the control of general stress response in Caulobacter crescentus.

    Lourenço, Rogério F; Kohler, Christian; Gomes, Suely L


    The extracytoplasmic function sigma factor σ(T) is the master regulator of general stress response in Caulobacter crescentus and controls the expression of its paralogue σ(U). In this work we showed that PhyR and NepR act, respectively, as positive and negative regulators of σ(T) expression and function. Biochemical data also demonstrated that NepR directly binds σ(T) and the phosphorylated form of PhyR. We also described the essential role of the histidine kinase gene CC3474, here denominated phyK, for expression of σ(T)-dependent genes and for resistance to stress conditions. Additionally, in vivo evidence of PhyK-dependent phosphorylation of PhyR is presented. This study also identified a conserved cysteine residue (C95) located in the periplasmic portion of PhyK that is crucial for the function of the protein. Furthermore, we showed that PhyK, PhyR and σ(T) regulate the same set of genes and that σ(T) apparently directly controls most of its regulon. In contrast, σ(U) seems to have a very modest contribution to the expression of a subset of σ(T)-dependent genes. In conclusion, this report describes the molecular mechanism involved in the control of general stress response in C. crescentus.

  17. Analysis on Relevant Risk Factors of Pseudomembranous Coliitis%伪膜性肠炎的相关危险因素研究



    Objective To investigate the risk factors of pseudomembranous colitis, so as to increase awareness of the disease and to develop targeted preventive measures. Methods A retrospective analysis was conducted of clinical data of 56 patients with pseudomembranous colitis diagnosed in our hospital from January 2009 to December 2010. Another 60 patients with non - pseudomembranous colitis were recruited as control group. A self - designed questionnaire survey was conducted among the subjects in both groups, including the age, sex, basic chronic disease, application of immunosuppressant, number of hospitalized day, intestinal surgery history, history of non - intestinal surgery, application of enteral nutrition, clean enema, cathartics , and antibiotics type and time of antibiotics application. The univariate analysis ( x2 test) was used to screen the relevant factors of pseudomembranous colitis. And multi - variable ( conditional Logistic regression ) analysis was used to determine the main risk factors of the disease. Results Univariate analysis showed that a statistically significant difference between the two groups in nine aspects of age, application of immunosuppressants, number of hospitalized day, intestinal surgery history, application of enteral nutrition, clean enema, cathartics, antibiotics types ≥3 , and antibiotic usage time ≥10 days ( P < 0. 05 ); Multiple conditional factors ( Logistic regression ) analysis showed that the age, application of immunosuppressants, number of hospitalized day, usage of clean enema, application of cathartics, antibiotics types ≥3 and antibiotics ≥10 days were the risk factors, being closely related to pseudomembranous colitis. Conclusion The pseudomembranous colitis related with many factors , so through the reasonable use of antibiotics, strengthen the monitoring in elderly patients, early enteral nutrition can people reduce the occurrence of false membranous enteritis.%目的 探讨伪膜性肠炎发生的相关危

  18. DNA polymorphisms and haplotype patterns of transcription factors involved in barley endosperm development are associated with key agronomic traits

    Stracke Silke


    genes only explained a minor part of the total genetic variation although they are known to be important factors influencing the expression of seed quality traits. Therefore, we assume that grain quality as well as plant height and flowering time are influenced by many factors each contributing a small part to the expression of the phenotype. A genome-wide association analysis could provide a more comprehensive picture of loci involved in the regulation of grain quality, thousand grain weight and the other agronomic traits that were analyzed in this study. However, despite available high-throughput genotyping arrays the marker density along the barely genome is still insufficient to cover all associations in a whole genome scan. Therefore, the candidate gene-based approach will further play an important role in barley association studies.

  19. DNA polymorphisms and haplotype patterns of transcription factors involved in barley endosperm development are associated with key agronomic traits


    selection on the nucleotide sequence of the four candidate loci. Despite significant associations, the analysed candidate genes only explained a minor part of the total genetic variation although they are known to be important factors influencing the expression of seed quality traits. Therefore, we assume that grain quality as well as plant height and flowering time are influenced by many factors each contributing a small part to the expression of the phenotype. A genome-wide association analysis could provide a more comprehensive picture of loci involved in the regulation of grain quality, thousand grain weight and the other agronomic traits that were analyzed in this study. However, despite available high-throughput genotyping arrays the marker density along the barely genome is still insufficient to cover all associations in a whole genome scan. Therefore, the candidate gene-based approach will further play an important role in barley association studies. PMID:20064201

  20. Transfer students in STEM majors at a Midwestern University: Academic and social involvement factors that influence student success

    Lopez, Carlos

    There is soon-to-be a shortage of qualified U.S. workers in science, technology, engineering, and mathematics (STEM). As a result, many science-related jobs are being filled by technically-skilled foreign workers. If the U.S wants to maintain its global economic leadership, then it must ensure a continuous growth of highly-trained individuals in STEM disciplines. Therefore, American institutions of higher education, including community colleges, must identify potential factors that contribute to the lack of interest in STEM majors, as well as the low rate of success of students who enter STEM majors but struggle to finish their degrees. The purpose of this study was to ascertain the perceptions of community college transfer students who are pursuing bachelor degrees in STEM majors at Iowa State University (ISU). What were their transfer experiences and what influenced their academic success in STEM. Participants were encouraged to share their transfer experiences while at the community college as well as their experiences on the ISU campus. They were also asked about their level of academic involvement, their relationships with faculty, and their participation in peer group activities prior to and after transferring. The research design included both quantitative and qualitative components, which provided an in-depth look at the experiences of STEM non-engineering and engineering students. Quantitative data include students' background characteristics, demographic information, and college activities at the community college and ISU. Qualitative data were used to illuminate students' overall transfer experience and their successful journey in STEM fields. The combination of quantitative and qualitative methods allowed a better understanding of the strategies students put into practice once they transfer from a community college to a four-year institution in pursuit of a STEM bachelor's degree. The results of this study suggest that there is an association among the

  1. Involvement of Krüppel-like factor 6 (KLF6) mutation in the development of nonpolypoid colorectal carcinoma


    AIM: To examine Krüppel-like factor 6 (KLF6) mutations in nonpolypoid-type tumors and alterations of K-ras, p53,and B-raf in relation between mutation and morphologic type, particularly nonpolypoid-type colorectal carcinomas.METHODS: Fifty-five early nonpolypoid colorectal carcinomas were analyzed. Loss of heterozygosity (LOH) of KLF6 and p53 was determined by microsatellite assay.Mutations of KLF6, K-ras, and B-raf were examined by polymerase chain reaction-single-strand conformation polymorphism followed by direct sequencing. In LOH-positive and/or mutation-positive tumors, multiple (4-7) samples in each tumor were microdissected and examined for genetic alterations, p53 expression was evaluated by immunohistochemistry.RESULTS: LOH of KLF6 and p53 was found in 14 of 29 (48.3%) and 14 of 31 (45.2%) tumors, respectively. In 10 of the 14 (71.4%) KLF6 LOH-positive tumors and 9 of the 14 (64.3%) p53 LOH-positive tumors, LOH was found in all of the microdissected samples. In 1 of the 10 (10.0%) KLF6 LOH-positive tumors, a single missense mutation was identified. K-ras and B-raf mutations were found in 5 of 55 (9.1%) and 6 of 55 (10.9%) tumors,respectively. However, these mutations were detected only in subsets of microdissected tumor samples.CONCLUSION: These data suggest that KLF6 and p53 mutations are involved in the development of nonpolypoid colorectal carcinoma, whereas K-ras and B-raf mutations are not.

  2. Global analysis of WRKY transcription factor superfamily in Setaria identifies potential candidates involved in abiotic stress signalling

    Mehanathan eMuthamilarasan


    Full Text Available Transcription factors (TFs are major players in stress signalling and constitute an integral part of signalling networks. Among the major TFs, WRKY proteins play pivotal roles in regulation of transcriptional reprogramming associated with stress responses. In view of this, genome- and transcriptome-wide identification of WRKY TF family was performed in the C4 model plants, Setaria italica (SiWRKY and S. viridis (SvWRKY, respectively. The study identified 105 SiWRKY and 44 SvWRKY proteins that were computationally analysed for their physicochemical properties. Sequence alignment and phylogenetic analysis classified these proteins into three major groups, namely I, II and III with majority of WRKY proteins belonging to group II (53 SiWRKY and 23 SvWRKY, followed by group III (39 SiWRKY and 11 SvWRKY and group I (10 SiWRKY and 6 SvWRKY. Group II proteins were further classified into 5 subgroups (IIa to IIe based on their phylogeny. Domain analysis showed the presence of WRKY motif and zinc finger-like structures in these proteins along with additional domains in a few proteins. All SiWRKY genes were physically mapped on the S. italica genome and their duplication analysis revealed that 10 and 8 gene pairs underwent tandem and segmental duplications, respectively. Comparative mapping of SiWRKY and SvWRKY genes in related C4 panicoid genomes demonstrated the orthologous relationships between these genomes. In silico expression analysis of SiWRKY and SvWRKY genes showed their differential expression patterns in different tissues and stress conditions. Expression profiling of candidate SiWRKY genes in response to stress (dehydration and salinity and hormone treatments (abscisic acid, salicylic acid and methyl jasmonate suggested the putative involvement of SiWRKY066 and SiWRKY082 in stress and hormone signalling. These genes could be potential candidates for further characterization to delineate their functional roles in abiotic stress signalling.

  3. Fibroblast growth factors 7 and 10 are involved in ameloblastoma proliferation via the mitogen-activated protein kinase pathway.

    Nakao, Yu; Mitsuyasu, Takeshi; Kawano, Shintaro; Nakamura, Norifumi; Kanda, Shiori; Nakamura, Seiji


    Ameloblastoma is an epithelial benign tumor of the odontogenic apparatus and its growth mechanisms are not well understood. Fibroblast growth factor (FGF) 3, FGF7 and FGF10, which are expressed by the neural crest-derived ectomesenchymal cells, induce the proliferation of odontogenic epithelial cells during tooth development. Therefore, we examined the expression and function of these FGFs in ameloblastoma. We examined 32 cases of ameloblastoma as well as AM-1 cells (an ameloblastoma cell line) and studied the expression of FGF3, FGF7, FGF10 and their specific receptors, namely, FGF receptor (FGFR) 1 and FGFR2. Proliferation, mitogen-activated protein kinase (MAPK) signaling and PI3K signaling were examined in AM-1 cells after the addition of FGF7, FGF10 and these neutralizing antibodies. The expression of FGF7, FGF10, FGFR1 and FGFR2 was detected in ameloblastoma cells and AM-1 cells, while that of FGF3 was not. FGF7 and FGF10 stimulated AM-1 cell proliferation and phosphorylation of p44/42 MAPK. However, Akt was not phosphorylated. Blocking the p44/42 MAPK pathway by using a specific mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor (U0126) completely neutralized the effects of FGF7 and FGF10 on AM-1 cell proliferation. However, Anti FGF7 and FGF10 neutralizing antibodies did not decrease cell proliferation and MAPK phosphorylation of AM-1 cells. These results suggested that FGF7 and FGF10 are involved in the proliferation of ameloblastoma cells through the MAPK pathway.

  4. Characterization of three Arabidopsis AP2/EREBP family transcription factors involved in ABA sensitivity,freeze and salt tolerance

    MEI WenQian; LEI Juan; Xu Yu; WEI Gang; ZHU YuXian


    AP2/EREBP transcription factors (TFs) play very important roles in plant development,hormonal regulation and stress response. Upon genome-wide cDNA cloning,phylogenetic and expression pattern analyses of this plant specific TF family,we found that three of the members including At1g71450,At1g50680 and At5g13910,were likely involved in responses to ABA,cold and salt. Complementary DNAs containing putative full-length ORFs of these three TFs were obtained and fused individually to the GAL4 DNA-binding domains. All the 3 genes functioned effectively as trans-activators using yeast one-hybrid assays. RT-PCR experiments showed that the At1g71450 gene was induced by ABA and low temperature; the At1g50680 gene was responsive to quite a few stress conditions,but especially to freezing temperature; and the At5g13910 gene was induced by high salt treatment,drought and ethylene. By searching the ABRC T-DNA insertion mutant stocks,we obtained knockout lines for these TFs. Homozygous ko1 (At1g71450) plants showed a hypersensitive response to ABA during seed germination and also in stomata movement. Homozygous ko2 (At1g50680) plants showed a significant reduction in plant freezing tolerance compared to the wild type after chilling treatment. Homozygous ko3 (At5g13910) were less tolerant to high salinity than wild type plants. Our data suggest that At1g71450 is a negative regulator in ABA signaling,while At1g50680 and At5g13910 are positive regulators in cold and salt stress responses,respectively.

  5. Identification and transcript profiles of citrus growth-regulating factor genes involved in the regulation of leaf and fruit development.

    Liu, Xiao; Guo, Ling-Xia; Jin, Long-Fei; Liu, Yong-Zhong; Liu, Tao; Fan, Yu-Hua; Peng, Shu-Ang


    Growth-regulating factor (GRF) is an important protein in GA-mediated response, with key roles in plant growth and development. However, it is not known whether or how the GRF proteins in citrus to regulate organ size. In this study, nine citrus GRF genes (CsGRF1-9) were validated from the 'Anliu' sweet orange (AL, Citrus sinensis cv. Anliu) by PCR amplification. They all contain two conserved motifs (QLQ and WRC) and have 3-4 exons. The transcript levels of genes were detected by qRT-PCR. Transcript analysis showed that (1) CsGRF 1, 2, 5, 6, 7, and 9 expressed predominantly in young leaf, CsGRF 3 and 4 expressed predominantly in fruit immature juice sacs and CsGRF 8 expressed predominantly in root; (2) all citrus GRF genes had significantly higher expression in young leaves than mature leaf; (3) in juice sacs, the transcript levels of CsGRF1, 4, 5, 6, and 8 increased significantly while the transcript levels of CsGRF2, 3, 7, and 9 had no significant change from 80 DAF to 100 DAF. Besides, GA3 treatment did not affect the transcript levels of CsGRF5 and CsGRF6 but significantly increased the transcript levels of the other seven CsGRF genes in young leaves. These results suggested that all CsGRF genes involve in the leaf development, CsGRF1, 4, 5, 6, and 8 act developmentally whilst CsGRF2, 3, 7, and 9 play fundamental roles in fruit cell enlargement, which may be through GA pathway or GA-independent pathway.

  6. A Grapevine TTG2-Like WRKY Transcription Factor Is Involved in Regulating Vacuolar Transport and Flavonoid Biosynthesis

    Amato, Alessandra; Cavallini, Erika; Zenoni, Sara; Finezzo, Laura; Begheldo, Maura; Ruperti, Benedetto; Tornielli, Giovanni Battista


    A small set of TTG2-like homolog proteins from different species belonging to the WRKY family of transcription factors were shown to share a similar mechanism of action and to control partially conserved biochemical/developmental processes in their native species. In particular, by activating P-ATPases residing on the tonoplast, PH3 from Petunia hybrida promotes vacuolar acidification in petal epidermal cells whereas TTG2 from Arabidopsis thaliana enables the accumulation of proanthocyanidins in the seed coat. In this work we functionally characterized VvWRKY26 identified as the closest grapevine homolog of PhPH3 and AtTTG2. When constitutively expressed in petunia ph3 mutant, VvWRKY26 can fulfill the PH3 function in the regulation of vacuolar pH and restores the wild type pigmentation phenotype. By a global correlation analysis of gene expression and by transient over-expression in Vitis vinifera, we showed transcriptomic relationships of VvWRKY26 with many genes related to vacuolar acidification and transport in grapevine. Moreover, our results indicate an involvement in flavonoid pathway possibly restricted to the control of proanthocyanidin biosynthesis that is consistent with its expression pattern in grape berry tissues. Overall, the results show that, in addition to regulative mechanisms and biological roles shared with TTG2-like orthologs, VvWRKY26 can play roles in fleshy fruit development that have not been previously reported in studies from dry fruit species. This study paves the way toward the comprehension of the regulatory network controlling vacuolar acidification and flavonoid accumulation mechanisms that contribute to the final berry quality traits in grapevine. PMID:28105033

  7. Involvement of brain-derived neurotrophic factor and neurogenesis in oestradiol neuroprotection of the hippocampus of hypertensive rats.

    Pietranera, L; Lima, A; Roig, P; De Nicola, A F


    The hippocampus of spontaneously hypertensive rats (SHR) and deoxycorticosterone (DOCA)-salt hypertensive rats shows decreased cell proliferation and astrogliosis as well as a reduced number of hilar cells. These defects are corrected after administration of 17β-oestradiol (E(2) ) for 2 weeks. The present work investigated whether E(2) treatment of SHR and of hypertensive DOCA-salt male rats modulated the expression of brain-derived neurotrophic factor (BDNF), a neurotrophin involved in hippocampal neurogenesis. The neurogenic response to E(2) was simultaneously determined by counting the number of doublecortin-immunopositive immature neurones in the subgranular zone of the dentate gyrus. Both hypertensive models showed decreased expression of BDNF mRNA in the granular zone of the dentate gyrus, without changes in CA1 or CA3 pyramidal cell layers, decreased BDNF protein levels in whole hippocampal tissue, low density of doublecortin (DCX)-positive immature neurones in the subgranule zone and decreased length of DCX+ neurites in the dentate gyrus. After s.c. implantation of a single E(2) pellet for 2 weeks, BDNF mRNA in the dentate gyrus, BDNF protein in whole hippocampus, DCX immunopositive cells and the length of DCX+ neurites were significantly raised in both SHR and DOCA-salt-treated rats. These results indicate that: (i) low BDNF expression and deficient neurogenesis distinguished the hippocampus of SHR and DOCA-salt hypertensive rats and (ii) E(2) was able to normalise these biologically important functions in the hippocampus of hypertensive animals.

  8. Identification and characterization of wheat drought-responsive MYB transcription factors involved in the regulation of cuticle biosynthesis

    Bi, Huihui; Luang, Sukanya; Li, Yuan; Bazanova, Natalia; Morran, Sarah; Song, Zhihong; Perera, M. Ann; Hrmova, Maria; Borisjuk, Nikolai; Lopato, Sergiy


    A plant cuticle forms a hydrophobic layer covering plant organs, and plays an important role in plant development and protection from environmental stresses. We examined epicuticular structure, composition, and a MYB-based regulatory network in two Australian wheat cultivars, RAC875 and Kukri, with contrasting cuticle appearance (glaucousness) and drought tolerance. Metabolomics and microscopic analyses of epicuticular waxes revealed that the content of β-diketones was the major compositional and structural difference between RAC875 and Kukri. The content of β-diketones remained the same while those of alkanes and primary alcohols were increased by drought in both cultivars, suggesting that the interplay of all components rather than a single one defines the difference in drought tolerance between cultivars. Six wheat genes encoding MYB transcription factors (TFs) were cloned; four of them were regulated in flag leaves of both cultivars by rapid dehydration and/or slowly developing cyclic drought. The involvement of selected MYB TFs in the regulation of cuticle biosynthesis was confirmed by a transient expression assay in wheat cell culture, using the promoters of wheat genes encoding cuticle biosynthesis-related enzymes and the SHINE1 (SHN1) TF. Two functional MYB-responsive elements, specifically recognized by TaMYB74 but not by other MYB TFs, were localized in the TdSHN1 promoter. Protein structural determinants underlying the binding specificity of TaMYB74 for functional DNA cis-elements were defined, using 3D protein molecular modelling. A scheme, linking drought-induced expression of the investigated TFs with downstream genes that participate in the synthesis of cuticle components, is proposed. PMID:27489236

  9. Mental Health Status and Relevant Factors of the Patients with Hepatitis B%乙肝患者心理健康状况及有关因素的调查

    梁秀娥; 任秋芸


    Objective:To study the the mental health and relevant factors of patients with hepatitis B. Methods: 58 cases of patients with hepatitis B were assessed with the Social Support Scale, Symptom Checklist-90 (SCL-90), Trait Coping Questionnaire and compared with healthy person. Results: All patients had obvious psychosomatic symptoms. The mental health level was negatively correlated with postive coping style and social support. Conclusion: Several psychosocial factors played an important role in the onset and trealment of Hepatitis B disease.

  10. Exploring factors relevant in the assessment of the return-to-work process of employees on long-term sickness absence due to a depressive disorder: a focus group study

    Muijzer Anna


    Full Text Available Abstract Background Efforts undertaken during the Return-to-Work (RTW process need to be sufficient in order to optimize the quality of the RTW process. The purpose of this study was to explore factors relevant to Return-to-Work Effort Sufficiency (RTW-ES in cases of sick-listed employees with a Depressive Disorder (DD. Method A case of a long-term sick-listed employee with a DD applying for disability benefits was used to gather arguments and grounds relevant to the assessment of RTW-ES. Two focus group meetings were held, consisting of Labor Experts working at the Dutch Social Insurance Institute. Factors were collected and categorized using the International Classification of Functioning, Disability and Health (ICF model. Results Sixteen factors relevant to RTW-ES assessment in a case of DD were found, categorized in the ICF-model under activities (e.g. functional capacity, personal (e.g. competencies, attitude and environmental domain (e.g. employer-employee relationship, or categorized under interventions, job accommodations and measures. Conclusions This study shows that 16 factors are relevant in the assessment of RTW-ES in employees sick-listed due to DD. Further research is necessary to expand this knowledge to other health conditions, and to investigate the impact of these results on the quality of the RTW-ES assessment.

  11. Identifying factors relevant in the assessment of return-to-work efforts in employees on long-term sickness absence due to chronic low back pain : a focus group study

    Muijzer, Anna; Geertzen, Jan H.; de Boer, Wout E.; Groothoff, Johan W.; Brouwer, Sandra


    Background: Efforts undertaken during the return to work (RTW) process need to be sufficient to prevent unnecessary applications for disability benefits. The purpose of this study was to identify factors relevant to RTW Effort Sufficiency (RTW-ES) in cases of sick-listed employees with chronic low b

  12. The Role of the Val66Met Polymorphism of the Brain Derived Neurotrophic Factor Gene in Coping Strategies Relevant to Depressive Symptoms.

    Warren Caldwell

    Full Text Available Disturbances of brain derived neurotrophic factor (BDNF signalling have been implicated in the evolution of depression, which likely arises, in part, as a result of diminished synaptic plasticity. Predictably, given stressor involvement in depression, BDNF is affected by recent stressors as well as stressors such as neglect experienced in early life. The effects of early life maltreatment in altering BDNF signalling may be particularly apparent among those individuals with specific BDNF polymorphisms. We examined whether polymorphisms of the Val66Met genotype might be influential in moderating how early-life events play out with respect to later coping styles, cognitive flexibility and depressive features. Among male and female undergraduate students (N = 124, childhood neglect was highly related to subsequent depressive symptoms. This outcome was moderated by the BDNF polymorphism in the sense that depressive symptoms appeared higher in Met carriers who reported low levels of neglect than in those with the Val/Val allele. However, under conditions of high neglect depressive symptoms only increased in the Val/Val individuals. In effect, the Met polymorphism was associated with depressive features, but did not interact with early life neglect in predicting later depressive features. It was further observed that among the Val/Val individuals, the relationship between neglect and depression was mediated by emotion-focused styles and diminished perceived control, whereas this mediation was not apparent in Met carriers. In contrast to the more typical view regarding this polymorphism, the data are consistent with the perspective that in the presence of synaptic plasticity presumably associated with the Val/Val genotype, neglect allows for the emergence of specific appraisal and coping styles, which are tied to depression. In the case of the reduced degree of neuroplasticity expected in the Met carriers, early life adverse experiences are not tied

  13. Involvement in Bullying among Children with Autism Spectrum Disorders: Parents' Perspectives on the Influence of School Factors

    Zablotsky, Benjamin; Bradshaw, Catherine P.; Anderson, Connie; Law, Paul


    Children with developmental disabilities are at an increased risk for involvement in bullying, and children with autism spectrum disorders (ASDs) may be at particular risk because of challenges with social skills and difficulty maintaining friendships, yet there has been little empirical research on involvement in bullying among children with ASD.…

  14. The rice eukaryotic translation initiation factor 3 subunit f (OseIF3f is involved in microgametogenesis

    Qi eLi


    Full Text Available Microgametogenesis is the postmeiotic pollen developmental phase when unicellular microspores develop into mature tricellular pollen. In rice, microgametogenesis can influence grain yields to a great degree because pollen abortion occurs more easily during microgametogenesis than during other stages of pollen development. However, our knowledge of the genes involved in microgametogenesis in rice remains limited. Due to the dependence of pollen development on the regulatory mechanisms of protein expression, we identified the encoding gene of the eukaryotic translation initiation factor 3, subunit f in Oryza sativa (OseIF3f. Immunoprecipitation combined with mass spectrometry confirmed that OseIF3f was a subunit of rice eIF3, which consisted of at least 12 subunits including eIF3a, eIF3b, eIF3c, eIF3d, eIF3e, eIF3f, eIF3g, eIF3h, eIF3i, eIF3k, eIF3l and eIF3m. OseIF3f showed high mRNA levels in immature florets and is highly abundant in developing anthers. Subcellular localization analysis showed that OseIF3f was localized to the cytosol and the endoplasmic reticulum in rice root cells. We further analyzed the biological function of OseIF3f using the double-stranded RNA-mediated interference (RNAi approach. The OseIF3f-RNAi lines grew normally at the vegetative stage but displayed a large reduction in seed production and pollen viability, which is associated with the down-regulation of OseIF3f. Further cytological observations of pollen development revealed that the OseIF3f-RNAi lines showed no obvious abnormalities at the male meiotic stage and the unicellular microspore stage. However, compared to the wild type, OseIF3f-RNAi lines contained a higher percentage of arrested unicellular pollen at the bicellular stage and a higher percentage of arrested unicellular and bicellular pollen, and aborted pollen at the tricellular stage. These results indicate that OseIF3f plays a role in microgametogenesis.

  15. Evidences for involvement of growth hormone and insulin-like growth factor in ovarian development of starry flounder (Platichthys stellatus).

    Xu, Yongjiang; Wang, Bin; Liu, Xuezhou; Shi, Bao; Zang, Kun


    Although gonadotrophins are major regulators of ovarian function in teleosts and other vertebrates, accumulating evidence indicates that the growth hormone (GH)-insulin-like growth factor (IGF) axis also plays an important role in fish reproduction. As a first step to understand the physiological role of the GH-IGF system in the ovarian development of starry flounder (Platichthys stellatus), the expression profiles of GH and IGF messenger RNAs (mRNAs) and plasma GH, IGF-I, estradiol-17β (E2), and testosterone (T) levels during the ovarian development were investigated. The developmental stages of ovaries were divided into five stages (II, III, IV, V, and VI) by histological analysis. The hepatosomatic index (HSI) and gonadosomatic index (GSI) values increased and peaked at stage IV and stage V, respectively, and then declined at stage VI. Pituitary GH mRNA levels decreased sharply at stage III and raised to top level at stage VI. The hepatic IGF-I mRNA levels ascended to maximum value at stage V and then declined significantly at stage VI. However, the hepatic IGF-II mRNA levels remained stable and increased significantly at stage VI. In contrast, the ovarian IGF-I mRNA levels increased gradually and peaked at stage VI. The ovarian IGF-II mRNA levels were initially stable and increased significantly at stage V until the top level at stage VI. Consistent with the pituitary GH mRNA levels, plasma GH levels reduced sharply at stage III and remained depressed until stage V and then raised remarkably at stage VI. Plasma IGF-I level peaked at stage V and then declined to initial level. Plasma E2 level peaked at stage IV and then dramatically descended to the basal level. Plasma T level peaked at stage V and then declined significantly back to the basal level. Based on statistical analysis, significant positive correlations between hepatic IGF-I mRNA and GSI, ovarian IGF-II mRNA and hepatic IGF-II mRNA, ovarian IGF-I mRNA and ovarian IGF-II mRNA, and plasma IGF-I and


    Ilinca Ilona


    Full Text Available Aim – this study consists in the constructing of a tridimensional musculoskeletal model for the attack hit and the quantification of mechanical stress, in order to prevent traumatism in the knee joint.Goal: Minimizing the risk of patellar tendonitis through prophylactic exercises that improve the muscular pattern.Material and methods. This study was conducted for a 9 month period on the feminine batch pertaining to the volley team of the Sport Club “Universities Craiova”. For this research we used the AMTI MSA 6 force platformand the software application “Anybody”. By using the force platform AMTI MSA 6 it became possible todetermine the reaction force of the ground according to the position of the centre of gravity at the time of the jumping and landing, after executing an attack hit. The software “Anybody” allowed the 3D musculoskeletal modelling and the calculation of the forces of the muscles involved, prior and after the application of theprophylactic exercises.Conclusions. The improvement of the values of muscular forces demonstrates the efficiency of the prophylactic exercises: for the quadriceps femoris we obtain an increase of 13,79%, for gastrocnemius 14,76%, for hamstring muscles a value of 14%, for rectus femoris 15,06% and for the gluteus major 14,63%.For the entire experimental batch, at the moment of jumping, there was a reduction of the compression force by38,48% for the dominant inferior limb, by 34,06% for the non-dominant inferior limb.At the moment of landing, there was a difference of 38,51% for the dominant limb and a difference of 28,82% for the non-dominant limb. By analyzing the evolution of compression forces, after Z, at the level of knee joint, after the application of prophylactic program. We find a decreasing of pressure forces by a better distribution of this force for the entire inferior limb joint, decreasing in this way the risk of trauma production by overtraining.Key words - risk factors

  17. Analyses prognostic factors relevant to sudden sensorineural hearing loss%突发性聋预后相关因素分析

    王军; 肖水芳; 曾镇罡; 甄甄; 张雪溪; 林枫; 董明敏; 卢伟; 秦兆冰


    目的 探讨突发性聋预后的相关因素.方法 采用国际通用的标准化临床研究方法,统一设计、统一方案进行前瞻性临床多中心研究.2007年8月至2011年10月全国33家医院共收集符合入组条件(年龄在18 ~ 65周岁之间,病程在2周以内,未经任何相关医疗处理)的单侧突发性聋患者1 024例,其中男性492例(48.05%),女性532例(51.95%);年龄为19 ~ 65岁,平均(41.2±12.8)岁.将患者按照听力曲线分为低中频下降型、中高频下降型、平坦下降型和全聋型四种类型并分别给予相应治疗.分析发病年龄、发病时间、听力下降程度、听力下降特点等因素对听力预后的影响.结果 各种类型突发性聋药物治疗的总有效率:低中频下降型最高,为90.73%;平坦下降型次之,为82.59%;全聋型为70.29%;中高频下降型为65.96%;各型之间总有效率比较,差异具有统计学意义(x2 =231.58,P=0.000).痊愈患者的平均年龄为(39.0±12.4)岁;显效患者的平均年龄为(40.8±12.9)岁;有效患者的平均年龄为(43.2±12.7)岁;无效患者的平均年龄为(43.5±13.2)岁;不同疗效患者之间平均年龄比较,差异具有统计学意义(F=8.08,P=0.000).从发病到开始接受治疗的时间,痊愈患者平均为(3.0±2.4)d,显效患者为(3.7±3.0)d,有效患者为(3.9±3.4)d,无效患者为(4.2±3.6)d;不同疗效患者之间比较,差异具有统计学意义(F=5.33,P=0.001).全频下降型(平坦下降型与全聋型)中治疗前平均听阈> 80 dBHL者痊愈率低(15.36%)、无效率高(26.68%).结论 不同听力曲线类型的突发性聋患者预后差异较大,低中频下降型疗效最好,平坦下降型次之,中高频下降型和全聋型效果不佳.发病年龄越轻,预后越好;发病后越早接受治疗,预后越好.听力下降程度重者,预后差.%Objective To investigate the prognostic factors relevant to sudden sensorineural hearing loss.Methods The internationally accepted

  18. Chronobiology: relevance for tuberculosis.

    Santos, Lígia Gabrielle; Pires, Gabriel Natan; Azeredo Bittencourt, Lia Rita; Tufik, Sergio; Andersen, Monica Levy


    Despite the knowledge concerning the pathogenesis of tuberculosis, this disease remains one of the most important causes of mortality worldwide. Several risk factors are well-known, such poverty, HIV infection, and poor nutrition, among others. However, some issues that may influence tuberculosis warrant further investigation. In particular, the chronobiological aspects related to tuberculosis have garnered limited attention. In general, the interface between tuberculosis and chronobiology is manifested in four ways: variations in vitamin D bioavailability, winter conditions, associated infections, and circannual oscillations of lymphocytes activity. Moreover, tuberculosis is related to the following chronobiological factors: seasonality, latitude, photoperiod and radiation. Despite the relevance of these topics, the relationship between them has been weakly reviewed. This review aims to synthesize the studies regarding the association between tuberculosis and chronobiology, as well as urge critical discussion and highlight its applicability to health policies for tuberculosis.

  19. Enhancement of pulmonary tumour seeding by human coagulation factors II, IX, X--an investigation into the possible mechanisms involved.

    Purushotham, A D; McCulloch, P; George, W D


    Warfarin inhibits metastasis in the animal model and injection of the Warfarin-dependent coagulation factor complex II, IX, X enhances pulmonary metastasis in the same model. We have studied two possible mechanisms responsible for the observed effect. Mtln3, rat mammary carcinoma cells, radiolabelled with 5-(125) Iodo-2'-deoxyuridine (IUDR) were injected intravenously in female Fisher 344 rats either alone or in combination with factor complex II, IX, X or bovine serum albumin. Following sacrifice at various intervals, measured lung radioactivity was significantly higher (20%) in animals administered cells with the factor complex than in the other two groups (P less than 0.001, ANOVA and Student's t-test). These results indicate increased entrapment of tumour cells in the pulmonary