WorldWideScience

Sample records for psychosocial mechanisms involved

  1. Psychosocial impact of involvement in the Special Olympics.

    Science.gov (United States)

    Crawford, Clare; Burns, Jan; Fernie, Bruce A

    2015-01-01

    Existing evidence suggests that people with intellectual disabilities are vulnerable to low self-esteem leading to additional psychosocial issues such as social exclusion and stress. Previous research into the involvement of Special Olympics (SO) of people with intellectual disabilities has indicted positive psychosocial outcomes. Involvement in sport is known generally to have psychological and social benefits. This study aimed to compare the psychosocial impact of involvement in sport through the SO to no or limited sports involvement, for a sample of people with intellectual disabilities. A cross sectional design was employed comparing three groups, SO, Mencap Sports, and Mencap No Sports on the variables: Self-esteem, quality of life, stress levels and social networks. One hundred and one participants were recruited either through the SO or Mencap. Data were collected through the completion of validated questionnaires by one to one interviews with the participants. Analysis revealed that self-esteem, quality of life, and stress were all significantly associated with SO involvement. Logistic regression analysis was used to explore whether scores on these variables were able to predict group membership. Self-esteem was found to be a significant predictor of group membership, those in the SO having the highest self-esteem. The findings provide further evidence of a positive association between sport involvement and increased psychological wellbeing, especially for those involved in the SO. The implications of these findings for practice and future research into the relationship between sport and psychological wellbeing within the learning disabled population are considered.

  2. Unravelling psychosis: psychosocial epidemiology, mechanism, and meaning.

    Science.gov (United States)

    Bebbington, Paul

    2015-04-25

    This paper reviews a revolution in our understanding of psychosis over the last 20 years. To a major extent, this has resulted from a process of cross-fertilization between psychosocial epidemiology and cognitive behavior therapy for psychosis (CBT-p). This encouraged complementary strategies for the acquisition and analysis of data. These include the use of a range of dependent variables related to psychosis, and the exploitation of data from cross-sectional and longitudinal epidemiological surveys, virtual reality experiments, experience sampling methodology, and treatment trials. The key element is to investigate social and psychological measures in relation to each other. This research has confirmed the role of the external social world in the development and persistence of psychotic disorder. In addition, several psychological drivers of psychotic experiences have been identified. There is now persuasive evidence that the influence of social factors in psychosis is significantly mediated by non-psychotic symptoms, particularly mood symptoms and other attributes of affect such as insomnia. Psychotic symptoms are also driven by reasoning biases such as jumping to conclusions and belief inflexibility, though little is known about social influences on such biases. It is now clear that there are many routes to psychosis and that it takes many forms. Treatment of all kinds should take account of this: the dependence of CBT-p on a detailed initial formulation in terms of psychological processes and social influences is an example of the required flexibility. Individual mediators are now being targeted in specific forms of CBT-p, with good effect. This in turn corroborates the hypothesized role of non-psychotic symptoms in mediation, and attests to the power of the approaches described.

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

    Science.gov (United States)

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

    2013-01-01

    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-…

  4. Psychosocial stress in pregnancy and preterm birth: associations and mechanisms.

    Science.gov (United States)

    Shapiro, Gabriel D; Fraser, William D; Frasch, Martin G; Séguin, Jean R

    2013-11-01

    Psychosocial stress during pregnancy (PSP) is a risk factor of growing interest in the etiology of preterm birth (PTB). This literature review assesses the published evidence concerning the association between PSP and PTB, highlighting established and hypothesized physiological pathways mediating this association. The PubMed and Web of Science databases were searched using the keywords "psychosocial stress", "pregnancy", "pregnancy stress", "preterm", "preterm birth", "gestational age", "anxiety", and "social support". After applying the exclusion criteria, the search produced 107 articles. The association of PSP with PTB varied according to the dimensions and timing of PSP. Stronger associations were generally found in early pregnancy, and most studies demonstrating positive results found moderate effect sizes, with risk ratios between 1.2 and 2.1. Subjective perception of stress and pregnancy-related anxiety appeared to be the stress measures most closely associated with PTB. Potential physiological pathways identified included behavioral, infectious, neuroinflammatory, and neuroendocrine mechanisms. Future research should examine the biological pathways of these different psychosocial stress dimensions and at multiple time points across pregnancy. Culture-independent characterization of the vaginal microbiome and noninvasive monitoring of cholinergic activity represent two exciting frontiers in this research.

  5. High School Drinker Typologies Predict Alcohol Involvement and Psychosocial Adjustment during Acclimation to College

    Science.gov (United States)

    Hersh, Matthew A.; Hussong, Andrea M.

    2006-01-01

    This study examined differences among distinct types of high school drinkers on their alcohol involvement and psychosocial adjustment during the first semester of college. Participants were 147 college freshmen (66% female; 86% Caucasian) from a large Southeastern public university who reported on high school drinking and college stress, affect,…

  6. Psychosocial health and well-being among obstetricians and midwives involved in traumatic childbirth

    DEFF Research Database (Denmark)

    Schrøder, Katja; Larsen, Pia Veldt; Jørgensen, Jan Stener

    2016-01-01

    Objective this study investigates the self-reported psychosocial health and well-being of obstetricians and midwives in Denmark during the most recent four weeks as well as their recall of their health and well-being immediately following their exposure to a traumatic childbirth. Material...... and methods a 2012 national survey of all Danish obstetricians and midwives (n=2098). The response rate was 59% of which 85% (n=1027) stated that they had been involved in a traumatic childbirth. The psychosocial health and well-being of the participants was investigated using six scales from the Copenhagen...... Psychosocial Questionnaire (COPSOQII). Responses were assessed on six scales: burnout, sleep disorders, general stress, depressive symptoms, somatic stress and cognitive stress. Associations between COPSOQII scales and participant characteristics were analysed using linear regression. Results midwives reported...

  7. Parental involvement in primary school education and children's academic and psychosocial development in Hong Kong

    OpenAIRE

    Wong, Sze-man; 黃思敏

    2015-01-01

    Researchers recognize the importance of parental practices at home and in school for children’s education. However, its effects on children’s psychosocial wellbeing remain unclear. Moreover, a majority of the extant literature focuses on western school-aged children. Cultural influences on parenting beliefs and strategies may give rise to different effects of parental involvement on academic performance and wellbeing among students in the Chinese culture. There is also a scant body of literat...

  8. Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis

    NARCIS (Netherlands)

    Beijers, R.; Buitelaar, J.K.; Weerth, C. de

    2014-01-01

    Accumulating evidence from preclinical and clinical studies indicates that maternal psychosocial stress and anxiety during pregnancy adversely affect child outcomes. However, knowledge on the possible mechanisms underlying these relations is limited. In the present paper, we review the most often

  9. Translating Patient Involvement into Clinical Practice: An Example from Psychosocial Cancer Rehabilitation in Denmark

    DEFF Research Database (Denmark)

    Ledderer, Loni; Nissen, Nina

    We examine meanings and practices of patient involvement, using a psychosocial cancer rehabilitation intervention in Denmark as an example. Drawing on Scandinavian sociological institutionalism and the concepts of translation and editing, we analyse three contexts in which understandings and inte......We examine meanings and practices of patient involvement, using a psychosocial cancer rehabilitation intervention in Denmark as an example. Drawing on Scandinavian sociological institutionalism and the concepts of translation and editing, we analyse three contexts in which understandings...... and intentions of patient involvement underlying the rehabilitation intervention are formed and translated: a call for research proposals; the design of a research study; and its implementation in clinical practice. Our analysis reveals diversity, fluidity and changing understandings and practices of ‘patient...... involvement’ as the concept is translated from one context into another. The emerging understandings and practices, we argue, are informed by the various actors’ perspectives and experiences, normative assumptions about healthcare behaviour, social and organisational routines and structures of the healthcare...

  10. Psychosocial Mechanisms Linking the Social Environment to Mental Health in African Americans.

    Directory of Open Access Journals (Sweden)

    Scherezade K Mama

    Full Text Available Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467 completed questionnaires on the social environment, psychosocial factors (stress, depressive symptoms, and racial discrimination, and mental health. Multiple-mediator models were used to assess direct and indirect effects of the social environment on mental health. Low social status in the community (p < .001 and U.S. (p < .001 and low social support (p < .001 were associated with poor mental health. Psychosocial factors significantly jointly mediated the relationship between the social environment and mental health in multiple-mediator models. Low social status and social support were associated with greater perceived stress, depressive symptoms, and perceived racial discrimination, which were associated with poor mental health. Results suggest the relationship between the social environment and mental health is mediated by psychosocial factors and revealed potential mechanisms through which social status and social support influence the mental health of African American men and women. Findings from this study provide insight into the differential effects of stress, depression and discrimination on mental health. Ecological approaches that aim to improve the social environment and psychosocial mediators may enhance health-related quality of life and reduce health disparities in African Americans.

  11. Growing up with adversity: From juvenile justice involvement to criminal persistence and psychosocial problems in young adulthood.

    Science.gov (United States)

    Basto-Pereira, Miguel; Miranda, Ana; Ribeiro, Sofia; Maia, Ângela

    2016-12-01

    Several studies have been carried out to investigate the effect of child maltreatment on juvenile justice involvement and future criminal life. However, little is known about the impact of other forms of adversity, beyond abuse and neglect, on juvenile delinquency and criminal persistence. The effect of early adversity on psychosocial problems is underexplored, particularly in juvenile delinquents. This study, using the Childhood Adverse Experiences (ACE) questionnaire, a tool accessing the exposure to different types of abuse, neglect and serious household dysfunction, explored the role of each adverse experience on juvenile justice involvement, persistence in crime and psychosocial problems during young adulthood. A Portuguese sample of 75 young adults with official records of juvenile delinquency in 2010/2011, and 240 young adults from a community sample completed ACE questionnaire and measures of psychosocial adjustment. Seven out of ten adverse experiences were significantly more prevalent in young adults with juvenile justice involvement than in the community sample, after matching the main demographic variables. The strongest predictor of juvenile justice involvement and criminal persistence during early adulthood was sexual abuse. Dimensions of child/adolescent emotional maltreatment and a mental illness in the household predicted a set of psychosocial problems in young adulthood. This study indicates that early adversity is significantly related to juvenile justice involvement, criminal persistence and psychosocial problems. This study also suggests that each experience has a different role in this process. There is an urgent need to screen, prevent and stop serious adversity. Future scientific directions and recommendations for policies are provided. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis

    NARCIS (Netherlands)

    Beijers, R.; Buitelaar, J.K.; Weerth, C. de

    2014-01-01

    Accumulating evidence from preclinical and clinical studies indicates that maternal psychosocial stress and anxiety during pregnancy adversely affect child outcomes. However, knowledge on the possible mechanisms underlying these relations is limited. In the present paper, we review the most often pr

  13. Why Does ADHD Confer Risk for Cigarette Smoking? A Review of Psychosocial Mechanisms

    Science.gov (United States)

    Glass, Kerrie; Flory, Kate

    2010-01-01

    Research has documented that adolescents and young adults with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for cigarette smoking, but less attention has examined why this risk exists. The current paper reviews the literature on different psychosocial mechanisms [self-medication hypothesis, social factors (social modeling,…

  14. Why Does ADHD Confer Risk for Cigarette Smoking? A Review of Psychosocial Mechanisms

    Science.gov (United States)

    Glass, Kerrie; Flory, Kate

    2010-01-01

    Research has documented that adolescents and young adults with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for cigarette smoking, but less attention has examined why this risk exists. The current paper reviews the literature on different psychosocial mechanisms [self-medication hypothesis, social factors (social modeling,…

  15. Internet Addiction and Psychosocial Maladjustment: Avoidant Coping and Coping Inflexibility as Psychological Mechanisms.

    Science.gov (United States)

    Cheng, Cecilia; Sun, Peizhen; Mak, Kwok-Kei

    2015-09-01

    This 6 month prospective study systematically tested some multivariate models that advanced the understanding of the psychological mechanisms underlying Internet addiction and psychosocial maladjustment. On the basis of previous theories, avoidant coping and coping inflexibility were proposed as underlying mechanisms. Participants were 271 Chinese undergraduates (75% women, Mage=20.49) who took part in both phases of this study. Structural equation modeling was performed to obtain the best fit models for both the cross-sectional and the prospective data. The cross-sectional model testing revealed statistically significant mediating effects for both avoidant coping (β=0.149 [95% CI 0.071-0.226], p=0.002) and coping flexibility (β=0.048 [95% CI 0.013-0.081], p=0.032). The prospective model testing further showed that avoidant coping mediated the relationship between Internet addiction and Time 2 psychosocial maladjustment (β=0.141 [95% CI 0.065-0.216], p=0.005), as well as that between coping flexibility and Time 2 psychosocial maladjustment (β=-0.096 [95% CI -0.161 to -0.031], p=0.015). This study was the first to establish theory-driven models, which unveiled an inflexible, avoidant coping style as psychological mechanisms that explained the link between Internet addiction and psychosocial maladjustment.

  16. Psychosocial Mechanisms Linking the Social Environment to Mental Health in African Americans.

    Science.gov (United States)

    Mama, Scherezade K; Li, Yisheng; Basen-Engquist, Karen; Lee, Rebecca E; Thompson, Deborah; Wetter, David W; Nguyen, Nga T; Reitzel, Lorraine R; McNeill, Lorna H

    2016-01-01

    Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467) completed questionnaires on the social environment, psychosocial factors (stress, depressive symptoms, and racial discrimination), and mental health. Multiple-mediator models were used to assess direct and indirect effects of the social environment on mental health. Low social status in the community (p discrimination, which were associated with poor mental health. Results suggest the relationship between the social environment and mental health is mediated by psychosocial factors and revealed potential mechanisms through which social status and social support influence the mental health of African American men and women. Findings from this study provide insight into the differential effects of stress, depression and discrimination on mental health. Ecological approaches that aim to improve the social environment and psychosocial mediators may enhance health-related quality of life and reduce health disparities in African Americans.

  17. PARTNER INVOLVEMENT: NEGOTIATING THE PRESENCE OF PARTNERS IN PSYCHOSOCIAL ASSESSMENT AS CONDUCTED BY MIDWIVES AND CHILD AND FAMILY HEALTH NURSES.

    Science.gov (United States)

    Rollans, Mellanie; Kohlhoff, Jane; Meade, Tanya; Kemp, Lynn; Schmied, Virginia

    2016-05-01

    Universal screening for maternal depression and assessment of psychosocial risks has been integrated into the routine perinatal care provided in many Australian hospitals, but to date, partners/fathers have been largely excluded from the process. This study explored the ways in which clinicians in health service settings include partners who attend antenatal and postnatal visits with women. Qualitative data were collected using observations (n = 54), interviews (n = 60), and discussion groups (n = 7) with midwives and child and family health nurses who conducted the appointments. Transcripts from observations, interviews, and discussion groups underwent qualitative analysis, and key themes were identified. Results showed partners to have little or no involvement in psychosocial assessment and depression screening. Thematic analysis revealed four key themes: negotiating partner exclusion, partial inclusion, women's business or a couple concern? and they know anyway. Partner involvement appeared to be challenged particularly by mandatory interpersonal violence screening, which, according to health service policy, is to be conducted confidentially. Overall, results highlighted partner involvement in perinatal depression screening and psychosocial assessment processes and identified some of the benefits such as partner disclosure, but also the challenges and complexities of inclusion of partners. Clinical implications and directions for further education and research are discussed. © 2016 Michigan Association for Infant Mental Health.

  18. Racial/Ethnic Disparities in Men's Health: Examining Psychosocial Mechanisms.

    Science.gov (United States)

    Brown, Tyson H; Hargrove, Taylor W; Griffith, Derek M

    2015-01-01

    This study uses data from the Health and Retirement Study and an approach informed by the Biopsychosocial Model of Racism as a Stressor to examine the extent to which socioeconomic status, stressors, discrimination, and neighborhood conditions are mechanisms underlying racial/ethnic disparities in functional limitations among men. Results reveal that racial/ethnic differences in socioeconomic status, stressors, discrimination, and neighborhood conditions-individually and collectively-account for a substantial proportion of racial/ethnic disparities in functional limitations. Findings suggest that the social determinants of health for men of color need to be more seriously considered in investigations of and efforts to address health disparities.

  19. Neurophysiological mechanisms involved in auditory perceptual organization

    Directory of Open Access Journals (Sweden)

    Aurélie Bidet-Caulet

    2009-09-01

    Full Text Available In our complex acoustic environment, we are confronted with a mixture of sounds produced by several simultaneous sources. However, we rarely perceive these sounds as incomprehensible noise. Our brain uses perceptual organization processes to independently follow the emission of each sound source over time. If the acoustic properties exploited in these processes are well-established, the neurophysiological mechanisms involved in auditory scene analysis have raised interest only recently. Here, we review the studies investigating these mechanisms using electrophysiological recordings from the cochlear nucleus to the auditory cortex, in animals and humans. Their findings reveal that basic mechanisms such as frequency selectivity, forward suppression and multi-second habituation shape the automatic brain responses to sounds in a way that can account for several important characteristics of perceptual organization of both simultaneous and successive sounds. One challenging question remains unresolved: how are the resulting activity patterns integrated to yield the corresponding conscious perceptsµ

  20. Major regulatory mechanisms involved in sperm motility.

    Science.gov (United States)

    Pereira, Rute; Sá, Rosália; Barros, Alberto; Sousa, Mário

    2017-01-01

    The genetic bases and molecular mechanisms involved in the assembly and function of the flagellum components as well as in the regulation of the flagellar movement are not fully understood, especially in humans. There are several causes for sperm immotility, of which some can be avoided and corrected, whereas other are related to genetic defects and deserve full investigation to give a diagnosis to patients. This review was performed after an extensive literature search on the online databases PubMed, ScienceDirect, and Web of Science. Here, we review the involvement of regulatory pathways responsible for sperm motility, indicating possible causes for sperm immotility. These included the calcium pathway, the cAMP-dependent protein kinase pathway, the importance of kinases and phosphatases, the function of reactive oxygen species, and how the regulation of cell volume and osmolarity are also fundamental components. We then discuss main gene defects associated with specific morphological abnormalities. Finally, we slightly discuss some preventive and treatments approaches to avoid development of conditions that are associated with unspecified sperm immotility. We believe that in the near future, with the development of more powerful techniques, the genetic causes of sperm immotility and the regulatory mechanisms of sperm motility will be better understand, thus enabling to perform a full diagnosis and uncover new therapies.

  1. Parenting as a Mechanism of Change in Psychosocial Treatment for Youth with ADHD, Predominantly Inattentive Presentation.

    Science.gov (United States)

    Haack, Lauren M; Villodas, Miguel; McBurnett, Keith; Hinshaw, Stephen; Pfiffner, Linda J

    2016-09-15

    We investigated whether parenting and child behavior improve following psychosocial treatment for Attention-Deficit/Hyperactivity Disorder, Predominantly Inattentive Presentation (ADHD-I) and whether parenting improvements mediate child outcomes. We analyzed data from a randomized clinical trial investigating the efficacy of a multicomponent psychosocial intervention (Child Life and Attention Skills, CLAS, n = 74) in comparison to Parent-Focused Treatment (PFT, n = 74) and treatment as usual (TAU, n = 51) for youth with ADHD-I (average child age = 8.6 years, range 7-11 years, 58 % boys). Child and parent/family functioning were assessed prior to treatment, immediately following treatment, and at follow-up into the subsequent school year using parent and teacher reports of inattention, organization, social skills, academic competency (teachers only), parenting daily hassles, and positive and negative parenting behaviors (parents only). Both treatment groups improved on negative parenting and home impairment, but only CLAS families also improved on positive parenting as well as academic impairment. Improvements in positive and negative parenting mediated treatment effects on child impairment independent of improvements in child inattention, implicating parenting as an important mechanism of change in psychosocial treatment for ADHD-I. Further, whereas parent-focused training produces improvements in negative parenting and impairment at home for children with ADHD-I, a multicomponent approach (incorporating child skills training and teacher consultation) more consistently produces improvements at school and in positive parenting, which may contribute to improvements in social skills into the next school year.

  2. Psychosocial experiences of breast cancer survivors involved in a dragon boat program: exploring links to positive psychological growth.

    Science.gov (United States)

    Sabiston, Catherine M; McDonough, Meghan H; Crocker, Peter R E

    2007-08-01

    This study explored psychosocial experiences of breast cancer survivors involved in dragon boat programs. Twenty women (M(age) = 58.69, SD = 6.85) were interviewed for 45-60 min about their experiences as members of survivor dragon boat teams. Interviews were analyzed using constructivist grounded theory methods. The dragon boat program facilitated social support from women with common challenges and a shared understanding of survivorship. It also provided opportunities to (re)gain a sense of personal control, develop new identities as athletes, and overcome physical challenges. Together these elements contributed to positive psychological growth and linked to the literature on posttraumatic growth. Future physical activity interventions targeting breast cancer survivors may benefit from developing strategies that share key characteristics of dragon boating.

  3. A matter of timing: developmental theories of romantic involvement and psychosocial adjustment.

    Science.gov (United States)

    Furman, Wyndol; Collibee, Charlene

    2014-11-01

    The present study compared two theories of the association between romantic involvement and adjustment: a social timetable theory and a developmental task theory. We examined seven waves of longitudinal data on a community based sample of 200 participants (Wave 1 mean age = 15 years, 10 months). In each wave, multiple measures of substance use, externalizing symptoms, and internalizing symptoms were gathered, typically from multiple reporters. Multilevel modeling revealed that greater levels of romantic involvement in adolescence were associated with higher levels of substance use and externalizing symptoms but became associated with lower levels in adulthood. Having a romantic partner was associated with greater levels of substance use, externalizing symptoms, and internalizing symptoms in adolescence but was associated with lower levels in young adulthood. The findings were not consistent with a social timetable theory, which predicts that nonnormative involvement is associated with poor adjustment. Instead, the findings are consistent with a developmental task theory, which predicts that precocious romantic involvement undermines development and adaptation, but when romantic involvement becomes a salient developmental task in adulthood, it is associated with positive adjustment. Discussion focuses on the processes that may underlie the changing nature of the association between romantic involvement and adjustment.

  4. Patterns of Romantic Involvement among Emerging Adults: Psychosocial Correlates and Precursors

    Science.gov (United States)

    Shulman, Shmuel; Scharf, Miri; Livne, Yaara; Barr, Tamuz

    2013-01-01

    The present study examined patterns of romantic involvement in 100 Israeli emerging adults (54 males) who were followed from age 22 to 29 years. Analyses of interviews at age 29 yielded four distinctive relational patterns that are associated with different levels of concurrent wellbeing: Intimately committed, Intimate, Non- intimately committed,…

  5. Feasibility of a Psychosocial Rehabilitation Intervention to Enhance the Involvement of Relatives in Cancer Rehabilitation: Pilot Study for a Randomized Controlled Trial

    DEFF Research Database (Denmark)

    Ledderer, Loni; la Cour, Karen; Mogensen, Ole

    2013-01-01

    Background Cancer often affects the quality of life and well-being of patients as well as their relatives. Previous studies have suggested that relatives should be involved in psychosocial rehabilitation to address the needs for an interpersonal relationship with others in the disease trajectory...

  6. Racial-Ethnic Protective Factors and Mechanisms in Psychosocial Prevention and Intervention Programs for Black Youth.

    Science.gov (United States)

    Jones, Shawn C T; Neblett, Enrique W

    2016-06-01

    Extending previous reviews related to cultural responsiveness in the treatment of ethnic minority youth, the current review provides a critical assessment and synthesis of both basic and applied research on the integration of three racial-ethnic protective factors (racial identity, racial socialization, Africentric worldview) in psychosocial prevention and intervention programs for Black children and adolescents. Seventeen programs meeting inclusion and exclusion criteria were evaluated for the extent to which racial-ethnic protective factors and related mechanisms were integrated, applied, and tested in such programs. A systematic assessment of these programs revealed that several prevention and intervention programs drew upon the three factors, particularly Africentric worldview. In addition, a number of studies hypothesized and assessed mechanisms, both those previously identified in conceptual literature and those that emerged from the interventions themselves. A set of recommendations encouraging the implementation of these factors into future prevention and intervention programs, examples of how clinicians can infuse these factors into psychotherapy, and areas for future research are discussed.

  7. Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation

    DEFF Research Database (Denmark)

    Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

    2011-01-01

    the mechanisms involved in the age-related defective bone formation. Evidence Acquisition: The mechanisms discussed in this review are based on a PubMed search and knowledge of the authors in the field. Evidence Synthesis: Available basic and clinical studies indicate that multiple mechanisms are involved...

  8. Molecular mechanisms involved in intestinal iron absorption

    Institute of Scientific and Technical Information of China (English)

    Paul Sharp; Surjit Kaila Srai

    2007-01-01

    Iron is an essential trace metal in the human diet due to its obligate role in a number of metabolic processes.In the diet, iron is present in a number of different forms, generally described as haem (from haemoglobin and myoglobin in animal tissue) and non-haem iron (including ferric oxides and salts, ferritin and lactoferrin).This review describes the molecular mechanisms that co-ordinate the absorption of iron from the diet and its release into the circulation. While many components of the iron transport pathway have been elucidated, a number of key issues still remain to be resolved. Future work in this area will provide a clearer picture regarding the transcellular flux of iron and its regulation by dietary and humoral factors.

  9. Psychosocial factors involved in memory and cognitive failures in people with myalgic encephalomyelitis/chronic fatigue syndrome

    Directory of Open Access Journals (Sweden)

    Attree EA

    2014-02-01

    Full Text Available Elizabeth A Attree,1 Megan A Arroll,1 Christine P Dancey,1 Charlene Griffith,1 Amolak S Bansal1,2 1Chronic Illness Research Team, School of Psychology, University of East London, London, UK; 2Department of Immunology and the Sutton CFS Service, St Helier Hospital, Carshalton, UK Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS is characterized by persistent emotional, mental, and physical fatigue accompanied by a range of neurological, autonomic, neuroendocrine, immune, and sleep problems. Research has shown that psychosocial factors such as anxiety and depression as well as the symptoms of the illness, have a significant impact on the quality of life of people with ME/CFS. In addition, individuals may suffer from deficits in memory and concentration. This study set out to explore the relationships between variables which have been found to contribute to cognitive performance, as measured by prospective and retrospective memory, and cognitive failures. Methods: Eighty-seven people with ME/CFS answered questionnaires measuring fatigue, depression, anxiety, social support, and general self-efficacy. These were used in a correlational design (multiple regression to predict cognitive function (self-ratings on prospective and retrospective memory, and cognitive failures. Results: Our study found that fatigue, depression, and general self-efficacy were directly associated with cognitive failures and retrospective (but not prospective memory. Conclusion: Although it was not possible in this study to determine the cause of the deficits, the literature in this area leads us to suggest that although the pathophysiological mechanisms of ME/CFS are unclear, abnormalities in the immune system, including proinflammatory cytokines, can lead to significant impairments in cognition. We suggest that fatigue and depression may be a result of the neurobiological effects of ME/CFS and in addition, that the neurobiological effects of the illness

  10. Adolescent Bullying Involvement and Psychosocial Aspects of Family and School Life: A Cross-Sectional Study from Guangdong Province in China

    OpenAIRE

    Hui Wang; Xiaolan Zhou; Ciyong Lu; Jie Wu; Xueqing Deng; Lingyao Hong; Xue Gao; Yuan He

    2012-01-01

    BACKGROUND: School bullying is an emerging problem in China. The present study aimed to measure the prevalence of bullying behaviors among Chinese adolescents and to examine the association of bullying and being bullied with family factors, school factors and indicators of psychosocial adjustment. METHODS: A cross-sectional study was conducted. A total of 8,342 middle school students were surveyed in four cities in the Guangdong Province. Self-reports on bullying involvement and information r...

  11. Psychosocial Factors Involved in Transitions from College to Postcollege Careers for Male NCAA Division-1 Basketball Players

    Science.gov (United States)

    Cummins, Paul; O'Boyle, Ian

    2015-01-01

    This article investigated the key psychosocial factors that impact upon National Collegiate Athletic Association (NCAA) Division-1 male basketball players, as they transition from college to postcollege athletic or nonathletic careers. Participants (N = 9) were current/former NCAA Division-1 basketball players. Four participants were selected…

  12. Expressive Writing for Gay-Related Stress: Psychosocial Benefits and Mechanisms Underlying Improvement

    Science.gov (United States)

    Pachankis, John E.; Goldfried, Marvin R.

    2010-01-01

    Objective: This study tested the effectiveness of an expressive writing intervention for gay men on outcomes related to psychosocial functioning. Method: Seventy-seven gay male college students (mean age = 20.19 years, SD = 1.99) were randomly assigned to write for 20 min a day for 3 consecutive days about either (a) the most stressful or…

  13. Adolescent bullying involvement and psychosocial aspects of family and school life: a cross-sectional study from Guangdong Province in China.

    Directory of Open Access Journals (Sweden)

    Hui Wang

    Full Text Available BACKGROUND: School bullying is an emerging problem in China. The present study aimed to measure the prevalence of bullying behaviors among Chinese adolescents and to examine the association of bullying and being bullied with family factors, school factors and indicators of psychosocial adjustment. METHODS: A cross-sectional study was conducted. A total of 8,342 middle school students were surveyed in four cities in the Guangdong Province. Self-reports on bullying involvement and information regarding family factors, school factors and psychosocial adjustment were collected. Descriptive statistics and multi-level logistic regression analysis were used to evaluate the prevalence of school bullying and explore potentially influential factors. RESULTS: Of the total sample, 20.83% (1,738 reported being involved in bullying behaviors. Of the respondents, 18.99% were victims of bullying, 8.60% were bullies and 6.74% both bullied themselves and bullied others. Factors that were determined to be correlated with bullying behaviors included grade, parental caring, consideration of suicide, running away from home, time spent online per day and being in a physical fight. CONCLUSION: Bullying was determined to be prevalent among Chinese adolescents. Given the concurrent psychosocial adjustment, family and school factors associated with bullying, as well as the potential long-term negative outcomes for these youth, this issue merits serious attention, both for future research and preventive intervention.

  14. Educability, skills and parental involvement: a factorial analysis of teacher perception scale for families in psychosocial risk

    OpenAIRE

    Rodríguez Garcés, Carlos; Centro de Investigación CIDCIE de la Universidad del Bío-Bío, Chillán

    2016-01-01

    Through the scale “Perception Teaching for Families Experiencing Psychosocial Risk” applied to 175 teachers in training, conducted an exploratory factor analysis (EFA). The AFE, with an explained variance of 43.9%, reveals the existence of four factors or dimensions: Implications Parental Education, features personological Attributive, Parental Participation and Attribution Genealogical. The subsequent descriptive analysis reports that there is a tarnished image by teachers of vulnerable chil...

  15. A 2-year follow-up study of people with severe mental illness involved in psychosocial rehabilitation.

    Science.gov (United States)

    Svedberg, Petra; Svensson, Bengt; Hansson, Lars; Jormfeldt, Henrika

    2014-08-01

    BACKGROUNDS. A focus on psychiatric rehabilitation in order to support recovery among persons with severe mental illness (SMI) has been given great attention in research and mental health policy, but less impact on clinical practice. Despite the potential impact of psychiatric rehabilitation on health and wellbeing, there is a lack of research regarding the model called the Psychiatric Rehabilitation Approach from Boston University (BPR). The aim was to investigate the outcome of the BPR intervention regarding changes in life situation, use of healthcare services, quality of life, health, psychosocial functioning and empowerment. The study has a prospective longitudinal design and the setting was seven mental health services who worked with the BPR in the county of Halland in Sweden. In total, 71 clients completed the assessment at baseline and of these 49 completed the 2-year follow-up assessments. The most significant finding was an improved psychosocial functioning at the follow-up assessment. Furthermore, 65% of the clients reported that they had mainly or almost completely achieved their self-formulated rehabilitation goals at the 2-year follow-up. There were significant differences with regard to health, empowerment, quality of life and psychosocial functioning for those who reported that they had mainly/completely had achieved their self-formulated rehabilitation goals compared to those who reported that they only had to a small extent or not at all reached their goals. Our results indicate that the BPR approach has impact on clients' health, empowerment, quality of life and in particular concerning psychosocial functioning.

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

    Science.gov (United States)

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

    2013-07-01

    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.

  17. Community-based organisations for vulnerable children in South Africa: Reach, psychosocial correlates, and potential mechanisms.

    Science.gov (United States)

    Yakubovich, A R; Sherr, L; Cluver, L D; Skeen, S; Hensels, I S; Macedo, A; Tomlinson, M

    2016-03-01

    Community-based organisations (CBOs) have the potential to provide high quality services for orphaned and vulnerable children in resource-limited settings. However, evidence is lacking as to whether CBOs are reaching those who are most vulnerable, whether attending these organisations is associated with greater psychosocial wellbeing, and how they might work. This study addressed these three questions using cross-sectional data from 1848 South African children aged 9-13. Data were obtained from the Young Carers and Child Community Care studies, which both investigated child wellbeing in South Africa using standardised self-report measures. Children from the Child Community Care study were all CBO attenders, whereas children from Young Carers were not receiving any CBO services, thereby serving as a comparison group. Multivariable regression analyses were used to test whether children attending CBOs were more deprived on socio-demographic variables (e.g., housing), and whether CBO attendance was in turn associated with better psychosocial outcomes (e.g., child depression). Mediation analysis was conducted to test whether more positive home environments mediated the association between CBO attendance and significantly higher psychological wellbeing. Overall, children attending CBOs did show greater vulnerability on most socio-demographic variables. For example, compared to children not attending any CBO, CBO-attending children tended to live in more crowded households (OR 1.22) and have been exposed to more community violence (OR 2.06). Despite their heightened vulnerability, however, children attending CBOs tended to perform better on psychosocial measures: for instance, showing fewer depressive symptoms (B=-0.33) and lower odds of experiencing physical (OR 0.07) or emotional abuse (OR 0.22). Indirect effects of CBO attendance on significantly higher child psychological wellbeing (lower depressive symptoms) was observed via lower rates of child abuse (B=-0.07) and

  18. Hard Work in Soft Regulation: A Discussion of the Social Mechanisms in OHS Management Standards and Possible Dilemmas in the Regulation of Psychosocial Work Environment

    Directory of Open Access Journals (Sweden)

    Pernille Hohnen

    2014-09-01

    Full Text Available Certified occupational health and safety (OHS management systems have become a global instrument in regulation of the work environment. However, their actual impact on OHS—in particular on softer psychosocial issues in the work environment—has been questioned. The most important standard of OHS management is OHSAS 18001, which has recently been supplemented with a British publically available guideline (PAS 1010 focusing specifically on psychosocial risk management. On the basis of the international literature on management standards, the present paper analyses OHSAS 18001 and PAS 1010 in order to understand the mechanism by which they work. The paper takes a social constructionist approach conceptualizing standards and their expected mechanisms as socially constructed—based on a particular kind of knowledge and logic—although they are presented as objective. Such a constructionist approach also emphasizes how standards transform specific work environment problems into generic procedures that can be audited. In the case of OHS standards, both the work environment in general and the psychosocial risks in particular are transformed into simple monocausal auditable relations whereby the complexity of psychosocial work environment issues seems to disappear. The new PAS 1010 guideline, which is particularly focusing on regulation of the psychosocial work environment, only partly succeeds in solving these shortcomings of OHSAS 18001.

  19. Damage response involves mechanisms conserved across plants, animals and fungi.

    Science.gov (United States)

    Hernández-Oñate, M A; Herrera-Estrella, A

    2015-08-01

    All organisms are constantly exposed to adverse environmental conditions including mechanical damage, which may alter various physiological aspects of growth, development and reproduction. In plant and animal systems, the damage response mechanism has been widely studied. Both systems posses a conserved and sophisticated mechanism that in general is aimed at repairing and preventing future damage, and causes dramatic changes in their transcriptomes, proteomes, and metabolomes. These damage-induced changes are mediated by elaborate signaling networks, which include receptors/sensors, calcium (Ca(2+)) influx, ATP release, kinase cascades, reactive oxygen species (ROS), and oxylipin signaling pathways. In contrast, our current knowledge of how fungi respond to injury is limited, even though various reports indicate that mechanical damage triggers reproductive processes. In fungi, the damage response mechanism has been studied more in depth in Trichoderma atroviride. Interestingly, these studies indicate that the mechanical damage response involves ROS, Ca(2+), kinase cascades, and lipid signaling pathways. Here we compare the response to mechanical damage in plants, animals and fungi and provide evidence that they appear to share signaling molecules and pathways, suggesting evolutionary conservation across the three kingdoms.

  20. Impact of psychosocial stress on airway inflammation and its mechanism in a murine model of allergic asthma

    Institute of Scientific and Technical Information of China (English)

    LI Bei; DUAN Xiao-hong; WU Jin-feng; LIU Bao-jun; LUO Qing-li; JIN Hua-liang; DU Yi-jie

    2013-01-01

    Background It has already been recognized that psychosocial stress evokes asthma exacerbation; however,the mechanism of how stress gets inside the body is not clear.This study aimed to observe the impact of psychosocial stress on airway inflammation and its mechanism in the ovalbumin-induced asthmatic mice combined with social disruption stress.Methods Thirty-six male BALB/c mice were randomly divided into:control group,asthma group (ovalbumin-induced),asthma plus social disruption stress group (SDR),and SDR group.The open field video tracking system was used to assess animal behaviors.The invasive pulmonary resistance (RL) and dynamic lung compliance (cdyn) test system from Buxco was applied to detect pulmonary function.The enzyme-linked immunosorbent assay (ELISA) was utilized to determine OVA-IgE,T-helper type 2 (Th2) cytokines (IL-4,IL-5,IL-13) and corticosterone in mouse serum,the Th2 cytokines (IL-4,IL-5,IL-13,IL-6,TNF-α) in bronchoalveolar lavage fluid (BALF),and IL-6 and TNF-α levels in the supernatant of splenocytes cultured in vitro.Hematoxylin-eosin (H&E) staining was used to assess airway inflammation in lung histology.The cell count kit-8 assay (CCK-8) was applied to evaluate the inhibitory effect of corticosterone on splenocyte proliferation induced by lipopolysacchadde (LPS).Real time-PCR and Western blotting were utilized to determine glucocorticoid receptor (GR) mRNA and GR protein expression in lungs.Results The open field test showed that combined allergen exposure and repeated stress significantly shortened the time the mice spent in the center of the open field (P <0.01),increased ambulatory activity (P <0.01) and the count of fecal boli (P <0.01),but deceased vertical activity (P <0.01).Results from pulmonary function demonstrated that airway hyperresponsiveness (AHR) was enhanced by psychosocial stress compared with allergy exposure alone.The ELISA results showed that cytokines in serum and BALF were significantly increased (P <0

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

    Directory of Open Access Journals (Sweden)

    Rosa Muñoz-Cano

    2017-09-01

    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.

  2. Toward a More Complex Understanding of Acculturation and Adjustment: Cultural Involvements and Psychosocial Functioning in Vietnamese Youth.

    Science.gov (United States)

    Nguyen, Huong H.; Messe, Lawrence A.; Stollak, Gary E.

    1999-01-01

    Examines link between acculturation and adjustment in 182 Vietnamese youths living in an Anglo-American community. Results indicate involvement in U.S. culture predicts positive functioning on personal, interpersonal, and academic levels. Involvement in the Vietnamese culture predicts positive family relationships. (MMU)

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

    Science.gov (United States)

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

    2013-01-01

    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…

  4. Psychosocial stress and liver disease status

    Institute of Scientific and Technical Information of China (English)

    Cristin Constantin Vere; Costin Teodor Streba; Letitia Maria Streba; Alin Gabriel Ionescu; Felix Sima

    2009-01-01

    "Psychosocial stress" is an increasingly common concept in the challenging and highly-demanding modern society of today. Organic response to stress implicates two major components of the stress system,namely the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Stress is anamnestically reported by patients during the course of disease, usually accompanied by a decline in their overall health status. As the mechanisms involving glucocorticoids and catecholamines have been deciphered, and their actions on immune cell function deeper understood, it has become clear that stress has an impact on hepatic inflammatory response. An increasing number of articles have approached the link between psychosocial stress and the negative evolution of hepatic diseases. This article reviews a number of studies on both human populations and animal models performed in recent years, all linking stress, mainly of psychosocial nature, and the evolution of three important liver-related pathological entities: viral hepatitis, cirrhosis and hepatocellular carcinoma.

  5. Mechanisms Involved in Exercise-Induced Cardioprotection: A Systematic Review

    Science.gov (United States)

    Borges, Juliana Pereira; Lessa, Marcos Adriano

    2015-01-01

    Background Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate. Objective To perform a systematic review of the studies that have addressed the mechanisms by which aerobic exercise promotes direct cardioprotection against ischemia and reperfusion injury. Methods A search was conducted using MEDLINE, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde, and Scientific Electronic Library Online databases. Data were extracted in a standardized manner by two independent researchers, who were responsible for assessing the methodological quality of the studies. Results The search retrieved 78 studies; after evaluating the abstracts, 30 studies were excluded. The manuscripts of the remaining 48 studies were completely read and, of these, 20 were excluded. Finally, 28 studies were included in this systematic review. Conclusion On the basis of the selected studies, the following are potentially involved in the cardioprotective response to exercise: increased heat shock protein production, nitric oxide pathway involvement, increased cardiac antioxidant capacity, improvement in ATP-dependent potassium channel function, and opioid system activation. Despite all the previous investigations, further research is still necessary to obtain more consistent conclusions. PMID:25830711

  6. Mechanisms Involved in Exercise-Induced Cardioprotection: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Juliana Pereira Borges

    2015-01-01

    Full Text Available Background: Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate. Objective: To perform a systematic review of the studies that have addressed the mechanisms by which aerobic exercise promotes direct cardioprotection against ischemia and reperfusion injury. Methods: A search was conducted using MEDLINE, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde, and Scientific Electronic Library Online databases. Data were extracted in a standardized manner by two independent researchers, who were responsible for assessing the methodological quality of the studies. Results: The search retrieved 78 studies; after evaluating the abstracts, 30 studies were excluded. The manuscripts of the remaining 48 studies were completely read and, of these, 20 were excluded. Finally, 28 studies were included in this systematic review. Conclusion: On the basis of the selected studies, the following are potentially involved in the cardioprotective response to exercise: increased heat shock protein production, nitric oxide pathway involvement, increased cardiac antioxidant capacity, improvement in ATP-dependent potassium channel function, and opioid system activation. Despite all the previous investigations, further research is still necessary to obtain more consistent conclusions.

  7. [Ocular involvement in spondylarthritis--new mechanisms, new therapies].

    Science.gov (United States)

    Itulescu, T C M; Alexandrescu, Cristina; Voinea, Liliana-Mary

    2014-01-01

    Spondyloarthrites (SPA) represent a group of heterogenous rheumatic diseases (ankylosing spondylitis/SA, psoriatic arthritis/PsA, reactive arthritis/ReA, spondyloarthritis in bowel inflammatory diseases/BID, undifferentiated spondyloarthritis/undif SpA) with distinct clinical features and common genetic predisposition (HLA-B27). SpA may also affect other organs, ocular involvement, represented by uveitis and conjunctivitis, being one of the most important extraskeletal manifestations. Pathogenic mechanisms of ocular involment in SpA are not entirely known; nevertheless, the inflammatory process which characterizes the main rheumatic diseases seems to be responsible for this extraskeletal manifestation. SpA treatment targeted at clinical remission has a favourable effect not only on articular but also on ocular involvement. The discovery of new pathogenic mechanisms of both rheumatic and eye disease in SpA have contributed to identification of new pathogenic therapies. The interdisciplinary team work of rheumatologists and ophtalmologists have prove essential for the management of SpA patients with ocular manifestations.

  8. Potential psychosocial mechanisms linking depression to immune function in elderly subjects

    NARCIS (Netherlands)

    Bouhuys, AL; Flentge, F; Oldehinkel, AJ; van den Berg, MD

    2004-01-01

    Although depression and immune changes in elderly subjects constitute a considerable health risk, mechanisms underlying the association between depression and immune function are unclear. The question of whether personality and social support can explain the variation in immune function during depre

  9. Psychosocial mechanisms of the pain and quality of life relationship for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

    Science.gov (United States)

    Krsmanovic, Adrijana; Tripp, Dean A; Nickel, J Curtis; Shoskes, Daniel A; Pontari, Michel; Litwin, Mark S; McNaughton-Collins, Mary F

    2014-11-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent, chronic pelvic pain condition largely unresponsive to medical interventions. Psychosocial risk factors are associated with poor outcomes in CP/CPPS, but have not been examined for their intervening roles between pain and reduced quality of life (QoL). This study aimed to determine if psychosocial risk factors (i.e., patient coping and catastrophizing) mediate the association between pain and QoL. Using a cross sectional design, 175 men with CP/CPPS (mean age 46.83; SD 10.86) were recruited from tertiary care urology clinics and completed questionnaires on demographics, pain, QoL, pain coping, depression, and catastrophizing. An exploratory factor analysis was conducted and aggregate factor scores were examined to improve the amount of meaningful measurement to be used in multiple mediations. The models specified multiple risk factors as mechanisms between pain and both physical and mental QoL as the primary outcome measurements. Four aggregate psychosocial factor scores were produced from the psychosocial measures (i.e., illness and wellness-focused behavioural coping, depression and catastrophizing). Illness-focused coping partially mediated the relationship between pain and physical QoL. However, catastrophizing and illness-focused coping fully mediated the relation between pain and mental QoL, showing the association between pain and mental QoL was no longer significant when catastrophizing and illness-focused coping were in the model. Psychosocial factors function as mechanisms between higher pain and they are associated diminished mental QoL. These results introduce illness-focused coping as an important biopsychosocial target in CP/CPPS management.

  10. Psychosocial mechanisms of the pain and quality of life relationship for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)

    Science.gov (United States)

    Krsmanovic, Adrijana; Tripp, Dean A.; Nickel, J. Curtis; Shoskes, Daniel A.; Pontari, Michel; Litwin, Mark S.; McNaughton-Collins, Mary F.

    2014-01-01

    Introduction: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent, chronic pelvic pain condition largely unresponsive to medical interventions. Psychosocial risk factors are associated with poor outcomes in CP/CPPS, but have not been examined for their intervening roles between pain and reduced quality of life (QoL). This study aimed to determine if psychosocial risk factors (i.e., patient coping and catastrophizing) mediate the association between pain and QoL. Methods: Using a cross sectional design, 175 men with CP/CPPS (mean age 46.83; SD 10.86) were recruited from tertiary care urology clinics and completed questionnaires on demographics, pain, QoL, pain coping, depression, and catastrophizing. An exploratory factor analysis was conducted and aggregate factor scores were examined to improve the amount of meaningful measurement to be used in multiple mediations. The models specified multiple risk factors as mechanisms between pain and both physical and mental QoL as the primary outcome measurements. Results: Four aggregate psychosocial factor scores were produced from the psychosocial measures (i.e., illness and wellness-focused behavioural coping, depression and catastrophizing). Illness-focused coping partially mediated the relationship between pain and physical QoL. However, catastrophizing and illness-focused coping fully mediated the relation between pain and mental QoL, showing the association between pain and mental QoL was no longer significant when catastrophizing and illness-focused coping were in the model. Conclusion: Psychosocial factors function as mechanisms between higher pain and they are associated diminished mental QoL. These results introduce illness-focused coping as an important biopsychosocial target in CP/CPPS management. PMID:25553153

  11. Towards recovery-oriented psychosocial interventions for bipolar disorder: Quality of life outcomes, stage-sensitive treatments, and mindfulness mechanisms.

    Science.gov (United States)

    Murray, Greg; Leitan, Nuwan D; Thomas, Neil; Michalak, Erin E; Johnson, Sheri L; Jones, Steven; Perich, Tania; Berk, Lesley; Berk, Michael

    2017-03-01

    Current adjunctive psychosocial interventions for bipolar disorder (BD) aim to impact illness course via information sharing/skill development. This focus on clinical outcomes contrasts with the emergent recovery paradigm, which prioritises adaptation to serious mental illness and movement towards personally meaningful goals. The aim of this review is to encourage innovation in the psychological management of BD by considering three recovery-oriented trends in the literature. First, the importance of quality of life as a target of recovery-oriented clinical work is considered. Second, the recent staging approach to BD is described, and we outline implications for psychosocial interventions tailored to stage. Finally, we review evidence suggesting that mindfulness-based psychosocial interventions have potential across early, middle and late stages of BD. It is concluded that the humanistic emphasis of the recovery paradigm provides a timely stimulus for development of a next generation of psychosocial treatments for people with BD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Complement involvement in periodontitis: molecular mechanisms and rational therapeutic approaches

    Science.gov (United States)

    Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D.

    2015-01-01

    The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis. PMID:26306443

  13. Quantum-Mechanical Calculations on Molecular Substructures Involved in Nanosystems

    Directory of Open Access Journals (Sweden)

    Beata Szefler

    2014-09-01

    Full Text Available In this review article, four ideas are discussed: (a aromaticity of fullerenes patched with flowers of 6-and 8-membered rings, optimized at the HF and DFT levels of theory, in terms of HOMA and NICS criteria; (b polybenzene networks, from construction to energetic and vibrational spectra computations; (c quantum-mechanical calculations on the repeat units of various P-type crystal networks and (d construction and stability evaluation, at DFTB level of theory, of some exotic allotropes of diamond D5, involved in hyper-graphenes. The overall conclusion was that several of the yet hypothetical molecular nanostructures herein described are serious candidates to the status of real molecules.

  14. Cellular and Humoral Mechanisms Involved in the Control of Tuberculosis

    Directory of Open Access Journals (Sweden)

    Joaquin Zuñiga

    2012-01-01

    Full Text Available Mycobacterium tuberculosis (Mtb infection is a major international public health problem. One-third of the world's population is thought to have latent tuberculosis, a condition where individuals are infected by the intracellular bacteria without active disease but are at risk for reactivation, if their immune system fails. Here, we discuss the role of nonspecific inflammatory responses mediated by cytokines and chemokines induced by interaction of innate receptors expressed in macrophages and dendritic cells (DCs. We also review current information regarding the importance of several cytokines including IL-17/IL-23 in the development of protective cellular and antibody-mediated protective responses against Mtb and their influence in containment of the infection. Finally, in this paper, emphasis is placed on the mechanisms of failure of Mtb control, including the immune dysregulation induced by the treatment with biological drugs in different autoimmune diseases. Further functional studies, focused on the mechanisms involved in the early host-Mtb interactions and the interplay between host innate and acquired immunity against Mtb, may be helpful to improve the understanding of protective responses in the lung and in the development of novel therapeutic and prophylactic tools in TB.

  15. Mechanisms involved in BACE upregulation associated to stress.

    Science.gov (United States)

    Martisova, Eva; Solas, Maite; Gerenu, Gorka; Milagro, Fermin I; Campion, Javier; Ramirez, Maria J

    2012-09-01

    The objective of the present work was to study a purported involvement of stress in amyloid pathology through the modulation of BACE expression. Early-life stressed rats (maternal separation, MS) showed significant increases in corticosterone levels, BACE expression and Aβ levels. The CpG7 site of the BACE promoter was significantly hypomethylated in MS, and corticosterone levels negatively correlated to the methylation status of CpG7. The activation of the stress-activated protein kinase JNK was also increased in MS rats. In SHSY-5Y neuroblastoma cells, corticosterone induced a rapid increase in BACE expression that was abolished by specific inhibiton of JNK activation or by spironolactone, a mineralocorticoid receptor antagonist, but not by mifepristone, a glucocorticoid receptor antagonist. Corticosterone was also able to increase pJNK expression and this effect was fully reverted by spironolactone. Mice chronically treated with corticosterone showed increased BACE and pJNK expression. These increases were reverted by treatment with spironolactone or with a JNK inhibitor. It is suggested that increased corticosterone levels associated to stress lead to increase BACE transcription both through epigenetic mechanisms and activation of JNK.

  16. Molecular mechanisms involved in chemoresistance in paediatric acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Stanković Tatjana

    2008-01-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is the most common paediatric cancer. Despite cure rates approaching 80%, resistance to treatment and disease relapse remain a significant clinical problem. Identification of the genes and biological pathways responsible for chemoresistance is therefore crucial for the design of novel therapeutic approaches aiming to improve patient survival. Mutations in the membrane transporter P-glycoprotein genes, genetic variations in drug-metabolising enzymes and defects in apoptotic pathways are mechanisms of chemoresistance common to a wide spectrum of cancers and also play a role in paediatric ALL. In addition, several recent microarray studies have identified transcriptional profiles specifically associated with chemoresistance and pointed to a number of potentially novel therapeutic targets. These microarray studies have shown that genes discriminating between clinically responsive and resistant leukaemias tend to be involved in cellular processes such as regulation of cell cycle, proliferation, and DNA repair. Here we review the outcomes of these microarray studies and also present our own investigations into apoptotic resistance to DNA double strand breaks (DSBs in paediatric ALL. We present stratification of paediatric ALL by the profile of DNA damage response following ionising radiation (IR in vitro. This approach allows classification of ALL tumours at presentation into IR-apoptotic sensitive and IR-apoptotic resistant. Furthermore, apoptotic resistant leukaemias exhibit abnormal response of NFkB pathway following irradiation and inhibition of this pathway can sensitise leukaemic cells to IR-induced DSBs.

  17. MECHANISMS INVOLVED IN MYCORRHIZAL WHEAT PROTECTION AGAINST POWDERY MILDEW.

    Science.gov (United States)

    Mustafa, G; Tisserant, B; Randoux, B; Fontaine, J; Sahraoui, A Lounes-Hadj; Reignault, Ph

    2014-01-01

    In France, the Ecophyto 2018 national action plan will set out to reduce the use of pesticides by 50% by 2018, if possible. To achieve this goal, the use of arbuscular mycorrhizal (AM) fungi could be a potential alternative method allowing the control of crop diseases. The inoculation by AM fungi has been demonstrated to protect plants against soil-borne pathogens, but little is known about their effectiveness against aerial pathogens, such as the biotrophic fungus Blumeria graminis f.sp. tritici (Bgt) causing wheat (Triticum aestivum) powdery mildew. In the present study, wheat plants were grown in pots, under controlled conditions. Using various phosphorus (P) concentrations, the effectiveness of three AM inocula (Rhizophagus irregularis (Ri), Funneliformis mosseae (Fm)) and Solrize, a mixture of Ri and Fm) in Orvantis wheat cultivar, were tested. After 42 days of culture, mycorrhizal (M) and non-mycorrhizal (NM) wheat plants were infected by Bgt. A satisfactory mycorrhizal rate was obtained with the phosphorus concentration P/5 (P corresponding to the dose used in wheat fields in = 62 mg/L). Our work shows, for the first time, (i) a protective effect of AM inoculation against wheat powdery mildew, reaching up to 73% with Fm inocula, and (ii) its ability to induce a systemic resistance in wheat. Thereafter, we investigated mechanisms involved in this protection. Control plants, M plants, infected plants by Bgt, and M-infected plants were compared at: (i) cytological level, our results revealed that papillae and whole-fluorescent cells presence was induced, conversely fungal haustorium formation in epidermal cells was reduced within M plants leaves (ii) enzymatic level-by assessing defense enzyme activities (lipoxygenase, peroxidase) known as defense markers were measured 24, 48, 72 and 96 hours after infection (hai). The importance of these activities in the defense pathways induced in wheat by AM fungi will be discussed.

  18. MOLECULAR DISSECTION OF THE CELLULAR MECHANISMS INVOLVED IN NICKEL HYPERACCUMULATION

    Energy Technology Data Exchange (ETDEWEB)

    Salt, David E.

    2001-06-01

    Hyperaccumulator plant species are able to accumulate between 1-5% of their biomass as metal. However, these plants are often small, slow growing, and do not produce a high biomass. Phytoextraction, a cost-effective, in situ, plant based approach to soil remediation takes advantage of the remarkable ability of hyperaccumulating plants to concentrate metals from the soil and accumulate them in their harvestable, above-ground tissues (Salt et al., 1998). However, to make use of the valuable genetic resources identified in metal hyperaccumulating species, it will be necessary to transfer this material to high biomass rapidly growing crop plants (Persans and Salt (2000)). These plants would then be ideally suited to the phytoremediation process, having the ability to produce large amount of metal-rich plant biomass for rapid harvest and soil cleanup. Although progress is being made in understanding the genetic basis of metal hyperaccumulation (Salt and Krdmer, 1999) a more complete understanding will be necessary before we can take full advantage of the genetic potential of these plants. Research funds provided by the DOE EMSP (DE-FG07-98ER20295) have been used to start to uncover the genetic processes involved in the hyperaccumulation of Ni in Thlaspi goesingense. Our strategy has focused on isolating and characterizing the key genetic information needed for expression of the metal-hyperaccumulation phenotype. In the last reporting period we determined that nickel tolerance was the key difference between the hyperaccumulator T. goesingense and the non-accumulator Thlaspi arvense. We also established that this nickel tolerance was primarily due to an enhanced ability to compartmentalize Ni in the leaf cell vacuoles of the hyperaccumulator. During the 2000-2001 reporting period we have been investigating the molecular genetic mechanism of this enhanced vacuolar accumulation of Ni in the hyperaccumulator.

  19. Homing orientation in salamanders: A mechanism involving chemical cues

    Science.gov (United States)

    Madison, D. M.

    1972-01-01

    A detailed description is given of experiments made to determine the senses and chemical cues used by salamanders for homing orientation. Sensory impairment and cue manipulative techniques were used in the investigation. All experiments were carried out at night. Results show that sense impaired animals did not home as readily as those who were blind but retained their sensory mechanism. This fact suggests that the olfactory mechanism is necessary for homing in the salamander. It was determined that after the impaired salamander regenerated its sensory mechanism it too returned home. It was concluded that homing ability in salamanders is direction independent, distant dependent, and vision independent.

  20. Molecular mechanisms involved in Weibel-Palade body exocytosis

    NARCIS (Netherlands)

    van Hooren, K.W.E.M.

    2014-01-01

    Endothelial cells form the barrier between the circulating blood and the underlying tissue. Endothelial cells contain specialized organelles called Weibel-Palade bodies that contain proteins involved in blood coagulation and inflammatory processes. In this thesis we describe a studies unraveling the

  1. Mechanisms Involved in Nematode Control by Endophytic Fungi.

    Science.gov (United States)

    Schouten, Alexander

    2016-08-04

    Colonization of plants by particular endophytic fungi can provide plants with improved defenses toward nematodes. Evidently, such endophytes can be important in developing more sustainable agricultural practices. The mechanisms playing a role in this quantitative antagonism are poorly understood but most likely multifactorial. This knowledge gap obstructs the progress regarding the development of endophytes or endophyte-derived constituents into biocontrol agents. In part, this may be caused by the fact that endophytic fungi form a rather heterogeneous group. By combining the knowledge of the currently characterized antagonistic endophytic fungi and their effects on nematode behavior and biology with the knowledge of microbial competition and induced plant defenses, the various mechanisms by which this nematode antagonism operates or may operate are discussed. Now that new technologies are becoming available and more accessible, the currently unresolved mechanisms can be studied in greater detail than ever before.

  2. Mechanisms Involved in Nematode Control by Endophytic Fungi

    NARCIS (Netherlands)

    Schouten, Sander

    2016-01-01

    Colonization of plants by particular endophytic fungi can provide plants with improved defenses toward nematodes. Evidently, such endophytes can be important in developing more sustainable agricultural practices. The mechanisms playing a role in this quantitative antagonism are poorly understood

  3. General mechanism for helium blistering involving displaced atom transport

    Energy Technology Data Exchange (ETDEWEB)

    McDonell, W.R.

    1979-01-01

    A mechanism developed to account for formation of vertically elongated blisters in high displacement environments produced by /sup 252/Cf alpha particles and fission fragments has been extended to formation of done-shaped blisters in the low displacement environments produced by simple helium ion beams. In this mechanism, transport of displaced atoms to relieve compressive stresses in the helium-implanted layer allows interconnections of small, subsurface bubbles to form the blister cavity. The same transport may cause thickening of the blister caps at low implantation energies. The transition from dome-shaped to vertically elongated blistering occurs between the 300 and 3000 displacements per helium atom produced by simple helium ions and /sup 252/Cf radiations respectively.

  4. Molecular mechanisms involved in mammalian primary sex determination.

    Science.gov (United States)

    She, Zhen-Yu; Yang, Wan-Xi

    2014-08-01

    Sex determination refers to the developmental decision that directs the bipotential genital ridge to develop as a testis or an ovary. Genetic studies on mice and humans have led to crucial advances in understanding the molecular fundamentals of sex determination and the mutually antagonistic signaling pathway. In this review, we summarize the current molecular mechanisms of sex determination by focusing on the known critical sex determining genes and their related signaling pathways in mammalian vertebrates from mice to humans. We also discuss the underlying delicate balance between testis and ovary sex determination pathways, concentrating on the antagonisms between major sex determining genes.

  5. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements.

    Science.gov (United States)

    Liu, Pengfei; Erez, Ayelet; Nagamani, Sandesh C Sreenath; Dhar, Shweta U; Kołodziejska, Katarzyna E; Dharmadhikari, Avinash V; Cooper, M Lance; Wiszniewska, Joanna; Zhang, Feng; Withers, Marjorie A; Bacino, Carlos A; Campos-Acevedo, Luis Daniel; Delgado, Mauricio R; Freedenberg, Debra; Garnica, Adolfo; Grebe, Theresa A; Hernández-Almaguer, Dolores; Immken, LaDonna; Lalani, Seema R; McLean, Scott D; Northrup, Hope; Scaglia, Fernando; Strathearn, Lane; Trapane, Pamela; Kang, Sung-Hae L; Patel, Ankita; Cheung, Sau Wai; Hastings, P J; Stankiewicz, Paweł; Lupski, James R; Bi, Weimin

    2011-09-16

    Complex genomic rearrangements (CGRs) consisting of two or more breakpoint junctions have been observed in genomic disorders. Recently, a chromosome catastrophe phenomenon termed chromothripsis, in which numerous genomic rearrangements are apparently acquired in one single catastrophic event, was described in multiple cancers. Here, we show that constitutionally acquired CGRs share similarities with cancer chromothripsis. In the 17 CGR cases investigated, we observed localization and multiple copy number changes including deletions, duplications, and/or triplications, as well as extensive translocations and inversions. Genomic rearrangements involved varied in size and complexities; in one case, array comparative genomic hybridization revealed 18 copy number changes. Breakpoint sequencing identified characteristic features, including small templated insertions at breakpoints and microhomology at breakpoint junctions, which have been attributed to replicative processes. The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism's life cycle.

  6. [Growing up under adversity in Germany : Design and methods of a developmental study on risk and protective mechanisms in families with diverse psychosocial risk].

    Science.gov (United States)

    Zimmermann, Peter; Vierhaus, Marc; Eickhorst, Andreas; Sann, Alexandra; Egger, Carine; Förthner, Judith; Gerlach, Jennifer; Iwanski, Alexandra; Liel, Christoph; Podewski, Fritz; Wyrwich, Sandra; Spangler, Gottfried

    2016-10-01

    Family adversity comprises many risk factors for parents and children. The German early intervention approach Frühe Hilfen aims at providing enduring, effective, and scientifically validated prevention and intervention for effective child protection against those risks. The study on risk and protective mechanisms in the development of families with diverse psychosocial risks aims at identifying those mechanisms that cause and stabilize or moderate and diminish maltreatment and neglect, as well as cognitive, social, and emotional developmental deviations in risk families, specifically in the current German social and child protection system. The study examines the development of competence and early behavior problems in a sample of infants and toddlers and the interaction quality with their caregivers by applying a longitudinal sequential-cohort design. The assessments include developmental tests, systematic observations, and questionnaire data. First results suggest stable risk group membership and moderate stability of single risk factors.

  7. Kinetics and mechanisms of reactions involving small aromatic reactive intermediates

    Energy Technology Data Exchange (ETDEWEB)

    Lin, M.C. [Emory Univ., Atlanta, GA (United States)

    1993-12-01

    Small aromatic radicals such as C{sub 6}H{sub 5}, C{sub 6}H{sub 5}O and C{sub 6}H{sub 4} are key prototype species of their homologs. C{sub 6}H{sub 5} and its oxidation product, C{sub 6}H{sub 5}O are believed to be important intermediates which play a pivotal role in hydrocarbon combustion, particularly with regard to soot formation. Despite their fundamental importance, experimental data on the reaction mechanisms and reactivities of these species are very limited. For C{sub 6}H{sub 5}, most kinetic data except its reactions with NO and NO{sub 2}, were obtained by relative rate measurements. For C{sub 6}H{sub 5}O, the authors have earlier measured its fragmentation reaction producing C{sub 5}H{sub 5} + CO in shock waves. For C{sub 6}H{sub 4}, the only rate constant measured in the gas phase is its recombination rate at room temperature. The authors have proposed to investigate systematically the kinetics and mechanisms of this important class of molecules using two parallel laser diagnostic techniques--laser resonance absorption (LRA) and resonance enhanced multiphoton ionization mass spectrometry (REMPI/MS). In the past two years, study has been focused on the development of a new multipass adsorption technique--the {open_quotes}cavity-ring-down{close_quotes} technique for kinetic applications. The preliminary results of this study appear to be quite good and the sensitivity of the technique is at least comparable to that of the laser-induced fluorescence method.

  8. Moderate stress enhances memory persistence: are adrenergic mechanisms involved?

    Science.gov (United States)

    Parfitt, Gustavo Morrone; Barbosa, Ândrea Kraemer; Campos, Renan Costa; Koth, André Peres; Barros, Daniela Martí

    2012-10-01

    Memory persistence in the inhibitory avoidance (IA) task has been recently shown to require a new event of consolidation 12 hr after acquisition. The immobilization stress (IS) model is largely used to study the effects of stress on memory. In this study we investigated the interactions between stress by immobilization and its effect on the persistence of memory, and also a possible effect mediated by β-adrenergic modulation of stress on memory persistence. An enhancement of long-term memory (LTM) persistence caused by stress through immobilization applied 12 hr after IA training was observed when the animals were submitted to 15 min or 1 hr of IS, but not to 3 hr. The reversal of this memory enhancement caused by IS was observed when the β-adrenergic antagonist propranolol was infused intraperitoneally prior to stress, which implies that β-adrenergic receptors are involved in stress enhancement of LTM persistence. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  9. Mechanisms involved in alternariol-induced cell cycle arrest

    Energy Technology Data Exchange (ETDEWEB)

    Solhaug, A., E-mail: Anita.Solhaug@vetinst.no [Norwegian Veterinary Institute, Oslo (Norway); Vines, L.L. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Ivanova, L.; Spilsberg, B. [Norwegian Veterinary Institute, Oslo (Norway); Holme, J.A. [Norwegian Institute of Public Health, Division of Environmental Medicine, Oslo (Norway); Pestka, J. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Collins, A. [University of Oslo, Department of Nutrition, Faculty of Medicine, Oslo (Norway); Eriksen, G.S. [Norwegian Veterinary Institute, Oslo (Norway)

    2012-10-15

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, is often found as a contaminant in fruit and cereal products. Here we employed the murine macrophage cell line RAW 264.7 to test the hypothesis that AOH causes toxicity as a response to DNA damage. AOH at concentrations of 15-30 {mu}M almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 {mu}M) significantly increased the level of reactive oxygen species (ROS). Furthermore, DNA base oxidations as well as DNA strand breaks and/or alkaline labile sites were detected by the comet assay after 2 h exposure of AOH. Cell death (mostly necrosis) was observed after prolonged exposure to the highest concentration of AOH (60 {mu}M for 24 and 48 h) in our study. The DNA damage response involved phosphorylation (activation) of histone H2AX and check point kinase-1- and 2 (Chk-1/2). Moreover, AOH activated p53 and increased the expression of p21, Cyclin B, MDM2, and Sestrin 2; likewise the level of several miRNA was affected. AOH-induced Sestrin 2 expression was regulated by p53 and could at least partly be inhibited by antioxidants, suggesting a role of ROS in the response. Interestingly, the addition of antioxidants did not inhibit cell cycle arrest. Although the formation of ROS by itself was not directly linked cell proliferation, AOH-induced DNA damage and resulting transcriptional changes in p21, MDM2, and Cyclin B likely contribute to the reduced cell proliferation; while Sestrin 2 would contribute to the oxidant defense.

  10. Mechanism involved in enhancement of osteoblast differentiation by hyaluronic acid

    Energy Technology Data Exchange (ETDEWEB)

    Kawano, Michinao [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Ariyoshi, Wataru [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Iwanaga, Kenjiro [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Okinaga, Toshinori [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Habu, Manabu [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Yoshioka, Izumi [Division of Oral and Maxillofacial Surgery, Department of Medicine of Sensory and Motor Organs, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Tominaga, Kazuhiro [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, Kitakyushu 803-8580 (Japan)

    2011-02-25

    Research highlights: {yields} In this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. {yields} MG63 cells were incubated with BMP-2 and HA for various time periods. {yields} Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. {yields} HA enhanced BMP-2 induces osteoblastic differentiation in MG63 cells via down-regulation of BMP-2 antagonists and ERK phosphorylation. -- Abstract: Objectives: Bone morphogenetic protein-2 (BMP-2) is expected to be utilized to fill bone defects and promote healing of fractures. However, it is unable to generate an adequate clinical response for use in bone regeneration. Recently, it was reported that glycosaminoglycans, including heparin, heparan sulfate, keratan sulfate, dermatan sulfate, chondroitin-4-sulfate, chondroitin-6-sulfate, and hyaluronic acid (HA), regulate BMP-2 activity, though the mechanism by which HA regulates osteogenic activities has not been fully elucidated. The aim of this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. Materials and methods: Monolayer cultures of osteoblastic lineage MG63 cells were incubated with BMP-2 and HA for various time periods. To determine osteoblastic differentiation, alkaline phosphatase (ALP) activity in the cell lysates was quantified. Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by Western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. To further elucidate the role of HA in enhancement of BMP-2-induced Smad signaling, mRNA expressions of the BMP-2 receptor antagonists noggin and follistatin were detected using real-time RT-PCR. Results: BMP-2-induced ALP activation, Smad 1/5/8 phosphorylation, and

  11. Cross-sectional study showed psychosocial variables, gender and family involvement played an important role in an adolescent weight management programme.

    Science.gov (United States)

    Prioste, Ana; Fonseca, Helena; Sousa, Pedro; Gaspar, Pedro; Machado, Maria do Céu

    2017-01-01

    This study aimed to investigate the psychosocial gains perceived by overweight adolescents attending a 12-week weight management programme and to analyse gender-specific differences. A quantitative cross-sectional study was conducted with a sample of 70 overweight adolescents aged between 12 and 18 (52.9% girls), evaluated at baseline and at week 12 using anthropometric measurements and self-reported questionnaires. We analysed gender-specific differences related to body self-esteem, social life, relationships with their family, physical comfort, health responsibility, perceived benefits of the intervention, self-efficacy and adherence. We further investigated whether the variables at week 12 would predict changes in their body mass index. While weight had a greater impact on the body self-esteem of girls, both at baseline and week 12, boys reported higher self-efficacy and adherence as well as a greater perception of the benefits of the intervention at week 12. The body mass index change was positively associated with body self-esteem, relationships within the family and self-efficacy and adherence. Gender specifics and the role of psychosocial variables must be taken into account during weight management programmes for adolescents, and it is important to include the family throughout the entire process. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  12. Psychosocial Accompaniment

    Directory of Open Access Journals (Sweden)

    Mary Watkins

    2015-08-01

    Full Text Available This essay advocates for a paradigm shift in psychology toward the activity and ethics of accompaniment. Accompaniment requires a reorientation of the subjectivity, interpersonal practices, and critical understanding of the accompanier so that (she can stand alongside others who desire listening, witnessing, advocacy, space to develop critical inquiry and research, and joint imagination and action to address desired and needed changes. The idea of “accompaniment” emerged in liberation theology in Latin America, and migrated into liberatory forms of psychology as “psychosocial accompaniment.” This essay explores accompaniment and its ethics from a phenomenological perspective, highlighting differences from mainstream stances in psychology. Attention is also given to the effects of accompaniment on the accompanier. Efforts to decolonize psychology require careful attention to the psychic decolonization of its practitioners and to the cultivation of decolonizing interpersonal practices that provide a relational and ethical foundation for joint research, restorative healing, and transformative action. Such practices endeavor through dialogue to build mutual respect and understanding, promote effective solidarity, and contribute to the empowerment of those marginalized. The decolonization of psychology should enable practitioners to be more effective in working for increased social, economic, and environmental justice; peace building and reconciliation; and local and global ecological sustainability.

  13. Psychosocial work environment and performance

    DEFF Research Database (Denmark)

    Edwards, Kasper; Møller, Niels

    2010-01-01

    Good psychosocial work environment has been assumed to result in good work performance. However, little documentation exists which support the claim and the same goes for the opposite claim. This paper reports the first findings from a combined quantitative and qualitative study of the relationship...... between psychosocial work environment and performance in a large Danish firm. The objects of the study were more than 45 customer centers’ with 9-20 employees each. Using a combination of the Copenhagen psychosocial questionnaire and data from the firms’ balanced scorecard system we show a positive...... and describe the mechanism underlying the observed relationship. It is observed that a specific leadership style is responsible for creating a good working environment which leads to good performance. The leadership style can be described as process oriented, supportive and consistent but also demanding....

  14. Psychosocial aspects of epilepsy.

    Science.gov (United States)

    Shah, Pravina

    2002-05-01

    Social attitudes towards epilepsy cause more distress to the patient and his/her near and dear ones, than the disease itself. The major psychosocial issues related to epilepsy are: Quality of medical management, overprotection, education, employment, marriage and pregnancy. Inadequate treatment is the major reason involved in psychosocial issues. Constant overprotection and pampering leads to behavioural pattern which makes epileptic patient dependent for ever. Education is hampered in epileptic persons. Teachers and students should have proper information regarding seizures. If seizures are well controlled, job opportunities increase. Employers and employees need to be educated about epilepsy. Self-employment is the best in epileptic patients. Regarding marriage, each patient is to be judged on individual merits and type of epilepsy. Society needs to be educated about the facts and consequences of epilepsy. Risk of anti-epileptic drug's usage is very insignificant compared to risk of seizures in pregnancy. So girls are advised to seek medical advice before pregnancy and during follow-up. With more and more support from the society, persons with epilepsy will have the courage and confidence to speak about themselves and their illness. It is only then that we will realise that persons with epilepsy are 'normal' or 'near-normal' and this will break the vicious cycle of stigma.

  15. Mechanism(s) involved in opioid drug abuse modulation of HAND.

    Science.gov (United States)

    Dutta, Raini; Roy, Sabita

    2012-07-01

    Drug abuse and HIV infection are interlinked. From the onset of the HIV/AIDS epidemic, the impact of illicit drug use on HIV disease progression has been a focus of many investigations. Both laboratory-based and epidemiological studies strongly indicate that drug abuse may exacerbate HIV disease progression and increase mortality and morbidity in these patients. Increase susceptibility to opportunistic infection has been implicated as one of the major causes for this detriment. Furthermore, opioids are known to elicit prevalence of neurodegenerative disorders in HIV-infected patients. Numerous authors have delineated various molecular as well as cellular mechanisms associated with neurological complications in these patients. This review gives an overview of these findings. Understanding the mechanisms will allow for the development of targeted therapies aimed at reducing the progression of neurocognitive decline in the drug abusing HIV infected individuals.

  16. Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Kaneuji, Takeshi [Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Ariyoshi, Wataru; Okinaga, Toshinori; Toshinaga, Akihiro [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Takahashi, Tetsu [Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan)

    2011-04-29

    Highlights: {yields} Effect of compressive force on osteoblasts were examined. {yields} Compressive force induced OPG expression and suppressed osteoclastogenesis. {yields} This enhancement of OPG is dependent on Wnt/Ca2+ signal pathway. -- Abstract: Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm{sup 2}) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-{kappa}B ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of I{kappa}B{alpha}, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca{sup 2+} pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-{kappa}B) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt

  17. Less reduction of psychosocial problems among adolescents with unmet communication needs.

    Science.gov (United States)

    Jager, Margot; Reijneveld, Sijmen A; Almansa, Josue; Metselaar, Janneke; Knorth, Erik J; De Winter, Andrea F

    2017-04-01

    Patient-professional communication has been suggested to be a major determinant of treatment outcomes in psychosocial care for children and adolescents. However, the mechanisms involved are largely unknown and no longitudinal studies have been performed. Our aim was, therefore, to assess over the course of 1 year, the impact of patient-centered communication on psychosocial problems of adolescents in psychosocial care, including the routes mediating this impact. We obtained data on 315 adolescents, aged 12-18 years, enrolled in child and adolescent social or mental health care. We assessed patient-centered communication by comparing the needs and experiences of adolescents with regard to three aspects of communication: affective quality, information provision, and shared decision-making. Changes in psychosocial problems comprised those reported by adolescents and their parents between baseline and 1 year thereafter. Potential mediators were treatment adherence, improvement of understanding, and improvement in self-confidence. We found a relationship between unmet needs for affective quality, information provision, and shared decision-making and less reduction of psychosocial problems. The association between the unmet need to share in decision-making and less reduction of psychosocial problems were partially mediated by less improvement in self-confidence (30 %). We found no mediators regarding affective quality and information provision. Our findings confirm that patient-centered communication is a major determinant of treatment outcomes in psychosocial care for adolescents. Professionals should be aware that tailoring their communication to individual patients' needs is vital to the effectiveness of psychosocial care.

  18. Mechanisms involved in the transport of mercuric ions in target tissues.

    Science.gov (United States)

    Bridges, Christy C; Zalups, Rudolfs K

    2017-01-01

    Mercury exists in the environment in various forms, all of which pose a risk to human health. Despite guidelines regulating the industrial release of mercury into the environment, humans continue to be exposed regularly to various forms of this metal via inhalation or ingestion. Following exposure, mercuric ions are taken up by and accumulate in numerous organs, including brain, intestine, kidney, liver, and placenta. In order to understand the toxicological effects of exposure to mercury, a thorough understanding of the mechanisms that facilitate entry of mercuric ions into target cells must first be obtained. A number of mechanisms for the transport of mercuric ions into target cells and organs have been proposed in recent years. However, the ability of these mechanisms to transport mercuric ions and the regulatory features of these carriers have not been characterized completely. The purpose of this review is to summarize the current findings related to the mechanisms that may be involved in the transport of inorganic and organic forms of mercury in target tissues and organs. This review will describe mechanisms known to be involved in the transport of mercury and will also propose additional mechanisms that may potentially be involved in the transport of mercuric ions into target cells.

  19. A theoretical study of the molecular mechanism of the GAPDH Trypanosoma cruzi enzyme involving iodoacetate inhibitor

    Science.gov (United States)

    Carneiro, Agnaldo Silva; Lameira, Jerônimo; Alves, Cláudio Nahum

    2011-10-01

    The glyceraldehyde-3-phosphate dehydrogenase enzyme (GAPDH) is an important biological target for the development of new chemotherapeutic agents against Chagas disease. In this Letter, the inhibition mechanism of GAPDH involving iodoacetate (IAA) inhibitor was studied using the hybrid quantum mechanical/molecular mechanical (QM/MM) approach and molecular dynamic simulations. Analysis of the potential energy surface and potential of mean force show that the covalent attachment of IAA inhibitor to the active site of the enzyme occurs as a concerted process. In addition, the energy terms decomposition shows that NAD+ plays an important role in stabilization of the reagents and transition state.

  20. Mechanisms involved in calcium deficiency development in tomato fruit in response to gibberellins

    Science.gov (United States)

    Although gibberellins (GAs) have been shown to induce the calcium deficiency disorder, blossom-end rot (BER), development in tomato fruit (Solanum lycopersicum), the mechanisms involved remain largely unexplored. Our objectives were to better understand how GAs and a GA biosynthesis inhibitor affect...

  1. EFFECTS OF AMINO ACIDS ON THE MEMBRANE POTENTIAL OF TOAD OOCYTES AND THE MECHANISMS INVOLVED

    Institute of Scientific and Technical Information of China (English)

    WANGYu-Feng; CHENGJiun; CHENGZhi-Ping

    1989-01-01

    The etTects of 23 amino acids on the membrane potential of toad ( Bufo bufo gargarizans ) oocytes and the mechanisms involved were investigated in vitro by means of microelectrode. At a concentration of I mmol/L-alanine, leucine and lyaine induced signfiant depolarization, and tryptophan provoked a marked hyperpolarization during

  2. [Psychosocial stress and cardiology].

    Science.gov (United States)

    Houppe, Jean-Pierre

    2013-06-01

    Psychosocial stress is a major independent risk and prognostic factor of cardiovascular events. It includes psychological, sociological and socioeconomic factors. Cardiovascular diseases are important providers of psychosocial stress. The knowledge of the cerebral development throughout the time allows to a better understanding of the relationship between psychosocial stress and cardiovascular risk. Psychosocial stress leads, on top of traditional cardiovascular risk factors, to the development or to the worsening of an endothelial dysfunction, of an inflammatory response and prothrombotic phenomenon. Anxiolytics and antidepressors are not very effective against psychosocial stress. Physical activity and psychotherapy are much more indicated, particularly cognitve-behavioral therapy. The ESC recommends an evaluation of psychosocial stress through a short questionnaire.

  3. Involvement Without Participation?

    DEFF Research Database (Denmark)

    Olsén, Peter

    2012-01-01

    The article presents a case study of a knowledge-intensive company that launched a 2-year project to improve their psychosocial working environment. All parties agreed on the project, and the methods used aimed to promote the involvement of the employees. Surprisingly, the psychosocial working...... and participation. In order to develop a more sustainable and viable psychosocial working environment, a broader and more democratic notion of organisational learning and managing is proposed....

  4. Involvement of the mechanoreceptors in the sensory mechanisms of manual and electrical acupuncture.

    Science.gov (United States)

    Yamamoto, Hiromi; Kawada, Toru; Kamiya, Atsunori; Miyazaki, Shunichi; Sugimachi, Masaru

    2011-02-24

    The modalities of acupuncture can be broadly classified into manual acupuncture (MA) and electroacupuncture (EA). Although MA has been reported to cause winding of tissue around the needle and subsequent activation of the sensory mechanoreceptors and nociceptors, the sensory mechanisms of acupuncture stimulation are not fully understood. To test the hypothesis that the involvement of the mechanoreceptors in the sensory mechanism is different in MA and EA, we examined the effects of a stretch-activated channel blocker gadolinium on the hemodynamic responses to hind limb MA and EA in anesthetized rats (n = 9). Gadolinium significantly attenuated the MA-induced bradycardic response (-22 ± 5 vs. -10 ± 3 bpm, Pmechanoreceptors are involved in the sensory mechanisms for both MA and EA.

  5. Seminal vesicle intraepithelial involvement by prostate cancer: putative mechanism and clinicopathological significance.

    Science.gov (United States)

    Miyai, Kosuke; Kristiansen, Anna; Egevad, Lars; Pina-Oviedo, Sergio; Divatia, Mukul K; Shen, Steven S; Miles, Brian J; Ayala, Alberto G; Park, Yong Wook; Ro, Jae Y

    2014-09-01

    We have recently shown seminal vesicle intraepithelial involvement of prostate cancer in cases with seminal vesicle invasion (pT3b). Based on the manner of seminal vesicle invasion, there could be 2 possible mechanisms of seminal vesicle intraepithelial involvement: direct intraepithelial invasion from prostate carcinoma in the muscular wall of seminal vesicles or intraepithelial involvement of cancer from the invaginated extraprostatic space (IES)/ejaculatory duct system to extraprostatic seminal vesicle. We aimed to clarify the manner and clinicopathological significance of seminal vesicle intraepithelial involvement. Of 1629 consecutive radical prostatectomies, 109 cases (6.7%) showed seminal vesicle invasion in whole-mounted radical prostatectomy specimens. In these pT3b cases, 18 (17%) showed seminal vesicle intraepithelial involvement by prostate cancer. Stromal invasion of the IES/ejaculatory duct system and ejaculatory duct intraepithelial invasion by prostate cancer were identified in 62 and 5 of 109 pT3b cases, respectively. However, the presence/absence of IES/ejaculatory duct system involvement by prostate cancer does not predict seminal vesicle intraepithelial involvement. No statistically significant correlation was observed between all pathologic parameters/biochemical recurrence and the presence/absence of seminal vesicle intra-epithelial involvement in the pT3b cases. These findings suggest that seminal vesicle intraepithelial involvement is more likely due to direct invasion of carcinoma from the muscular wall of seminal vesicles rather than intraepithelial extension from the ejaculatory duct system in the IES. Further studies with a substantially greater case number are needed to clarify the clinicopathological significance of seminal vesicle intraepithelial involvement in a better manner.

  6. Cell resistance to the Cytolethal Distending Toxin involves an association of DNA repair mechanisms

    Science.gov (United States)

    Bezine, Elisabeth; Malaisé, Yann; Loeuillet, Aurore; Chevalier, Marianne; Boutet-Robinet, Elisa; Salles, Bernard; Mirey, Gladys; Vignard, Julien

    2016-01-01

    The Cytolethal Distending Toxin (CDT), produced by many bacteria, has been associated with various diseases including cancer. CDT induces DNA double-strand breaks (DSBs), leading to cell death or mutagenesis if misrepaired. At low doses of CDT, other DNA lesions precede replication-dependent DSB formation, implying that non-DSB repair mechanisms may contribute to CDT cell resistance. To address this question, we developed a proliferation assay using human cell lines specifically depleted in each of the main DNA repair pathways. Here, we validate the involvement of the two major DSB repair mechanisms, Homologous Recombination and Non Homologous End Joining, in the management of CDT-induced lesions. We show that impairment of single-strand break repair (SSBR), but not nucleotide excision repair, sensitizes cells to CDT, and we explore the interplay of SSBR with the DSB repair mechanisms. Finally, we document the role of the replicative stress response and demonstrate the involvement of the Fanconi Anemia repair pathway in response to CDT. In conclusion, our work indicates that cellular survival to CDT-induced DNA damage involves different repair pathways, in particular SSBR. This reinforces a model where CDT-related genotoxicity primarily involves SSBs rather than DSBs, underlining the importance of cell proliferation during CDT intoxication and pathogenicity. PMID:27775089

  7. Cissus sicyoides: Pharmacological Mechanisms Involved in the Anti-Inflammatory and Antidiarrheal Activities

    Science.gov (United States)

    Beserra, Fernando Pereira; de Cássia Santos, Raquel; Périco, Larissa Lucena; Rodrigues, Vinicius Peixoto; de Almeida Kiguti, Luiz Ricardo; Saldanha, Luiz Leonardo; Pupo, André Sampaio; da Rocha, Lúcia Regina Machado; Dokkedal, Anne Lígia; Vilegas, Wagner; Hiruma-Lima, Clélia Akiko

    2016-01-01

    The objective of this study was to evaluate the pharmacological mechanisms involved in anti-inflammatory and antidiarrheal actions of hydroalcoholic extract obtained from the leaves of Cissus sicyoides (HECS). The anti-inflammatory effect was evaluated by oral administration of HECS against acute model of edema induced by xylene, and the mechanisms of action were analysed by involvement of arachidonic acid (AA) and prostaglandin E2 (PGE2). The antidiarrheal effect of HECS was observed and we analyzed the motility and accumulation of intestinal fluid. We also analyzed the antidiarrheal mechanisms of action of HECS by evaluating the role of the opioid receptor, α2 adrenergic receptor, muscarinic receptor, nitric oxide (NO) and PGE2. The oral administration of HECS inhibited the edema induced by xylene and AA and was also able to significantly decrease the levels of PGE2. The extract also exhibited significant anti-diarrheal activity by reducing motility and intestinal fluid accumulation. This extract significantly reduced intestinal transit stimulated by muscarinic agonist and intestinal secretion induced by PGE2. Our data demonstrate that the mechanism of action involved in the anti-inflammatory effect of HECS is related to PGE2. The antidiarrheal effect of this extract may be mediated by inhibition of contraction by acting on the intestinal smooth muscle and/or intestinal transit. PMID:26805827

  8. Cissus sicyoides: Pharmacological Mechanisms Involved in the Anti-Inflammatory and Antidiarrheal Activities

    Directory of Open Access Journals (Sweden)

    Fernando Pereira Beserra

    2016-01-01

    Full Text Available The objective of this study was to evaluate the pharmacological mechanisms involved in anti-inflammatory and antidiarrheal actions of hydroalcoholic extract obtained from the leaves of Cissus sicyoides (HECS. The anti-inflammatory effect was evaluated by oral administration of HECS against acute model of edema induced by xylene, and the mechanisms of action were analysed by involvement of arachidonic acid (AA and prostaglandin E2 (PGE2. The antidiarrheal effect of HECS was observed and we analyzed the motility and accumulation of intestinal fluid. We also analyzed the antidiarrheal mechanisms of action of HECS by evaluating the role of the opioid receptor, α2 adrenergic receptor, muscarinic receptor, nitric oxide (NO and PGE2. The oral administration of HECS inhibited the edema induced by xylene and AA and was also able to significantly decrease the levels of PGE2. The extract also exhibited significant anti-diarrheal activity by reducing motility and intestinal fluid accumulation. This extract significantly reduced intestinal transit stimulated by muscarinic agonist and intestinal secretion induced by PGE2. Our data demonstrate that the mechanism of action involved in the anti-inflammatory effect of HECS is related to PGE2. The antidiarrheal effect of this extract may be mediated by inhibition of contraction by acting on the intestinal smooth muscle and/or intestinal transit.

  9. Tissue transglutaminase is involved in mechanical load-induced osteogenic differentiation of human ligamentum flavum cells.

    Science.gov (United States)

    Chao, Yuan-Hung; Huang, Shih-Yung; Yang, Ruei-Cheng; Sun, Jui-Sheng

    2016-07-01

    Mechanical load-induced osteogenic differentiation might be the key cellular event in the calcification and ossification of ligamentum flavum. The aim of this study was to investigate the influence of tissue transglutaminase (TGM2) on mechanical load-induced osteogenesis of ligamentum flavum cells. Human ligamentum flavum cells were obtained from 12 patients undergoing lumbar spine surgery. Osteogenic phenotypes of ligamentum flavum cells, such as alkaline phosphatase (ALP), Alizarin red-S stain, and gene expression of osteogenic makers were evaluated following the administration of mechanical load and BMP-2 treatment. The expression of TGM2 was evaluated by real-time PCR, Western blotting, and enzyme-linked immunosorbent assay (ELISA) analysis. Our results showed that mechanical load in combination with BMP-2 enhanced calcium deposition and ALP activity. Mechanical load significantly increased ALP and OC gene expression on day 3, whereas BMP-2 significantly increased ALP, OPN, and Runx2 on day 7. Mechanical load significantly induced TGM2 gene expression and enzyme activity in human ligamentum flavum cells. Exogenous TGM2 increased ALP and OC gene expression; while, inhibited TG activity significantly attenuated mechanical load-induced and TGM2-induced ALP activity. In summary, mechanical load-induced TGM2 expression and enzyme activity is involved in the progression of the calcification of ligamentum flavum.

  10. [Involvement of adrenergic mechanisms in developing the nervous syndrome of high pressure and nitrogen narcosis].

    Science.gov (United States)

    Sledkov, A I; Bernarskii, K V; Shilina, M N

    1996-01-01

    Involvement of the adrenergic mediator system in central mechanisms of hyperbaric nitrogen narcosis or the high pressure nervous syndrome (NSHP) produced by nitrogen or heliox gas mixtures under increased pressure was studied in mice and rabbit experiments with the use of pharmacological substances-analyzers. Accumulated data are indicative of lack of a significant role of the adrenergic system in the NSHP genesis and a protective effect of activation of the central but not peripheric adrenergic mediation in development of the behavioural and electrophysiological symptomatics of nitrogen narcosis. Mechanisms of NSHP and nitrogen narcosis and possible principles of pharmacological correction are under discussion.

  11. Molecular Mechanisms Involved in Mesenchymal Stem Cell Migration to the Site of Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Katarina Kollar

    2009-01-01

    Full Text Available Mesenchymal stem cells or multipotent mesenchymal stromal cells (both referred to as MSC have been shown in some studies to have a beneficial effect on myocardial recovery after infarct. Current strategies for MSC delivery to heart involve intravenous, intraarterial, and intramuscular delivery. Different routes of MSC delivery and a lack of knowledge of the mechanisms that MSC utilise to migrate in vivo has most likely led to the marked variations in results that have been found. This review aims to summarise the current knowledge of MSC migratory mechanisms and looks to future methods of MSC manipulation prior to delivery in order to enhance MSC migration and engraftment.

  12. A qualitative study examining psychosocial distress and coping mechanisms among orphan and vulnerable children living in institutional care in New Delhi, India

    Directory of Open Access Journals (Sweden)

    Abhishek Saraswat

    2017-07-01

    Full Text Available Introduction: India is home to the largest population of orphaned children in the South Asia, who are at increased risk of poor psychosocial well-being. In the Indian context, literature on the psychosocial well-being of orphans and vulnerable children (OVC is scarce. Our research was aimed at fulfilling this gap by understanding self-reported psychosocial distress among OVC and subsequent coping strategies adopted during their stay at orphanages. Methods: The present study was conducted in three randomly selected orphanages of Delhi, India, during August-December 2016. Fifteen children (M = 9, F = 6 aged 10-17, were selected for in-depth interviews through a non-probability purposive sampling. Descriptive analysis was used to describe the characteristics of the study participants. Data analysis required the examination and comparison of interview transcripts for content analysis and themes identification. Results and Discussion: Our findings revealed psychological turmoil and poor social cognition among OVC. Even though children were happy to enjoy their basic necessities of life, the majority of them faced parental bereavement yearning for love, and desiring advocacy and guidance in life. OVC showed low self-concept and lack of purpose in life. Isolation from outside world resulted in feelings of mistrust among OVC. They also felt stigmatized, socially excluded and remained distressed. Coping strategies adopted by OVC included praying to God, forgetting parents, shifting focus, avoiding crowded places, and treating inmates as their family. They also reported indulgence in self-discrimination, substance abuse, and delinquency to avoid psychosocial distress. Conclusions: Ongoing programs aimed exclusively at fulfilling materialistic needs of OVC could lose focus on their psychosocial issues. New robust interventions are required not only for sufficing the quality services, but also for identifying psychological issues, enhancing social skills

  13. Mechanisms involved in VPAC receptors activation and regulation: lessons from pharmacological and mutagenesis studies.

    Directory of Open Access Journals (Sweden)

    Ingrid eLanger

    2012-10-01

    Full Text Available VIP plays diverse and important role in human physiology and physiopathology and their receptors constitute potential targets for the treatment of several diseases such as neurodegenerative disorder, asthma, diabetes and inflammatory diseases. This article reviews the current knowledge regarding the two VIP receptors, VPAC1 and VPAC2, with respect to mechanisms involved in receptor activation, G protein coupling, signaling, regulation and oligomerization.

  14. Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking

    Science.gov (United States)

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2011-01-01

    Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation, although its detailed mechanism of action has yet to be elucidated. To further examine its potential as a CNS modulating agent as well as its mechanism of action, we investigated the effects of clavulanic acid in neuronal cells. Our results indicate that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity chromatography we were able to identify two proteins, Munc18-1 and Rab4 that potentially bind to clavulanic acid and play a critical role in neurosecretion and the vesicle trafficking process. Consistent with this result, an increase in the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid treated cells. Overall, these data suggest that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders, such as depression. PMID:21964384

  15. Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking.

    Science.gov (United States)

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2011-10-24

    Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation, although its detailed mechanism of action has yet to be elucidated. To further examine its potential as a CNS modulating agent as well as its mechanism of action, we investigated the effects of clavulanic acid in neuronal cells. Our results indicate that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity chromatography we were able to identify two proteins, Munc18-1 and Rab4 that potentially bind to clavulanic acid and play a critical role in neurosecretion and the vesicle trafficking process. Consistent with this result, an increase in the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid treated cells. Overall, these data suggest that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders, such as depression.

  16. Evidence of involvement of central neural mechanisms in generating fibromyalgia pain.

    Science.gov (United States)

    Staud, Roland

    2002-08-01

    Fibromyalgia syndrome (FMS) is characterized by widespread pain, fatigue, sleep abnormalities, and distress. Because FMS lacks consistent evidence of tissue abnormalities, recent investigations have focused on central nervous system mechanisms of pain. Abnormal temporal summation of second pain (wind-up) and central sensitization have been described recently in patients with FMS. Wind-up and central sensitization, which rely on central pain mechanisms, occur after prolonged C-nociceptor input and depend on activation of nociceptor-specific neurons and wide dynamic range neurons in the dorsal horn of the spinal cord. Other abnormal central pain mechanisms recently detected in patients with FMS include diffuse noxious inhibitory controls. These pain inhibitory mechanisms rely on spinal cord and supraspinal systems involving pain facilitatory and pain inhibitory pathways. Brain-imaging techniques that can detect neuronal activation after nociceptive stimuli have provided additional evidence for abnormal central pain mechanisms in FMS. Brain images have corroborated the augmented reported pain experience of patients with fibromyalgia during experimental pain stimuli. In addition, thalamic activity, which contributes significantly to pain processing, was decreased in fibromyalgia. However, central pain mechanisms of fibromyalgia may not depend exclusively on neuronal activation. Neuroglial activation has been found to play an important role in the induction and maintenance of chronic pain. These findings may have important implications for future research and the treatment of fibromyalgia pain.

  17. Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

    Directory of Open Access Journals (Sweden)

    J.C. Brenes

    2012-04-01

    Full Text Available Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG and inferior colliculus (IC, produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing. These defensive reaction responses are critically mediated by γ-aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 μL, a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.

  18. Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

    Energy Technology Data Exchange (ETDEWEB)

    Brenes, J.C. [Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg (Germany); Broiz, A.C.; Bassi, G.S. [Instituto de Neurociências e Comportamento, Campus USP, Ribeirão Preto, SP (Brazil); Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Schwarting, R.K.W. [Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg (Germany); Brandão, M.L. [Instituto de Neurociências e Comportamento, Campus USP, Ribeirão Preto, SP (Brazil); Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-03-09

    Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by {sub Y}-aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 µL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.

  19. Peripheral and Central Mechanisms Involved in the Hormonal Control of Male and Female Reproduction.

    Science.gov (United States)

    Rudolph, L M; Bentley, G E; Calandra, R S; Paredes, A H; Tesone, M; Wu, T J; Micevych, P E

    2016-07-01

    Reproduction involves the integration of hormonal signals acting across multiple systems to generate a synchronised physiological output. A critical component of reproduction is the luteinising hormone (LH) surge, which is mediated by oestradiol (E2 ) and neuroprogesterone interacting to stimulate kisspeptin release in the rostral periventricular nucleus of the third ventricle in rats. Recent evidence indicates the involvement of both classical and membrane E2 and progesterone signalling in this pathway. A metabolite of gonadotrophin-releasing hormone (GnRH), GnRH-(1-5), has been shown to stimulate GnRH expression and secretion, and has a role in the regulation of lordosis. Additionally, gonadotrophin release-inhibitory hormone (GnIH) projects to and influences the activity of GnRH neurones in birds. Stress-induced changes in GnIH have been shown to alter breeding behaviour in birds, demonstrating another mechanism for the molecular control of reproduction. Peripherally, paracrine and autocrine actions within the gonad have been suggested as therapeutic targets for infertility in both males and females. Dysfunction of testicular prostaglandin synthesis is a possible cause of idiopathic male infertility. Indeed, local production of melatonin and corticotrophin-releasing hormone could influence spermatogenesis via immune pathways in the gonad. In females, vascular endothelial growth factor A has been implicated in an angiogenic process that mediates development of the corpus luteum and thus fertility via the Notch signalling pathway. Age-induced decreases in fertility involve ovarian kisspeptin and its regulation of ovarian sympathetic innervation. Finally, morphological changes in the arcuate nucleus of the hypothalamus influence female sexual receptivity in rats. The processes mediating these morphological changes have been shown to involve the rapid effects of E2 controlling synaptogenesis in this hypothalamic nucleus. In summary, this review highlights new

  20. Phytoremediation potential of the novel atrazine tolerant Lolium multiflorum and studies on the mechanisms involved

    Energy Technology Data Exchange (ETDEWEB)

    Merini, Luciano J. [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina); Bobillo, Cecilia [Servicio de Huellas Digitales Geneticas, Facultad de Farmacia y Bioquimica, Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires, Junin 956, BS As (Argentina); Cuadrado, Virginia [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina); Corach, Daniel [Servicio de Huellas Digitales Geneticas, Facultad de Farmacia y Bioquimica, Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires, Junin 956, BS As (Argentina); Giulietti, Ana M., E-mail: agiule@ffyb.uba.a [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina)

    2009-11-15

    Atrazine impact on human health and the environment have been extensively studied. Phytoremediation emerged as a low cost, environmental friendly biotechnological solution for atrazine pollution in soil and water. In vitro atrazine tolerance assays were performed and Lolium multiflorum was found as a novel tolerant species, able to germinate and grow in the presence of 1 mg kg{sup -1} of the herbicide. L. multiflorum presented 20% higher atrazine removal capacity than the natural attenuation, with high initial degradation rate in microcosms. The mechanisms involved in atrazine tolerance such as mutation in psbA gene, enzymatic detoxification via P{sub 450} or chemical hydrolysis through benzoxazinones were evaluated. It was demonstrated that atrazine tolerance is conferred by enhanced enzymatic detoxification via P{sub 450}. Due to its atrazine degradation capacity in soil and its agronomical properties, L. multiflorum is a candidate for designing phytoremediation strategies for atrazine contaminated agricultural soils, especially those involving run-off avoiding. - Finding of a novel atrazine-tolerant species, as a potential candidate for phytoremediating herbicide-contaminated agriculture soils and elucidation of the mechanisms involved in tolerance.

  1. Human axillary apocrine glands: proteins involved in the apocrine secretory mechanism.

    Science.gov (United States)

    Stoeckelhuber, Mechthild; Schubert, Christoph; Kesting, Marco R; Loeffelbein, Denys J; Nieberler, Markus; Koehler, Claudia; Welsch, Ulrich

    2011-02-01

    The apocrine secretory mechanism is a mode of secretion by which the apical part of the cell cytoplasm is pinched off, which leads to the formation of an aposome. The distinct mechanism of formation and decapitation of the aposome is not well investigated. Only few proteins are known that are involved in this secretory mechanism. We studied the human axillary apocrine gland and looked at proteins associated with cytokinesis, a process that is comparable to the pinching-off mechanism of apocrine glandular cells. By immunohistochemistry, we detected actin, myosin II, cytokeratin 7 and 19, α- and β-tubulin, anillin, cofilin, syntaxin 2, vamp8/endobrevin and septin 2. In highly active glandular cells, these proteins are located at the base of the apical protrusion when the aposome is in the process of being released or are concentrated in the cap of the apical protrusion. These findings demonstrate new insights on apocrine secretory mechanisms and point to similarities to the terminal step of cytokinesis, which is regulated by a SNARE-mediated membrane fusion event.

  2. Review of endocrine disorders associated with environmental toxicants and possible involved mechanisms.

    Science.gov (United States)

    Maqbool, Faheem; Mostafalou, Sara; Bahadar, Haji; Abdollahi, Mohammad

    2016-01-15

    Endocrine disrupting chemicals (EDC) are released into environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDC have major risks for human by targeting different organs and systems in the body. Multiple mechanisms are involved in targeting the normal system, through estrogen receptors, nuclear receptors and steroidal receptors activation. In this review, different methods by which xenobiotics stimulate signaling pathways and genetic mutation or DNA methylation have been discussed. These methods help to understand the results of xenobiotic action on the endocrine system. Endocrine disturbances in the human body result in breast cancer, ovarian problems, thyroid eruptions, testicular carcinoma, Alzheimer disease, schizophrenia, nerve damage and obesity. EDC characterize a wide class of compounds such as organochlorinated pesticides, industrial wastes, plastics and plasticizers, fuels and numerous other elements that exist in the environment or are in high use during daily life. The interactions and mechanism of toxicity in relation to human general health problems, especially endocrine disturbances with particular reference to reproductive problems, diabetes, and breast, testicular and ovarian cancers should be deeply investigated. There should also be a focus on public awareness of these EDC risks and their use in routine life. Therefore, the aim of this review is to summarize all evidence regarding different physiological disruptions in the body and possible involved mechanisms, to prove the association between endocrine disruptions and human diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Potential Mechanisms Involved in Ceramide-induced Apoptosis in Human Colon Cancer HT29 Cells

    Institute of Scientific and Technical Information of China (English)

    JING WANG; XIAO-WEN LV; YU-GUO DU

    2009-01-01

    Objective To investigate the potential mechanisms of cell death after the treatment with ceramide. Methods MTT assay,DNA ladder, reporter assay, FACS and Western blot assay were employed to investigate the potential mechanisms of cell death after the treatment with C2-ceramide. Results A short-time treatment with C2-ceramide induced cell death, which was associated with p38 MAP kinase activation, but had no links with typical caspase activation or PARP degradation. Rather than caspase inhibitor, Inhibitor of p38 MAP kinase blocked cell death induced by a short-time treatment with ceramide (12 h). Moreover, incubation of cells with ceramide for a long time (>12 h) increased subGl, but reduced S phase accompanied by caspase-dependent and caspase-independent changes including NFκB activation. Conclusion Ceramide-induced cell apoptosis involves both caspase-dependent and -independent signaling pathway. Caspase-independent cell death occurring in a relatively early stage, which is mediated via p38 MAP kinase, can progress into a stage involving both caspase-dependent and -independent mechanisms accompanied by cell signaling of MAPKs and NFκB.

  4. Post-disaster psychosocial services across Europe: The TENTS project

    DEFF Research Database (Denmark)

    Witteveen, A. B.; Bisson, J. I.; Ajdukovic, D.

    2012-01-01

    of a cross-sectional web-based survey completed in 2008 by two hundred and eighty-six representatives of organizations involved in psychosocial responses to trauma and disaster from thirty-three different countries across Europe. The survey addressed planning and delivery of psychosocial care after disaster......, methods of screening and diagnosis, types of interventions used, and other aspects of psychosocial care after trauma. The findings showed that planning and delivery of psychosocial care was inconsistent across Europe. Countries in East Europe seemed to have less central coordination of the post......At present post-disaster activities and plans seem to vary widely. An adequate estimation of the availability of post-disaster psychosocial services across Europe is needed in order to compare them with recently developed evidence-informed psychosocial care guidelines. Here we report on the results...

  5. Psychosocial perspectives and the issue of prevention in childhood obesity.

    Science.gov (United States)

    Stein, Daniel; Weinberger-Litman, Sarah L; Latzer, Yael

    2014-01-01

    A dramatic increase in childhood overweight/obesity has been recognized globally over the past 50 years. This observed increase may reflect genetic, as well as psychological, environmental, and socio-cultural influences. In the first part of this review, we present an updated summary of the psychosocial factors associated with this change and discuss possible ways in which they operate. Among these factors, lower socio economic status (in both industrialized and non-industrialized countries), being female, belonging to a minority group, and being exposed to adverse life events may all be associated with a greater risk of childhood overweight/obesity. These influences may be mediated via a variety of mechanisms, in particular above-average food intake of low nutritional quality and reduction in physical activity. Other important psychosocial mediators include the influence of the family and peer environment, and exposure to the media. In the second part of the review, we discuss the potential of psychosocial prevention programs to intervene in the processes involved in the rise of childhood overweight/obesity. Two points are emphasized. First, prevention programs should be multidisciplinary, combining the knowledge of experts from different professions, and taking into consideration the important role of the family environment and relevant influential social organizations, particularly school. Second, effective change is unlikely to occur without large-scale programs carried out on a public policy level.

  6. Psychosocial perspectives and the issue of prevention in childhood obesity

    Directory of Open Access Journals (Sweden)

    Daniel eStein

    2014-07-01

    Full Text Available A dramatic increase in childhood overweight/obesity has been recognized globally over the past 50 years. This observed increase may reflect genetic, as well as psychological, environmental, and socio-cultural influences. In the first part of this review we present an updated summary of the psychosocial factors associated with this change and discuss possible ways in which they operate. Among these factors , lower socio economic status (in both industrialized and non-industrialized countries, being female, belonging to a minority group, and being exposed to adverse life events may all be associated with a greater risk of childhood overweight/obesity. These influences may be mediated via a variety of mechanisms, in particular above average food intake of low nutritional quality, and reduction in physical activity. Other important psychosocial mediators include the influence of the family and peer environment, and exposure to the media.In the second part of the review we discuss the potential of psychosocial prevention programs to intervene in the processes involved in the rise of childhood overweight/obesity. Two points are emphasized. Firstly, prevention programs should be multidisciplinary, combining the knowledge of experts from different professions, and taking into consideration the important role of the family environment and relevant influential social organizations, particularly school. Secondly, effective change is unlikely to occur without large-scale programs carried out on a public policy level.

  7. Assessment of Mechanisms Involved in Antinociception Produced by the Alkaloid Caulerpine

    Directory of Open Access Journals (Sweden)

    Luiz Henrique Agra Cavalcante-Silva

    2014-09-01

    Full Text Available In previous works we showed that oral administration of caulerpine, a bisindole alkaloid isolated from algae of the genus Caulerpa, produced antinociception when assessed in chemical and thermal models of nociception. In this study, we evaluated the possible mechanism of action of this alkaloid in mice, using the writhing test. The antinociceptive effect of caulerpine was not affected by intraperitoneal (i.p. pretreatment of mice with naloxone, flumazenil, l-arginine or atropine, thus discounting the involvement of the opioid, GABAergic, l-arginine-nitric oxide and (muscarinic cholinergic pathways, respectively. In contrast, i.p. pretreatment with yohimbine, an α2-adrenoceptor antagonist, or tropisetron, a 5-HT3 antagonist, significantly blocked caulerpine-induced antinociception. These results suggest that caulerpine exerts its antinociceptive effect in the writhing test via pathways involving α2-adrenoceptors and 5-HT3 receptors. In summary, this alkaloid could be of interest in the development of new dual-action analgesic drugs.

  8. Phytoremediation potential of the novel atrazine tolerant Lolium multiflorum and studies on the mechanisms involved.

    Science.gov (United States)

    Merini, Luciano J; Bobillo, Cecilia; Cuadrado, Virginia; Corach, Daniel; Giulietti, Ana M

    2009-11-01

    Atrazine impact on human health and the environment have been extensively studied. Phytoremediation emerged as a low cost, environmental friendly biotechnological solution for atrazine pollution in soil and water. In vitro atrazine tolerance assays were performed and Lolium multiflorum was found as a novel tolerant species, able to germinate and grow in the presence of 1 mg kg(-1) of the herbicide. L. multiflorum presented 20% higher atrazine removal capacity than the natural attenuation, with high initial degradation rate in microcosms. The mechanisms involved in atrazine tolerance such as mutation in psbA gene, enzymatic detoxification via P(450) or chemical hydrolysis through benzoxazinones were evaluated. It was demonstrated that atrazine tolerance is conferred by enhanced enzymatic detoxification via P(450). Due to its atrazine degradation capacity in soil and its agronomical properties, L. multiflorum is a candidate for designing phytoremediation strategies for atrazine contaminated agricultural soils, especially those involving run-off avoiding.

  9. Mechanisms Involved in the Pro-Apoptotic Effect of Melatonin in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Isaac Antolín

    2013-03-01

    Full Text Available It is well established that melatonin exerts antitumoral effects in many cancer types, mostly decreasing cell proliferation at low concentrations. On the other hand, induction of apoptosis by melatonin has been described in the last few years in some particular cancer types. The cytotoxic effect occurs after its administration at high concentrations, and the molecular pathways involved have been only partially determined. Moreover, a synergistic effect has been found in several cancer types when it is administered in combination with chemotherapeutic agents. In the present review, we will summarize published work on the pro-apoptotic effect of melatonin in cancer cells and the reported mechanisms involved in such action. We will also construct a hypothesis on how different cell signaling pathways may relate each other on account for such effect.

  10. Pathogenic Mechanisms Involved in the Hematological Alterations of Arenavirus-induced Hemorrhagic Fevers

    Directory of Open Access Journals (Sweden)

    Roberto G. Pozner

    2013-01-01

    Full Text Available Viral hemorrhagic fevers (VHFs caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.

  11. Pathogenic mechanisms involved in the hematological alterations of arenavirus-induced hemorrhagic fevers.

    Science.gov (United States)

    Schattner, Mirta; Rivadeneyra, Leonardo; Pozner, Roberto G; Gómez, Ricardo M

    2013-01-21

    Viral hemorrhagic fevers (VHFs) caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.

  12. Mechanisms regulating proteostasis are involved in sympatric speciation of the blind mole rat, Spalax galili.

    Science.gov (United States)

    Rodriguez, Karl A; Li, Kexin; Nevo, Eviatar; Buffenstein, Rochelle

    2016-01-01

    Genome-wide analysis demonstrates extensive genomic adaptive complexes involved in sympatric speciation between blind mole rats (Spalax galili) in abutting populations living in basalt and chalk soils. Among the gene ontology (GO) enrichment, musculature and metabolism stood out in basalt dwellers while nutrition and neurogenetics were highlighted in chalk residents. Measurements of mechanisms regulating protein homeostasis inspired by these GO terms suggest that at the proteomic level there is also a habitat/soil-type driven divergence with the basalt residents exhibiting higher proteasome activity whereas elevated levels of markers of autophagy are evident in the chalk inhabitants.

  13. Multiple mechanisms involved in oxytocin-induced modulation of myometrial contractility

    Institute of Scientific and Technical Information of China (English)

    Anatoly SHMYGOL; Joanna GULLAM; Andrew BLANKS; Steven THORNTON

    2006-01-01

    Oxytocin is a small peptide hormone with multiple sites of action in human body.It regulates a large number of reproduction-related processes in all species.Particularly important is its ability to stimulate uterine contractility.This is achieved by multiple mechanisms involving sarcoplasmic reticulum Ca2+ release and sensitization of the contractile apparatus to Ca2+.In this paper,we review the data published by US and other groups on oxytocin-induced modulation of uterine contractility.We conclude that sensitization of contractile apparatus to Ca2+ is the most relevant physiological effect of oxytocin on human myometrium.

  14. A review on the molecular mechanisms involved in insulin resistance induced by organophosphorus pesticides.

    Science.gov (United States)

    Lasram, Mohamed Montassar; Dhouib, Ines Bini; Annabi, Alya; El Fazaa, Saloua; Gharbi, Najoua

    2014-08-01

    There is increasing evidence reporting that organophosphorus pesticides (OPs) impair glucose homeostasis and cause insulin resistance and type 2 diabetes. Insulin resistance is a complex metabolic disorder that defies explanation by a single etiological pathway. Formation of advanced glycation end products, accumulation of lipid metabolites, activation of inflammatory pathways and oxidative stress have all been implicated in the pathogenesis of insulin resistance. Ultimately, these molecular processes activate a series of stress pathways involving a family of serine kinases, which in turn have a negative effect on insulin signaling. Experimental and clinical data suggest an association between these molecular mechanisms and OPs compounds. It was first reported that OPs induce hyperglycemia. Then a concomitant increase of blood glucose and insulin was pointed out. For some years only, we have begun to understand that OPs promote insulin resistance and increase the risk of type 2 diabetes. Overall, this review outlines various mechanisms that lead to the development of insulin resistance by OPs exposure.

  15. Cholinergic deficiency involved in vascular dementia:possible mechanism and strategy of treatment

    Institute of Scientific and Technical Information of China (English)

    Juan WANG; Hai-yan ZHANG; Xi-can TANG

    2009-01-01

    Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence.Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment.Moreover,cholinergic therapies have shown promising effects on cognitive improvement in VaD patients.The precise mechanisms of these cholinergic agents are currently not fully understood;however,accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway,in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation,although regulation of oxidative stress and energy metabolism,alleviation of apoptosis may also be involved.In this paper,we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.

  16. Psychosocial stress and inflammation in cancer.

    Science.gov (United States)

    Powell, N D; Tarr, A J; Sheridan, J F

    2013-03-01

    Stress-induced immune dysregulation results in significant health consequences for immune related disorders including viral infections, chronic autoimmune disease, and tumor growth and metastasis. In this mini-review we discuss the sympathetic, neuroendocrine and immunologic mechanisms by which psychosocial stress can impact cancer biology. Both human and animal studies have shown the sympathetic and neuroendocrine responses to psychosocial stress significantly impacts cancer, in part, through regulation of inflammatory mediators. Psychosocial stressors stimulate neuroendocrine, sympathetic, and immune responses that result in the activation of the hypothalamic-pituitary-adrenal (HPA)-axis, sympathetic nervous system (SNS), and the subsequent regulation of inflammatory responses by immune cells. Social disruption (SDR) stress, a murine model of psychosocial stress and repeated social defeat, provides a novel and powerful tool to probe the mechanisms leading to stress-induced alterations in inflammation, tumor growth, progression, and metastasis. In this review, we will focus on SDR as an important model of psychosocial stress in understanding neural-immune mechanisms in cancer.

  17. Are calcium oxalate crystals involved in the mechanism of acute renal failure in ethylene glycol poisoning?

    Science.gov (United States)

    McMartin, Kenneth

    2009-11-01

    Ethylene glycol (EG) poisoning often results in acute renal failure, particularly if treatment with fomepizole or ethanol is delayed because of late presentation or diagnosis. The mechanism has not been established but is thought to result from the production of a toxic metabolite. A literature review utilizing PubMed identified papers dealing with renal toxicity and EG or oxalate. The list of papers was culled to those relevant to the mechanism and treatment of the renal toxicity associated with either compound. ROLE OF METABOLITES: Although the "aldehyde" metabolites of EG, glycolaldehyde, and glyoxalate, have been suggested as the metabolites responsible, recent studies have shown definitively that the accumulation of calcium oxalate monohydrate (COM) crystals in kidney tissue produces renal tubular necrosis that leads to kidney failure. In vivo studies in EG-dosed rats have correlated the severity of renal damage with the total accumulation of COM crystals in kidney tissue. Studies in cultured kidney cells, including human proximal tubule (HPT) cells, have demonstrated that only COM crystals, not the oxalate ion, glycolaldehyde, or glyoxylate, produce a necrotic cell death at toxicologically relevant concentrations. COM CRYSTAL ACCUMULATION: In EG poisoning, COM crystals accumulate to high concentrations in the kidney through a process involving adherence to tubular cell membranes, followed by internalization of the crystals. MECHANISM OF TOXICITY: COM crystals have been shown to alter membrane structure and function, to increase reactive oxygen species and to produce mitochondrial dysfunction. These processes are likely to be involved in the mechanism of cell death. Accumulation of COM crystals in the kidney is responsible for producing the renal toxicity associated with EG poisoning. The development of a pharmacological approach to reduce COM crystal adherence to tubular cells and its cellular interactions would be valuable as this would decrease the renal

  18. Towards a psychosocial psychoanalysis

    OpenAIRE

    Frosh, Stephen

    2016-01-01

    From its beginning, psychoanalysis has always been a 'personal' affair. This paper presents an autobiographical account of engagement with psychoanalysis as an academic discipline, exploring particularly how it has become central to my concerns in psychosocial studies.

  19. The mechanism of sperm-egg interaction and the involvement of IZUMO1 in fusion.

    Science.gov (United States)

    Inoue, Naokazu; Ikawa, Masahito; Okabe, Masaru

    2011-01-01

    An average human ejaculate contains over 100 million sperm, but only a few succeed in accomplishing the journey to an egg by migration through the female reproductive tract. Among these few sperm, only one participates in fertilization. There might be an ingenious molecular mechanism to ensure that the very best sperm fertilize an egg. However, recent gene disruption experiments in mice have revealed that many factors previously described as important for fertilization are largely dispensable. One could argue that the fertilization mechanism is made robust against gene disruptions. However, this is not likely, as there are already six different gene-disrupted mouse lines (Calmegin, Adam1a, Adam2, Adam3, Ace and Pgap1), all of which result in male sterility. The sperm from these animals are known to have defective zona-binding ability and at the same time lose oviduct-migrating ability. Concerning sperm-zona binding, the widely accepted involvement of sugar moiety on zona pellucida 3 (ZP3) is indicated to be dispensable by gene disruption experiments. Thus, the landscape of the mechanism of fertilization is revolving considerably. In the sperm-egg fusion process, CD9 on egg and IZUMO1 on sperm have emerged as essential factors. This review focuses on the mechanism of fertilization elucidated by gene-manipulated animals.

  20. The mechanism of sperm-egg interaction and the involvement of IZUM01 in fusion

    Institute of Scientific and Technical Information of China (English)

    Naokazu Inoue; Masahito Ikawa; Masaru Okabe

    2011-01-01

    An average human ejaculate contains over 100 million sperm,but only a few succeed in accomplishing the journey to an egg by migration through the female reproductive tract.Among these few sperm,only one participates in fertilization.There might be an ingenious molecular mechanism to ensure that the very best sperm fertilize an egg.However,recent gene disruption experiments in mice have revealed that many factors previously described as important for fertilization are largely dispensable.One could argue that the fertilization mechanism is made robust against gene disruptions.However,this is not likely,as there are already six different gene-disrupted mouse lines (Calmegin,Adam1a,Adam2,Adam3,Aceand Pgap1),all of which result in male sterility.The sperm from these animals are known to have defective zona-binding ability and at the same time lose oviduct-migrating ability.Concerning spermzona binding,the widely accepted involvement of sugar moiety on zona pellucida 3 (ZP3) is indicated to be dispensable by gene disruption experiments.Thus,the landscape of the mechanism of fertilization is revolving considerably.In the sperm-egg fusion process,CD9 on egg and IZUM01 on sperm have emerged as essential factors.This review focuses on the mechanism of fertilization elucidated by gene-manipulated animals.

  1. Epigenetic mechanisms in the development of memory and their involvement in certain neurological diseases.

    Science.gov (United States)

    Rosales-Reynoso, M A; Ochoa-Hernández, A B; Juárez-Vázquez, C I; Barros-Núñez, P

    Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases. Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Mechanism of electron transfer reaction of ternary dipicolinatochromium(III) complex involving oxalate as secondary ligand

    Indian Academy of Sciences (India)

    Hassan Amroun Ewais; Iqbal Mohamed Ibrhium Ismail

    2013-09-01

    Mechanism of electron transfer reaction of ternary Mechanism of the oxidation of [CrIII(DPA)(OX)(H2O)]− (DPA = dipicolinate and OX = oxalate) by periodate in aqueous acidic medium has been studied spectrophotometrically over the pH range of 4.45-5.57 at different temperatures. The reaction is first order with respect to both [IO$^{−}_{4}$] and the complex concentration, and it obeys the following rate law: $$d[{\\text Cr}^{\\text{VI}}]/dt = k_6K_4K_6[{\\text IO}^−_4][{\\text{Cr}}^{\\text{III}}]_{\\text{T}}/\\{([H^+] + K_4) + (K_5[H+] + K_6K_4)[{\\text{IO}}^{−}_{4}]\\}.$$ The rate of the reaction increases with increasing pH due to the deprotonation equilibria of the complex. The experimental rate law is consistent with a mechanism in which the deprotonated form [CrIII(DPA)(OX)(OH)]2− is more reactive than the conjugated acid. It is proposed that electron transfer proceeds through an inner-sphere mechanism via coordination of IO$^{−}_{4}$ to chromium(III). Thermodynamic activation parameters were calculated using the transition state theory equation.dipicolinatochromium(III) complex involving oxalate as secondary ligand

  3. Antinociceptive Activity of Methanol Extract of Muntingia calabura Leaves and the Mechanisms of Action Involved

    Directory of Open Access Journals (Sweden)

    M. H. Mohd. Sani

    2012-01-01

    Full Text Available Muntingia calabura L. (family Elaeocarpaceae has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract of M. calabura leaves (MEMC and to elucidate the possible mechanism of antinociception involved. The in vivo chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test and thermal (hot plate test models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P<0.05 antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO donor, NG-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS, methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP pathway, or their combination also caused significant (P<0.05 change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.

  4. Astrocytes are involved in trigeminal dynamic mechanical allodynia: potential role of D-serine.

    Science.gov (United States)

    Dieb, W; Hafidi, A

    2013-09-01

    Trigeminal neuropathic pain affects millions of people worldwide. Despite decades of study on the neuronal processing of pain, mechanisms underlying enhanced pain states after injury remain unclear. N-methyl-D-aspartate (NMDA) receptor-dependent changes play a critical role in triggering central sensitization in neuropathic pain. These receptors are regulated at the glycine site through a mandatory endogenous co-agonist D-serine, which is synthesized by astrocytes. Therefore, the present study was carried out to determine whether astrocytes are involved, through D-serine secretion, in dynamic mechanical allodynia (DMA) obtained after chronic constriction of the infraorbital nerve (CCI-IoN) in rats. Two weeks after CCI-IoN, an important reaction of astrocytes was present in the medullary dorsal horn (MDH), as revealed by an up-regulation of glial fibrillary acidic protein (GFAP) in allodynic rats. In parallel, an increase in D-serine synthesis, which co-localized with its synthesis enzyme serine racemase, was strictly observed in astrocytes. Blocking astrocyte metabolism by intracisternal delivery of fluorocitrate alleviated DMA. Furthermore, the administration of D-amino-acid oxidase (DAAO), a D-serine-degrading enzyme, or that of L-serine O-sulfate (LSOS), a serine racemase inhibitor, significantly decreased pain behavior in allodynic rats. These results demonstrate that astrocytes are involved in the modulation of orofacial post-traumatic neuropathic pain via the release of the gliotransmitter D-serine.

  5. Mechanism involved in phagocytosis and killing of Listeria monocytogenes by Acanthamoeba polyphaga.

    Science.gov (United States)

    Akya, Alisha; Pointon, Andrew; Thomas, Connor

    2009-10-01

    Intra-cellular pathogen, Listeria monocytogenes, is capable of invasion and survival within mammalian cells. However, Acanthamoeba polyphaga trophozoites phagocytose and rapidly degrade Listeria cells. In order to provide more information on amoeba phagocytosis and killing mechanisms, this study used several inhibitor agents known to affect the phagocytosis and killing of bacteria by eukaryotes. Amoebae were pre-treated with mannose, cytochalasin D, wortmannin, suramin, ammonium chloride, bafilomycin A and monensin followed by co-culture with bacteria. Phagocytosis and killing of bacterial cells by amoeba trophozoites was assessed using plate counting methods and microscopy. The data presented indicates that actin polymerisation and cytoskeletal rearrangement are involved in phagocytosis of L. monocytogenes cells by A. polyphaga trophozoites. Further, both phagosomal acidification and phagosome-lysosome fusion are involved in killing and degradation of L. monocytogenes cells by A. polyphaga. However, the mannose-binding protein receptor does not play an important role in uptake of bacteria by amoeba trophozoites. In conclusion, this data reveals the similar principles of molecular mechanisms used by different types of eukaryotes in uptake and killing of bacteria.

  6. Viral fitness: relation to drug resistance mutations and mechanisms involved: nucleoside reverse transcriptase inhibitor mutations.

    Science.gov (United States)

    Weber, Jan; Henry, Kenneth R; Arts, Eric J; Quiñones-Mateu, Miguel E

    2007-03-01

    Nucleoside and nucleotide reverse transcriptase inhibitors constitute the backbone of highly active antiretroviral therapy in the treatment of HIV-1 infection. One of the major obstacles in achieving the long-term efficacy of anti-HIV-1 therapy is the development of resistance. The advent of resistance mutations is usually accompanied by a change in viral replicative fitness. This review focuses on the most common nucleoside reverse transcriptase inhibitor-associated mutations and their effects on HIV-1 replicative fitness. Recent studies have explained the two main mechanisms of resistance to nucleoside reverse transcriptase inhibitors and their role in HIV-1 replicative fitness. The first involves mutations directly interfering with binding or incorporation and seems to impact replicative fitness more adversely than the second mechanism, which involves enhanced excision of the newly incorporated analogue. Further studies have helped explain the antagonistic effects between amino acid substitutions, K65R, L74V, M184V, and thymidine analogue mutations, showing how viral replicative fitness influences the evolution of thymidine analogue resistance pathways. Nucleoside reverse transcriptase inhibitor resistance mutations impact HIV-1 replicative fitness to a lesser extent than protease resistance mutations. The monitoring of viral replicative fitness may help in the management of HIV-1 infection in highly antiretroviral-experienced individuals.

  7. Mechanisms and neuronal networks involved in reactive and proactive cognitive control of interference in working memory.

    Science.gov (United States)

    Irlbacher, Kerstin; Kraft, Antje; Kehrer, Stefanie; Brandt, Stephan A

    2014-10-01

    Cognitive control can be reactive or proactive in nature. Reactive control mechanisms, which support the resolution of interference, start after its onset. Conversely, proactive control involves the anticipation and prevention of interference prior to its occurrence. The interrelation of both types of cognitive control is currently under debate: Are they mediated by different neuronal networks? Or are there neuronal structures that have the potential to act in a proactive as well as in a reactive manner? This review illustrates the way in which integrating knowledge gathered from behavioral studies, functional imaging, and human electroencephalography proves useful in answering these questions. We focus on studies that investigate interference resolution at the level of working memory representations. In summary, different mechanisms are instrumental in supporting reactive and proactive control. Distinct neuronal networks are involved, though some brain regions, especially pre-SMA, possess functions that are relevant to both control modes. Therefore, activation of these brain areas could be observed in reactive, as well as proactive control, but at different times during information processing.

  8. Role of the endocannabinoid system in the mechanisms involved in the LPS-induced preterm labor.

    Science.gov (United States)

    Bariani, María Victoria; Domínguez Rubio, Ana Paula; Cella, Maximiliano; Burdet, Juliana; Franchi, Ana María; Aisemberg, Julieta

    2015-12-01

    Prematurity is the leading cause of perinatal morbidity and mortality worldwide. There is a strong causal relationship between infection and preterm births. Intrauterine infection elicits an immune response involving the release of inflammatory mediators like cytokines and prostaglandins (PG) that trigger uterine contractions and parturition events. Anandamide (AEA) is an endogenous ligand for the cannabinoid receptors CB1 and CB2. Similarly to PG, endocannabinoids are implicated in different aspects of reproduction, such as maintenance of pregnancy and parturition. Little is known about the involvement of endocannabinoids on the onset of labor in an infectious milieu. Here, using a mouse model of preterm labor induced by lipopolysaccharide (LPS), we explored changes on the expression of components of endocannabinoid system (ECS). We have also determined whether AEA and CB antagonists alter PG production that induces labor. We observed an increase in uterine N-acylphosphatidylethanolamine-specific phospholipase D expression (NAPE-PLD, the enzyme that synthesizes AEA) upon LPS treatment. Activity of catabolic enzyme fatty acid amide hydrolase (FAAH) did not change significantly. In addition, we also found that LPS modulated uterine cannabinoid receptors expression by downregulating Cb2 mRNA levels and upregulating CB1 protein expression. Furthermore, LPS and AEA induced PGF2a augmentation, and this was reversed by antagonizing CB1 receptor. Collectively, our results suggest that ECS may be involved in the mechanism by which infection causes preterm birth. © 2015 Society for Reproduction and Fertility.

  9. Estradiol decreases cortical reactive astrogliosis after brain injury by a mechanism involving cannabinoid receptors.

    Science.gov (United States)

    López Rodríguez, Ana Belén; Mateos Vicente, Beatriz; Romero-Zerbo, Silvana Y; Rodriguez-Rodriguez, Noé; Bellini, María José; Rodriguez de Fonseca, Fernando; Bermudez-Silva, Francisco Javier; Azcoitia, Iñigo; Garcia-Segura, Luis M; Viveros, María-Paz

    2011-09-01

    The neuroactive steroid estradiol reduces reactive astroglia after brain injury by mechanisms similar to those involved in the regulation of reactive gliosis by endocannabinoids. In this study, we have explored whether cannabinoid receptors are involved in the effects of estradiol on reactive astroglia. To test this hypothesis, the effects of estradiol, the cannabinoid CB1 antagonist/inverse agonist AM251, and the cannabinoid CB2 antagonist/inverse agonist AM630 were assessed in the cerebral cortex of male rats after a stab wound brain injury. Estradiol reduced the number of vimentin immunoreactive astrocytes and the number of glial fibrillary acidic protein immunoreactive astrocytes in the proximity of the wound. The effect of estradiol was significantly inhibited by the administration of either CB1 or CB2 receptor antagonists. The effect of estradiol may be in part mediated by alterations in endocannabinoid signaling because the hormone increased in the injured cerebral cortex the messenger RNA levels of CB2 receptors and of some of the enzymes involved in the synthesis and metabolism of endocannabinoids. These findings suggest that estradiol may decrease reactive astroglia in the injured brain by regulating the activity of the endocannabinoid system.

  10. Novel mechanisms of sildenafil in pulmonary hypertension involving cytokines/chemokines, MAP kinases and Akt.

    Directory of Open Access Journals (Sweden)

    Tamas Kiss

    Full Text Available Pulmonary arterial hypertension (PH is associated with high mortality due to right ventricular failure and hypoxia, therefore to understand the mechanism by which pulmonary vascular remodeling initiates these processes is very important. We used a well-characterized monocrotaline (MCT-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt pathway and nuclear factor (NF-κB activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. Besides its protective effect on lung morphology, sildenafil suppressed multiple cytokines involved in neutrophil and mononuclear cells recruitment including cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2α/β, tissue inhibitor of metalloproteinase (TIMP-1, interleukin (IL-1α, lipopolysaccharide induced CXC chemokine (LIX, monokine induced by gamma interferon (MIG, macrophage inflammatory protein (MIP-1α, and MIP-3α. NF-κB activation and phosphorylation were also attenuated by sildenafil. Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension.

  11. Mechanisms involved in the nociception triggered by the venom of the armed spider Phoneutria nigriventer.

    Directory of Open Access Journals (Sweden)

    Camila Gewehr

    Full Text Available BACKGROUND: The frequency of accidental spider bites in Brazil is growing, and poisoning due to bites from the spider genus Phoneutria nigriventer is the second most frequent source of such accidents. Intense local pain is the major symptom reported after bites of P. nigriventer, although the mechanisms involved are still poorly understood. Therefore, the aim of this study was to identify the mechanisms involved in nociception triggered by the venom of Phoneutria nigriventer (PNV. METHODOLOGY/PRINCIPAL FINDINGS: Twenty microliters of PNV or PBS was injected into the mouse paw (intraplantar, i.pl.. The time spent licking the injected paw was considered indicative of the level of nociception. I.pl. injection of PNV produced spontaneous nociception, which was reduced by arachnid antivenin (ArAv, local anaesthetics, opioids, acetaminophen and dipyrone, but not indomethacin. Boiling or dialysing the venom reduced the nociception induced by the venom. PNV-induced nociception is not dependent on glutamate or histamine receptors or on mast cell degranulation, but it is mediated by the stimulation of sensory fibres that contain serotonin 4 (5-HT4 and vanilloid receptors (TRPV1. We detected a kallikrein-like kinin-generating enzyme activity in tissue treated with PNV, which also contributes to nociception. Inhibition of enzymatic activity or administration of a receptor antagonist for kinin B2 was able to inhibit the nociception induced by PNV. PNV nociception was also reduced by the blockade of tetrodotoxin-sensitive Na(+ channels, acid-sensitive ion channels (ASIC and TRPV1 receptors. CONCLUSION/SIGNIFICANCE: Results suggest that both low- and high-molecular-weight toxins of PNV produce spontaneous nociception through direct or indirect action of kinin B2, TRPV1, 5-HT4 or ASIC receptors and voltage-dependent sodium channels present in sensory neurons but not in mast cells. Understanding the mechanisms involved in nociception caused by PNV are of

  12. Genes and mechanisms involved in beta-amyloid generation and Alzheimer's disease.

    Science.gov (United States)

    Steiner, H; Capell, A; Leimer, U; Haass, C

    1999-01-01

    Alzheimer's disease is characterized by the invariable accumulation of senile plaques that are predominantly composed of amyloid beta-peptide (Abeta). Abeta is generated by proteolytic processing of the beta-amyloid precursor protein (betaAPP) involving the combined action of beta- and gamma-secretase. Cleavage within the Abeta domain by alpha-secretase prevents Abeta generation. In some very rare cases of familial AD (FAD), mutations have been identified within the betaAPP gene. These mutations are located close to or at the cleavage sites of the secretases and pathologically effect betaAPP processing by increasing Abeta production, specifically its highly amyloidogenic 42 amino acid variant (Abeta42). Most of the mutations associated with FAD have been identified in the two presenilin (PS) genes, particularly the PS1 gene. Like the mutations identified within the betaAPP gene, mutations in PS1 and PS2 cause the increased generation of Abeta42. PS1 has been shown to be functionally involved in Notch signaling, a key process in cellular differentation, and in betaAPP processing. A gene knock out of PS1 in mice leads to an embryonic lethal phenotype similar to that of mice lacking Notch. In addition, absence of PS1 results in reduced gamma-secretase cleavage and leads to an accumulation of betaAPP C-terminal fragments and decreased amounts of Abeta. Recent work may suggest that PS1 could be the gamma-secretase itself, exhibiting the properties of a novel aspartyl protease. Mutagenesis of either of two highly conserved intramembraneous aspartate residues of PS1 leads to reduced Abeta production as observed in the PS1 knockout. A corresponding mutation in PS2 interfered with betaAPP processing and Notch signaling suggesting a functional redundancy of both presenilins. In this issue, some of the recent work on the molecular mechanisms involved in Alzheimer's disease (AD) as well as novel diagnostic approaches and risk factors for AD will be discussed. In the first

  13. Peptide Bond Synthesis by a Mechanism Involving an Enzymatic Reaction and a Subsequent Chemical Reaction.

    Science.gov (United States)

    Abe, Tomoko; Hashimoto, Yoshiteru; Zhuang, Ye; Ge, Yin; Kumano, Takuto; Kobayashi, Michihiko

    2016-01-22

    We recently reported that an amide bond is unexpectedly formed by an acyl-CoA synthetase (which catalyzes the formation of a carbon-sulfur bond) when a suitable acid and l-cysteine are used as substrates. DltA, which is homologous to the adenylation domain of nonribosomal peptide synthetase, belongs to the same superfamily of adenylate-forming enzymes, which includes many kinds of enzymes, including the acyl-CoA synthetases. Here, we demonstrate that DltA synthesizes not only N-(d-alanyl)-l-cysteine (a dipeptide) but also various oligopeptides. We propose that this enzyme catalyzes peptide synthesis by the following unprecedented mechanism: (i) the formation of S-acyl-l-cysteine as an intermediate via its "enzymatic activity" and (ii) subsequent "chemical" S → N acyl transfer in the intermediate, resulting in peptide formation. Step ii is identical to the corresponding reaction in native chemical ligation, a method of chemical peptide synthesis, whereas step i is not. To the best of our knowledge, our discovery of this peptide synthesis mechanism involving an enzymatic reaction and a subsequent chemical reaction is the first such one to be reported. This new process yields peptides without the use of a thioesterified fragment, which is required in native chemical ligation. Together with these findings, the same mechanism-dependent formation of N-acyl compounds by other members of the above-mentioned superfamily demonstrated that all members most likely form peptide/amide compounds by using this novel mechanism. Each member enzyme acts on a specific substrate; thus, not only the corresponding peptides but also new types of amide compounds can be formed.

  14. Involvement of endothelium-dependent and -independent mechanisms in midazolam-induced vasodilation.

    Science.gov (United States)

    Colussi, Gian Luca; Di Fabio, Alessandro; Catena, Cristiana; Chiuch, Alessandra; Sechi, Leonardo A

    2011-08-01

    Benzodiazepine (BDZ) infusion has been shown to reduce blood pressure in both humans and animals. Although the inhibitory effects of BDZ on the central nervous system have been well documented, less is known about the direct effects of BDZ on the vascular bed. The aims of this study were to assess the effects of the BDZ midazolam on the vascular system in C57/BL6 mouse aortic rings and to investigate the mechanisms of its direct vascular action. We found that midazolam induced reversible, dose-dependent vasodilation in potassium- and phenylephrine-precontracted rings. In rings that were precontracted with potassium or phenylephrine, treatment with 10 μmol l(-1) midazolam increased vasodilation by 15 and 60%, respectively, compared with baseline. Vasodilation increased by 80 and 87%, respectively, after treatment with 50 μmol l(-1) midazolam. Only the low concentration of midazolam (10 μmol l(-1)) induced endothelium-dependent vasodilation in phenylephrine-precontracted rings. Vasodilation increased by 60% in rings with endothelium and by 20% in rings without endothelium. Conversely, only the high concentration of midazolam (50 μmol l(-1)) reduced the CaCl(2)-induced vasoconstriction of aortic rings with EC(50) (the concentration giving 50% of the maximal effect) values of 1 and 6 mmol l(-1) for vehicle- and midazolam-treated rings, respectively. Furthermore, the incubation of phenylephrine-precontracted rings with an inhibitor of the nitric oxide synthase (NOS) NG-nitro-L-arginine methyl ester or the inhibitors of central or peripheral type BDZ receptors (flumazenil or PK 11195, respectively) produced no change in midazolam-induced vasodilation. Thus, low concentrations of midazolam induce vasodilation via an endothelium-dependent mechanism that does not involve NO production. In contrast, high concentrations of midazolam induce vasodilation via an endothelium-independent mechanism that implies reduced sensitivity of aortic rings to calcium ions. Additionally

  15. Coral bleaching under thermal stress: putative involvement of host/symbiont recognition mechanisms

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    Tambutte Sylvie

    2009-08-01

    Full Text Available Abstract Background Coral bleaching can be defined as the loss of symbiotic zooxanthellae and/or their photosynthetic pigments from their cnidarian host. This major disturbance of reef ecosystems is principally induced by increases in water temperature. Since the beginning of the 1980s and the onset of global climate change, this phenomenon has been occurring at increasing rates and scales, and with increasing severity. Several studies have been undertaken in the last few years to better understand the cellular and molecular mechanisms of coral bleaching but the jigsaw puzzle is far from being complete, especially concerning the early events leading to symbiosis breakdown. The aim of the present study was to find molecular actors involved early in the mechanism leading to symbiosis collapse. Results In our experimental procedure, one set of Pocillopora damicornis nubbins was subjected to a gradual increase of water temperature from 28°C to 32°C over 15 days. A second control set kept at constant temperature (28°C. The differentially expressed mRNA between the stressed states (sampled just before the onset of bleaching and the non stressed states (control were isolated by Suppression Subtractive Hybridization. Transcription rates of the most interesting genes (considering their putative function were quantified by Q-RT-PCR, which revealed a significant decrease in transcription of two candidates six days before bleaching. RACE-PCR experiments showed that one of them (PdC-Lectin contained a C-Type-Lectin domain specific for mannose. Immunolocalisation demonstrated that this host gene mediates molecular interactions between the host and the symbionts suggesting a putative role in zooxanthellae acquisition and/or sequestration. The second gene corresponds to a gene putatively involved in calcification processes (Pdcyst-rich. Its down-regulation could reflect a trade-off mechanism leading to the arrest of the mineralization process under stress

  16. MicroRNA: biogenetic and functional mechanisms and involvements in cell differentiation and cancer.

    Science.gov (United States)

    Tsuchiya, Soken; Okuno, Yasushi; Tsujimoto, Gozoh

    2006-08-01

    MicroRNAs (miRNAs) are endogenous small noncoding RNAs (20-23 nucleotides) that negatively regulate the gene expressions at the posttranscriptional level by base pairing to the 3' untranslated region of target messenger RNAs. Hundreds of miRNAs have been identified in humans and evolutionarily conserved from plants to animals. It is revealed that miRNAs regulate various physiological and pathological pathways such as cell differentiation, cell proliferation, and tumoriogenesis. By the computational analysis, it is predicted that 30% of protein-encoding genes are regulated by miRNAs. In this review, we discuss recent remarkable advances in the miRNA biogenetic and functional mechanisms and the involvements of miRNAs in cell differentiation, especially in hematopoietic lineages, and cancer. These evidences offer the possibility that miRNAs would be potentially useful for drug discovery.

  17. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    Energy Technology Data Exchange (ETDEWEB)

    Massi, Paola [Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Via Vanvitelli 32, 20129 Milan (Italy); Valenti, Marta; Solinas, Marta; Parolaro, Daniela, E-mail: daniela.parolaro@uninsubria.it [Department of Structural and Functional Biology, Section of Pharmacology, Center of Neuroscience, University of Insubria, Via A. da Giussano 10, 20152 Busto Arsizio, Varese (Italy)

    2010-05-26

    Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

  18. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Paola Massi

    2010-05-01

    Full Text Available Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

  19. Spinal toll like receptor 3 is involved in chronic pancreatitis-induced mechanical allodynia of rat

    Directory of Open Access Journals (Sweden)

    Feng Quan-Xing

    2011-02-01

    Full Text Available Abstract Background Mechanisms underlying pain in chronic pancreatitis (CP are incompletely understood. Our previous data showed that astrocytes were actively involved. However, it was unclear how astrocytic activation was induced in CP conditions. In the present study, we hypothesized that toll-like receptors (TLRs were involved in astrocytic activation and pain behavior in CP-induced pain. Results To test our hypothesis, we first investigated the changes of TLR2-4 in the rat CP model induced by intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS. Western blot showed that after TNBS infusion, TLR3, but not TLR2 or TLR4, was increased gradually and maintained at a very high level for up to 5 w, which correlated with the changing course of mechanical allodynia. Double immunostaining suggested that TLR3 was highly expressed on astrocytes. Infusion with TLR3 antisense oligodeoxynucleotide (ASO dose-dependently attenuated CP-induced allodynia. CP-induced astrocytic activation in the spinal cord was also significantly suppressed by TLR3 ASO. Furthermore, real-time PCR showed that IL-1β, TNF-α, IL-6 and monocyte chemotactic protein-1 (MCP-1 were significantly increased in spinal cord of pancreatic rats. In addition, TLR3 ASO significantly attenuated CP-induced up-regulation of IL-1β and MCP-1. Conclusions These results suggest a probable "TLR3-astrocytes-IL-1β/MCP-1" pathway as a positive feedback loop in the spinal dorsal horn in CP conditions. TLR3-mediated neuroimmune interactions could be new targets for treating persistent pain in CP patients.

  20. Cellular mechanisms involved in CO(2) and acid signaling in chemosensitive neurons.

    Science.gov (United States)

    Putnam, Robert W; Filosa, Jessica A; Ritucci, Nicola A

    2004-12-01

    An increase in CO(2)/H(+) is a major stimulus for increased ventilation and is sensed by specialized brain stem neurons called central chemosensitive neurons. These neurons appear to be spread among numerous brain stem regions, and neurons from different regions have different levels of chemosensitivity. Early studies implicated changes of pH as playing a role in chemosensitive signaling, most likely by inhibiting a K(+) channel, depolarizing chemosensitive neurons, and thereby increasing their firing rate. Considerable progress has been made over the past decade in understanding the cellular mechanisms of chemosensitive signaling using reduced preparations. Recent evidence has pointed to an important role of changes of intracellular pH in the response of central chemosensitive neurons to increased CO(2)/H(+) levels. The signaling mechanisms for chemosensitivity may also involve changes of extracellular pH, intracellular Ca(2+), gap junctions, oxidative stress, glial cells, bicarbonate, CO(2), and neurotransmitters. The normal target for these signals is generally believed to be a K(+) channel, although it is likely that many K(+) channels as well as Ca(2+) channels are involved as targets of chemosensitive signals. The results of studies of cellular signaling in central chemosensitive neurons are compared with results in other CO(2)- and/or H(+)-sensitive cells, including peripheral chemoreceptors (carotid body glomus cells), invertebrate central chemoreceptors, avian intrapulmonary chemoreceptors, acid-sensitive taste receptor cells on the tongue, and pain-sensitive nociceptors. A multiple factors model is proposed for central chemosensitive neurons in which multiple signals that affect multiple ion channel targets result in the final neuronal response to changes in CO(2)/H(+).

  1. Molecular characterization of HIV-1 subtype C gp-120 regions potentially involved in virus adaptive mechanisms.

    Directory of Open Access Journals (Sweden)

    Alessandra Cenci

    Full Text Available The role of variable regions of HIV-1 gp120 in immune escape of HIV has been investigated. However, there is scant information on how conserved gp120 regions contribute to virus escaping. Here we have studied how molecular sequence characteristics of conserved C3, C4 and V3 regions of clade C HIV-1 gp120 that are involved in HIV entry and are target of the immune response, are modulated during the disease course. We found an increase of "shifting" putative N-glycosylation sites (PNGSs in the α2 helix (in C3 and in C4 and an increase of sites under positive selection pressure in the α2 helix during the chronic stage of disease. These sites are close to CD4 and to co-receptor binding sites. We also found a negative correlation between electric charges of C3 and V4 during the late stage of disease counteracted by a positive correlation of electric charges of α2 helix and V5 during the same stage. These data allow us to hypothesize possible mechanisms of virus escape involving constant and variable regions of gp120. In particular, new mutations, including new PNGSs occurring near the CD4 and CCR5 binding sites could potentially affect receptor binding affinity and shield the virus from the immune response.

  2. Beyond free education policy: a focus on psychosocial correlates of ...

    African Journals Online (AJOL)

    Beyond free education policy: a focus on psychosocial correlates of school ... Parents' Attitude towards School, Parental Involvement and Peer Influence) ... A sample of 300 secondary school students drawn from the 3 Local Government Areas ...

  3. Protein Machineries Involved in the Attachment of Heme to Cytochrome c: Protein Structures and Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Carlo Travaglini-Allocatelli

    2013-01-01

    Full Text Available Cytochromes c (Cyt c are ubiquitous heme-containing proteins, mainly involved in electron transfer processes, whose structure and functions have been and still are intensely studied. Surprisingly, our understanding of the molecular mechanism whereby the heme group is covalently attached to the apoprotein (apoCyt in the cell is still largely unknown. This posttranslational process, known as Cyt c biogenesis or Cyt c maturation, ensures the stereospecific formation of the thioether bonds between the heme vinyl groups and the cysteine thiols of the apoCyt heme binding motif. To accomplish this task, prokaryotic and eukaryotic cells have evolved distinctive protein machineries composed of different proteins. In this review, the structural and functional properties of the main maturation apparatuses found in gram-negative and gram-positive bacteria and in the mitochondria of eukaryotic cells will be presented, dissecting the Cyt c maturation process into three functional steps: (i heme translocation and delivery, (ii apoCyt thioreductive pathway, and (iii apoCyt chaperoning and heme ligation. Moreover, current hypotheses and open questions about the molecular mechanisms of each of the three steps will be discussed, with special attention to System I, the maturation apparatus found in gram-negative bacteria.

  4. A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel

    Directory of Open Access Journals (Sweden)

    Andrew P. Wojtovich

    2013-03-01

    Full Text Available Opening of BK-type Ca2+ activated K+ channels protects the heart against ischemia-reperfusion (IR injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse perfused heart model of IR injury. As anticipated, deletion of the Slo1 gene blocked this protection. However, in an isolated cardiomyocyte model of IR injury, protection by NS1619 and NS11021 was insensitive to Slo1 deletion. These data suggest that protection in intact hearts occurs by a non-cardiomyocyte autonomous, SLO1-dependent, mechanism. In this regard, an in-situ assay of intrinsic cardiac neuronal function (tachycardic response to nicotine revealed that NS1619 preserved cardiac neurons following IR injury. Furthermore, blockade of synaptic transmission by hexamethonium suppressed cardioprotection by NS1619 in intact hearts. These results suggest that opening SLO1 protects the heart during IR injury, via a mechanism that involves intrinsic cardiac neurons. Cardiac neuronal ion channels may be useful therapeutic targets for eliciting cardioprotection.

  5. Exploring the temporal mechanism involved in the pitch of unresolved harmonics.

    Science.gov (United States)

    Kaernbach, C; Bering, C

    2001-08-01

    This paper continues a line of research initiated by Kaernbach and Demany [J. Acoust. Soc. Am. 104, 2298-2306 (1998)], who employed filtered click sequences to explore the temporal mechanism involved in the pitch of unresolved harmonics. In a first experiment, the just noticeable difference (jnd) for the fundamental frequency (F0) of high-pass filtered and low-pass masked click trains was measured, with F0 (100 to 250 Hz) and the cut frequency (0.5 to 6 kHz) being varied orthogonally. The data confirm the result of Houtsma and Smurzynski [J. Acoust. Soc. Am. 87, 304-310 (1990)] that a pitch mechanism working on the temporal structure of the signal is responsible for analyzing frequencies higher than ten times the fundamental. Using high-pass filtered click trains, however, the jnd for the temporal analysis is at 1.2% as compared to 2%-3% found in studies using band-pass filtered stimuli. Two further experiments provide evidence that the pitch of this stimulus can convey musical information. A fourth experiment replicates the finding of Kaernbach and Demany on first- and second-order regularities with a cut frequency of 2 kHz and extends the paradigm to binaural aperiodic click sequences. The result suggests that listeners can detect first-order temporal regularities in monaural click streams as well as in binaurally fused click streams.

  6. Seismic behavior and mechanism analysis of innovative precast shear wall involving vertical joints

    Institute of Scientific and Technical Information of China (English)

    孙建; 邱洪兴

    2015-01-01

    To study the seismic performance and load-transferring mechanism of an innovative precast shear wall (IPSW) involving vertical joints, an experimental investigation and theoretical analysis were successively conducted on two test walls. The test results confirm the feasibility of the novel joints as well as the favorable seismic performance of the walls, even though certain optimization measures should be taken to improve the ductility. The load-transferring mechanism subsequently is theoretically investigated based on the experimental study. The theoretical results show the load-transferring route of the novel joints is concise and definite. During the elastic stage, the vertical shear stress in the connecting steel frame (CSF) distributes uniformly;and each high-strength bolt (HSB) primarily delivers vertical shear force. However, the stress in the CSF redistributes when the walls develop into the elastic-plastic stage. At the ultimate state, the vertical shear stress and horizontal normal stress in the CSF distribute linearly;and the HSBs at both ends of the CSF transfer the maximum shear forces.

  7. Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Jing Wang; Xiao-Wen Lv; Jie-Ping Shi; Xiao-Song Hu

    2007-01-01

    AIM:To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells.Possible molecular mechanisms were explored.METHODS:[3-(4,5)-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide(MTT)assay,plasmid transfection,reporter assay,FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells.RESULTS:C2-ceramide was found to inhibit the growth of Bel7402 cells by inducing cell cycle arrest.During the process,the expression of p21 protein increased,while that of cyclinD1,phospho-ERK1/2 and c-myc decreased.Furthermore,the level of CDK7 was downregulated,while the transcriptional activity of PPARγ was upregulated.Addition of GW9662,which is a PPARγ specific antagonist,could reserve the modulation action on CDK7.CONCLUSION:Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7,at least partly,through PPARγ activation.The ERK signaling pathway was involved in this process.

  8. Mechanism of microglia neuroprotection: Involvement of P2X7, TNFα, and valproic acid.

    Science.gov (United States)

    Masuch, Annette; Shieh, Chu-Hsin; van Rooijen, Nico; van Calker, Dietrich; Biber, Knut

    2016-01-01

    Recently, we have demonstrated that ramified microglia are neuroprotective in N-methyl-D-aspartate (NMDA)-induced excitotoxicity in organotypic hippocampal slice cultures (OHSCs). The present study aimed to elucidate the underlying neuron-glia communication mechanism. It is shown here that pretreatment of OHSC with high concentrations of adenosine 5'-triphosphate (ATP) reduced NMDA-induced neuronal death only in presence of microglia. Specific agonists and antagonists identified the P2X7 receptor as neuroprotective receptor which was confirmed by absence of ATP-dependent neuroprotection in P2X7-deficient OHSC. Microglia replenished chimeric OHSC consisting of wild-type tissue replenished with P2X7-deficient microglia confirmed the involvement of microglial P2X7 receptor in neuroprotection. Stimulation of P2X7 in primary microglia induced tumor necrosis factor α (TNFα) release and blocking TNFα by a neutralizing antibody in OHSC abolished neuroprotection by ATP. OHSC from TNFα-deficient mice show increased exicitoxicity and activation of P2X7 did not rescue neuronal survival in the absence of TNFα. The neuroprotective effect of valproic acid (VPA) was strictly dependent on the presence of microglia and was mediated by upregulation of P2X7 in the cells. The present study demonstrates that microglia-mediated neuroprotection depends on ATP-activated purine receptor P2X7 and induction of TNFα release. This neuroprotective pathway was strengthened by VPA elucidating a novel mechanism for the neuroprotective function of VPA.

  9. A host defense mechanism involving CFTR-mediated bicarbonate secretion in bacterial prostatitis.

    Directory of Open Access Journals (Sweden)

    Chen Xie

    Full Text Available BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(- and HCO(3(-, in mediating prostate HCO(3(- secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II, along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3(- content (>50 mM, rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3(- on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3(- secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3(- secretion may be up-regulated in prostatitis as a host defense mechanism.

  10. Mechanism of oxidative stress involved in the toxicity of ZnO nanoparticles against eukaryotic cells

    Directory of Open Access Journals (Sweden)

    M. Saliani

    2016-01-01

    Full Text Available ZnO NPs (zinc oxide nanoparticles has generated significant scientific interest as a novel antibacterial and anticancer agent. Since oxidative stress is a critical determinant of ZnO NPs-induced damage, it is necessary to characterize their underlying mode of action. Different structural and physicochemical properties of ZnO NPs such as particle surface, size, shape, crystal structure, chemical position, and presence of metals can lead to changes in biological activities including ROS (reactive oxygen species production. However, there are some inconsistencies in the literature on the relation between the physicochemical features of ZnO NPs and their plausible oxidative stress mechanism. Herein, the possible oxidative stress mechanism of ZnO NPs was reviewed. This is worthy of further detailed evaluations in order to improve our understanding of vital NPs characteristics governing their toxicity. Therefore, this study focuses on the different reported oxidative stress paradigms induced by ZnO NPs including ROS generated by NPs, oxidative stress due to the NPs-cell interaction, and role of the particle dissolution in the oxidative damage. Also, this study tries to characterize and understand the multiple pathways involved in oxidative stress induced by ZnO NPs. Knowledge about different cellular signaling cascades stimulated by ZnO NPs lead to the better interpretation of the toxic influences induced by the cellular and acellular parameters. Regarding the potential benefits of toxic effects of ZnO NPs, in-depth evaluation of their toxicity mechanism and various effects of these nanoparticles would facilitate their implementation for biomedical applications.

  11. Analysis of regulatory network involved in mechanical induction of embryonic stem cell differentiation.

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    Xinan Zhang

    Full Text Available Embryonic stem cells are conventionally differentiated by modulating specific growth factors in the cell culture media. Recently the effect of cellular mechanical microenvironment in inducing phenotype specific differentiation has attracted considerable attention. We have shown the possibility of inducing endoderm differentiation by culturing the stem cells on fibrin substrates of specific stiffness. Here, we analyze the regulatory network involved in such mechanically induced endoderm differentiation under two different experimental configurations of 2-dimensional and 3-dimensional culture, respectively. Mouse embryonic stem cells are differentiated on an array of substrates of varying mechanical properties and analyzed for relevant endoderm markers. The experimental data set is further analyzed for identification of co-regulated transcription factors across different substrate conditions using the technique of bi-clustering. Overlapped bi-clusters are identified following an optimization formulation, which is solved using an evolutionary algorithm. While typically such analysis is performed at the mean value of expression data across experimental repeats, the variability of stem cell systems reduces the confidence on such analysis of mean data. Bootstrapping technique is thus integrated with the bi-clustering algorithm to determine sets of robust bi-clusters, which is found to differ significantly from corresponding bi-clusters at the mean data value. Analysis of robust bi-clusters reveals an overall similar network interaction as has been reported for chemically induced endoderm or endodermal organs but with differences in patterning between 2-dimensional and 3-dimensional culture. Such analysis sheds light on the pathway of stem cell differentiation indicating the prospect of the two culture configurations for further maturation.

  12. Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms.

    Science.gov (United States)

    Srinivasan, Padmanabhan; Kapadia, Rubina; Biswas, Arundhati; Said, Hamid M

    2014-11-01

    Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5'-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na(+) dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.

  13. Mechanisms involved in calcium oxalate endocytosis by Madin-Darby canine kidney cells

    Directory of Open Access Journals (Sweden)

    A.H. Campos

    2000-01-01

    Full Text Available Calcium oxalate (CaOx crystals adhere to and are internalized by tubular renal cells and it seems that this interaction is related (positively or negatively to the appearance of urinary calculi. The present study analyzes a series of mechanisms possibly involved in CaOx uptake by Madin-Darby canine kidney (MDCK cells. CaOx crystals were added to MDCK cell cultures and endocytosis was evaluated by polarized light microscopy. This process was inhibited by an increase in intracellular calcium by means of ionomycin (100 nM; N = 6; 43.9% inhibition; P<0.001 or thapsigargin (1 µM; N = 6; 33.3% inhibition; P<0.005 administration, and via blockade of cytoskeleton assembly by the addition of colchicine (10 µM; N = 8; 46.1% inhibition; P<0.001 or cytochalasin B (10 µM; N = 8; 34.2% inhibition; P<0.001. Furthermore, CaOx uptake was reduced when the activity of protein kinase C was inhibited by staurosporine (10 nM; N = 6; 44% inhibition; P<0.01, or that of cyclo-oxygenase by indomethacin (3 µM; N = 12; 17.2% inhibition; P<0.05; however, the uptake was unaffected by modulation of potassium channel activity with glibenclamide (3 µM; N = 6, tetraethylammonium (1 mM; N = 6 or cromakalim (1 µM; N = 6. Taken together, these data indicate that the process of CaOx internalization by renal tubular cells is similar to the endocytosis reported for other systems. These findings may be relevant to cellular phenomena involved in early stages of the formation of renal stones.

  14. Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism(s) involved in its anti‐inflammatory effect

    National Research Council Canada - National Science Library

    Shen, Yuh‐Chiang; Chen, Chieh‐Fu; Chiou, Wen‐Fei

    2002-01-01

    .... To further elucidate the possible mechanism(s) underlying the ANDRO's effect, N ‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP)‐induced adhesion and transmigration of isolated peripheral human neutrophils were studied...

  15. Involvement of metabolites in early defense mechanism of oil palm (Elaeis guineensis Jacq.) against Ganoderma disease.

    Science.gov (United States)

    Nusaibah, S A; Siti Nor Akmar, A; Idris, A S; Sariah, M; Mohamad Pauzi, Z

    2016-12-01

    Understanding the mechanism of interaction between the oil palm and its key pathogen, Ganoderma spp. is crucial as the disease caused by this fungal pathogen leads to a major loss of revenue in leading palm oil producing countries in Southeast Asia. Here in this study, we assess the morphological and biochemical changes in Ganoderma disease infected oil palm seedling roots in both resistant and susceptible progenies. Rubber woodblocks fully colonized by G. boninense were applied as a source of inoculum to artificially infect the roots of resistant and susceptible oil palm progenies. Gas chromatography-mass spectrometry was used to measure an array of plant metabolites in 100 resistant and susceptible oil palm seedling roots treated with pathogenic Ganoderma boninense fungus. Statistical effects, univariate and multivariate analyses were used to identify key-Ganoderma disease associated metabolic agitations in both resistant and susceptible oil palm root tissues. Ganoderma disease related defense shifts were characterized based on (i) increased antifungal activity in crude extracts, (ii) increased lipid levels, beta- and gamma-sitosterol particularly in the resistant progeny, (iii) detection of heterocyclic aromatic organic compounds, benzo [h] quinoline, pyridine, pyrimidine (iv) elevation in antioxidants, alpha- and beta-tocopherol (iv) degraded cortical cell wall layers, possibly resulting from fungal hydrolytic enzyme activity needed for initial penetration. The present study suggested that plant metabolites mainly lipids and heterocyclic aromatic organic metabolites could be potentially involved in early oil palm defense mechanism against G. boninense infection, which may also highlight biomarkers for disease detection, treatment, development of resistant variety and monitoring. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  16. Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jun [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Department of Pharmacology, College of Medicine, Wuhan University of Science and Technology, Wuhan (China); Cao, Hui [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wang, Hongjie [Section of Neurobiology, Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL (United States); Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xiang, Ming, E-mail: xiangming@mails.tjmu.edu.cn [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China)

    2015-06-15

    Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation.

  17. [Psychosocial aspects of halitosis

    NARCIS (Netherlands)

    Jongh, A. de; Baat, C. de; Horstman, M.

    2012-01-01

    Using a representative sample from the Dutch population, some psychosocial aspects of halitosis were examined. The results of the survey showed that almost 90% of the Dutch population aged 16 years and older were regularly faced with halitosis. Forty percent reported to be exposed to someone with ha

  18. Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia.

    Directory of Open Access Journals (Sweden)

    Bassam R Ali

    Full Text Available Hereditary haemorrhagic telangiectasia (HHT is an autosomal dominant genetic condition affecting the vascular system and is characterised by epistaxis, arteriovenous malformations and mucocutaneous and gastrointestinal telangiectases. This disorder affects approximately 1 in 8,000 people worldwide. Significant morbidity is associated with this condition in affected individuals, and anaemia can be a consequence of repeated haemorrhages from telangiectasia in the gut and nose. In the majority of the cases reported, the condition is caused by mutations in either ACVRL1 or endoglin genes, which encode components of the TGF-beta signalling pathway. Numerous missense mutations in endoglin have been reported as causative defects for HHT but the exact underlying cellular mechanisms caused by these mutations have not been fully established despite data supporting a role for the endoplasmic reticulum (ER quality control machinery. For this reason, we examined the subcellular trafficking of twenty-five endoglin disease-causing missense mutations. The mutant proteins were expressed in HeLa and HEK293 cell lines, and their subcellular localizations were established by confocal fluorescence microscopy alongside the analysis of their N-glycosylation profiles. ER quality control was found to be responsible in eight (L32R, V49F, C53R, V125D, A160D, P165L, I271N and A308D out of eleven mutants located on the orphan extracellular domain in addition to two (C363Y and C382W out of thirteen mutants in the Zona Pellucida (ZP domain. In addition, a single intracellular domain missense mutant was examined and found to traffic predominantly to the plasma membrane. These findings support the notion of the involvement of the ER's quality control in the mechanism of a significant number, but not all, missense endoglin mutants found in HHT type 1 patients. Other mechanisms including loss of interactions with signalling partners as well as adverse effects on functional

  19. Neural mechanisms involved in the oral representation of percussion music: an fMRI study.

    Science.gov (United States)

    Tsai, Chen-Gia; Chen, Chien-Chung; Chou, Tai-Li; Chen, Jyh-Horng

    2010-11-01

    Numerous music cultures use nonsense syllables to represent percussive sounds. Covert reciting of these syllable sequences along with percussion music aids active listeners in keeping track of music. Owing to the acoustic dissimilarity between the representative syllables and the referent percussive sounds, associative learning is necessary for the oral representation of percussion music. We used functional magnetic resonance imaging (fMRI) to explore the neural processes underlying oral rehearsals of music. There were four music conditions in the experiment: (1) passive listening to unlearned percussion music, (2) active listening to learned percussion music, (3) active listening to the syllable representation of (2), and (4) active listening to learned melodic music. Our results specified two neural substrates of the association mechanisms involved in the oral representation of percussion music. First, information integration of heard sounds and the auditory consequences of subvocal rehearsals may engage the right planum temporale during active listening to percussion music. Second, mapping heard sounds to articulatory and laryngeal gestures may engage the left middle premotor cortex.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Visfatin is involved in promotion of colorectal carcinoma malignancy through an inducing EMT mechanism.

    Science.gov (United States)

    Yang, Jing; Zhang, Kun; Song, Haixing; Wu, Mingbo; Li, Jingyi; Yong, Ziyi; Jiang, Sheng; Kuang, Xi; Zhang, Tao

    2016-05-31

    Increasing evidences suggested visfatin, a newly discovered obesity-induced adipocytokine, is involved in promotion of cancer malignancy and correlated with worse clinical prognosis. While its effects and mechanisms on progression of colorectal cancer (CRC) remain unclear. Our clinical data show that visfatin protein is over expressed, positive associated with lymph node metastasis, high-grade tumor, and poor prognosis in 87 CRC patients. The levels of plasma visfatin are significantly upregulated in Stage IV colon cancer. Visfatin can significantly promote the in vitro migration and invasion of CRC cells via induction epithelial mesenchymal transition (EMT). It can increase the expression and nuclear translocation of Snail, a key transcription factor in regulating EMT. While silencing of Snail attenuates visfatin induced EMT. Further studies reveal visfatin can inhibit the association of Snail with GSK-3β and subsequently suppress ubiquitylation of Snail. In addition, visfatin can increase the expression and nuclear translocation of β-catenin, elevate its binding with Snail promoter, and then increase the transcription of Snail. While inhibitor of PI3K/Akt, LY294002, abolishes visfatin induced up regulation of Snail, Vimentin (Vim), β-catenin, and phosphorylated GSK-3β. In summary, our data suggest that increased expression of visfatin are associated with a more aggressive phenotype of CRC patients. It can trigger the EMT of CRC cells via Akt/GSK-3β/β-catenin signals.

  2. Orientation mechanisms and sensory organs involved in host location in a dipteran parasitoid larva.

    Science.gov (United States)

    Crespo, José E; Lazzari, Claudio R; Castelo, Marcela K

    2011-01-01

    The robber fly Mallophora ruficauda is one of the principal pests of apiculture in the Pampas region of Argentina. Larvae are solitary ectoparasitoids of third-instar scarab beetle larvae. Females of M. ruficauda do not lay eggs on or near the hosts, but on tall grasses. After hatching, larvae are dispersed by the wind and drop to the ground, where they dig and search for potential hosts. It is known that second-instar larvae of M. ruficauda exhibit active host-searching behaviour towards their preferred hosts, i.e., third-instar larvae of Cyclocephala signaticollis. Although host-location seems to be mediated by chemical cues, the mechanism of orientation and the sensory organs involved in host location remain unknown. We carried out behavioural experiments in the laboratory to address these questions. We also tested whether the orientation behaviour is exclusively based on the use of chemical cues. We found that larvae of M. ruficauda detect the chemicals with chemosensilla on the maxillary palps. Only one maxillary palp suffices for orientation, but their bilateral ablation abolishes orientation. Besides, an hexane extract of the host body was as attractive as a live host. Our results support that M. ruficauda larvae find their hosts underground by means of chemoklinotaxis.

  3. Gene expression modulation and the molecular mechanisms involved in Nelfinavir resistance in Leishmania donovani axenic amastigotes.

    Science.gov (United States)

    Kumar, Pranav; Lodge, Robert; Raymond, Frédéric; Ritt, Jean-François; Jalaguier, Pascal; Corbeil, Jacques; Ouellette, Marc; Tremblay, Michel J

    2013-08-01

    Drug resistance is a major public health challenge in leishmaniasis chemotherapy, particularly in the case of emerging Leishmania/HIV-1 co-infections. We have delineated the mechanism of cell death induced by the HIV-1 protease inhibitor, Nelfinavir, in the Leishmania parasite. In order to further study Nelfinavir-Leishmania interactions, we selected Nelfinavir-resistant axenic amastigotes in vitro and characterized them. RNA expression profiling analyses and comparative genomic hybridizations of closely related Leishmania species were used as a screening tool to compare Nelfinavir-resistant and -sensitive parasites in order to identify candidate genes involved in drug resistance. Microarray analyses of Nelfinavir-resistant and -sensitive Leishmania amastigotes suggest that parasites regulate mRNA levels either by modulating gene copy numbers through chromosome aneuploidy, or gene deletion/duplication by homologous recombination. Interestingly, supernumerary chromosomes 6 and 11 in the resistant parasites lead to upregulation of the ABC class of transporters. Transporter assays using radiolabelled Nelfinavir suggest a greater drug accumulation in the resistant parasites and in a time-dependent manner. Furthermore, high-resolution electron microscopy and measurements of intracellular polyphosphate levels showed an increased number of cytoplasmic vesicular compartments known as acidocalcisomes in Nelfinavir-resistant parasites. Together these results suggest that Nelfinavir is rapidly and dramatically sequestered in drug-induced intracellular vesicles.

  4. [Oncogenes RET/PTC and mechanisms of their involvement in thyroid cancerogenesis].

    Science.gov (United States)

    Voskoboĭnyk, L H

    2009-01-01

    Papillary thyroid carcinomas are the most common type of thyroid oncopathology, and are rather often associated with the expression of RET/PTC oncogens. The first oncogen RET/PTC1 was isolated more than 20 years ago. Now 13 different forms of RET/PTC are known, and 12 different partner-genes are described, that could be involved in formation of RET/PTC oncogenes. The most common of them are RET/PTC1 and RET/PTC3 forms. The great majority of oncogens RET/PTC, except for two--ELKS-RET and HOOK3-RET, have been founded in radioaction-induced thyroid tumors. There is an opinion that the key role in development of papillary thyroid carcinomas belongs to RET/PTC oncogens. The data about different types of RET/PTC oncogens, factors, that lead to their formation have been described in the present review. Also different mechanisms of activation of transduction pathways and gene's expression in thyroid cells after RET/PTC induction have been presented.

  5. Molecular mechanisms involved in the pathogenesis of alphavirus-induced arthritis.

    Science.gov (United States)

    Assunção-Miranda, Iranaia; Cruz-Oliveira, Christine; Da Poian, Andrea T

    2013-01-01

    Arthritogenic alphaviruses, including Ross River virus (RRV), Chikungunya virus (CHIKV), Sindbis virus (SINV), Mayaro virus (MAYV), O'nyong-nyong virus (ONNV), and Barmah Forest virus (BFV), cause incapacitating and long lasting articular disease/myalgia. Outbreaks of viral arthritis and the global distribution of these diseases point to the emergence of arthritogenic alphaviruses as an important public health problem. This review discusses the molecular mechanisms involved in alphavirus-induced arthritis, exploring the recent data obtained with in vitro systems and in vivo studies using animal models and samples from patients. The factors associated to the extension and persistence of symptoms are highlighted, focusing on (a) virus replication in target cells, and tissues, including macrophages and muscle cells; (b) the inflammatory and immune responses with recruitment and activation of macrophage, NK cells and T lymphocytes to the lesion focus and the increase of inflammatory mediators levels; and (c) the persistence of virus or viral products in joint and muscle tissues. We also discuss the importance of the establishment of novel animal models to test new molecular targets and to develop more efficient and selective drugs to treat these diseases.

  6. Molecular Mechanisms Involved in the Pathogenesis of Alphavirus-Induced Arthritis

    Directory of Open Access Journals (Sweden)

    Iranaia Assunção-Miranda

    2013-01-01

    Full Text Available Arthritogenic alphaviruses, including Ross River virus (RRV, Chikungunya virus (CHIKV, Sindbis virus (SINV, Mayaro virus (MAYV, O'nyong-nyong virus (ONNV, and Barmah Forest virus (BFV, cause incapacitating and long lasting articular disease/myalgia. Outbreaks of viral arthritis and the global distribution of these diseases point to the emergence of arthritogenic alphaviruses as an important public health problem. This review discusses the molecular mechanisms involved in alphavirus-induced arthritis, exploring the recent data obtained with in vitro systems and in vivo studies using animal models and samples from patients. The factors associated to the extension and persistence of symptoms are highlighted, focusing on (a virus replication in target cells, and tissues, including macrophages and muscle cells; (b the inflammatory and immune responses with recruitment and activation of macrophage, NK cells and T lymphocytes to the lesion focus and the increase of inflammatory mediators levels; and (c the persistence of virus or viral products in joint and muscle tissues. We also discuss the importance of the establishment of novel animal models to test new molecular targets and to develop more efficient and selective drugs to treat these diseases.

  7. Noradrenergic mechanism involved in the nociceptive modulation of hippocampal CA3 region of normal rats.

    Science.gov (United States)

    Jin, Hua; Teng, Yueqiu; Zhang, Xuexin; Yang, Chunxiao; Xu, Manying; Yang, Lizhuang

    2014-06-27

    Norepinephrine (NE) is an important neurotransmitter in the brain, and regulates antinociception. However, the mechanism of action of NE on pain-related neurons in the hippocampal CA3 region is not clear. This study examines the effects of NE, phentolamine on the electrical activities of pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the hippocampal CA3 region of rats. Trains of electric impulses applied to the right sciatic nerve were used as noxious stimulation. The electrical activities of PENs or PINs in the hippocampal CA3 region were recorded by using a glass microelectrode. Our results revealed that, in the hippocampal CA3 region, the intra-CA3 region microinjection of NE decreased the pain-evoked discharged frequency and prolonged the discharged latency of PEN, and increased the pain-evoked discharged frequency and shortened discharged inhibitory duration (ID) of PIN, exhibiting the specific analgesic effect of NE. While intra-CA3 region microinjection of phentolamine produced the opposite response. It implies that phentolamine can block the effect of endogenous NE to cause the enhanced response of PEN and PIN to noxious stimulation. On the basis of above findings we can deduce that NE, phentolamine and alpha-adrenoceptor are involved in the modulation of nociceptive information transmission in the hippocampal CA3 region.

  8. Molecular mechanisms involved in the response to desiccation stress and persistence in Acinetobacter baumannii.

    Science.gov (United States)

    Gayoso, Carmen M; Mateos, Jesús; Méndez, José A; Fernández-Puente, Patricia; Rumbo, Carlos; Tomás, María; Martínez de Ilarduya, Oskar; Bou, Germán

    2014-02-07

    Desiccation tolerance contributes to the maintenance of bacterial populations in hospital settings and may partly explain its propensity to cause outbreaks. Identification and relative quantitation of proteins involved in bacterial desiccation tolerance was made using label-free quantitation and iTRAQ labeling. Under desiccating conditions, the population of the Acinetobacter baumannii clinical strain AbH12O-A2 decreased in the first week, and thereafter, a stable population of 0.5% of the original population was maintained. Using label-free quantitation and iTRAQ labeling, 727 and 765 proteins, respectively, were detected; 584 of them by both methods. Proteins overexpressed under desiccation included membrane and periplasmic proteins. Proteins associated with antimicrobial resistance, efflux pumps, and quorum quenching were overexpressed in the samples subjected to desiccation stress. Electron microscopy revealed clear morphological differences between desiccated and control bacteria. We conclude that A. baumannii is able to survive long periods of desiccation through the presence of cells in a dormant state, via mechanisms affecting control of cell cycling, DNA coiling, transcriptional and translational regulation, protein stabilization, antimicrobial resistance, and toxin synthesis, and that a few surviving cells embedded in a biofilm matrix are able to resume growth and restore the original population in appropriate environmental conditions following a "bust-and-boom" strategy.

  9. Superoxide anions and hydrogen peroxide induce hepatocyte death by different mechanisms : Involvement of JNK and ERK MAP kinases

    NARCIS (Netherlands)

    Conde de la Rosa, L; Schoemaker, MH; Vrenken, TE; Buist-Homan, M; Havinga, R; Jansen, PLM; Moshage, H

    2006-01-01

    Background/Aims: In liver diseases, reactive oxygen species (ROS) are involved in cell death and liver injury, but the mechanisms are not completely elucidated. To elucidate the mechanisms of hepatocyte cell death induced by the ROS superoxide anions and hydrogen peroxide, primary cultures of hepato

  10. Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1998 annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Bull, R.J.; Thrall, B.D.; Sasser, L.B.; Miller, J.H.; Schultz, I.R.

    1998-06-01

    'The objective of this project is to develop critical data for changing risk-based clean-up standards for trichloroethylene (TCE). The project is organized around two interrelated tasks: Task 1 addresses the tumorigenic and dosimetry issues for the metabolites of TCE that produce liver cancer in mice, dichloroacetate (DCA) and trichloroacetate (TCA). Early work had suggested that TCA was primarily responsible for TCE-induced liver tumors, but several, more mechanistic observations suggest that DCA may play a prominent role. This task is aimed at determining the basis for the selection hypothesis and seeks to prove that this mode of action is responsible for TCE-induced tumors. This project will supply the basic dose-response data from which low-dose extrapolations would be made. Task 2 seeks specific evidence that TCA and DCA are capable of promoting the growth of spontaneously initiated cells from mouse liver, in vitro. The data provide the clearest evidence that both metabolites act by a mechanism of selection rather than mutation. These data are necessary to select between a linear (i.e. no threshold) and non-linear low-dose extrapolation model. As of May of 1998, this research has identified two plausible modes of action by which TCE produces liver tumors in mice. These modes of action do not require the compounds to be mutagenic. The bulk of the experimental evidence suggests that neither TCE nor the two hepatocarcinogenic metabolites of TCE are mutagenic. The results from the colony formation assay clearly establish that both of these metabolites cause colony growth from initiated cells that occur spontaneously in the liver of B 6 C 3 F 1 mice, although the phenotypes of the colonies differ in the same manner as tumors differ, in vivo. In the case of DCA, a second mechanism may occur at a lower dose involving the release of insulin. This observation is timely as it was recently reported that occupational exposures to trichloroethylene results in 2 to 4

  11. Psychosocial screening and assessment in oncology and palliative care settings.

    Science.gov (United States)

    Grassi, Luigi; Caruso, Rosangela; Sabato, Silvana; Massarenti, Sara; Nanni, Maria G; The UniFe Psychiatry Working Group Coauthors

    2014-01-01

    Psychiatric and psychosocial disorders among cancer patients have been reported as a major consequence of the disease and treatment. The problems in applying a pure psychiatric approach have determined the need for structuring more defined methods, including screening for distress and emotional symptoms and a more specific psychosocial assessment, to warrant proper care to cancer patients with psychosocial problems. This review examines some of the most significant issues related to these two steps, screening and assessment of psychosocial morbidity in cancer and palliative care. With regard to this, the many different variables, such as the factors affecting individual vulnerability (e.g., life events, chronic stress and allostatic load, well-being, and health attitudes) and the psychosocial correlates of medical disease (e.g., psychiatric disturbances, psychological symptoms, illness behavior, and quality of life) which are possibly implicated not only in "classical" psychiatric disorders but more broadly in psychosocial suffering. Multidimensional tools [e.g., and specific psychosocially oriented interview (e.g., the Diagnostic Criteria for Psychosomatic Research)] represent a way to screen for and assess emotional distress, anxiety and depression, maladaptive coping, dysfunctional attachment, as well as other significant psychosocial dimensions secondary to cancer, such as demoralization and health anxiety. Cross-cultural issues, such as language, ethnicity, race, and religion, are also discussed as possible factors influencing the patients and families perception of illness, coping mechanisms, psychological response to a cancer diagnosis.

  12. Psychosocial screening and assessment in oncology and palliative care settings

    Directory of Open Access Journals (Sweden)

    Luigi eGrassi

    2015-01-01

    Full Text Available Psychiatric and psychosocial disorders among cancer patients have been reported as a major consequence of the disease and treatment. The problems in applying a pure psychiatric approach have determined the need for structuring more defined methods, including screening for distress and emotional symptoms and a more specific psychosocial assessment, to warrant proper care to cancer patients with psychosocial problems. This review examines some of the most significant issues related to these two steps, screening and assessment of psychosocial morbidity in cancer and palliative care. With regard to this , the many different variables, such as the factors affecting individual vulnerability (e.g. life events, chronic stress and allostatic load, well-being, and health attitudes and the psychosocial correlates of medical disease (e.g. psychiatric disturbances, psychological symptoms, illness behavior, and quality of life which are possibly implicated not only in classical psychiatric disorders but more broadly in psychosocial suffering. Multidimensional tools (e.g. and specific psychosocially oriented interview (e.g. the Diagnostic Criteria for Psychosomatic Research - DCPR represent a way to screen for and assess emotional distress, anxiety and depression, maladaptive coping, dysfunctional attachment, as well as other significant psychosocial dimensions secondary to cancer, such as demoralization and health anxiety. Cross-cultural issues, such as language, ethnicity, race, and religion, are also discussed as possible factors influencing the patients and families perception of illness, coping mechanisms, psychological response to a cancer diagnosis.

  13. Study of the Genes and Mechanism Involved in the Radioadaptive Response

    Science.gov (United States)

    Dasgupta, Pushan R.

    2009-01-01

    The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor

  14. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?

    Science.gov (United States)

    Sagai, Masaru; Bocci, Velio

    2011-12-20

    stress. Recently these concepts have become widely accepted. The versatility of ozone in treating vascular and degenerative diseases as well as skin lesions, hernial disc and primary root carious lesions in children is emphasized. Further researches able to elucidate whether the mechanisms of action of ozone therapy involve nuclear transcription factors, such as Nrf2, NFAT, AP-1, and HIF-1α are warranted.

  15. Physiological mechanisms involved in resistance to cotton verticillium wilt induced by AM fungi

    Institute of Scientific and Technical Information of China (English)

    LIU Bing-jiang; LIU Run-jin

    2004-01-01

    @@ It was proved that arbuscular mycorrhizal (AM) fungi played an important role in increasing plant resistance to soilborne pathogens, especially when plants were pre-inoculated with AM fungi.Mechanisms involved in this phenomenon are not yet well understood. On the basis of the former experiment results in our lab, effects of AM fungi on cotton Verticillium wilt and the mechanisms of increasing disease resisitance by the tested fungi were studied in pot culture under greenhouse conditions. Two cotton cutivars Litai 8 and 86-1 which are susceptible to Verticillium dahliae were pre-inoculated with Glomus fasiculatum, and Gigaspora margarita, then inoculated with the strain of Verticillium dahliae, namely "An-Yang" (belong to intermediate virulent type) 30 days after the former inoculation. Results showed that AM fungi could improve the growth and development of cotton plants, increase plants dry mass, decrease incidence and disease index of Verticillium wilt of cotton plants, inhibit the infection and development of V. dahliae to different extent in the rhizosphere of cotton pre-inoculated with AM fungi, while the colonization and spore numbers of AM fungi were not reduced significantly by this pathogen. The defence enzymes, such as phenylalanine ammonia-lyase (PAL), chitinase, β-1, 3-glucanase, peroxidase, polyphenoloxidase (PPO) were induced, and their activities and peak increased by AM fungi in roots and leaves, and the increasing speed and peak of the enzyme activity were higher in treatment with AM fungus preinoculation than the inoculation with only V. dahliae, which suggested that defense response was activated by AM fungi, and then made the cotton to react strongly and rapidly to the infection of V. dahliae. In addition, AM fungi decreased the content of malondiadehyde (MDA) in cotton roots and leaves,protected membrane system and alleviated the damage caused by the pathogen. The AM fungus,Glomus fasiculatum showed the superior effects of biological

  16. The central anorexigenic mechanism of adrenocorticotropic hormone involves the caudal hypothalamus in chicks.

    Science.gov (United States)

    Shipp, Steven L; Yi, Jiaqing; Dridi, Sami; Gilbert, Elizabeth R; Cline, Mark A

    2015-10-01

    Adrenocorticotropic hormone (ACTH), consisting of 39 amino acids, is most well-known for its involvement in an organism's response to stress. It also participates in satiety, as exogenous ACTH causes decreased food intake in rats. However, its anorexigenic mechanism is not well understood in any species and its effect on appetite is not reported in the avian class. Thus, the present study was designed to evaluate central ACTH's effect on food intake and to elucidate the mechanism mediating this response using broiler chicks. Chicks that received intracerebroventricular (ICV) injection of 1, 2, or 4 nmol of ACTH reduced food intake, under both ad libitum and 180 min fasted conditions. Water intake was also reduced in ACTH-injected chicks under both feeding conditions, but when measured without access to feed it was not affected. Blood glucose was not affected in either feeding condition. Following ACTH injection, c-Fos immunoreactivity was quantified in key appetite-associated hypothalamic nuclei including the ventromedial hypothalamus (VMH), dorsomedial hypothalamus, lateral hypothalamus (LH), arcuate nucleus (ARC) and the parvo- and magno-cellular portions of the paraventricular nucleus. ACTH-injected chicks had increased c-Fos immunoreactivity in the VMH, LH, and ARC. Hypothalamus was collected at 1h post-injection, and real-time PCR performed to measure mRNA abundance of some appetite-associated factors. Neuropeptide Y, pro-opiomelanocortin, glutamate decarboxylase 1, melanocortin receptors 2-5, and urocortin 3 mRNA abundance was not affected by ACTH treatment. However, expression of corticotropin releasing factor (CRF), urotensin 2 (UT), agouti-related peptide (AgRP), and orexin (ORX), and melanocortin receptor 1 (MC1R) mRNA decreased in the hypothalamus of ACTH-injected chicks. In conclusion, ICV ACTH causes decreased food intake in chicks, and is associated with VMH, LH, and ARC activation, and a decrease in hypothalamic mRNA abundance of CRF, UT, AgRP, ORX

  17. Molecular mechanisms involved in the hormonal prevention of aging in the rat.

    Science.gov (United States)

    Tresguerres, Jesús A F; Kireev, Roman; Tresguerres, Ana F; Borras, Consuelo; Vara, Elena; Ariznavarreta, Carmen

    2008-02-01

    Previous data from our group have provided support for the role of GH, melatonin and estrogens in the prevention of aging of several physiological parameters from bone, liver metabolism, vascular activity, the central nervous system (CNS), the immune system and the skin. In the present work data on the molecular mechanisms involved are presented. A total of 140 male and female rats have been submitted to different treatments over 10 weeks, between 22 and 24 months of age. Males have been treated with GH and melatonin. Females were divided in two groups: intact and castrated at 12 months of age. The first group was treated with GH and melatonin and the second with the two latter compounds and additionally with estradiol and Phytosoya. Aging was associated with a reduction in the number of neurons of the hylus of the dentate gyrus of the hippocampus and with a reduction of neurogenesis. GH treatment increased the number of neurons but did not increase neurogenesis thus suggesting a reduction of apoptosis. This was supported by the reduction in nucleosomes and the increase in Bcl2 observed in cerebral homogenates together with an increase in sirtuin2 and a reduction of caspases 9 and 3. Melatonin, estrogen and Phytosoya treatments increased neurogenesis but did not enhance the total number of neurons. Aging induced a significant increase in mitochondrial nitric oxide in the hepatocytes, together with a reduction in the mitochondrial fraction content in cytochrome C and an increase of this compound in the cytosolic fraction. Reductions of glutathione peroxidase and glutathione S-transferase were also detected, thus indicating oxidative stress and possibly apoptosis. Treatment for 2.5 months of old rats with GH and melatonin were able to significantly and favourably affect age-induced deteriorations, thus reducing oxidative damage. Keratinocytes obtained from old rats in primary culture showed an increase in lipoperoxides, caspases 8 and 3 as well as a reduction in Bcl2

  18. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?

    Directory of Open Access Journals (Sweden)

    Sagai Masaru

    2011-12-01

    moderate oxidative stress. Recently these concepts have become widely accepted. The versatility of ozone in treating vascular and degenerative diseases as well as skin lesions, hernial disc and primary root carious lesions in children is emphasized. Further researches able to elucidate whether the mechanisms of action of ozone therapy involve nuclear transcription factors, such as Nrf2, NFAT, AP-1, and HIF-1α are warranted.

  19. Pathophysiological mechanisms involved in non-alcoholicsteatohepatitis and novel potential therapeutic targets

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a major healthcare problem and represents the hepatic expression ofthe metabolic syndrome. NAFLD is classified as nonalcoholicfatty liver (NAFL) or simple steatosis, and nonalcoholicsteatohepatitis (NASH). NASH is characterizedby the presence of steatosis and inflammation withor without fibrosis. The physiopathology of NAFL andNASH and their progression to cirrhosis involve severalparallel and interrelated mechanisms, such as, insulinresistance (IR), lipotoxicity, inflammation, oxidativestress, and recently the gut-liver axis interaction has beendescribed. Incretin-based therapies could play a role inthe treatment of NAFLD. Glucagon-like peptide-1 (GLP-1)is an intestinal mucosa-derived hormone which is secretedinto the bloodstream in response to nutrient ingestion;it favors glucose-stimulated insulin secretion, inhibitionof postprandial glucagon secretion and delayed gastricemptying. It also promotes weight loss and is involvedin lipid metabolism. Once secreted, GLP-1 is quicklydegraded by dipeptidyl peptidase-4 (DPP-4). Therefore,DPP-4 inhibitors are able to extend the activity of GLP-1.Currently, GLP-1 agonists and DPP-4 inhibitors representattractive options for the treatment of NAFLD andNASH. The modulation of lipid and glucose metabolismthrough nuclear receptors, such as the farsenoid Xreceptor, also constitutes an attractive therapeutic target.Obeticholic acid is a potent activator of the farnesoidX nuclear receptor and reduces liver fat content andfibrosis in animal models. Ursodeoxycholic acid (UDCA)is a hydrophilic bile acid with immunomodulatory, antiinflammatory,antiapoptotic, antioxidant and antifibroticproperties. UDCA can improve IR and modulatelipid metabolism through its interaction with nuclearreceptors such as, TGR5, farnesoid X receptor-a, orthe small heterodimeric partner. Finally, pharmacologicmodulation of the gut microbiota could have a role in thetherapy of NAFLD and

  20. Helminth 2-Cys peroxiredoxin drives Th2 responses through a mechanism involving alternatively activated macrophages

    Science.gov (United States)

    Donnelly, Sheila; Stack, Colin M.; O'Neill, Sandra M.; Sayed, Ahmed A.; Williams, David L.; Dalton, John P.

    2008-01-01

    During helminth infections, alternatively activated macrophages (AAMacs) are key to promoting Th2 responses and suppressing Th1-driven inflammatory pathology. Th2 cytokines IL-4 and/or IL-13 are believed to be important in the induction and activation of AAMacs. Using murine models for the helminth infections caused by Fasciola hepatica (Fh) and Schistosoma mansoni (Sm), we show that a secreted antioxidant, peroxiredoxin (Prx), induces alternative activation of macrophages. These activated, Ym1-expressing macrophages enhanced the secretion of IL-4, IL-5, and IL-13 from naive CD4+ T cells. Administration of recombinant FhPrx and SmPrx to wild-type and IL-4−/− and IL-13−/− mice induced the production of AAMacs. In addition, Prx stimulated the expression of markers of AAMacs (particularly, Ym1) in vitro, and therefore can act independently of IL-4/IL-13 signaling. The immunomodulatory property of Prx is not due to its antioxidant activity, as an inactive recombinant variant with active site Cys residues replaced by Gly could also induce AAMacs and Th2 responses. Immunization of mice with recombinant Prx or passive transfer of anti-Prx antibodies prior to infection with Fh not only blocked the induction of AAMacs but also the development of parasite-specific Th2 responses. We propose that Prx activates macrophages as an initial step in the induction of Th2 responses by helminth parasites and is thereby a novel pathogen-associated molecular pattern.—Donnelly, S., Stack, C. M., O'Neill, S. M., Sayed, A. A., Williams, D. L., Dalton, J. P. Helminth 2-Cys peroxiredoxin drives Th2 responses through a mechanism involving alternatively activated macrophages. PMID:18708590

  1. The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity.

    Science.gov (United States)

    Gordillo, Miriam; Vega, Hugo; Trainer, Alison H; Hou, Fajian; Sakai, Norio; Luque, Ricardo; Kayserili, Hülya; Basaran, Seher; Skovby, Flemming; Hennekam, Raoul C M; Uzielli, Maria L Giovannucci; Schnur, Rhonda E; Manouvrier, Sylvie; Chang, Susan; Blair, Edward; Hurst, Jane A; Forzano, Francesca; Meins, Moritz; Simola, Kalle O J; Raas-Rothschild, Annick; Schultz, Roger A; McDaniel, Lisa D; Ozono, Keiichi; Inui, Koji; Zou, Hui; Jabs, Ethylin Wang

    2008-07-15

    Roberts syndrome/SC phocomelia (RBS) is an autosomal recessive disorder with growth retardation, craniofacial abnormalities and limb reduction. Cellular alterations in RBS include lack of cohesion at the heterochromatic regions around centromeres and the long arm of the Y chromosome, reduced growth capacity, and hypersensitivity to DNA damaging agents. RBS is caused by mutations in ESCO2, which encodes a protein belonging to the highly conserved Eco1/Ctf7 family of acetyltransferases that is involved in regulating sister chromatid cohesion. We identified 10 new mutations expanding the number to 26 known ESCO2 mutations. We observed that these mutations result in complete or partial loss of the acetyltransferase domain except for the only missense mutation that occurs in this domain (c.1615T>G, W539G). To investigate the mechanism underlying RBS, we analyzed ESCO2 mutations for their effect on enzymatic activity and cellular phenotype. We found that ESCO2 W539G results in loss of autoacetyltransferase activity. The cellular phenotype produced by this mutation causes cohesion defects, proliferation capacity reduction and mitomycin C sensitivity equivalent to those produced by frameshift and nonsense mutations associated with decreased levels of mRNA and absence of protein. We found decreased proliferation capacity in RBS cell lines associated with cell death, but not with increased cell cycle duration, which could be a factor in the development of phocomelia and cleft palate in RBS. In summary, we provide the first evidence that loss of acetyltransferase activity contributes to the pathogenesis of RBS, underscoring the essential role of the enzymatic activity of the Eco1p family of proteins.

  2. Mechanisms involved in the selective transfer of long chain polyunsaturted fatty acids to the fetus

    Directory of Open Access Journals (Sweden)

    Alfonso eGil-Sánchez

    2011-09-01

    Full Text Available The concentration of long chain polyunsaturated fatty acid (LCPUFA in the fetal brain increases dramatically from the third trimester until 18 months of life. Several studies have shown an association between the percentage of maternal plasma docosahexaenoic acid (DHA during gestation and development of the cognitive functions in the neonate. Since only very low levels of LCPUFA are synthesized in the fetus and placenta, their primary source for the fetus is that of maternal origin. Both in vitro and human in vivo studies using labelled fatty acids have shown the preferential transfer of LCPUFA from the placenta to the fetus compared with other fatty acids, although the mechanisms involved are still uncertain. The placenta takes up circulating maternal non-esterified fatty acids (NEFA and fatty acids released mainly by maternal lipoprotein lipase and endothelial lipase. These NEFA may enter the cell by passive diffusion or by means of membrane carrier proteins. Once in the cytosol, NEFA bind to cytosolic fatty acid-binding proteins for transfer to the fetal circulation or can be oxidized within the trophoblasts and even re-esterified and stored in lipid droplets (LD. Although trophoblast cells are not specialized in lipid storage, LCPUFA may up-regulate peroxisome proliferator activated receptor-γ (PPARγ and hence the gene expression of fatty acid transport carriers, fatty acid acyl-CoA synthetases and adipophilin or other enzymes related with lipolysis, modifying their rate of placental transfer and metabolization. The placental transfer of LCPUFA during pregnancy seems to be a key factor in the neurological development of the fetus. Increased knowledge on the factors that modify placental transfer of fatty acids would contribute to our understanding of this complex process.

  3. Psychosocial Intervention Model

    DEFF Research Database (Denmark)

    Singla, Rashmi

    2007-01-01

    criticises the reductionistic dichotomy - either own or parental choice - and appeals for broader concepts, which focus both on own choice and parental acceptance. The article also throws light on some strategic services dealing with ethnic minority youths' intimate partnership formation problems U.......K. as well as Nordic countries. Finally a model for psychosocial intervention is presented which directs attention to the issues of ageism, sexism as well as racism at personal, interpersonal and structural levels....

  4. Involvement of lignin and hormones in the response of woody poplar taproots to mechanical stress.

    Science.gov (United States)

    Trupiano, Dalila; Di Iorio, Antonino; Montagnoli, Antonio; Lasserre, Bruno; Rocco, Mariapina; Grosso, Alessandro; Scaloni, Andrea; Marra, Mauro; Chiatante, Donato; Scippa, Gabriella S

    2012-09-01

    Mechanical stress is a widespread condition caused by numerous environmental factors that severely affect plant stability. In response to mechanical stress, plants have evolved complex response pathways able to detect mechanical perturbations and inducing a suite of modifications in order to improve anchorage. The response of woody roots to mechanical stresses has been studied mainly at the morphological and biomechanical level, whereas investigations on the factors triggering these important alterations are still at the initial stage. Populus has been widely used to study the response of stem to different mechanical stresses and, since it has the first forest tree genome to be decoded, represents a model woody plant for addressing questions on the mechanisms controlling adaptation of woody roots to changing environments. In this study, a morphological and physiological analysis was used to investigate factors controlling modifications in Populus nigra woody taproots subjected to mechanical stress. An experimental model analyzing spatial and temporal mechanical force distribution along the woody taproot axis enabled us to compare the events occurring in its above-, central- and below-bending sectors. Different morphogenetic responses and local variations of lignin and plant hormones content have been observed, and a relation with the distribution of the mechanical forces along the stressed woody taproots is hypothesized. We investigated the differences of the response to mechanical stress induction during the time; in this regard, we present data referring to the effect of mechanical stress on plant transition from its condition of winter dormancy to that of full vegetative activity.

  5. [Adolescent psychosocial development].

    Science.gov (United States)

    Gaete, Verónica

    2015-01-01

    It is increasingly necessary that pediatricians have greater knowledge of adolescent health. To begin with they should be familiar with the psychosocial development of this period, an issue which is imperative for the health care of the age group. With that purpose, this article reviews the normal adolescent psychosocial development. Adolescence is a stage that has been progressively prolonged, during which fast and big changes occur, that lead human beings to become biologically, psychologically and socially mature, and potentially able to live independently. Developmental tasks of this period are the establishment of identity and the achievement of autonomy. Although it is a process of high individual variability in terms of its beginning and end, the progression through stages, the synchrony of development between the various areas, and in other aspects, the psychosocial development of this period usually have common characteristics and a progressive pattern of 3 phases: early, middle and late adolescence. Psychological, cognitive, social, sexual and moral development of young people in each of them are described in this article. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Psychosocial aspects of strabismus

    Directory of Open Access Journals (Sweden)

    Jablan Branka

    2014-01-01

    Full Text Available Binocular vision is characterized by a harmonious relation between sensory and motor systems of both eyes. This relation enables directing visual axes toward the observed object simultaneously, fusing images from two eyes, and the sense of threedimensionality. Motility and binocular vision disorders occur in manifest and latent strabismus. The irregular position of eyes in strabismus is perceived by most people as an esthetic defect. Also, psychosocial consequences and the importance of treating strabismus are very superficially explained in this context. Bearing in mind the results of recent researches, which indicate that individuals of all ages with strabismus face different difficulties in psychosocial functioning, we believe that this issue in our surroundings should be dealt with. Strabismus leads to forming prejudices which usually have a negative impact on socialization and employment opportunities. Timely treatment of strabismus has a positive influence on the functionality of binocular vision, building self-esteem and self-satisfaction, being accepted by typically developing population, the quality and quantity of social interaction. The aim of this paper is to present the relation between strabismus and psychosocial reactions with regard to the available literature. [Projekat Ministarstva nauke Republike Srbije, br. 179025: Kreiranje Protokola za procenu edukativnih potencijala dece sa smetnjama u razvoju kao kriterijuma za izradu individualnih obrazovnih programa i br. 179017: Socijalna participacija osoba sa intelektualnom ometenošću

  7. Gestational surrogacy: Psychosocial aspects

    Directory of Open Access Journals (Sweden)

    Nicolás Ruiz-Robledillo

    2016-12-01

    Full Text Available Innovation in assisted reproductive technologies together with increased infertility and new family structures are increasing the use of gestational surrogacy as a means to have children. Before, during and after the process, it is necessary to study the psychosocial characteristics of triad members: the gestational surrogate, intended parents, and offspring. Research has indicated positive adaptation to the process and benefits for all members of the triad. Altruism is the main motivation of surrogates. Notably, psychological well-being has been found to be higher in individuals who have become parents through surrogacy than in those who have used egg donation or have followed a natural process of conception. Moreover, no differences in psychosocial characteristics have been observed in the offspring, compared with children born through natural conception or egg donation. Results highlight the positive aspects of surrogacy. Future research should investigate psychosocial factors that modulate the process, acting as risk and protective factors for well-being of the triad members, and identify the optimal profiles of surrogates for the process to be a success.

  8. Mechanisms involved in the psychological distress of Black Caribbeans in the United States

    Science.gov (United States)

    Govia, Ishtar O.

    The mental health of ethnic minorities in the United States is of urgent concern. The accelerated growth of groups of ethnic minorities and immigrants in the United States and the stressors to which they are exposed, implores academic researchers to investigate more deeply health disparities and the factors that exacerbate or minimize such inequalities. This dissertation attended to that concern. It used data from the National Survey of American Life (NSAL), the first survey with a national representative sample of Black Caribbeans, to explore mechanisms that involved in the psychological distress of Black Caribbeans in the United States. In a series of three studies, the dissertation investigated the role and consequence of (1) chronic discrimination, immigration factors, and closeness to ethnic and racial groups; (2) personal control and social support; and (3) family relations and social roles in the psychological distress of Black Caribbeans. Study 1 examined how the associations between discrimination and psychological distress were buffered or exacerbated by closeness to ethnic group and closeness to racial group. It also examined how these associations differed depending on immigration factors. Results indicated that the buffering or exacerbating effect of ethnic and racial group closeness varied according to the type of discrimination (subtle or severe) and were more pronounced among those born in the United States. Using the stress process framework, Study 2 tested moderation and mediation models of the effects of social support and personal control in the association between discrimination and distress. Results from a series of analyses on 579 respondents suggested that personal control served as a mediator in this relationship and that emotional support exerted a direct distress deterring function. Study 3 investigated sex differences in the associations between social roles, intergenerational family relationship perceptions and distress. Results

  9. Mangiferin, a natural xanthone, accelerates gastrointestinal transit in mice involving cholinergic mechanism

    Science.gov (United States)

    Morais, Talita Cavalcante; Lopes, Synara Cavalcante; Carvalho, Karine Maria Martins Bezerra; Arruda, Bruno Rodrigues; de Souza, Francisco Thiago Correia; Trevisan, Maria Teresa Salles; Rao, Vietla Satyanarayana; Santos, Flávia Almeida

    2012-01-01

    AIM: To investigate the effects of mangiferin on gastrointestinal transit (GIT) in normal and constipated mice, together with the possible mechanism. METHODS: Intragastrically-administered charcoal meal was used to measure GIT in overnight starved Swiss mice. In the first experiments, mangiferin (3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg, po) or tegaserod (1 mg/kg, ip) were administered 30 min before the charcoal meal to study their effects on normal transit. In the second series, mangiferin (30 mg/kg) was tested on delayed GIT induced by several different pharmacological agonists (morphine, clonidine, capsaicin) or antagonists (ondansetron, verapamil, and atropine) whereas in the third series, mangiferin (30 mg/kg, 100 mg/kg and 300 mg/kg) or tegaserod (1 mg/kg) were tested on 6 h fecal pellets outputted by freely fed mice. The ratio of wet to dry weight was calculated and used as a marker of fecal water content. RESULTS: Mangiferin administered orally significantly (P < 0.05) accelerated GIT at 30 mg/kg and 100 mg/kg (89% and 93%, respectively), similarly to 5-hydroxytryptamine4 (5-HT4) agonist tegaserod (81%) when compared to vehicle-treated control (63%). Co-administered mangiferin (30 mg/kg) totally reversed the inhibitory effect of opioid agonist morphine, 5-HT3-receptor antagonist ondansetron and transient receptor potential vanilloid-1 receptor agonist capsaicin on GIT, but only to a partial extent with the GIT-delay induced by α2-adrenoceptor agonist clonidine, and calcium antagonist verapamil. However, co-administered atropine completely blocked the stimulant effect of mangiferin on GIT, suggesting the involvement of muscarinic acetylcholine receptor activation. Although mangiferin significantly enhanced the 6 h fecal output at higher doses (245.5 ± 10.43 mg vs 161.9 ± 10.82 mg and 227.1 ± 20.11 mg vs 161.9 ± 10.82 mg of vehicle-treated control, at 30 and 100 mg/kg, P < 0.05, respectively), the effect of tegaserod was more potent (297.4 ± 7.42 mg

  10. Mangiferin, a natural xanthone, accelerates gastrointestinal transit in mice involving cholinergic mechanism

    Institute of Scientific and Technical Information of China (English)

    Talita Cavalcante Morais; Synara Cavalcante Lopes; Karine Maria Martins Bezerra Carvalho; Bruno Rodrigues Arruda; Francisco Thiago Correia de Souza; Maria Teresa Salles Trevisan; Vietla Satyanarayana Rao; Flávia Almeida Santos

    2012-01-01

    AIM:To investigate the effects of mangiferin on gastrointestinal transit (GIT) in normal and constipated mice,together with the possible mechanism.METHODS:Intragastrically-administered charcoal meal was used to measure GIT in overnight starved Swiss mice.In the first experiments,mangiferin (3 mg/kg,10mg/kg,30 mg/kg,and 100 mg/kg,po) or tegaserod (1mg/kg,ip) were administered 30 min before the charcoal meal to study their effects on normal transit.In the second series,mangiferin (30 mg/kg) was tested on delayed GIT induced by several different pharmacological agonists (morphine,clonidine,capsaicin) or antagonists (ondansetron,verapamil,and atropine) whereas in the third series,mangiferin (30 mg/kg,100mg/kg and 300 mg/kg) or tegaserod (1 mg/kg) were tested on 6 h fecal pellets outputted by freely fed mice.The ratio of wet to dry weight was calculated and used as a marker of fecal water content.RESULTS:Mangiferin administered orally significantly (P < 0.05) accelerated GIT at 30 mg/kg and 100 mg/kg (89%and 93%,respectively),similarly to 5-hydroxytryptamine4 (5-HT4) agonist tegaserod (81%) when compared to vehicle-treated control (63%).Co-administered mangiferin (30 mg/kg) totally reversed the inhibitory effect of opioid agonist morphine,5-HT3-receptor antagonist ondansetron and transient receptor potential vanilloid-1 receptor agonist capsaicin on GIT,but only to a partial extent with the GIT-delay induced by α2-adrenoceptor agonist clonidine,and calcium antagonist verapamil.However,co-administered atropine completely blocked the stimulant effect of mangiferin on GIT,suggesting the involvement of muscarinic acetylcholine receptor activation.Although mangiferin significantly enhanced the 6 h fecal output at higher doses (245.5 ± 10.43 mg vs 161.9 ± 10.82 mg and 227.1 ± 20.11 mg vs 161.9 ±10.82 mg of vehicle-treated control,at 30 and 100 mg/kg,P < 0.05,respectively),the effect of tegaserod was more potent (297.4 ± 7.42 mg vs 161.9 ± 10.82 mg of

  11. PSYCHOSOCIAL ASPECTS OF PATERNAL IDENTITY CONSTRUCTION

    OpenAIRE

    Gabriela Teixeira VIEIRA; Nascimento, Adriano Roberto Afonso

    2013-01-01

    Abstract: This study aims to analyze from the perspective of Social Identity Theory the psychosocial aspects involved in the construction of fatherhood from the viewpoint of 14 fathers, between the ages of 20 and 50, all parents of their first child, aged 2-7 months, living in the metropolitan area of Belo Horizonte. Interviews were conducted from a semi-structured script, which subsequently were subjected to content analysis. The categories were organized according to the three components of...

  12. Psychosocial adjustment and craniofacial malformations in childhood.

    Science.gov (United States)

    Pertschuk, M J; Whitaker, L A

    1985-02-01

    Forty-three children between the ages of 6 and 13 years with congenital facial anomalies underwent psychosocial evaluation prior to surgery. Also evaluated were healthy children matched to the craniofacial subjects by sex, age, intelligence, and economic background. Relative to this comparison group, the craniofacial children were found to have poorer self-concept, greater anxiety at the time of evaluation, and more introversion. Parents of the craniofacial children noted more frequent negative social encounters for their children and more hyperactive behavior at home. Teachers reported more problematic classroom behavior. Examination of these results revealed craniofacial malformations to be associated with psychosocial limitations rather than marked deficits. These children tended to function less well than the comparison children, but with few exceptions, they were not functioning in a psychosocially deviant range. Explanations for the observed circumscribed impact of facial deformity include the use of denial as a coping mechanism, possible diminished significance of appearance for younger children, and the restricted environment experienced by most of the subjects. It can be predicted that time would render these protective influences ineffective, so that adolescent and young adult patients could be at far greater psychosocial risk.

  13. A novel mechanism of hippocampal LTD involving muscarinic receptor-triggered interactions between AMPARs, GRIP and liprin-α

    Directory of Open Access Journals (Sweden)

    Dickinson Bryony A

    2009-06-01

    Full Text Available Abstract Background Long-term depression (LTD in the hippocampus can be induced by activation of different types of G-protein coupled receptors, in particular metabotropic glutamate receptors (mGluRs and muscarinic acethycholine receptors (mAChRs. Since mGluRs and mAChRs activate the same G-proteins and isoforms of phospholipase C (PLC, it would be expected that these two forms of LTD utilise the same molecular mechanisms. However, we find a distinct mechanism of LTD involving GRIP and liprin-α. Results Whilst both forms of LTD require activation of tyrosine phosphatases and involve internalisation of AMPARs, they use different molecular interactions. Specifically, mAChR-LTD, but not mGluR-LTD, is blocked by peptides that inhibit the binding of GRIP to the AMPA receptor subunit GluA2 and the binding of GRIP to liprin-α. Thus, different receptors that utilise the same G-proteins can regulate AMPAR trafficking and synaptic efficacy via distinct molecular mechanisms. Conclusion Our results suggest that mAChR-LTD selectively involves interactions between GRIP and liprin-α. These data indicate a novel mechanism of synaptic plasticity in which activation of M1 receptors results in AMPAR endocytosis, via a mechanism involving interactions between GluA2, GRIP and liprin-α.

  14. A Novel Bio-Psychosocial-Behavioral Treatment Model in Schizophrenia.

    Science.gov (United States)

    Kim, Yong-Ku; Choi, Joonho; Park, Seon-Cheol

    2017-03-30

    Despite the substantial burden of illness in schizophrenia, there has been a discrepancy between the beneficial effects of an increased use of antipsychotic medications and achieving limited recovery or remission. Because the focus of the most common antipsychotic medications is on dopamine, which is associated with positive symptoms, there is an unmet need for patients with negative symptoms. Since cognitive and negative symptoms rather than positive symptoms are more closely associated with psychosocial impairments in patients with schizophrenia, the non-dopaminergic systems including glutamate and γ-aminobutyric acid (GABA) of the prefrontal cortex should be of concern as well. The balance of excitation and inhibition has been associated with epigenetic modifications and thus can be analyzed in terms of a neurodevelopmental and neural circuitry perspective. Hence, a novel bio-psychosocial-behavioral model for the treatment of schizophrenia is needed to account for the non-dopaminergic systems involved in schizophrenia, rather than dopaminergic mechanisms. This model can be understood from the viewpoint of neurodevelopment and neural circuitry and should include the staging care, personalized care, preventive care, reducing the cognitive deficits, and reducing stigma. Thomas R. Insel proposed this as a goal for schizophrenia treatment to be achieved by 2030.

  15. MECHANISMS INVOLVED IN TRICHLOROETHYLENE INDUCED LIVER CANCER: IMPORTANCE TO ENVIRONMENTAL CLEANUP

    Energy Technology Data Exchange (ETDEWEB)

    Bull, Richard J.; Thrall, Brain D.

    2001-12-31

    Trichloroethylene (TCE) is a common contaminant of groundwater as a result of poor disposal practices of the past. As a consequence, this solvent is the focus of many clean-up operations of uncontrolled hazardous waste sites. TCE is carcinogenic in both mice and rats, but at different sites, the liver and kidney, respectively (NCI 1976; NTP 1988; NTP 1990). Liver tumor induction in mice has been the tumor most critical from the standpoint of environmental regulation (Bull 2000). Under the proposed cancer risk guidelines of the Environmental Protection Agency (EPA 1996), identifying the dose-response behavior of key events involved in carcinogenic responses can be used for developing alternative risk assessments. A major difficulty in developing alternative approaches for TCE is the fact that three of its metabolites are capable of inducing liver cancer in mice (Bull et al. 1990; Daniel et al. 1992; DeAngelo et al. 1999; Pereria 1996). Two of these metabolites have distinct modes of action, dichloroacetate (DCA) and trichloroacetate (TCA). The third metabolite, chloral hydrate, is probably active as a result of its conversion to one or both of these two metabolites. Ordinarily, the first approach to assigning causality to a metabolite in tumorigenesis would be an attempt to measure its concentration in the body and associate that with tumorigenic concentrations observed when the compound is itself administered. This can be done with relative ease with TCA. However, it has been more difficult with DCA since blood levels of this metabolite after exposure to carcinogenic doses of DCA fall rapidly below detection limits (Kato-Weinstein et al. 1998; Merdink et al. 1998). Mutations in the ras protooncogene have been used to determine if distinct patterns of DNAsequence alterations can provide indications of the type of DNA damage that might be produced by carcinogens. The presence of ras mutations in chemically-induced tumors was suggested as a means o f determining

  16. Identification and Characterization of the Phage Gene sav, Involved in Sensitivity to the Lactococcal Abortive Infection Mechanism AbiV

    DEFF Research Database (Denmark)

    Haaber, Jakob Brandt Borup; Rousseau, G. M.; Hammer, Karin

    2009-01-01

    Lactococcus lactis phage mutants that are insensitive to the recently characterized abortive infection mechanism AbiV were isolated and analyzed in an effort to elucidate factors involved in the sensitivity to AbiV. Whole-genome sequencing of the phage mutants p2.1 and p2.2 revealed mutations in ...

  17. Study of the Chemical Mechanism Involved in the Formation of Tungstite in Benzyl Alcohol by the Advanced QEXAFS Technique

    DEFF Research Database (Denmark)

    Olliges‐Stadler, Inga; Stötzel, Jan; Koziej, Dorota

    2012-01-01

    Insight into the complex chemical mechanism for the formation of tungstite nanoparticles obtained by the reaction of tungsten hexachloride with benzyl alcohol is presented herein. The organic and inorganic species involved in the formation of the nanoparticles were studied by time‐dependent gas...

  18. Swarming mechanisms in the yellow fever mosquito: aggregation pheromones involved in the mating behavior of Aedes aegypti

    Science.gov (United States)

    Mosquitoes of various species mate in swarms comprised of tens to thousands flying males. Yet little information is known about mosquito swarming mechanism. Discovering chemical cues involved in mosquito biology leads to better adaptation of disease control interventions. In this study, we aimed ...

  19. A Mechanism for Land-Atmosphere Feedback Involving Planetary Wave Structures

    Science.gov (United States)

    Koster, Randal D.; Chang, Yehui; Schubert, Siegfried D.

    2014-01-01

    While the ability of land surface conditions to influence the atmosphere has been demonstrated in various modeling and observational studies, the precise mechanisms by which land-atmosphere feedback occurs are still largely unknown particularly the mechanisms that allow land moisture state in one region to affect atmospheric conditions in another. Such remote impacts are examined here in the context of atmospheric general circulation model (AGCM) simulations, leading to the identification of one potential mechanism: the phase-locking and amplification of a planetary wave through the imposition of a spatial pattern of soil moisture at the land surface. This mechanism, shown here to be relevant in the AGCM, apparently also operates in nature, as suggested by supporting evidence found in reanalysis data.

  20. Molecular mechanism for the involvement of nuclear receptor FXR in HBV-associated hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yong-dong Niu

    2011-08-01

    Full Text Available Farnesoid X receptor (FXR, also termed nuclear receptor NR1H4 is critically involved in the regulation of nascent bile formation and bile acid enterohepatic circulation. FXR and bile acids have been shown to play roles in liver regeneration and inflammatory responses. There is increasing evidence suggesting that FXR and the FXR signaling pathway are involved in the pathophysiology of a wide range of liver diseases, such as viral hepatitis, cirrhosis, and hepatocellular carcinoma (HCC. Here we discuss the latest discoveries of FXR functions with relevance to bile acid metabolism and HBV-associated HCC. More specifically, the goal of this review is to discuss the roles of FXR and bile acids in regulating HBV replication and how disregulation of the FXR-bile acid signaling pathway is involved in HBV-associated hepatocarcinogenesis.

  1. [Psychosocial aspects of preeclampsia].

    Science.gov (United States)

    Szita, Bernadett; Baji, Ildikó; Rigó, János

    2015-12-13

    Distress conditions during pregnancy may contribute to the development of preeclampsia by altering functions of the neuroendocrine and immune systems, e.g. activation of the hypothalamic-pituitary-adrenal axis and increase in plasma proinflammatory cytokines. Preeclampsia may also precipitate mental health problems due to long-term hospitalization or unpredictable and uncontrollable events such as preterm labor and newborn complications. Besides, preeclampsia may induce persistent neurocognitive complaints with a negative impact on patients' quality of life. As growing evidence indicates that poor maternal mental health has an adverse effect on pregnancy outcome and fetal development, psychosocial interventions may be beneficial for women with preeclampsia.

  2. Cumulative asbestos exposure for US automobile mechanics involved in brake repair (circa 1950s-2000).

    Science.gov (United States)

    Finley, Brent L; Richter, Richard O; Mowat, Fionna S; Mlynarek, Steve; Paustenbach, Dennis J; Warmerdam, John M; Sheehan, Patrick J

    2007-11-01

    We analyzed cumulative lifetime exposure to chrysotile asbestos experienced by brake mechanics in the US during the period 1950-2000. Using Monte Carlo methods, cumulative exposures were calculated using the distribution of 8-h time-weighted average exposure concentrations for brake mechanics and the distribution of job tenure data for automobile mechanics. The median estimated cumulative exposures for these mechanics, as predicted by three probabilistic models, ranged from 0.16 to 0.41 fibers per cubic centimeter (f/cm(3)) year for facilities with no dust-control procedures (1970s), and from 0.010 to 0.012 f/cm(3) year for those employing engineering controls (1980s). Upper-bound (95%) estimates for the 1970s and 1980s were 1.96 to 2.79 and 0.07-0.10 f/cm(3) year, respectively. These estimates for US brake mechanics are consistent with, but generally slightly lower than, those reported for European mechanics. The values are all substantially lower than the cumulative exposure of 4.5 f/cm(3) year associated with occupational exposure to 0.1 f/cm(3) of asbestos for 45 years that is currently permitted under the current occupational exposure limits in the US. Cumulative exposures were usually about 100- to 1,000-fold less than those of other occupational groups with asbestos exposure for similar time periods. The cumulative lifetime exposure estimates presented here, combined with the negative epidemiology data for brake mechanics, could be used to refine the risk assessments for chrysotile-exposed populations.

  3. Sensitizing Children to the Social and Emotional Mechanisms Involved in Racism: A Program Evaluation

    Science.gov (United States)

    Triliva, Sofia; Anagnostopoulou, Tanya; Vleioras, Georgios

    2014-01-01

    This paper describes and discusses the results of an intervention aiming to sensitize children to the social and emotional processes involved in racism. The intervention was applied and evaluated in 10 Greek elementary schools. The goals and the intervention methods of the program modules are briefly outlined and the results of the program…

  4. Overview of mechanisms involved during the quenching and partitioning process in steels

    NARCIS (Netherlands)

    Santofimia, M.J.; Zhao, L.; Sietsma, J.

    2011-01-01

    The application of the quenching and partitioning (Q&P) process in steels involves a microstructural evolution that is more complex than just the formation of martensite followed by carbon partitioning from martensite to austenite. Examples of this complexity are the formation of epitaxial ferrite

  5. The Role and Mechanisms of Action of Glucocorticoid Involvement in Memory Storage

    Directory of Open Access Journals (Sweden)

    Carmen Sandi

    1998-01-01

    integral aspect of the neurobiological mechanism underlying memory formation. By reviewing the work carried out in different learning models in chicks (passive avoidance learning and rats (spatial orientation in the Morris water maze and contextual fear conditioning, a role for brain corticosterone action through the glucocorticoid receptor type on the mechanisms of memory consolidation is hypothesized. Evidence is also presented to relate post-training corticosterone levels to the strength of memory storage. Finally, the possible molecular mechanisms that might mediate the influences of glucocorticoids in synaptic plasticity subserving long-term memory formation are considered, mainly by focusing on studies implicating a steroid action through (i glutamatergic transmission and (ii cell adhesion molecules.

  6. The Role and Mechanisms of Action of Glucocorticoid Involvement in Memory Storage

    Science.gov (United States)

    Sandi, Carmen

    1998-01-01

    Adrenal steroid hormones modulate learning and memory processes by interacting with specific glucocorticoid receptors at different brain areas. In this article, certain components of the physiological response to stress elicited by learning situations are proposed to form an integral aspect of the neurobiological mechanism underlying memory formation. By reviewing the work carried out in different learning models in chicks (passive avoidance learning) and rats (spatial orientation in the Morris water maze and contextual fear conditioning), a role for brain corticosterone action through the glucocorticoid receptor type on the mechanisms of memory consolidation is hypothesized. Evidence is also presented to relate post-training corticosterone levels to the strength of memory storage. Finally, the possible molecular mechanisms that might mediate the influences of glucocorticoids in synaptic plasticity subserving long-term memory formation are considered, mainly by focusing on studies implicating a steroid action through (i) glutamatergic transmission and (ii) cell adhesion molecules. PMID:9920681

  7. Lessons learned about psychosocial responses to disaster and mass trauma: an international perspective

    OpenAIRE

    Reifels, Lennart; Pietrantoni, Luca; Prati, Gabriele; Kim, Yoshiharu; Kilpatrick, Dean G.; Dyb, Grete; Halpern, James; Olff, Miranda; Brewin, Chris R; O’Donnell, Meaghan

    2013-01-01

    At the 13th meeting of the European Society for Traumatic Stress Studies in 2013, a symposium was held that brought together international researchers and clinicians who were involved in psychosocial responses to disaster. A total of six disasters that occurred in five countries were presented and discussed. Lessons learned from these disasters included the need to: (1) tailor the psychosocial response to the specific disaster, (2) provide multi-dimensional psychosocial care, (3) target at-ri...

  8. Psychosocial complaints and physical therapy.

    NARCIS (Netherlands)

    Dekker, J.; Valk, R.W.A. van der; Verhaak, P.F.M.

    1995-01-01

    The aim of this study was to describe the disorders and the treatment of patients whose complaints were evaluated as being solely somatic in nature, as being somatic and having psychosocial consequences, or as being (at least partially) of a psychosocial origin. Data were used from a survey on physi

  9. Psychosocial Aspects of Heart Transplantation.

    Science.gov (United States)

    Suszycki, Lee H.

    1988-01-01

    Presents an overview of medical and psychosocial aspects of heart transplantation, with a focus on the program at Columbia-Presbyterian Medical Center. Describes social workers' interventions which help patients and families to achieve optimal psychosocial functioning before and after transplantation. (Author/ABL)

  10. Psychosocial complaints and physical therapy.

    NARCIS (Netherlands)

    Dekker, J.; Valk, R.W.A. van der; Verhaak, P.F.M.

    1995-01-01

    The aim of this study was to describe the disorders and the treatment of patients whose complaints were evaluated as being solely somatic in nature, as being somatic and having psychosocial consequences, or as being (at least partially) of a psychosocial origin. Data were used from a survey on physi

  11. Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms

    Directory of Open Access Journals (Sweden)

    Wigard P. Kloosterman

    2012-06-01

    Full Text Available Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements.

  12. Physical and Psychosocial Environments Associated with Networked Classrooms

    Science.gov (United States)

    Zandvliet, David B.; Fraser, Barry J.

    2005-01-01

    This article reports a study of the learning environments in computer networked classrooms. The study is unique in that it involved an evaluation of both the physical and psychosocial classroom environments in these computerised settings through the use of a combination of questionnaires and ergonomic evaluations. The study involved administering…

  13. Study of the effects of dietary polyunsaturated fatty acids: Molecular mechanisms involved in intestinal inflammation

    OpenAIRE

    Knoch, Bianca; Matthew P.G. Barnett; McNabb, Warren C.; Roy, Nicole C.

    2009-01-01

    The use of «omic» techniques in combination with model systems and molecular tools allows to understand how foods and food components act on metabolic pathways to regulate transcriptional processes. Polyunsaturated fatty acids have distinctive nutritional and metabolic effects because they give rise to lipid mediated products and affect the expression of various genes involved in intestinal inflammation. The present review focuses on the molecular effects of dietary polyunsaturated fatty acid...

  14. VIGS for dissecting mechanisms involved in the symbiotic interaction of microbes with plants

    DEFF Research Database (Denmark)

    Grønlund, Mette

    2015-01-01

    Virus-induced gene silencing (VIGS) is an alternative reverse genetics tool for silencing of genes in some plants which are difficult to transform. The pea early browning virus (PEBV) has been developed as a VIGS vector and used in pea for functional analysis of several genes. Here, a PEBV-VIGS p......-VIGS protocol is described which is suitable for reverse genetics studies in pea for genes involved in the symbiosis with arbuscular mycorrhizal fungi and Rhizobium....

  15. A case of primary spinal myoclonus: clinical presentation and possible mechanisms involved

    OpenAIRE

    Campos Cynthia Resende; Limongi João Carlos Papaterra; Machado Flávia Costa Nunes; Brotto Mário Wilson Iervolino

    2003-01-01

    Spinal myoclonus is a rare movement disorder characterized by myoclonic involvement of a group of muscles supplied by a few contiguous segments of the spinal cord. Structural lesions are usually the cause, but in primary spinal myoclonus the etiology remains unknown. We present the case of a 26-year-old woman with cervical spinal myoclonus in which both clinical and electromyographic findings pointed to the segment C1-C3 as the origin of the myoclonus. Laboratorial examinations were normal an...

  16. Mechanism of Microglia Neuroprotection : Involvement of P2X7, TNF alpha, and Valproic Acid

    NARCIS (Netherlands)

    Masuch, Annette; Shieh, Chu-Hsin; van Rooijen, Nico; van Calker, Dietrich; Biber, Knut

    2016-01-01

    Recently, we have demonstrated that ramified microglia are neuroprotective in N-methyl-D-aspartate (NMDA)-induced excitotoxicity in organotypic hippocampal slice cultures (OHSCs). The present study aimed to elucidate the underlying neuron-glia communication mechanism. It is shown here that pretreatm

  17. "Coding" and "Decoding": hypothesis for the regulatory mechanism involved in heparan sulfate biosynthesis.

    Science.gov (United States)

    Zhang, Xu; Wang, Fengshan; Sheng, Juzheng

    2016-06-16

    Heparan sulfate (HS) is widely distributed in mammalian tissues in the form of HS proteoglycans, which play essential roles in various physiological and pathological processes. In contrast to the template-guided processes involved in the synthesis of DNA and proteins, HS biosynthesis is not believed to involve a template. However, it appears that the final structure of HS chains was strictly regulated. Herein, we report research based hypothesis that two major steps, namely "coding" and "decoding" steps, are involved in the biosynthesis of HS, which strictly regulate its chemical structure and biological activity. The "coding" process in this context is based on the distribution of sulfate moieties on the amino groups of the glucosamine residues in the HS chains. The sulfation of these amine groups is catalyzed by N-deacetylase/N-sulfotransferase, which has four isozymes. The composition and distribution of sulfate groups and iduronic acid residues on the glycan chains of HS are determined by several other modification enzymes, which can recognize these coding sequences (i.e., the "decoding" process). The degree and pattern of the sulfation and epimerization in the HS chains determines the extent of their interactions with several different protein factors, which further influences their biological activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Psychosocial work environment and performance

    DEFF Research Database (Denmark)

    Edwards, Kasper; Møller, Niels

    2010-01-01

    between psychosocial work environment and performance in a large Danish firm. The objects of the study were more than 45 customer centers’ with 9-20 employees each. Using a combination of the Copenhagen psychosocial questionnaire and data from the firms’ balanced scorecard system we show a positive......Good psychosocial work environment has been assumed to result in good work performance. However, little documentation exists which support the claim and the same goes for the opposite claim. This paper reports the first findings from a combined quantitative and qualitative study of the relationship...... significant correlation between performance and psychosocial work environment. A sample of 12 departments was selected for in-depth qualitative study based on their relative change in performance and psychosocial work environment between 2005 and 2007. Through the qualitative study we are able to identity...

  19. Are immunological mechanisms involved in colon cancer and are they possible markers for biotherapy improvement?

    Science.gov (United States)

    Berghella, Anna Maria; Contasta, Ida; Pellegrini, Patrizia; Del Beato, Tiziana; Adorno, Domenico

    2006-10-01

    This paper focuses on our data on colon cancer patients. Our overall results lead us to believe that the suppressive effect of specific cytokines in colon cancer patients alters the functionality of TH1 and TH2 subsets of CD4+ T-cells, with an expansion of TH2 cells and a malfunctioning of TH1 cells. This immunological disregulation appears to increase with stage progression, suggesting a direct role in the mechanisms that allow the tumour to locate and expand within the host. It is also clear that in order to identify disease markers and generate an in vivo immune response that corrects the imbalance between TH1 and TH2 cells, we need to understand how tumour mechanisms cause this imbalance to begin with.

  20. Molecular mechanisms involved in the bidirectional relationship between diabetes mellitus and periodontal disease

    Directory of Open Access Journals (Sweden)

    Harpreet Singh Grover

    2013-01-01

    Full Text Available Both diabetes and periodontitis are chronic diseases. Diabetes has many adverse effects on the periodontium, and conversely periodontitis may have deleterious effects further aggravating the condition in diabetics. The potential common pathophysiologic pathways include those associated with inflammation, altered host responses, altered tissue homeostasis, and insulin resistance. This review examines the relationship that exists between periodontal diseases and diabetes mellitus with a focus on potential common pathophysiologic mechanisms.

  1. Involvement of epigenetic mechanisms in the development of posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Tomaž Zupanc

    2012-03-01

    victims with no childhood abuse were found. It was suggested that changes in glucocorticoid system are mediated by tissue-specific changes in gene expression. Recent studies suggest that epigenetic mechanisms may play an important role in the interplay between stress exposure and genetic vulnerability. Conclusions: Integrating epigenetics into a model that permits prior experience to have a central role in determining individual differences is also consistent with a developmental perspective of PTSD vulnerability.

  2. Molecular mechanisms involved in the bidirectional relationship between diabetes mellitus and periodontal disease.

    Science.gov (United States)

    Grover, Harpreet Singh; Luthra, Shailly

    2013-05-01

    Both diabetes and periodontitis are chronic diseases. Diabetes has many adverse effects on the periodontium, and conversely periodontitis may have deleterious effects further aggravating the condition in diabetics. The potential common pathophysiologic pathways include those associated with inflammation, altered host responses, altered tissue homeostasis, and insulin resistance. This review examines the relationship that exists between periodontal diseases and diabetes mellitus with a focus on potential common pathophysiologic mechanisms.

  3. Molecular mechanisms involved in the bidirectional relationship between diabetes mellitus and periodontal disease

    Science.gov (United States)

    Grover, Harpreet Singh; Luthra, Shailly

    2013-01-01

    Both diabetes and periodontitis are chronic diseases. Diabetes has many adverse effects on the periodontium, and conversely periodontitis may have deleterious effects further aggravating the condition in diabetics. The potential common pathophysiologic pathways include those associated with inflammation, altered host responses, altered tissue homeostasis, and insulin resistance. This review examines the relationship that exists between periodontal diseases and diabetes mellitus with a focus on potential common pathophysiologic mechanisms. PMID:24049328

  4. Phenanthrene causes ocular developmental toxicity in zebrafish embryos and the possible mechanisms involved

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Lixing [State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005 (China); Wang, Chonggang [State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005 (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China); Zhang, Youyu; Wu, Meifang [State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005 (China); Zuo, Zhenghong, E-mail: zuozhenghong@xmu.edu.cn [State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005 (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China)

    2013-10-15

    Highlights: • Phe exposure caused obvious morphological changes in the retina. • Phe exposure caused apoptosis and reduction of cell proliferation in the retina. • Phe causes ocular toxicity might be via the AhR/Zeb1/Mitf/Pax6 signaling pathway. • AhR is a repressor of Zeb1. -- Abstract: Recent studies show that polycyclic aromatic hydrocarbons (PAHs) may be a candidate cause of developmental defects of the retina, but the mechanism is still unclear. We evaluated the mechanism(s) underlying PAH-induced retinal development defects due to exposure to environmental concentrations of Phenanthrene (Phe) in zebrafish. We found that exposure to environmental concentrations of Phe caused obvious morphological changes, developmental retardation, apoptosis, and reduction of cell proliferation in the retina. Our results indicated that Phe could cause visual system developmental defects. Phe exposure up-regulated aryl hydrocarbon receptor (AhR) and microphthalmia-associated transcription factor (Mtif) expression, and down-regulated zinc finger E-box binding homeobox 1 (Zeb1) and paired box 6 (Pax6). Moreover, we demonstrated that AhR was a repressor of Zeb1. We propose that Phe's ocular toxicity is mediated by up-regulating AhR, which then down-regulates Zeb1, in turn inducing Mitf expression while inhibiting Pax6 expression.

  5. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    DEFF Research Database (Denmark)

    Wong, Jaslyn E M M; Midtgaard, Søren Roi; Gysel, Kira

    2015-01-01

    LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multi......LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement...... of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering...... solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers...

  6. Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

    Science.gov (United States)

    Berrendero, Fernando; Robledo, Patricia; Trigo, José Manuel; Martín-García, Elena; Maldonado, Rafael

    2010-01-01

    Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

  7. Molecular mechanisms involved in secretory vesicle recruitment to the plasma membrane in beta-cells.

    Science.gov (United States)

    Varadi, Aniko; Ainscow, E K; Allan, V J; Rutter, G A

    2002-04-01

    Glucose stimulates the release of insulin in part by activating the recruitment of secretory vesicles to the cell surface. While this movement is known to be microtubule-dependent, the molecular motors involved are undefined. Active kinesin was found to be essential for vesicle translocation in live beta-cells, since microinjection of cDNA encoding dominant-negative KHC(mut) (motor domain of kinesin heavy chain containing a Thr(93)-->Asn point mutation) blocked vesicular movements. Moreover, expression of KHC(mut) strongly inhibited the sustained, but not acute, stimulation of secretion by glucose. Thus, vesicles released during the first phase of insulin secretion exist largely within a translocation-independent pool. Kinesin-driven anterograde movement of vesicles is then necessary for the sustained (second phase) of insulin release. Kinesin may, therefore, represent a novel target for increases in intracellular ATP concentrations in response to elevated extracellular glucose and may be involved in the ATP-sensitive K+channel-independent stimulation of secretion by the sugar.

  8. Mechanisms involved in carbachol-induced Ca2+ sensitization of contractile elements in rat proximal and distal colon

    OpenAIRE

    Takeuchi, Tadayoshi; Kushida, Masahiko; Hirayama, Nobue; Kitayama, Muneyoshi; Fujita, Akikazu; Hata, Fumiaki

    2004-01-01

    Mechanisms involved in Ca2+ sensitization of contractile elements induced by the activation of muscarinic receptors in membrane-permeabilized preparations of the rat proximal and distal colon were studied.In α-toxin-permeabilized preparations from the rat proximal and distal colon, Ca2+ induced a rapid phasic and subsequent tonic component. After Ca2+-induced contraction reached a plateau, guanosine 5′-triphosphate (GTP) and carbachol (CCh) in the presence of GTP further contracted preparatio...

  9. Swarming Mechanisms in the Yellow Fever Mosquito: Aggregation Pheromones are Involved in the Mating Behavior of Aedes aegypti

    Science.gov (United States)

    2014-12-01

    Vol. 39, no. 2 Journal of Vector Ecology 347 Swarming mechanisms in the yellow fever mosquito : aggregation pheromones are involved in the mating...behavior of Aedes aegypti Emadeldin Y. Fawaz1, Sandra A. Allan2, Ulrich R. Bernier2, Peter J. Obenauer3, and Joseph W. Diclaro II1 1Vector Biology ...Accepted 15 July 2014 ABSTRACT: Mosquitoes of various species mate in swarms comprised of tens of thousands of flying males. In this study, we examined

  10. A novel mechanism involved in the coupling of mitochondrial biogenesis to oxidative phosphorylation

    Directory of Open Access Journals (Sweden)

    Jelena Ostojić

    2014-01-01

    Full Text Available Mitochondria are essential organelles that are central to a multitude of cellular processes, including oxidative phosphorylation (OXPHOS, which produces most of the ATP in animal cells. Thus it is important to understand not only the mechanisms and biogenesis of this energy production machinery but also how it is regulated in both physiological and pathological contexts. A recent study by Ostojić et al. [Cell Metabolism (2013 18, 567-577] has uncovered a regulatory loop by which the biogenesis of a major enzyme of the OXPHOS pathway, the respiratory complex III, is coupled to the energy producing activity of the mitochondria.

  11. GR-127935-sensitive mechanism mediating hypotension in anesthetized rats: are 5-HT5B receptors involved?

    Science.gov (United States)

    Sánchez-Maldonado, Carolina; López-Sánchez, Pedro; Anguiano-Robledo, Liliana; Leopoldo, Marcello; Lacivita, Enza; Terrón, José A

    2015-04-01

    The 5-HT1B/1D receptor antagonist, GR-127935, inhibits hypotensive responses produced by the 5-HT1A, 5-HT1B/1D and 5-HT7 receptor agonist, and 5-HT5A/5B receptor ligand, 5-carboxamidotryptamine (5-CT), in rats. This work further characterized the above mechanism using more selective 5-HT1B and 5-HT1D receptor antagonists. Also, expression of 5-HT5A and 5-HT5B receptor mRNAs in blood vessels was searched by reverse transcription polymerase chain reaction. Decreases in diastolic blood pressure induced by 5-CT (0.001-10 μg/kg, intravenously) were analyzed in anesthetized rats that had received intravenous vehicle (1 mL/kg), SB-224289 (5-HT1B antagonist; 0.3 and 1.0 mg/kg), BRL15572 (5-HT1D antagonist; 0.3 and 1.0 mg/kg), SB-224289 + BRL15572 (0.3 mg/kg, each), or SB-224289 + BRL15572 (0.3 mg/kg, each) + GR-127935 (1 mg/kg). Because only the latter treatment inhibited 5-CT-induced hypotension, suggestive of a mechanism unrelated to 5-HT1B/1D receptors, the effects of antagonists/ligands at 5-HT5A (SB-699551, 1 mg/kg), 5-HT6 (SB-399885, 1 mg/kg), and 5-HT1B/1D/5A/5B/7 receptors (ergotamine, 0.1 mg/kg) on 5-CT-induced hypotension were tested. Interestingly, only ergotamine blocked 5-CT-induced responses; this effect closely paralleled that of SB-224289 + BRL-15572 + GR-127935. Neither did ergotamine nor GR-127935 inhibit hypotensive responses induced by the 5-HT7 receptor agonist, LP-44. Faint but clear bands corresponding to 5-HT5A and 5-HT5B receptor mRNAs in aorta and mesenteric arteries were detected. Results suggest that the GR-127935-sensitive mechanism mediating hypotension in rats is unrelated to 5-HT1B, 5-HT1D, 5-HT5A, 5-HT6, and 5-HT7 receptors. This mechanism, however, resembles putative 5-HT5B receptors.

  12. Involvement of TACE in colon inflammation: a novel mechanism of regulation via SIRT-1 activation.

    Science.gov (United States)

    Sharma, Manoranjan; Mohapatra, Jogeswar; Wagh, Akshaya; Patel, Hiren M; Pandey, Dheerendra; Kadam, Shekhar; Argade, Anil; Deshpande, Shrikalp S; Shah, Gourang B; Chatterjee, Abhijit; Jain, Mukul R

    2014-03-01

    TNF-α converting enzyme (TACE) processes the membrane TNF-α to release the bioactive soluble TNF-α. Several evidences suggest the involvement of TNF-α and TACE in inflammatory bowel disease (IBD). Tissue inhibitor of metalloproteinase (TIMP)-3, an endogenous inhibitor of TACE, is positively associated with silent information regulator (SIRT)-1. We aimed to study the expression of TACE, TIMP-3 and SIRT-1 at different stages of colitis and how TACE is regulated in response to SIRT-1 activation. Acute colitis was induced by 3.5% dextran sulfate sodium (DSS) in drinking water for 5days and levels of cytokines and mRNA expression of TACE, TIMP-3 and SIRT-1 were measured in colon at different time intervals. Next, the effect of SIRT-1 activator (resveratrol) or a selective TACE inhibitor (compound 11p) treatment was evaluated. Elevated levels of TNF-α, interleukin (IL)-6, IL-1β, interferon (IFN)-γ and IL-17 were observed during DSS exposure phase which restored to the normal level after DSS removal. A significant increase in TACE and suppression in TIMP-3 and SIRT-1 mRNA level was observed during DSS exposure phase which reverts back to normal towards the remission phase. Treatment with resveratrol significantly elevated SIRT-1 and TIMP-3 and suppressed TACE mRNA expression and was associated with amelioration of disease. Furthermore, treatment with selective TACE inhibitor significantly suppressed body weight loss, disease activity index, colonic myeloperoxidase activity and the elevated levels of cytokines after DSS challenge. These results strongly emphasize the involvement of TACE in colon inflammation and inhibition of TACE directly or indirectly via SIRT-1 activation ameliorates colitis.

  13. Mechanism of Anti-glioblastoma Effect of Temzolomide Involved in ROS-Mediated SIRT 1 Pathway

    Directory of Open Access Journals (Sweden)

    Yuan Jiang

    2014-03-01

    Full Text Available Objective: To explore the new molecular mechanism of anti-tumor effect of temzolomide (TMZon glioblastoma cell strain. Methods: MTT methods and Hoechst 33342 staining method were applied to determine the effect of TMZ on the proliferation and apoptosis of glioblastoma cell strains U251 and SHG44, while flow cytometry was used to detect the impact of TMZ on cellular cycles. Additionally, DCFH-DA probe was adopted to test intracellular reactive oxygen species (ROS level while Real-time PCR and Western blot tests were applied to determine the influence of TMZ on SIRT1 expression. Results: TMZ in different concentrations added into glioblastoma cell strain for 72 h could concentration-dependently inhibit the proliferation of glioblastoma cells, 100 μmol/L of which could also block cells in phase G2/M and improve cellular apoptosis. In addition, TMZ could evidently increase intracellular ROS level so as to activate SIRT1. Conclusion: The mechanism of anti-tumor effect of TMZ on glioblastoma may be associated with ROS-induced SIRT1 pathway, providing theoretical basis for the clinical efficacy of TMZ.

  14. Mechanism of Anti-glioblastoma Effect of Temzolomide Involved in ROS-Mediated SIRT 1 Pathway

    Institute of Scientific and Technical Information of China (English)

    Jiang Yuan; Sun Yan; Yuan Yuan

    2014-01-01

    Objective:To explore the new molecular mechanism of anti-tumor effect of temzolomide (TMZ) on glioblastoma cell strain. Methods:MTT methods and Hoechst 33342 staining method were applied to determine the effect of TMZ on the proliferation and apoptosis of glioblastoma cell strains U251 and SHG44, while lfow cytometry was used to detect the impact of TMZ on cellular cycles. Additionally, DCFH-DA probe was adopted to test intracellular reactive oxygen species (ROS) level while Real-time PCR and Western blot tests were applied to determine the inlfuence of TMZ on SIRT1 expression. Results: TMZ in different concentrations added into glioblastoma cell strain for 72 h could concentration-dependently inhibit the proliferation of glioblastoma cells, 100 μmol/L of which could also block cells in phase G2/M and improve cellular apoptosis. In addition, TMZ could evidently increase intracellular ROS level so as to activate SIRT1. Conclusion: The mechanism of anti-tumor effect of TMZ on glioblastoma may be associated with ROS-induced SIRT1 pathway, providing theoretical basis for the clinical efifcacy of TMZ.

  15. A cell-regulatory mechanism involving feedback between contraction and tissue formation guides wound healing progression.

    Directory of Open Access Journals (Sweden)

    Clara Valero

    Full Text Available Wound healing is a process driven by cells. The ability of cells to sense mechanical stimuli from the extracellular matrix that surrounds them is used to regulate the forces that cells exert on the tissue. Stresses exerted by cells play a central role in wound contraction and have been broadly modelled. Traditionally, these stresses are assumed to be dependent on variables such as the extracellular matrix and cell or collagen densities. However, we postulate that cells are able to regulate the healing process through a mechanosensing mechanism regulated by the contraction that they exert. We propose that cells adjust the contraction level to determine the tissue functions regulating all main activities, such as proliferation, differentiation and matrix production. Hence, a closed-regulatory feedback loop is proposed between contraction and tissue formation. The model consists of a system of partial differential equations that simulates the evolution of fibroblasts, myofibroblasts, collagen and a generic growth factor, as well as the deformation of the extracellular matrix. This model is able to predict the wound healing outcome without requiring the addition of phenomenological laws to describe the time-dependent contraction evolution. We have reproduced two in vivo experiments to evaluate the predictive capacity of the model, and we conclude that there is feedback between the level of cell contraction and the tissue regenerated in the wound.

  16. Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving CCK.

    Science.gov (United States)

    Jeon, Tae-Il; Seo, Young-Kyo; Osborne, Timothy F

    2011-08-15

    T2Rs (bitter taste-sensing type 2 receptors) are expressed in the oral cavity to prevent ingestion of dietary toxins through taste avoidance. They are also expressed in other cell types, including gut enteroendocrine cells, where their physiological role is enigmatic. Previously, we proposed that T2R-dependent CCK (cholecystokinin) secretion from enteroendocrine cells limits absorption of dietary toxins, but an active mechanism was lacking. In the present study we show that T2R signalling activates ABCB1 (ATP-binding cassette B1) in intestinal cells through a CCK signalling mechanism. PTC (phenylthiocarbamide), an agonist for the T2R38 bitter receptor, increased ABCB1 expression in both intestinal cells and mouse intestine. PTC induction of ABCB1 was decreased by either T2R38 siRNA (small interfering RNA) or treatment with YM022, a gastrin receptor antagonist. Thus gut ABCB1 is regulated through signalling by CCK/gastrin released in response to PTC stimulation of T2R38 on enteroendocrine cells. We also show that PTC increases the efflux activity of ABCB1, suggesting that T2R signalling limits the absorption of bitter tasting/toxic substances through modulation of gut efflux membrane transporters.

  17. 心理弹性的心理社会及生物学机制%The Psychosocial and Biological Mechanism of Resilience

    Institute of Scientific and Technical Information of China (English)

    李丽; 谢光荣

    2012-01-01

    Resilience refers to a dynamic process encompassing coping successfully and positive adaptation within acute stress, trauma or more chronic forms of adversity. The studies of resilient mechanism mainly focus on psycho -social and biological field. In this paper, we explore the mechanism in the role of individual, family, social, Neurobiology and molecular genetics factors of resilience. Finally, the future research trends in the relevant areas were discussed.%心理弹性是个体在经历急性压力、创伤或者更多不同形式的慢性压力时成功应对、积极适应的动态过程,对心理弹性机制的研究有心理社会及生物学两种研究取向.探索了心理弹性的个人、家庭、社会环境、神经生物、分子遗传学因素以及它们的作用机制过程,并对今后的研究进行了展望.

  18. PSYCHOSOCIAL IMPACT OF LAPINDO MUD DISASTER

    Directory of Open Access Journals (Sweden)

    Mundakir Mundakir

    2017-04-01

    Full Text Available Introduction: Lapindo mud disaster that occurred since 29 May 2006 is considered as the longest disaster that occurred in Indonesia. This disaster has caused damage and lost of property which has been affecting the viability of the residents of the affected areas. Psychosocial well being is one af the impacts of disaster. Research was conducted using qualitative design with descriptive phenomenology method. The purpose required of this research was to identify the psychological impact, social impact, and hope for the settlement of problems and health services. Method: Number of participants were involved in this research based on the saturation of data was 7 people. This study used purposive sampling technique using the key informant. Procedure of data collection techniques using depth interviews with a semi-structured form of used questions. The Digital Voice Record was utilized to record the interviews, and verbatim transcripts made and analyzed using the methods of Colaizi (1978, in Daymon and Dolloway, 2008. Result: This study revealed 9 theme of core and 2 additional theme. Nine the core theme is emotional changes, cognitive changes, coping mechanism, changes in family function, changes in social relationships, social support, hope to the problem to the government and PT Lapindo, physical health service needs and psychological health. Discussion: While two additional theme that is risk and growth trouble, and distres spiritual. Conclusion of this research society of victim of mud of Lapindo experience of impact of psikosoial and hope to government and PT Lapindo settle the payment phase II (80% and also provide service of health of physical and also psikososial. This research recommend the importance of intervention of psikososial to society of victim and research of continuation after society of victim take possession of new residences.

  19. Modeling of glycerol-3-phosphate transporter suggests a potential 'tilt' mechanism involved in its function.

    Science.gov (United States)

    Tsigelny, Igor F; Greenberg, Jerry; Kouznetsova, Valentina; Nigam, Sanjay K

    2008-10-01

    Many major facilitator superfamily (MFS) transporters have similar 12-transmembrane alpha-helical topologies with two six-helix halves connected by a long loop. In humans, these transporters participate in key physiological processes and are also, as in the case of members of the organic anion transporter (OAT) family, of pharmaceutical interest. Recently, crystal structures of two bacterial representatives of the MFS family--the glycerol-3-phosphate transporter (GlpT) and lac-permease (LacY)--have been solved and, because of assumptions regarding the high structural conservation of this family, there is hope that the results can be applied to mammalian transporters as well. Based on crystallography, it has been suggested that a major conformational "switching" mechanism accounts for ligand transport by MFS proteins. This conformational switch would then allow periodic changes in the overall transporter configuration, resulting in its cyclic opening to the periplasm or cytoplasm. Following this lead, we have modeled a possible "switch" mechanism in GlpT, using the concept of rotation of protein domains as in the DynDom program17 and membranephilic constraints predicted by the MAPAS program.(23) We found that the minima of energies of intersubunit interactions support two alternate positions consistent with their transport properties. Thus, for GlpT, a "tilt" of 9 degrees -10 degrees rotation had the most favorable energetics of electrostatic interaction between the two halves of the transporter; moreover, this confirmation was sufficient to suggest transport of the ligand across the membrane. We conducted steered molecular dynamics simulations of the GlpT-ligand system to explore how glycerol-3-phosphate would be handled by the "tilted" structure, and obtained results generally consistent with experimental mutagenesis data. While biochemical data remain most consistent with a single-site alternating access model, our results raise the possibility that, while the

  20. Potassium channel and NKCC cotransporter involvement in ocular refractive control mechanisms.

    Directory of Open Access Journals (Sweden)

    Sheila G Crewther

    Full Text Available Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/-10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5 mM Ba(2+ and 10(-5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba(2+ but significant change only for negative lens defocus with bumetanide (Rx(SAL(-10D = -8.6 +/- .9 D; Rx(Ba2+(-10D = -2.9 +/- .9 D; Rx(Bum(-10D = -2.9 +/- .9 D; Rx(SAL(+10D = +8.2 +/- .9 D; Rx(Ba2+(+10D = +2.8 +/- 1.3 D; Rx(Bum(+10D = +8.0 +/- .7 D. Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba(2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a

  1. Mechanisms Involved in Thromboxane A2-induced Vasoconstriction of Rat Intracavernous Small Penile Arteries

    DEFF Research Database (Denmark)

    Grann, Martin; Comerma Steffensen, Simon Gabriel; Arcanjo, Daniel Dias Rufino

    2015-01-01

    relaxation in rat mesenteric arteries. Our findings suggest that U46619 contraction depends on Ca2+ influx through L-type and TRP channels, and ROCKdependent mechanisms in penile arteries. Inhibition of the ROCK pathway is a potential approach for the treatment of erectile dysfunction associated......Diabetes is associated with erectile dysfunction and with hypercontractility in erectile tissue and this is in part ascribed to increased formation of thromboxane. Rho kinase (ROCK) is a key regulator of calcium sensitization and contraction in vascular smooth muscle. This study investigated...... the role of calcium and ROCK in contraction evoked by activation of the thromboxane receptors. Rat intracavernous penile arteries were mounted for isometric tension and intracellular calcium ([Ca2+]i) recording and corpus cavernosum for measurements of MYPT1 phosphorylation. In penile arteries, U46619...

  2. The Micro-mechanism Involved and Wollastonite Signature in the Calcareous Precipitates of Marine Isolates.

    Science.gov (United States)

    Sarayu, K; Iyer, Nagesh R; Annaselvi, M; Ramachandra Murthy, A

    2016-03-01

    Micro-mechanical studies connecting the influence of extrinsic factors over intrinsic factors on 30 calcareous isolates obtained from marine sediment biofilms of the Bay of Bengal (Indian Ocean) revealed that the fate of calcareous crystal precipitation is highly dependent on factors like extracellular polysaccharides (EPS), organic carbon and nutrition. Further studies exemplified that EPS and the organic carbon secreted by the isolates controlled the dissemination of the calcareous crystals precipitated. From the study, it is evident that an EPS concentration of 7-15 mg l(-1) was found to enhance the dissemination of the calcareous crystals. Atomic force micrographs explain the nucleation behaviour and morphology of the calcareous crystals precipitated. X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDAX) showed that the crystals were mainly composed of calcite and partially wollastonite.

  3. Mechanisms Involved in Trichloroethylene-Induced Liver Cancer: Importance to Environmental Cleanup

    Energy Technology Data Exchange (ETDEWEB)

    Bull, Richard J.; Thrall, Brian D.

    2000-06-01

    The project is organized around two interrelated tasks: Task 1 develops the basic dosimetry parameters and provides in vivo data describing the mode of action tumorigenic and for the metabolites of TCE that produce liver cancer in mice, dichloroacetate (DCA) and trichloroacetate (TCA). Early work suggested that TCA was primarily responsible for TCE-induced liver tumor. More recent, mechanistic observations indicated that DCA played a prominent role. Therefore, studies were designed to determine whether the effects of DCA were mediated through a mode of action that affects primarily tumor growth rates. Task 2 seeks specific evidence that TCA and DCA are capable of promoting the growth of spontaneously initiated cells from mouse liver, in vitro. The data provide the clearest evidence that both metabolites act by a mechanism of selection rather than mutation. These data are necessary to select between a linear (i.e. no threshold) and non-linear low-dose extrapolation models.

  4. Serotonergic mechanisms involved in the suppression of feeding by 5-HTP in rats.

    Science.gov (United States)

    Ju, C Y; Tsai, C T

    1995-01-01

    The effect of 5-hydroxytryptophan (5-HTP), the serotonin precursor, on food intake in rats was investigated in this study. 5-HTP (100 mg/kg, i.p.) reduced food intake by 68.9% of control level. The anorectic effect of 5-HTP was antagonized by cyproheptadine (CYP, 4 mg/kg, i.p.), a serotonin receptor blockade. However, the anorectic effect of 5-HTP was also antagonized by propranolol (PROP 1mg/kg, i.p.) and sulpiride (SULP, 20 mg/kg, i.p.), while Pinodol (PIN 2mg/kg, i.p.) and Haloperidol (HAL 0.5 mg/kg, i.p) did not affect the suppressive effect of 5-HTP on food intake by 5-HTP. These results indicates that the anorectic action of 5-HTP was mediated by the serotonergic mechanism through 5-HT1 and 5-HT2 receptors.

  5. Calcium ion involvement in growth inhibition of mechanically stressed soybean (Glycine max) seedlings

    Science.gov (United States)

    Jones, R. S.; Mitchell, C. A.

    1989-01-01

    A 40-50% reduction in soybean [Glycine max (L.) Merr. cv. Century 84] hypocotyl elongation occurred 24 h after application of mechanical stress. Exogenous Ca2+ at 10 mM inhibited growth by 28% if applied with the Ca2+ ionophore A23187 to the zone of maximum hypocotyl elongation. La3+ was even more inhibitory than Ca2+, especially above 5 mM. Treatment with ethyleneglycol-bis-(beta-aminoethylether)-N, N, N', N'-tetraacetic acid (EGTA) alone had no effect on growth of non-stressed seedlings at the concentrations used but negated stress-induced growth reduction by 36% at 4 mM when compared to non-treated, stressed controls. Treatment with EDTA was ineffective in negating stress-induced growth inhibition. Calmodulin antagonists calmidazolium, chlorpromazine, and 48/80 also negated stress-induced growth reduction by 23, 50, and 35%, respectively.

  6. Molecular mechanisms involved in adaptive responses to radiation, UV light, and heat.

    Science.gov (United States)

    Takahashi, Akihisa; Ohnishi, Takeo

    2009-09-01

    Viable organisms recognize and respond to environmental changes or stresses. When these environmental changes and their responses by organisms are extreme, they can limit viability. However, organisms can adapt to these different stresses by utilizing different possible responses via signal transduction pathways when the stress is not lethal. In particular, prior mild stresses can provide some aid to prepare organisms for subsequent more severe stresses. These adjustments or adaptations for future stresses have been called adaptive responses. These responses are present in bacteria, plants and animals. The following review covers recent research which can help describe or postulate possible mechanisms which may be active in producing adaptive responses to radiation, ultraviolet light, and heat.

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

    Science.gov (United States)

    Gaut, Carrie; Sugaya, Kiminobu

    2015-01-01

    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.

  8. [Cytological mechanisms involved in assimilation of n-alkanes by yeasts].

    Science.gov (United States)

    Meĭsel', M N; Medvedeva, G A; Kozlova, T M

    1976-01-01

    The paper describes cytological mechanism of adaptation of yeasts to assimilation of aliphatic hydrocarbons added to a growth medium as a sole source of carbon. The process was studied by light optical and electron microscopy, employing fluorescent labelling and electron microscopy contrasting. Two types of yeasts were found, which differed by the response of the cell walls to hydrocarbons: those that formed "channels" and those that did not form them. Cytological response to hydrocarbon assimilation was detected also in the mitochondria and canals of the endoplasmic reticulum. Components of the Golgi apparatus may also participate in this process, in particular, in formation of peroxisomes (microbodies). Close contacts of the yeast cells with the hydrocarbon being assimilated is important; assimilation may start in a close vicinity of the cell walls. The rate of flavin production by Candida tropicalis 303 IBFM increases during growth on solid paraffins, beginning with C20-paraffin.

  9. Breast cancer: mechanisms involved in action of phytoestrogens and epigenetic changes.

    Science.gov (United States)

    Dagdemir, Aslihan; Durif, Julie; Ngollo, Marjolaine; Bignon, Yves-Jean; Bernard-Gallon, Dominique

    2013-01-01

    In this review, we consider phytoestrogens and different epigenetic modifications in breast cancer. Epigenetic phenomena are mediated by several molecular mechanisms comprising histone modifications, small non-coding or anti-sense RNA and DNA methylation. These different modifications are closely interrelated. De-regulation of gene expression is a hallmark of cancer. Although genetic lesions have been the focus of cancer research for many years, it has become increasingly recognized that aberrant epigenetic modifications also play major roles in breast carcinogenesis. The incidence and mortality rates of breast cancer are high in the Western world compared with countries in Asia. There are also differences in the breast cancer incidence rates in different Western countries. This could be related to phytoestrogens.

  10. Intrauterine infection/inflammation during pregnancy and offspring brain damages: Possible mechanisms involved

    Directory of Open Access Journals (Sweden)

    Golan Hava

    2004-04-01

    Full Text Available Abstract Intrauterine infection is considered as one of the major maternal insults during pregnancy. Intrauterine infection during pregnancy could lead to brain damage of the developmental fetus and offspring. Effects on the fetal, newborn, and adult central nervous system (CNS may include signs of neurological problems, developmental abnormalities and delays, and intellectual deficits. However, the mechanisms or pathophysiology that leads to permanent brain damage during development are complex and not fully understood. This damage may affect morphogenic and behavioral phenotypes of the developed offspring, and that mice brain damage could be mediated through a final common pathway, which includes over-stimulation of excitatory amino acid receptor, over-production of vascularization/angiogenesis, pro-inflammatory cytokines, neurotrophic factors and apoptotic-inducing factors.

  11. Anticonvulsants Teratogenic Mechanism Involves Alteration of Bioelectrically-controlled Processes in the Embryo. A hypothesis

    Science.gov (United States)

    Hernández-Díaz, Sonia; Levin, Michael

    2014-01-01

    Maternal use of anticonvulsants during the first trimester of pregnancy has been associated with an elevated risk of major congenital malformations in the offspring. Whether the increased risk is caused by the specific pharmacological mechanisms of certain anticonvulsants, the underlying epilepsy, or common genetic or environmental risk factors shared by epilepsy and malformations is controversial. We hypothesize that anticonvulsant therapies during pregnancy that attain more successful inhibition of neurotransmission might lead to both better seizure control in the mother and stronger alteration of bioelectrically-controlled processes in the embryo that result in structural malformations. If our theory were correct, development of pharmaceuticals that do not alter cell resting transmembrane voltage levels could result in safer drugs. PMID:24815983

  12. Effects of high fluoride intake on child mental work capacity: preliminary investigation into the mechanisms involved

    Energy Technology Data Exchange (ETDEWEB)

    Li, Y.; Li, X.J.; Wei, S.Q. [Child & Adolescent Hygiene Teaching Research Station, Chengdu (China)

    2008-10-15

    A study was carried out on 157 children, age 12-13, from a coal-burning fluorosis endemic area together with an experiment looking into the effect of high fluoride intake in animals. The results showed that early, prolonged high fluoride intake causes a decrease in a child's mental work capacity and that prolonged high uptake of fluoride causes a child's levels of hair zinc to drop. A multifactoral correlative analysis demonstrated a direct correlation between hair zinc and mental work capacity. The decrease of 5-hydroxyindoleacetic acid and the increase of norepinephrine in animal brains exposed to high levels of fluoride suggest a possible mechanism for mental work capacity deficits in children. However, further research is necessary.

  13. A tumor-suppressing mechanism in Drosophila involving cell competition and the Hippo pathway

    Science.gov (United States)

    Menéndez, Javier; Pérez-Garijo, Ainhoa; Calleja, Manuel; Morata, Ginés

    2010-01-01

    Mutant larvae for the Drosophila gene lethal giant larva (lgl) develop neoplastic tumors in imaginal discs. However, lgl mutant clones do not form tumors when surrounded by wild-type tissue, suggesting the existence of a tumor-suppressing mechanism. We have investigated the tumorigenic potential of lgl mutant cells by generating wing compartments that are entirely mutant for lgl and also inducing clones of various genetic combinations of lgl− cells. We find that lgl− compartments can grow indefinitely but lgl− clones are eliminated by cell competition. lgl mutant cells may form tumors if they acquire constitutive activity of the Ras pathway (lgl− UAS-rasV12), which confers proliferation advantage through inhibition of the Hippo pathway. Yet, the majority of lgl− UAS-rasV12 clones are eliminated in spite of their high proliferation rate. The formation of a tumor requires in addition the formation of a microenvironment that allows mutant cells to evade cell competition. PMID:20679206

  14. Dopamine receptor-mediated mechanisms involved in the expression of learned activity of primate striatal neurons.

    Science.gov (United States)

    Watanabe, K; Kimura, M

    1998-05-01

    To understand the mechanisms by which basal ganglia neurons express acquired activities during and after behavioral learning, selective dopamine (DA) receptor antagonists were applied while recording the activity of striatal neurons in monkeys performing behavioral tasks. In experiment 1, a monkey was trained to associate a click sound with a drop of reward water. DA receptor antagonists were administered by micropressure using a stainless steel injection cannula (300 microm ID) through which a Teflon-coated tungsten wire for recording neuronal activity had been threaded. Responses to sound by tonically active neurons (TANs), a class of neurons in the primate striatum, were recorded through a tungsten wire electrode during the application of either D1- or D2-class DA receptor antagonists (total volume one of the surrounding barrels. SCH23390 (10 mM, pH 4.5) and (-)-sulpiride (10 mM, pH 4.5) were used. The effects of iontophoresis of both D1- and D2-class antagonists were examined in 40 TANs. Of 40 TANs from which recordings were made, responses were suppressed exclusively by the D2-class antagonist in 19 TANs, exclusively by the D1-class antagonist in 3 TANs, and by both D1- and D2-class antagonists in 7 TANs. When 0.9% NaCl, saline, was applied by pressure (<1 microl) or by iontophoresis (<30 nA) as a control, neither the background discharge rates nor the responses of TANs were significantly influenced. Background discharge rate of TANs was also not affected by D1- or D2-class antagonists applied by either micropressure injection or iontophoresis. It was concluded that the nigrostriatal DA system enables TANs to express learned activity primarily through D2-class and partly through D1-class receptor-mediated mechanisms in the striatum.

  15. A pathogenic mechanism in Huntington's disease involves small CAG-repeated RNAs with neurotoxic activity.

    Science.gov (United States)

    Bañez-Coronel, Mónica; Porta, Silvia; Kagerbauer, Birgit; Mateu-Huertas, Elisabet; Pantano, Lorena; Ferrer, Isidre; Guzmán, Manuel; Estivill, Xavier; Martí, Eulàlia

    2012-01-01

    Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene. The abnormally extended polyglutamine in the HTT protein encoded by the CAG repeats has toxic effects. Here, we provide evidence to support that the mutant HTT CAG repeats interfere with cell viability at the RNA level. In human neuronal cells, expanded HTT exon-1 mRNA with CAG repeat lengths above the threshold for complete penetrance (40 or greater) induced cell death and increased levels of small CAG-repeated RNAs (sCAGs), of ≈21 nucleotides in a Dicer-dependent manner. The severity of the toxic effect of HTT mRNA and sCAG generation correlated with CAG expansion length. Small RNAs obtained from cells expressing mutant HTT and from HD human brains significantly decreased neuronal viability, in an Ago2-dependent mechanism. In both cases, the use of anti-miRs specific for sCAGs efficiently blocked the toxic effect, supporting a key role of sCAGs in HTT-mediated toxicity. Luciferase-reporter assays showed that expanded HTT silences the expression of CTG-containing genes that are down-regulated in HD. These results suggest a possible link between HD and sCAG expression with an aberrant activation of the siRNA/miRNA gene silencing machinery, which may trigger a detrimental response. The identification of the specific cellular processes affected by sCAGs may provide insights into the pathogenic mechanisms underlying HD, offering opportunities to develop new therapeutic approaches.

  16. Mechanical stretch upregulates proteins involved in Ca2+ sensitization in urinary bladder smooth muscle hypertrophy.

    Science.gov (United States)

    Boopathi, Ettickan; Gomes, Cristiano; Zderic, Stephen A; Malkowicz, Bruce; Chakrabarti, Ranjita; Patel, Darshan P; Wein, Alan J; Chacko, Samuel

    2014-09-15

    Partial bladder outlet obstruction (pBOO)-induced remodeling of bladder detrusor smooth muscle (DSM) is associated with the modulation of cell signals regulating contraction. We analyzed the DSM from obstructed murine urinary bladders for the temporal regulation of RhoA GTPase and Rho-activated kinase (ROCK), which are linked to Ca(2+) sensitization. In addition, the effects of equibiaxial cell stretch, a condition thought to be associated with pBOO-induced bladder wall smooth muscle hypertrophy and voiding frequency, on the expression of RhoA, ROCK, and C-kinase-activated protein phosphatase I inhibitor (CPI-17) were investigated. DSM from 1-, 3-, 7-, and 14-day obstructed male mice bladders and benign prostatic hyperplasia (BPH)-induced obstructed human bladders revealed overexpression of RhoA and ROCK-β at the mRNA and protein levels compared with control. Primary human bladder myocytes seeded onto type I collagen-coated elastic silicone membranes were subjected to cyclic equibiaxial stretch, mimicking the cellular mechanical stretch in the bladder in vivo, and analyzed for the expression of RhoA, ROCK-β, and CPI-17. Stretch caused a significant increase of RhoA, ROCKβ, and CPI-17 expression. The stretch-induced increase in CPI-17 expression occurs at the transcriptional level and is associated with CPI-17 promoter binding by GATA-6 and NF-κB, the transcription factors responsible for CPI-17 gene transcription. Cell stretch caused by bladder overdistension in pBOO is the likely mechanism for initiating overexpression of the signaling proteins regulating DSM tone.

  17. Growth capacity and biochemical mechanisms involved in rhizobia tolerance to salinity and water deficit.

    Science.gov (United States)

    Mhamdi, Rakia; Nouairi, Issam; ben Hammouda, Thouraya; Mhamdi, Ridha; Mhadhbi, Haythem

    2015-04-01

    The aim of the present study was to evaluate abiotic stress tolerance of rhizobial strains belonging to Mesorhizobium, Sinorhizobium, and Rhizobium genera, as well as to investigate specie specific stress response mechanisms. Effect of NaCl and PEG on growth capacity, protein, lipid peroxydation (MDA), membrane fatty acid composition and antioxidant enzymes were investigated. Growth capacity and viability of overall rhizobia strains decreased proportionally to the increase of NaCl and PEG levels in the medium. Sinorhizobium strains appeared the most tolerant, where 4H41strain was able to grow at 800 mM NaCl and 40% PEG. On the other hand, growth of R. gallicum and M. mediterraneum was inhibited by 200 mM NaCl. The content of MDA was unchanged in Sinorhizobium strains under both stresses. For Mesorhizobium, only PEG treatment increased the content of MDA. Amount of the C19:0 cyclo fatty-acid was increased in both Sinorhizobium and Mesorhizobium tolerant strains. NaCl stress increased Superoxide dismutase (SOD) activity of overall species; especially the most tolerant strain 4H41. Both treatments increased catalase (CAT) activity in 4H41, TII7, and 835 strains. Obtained results suggest that major response of tolerant Sinorhizobium and Mesorhizobium strains to NaCl and PEG stresses is a preferential accumulation of the C19:0 cyclo fatty acid within bacterial membrane as mechanism to reduce fluidity and maintain integrity. Cell integrity and functioning is also assured by maintaining and/or increasing activity of SOD and CAT antioxidant enzymes for tolerant strains to omit structural and functional damages related to reactive oxygen species overproduced under stressful conditions.

  18. Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women.

    Science.gov (United States)

    Ma, Yidan; Zhao, Guang; Tu, Shen; Zheng, Yong

    2015-01-01

    A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females) in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed.

  19. Attentional Biases toward Attractive Alternatives and Rivals: Mechanisms Involved in Relationship Maintenance among Chinese Women.

    Directory of Open Access Journals (Sweden)

    Yidan Ma

    Full Text Available A long-term romantic relationship can offer many benefits to committed individuals. Thus, humans possess relationship maintenance mechanisms to protect against threats from those who serve as attractive alternatives or intrasexual rivals. Many studies have indicated that romantic love can act as a commitment device to activate these mechanisms. To examine the attentional bias associated with relationship maintenance among 108 college students (49 single and 59 committed females in China, we used a semantic priming procedure to activate mental representations associated with romantic love and then asked participants to complete a dot-probe task for the purpose of making a distinction between the engage and disengage components of attention. No significant engaging effects toward attractive faces were observed among committed females, but the following significant disengaging effects were found: when primed with romantic love, single females showed increased attention toward and difficulty in disengaging from attractive male faces, whereas females already in a committed relationship did not alter their attention, remaining as inattentive to attractive alternatives as they were in the baseline condition. In addition, committed females responded to love priming by exhibiting difficulty in disengaging from attractive rivals. The present findings provide evidence in the Chinese cultural context for the existence of early-stage attentional processes in the domain of relationship maintenance that committed Chinese females protected an ongoing relationship by not only being inattentive to attractive males who could serve as attractive alternatives, but also being more attentive to attractive females who could be potential rivals when mental representations associated with romantic love were primed.

  20. Managing psychosocial adjustment to aphasia.

    Science.gov (United States)

    Müller, D

    1999-01-01

    This article argues for incorporating psychosocial adjustment into treatment plans for people with aphasia. It proposes that rehabilitation is a social rather than a medical construct and that by adopting a broad range of intervention strategies, more effective approaches to reintegration can be adopted. Outcome measures relating to self-esteem are judged to be central to evaluating the efficacy of treatment. The role of social factors in managing psychosocial adjustment are considered alongside individual and family approaches to counseling. It is concluded that clinicians need to broaden their treatment program to include psychosocial adjustment in rehabilitation.

  1. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Jaslyn E. M. M. [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Midtgaard, Søren Roi [University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark); Gysel, Kira [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Thygesen, Mikkel B.; Sørensen, Kasper K.; Jensen, Knud J. [University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Stougaard, Jens; Thirup, Søren; Blaise, Mickaël, E-mail: mickael.blaise@cpbs.cnrs.fr [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark)

    2015-03-01

    The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

  2. Oxidative stress in the pathophysiology of metabolic syndrome: which mechanisms are involved?

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    Thalia M. T. Avelar

    2015-08-01

    Full Text Available ABSTRACTMetabolic syndrome (MS is a combination of cardiometabolic risk factors, including obesity, hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension. Several studies report that oxidative condition caused by overproduction of reactive oxygen species (ROS plays an important role in the development of MS. Our body has natural antioxidant system to reduce oxidative stress, which consists of numerous endogenous and exogenous components and antioxidants enzymes that are able to inactivate ROS. The main antioxidant defense enzymes that contribute to reduce oxidative stress are superoxide dismutase (SOD, catalase (CAT and gluthatione peroxidase (GPx. The high-density lipoprotein cholesterol (HDL-c is also associated with oxidative stress because it presents antioxidant and anti-inflammatory properties. HDL-c antioxidant activity may be attributed at least in part, to serum paraoxonase 1 (PON1 activity. Furthermore, derivatives of reactive oxygen metabolites (d-ROMs also stand out as acting in cardiovascular disease and diabetes, by the imbalance in ROS production, and close relationship with inflammation. Recent reports have indicated the gamma-glutamyl transferase (GGT as a promising biomarker for diagnosis of MS, because it is related to oxidative stress, since it plays an important role in the metabolism of extracellular glutathione. Based on this, several studies have searched for better markers for oxidative stress involved in development of MS.

  3. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase.

    Science.gov (United States)

    Wong, Jaslyn E M M; Midtgaard, Søren Roi; Gysel, Kira; Thygesen, Mikkel B; Sørensen, Kasper K; Jensen, Knud J; Stougaard, Jens; Thirup, Søren; Blaise, Mickaël

    2015-03-01

    LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

  4. IL-5-overexpressing mice exhibit eosinophilia and altered wound healing through mechanisms involving prolonged inflammation.

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    Leitch, Victoria D; Strudwick, Xanthe L; Matthaei, Klaus I; Dent, Lindsay A; Cowin, Allison J

    2009-02-01

    Leucocytes are essential in healing wounds and are predominantly involved in the inflammatory and granulation stages of wound repair. Eosinophils are granulocytic leucocytes and are specifically regulated by interleukin-5 (IL-5), a cytokine produced by T helper 2 (Th2) cells. To characterize more clearly the role of the IL-5 and eosinophils in the wound healing process, IL-5-overexpressing and IL-5-deficient mice were used as models of eosinophilia and eosinophil depletion, respectively. Our results reveal a significantly altered inflammatory response between IL-5-overexpressing and IL-5 knockout mice post-wounding. Healing was significantly delayed in IL-5-overexpressing mice with wounds gaping wider and exhibiting impaired re-epithelialization. A delay in collagen deposition was observed suggesting a direct effect on matrix synthesis. A significant increase in inflammatory cell infiltration, particularly eosinophils and CD4(+) cells, one of the main cell types which secrete IL-5, was observed in IL-5-overexpressing mice wounds suggesting that one of the main roles of IL-5 in wound repair may be to promote the infiltration of eosinophils into healing wounds. Healing is delayed in IL-5-overexpressing mice and this corresponds to significantly increased levels of eosinophils and CD4(+) cells within the wound site that may contribute to and exacerbate the inflammatory response, resulting in detrimental wound repair.

  5. Modelling and pathway identification involving the transport mechanism of a complex metabolic system in batch culture

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    Yuan, Jinlong; Zhang, Xu; Zhu, Xi; Feng, Enmin; Yin, Hongchao; Xiu, Zhilong

    2014-06-01

    The bio-dissimilation of glycerol to 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae (K. pneumoniae) can be characterized by a complex metabolic system of interactions among biochemical fluxes, metabolic compounds, key enzymes and genetic regulation. In this paper, in consideration of the fact that the transport ways of 1,3-PD and glycerol with different weights across cell membrane are still unclear in batch culture, we consider 121 possible metabolic pathways and establish a novel mathematical model which is represented by a complex metabolic system. Taking into account the difficulty in accurately measuring the concentration of intracellular substances and the absence of equilibrium point for the metabolic system of batch culture, the novel approach used here is to define quantitatively biological robustness of the intracellular substance concentrations for the overall process of batch culture. To determine the most possible metabolic pathway, we take the defined biological robustness as cost function and establish an identification model, in which 1452 system parameters and 484 pathway parameters are involved. Simultaneously, the identification model is subject to the metabolic system, continuous state constraints and parameter constraints. As such, solving the identification model by a serial program is a very complicated task. We propose a parallel migration particle swarm optimization algorithm (MPSO) capable of solving the identification model in conjunction with the constraint transcription and smoothing approximation techniques. Numerical results show that the most possible metabolic pathway and the corresponding metabolic system can reasonably describe the process of batch culture.

  6. An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields

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    Jack A. Tuszynski

    2016-11-01

    Full Text Available Long-standing research on electric and electromagnetic field interactions with biological cells and their subcellular structures has mainly focused on the low- and high-frequency regimes. Biological effects at intermediate frequencies between 100 and 300 kHz have been recently discovered and applied to cancer cells as a therapeutic modality called Tumor Treating Fields (TTFields. TTFields are clinically applied to disrupt cell division, primarily for the treatment of glioblastoma multiforme (GBM. In this review, we provide an assessment of possible physical interactions between 100 kHz range alternating electric fields and biological cells in general and their nano-scale subcellular structures in particular. This is intended to mechanistically elucidate the observed strong disruptive effects in cancer cells. Computational models of isolated cells subject to TTFields predict that for intermediate frequencies the intracellular electric field strength significantly increases and that peak dielectrophoretic forces develop in dividing cells. These findings are in agreement with in vitro observations of TTFields’ disruptive effects on cellular function. We conclude that the most likely candidates to provide a quantitative explanation of these effects are ionic condensation waves around microtubules as well as dielectrophoretic effects on the dipole moments of microtubules. A less likely possibility is the involvement of actin filaments or ion channels.

  7. Mechanisms of Involvement of Eicosanoids and their Precursors in the Pathophysiology and Treatment of Schizophrenia.

    Science.gov (United States)

    Schmidt, Luise; Ceglarek, Uta; Kortz, Linda; Hoop, Marcus; Kirkby, Kenneth Clifford; Thiery, Joachim; Himmerich, Hubertus

    2013-09-01

    The pathophysiology of schizophrenia has not been fully elucidated but there are converging leads to understanding this complex psychiatric disorder. One family of molecules that may play a crucial role in the development of schizophrenia is the eicosanoids. Review of the literature on eicosanoids in patients with schizophrenia points to findings in three areas: precursor molecules such as polyunsaturated fatty acids (PUFAs) and specifically arachidonic acid (AA), the actions of specific eicosanoids such as thromboxane A2 (TxA2), thromboxane B2 (TxB2) and prostaglandin E2 (PGE2), and enzymes with important functions in eicosanoid metabolism such as cyclooxygenase 2 (COX-2). It has also been found that classical as well as second generation antipsychotics, drugs used to treat schizophrenia, influence eicosanoid metabolism. For example, clozapine and its metabolite N-desmethylclozapine (NDMC) decreased TxB2 production in vitro. Eicosanoids and the enzymes involved in their metabolism may provide novel future drug targets. Therapeutic response to COX-2 inhibitors has already been demonstrated in patients at an early stage of schizophrenia. COX-2 inhibitors may exert this therapeutic action through their effects in reducing PGE2, type-2 cytokine and kynurenic acid production and strengthening glutamatergic neurotransmission.

  8. Mechanisms involved in the anti-inflammatory action of inhaled tea tree oil in mice.

    Science.gov (United States)

    Golab, Mateusz; Skwarlo-Sonta, Krystyna

    2007-03-01

    Tea tree oil (TTO) is well known as an antimicrobial and immunomodulatory agent. In the present study we confirmed the anti-inflammatory properties of TTO and investigated the involvement of the hypothalamic-pituitary-adrenal (HPA) axis in the immunomodulatory action of TTO administered by inhalation. Sexually mature, 6-8-week-old, C(57)BI(10) x CBA/H (F(1)) male mice were used. One group of animals was injected intra-peritoneally (ip) with Zymosan to elicit peritoneal inflammation and was then submitted to four sessions of TTO inhalation (15 mins each). Some of the mice were simultaneously injected ip with Antalarmin, a CRH-1 receptor antagonist, to block HPA axis functions. Twenty-four hours after the injections the mice were killed by CO(2) asphyxia, and peritoneal leukocytes (PTLs) were isolated and counted. Levels of reactive oxygen species (ROS) and cyclooxygenase (COX) activity in PTLs were assessed by fluorimetric and colorimetric assays, respectively. The results obtained show that sessions of TTO inhalation exert a strong anti-inflammatory influence on the immune system stimulated by Zymosan injection, while having no influence on PTL number, ROS level, and COX activity in mice without inflammation. The HPA axis was shown to mediate the anti-inflammatory effect of TTO; Antalarmin abolished the influence of inhaled TTO on PTL number and their ROS production in mice with experimental peritonitis, but it had no effect on these parameters in mice without inflammation.

  9. Molecular Dissection of the Cellular Mechanisms Involved in Nickel Hyperaccumulation in Plants

    Energy Technology Data Exchange (ETDEWEB)

    Salt, David E.

    1999-06-01

    Phytoremediation, the use of plants for environmental cleanup of pollutants, including toxic metals, holds the potential to allow the economic restoration of heavy metal and radionuclide contaminated sites. A number of terrestrial plants are known to naturally accumulate high levels of metals in their shoots (1-2% dry weight), and these plants have been termed metal-hyperaccumulators. Clearly, the genetic traits that determines metal-hyperaccumulation offers the potential for the development of practical phytoremediation processes. Our long-term objective is to rationally design and generate plants ideally suited for phytoremediation using this unique genetic material. Initially, our strategy will focus on isolating and characterizing the key genetic information needed for expression of the metal-hyperaccumulation phenotype. Recently, histidine has been shown to play a major role in Ni hyperaccumulation. Based on this information we propose to investigate, at the molecular level, the role of histidine biosynthesis in Ni hyperaccumulation in Thlaspi goesingense, a Ni hyperaccumulator species. We will clone key genes involved in histidine biosynthesis. We will characterize their transcriptional and post transcriptional regulation by histidine, Ni. We will determine if any of these genes are essential and sufficient for Ni hyperaccumulation by their expression in the non-hyperaccumulator Arabidopsis thaliana.

  10. Clinical--imaging aspects of young permanent teeth traumas and the ethiopatogenic mechanisms involved.

    Science.gov (United States)

    Nemţoi, A; Dănila, I; Lăduncă, Oana; Petcu, Ana; Bamboi, Ana; Haba, Danisia

    2013-01-01

    Dental trauma occurring to children and teenagers all over the world represents a serious issue in Public Health. This present study wants to investigate the etiology and the environment in which the dental trauma occurs and also wants to establish a connection between dental trauma and social-economic status. The study was made to collect information about dental trauma on human subjects involving 372 children and teenagers, both female and male, between 8 and 20 years of age. The data obtained from the clinical and radiological exams for each patient have been registered in a special conceived register, which represented a stage of the study. The frequency of dental trauma varied from 62.1% for males to 37.9% for women. Most of them have suffered from dental trauma between the age of 14 and 16 (30.1%), and a few between 18 and 20 years (2.2%). Dental trauma has occurred most frequently in school, during sports lessons, followed by those in public places like the street (23.1%), from which 17.1% have been associated with bicycle accidents, 3.5% with scooter accidents and 2.5% with car accidents. Children and teenagers who live in areas with a low social economic level have been the fewest to seek medical attention due to difficult access to medical services. Overall, this study wanted to present the importance of knowing the frequency of dental trauma in children and teenagers and to point out the need of promoting medical education to parents regarding the means they can use to reduce the risk factors associated with dental trauma.

  11. A systems toxicology approach to elucidate the mechanisms involved in RDX species-specific sensitivity.

    Science.gov (United States)

    Warner, Christopher M; Gust, Kurt A; Stanley, Jacob K; Habib, Tanwir; Wilbanks, Mitchell S; Garcia-Reyero, Natàlia; Perkins, Edward J

    2012-07-17

    Interspecies uncertainty factors in ecological risk assessment provide conservative estimates of risk where limited or no toxicity data is available. We quantitatively examined the validity of interspecies uncertainty factors by comparing the responses of zebrafish (Danio rerio) and fathead minnow (Pimephales promelas) to the energetic compound 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), a known neurotoxicant. Relative toxicity was measured through transcriptional, morphological, and behavioral end points in zebrafish and fathead minnow fry exposed for 96 h to RDX concentrations ranging from 0.9 to 27.7 mg/L. Spinal deformities and lethality occurred at 1.8 and 3.5 mg/L RDX respectively for fathead minnow and at 13.8 and 27.7 mg/L for zebrafish, indicating that zebrafish have an 8-fold greater tolerance for RDX than fathead minnow fry. The number and magnitude of differentially expressed transcripts increased with increasing RDX concentration for both species. Differentially expressed genes were enriched in functions related to neurological disease, oxidative-stress, acute-phase response, vitamin/mineral metabolism and skeletal/muscular disorders. Decreased expression of collagen-coding transcripts were associated with spinal deformity and likely involved in sensitivity to RDX. Our work provides a mechanistic explanation for species-specific sensitivity to RDX where zebrafish responded at lower concentrations with greater numbers of functions related to RDX tolerance than fathead minnow. While the 10-fold interspecies uncertainty factor does provide a reasonable cross-species estimate of toxicity in the present study, the observation that the responses between ZF and FHM are markedly different does initiate a call for concern regarding establishment of broad ecotoxicological conclusions based on model species such as zebrafish.

  12. Mechanism of cancer drug resistance and the involvement of noncoding RNAs.

    Science.gov (United States)

    Xia, Hongping; Hui, Kam M

    2014-01-01

    Drug resistance is one of the major reasons for the failure of cancer therapies. Although our understanding of resistance to targeted cancer drugs remains incomplete, new and more creative approaches are being exploited to intercept this phenomenon. Considerable advances have been made in our understanding that cancer drug resistance can be caused by alterations of drug efflux, increases in drug metabolism, mutations of drug targets, alterations in DNA repair and cell cycle, changes in cell apoptosis and autophagy, induction of epithelial-mesenchymal transition (EMT) and the generation of cancer stem cells (CSCs). Furthermore, intracellular signalling pathways have been shown to play key physiological roles and the abnormal activation of signalling pathways may be correlated with drug resistance. Recently, noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have emerged as important regulators of gene expression and alternative splicing, which provides cells with yet another mode to greatly increase regulatory complexity and fine-tune their transcriptome and can rapidly adjust their proteome in response to stimuli. Consequently, a wide variety of biological functions have been shown to depend on the coordinated interactions between noncoding RNAs and cellular signalling networks to achieve a concerted desired physiological outcome, whereas mutations and dysregulation of ncRNAs have been linked to diverse human diseases, including cancer drug resistance. In this review, we will discuss recent findings on the multiple molecular roles of regulatory ncRNAs on the signalling pathways involved in cancer drug resistance and the therapeutic potential of reverse drug resistance.

  13. Permeability of membranes to amino acids and modified amino acids: mechanisms involved in translocation

    Science.gov (United States)

    Chakrabarti, A. C.; Deamer, D. W. (Principal Investigator); Miller, S. L. (Principal Investigator)

    1994-01-01

    The amino acid permeability of membranes is of interest because they are one of the key solutes involved in cell function. Membrane permeability coefficients (P) for amino acid classes, including neutral, polar, hydrophobic, and charged species, have been measured and compared using a variety of techniques. Decreasing lipid chain length increased permeability slightly (5-fold), while variations in pH had only minor effects on the permeability coefficients of the amino acids tested in liposomes. Increasing the membrane surface charge increased the permeability of amino acids of the opposite charge, while increasing the cholesterol content decreased membrane permeability. The permeability coefficients for most amino acids tested were surprisingly similar to those previously measured for monovalent cations such as sodium and potassium (approximately 10(-12)-10(-13) cm s-1). This observation suggests that the permeation rates for the neutral, polar and charged amino acids are controlled by bilayer fluctuations and transient defects, rather than partition coefficients and Born energy barriers. Hydrophobic amino acids were 10(2) more permeable than the hydrophilic forms, reflecting their increased partition coefficient values. External pH had dramatic effects on the permeation rates for the modified amino acid lysine methyl ester in response to transmembrane pH gradients. It was established that lysine methyl ester and other modified short peptides permeate rapidly (P = 10(-2) cm s-1) as neutral (deprotonated) molecules. It was also shown that charge distributions dramatically alter permeation rates for modified di-peptides. These results may relate to the movement of peptides through membranes during protein translocation and to the origin of cellular membrane transport on the early Earth.

  14. Auxin-induced growth of Avena coleoptiles involves two mechanisms with different pH optima

    Science.gov (United States)

    Cleland, R. E.

    1992-01-01

    Although rapid auxin-induced growth of coleoptile sections can persist for at least 18 hours, acid-induced growth lasts for a much shorter period of time. Three theories have been proposed to explain this difference in persistence. To distinguish between these theories, the pH dependence for auxin-induced growth of oat (Avena sativa L.) coleoptiles has been determined early and late in the elongation process. Coleoptile sections from which the outer epidermis was removed to facilitate buffer entry were incubated, with or without 10 micromolar indoleacetic acid, in 20 millimolar buffers at pH 4.5 to 7.0 to maintain a fixed wall pH. During the first 1 to 2 hours after addition of auxin, elongation occurs by acid-induced extension (i.e. the pH optimum is <5 and the elongation varies inversely with the solution pH). Auxin causes no additional elongation because the buffers prevent further changes in wall pH. After 60 to 90 minutes, a second mechanism of auxin-induced growth, whose pH optimum is 5.5 to 6.0, predominates. It is proposed that rapid growth responses to changes in auxin concentration are mediated by auxin-induced changes in wall pH, whereas the prolonged, steady-state growth rate is controlled by a second, auxin-mediated process whose pH optimum is less acidic.

  15. Adaptation of grapevine flowers to cold involves different mechanisms depending on stress intensity.

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    Mélodie Sawicki

    Full Text Available Grapevine flower development and fruit set are influenced by cold nights in the vineyard. To investigate the impact of cold stress on carbon metabolism in the inflorescence, we exposed the inflorescences of fruiting cuttings to chilling and freezing temperatures overnight and measured fluctuations in photosynthesis and sugar content. Whatever the temperature, after the stress treatment photosynthesis was modified in the inflorescence, but the nature of the alteration depended on the intensity of the cold stress. At 4°C, photosynthesis in the inflorescence was impaired through non-stomatal limitations, whereas at 0°C it was affected through stomatal limitations. A freezing night (-3°C severely deregulated photosynthesis in the inflorescence, acting primarily on photosystem II. Cold nights also induced accumulation of sugars. Soluble carbohydrates increased in inflorescences exposed to -3°C, 0°C and 4°C, but starch accumulated only in inflorescences of plants treated at 0 and -3°C. These results suggest that inflorescences are able to cope with cold temperatures by adapting their carbohydrate metabolism using mechanisms that are differentially induced according to stress intensity.

  16. Involvement of a joker mutation in a polymerase-independent lethal mutagenesis escape mechanism.

    Science.gov (United States)

    Agudo, Rubén; de la Higuera, Ignacio; Arias, Armando; Grande-Pérez, Ana; Domingo, Esteban

    2016-07-01

    We previously characterized a foot-and-mouth disease virus (FMDV) with three amino acid replacements in its polymerase (3D) that conferred resistance to the mutagenic nucleoside analogue ribavirin. Here we show that passage of this mutant in the presence of high ribavirin concentrations resulted in selection of viruses with the additional replacement I248T in 2C. This 2C substitution alone (even in the absence of replacements in 3D) increased FMDV fitness mainly in the presence of ribavirin, prevented an incorporation bias in favor of A and U associated with ribavirin mutagenesis, and conferred the ATPase activity of 2C decreased sensitivity to ribavirin-triphosphate. Since in previous studies we described that 2C with I248T was selected under different selective pressures, this replacement qualifies as a joker substitution in FMDV evolution. The results have identified a role of 2C in nucleotide incorporation, and have unveiled a new polymerase-independent mechanism of virus escape to lethal mutagenesis.

  17. Auxin-induced growth of Avena coleoptiles involves two mechanisms with different pH optima

    Science.gov (United States)

    Cleland, R. E.

    1992-01-01

    Although rapid auxin-induced growth of coleoptile sections can persist for at least 18 hours, acid-induced growth lasts for a much shorter period of time. Three theories have been proposed to explain this difference in persistence. To distinguish between these theories, the pH dependence for auxin-induced growth of oat (Avena sativa L.) coleoptiles has been determined early and late in the elongation process. Coleoptile sections from which the outer epidermis was removed to facilitate buffer entry were incubated, with or without 10 micromolar indoleacetic acid, in 20 millimolar buffers at pH 4.5 to 7.0 to maintain a fixed wall pH. During the first 1 to 2 hours after addition of auxin, elongation occurs by acid-induced extension (i.e. the pH optimum is Auxin causes no additional elongation because the buffers prevent further changes in wall pH. After 60 to 90 minutes, a second mechanism of auxin-induced growth, whose pH optimum is 5.5 to 6.0, predominates. It is proposed that rapid growth responses to changes in auxin concentration are mediated by auxin-induced changes in wall pH, whereas the prolonged, steady-state growth rate is controlled by a second, auxin-mediated process whose pH optimum is less acidic.

  18. A POTENTIAL MECHANISM OF BREAKTHROUGH BLEEDING ASSOCIATED WITH PROGESTIN: INVOLVEMENT IN ALTERATION OF ENDOMETRIAL ENDOTHELIAL CELLS

    Institute of Scientific and Technical Information of China (English)

    Gui-hua Sha; Shou-qing Lin

    2008-01-01

    Objective To explore the potential mechanism of breakthrough bleeding associated with progestin with in vitro methods.Methods The isolation and culture of human endometrial endothelial cells (HEECs) was performed with themethod established in our laboratory. The content and activity of urokinase-type plasminogen activator (uPA) and the content of plasminogen activator inhibitor-1 ( PAI-1 ) in cell supernatants after incubated with different concentrations of progesterone (0-5 μmol/L) and 17β-estradiol (0, 0.1, or 1 nmol/L) were measured by method of ELISA. Apoptosis rate of HEECs was measured by flow eytometry. Viable cell count was measured by MTr.Results The increased level of progesterone (0.5-5 μmol/L) combined with 17β-estmdiol elevated content and activity of uPA while the production of PAI-1 remained unchanged. The apoptosis of HEECs was inhibited along with the increment of total viable cell counts at higher ooneenwations of progesterone with 17β-estradiol.Conclusion The inhibition of apoptosis and increased content and activity of uPA may contribute to the occurrence of irregular bleeding associated with progestin use to some extent.

  19. Kindling-induced learning deficiency and possible cellular and molecular involved mechanisms.

    Science.gov (United States)

    Sherafat, Mohammad Amin; Ronaghi, Abdolaziz; Ahmad-Molaei, Leila; Nejadhoseynian, Mohammad; Ghasemi, Rasoul; Hosseini, Arman; Naderi, Nima; Motamedi, Fereshteh

    2013-06-01

    Hippocampus learning disturbance is a major symptom of patients with seizure, hence hippocampal dysfunction has essential role in worsening the disease. Hippocampal formation includes neurons and myelinated fibers that are necessary for acquisition and consolidation of memory, long-term potentiation and learning activity. The exact mechanism by which seizure can decrease memory and learning activity of hippocampus remains unknown. In the present study, electrical kindling-induced learning deficit in rats was evaluated by Morris water maze (MWM) test. The hippocampus was removed and changes in neurons and myelin sheaths around hippocampal fibers were investigated using histological and immunohistochemical methods. Demyelination was assessed by luxol fast blue staining, and immunohistological staining of myelin-binding protein (MBP). The TUNEL assay was used for evaluation of neuronal apoptosis and the glial fibriliary acetic protein (GFAP) was used for assessment of inflammatory reaction. The results indicated that electrical kindling of hippocampus could induce deficiency in spatial learning and memory as compared to control group. In addition, electrical kindling caused damage to the myelin sheath around hippocampal fibers and produced vast demyelination. Furthermore, an increase in the number of apoptotic cells in hippocampal slices was observed. In addition, inflammatory response was higher in kindled animals as compared to the control group. The results suggested that the decrease in learning and memory in kindled animals is likely due to demyelination and augmentation in apoptosis rate accompanied by inflammatory reaction in hippocampal neurons of kindled rats.

  20. Paracrine mechanisms involved in the control of early stages of mammalian spermatogenesis

    Directory of Open Access Journals (Sweden)

    Pellegrino eRossi

    2013-11-01

    Full Text Available Within the testis, Sertoli cell is the primary target of pituitary FSH. Several growth factors have been described to be produced specifically by Sertoli cells and modulate male germ cell development through paracrine mechanisms. Some have been shown to act directly on spermatogonia such as GDNF, which acts on self-renewal of spermatogonial stem cells (SSCs while inhibiting their differentiation; BMP4, which has both a proliferative and differentiative effect on these cells, and KL, which stimulates the KIT tyrosine-kinase receptor expressed by differentiating spermatogonia (but not by SSCs. KL not only controls the proliferative cycles of KIT positive spermatogonia, but it also stimulates the expression of genes that are specific of the early phases of meiosis, whereas the expression of typical spermatogonial markers is down-regulated. On the contrary, FGF9 acts as a meiotic inhibiting substance both in fetal gonocytes and in post-natal spermatogonia through the induction of the RNA-binding protein NANOS2. Vitamin A, which is metabolized to Retinoic Acid in Sertoli cells, controls both SSCs differentiation through KIT induction and NANOS2 inhibition, and meiotic entry of differentiating spermatogonia through STRA8 upregulation.

  1. Endocannabinoids are involved in male vertebrate reproduction: regulatory mechanisms at central and gonadal level

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    Patrizia eBovolin

    2014-04-01

    Full Text Available Endocannabinoids are natural lipids regulating a large array of physiological functions and behaviors in vertebrates. The endocannabinoid system is highly conserved in evolution and comprises several specific receptors (type-1 and type-2 cannabinoid receptors, their endogenous ligands (e.g. anandamide and 2-arachidonoylglycerol, and a number of biosynthetic and degradative enzymes. In the last few years, endocannabinoids have been described as critical signals in the control of male and female reproduction at multiple levels: centrally, by targeting hypothalamic Gonadotropin-Releasing-Hormone secreting neurons and pituitary, and locally, with direct effects on the gonads. These functions are supported by the extensive localization of cannabinoid receptors and endocannabinoid metabolic enzymes at different levels of the hypothalamic-pituitary-gonadal axis in mammals, as well as bonyfish and amphibians. In vivo and in vitro studies indicate that endocannabinoids centrally regulate gonadal functions by modulating the Gonadotropin Releasing Hormone-gonadotropin-steroid network through direct and indirect mechanisms. Several proofs of local endocannabinoid regulation have been found in the testis and male genital tracts, since endocannabinoids control Sertoli and Leydig cells activity, germ cell progression, as well as the acquisition of sperm functions. A comparative approach usually is a key step in the study of physiological events leading to the building of a general model. Thus, in this review we summarize the action of endocannabinoids at different levels of the male reproductive axis, with special emphasis, where appropriate, on data from non-mammalian vertebrates.

  2. Effects of nitric oxide on magnocellular neurons of the supraoptic nucleus involve multiple mechanisms

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    M.P. da Silva

    2014-02-01

    Full Text Available Physiological evidence indicates that the supraoptic nucleus (SON is an important region for integrating information related to homeostasis of body fluids. Located bilaterally to the optic chiasm, this nucleus is composed of magnocellular neurosecretory cells (MNCs responsible for the synthesis and release of vasopressin and oxytocin to the neurohypophysis. At the cellular level, the control of vasopressin and oxytocin release is directly linked to the firing frequency of MNCs. In general, we can say that the excitability of these cells can be controlled via two distinct mechanisms: 1 the intrinsic membrane properties of the MNCs themselves and 2 synaptic input from circumventricular organs that contain osmosensitive neurons. It has also been demonstrated that MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the study of their intrinsic membrane properties became imperative to explain the osmosensitivity of MNCs. In addition to this, the discovery that several neurotransmitters and neuropeptides can modulate their electrical activity greatly increased our knowledge about the role played by the MNCs in fluid homeostasis. In particular, nitric oxide (NO may be an important player in fluid balance homeostasis, because it has been demonstrated that the enzyme responsible for its production has an increased activity following a hypertonic stimulation of the system. At the cellular level, NO has been shown to change the electrical excitability of MNCs. Therefore, in this review, we focus on some important points concerning nitrergic modulation of the neuroendocrine system, particularly the effects of NO on the SON.

  3. Effects of nitric oxide on magnocellular neurons of the supraoptic nucleus involve multiple mechanisms.

    Science.gov (United States)

    Silva, M P da; Cedraz-Mercez, P L; Varanda, W A

    2014-02-01

    Physiological evidence indicates that the supraoptic nucleus (SON) is an important region for integrating information related to homeostasis of body fluids. Located bilaterally to the optic chiasm, this nucleus is composed of magnocellular neurosecretory cells (MNCs) responsible for the synthesis and release of vasopressin and oxytocin to the neurohypophysis. At the cellular level, the control of vasopressin and oxytocin release is directly linked to the firing frequency of MNCs. In general, we can say that the excitability of these cells can be controlled via two distinct mechanisms: 1) the intrinsic membrane properties of the MNCs themselves and 2) synaptic input from circumventricular organs that contain osmosensitive neurons. It has also been demonstrated that MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the study of their intrinsic membrane properties became imperative to explain the osmosensitivity of MNCs. In addition to this, the discovery that several neurotransmitters and neuropeptides can modulate their electrical activity greatly increased our knowledge about the role played by the MNCs in fluid homeostasis. In particular, nitric oxide (NO) may be an important player in fluid balance homeostasis, because it has been demonstrated that the enzyme responsible for its production has an increased activity following a hypertonic stimulation of the system. At the cellular level, NO has been shown to change the electrical excitability of MNCs. Therefore, in this review, we focus on some important points concerning nitrergic modulation of the neuroendocrine system, particularly the effects of NO on the SON.

  4. Functional dyspepsia: Are psychosocial factors of relevance?

    Institute of Scientific and Technical Information of China (English)

    Sandra Barry; Timothy G Dinan

    2006-01-01

    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.

  5. Study of catalase adsorption on two mixed-mode ligands and the mechanism involved therein.

    Science.gov (United States)

    Shiva Ranjini, S; Vijayalakshmi, M A

    2012-11-01

    Mixed-mode chromatography sorbents n-hexylamine HyperCel™ (HEA) and phenylpropylamine HyperCel™ (PPA) were evaluated for the study of adsorption of catalase from two different sources. Various parameters such as buffer composition, ionic strength and pH were investigated to study the mechanism of interaction of commercially available pre-purified catalase from Bovine liver, purified catalase from black gram (Vigna mungo) and crude extract of black gram containing catalase with these mixed-mode ligands. A simple and economical screening protocol for identifying optimal buffer conditions for adsorption and desorption of catalase was established with micro volumes of the sorbent in batch mode. With HEA HyperCel, it was observed that pre-purified catalase from both bovine liver and black gram was completely retained at pH 7.0, irrespective of the presence or absence of NaCl in the adsorption buffer, whereas the catalase from crude extract of black gram was completely retained only in the presence of 0.2 M salt in the adsorption buffer. The elution of catalase from both the sources was accomplished by lowering the pH to 4.5 in absence of salt. In case of PPA HyperCel, catalase from both the sources was very strongly adsorbed under different buffer conditions studied, and elution did not yield a significant catalase activity. From the screening experiments, it could be concluded that the interaction of catalase with HEA HyperCel could be dominated by hydrophobic forces with minor contributions from ionic interaction and with PPA HyperCel, it could be a combination of different non-covalent interactions acting on different loci on the surface of the protein.

  6. Obesity Weighs down Memory through a Mechanism Involving the Neuroepigenetic Dysregulation of Sirt1.

    Science.gov (United States)

    Heyward, Frankie D; Gilliam, Daniel; Coleman, Mark A; Gavin, Cristin F; Wang, Jing; Kaas, Garrett; Trieu, Richard; Lewis, John; Moulden, Jerome; Sweatt, J David

    2016-01-27

    Aberrant gene expression within the hippocampus has recently been implicated in the pathogenesis of obesity-induced memory impairment. Whether a dysregulation of epigenetic modifications mediates this disruption in gene transcription has yet to be established. Here we report evidence of obesity-induced alterations in DNA methylation of memory-associated genes, including Sirtuin 1 (Sirt1), within the hippocampus, and thus offer a novel mechanism by which SIRT1 expression within the hippocampus is suppressed during obesity. Forebrain neuron-specific Sirt1 knock-out closely recapitulated the memory deficits exhibited by obese mice, consistent with the hypothesis that the high-fat diet-mediated reduction of hippocampal SIRT1 could be responsible for obesity-linked memory impairment. Obese mice fed a diet supplemented with the SIRT1-activating molecule resveratrol exhibited increased hippocampal SIRT1 activity and preserved hippocampus-dependent memory, further strengthening this conclusion. Thus, our findings suggest that the memory-impairing effects of diet-induced obesity may potentially be mediated by neuroepigenetic dysregulation of SIRT1 within the hippocampus. Previous studies have implicated transcriptional dysregulation within the hippocampus as being a relevant pathological concomitant of obesity-induced memory impairment, yet a deeper understanding of the basis for, and etiological significance of, transcriptional dysregulation in this context is lacking. Here we present the first evidence of epigenetic dysregulation (i.e., altered DNA methylation and hydroxymethylation) of memory-related genes, including Sirt1, within the hippocampus of obese mice. Furthermore, experiments using transgenic and pharmacological approaches strongly implicate reduced hippocampal SIRT1 as being a principal pathogenic mediator of obesity-induced memory impairment. This paper offers a novel working model that may serve as a conceptual basis for the development of therapeutic

  7. Mechanisms involved in the association between periodontitis and complications in pregnancy.

    Directory of Open Access Journals (Sweden)

    Marcela eYang

    2015-01-01

    Full Text Available The association between periodontitis and gestation complications such as premature delivery, low weight at birth and preeclampsia has been suggested. Nevertheless, epidemiological data have shown contradictory data, mainly due to differences in clinical parameters of periodontitis assessment. Furthermore, differences in microbial composition and immune response between aggressive and chronic periodontitis are not addressed by these epidemiological studies. We aimed to review the current data on the association between gestation complications and periodontitis, and the mechanisms underlying this association. Shifts in the microbial composition of the subgingival biofilm may occur during pregnancy, leading to a potentially more hazardous microbial community. Pregnancy is characterized by physiological immune tolerance. However, the infection leads to a shift in maternal immune response to a pathogenic pro-inflammatory response, with production of inflammatory cytokines and toxic products. In women with periodontitis, the infected periodontal tissues may act as reservoirs of bacteria and their products which can disseminate to the fetus-placenta unit. In severe periodontitis patients, the infection agents and their products are able to activate inflammatory signaling pathways locally and in extra-oral sites, including the placenta-fetal unit, which may not only induce preterm labor, but also lead to preeclampsia and restrict intrauterine growth. Despite these evidences, the effectiveness of periodontal treatment in preventing gestational complications was still not established since it may be influenced by several factors such as severity of disease, composition of microbial community, treatment strategy, and period of treatment throughout pregnancy. This lack of scientific evidence does not exclude the need to control infection and inflammation in periodontitis patients during pregnancy, and treatment protocols should be validated.

  8. Mechanisms Involved in the Association between Periodontitis and Complications in Pregnancy

    Science.gov (United States)

    Zi, Marcela Yang Hui; Longo, Priscila Larcher; Bueno-Silva, Bruno; Mayer, Marcia Pinto Alves

    2015-01-01

    The association between periodontitis and some of the problems with pregnancy such as premature delivery, low weight at birth, and preeclampsia (PE) has been suggested. Nevertheless, epidemiological data have shown contradictory data, mainly due to differences in clinical parameters of periodontitis assessment. Furthermore, differences in microbial composition and immune response between aggressive and chronic periodontitis are not addressed by these epidemiological studies. We aimed to review the current data on the association between some of these problems with pregnancy and periodontitis, and the mechanisms underlying this association. Shifts in the microbial composition of the subgingival biofilm may occur during pregnancy, leading to a potentially more hazardous microbial community. Pregnancy is characterized by physiological immune tolerance. However, the infection leads to a shift in maternal immune response to a pathogenic pro-inflammatory response, with production of inflammatory cytokines and toxic products. In women with periodontitis, the infected periodontal tissues may act as reservoirs of bacteria and their products that can disseminate to the fetus-placenta unit. In severe periodontitis patients, the infection agents and their products are able to activate inflammatory signaling pathways locally and in extra-oral sites, including the placenta-fetal unit, which may not only induce preterm labor but also lead to PE and restrict intrauterine growth. Despite these evidences, the effectiveness of periodontal treatment in preventing gestational complications was still not established since it may be influenced by several factors such as severity of disease, composition of microbial community, treatment strategy, and period of treatment throughout pregnancy. This lack of scientific evidence does not exclude the need to control infection and inflammation in periodontitis patients during pregnancy, and treatment protocols should be validated. PMID:25688342

  9. Nephropathy and hepatopathy in weaned piglets provoked by natural ochratoxin A and involved mechanisms.

    Science.gov (United States)

    Zhang, Zheqian; Gan, Fang; Xue, Hongxia; Liu, Yunhuan; Huang, Da; Khan, Alam Zeb; Chen, Xingxiang; Huang, Kehe

    2016-04-01

    Ochratoxin A (OTA) contamination is a worldwide problem in pig industry. The objectives of the present study were to investigate the toxicity of natural OTA in weaned piglets and to further explore the underlying mechanisms. Totally, 36 crossbred ([Landrace × Yorkshire] × Duroc) piglets were randomly divided into 3 groups (three replicates per group, 4 piglets per replicate), and fed a basal diet (Con group) and basal diets added with 0.4 mg (OTA-L group) or 0.8 mg OTA/kg (OTA-H group), respectively for 42 days. The results showed that growth performance was significantly decreased (P<0.05) in OTA added groups compared with Con group. OTA concentration was relatively high in serum and OTA concentration in kidney was higher than in liver, respectively. AST, creatinine and urea in serum of OTA added groups were significantly increased (P<0.05), while glucose, total protein, albumin and globulin in serum of OTA added groups were significantly decreased (P<0.05) compared with Con group. Degenerative changes were observed in the epithelial cells of proximal tubules and in hepatocytes of OTA added groups. Antioxidant capacities in blood of OTA added groups and in kidney of OTA-H group were significantly decreased (P<0.05) compared with Con group. The mRNA expressions of bcl-2 were up-regulated, mRNA expressions of bax were down-regulated and the ratio of bcl-2 and bax was increased in kidney and liver of OTA added groups compared with Con group. In conclusion, OTA could reduce antioxidant capacity and suppress apoptosis in tissues and cause degenerative changes in the epithelial cells in proximal tubules and hepatic cells, which may have a negative effect on the growth performance of piglets.

  10. Mechanisms Involved in Thromboxane A2 -induced Vasoconstriction of Rat Intracavernous Small Penile Arteries.

    Science.gov (United States)

    Grann, Martin; Comerma-Steffensen, Simon; Arcanjo, Daniel D R; Simonsen, Ulf

    2016-10-01

    Diabetes is associated with erectile dysfunction and with hypercontractility in erectile tissue and this is in part ascribed to increased formation of thromboxane. Rho kinase (ROCK) is a key regulator of calcium sensitization and contraction in vascular smooth muscle. This study investigated the role of calcium and ROCK in contraction evoked by activation of the thromboxane receptors. Rat intracavernous penile arteries were mounted for isometric tension and intracellular calcium ([Ca(2+) ]i ) recording and corpus cavernosum for measurements of MYPT1 phosphorylation. In penile arteries, U46619 by activation of thromboxane receptors concentration dependently increased calcium and contraction. U46619-induced calcium influx was blocked by nifedipine, a blocker of L-type calcium channels, and by 2-aminoethoxydiphenyl borate, a blocker of transient receptor potential (TRP) channels. Inhibitors of ROCK, Y27632 and glycyl-H1152P, concentration dependently reduced U46619-induced contraction, but only Y27632 reduced [Ca(2+) ]i levels in the penile arteries activated with either high extracellular potassium or U46619. MYPT-Thr(850) phosphorylation in corpus cavernous strips was increased in response to U46619 through activation of TP receptors and was found to be a direct result of phosphorylation by ROCK. Y27632 induced less relaxation in mesenteric arteries, H1152P induced equipotent relaxations, and a protein kinase C inhibitor, Ro-318220, failed to relax intracavernous penile arteries, but induced full relaxation in rat mesenteric arteries. Our findings suggest that U46619 contraction depends on Ca(2+) influx through L-type and TRP channels, and ROCK-dependent mechanisms in penile arteries. Inhibition of the ROCK pathway is a potential approach for the treatment of erectile dysfunction associated with hypertension and diabetes.

  11. The mechanism involved in the loss of PTEN expression in NSCLC tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Gang; Zhao, Jingfeng; Peng, Xianjing [Department of Radiology, Xiangya Hospital, Central South University, Changsha 410008 (China); Liang, Jian; Deng, Xin [Ruikang Hospital, Guangxi University of Traditional Chinese Medicine, Nanning 530003 (China); Chen, Yuxiang, E-mail: chenyx008@yahoo.cn [Department of Radiology, Xiangya Hospital, Central South University, Changsha 410008 (China); School of Biological Science and Technology, Central South University, Changsha 410008 (China)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer Radiation stimulates PTEN reexpression in NSCLC independent of p53 activation. Black-Right-Pointing-Pointer PTEN reexpression is mediated by miR-29b overexpression. Black-Right-Pointing-Pointer miR-29b regulates Dnmts expression in NSCLC tumor cells. Black-Right-Pointing-Pointer Target therapy could be established by overexpressing miR-29b expression. -- Abstract: Loss of PTEN expression is observed in most non-small cell lung cancers (NSCLC). However, the mechanism by which PTEN expression is regulated in NSCLC has not been fully elucidated. In this study, we investigated the role of DNA methyltransferases (Dnmts), microRNA-29b (miR-29b), and anti-miR-29b inhibitor in PTEN promoter methylation and PTEN gene expression in H358 NSCLC cells in vitro and in vivo. PTEN mRNA was measured by RT-PCR. PTEN and Dnmts protein levels were measured by Western blot. miR-29b expression was detected by Northern blot. A xenograft H358 tumor mouse model was established by subcutaneously inoculating H358 cells into the right hind limbs of nude mice. We found that radiation induced cell apoptosis and hypomethylation in PTEN promoter, PTEN and miR-29b expression, and downregulation of Dnmt1, 3a and 3b expression in H358 tumor cells. The effect of radiation on gene expression and apoptosis was blocked by anti-miR-29b inhibitor. In the xenograft H358 tumor model, anti-miR-29b inhibitor reversed radiation-induced tumor growth delay, PTEN reexpression and downregulation of Dnmts expression. Our study suggested that miR-29b is an upstream molecule of PTEN. miR-29b regulates PTEN gene expression through downregulating Dnmts expression and subsequently induces hypomethylation in PTEN promoter. Targeting therapy could be established in NSCLC by upregulating miR-29b expression.

  12. The Vulnerability of Vessels Involved in the Role of Embolism and Hypoperfusion in the Mechanisms of Ischemic Cerebrovascular Diseases

    Directory of Open Access Journals (Sweden)

    Yong Peng Yu

    2016-01-01

    Full Text Available Accurate definition and better understanding of the mechanisms of stroke are crucial as this will guide the effective care and therapy. In this paper, we review the previous basic and clinical researches on the causes or mechanisms of ischemic cerebrovascular diseases (ICVD and interpret the correlation between embolism and hypoperfusion based on vascular stenosis and arterial intimal lesions. It was suggested that if there is no embolus (dynamic or in situ emboli, there might be no cerebral infarction. Three kinds of different clinical outcomes of TIA were theoretically interpreted based on its mechanisms. We suppose that there is a correlation between embolism and hypoperfusion, and which mechanisms (hypoperfusion or hypoperfusion induced microemboli playing the dominant role in each type of ICVD depends on the unique background of arterial intimal lesions (the vulnerability of vessels. That is to say, the vulnerability of vessels is involved in the role of embolism and hypoperfusion in the mechanisms of ischemic cerebrovascular diseases. This inference might enrich and provide better understandings for the underlying etiologies of ischemic cerebrovascular events.

  13. Cell phones: the psychosocial risks.

    Science.gov (United States)

    Sansone, Randy A; Sansone, Lori A

    2013-01-01

    Cell phones are a relatively novel and evolving technology. While the potential benefits of this technology continue to emerge, so do the potential psychosocial risks. For example, one psychosocial risk is user stress, which appears to be related to feeling compelled to promptly respond to cell-phone activity in order to maintain spontaneity and access with others. Other potential psychosocial risks include disruptions in sleep; the user's risk of exposure to cyberbullying, particularly the unwanted exposure of photographs and/or videos of the victim; and overuse, particularly among adolescents. With regard to the latter phenomenon, the boundaries among overuse, misuse, dependence, and addiction are not scientifically clear. Therefore, while cell phones are a convenient and expedient technology, they are not without their potential psychosocial hazards.

  14. 涉诉信访终结机制研究%Research on Mechanism of Settling Petition Involving Lawsuit

    Institute of Scientific and Technical Information of China (English)

    宋春龙; 徐琦

    2012-01-01

    Mechanism of settling petition involving lawsuit is an important part to the system of solving of China. Due to problems in the practice, it's necessary to establish a complete system of As the first step on the ladder to the system of petition involving lawsuit, the mechanism of settling dispute re- this field. petition in- volving lawsuit needs to be systematized based on theories. Courts of each level have come up with different petition settling mechanisms, which can be served as practical support to the integration and improvement of this system.%涉诉信访制度是我国多元化解纷机制的重要组成部分,由于在实践中所存在的问题,有必要对其进行完整的制度构建。涉诉信访的终结机制作为打开涉诉信访制度的突破口,亟须系统化、理论化的构建。各级法院在实践中也总结出了不同的终结机制,为整个制度的整合与完整提供了实践支持。

  15. Psychosocial stress among Danish vicars

    DEFF Research Database (Denmark)

    Gyntelberg, F; Hein, H O; Suadicani, P

    2012-01-01

    Burnout and depression are common among clergy members of several religions and denominations. Despite this, no studies have analysed whether differences in psychosocial workloads between vicars and others explain their higher prevalence of stress-related symptoms.......Burnout and depression are common among clergy members of several religions and denominations. Despite this, no studies have analysed whether differences in psychosocial workloads between vicars and others explain their higher prevalence of stress-related symptoms....

  16. Automatic polarographic elucidation of electrode mechanisms by means of a knowledge-based system, part 3: Mechanisms ECE, EE and mechanisms involving adsorption

    NARCIS (Netherlands)

    Palys, M.J.; Palys, M.J.; Bos, M.; van der Linden, W.E.

    1993-01-01

    The previously described expert system has been extended: rules allowing the elucidation of a larger number of mechanisms have been added and automatic control of additional experimental parameters such as concentration and composition of the solution in the cell and the electrode size has been made

  17. Neuroplasticity, Psychosocial Genomics, and the Biopsychosocial Paradigm in the 21st Century

    Science.gov (United States)

    Garland, Eric L.; Howard, Matthew Owen

    2009-01-01

    The biopsychosocial perspective is a foundation of social work theory and practice. Recent research on neuroplasticity and psychosocial genomics lends compelling support to this perspective by elucidating mechanisms through which psychosocial forces shape neurobiology. Investigations of neuroplasticity demonstrate that the adult brain can continue…

  18. MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation

    DEFF Research Database (Denmark)

    Leucci, E; Cocco, M; Onnis, A

    2008-01-01

    at the standardization of FISH procedures in lymphoma diagnosis, we found that five cases out of 35 classic endemic BLs were negative for MYC translocations by using a split-signal as well as a dual-fusion probe. Here we investigated the expression pattern of miRNAs predicted to target c-Myc, in BL cases, to clarify...... whether alternative pathogenetic mechanisms may be responsible for lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of small RNAs that are able to regulate gene expression at the post-transcriptional level. Several studies have reported their involvement in cancer...

  19. [Psychosocial aspects of halitosis].

    Science.gov (United States)

    de Jongh, A; de Baat, C; Horstman, M

    2012-09-01

    Using a representative sample from the Dutch population, some psychosocial aspects of halitosis were examined. The results of the survey showed that almost 90% of the Dutch population aged 16 years and older were regularly faced with halitosis. Forty percent reported to be exposed to someone with halitosis at least once a week, men significantly more frequently than women. Although less strongly than body odour, halitosis was reported as being one of the most severe 'let-downs' in social interactions. The greater the social distance between subjects, the less likely is the chance that a person's attention will be drawn to halitosis experienced. When it comes to an unknown person, the chance was no more than 7%, suggesting that it is problematic to draw a person's attention to the presence of halitosis. Considering the potential social consequences of halitosis is it important that dentists and dental hygienists draw patients' attention to the presence of halitosis, when this is the case, thereby encouraging them to seek adequate treatment.

  20. Prevalence and correlates for psychosocial distress among in-school adolescents in Zambia

    Directory of Open Access Journals (Sweden)

    Seter eSiziya

    2015-07-01

    Full Text Available There is scanty information on correlates for psychosocial distress in Zambia. Secondary analysis was conducted using data collected in 2004 in Zambia during the global school-based health survey to determine the prevalence and correlates for psychosocial distress. Logistic regression analyses were used to estimate magnitudes of associations between exposure factors and the outcome, while the Yates’ corrected Chi-squared test was used to compare proportions at the 5% significance level. A total of 2257 students participated in the survey of which 54.2% were males. Males were generally older than females (p<0.001. Significantly more females than males were bullied (p=0.036, involved in a fight (p=0.019 and consumed alcohol (p=0.012. Psychosocial distress was detected in 15.7% of the participants (14.4% of males and 16.8% of females. Age less than 14 years, male gender, parental support for males and having close friends were protective factors against psychosocial distress. Risk factors for psychosocial distress were: being bullied, involvement in a fight, alcohol consumption, being physically active and parental support. . Age less than 14 years, male gender, parental support for males, having close friends, being bullied, involvement in a fight, alcohol consumption, being physically active and parental support were significantly associated with psychosocial distress. The prevalence of psychosocial distress among adolescents in Zambia appears to be common. There is a need to validate the psychosocial distress indicators that were used in the current study.

  1. Visual loss in HIV-associated cryptococcal meningitis: A case series and review of the mechanisms involved

    Directory of Open Access Journals (Sweden)

    Anand Moodley

    2015-04-01

    Full Text Available Permanent visual loss is a devastating yet preventable complication of cryptococcal meningitis. Early and aggressive management of cerebrospinal fluid pressure in conjunction with antifungal therapy is required. Historically, the mechanisms of visual loss in cryptococcal meningitis have included optic neuritis and papilloedema. Hence, the basis of visual loss therapy has been steroid therapy and intracranial pressure lowering without clear guidelines. With the use of high-resolution magnetic resonance imaging of the optic nerve, an additional mechanism has emerged, namely an optic nerve sheath compartment syndrome (ONSCS caused by severely elevated intracranial pressure and fungal loading in the peri-optic space. An improved understanding of these mechanisms and recognition of the important role played by raised intracranial pressure allows for more targeted treatment measures and better outcomes. In the present case series of 90 HIV co-infected patients with cryptococcal meningitis, we present the clinical and electrophysiological manifestations of Cryptococcus-induced visual loss and review the mechanisms involved.

  2. Arbuscular Mycorrhizal Fungi for the Biocontrol of Plant-Parasitic Nematodes: A Review of the Mechanisms Involved.

    Science.gov (United States)

    Schouteden, Nele; De Waele, Dirk; Panis, Bart; Vos, Christine M

    2015-01-01

    Arbuscular mycorrhizal fungi (AMF) are obligate root symbionts that can protect their host plant against biotic stress factors such as plant-parasitic nematode (PPN) infection. PPN consist of a wide range of species with different life styles that can cause major damage in many important crops worldwide. Various mechanisms have been proposed to play a role in the biocontrol effect of AMF against PPN. This review presents an overview of the different mechanisms that have been proposed, and discusses into more detail the plausibility of their involvement in the biocontrol against PPN specifically. The proposed mechanisms include enhanced plant tolerance, direct competition for nutrients and space, induced systemic resistance (ISR) and altered rhizosphere interactions. Recent studies have emphasized the importance of ISR in biocontrol and are increasingly placing rhizosphere effects on the foreground as well, both of which will be the focal point of this review. Though AMF are not yet widely used in conventional agriculture, recent data help to develop a better insight into the modes of action, which will eventually lead toward future field applications of AMF against PPN. The scientific community has entered an exciting era that provides the tools to actually unravel the underlying molecular mechanisms, making this a timely opportunity for a review of our current knowledge and the challenges ahead.

  3. Psychosocial Factors Predicting First-Year College Student Success

    Science.gov (United States)

    Krumrei-Mancuso, Elizabeth J.; Newton, Fred B.; Kim, Eunhee; Wilcox, Dan

    2013-01-01

    This study made use of a model of college success that involves students achieving academic goals and life satisfaction. Hierarchical regressions examined the role of six psychosocial factors for college success among 579 first-year college students. Academic self-efficacy and organization and attention to study were predictive of first semester…

  4. Psychosocial Intimacy and Identity: From Early Adolescence to Emerging Adulthood

    Science.gov (United States)

    Montgomery, Marilyn J.

    2005-01-01

    Age and gender differences in patterns of behavior and experience, cognitive beliefs, affective involvement, and psychosocial functioning in romantic relationships were observed in 473 adolescents and emerging adults (ages 12-24). Older adolescents indicated more dating experiences, times in love, passion, identity, and intimacy. They also…

  5. Efficacy of Psychosocial Treatments for Geriatric Depression: A Quantitative Review.

    Science.gov (United States)

    Scogin, Forrest; McElreath, Lisa

    1994-01-01

    Conducted meta-analysis of 17 studies examining efficacy of psychosocial treatments for depression among older adults. Treatments were reliably more effective than no-treatment on self-rated and clinician-rated measures of depression. Effect sizes for studies involving participants with major depression disorder were reliably different from zero,…

  6. Enhancement of non-heme iron absorption by anchovy (Engraulis japonicus) muscle protein hydrolysate involves a nanoparticle-mediated mechanism.

    Science.gov (United States)

    Wu, Haohao; Zhu, Suqin; Zeng, Mingyong; Liu, Zunying; Dong, Shiyuan; Zhao, Yuanhui; Huang, Hai; Lo, Y Martin

    2014-08-27

    The mechanisms by which meat enhances human absorption of non-heme iron remain unknown. Recently, anchovy (Engraulis japonicus) muscle protein hydrolysate (AMPH) was found to mediate the formation of nanosized ferric hydrolysis products in vitro. The current paper evaluates the effects of AMPH on the bioavailability and the intestinal speciation of non-heme iron in rats, followed by an investigation of cellular uptake pathways of in vitro-formed AMPH-stabilized nanosized ferric hydrolysis products (ANPs) by polarized human intestinal epithelial (Caco-2) cells. The hemoglobin regeneration efficiencies in anemic rats followed the order ferric citrate (9.79 ± 2.02%) iron in the groups of FC+AMPH, FeSO4, and ANPs were significantly lower than the corresponding hemoglobin regeneration efficiencies (P iron in intestinal iron absorption from FC+AMPH, FeSO4, and ANPs. Calcein-fluorescence measurements of the labile iron pool of polarized Caco-2 cells revealed the involvement of both divalent transporter 1 and endocytosis in apical uptake of ANPs, with endocytosis dominating at acidic extracellular pH. Overall, AMPH enhancement of non-heme iron absorption involves a nanoparticle-mediated mechanism.

  7. The effect of nutrition on the neural mechanisms potentially involved in melatonin-stimulated LH secretion in female Mediterranean goats.

    Science.gov (United States)

    Zarazaga, Luis A; Celi, Irma; Guzmán, José Luis; Malpaux, Benoît

    2011-12-01

    This research examines which neural mechanisms among the endogenous opioid, dopaminergic, serotonergic and excitatory amino acid systems are involved in the stimulation of LH secretion by melatonin implantation and their modulation by nutritional level. Female goats were distributed to two experimental groups that received either 1.1 (group H; n=24) or 0.7 (group L; n=24) times their nutritional maintenance requirements. Half of each group was implanted with melatonin after a long-day period. Plasma LH concentrations were measured twice per week. The effects of i.v. injections of naloxone, pimozide, cyproheptadine and N-methyl-d,l-aspartate (NMDA) on LH secretion were assessed the day before melatonin implantation and again on days 30 and 45. The functioning of all but the dopaminergic systems was clearly modified by the level of nutrition, melatonin implantation and time elapsed since implantation. Thirty days after implantation, naloxone increased LH concentrations irrespective of the level of nutrition (Pgoats (HM; Pnutritional level and melatonin implantation. Endogenous opioids seem to be most strongly involved in the inhibition of LH secretion on days 30 and 45 after melatonin implantation. However, the serotonergic mechanism appears to be most influenced by nutritional level.

  8. [Psychosocial factors in duodenal ulcer].

    Science.gov (United States)

    de la Gándara Martín, J J; de Dios Francos, A; de Diego Herrero, E; Goñi Labat, A I; Hernández Herrero, H; Pozo de Castro, J V

    1994-01-01

    "Burn-out" is a kind of assistential laboral stress which affects the professions which involve an interpersonal relationship with beneficiaries of the job, such us health workers. It originates emotional alterations which lead to feelings of emptiness and personal failure or laboral inability. The revisions about studies of mental disorders in health workers fall upon such laboral stress and remark that in such professional people there is a bigger prevalence of disorders because of the use of substances and of depression. To analyse the mental disorders in health workers by means of the retrospective study of a sample in a general hospital which asked for a psychiatric consultation, sociodemographic variables, clinico-diagnostic and variables related to laboral activity were analysed. The sample is constituted by 112 patients of an average age of forty years old and preferentially females (79.5%). In the sample, some professions are represented above all expectations; they are nurses, physicians, the laboral category of "boss and managers" and the laboral regimen of "permanents". The more frequent psychiatric disorders were the adjustment disorders and code V, the affective disorders and the anxiety disorders (23-33%), the disorders caused by the use of substances and the psychotic disorders are limited (5%). The laboral activity was considered an important factor in 43% of the cases and the mental disorder caused laboral inability, transitory or permanent in half of the patients. It is detected a relationship between the diagnostic and variables such as sex, laboral category, laboral inability, psychosocial stress level and GAF and there hasn't been detected any association between mental disorders and age, profession, laboral regimen and laboral stress.

  9. On the Path of Election and Martyrdom: Some Psychic Mechanisms Involved in the Anders Behring Breivik's Determination as a Terrorist.

    Science.gov (United States)

    Cotti, Patricia

    2015-08-01

    On 22 July 2011, the Norwegian Anders Behring Breivik carried out two attacks in Oslo that cost the lives of 77 people, injured many others, and plunged the entire Norwegian nation into mourning. When he was arrested, Breivik presented himself as a member of the Knights Templar, whose mission is to defend the Christian Western world. He considers that he has sacrificed himself by his actions for his people and says that he has prepared himself for martyrdom. In analysing Breivik's words and writings, this article attempts to identify the thought mechanisms involved in Breivik's idea of election (megalomania) and martyrology. It highlights the importance of a mechanism of "return to the sender," whereby Breivik returns the reproaches directed at him by an agency of judgment (ego ideal or superegoic object). It emphasizes the existence of a "burning desire" and yearning (Sehnsucht) for this same persecuting superegoic object, an object that Breivik constantly wants to find again, even if in death. Taking into consideration Searles's hypothesis that the sense of being persecuted is a defence against the impossibility of mourning, and also H. Blum's hypothesis that persecutory feelings are indicative of fears of a "regressive loss of object constancy," the different psychic mechanisms and modes of functioning underlying Breivik's terrorist determination are related here to what we know about his affective development and infantile relationships.

  10. Identification of up-regulated proteins potentially involved in the antagonism mechanism of Bacillus amyloliquefaciens G1.

    Science.gov (United States)

    Cao, Haipeng; Zheng, Weidong; He, Shan; Wang, Hao; Wang, Tu; Lu, Liqun

    2013-06-01

    The use of Bacillus probiotics has been demonstrated as a promising method in the biocontrol of bacterial diseases in aquaculture. However, the molecular antibacterial mechanism of Bacillus still remains unclear. In order to explore the antibacterial mechanism of the potential antagonistic Bacillus amyloliquefaciens strain G1, comparative proteomics between B. amyloliquefaciens strain G1 and its non-antagonistic mutant strain was investigated. The 2-dimensional electrophoresis gel maps of their total extracted proteins were described and 42 different proteins were found to be highly expressed in strain G1 in comparison with those in the mutant strain. 35 of these up-regulated proteins were successfully identified using MALDI-TOF-TOF MS and databank analysis, and their biological functions were analyzed through the KEGG database. The increased expression of these proteins suggested that high levels of energy metabolism, biosynthesis and stress resistance could play important roles in strain G1's antagonism. To our knowledge, this is the first report on the proteins involved in the antagonism mechanism of B. amyloliquefaciens using a proteomic approach and the proteomic data also contribute to a better understanding of the molecular basis for the antagonism of B. amyloliquefaciens.

  11. Urticarial dermographism: clinical features and response to psychosocial stress.

    Science.gov (United States)

    Wallengren, Joanna; Isaksson, Anders

    2007-01-01

    Studies report that urticarial dermographism is exacerbated by "life events" and emotions. The aim of this study was to determine what aspects of life quality are affected by symptomatic dermographism and whether acute stress is a potential triggering factor. A total of 21 adult patients with urticarial dermographism completed a questionnaire on symptoms and quality of life. Twelve patients agreed to enrol in the study, which involved provocation by prick test and dermographism before and after a standardized psychosocial stress test (Trier Social Stress Test). Seventeen age-matched controls underwent corresponding tests. Of the patients answering the questionnaire, 43% reported that their disease had an impact on their quality of life and 33% that psychosocial stress precipitated the symptoms. However, the dermographic reaction in patients with urticaria factitia was not significantly intensified after the stress test. We conclude that the acute psychosocial stress test does not alter the magnitude of the dermographic reactions.

  12. Lessons learned from Shuttle/Mir: psychosocial countermeasures

    Science.gov (United States)

    Kanas, Nick; Salnitskiy, Vyacheslav; Grund, Ellen M.; Gushin, Vadim; Weiss, Daniel S.; Kozerenko, Olga; Sled, Alexander; Marmar, Charles R.

    2002-01-01

    BACKGROUND: During future long-duration space missions, countermeasures need to be developed to deal with psychosocial issues that might impact negatively on crewmember performance and well-being. METHODS: In our recently completed NASA-funded study of 5 U.S. astronauts, 8 Russian cosmonauts, and 42 U.S. and 16 Russian mission control personnel who participated in the Shuttle/Mir program, we evaluated a number of important psychosocial issues such as group tension, cohesion, leadership role, and the displacement of negative emotions from crewmembers to people in mission control and from mission control personnel to management. RESULTS: Based on our findings, which are reviewed, a number of psychosocial countermeasures are suggested to help ameliorate the negative impact of potential psychosocial problems during future manned space missions. CONCLUSIONS: Crewmembers should be selected not only to rule out psychopathology but also to select-in for group compatibility and facility in a common language. Training should include briefings and team building related to a number of psychosocial issues and should involve both crewmembers and mission control personnel. During the mission, both experts on the ground and the crewmembers themselves should be alert to potential interpersonal problems, including the displacement of negative emotions from the crew to the ground. Supportive activities should consist of both individual and interpersonal strategies, including an awareness of changing leisure time needs. Finally, attention should be given to postmission readjustment and to supporting the families on Earth.

  13. Metal and metalloid foliar uptake by various plant species exposed to atmospheric industrial fallout: Mechanisms involved for lead

    Energy Technology Data Exchange (ETDEWEB)

    Schreck, E., E-mail: eva.schreck@ensat.fr [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France); Foucault, Y. [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France); STCM, Societe de Traitements Chimiques des Metaux, 30 Avenue de Fondeyre 31200 Toulouse (France); Sarret, G. [ISTerre (UMR 5275), Universite J. Fourier and CNRS, BP 53, 38041 Grenoble cedex 9 (France); Sobanska, S. [LASIR (UMR CNRS 8516), Universite de Lille 1, Bat. C5, 59655 Villeneuve d' Ascq cedex (France); Cecillon, L. [ISTerre (UMR 5275), Universite J. Fourier and CNRS, BP 53, 38041 Grenoble cedex 9 (France); Castrec-Rouelle, M. [Universite Pierre and Marie Curie (UPMC-Paris 6), Bioemco (Biogeochimie et Ecologie des Milieux Continentaux), Site Jussieu, Tour 56, 4 Place Jussieu, 75252 Paris cedex 05 (France); Uzu, G. [Laboratoire d' Aerologie (UMR 5560), OMP, UPS 14, Avenue Edouard Belin, 31400 Toulouse (France); GET (UMR 5563), IRD, 14, Avenue Edouard Belin, 31400 Toulouse (France); Dumat, C. [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France)

    2012-06-15

    Fine and ultrafine metallic particulate matters (PMs) are emitted from metallurgic activities in peri-urban zones into the atmosphere and can be deposited in terrestrial ecosystems. The foliar transfer of metals and metalloids and their fate in plant leaves remain unclear, although this way of penetration may be a major contributor to the transfer of metals into plants. This study focused on the foliar uptake of various metals and metalloids from enriched PM (Cu, Zn, Cd, Sn, Sb, As, and especially lead (Pb)) resulting from the emissions of a battery-recycling factory. Metal and metalloid foliar uptake by various vegetable species, exhibiting different morphologies, use (food or fodder) and life-cycle (lettuce, parsley and rye-grass) were studied. The mechanisms involved in foliar metal transfer from atmospheric particulate matter fallout, using lead (Pb) as a model element was also investigated. Several complementary techniques (micro-X-ray fluorescence, scanning electron microscopy coupled with energy dispersive X-ray microanalysis and time-of-flight secondary ion mass spectrometry) were used to investigate the localization and the speciation of lead in their edible parts, i.e. leaves. The results showed lead-enriched PM on the surface of plant leaves. Biogeochemical transformations occurred on the leaf surfaces with the formation of lead secondary species (PbCO{sub 3} and organic Pb). Some compounds were internalized in their primary form (PbSO{sub 4}) underneath an organic layer. Internalization through the cuticle or penetration through stomata openings are proposed as two major mechanisms involved in foliar uptake of particulate matter. - Graphical abstract: Overall picture of performed observations and mechanisms potentially involved in lead foliar uptake. Highlights: Black-Right-Pointing-Pointer Foliar uptake of metallic particulate matter (PM) is of environmental and health concerns. Black-Right-Pointing-Pointer The leaf morphology influences the adsorption

  14. Resistance to coumaphos and diazinon in Boophilus microplus (Acari: Ixodidae) and evidence for the involvement of an oxidative detoxification mechanism.

    Science.gov (United States)

    Li, Andrew Y; Davey, Ronald B; Miller, Robert J; George, John E

    2003-07-01

    The levels of resistance to two organophosphate acaricides, coumaphos and diazinon, in several Mexican strains of Boophilus microplus (Canestrini) were evaluated using the FAO larval packet test. Regression analysis of LC50 data revealed a significant cross-resistance pattern between those two acaricides. Metabolic mechanisms of resistance were investigated with synergist bioassays. Piperonyl butoxide (PBO) reduced coumaphos toxicity in susceptible strains, but synergized coumaphos toxicity in resistant strains. There was a significant correlation between PBO synergism ratios and the coumaphos resistance ratios. The results suggest that an enhanced cytochrome P450 monooxygenase (cytP450)-mediated detoxification mechanism may exist in the resistant strains, in addition to the cytP450-mediated metabolic pathway that activates coumaphos. PBO failed to synergize diazinon toxicity in resistant strains, suggesting the cytP450 involved in detoxification were specific. Triphenylphosphate (TPP) synergized toxicity of both acaricides in both susceptible and resistant strains, and there was no correlation between TPP synergism ratios and the LC50 estimates for either acaricide. Esterases may not play a major role in resistance to coumaphos and diazinon in those strains. Bioassays with diethyl maleate (DEM) revealed a significant correlation between DEM synergism ratios and LC50 estimates for diazinon, suggesting a possible role for glutathione S-transferases in diazinon detoxification. Resistance to coumaphos in the Mexican strains of B. microplus was likely to be conferred by both a cytP450-mediated detoxification mechanism described here and the mechanism of insensitive acetylcholinesterases reported elsewhere. The results of this study also underscore the potential risk of coumaphos resistance in B. microplus from Mexico to the U.S. cattle fever tick eradication program.

  15. Dehydrocoupling reactions of dimethylamine-borane by Pt(II) complexes: a new mechanism involving deprotonation of boronium cations.

    Science.gov (United States)

    Roselló-Merino, Marta; López-Serrano, Joaquín; Conejero, Salvador

    2013-07-31

    Coordinatively unsaturated Pt(II) complex [Pt(I(t)Bu')(I(t)Bu)](+) stabilized by N-heterocyclic carbene (NHC) ligands dehydrogenates N,N-dimethylamineborane through a mechanism that involves hydride abstraction, assisted by an amine, to yield a platinum-hydride complex [PtH(I(t)Bu')(I(t)Bu)] with concomitant formation of the boronium cation [(NHMe2)2BH2](+). This latter species is very likely in equilibrium with the THF stabilized borenium cation [(NHMe2)(THF)BH2](+), bearing an acidic NH group that is able to protonate the platinum hydride [PtH(I(t)Bu')(I(t)Bu)] releasing H2, the amino borane H2B-NMe2 and regenerating the catalytic [Pt](+) species.

  16. Mechanisms of a novel anticancer therapeutic strategy involving atmospheric pressure plasma-mediated apoptosis and DNA strand break formation.

    Science.gov (United States)

    Chung, Woo-Hyun

    2016-01-01

    Atmospheric pressure plasma has been developed for a variety of biomedical applications due to its chemically reactive components. Recently, the plasma has emerged as a promising novel cancer therapy based on its ability to selectively ablate cancer cells while leaving normal cells essentially unaffected. The therapeutic effect of plasma is attributed to intracellular generation of reactive oxygen/nitrogen species (ROS/RNS) leading to mitochondria-mediated apoptosis and to activation of the DNA damage checkpoint signaling pathway via severe DNA strand break formation. However, the biochemical mechanisms responsible for appropriate activation of these physiological events and which pathway is more crucial for plasma-mediated cytotoxicity have not been clarified. Understanding the molecular link between ROS/RNS-mediated apoptosis and DNA damage-involved chromosome instability is critical for the development of more efficacious therapeutic strategies for selective killing of diverse cancer cells.

  17. Pharmacological Augmentation of Psychosocial and Remediation Training Efforts in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Philip D. Harvey

    2017-09-01

    Full Text Available Pharmacological approaches to cognitive enhancement have received considerable attention but have not had considerable success in improving their cognitive and functional targets. Other intervention strategies, such as cognitive remediation therapy (CRT, have been shown to enhance cognitive performance but have not been found to improve functional outcomes without additional psychosocial interventions. Recently, several studies have attempted to enhance the effects of CRT by adding pharmacological interventions to the CRT treatments. In addition, as CRT has been shown to synergistically improve the effects of psychosocial interventions, the combination of pharmacological therapies aimed at cognition and psychosocial interventions may itself provide a promising strategy for improving functional outcomes. This review and commentary examines the current state of interventions combining CRT and psychosocial treatments with pharmacological augmentation. Our focus is on the specific level of effect of the pharmacological intervention, which could be enhancing motivation, training efficiency, or the consolidation of therapeutic gains. Different pharmacological strategies (e.g., stimulants, plasticity-inducing agents, or attentional or alertness enhancers may have the potential to lead to different types of gains when combined with CRT or psychosocial interventions. The relative potential of these different mechanisms for immediate and durable effects is considered.

  18. Metal and metalloid foliar uptake by various plant species exposed to atmospheric industrial fallout: mechanisms involved for lead.

    Science.gov (United States)

    Schreck, E; Foucault, Y; Sarret, G; Sobanska, S; Cécillon, L; Castrec-Rouelle, M; Uzu, G; Dumat, C

    2012-06-15

    Fine and ultrafine metallic particulate matters (PMs) are emitted from metallurgic activities in peri-urban zones into the atmosphere and can be deposited in terrestrial ecosystems. The foliar transfer of metals and metalloids and their fate in plant leaves remain unclear, although this way of penetration may be a major contributor to the transfer of metals into plants. This study focused on the foliar uptake of various metals and metalloids from enriched PM (Cu, Zn, Cd, Sn, Sb, As, and especially lead (Pb)) resulting from the emissions of a battery-recycling factory. Metal and metalloid foliar uptake by various vegetable species, exhibiting different morphologies, use (food or fodder) and life-cycle (lettuce, parsley and rye-grass) were studied. The mechanisms involved in foliar metal transfer from atmospheric particulate matter fallout, using lead (Pb) as a model element was also investigated. Several complementary techniques (micro-X-ray fluorescence, scanning electron microscopy coupled with energy dispersive X-ray microanalysis and time-of-flight secondary ion mass spectrometry) were used to investigate the localization and the speciation of lead in their edible parts, i.e. leaves. The results showed lead-enriched PM on the surface of plant leaves. Biogeochemical transformations occurred on the leaf surfaces with the formation of lead secondary species (PbCO(3) and organic Pb). Some compounds were internalized in their primary form (PbSO(4)) underneath an organic layer. Internalization through the cuticle or penetration through stomata openings are proposed as two major mechanisms involved in foliar uptake of particulate matter.

  19. Tetrahydrocannabinol Induces Brain Mitochondrial Respiratory Chain Dysfunction and Increases Oxidative Stress: A Potential Mechanism Involved in Cannabis-Related Stroke

    Directory of Open Access Journals (Sweden)

    Valérie Wolff

    2015-01-01

    Full Text Available Cannabis has potential therapeutic use but tetrahydrocannabinol (THC, its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities Vmax (complexes I, III, and IV activities, Vsucc (complexes II, III, and IV activities, Vtmpd (complex IV activity, together with mitochondrial coupling (Vmax/V0, were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2 production, measured with Amplex Red. THC significantly decreased Vmax (−71%; P<0.0001, Vsucc (−65%; P<0.0001, and Vtmpd (−3.5%; P<0.001. Mitochondrial coupling (Vmax/V0 was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P<0.001. Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P<0.05 and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P<0.001. Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient’s vulnerability to stroke.

  20. Mecanismos envolvidos na cicatrização: uma revisão Mechanisms involved in wound healing: a revision

    Directory of Open Access Journals (Sweden)

    Carlos Aberto Balbino

    2005-03-01

    Full Text Available Os mecanismos envolvidos no processo de reparo de tecidos estão revisados nesse trabalho. O processo de cicatrização ocorre fundamentalmente em três fases: inflamação, formação de tecido de granulação e deposição de matriz extracelular e remodelação. Os eventos celulares e tissulares de cada uma dessas fases estão descritos e discutidos. Os mediadores químicos estão correlacionados com os eventos do processo de cicatrização e as células envolvidas. Especial ênfase é dada à participação dos fatores de crescimento.The mechanisms involved in tissue repair are revised. The wound healing process occurs basically in three phases: inflammation, formation of granulating tissue and extracellular tissue deposition, and tissue remodeling. The cellular and tissue events of each phase are described and discussed. The chemical mediators and their interplay with the wound healing events and cells involved are also discussed. However, especial attention was given to the role played by the growth factors in the tissue repair process.

  1. Initial study on the possible mechanisms involved in the effects of high doses of perfluorooctane sulfonate (PFOS) on prolactin secretion.

    Science.gov (United States)

    Salgado, R; Pereiro, N; López-Doval, S; Lafuente, A

    2015-09-01

    Perfluorooctane sulfonate (PFOS) is a fluorinated organic compound. This chemical is neurotoxic and can alter the pituitary secretion. This is an initial study aimed at knowing the toxic effects of high doses of PFOS on prolactin secretion and the possible mechanisms involved in these alterations. For that, adult male rats were orally treated with 3.0 and 6.0 mg of PFOS/kg body weight (b.w.)/day for 28 days. At the end of the treatment, the serum levels of prolactin and estradiol as well as the concentration of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and gamma-aminobutyric acid (GABA) were quantified in the anterior and in the mediobasal hypothalamus. PFOS, at the administered doses, reduced prolactin and estradiol secretion, increased the concentration of dopamine and GABA in the anterior hypothalamus, and decreased the ratios DOPAC/dopamine and HVA/dopamine in this same hypothalamic area. The outcomes reported in this study suggest that (1) high doses of PFOS inhibit prolactin secretion in adult male rats; (2) only the periventricular-hypophysial dopaminergic (PHDA) neurons seem to be involved in this inhibitory effect but not the tuberoinfundibular dopaminergic (TIDA) and the tuberohypophysial dopaminergic (THDA) systems; (3) GABAergic cells from the paraventricular and supraoptic nuclei could be partially responsible for the PFOS action on prolactin secretion; and finally (4) estradiol might take part in the inhibition exerted by elevated concentration of PFOS on prolactin release.

  2. Mechanisms of formation and function of eosinophil lipid bodies: inducible intracellular sites involved in arachidonic acid metabolism

    Directory of Open Access Journals (Sweden)

    Bozza Patricia T

    1997-01-01

    Full Text Available Lipid bodies, inducible lipid-rich cytoplasmic inclusions, are characteristically abundant in cells associated with inflammation, including eosinophils. Here we reviewed the formation and function of lipid bodies in human eosinophils. We now have evidence that the formation of lipid bodies is not attributable to adverse mechanisms, but is centrally mediated by specific signal transduction pathways. Arachidonic acid and other cis fatty acids by an NSAID-inhibitable process, diglycerides, and PAF by a 5-lipoxygenase dependent pathway are potent stimulators of lipid body induction. Lipid body formation develops rapidly by processes that involve PKC, PLC, and de novo mRNA and protein synthesis. These structures clearly serve as repositoires of arachidonyl-phospholipids and are more than inert depots. Specific enzymes, including cytosolic phospholipase A2, MAP kinases, lipoxygenases and cyclooxygenases, associate with lipid bodies. Lipid bodies appear to be dynamic, organelle-like structures involved in intracellular pathways of lipid mobilization and metabolism. Indeed, increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. We hypothesize that lipid bodies are distinct inducible sites for generating eicosanoids as paracrine mediators with varied activities in inflammation. The capacity of lipid body formation to be specifically and rapidly induced in leukocytes enhances eicosanoid mediator formation, and conversely pharmacologic inhibition of lipid body induction represents a potential novel and specific target for anti-inflammatory therapy.

  3. Involvement of β-defensin 130 (DEFB130) in the macrophage microbicidal mechanisms for killing Plasmodium falciparum

    Science.gov (United States)

    Terkawi, Mohamad Alaa; Takano, Ryo; Furukawa, Atsushi; Murakoshi, Fumi; Kato, Kentaro

    2017-01-01

    Understanding the molecular defense mechanism of macrophages and identifying their effector molecules against malarial parasites may provide important clues for the discovery of new therapies. To analyze the immunological responses of malarial parasite-induced macrophages, we used DNA microarray technology to examine the gene profile of differentiated macrophages phagocytizing Plasmodium falciparum-parasitized erythrocytes (iRBC). The transcriptional gene profile of macrophages in response to iRBCs represented 168 down-regulated genes, which were mainly involved in the cellular immune response, and 216 upregulated genes, which were involved in cellular proteolysis, growth, and adhesion. Importantly, the specific upregulation of β-defensin 130 (DEFB130) in these macrophages suggested a possible role for DEFB130 in malarial parasite elimination. Differentiated macrophages phagocytizing iRBCs exhibited an increase in intracellular DEFB130 levels and DEFB130 appeared to accumulate at the site of iRBC engulfment. Transfection of esiRNA-mediated knockdown of DEFB130 into macrophages resulted in a remarkable reduction in their antiplasmodial activity in vitro. Furthermore, DEFB130 synthetic peptide exhibited a modest toxic effect on P. falciparum in vitro and P. yoelii in vivo, unlike scrambled DEFB130 peptide, which showed no antiplasmodial activity. Together, these results suggest that DEFB130 might be one of the macrophage effector molecules for eliminating malarial parasites. Our data broaden our knowledge of the immunological response of macrophages to iRBCs and shed light on a new target for therapeutic intervention. PMID:28181499

  4. Mechanisms involved in the vasorelaxant effects produced by the acute application of amfepramone in vitro to rat aortic rings

    Energy Technology Data Exchange (ETDEWEB)

    López-Canales, J.S. [Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City (Mexico); Department of Cellular Biology, National Institute of Perinatology, Mexico City (Mexico); Lozano-Cuenca, J.; Muãoz-Islas, E.; Aguilar-Carrasco, J.C. [Department of Cellular Biology, National Institute of Perinatology, Mexico City (Mexico); López-Canales, O.A.; López-Mayorga, R.M.; Castillo-Henkel, E.F.; Valencia-Hernández, I.; Castillo-Henkel, C. [Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City (Mexico)

    2015-03-27

    Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca{sup 2+}-activated K{sup +} channels were involved in this effect.

  5. Huang Qi Jian Zhong Pellet Attenuates TNBS-Induced Colitis in Rats via Mechanisms Involving Improvement of Energy Metabolism.

    Science.gov (United States)

    Liu, Duan-Yong; Pan, Chun-Shui; Liu, Yu-Ying; Wei, Xiao-Hong; Zhou, Chang-Man; Sun, Kai; He, Ke; Li, Chong; Yan, Li; Fan, Jing-Yu; Wang, Chuan-She; Hibi, Toshifumi; Liu, Hong-Ning; Han, Jing-Yan

    2013-01-01

    Huang Qi Jian Zhong Pellet (HQJZ) is a famous Chinese medicine formula for treatment of various gastrointestinal tract diseases. This study investigated the role of HQJZ in 2,4,6-trinitrobenzene sulfonic acid- (TNBS-) induced colitis and its underlying mechanism. Colonic mucosal injury was induced by TNBS in the Sprague-Dawley rats. In the HQJZ treatment group, HQJZ was administered (2 g/kg) for 14 days starting from day 1 after TNBS infusion. Colonic mucosal injury occurred obviously 1 day after TNBS challenge and did not recover distinctively until day 15, including an increase in macro- and microscopic scores, a colonic weight index, a decrease in colonic length, a number of functional capillaries, and blood flow. Inverted intravital microscopy and ELISA showed colonic microcirculatory disturbances and inflammatory responses after TNBS stimulation, respectively. TNBS decreased occludin, RhoA, and ROCK-I, while increasing Rac-1, PAK-1, and phosphorylated myosin light chain. In addition, ATP content and ATP5D expression in colonic mucosa decreased after TNBS challenge. Impressively, treatment with HQJZ significantly attenuated all of the alterations evoked by TNBS, promoting the recovery of colonic injury. The present study demonstrated HQJZ as a multitargeting management for colonic mucosal injury, which set in motion mechanisms involving improvement of energy metabolism.

  6. Huang Qi Jian Zhong Pellet Attenuates TNBS-Induced Colitis in Rats via Mechanisms Involving Improvement of Energy Metabolism

    Directory of Open Access Journals (Sweden)

    Duan-Yong Liu

    2013-01-01

    Full Text Available Huang Qi Jian Zhong Pellet (HQJZ is a famous Chinese medicine formula for treatment of various gastrointestinal tract diseases. This study investigated the role of HQJZ in 2,4,6-trinitrobenzene sulfonic acid- (TNBS- induced colitis and its underlying mechanism. Colonic mucosal injury was induced by TNBS in the Sprague-Dawley rats. In the HQJZ treatment group, HQJZ was administered (2 g/kg for 14 days starting from day 1 after TNBS infusion. Colonic mucosal injury occurred obviously 1 day after TNBS challenge and did not recover distinctively until day 15, including an increase in macro- and microscopic scores, a colonic weight index, a decrease in colonic length, a number of functional capillaries, and blood flow. Inverted intravital microscopy and ELISA showed colonic microcirculatory disturbances and inflammatory responses after TNBS stimulation, respectively. TNBS decreased occludin, RhoA, and ROCK-I, while increasing Rac-1, PAK-1, and phosphorylated myosin light chain. In addition, ATP content and ATP5D expression in colonic mucosa decreased after TNBS challenge. Impressively, treatment with HQJZ significantly attenuated all of the alterations evoked by TNBS, promoting the recovery of colonic injury. The present study demonstrated HQJZ as a multitargeting management for colonic mucosal injury, which set in motion mechanisms involving improvement of energy metabolism.

  7. Characterization of the mechanisms of action and nitric oxide species involved in the relaxation induced by the ruthenium complex.

    Science.gov (United States)

    Bonaventura, Daniella; Oliveira, Fabiana S; Lunardi, Claure N; Vercesi, Juliana A; da Silva, Roberto S; Bendhack, Lusiane M

    2006-12-01

    Nitric oxide (NO) plays an important role in the control of vascular tone. NO donors have therapeutic use and the most used NO donors, nitroglycerin and sodium nitroprusside have problems in their use. Thus, new NO donors have been synthesized to minimize these undesirable effects. Nytrosil ruthenium complexes have been studied as a new class of NO donors. trans-[RuCl([15]aneN(4))NO](2+), induces vasorelaxation only in presence of reducing agent. In this study, we characterized the mechanisms of vasorelaxation of trans-[RuCl([15]aneN(4))NO](2+) in denuded rat aorta and identified which NO forms are involved in this relaxation. We also evaluated the effect of this NO donor in decreasing the cytosolic Ca(2+) concentration ([Ca(2+)]c) of the vascular smooth muscle cells. Vasorelaxation to trans-[RuCl([15]aneN(4))NO](2+) (E(max): 101.8 +/- 2.3%, pEC(50): 5.03 +/- 0.15) was almost abolished in the presence of the NO* scavenger hydroxocobalamin (E(max): 4.0 +/- 0.4%; P < 0.001) and it was partially inhibited by the NO(-) scavenger L-cysteine (E(max): 79.9 +/- 6.9%, pEC(50): 4.41 +/- 0.06; P < 0.05). The guanylyl cyclase inhibitor ODQ reduced the E(max) (57.7 +/- 4.0%, P < 0.001) and pEC(50) (4.21 +/- 0.42, P < 0.01) and the combination of ODQ and TEA abolished the response to trans-[RuCl([15]aneN(4))NO](2+). The blockade of voltage-dependent (K(v)), ATP-sensitive (K(ATP)), and Ca(2+)-activated (K(Ca) K(+) channels reduced the vasorelaxation induced by trans-[RuCl([15]aneN(4))NO](2+). This compound significantly reduced [Ca(2+)]c (from 100% to 85.9 +/- 3.5%, n = 4). In conclusion, our data demonstrate that this NO donor induces vascular relaxation involving NO* and NO(-) species, that is associated to a decrease in [Ca(2+)]c. The mechanisms of vasorelaxation involve guanylyl cyclase activation, cGMP production and K(+) channels activation.

  8. Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs.

    Directory of Open Access Journals (Sweden)

    Huizheng Wang

    Full Text Available BACKGROUND: Polyhydroxyalkanoates (PHAs have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC, which belongs to (R-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic. METHODOLOGY/PRINCIPAL FINDINGS: We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC. CONCLUSIONS/SIGNIFICANCE: The data in our study reveal the regulatory mechanism of an (R-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  9. Effects and mechanisms of 3α,5α,-THP on emotion, motivation, and reward functions involving pregnane xenobiotic receptor

    Directory of Open Access Journals (Sweden)

    Cheryl A Frye

    2012-01-01

    Full Text Available Progestogens [progesterone (P4 and its products] play fundamental roles in the development and/or function of the central nervous system during pregnancy. We, and others, have investigated the role of pregnane neurosteroids for a plethora of functional effects beyond their pro-gestational processes. Emerging findings regarding the effects, mechanisms, and sources of neurosteroids have challenged traditional dogma about steroid action. How the P4 metabolite and neurosteroid, 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP, influences cellular functions and behavioral processes involved in emotion/affect, motivation, and reward, is the focus of the present review. To further understand these processes, we have utilized an animal model assessing the effects, mechanisms, and sources of 3α,5α-THP. In the ventral tegmental area (VTA, 3α,5α-THP has actions to facilitate affective, and motivated, social behaviors through non-traditional targets, such as GABA, glutamate, and dopamine receptors. 3α,5α-THP levels in the midbrain VTA both facilitate, and/or are enhanced by, affective and social behavior. The pregnane xenobiotic receptor (PXR mediates the production of, and/or metabolism to, various neurobiological factors. PXR is localized to the midbrain VTA of rats. The role of PXR to influence 3α,5α-THP production from central biosynthesis, and/or metabolism of peripheral P4, in the VTA, as well as its role to facilitate, or be increased by, affective/social behaviors is under investigation. Investigating novel behavioral functions of 3α,5α-THP extends our knowledge of the neurobiology of progestogens, relevant for affective/social behaviors, and their connections to systems that regulate affect and motivated processes, such as those important for stress regulation and neuropsychiatric disorders (anxiety, depression, schizophrenia, drug dependence. Thus, further understanding of 3α,5α-THP’s role and mechanisms to enhance affective and motivated

  10. Effects and Mechanisms of 3α,5α,-THP on Emotion, Motivation, and Reward Functions Involving Pregnane Xenobiotic Receptor.

    Science.gov (United States)

    Frye, Cheryl A; Paris, J J; Walf, A A; Rusconi, J C

    2011-01-01

    Progestogens [progesterone (P(4)) and its products] play fundamental roles in the development and/or function of the central nervous system during pregnancy. We, and others, have investigated the role of pregnane neurosteroids for a plethora of functional effects beyond their pro-gestational processes. Emerging findings regarding the effects, mechanisms, and sources of neurosteroids have challenged traditional dogma about steroid action. How the P(4) metabolite and neurosteroid, 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP), influences cellular functions and behavioral processes involved in emotion/affect, motivation, and reward, is the focus of the present review. To further understand these processes, we have utilized an animal model assessing the effects, mechanisms, and sources of 3α,5α-THP. In the ventral tegmental area (VTA), 3α,5α-THP has actions to facilitate affective, and motivated, social behaviors through non-traditional targets, such as GABA, glutamate, and dopamine receptors. 3α,5α-THP levels in the midbrain VTA both facilitate, and/or are enhanced by, affective and social behavior. The pregnane xenobiotic receptor (PXR) mediates the production of, and/or metabolism to, various neurobiological factors. PXR is localized to the midbrain VTA of rats. The role of PXR to influence 3α,5α-THP production from central biosynthesis, and/or metabolism of peripheral P(4), in the VTA, as well as its role to facilitate, or be increased by, affective/social behaviors is under investigation. Investigating novel behavioral functions of 3α,5α-THP extends our knowledge of the neurobiology of progestogens, relevant for affective/social behaviors, and their connections to systems that regulate affect and motivated processes, such as those important for stress regulation and neuropsychiatric disorders (anxiety, depression, schizophrenia, drug dependence). Thus, further understanding of 3α,5α-THP's role and mechanisms to enhance affective and motivated processes

  11. Configurations of Common Childhood Psychosocial Risk Factors

    Science.gov (United States)

    Copeland, William; Shanahan, Lilly; Costello, E. Jane; Angold, Adrian

    2009-01-01

    Background: Co-occurrence of psychosocial risk factors is commonplace, but little is known about psychiatrically-predictive configurations of psychosocial risk factors. Methods: Latent class analysis (LCA) was applied to 17 putative psychosocial risk factors in a representative population sample of 920 children ages 9 to 17. The resultant class…

  12. Cyberaddictions: toward a psychosocial perspective.

    Science.gov (United States)

    Suissa, Amnon Jacob

    2014-12-01

    The concept of cyberaddiction is far from being unanimously accepted by scientists (Ko, Yen, Yen, Chen, & Chen, 2012; Pezoa-Jares, Espinoza-Luna & Vasquez-Medina, 2012; Nadeau & et al. 2011; Perraton, Fusaro & Bonenfant, 2011. The same is true of addiction to videogames (Hellman, Schoenmakers, Nordstrom, & Van Holst 2013); Coulombe (2010); or to Facebook (Andreassen et al. 2012; Levard & Soulas, 2010). While certain researchers wished to see this condition included in the DSM-5, others question the operational and practical basis for the diagnostic criteria (Block, 2008). Through a review of litterature and results from research findings; the aim of this article is to propose a psychosocial perspective for the cyberaddiction phenomenon. By a psychosocial perspective, we mean the inclusion of social determinants (weak social ties, social exclusion, hyper individualism, poverty, unemployment, etc) and not only the individual characteristics associated with the disease model in the addiction field. To what extent social conditions and cyberaddiction behaviors constitute a potential pathology ? Can we include a psychosocial approach to gain a more general picture of this contemporary issue? In response to these questions, a contextualization and an attempt to define cyberaddiction will be followed by an analysis of some major issues in the development of this type of addiction. As a conclusion, a demonstration of the cycle of addiction on how people develop addictions, including cyberaddictions, will be done within a psychosocial perspective in order to seize the multifactorial aspects of this addiction.

  13. Psychosocial risks and job performance

    NARCIS (Netherlands)

    Klein Hesselink, J.; Oeij, P.; Kraan, K.O.

    2014-01-01

    In this article, we concentrate on explaining job performance from the perspective of psychosocial risks in the work environment. Many risks may hinder good job performance. The article does not concentrate on physical (such as, carrying heavy loads) or environmental risks (such as, extreme heat or

  14. Cooley's Anemia: A Psychosocial Directory.

    Science.gov (United States)

    National Center for Education in Maternal and Child Health, Washington, DC.

    The directory is intended to aid patients and their families who are coping with the genetic disorder of Cooley's anemia. A brief review of the disease covers background, genetics, symptoms, effect on the patient, treatment, and current research. The next section looks at psychosocial needs at various times (time of diagnosis, infancy and toddler…

  15. Psychosocial Issues in Learning Disabilities.

    Science.gov (United States)

    Heisler, Alice B.

    1983-01-01

    Emotional development from infancy to adolescence is traced and the effects of psychosocial issues on a child with a learning disability are considered for five of E. Erikson's seven proposed stages (trust, autonomy, initiative, industry, adolescence). The need for intervention and parent counseling at each state is emphasized. (CL)

  16. Psychosocial aspects of androgenetic alopecia

    NARCIS (Netherlands)

    A. van der Donk (Jos)

    1992-01-01

    textabstractThe main objective of the studies described in this thesis is to study the psychosocial problems of men and women with androgenetic alopecia who applied for treatment. In chapter 2, the psychological characteristics of 59 men with androgenetic alopecia from a sample of the general popula

  17. Psychosocial aspects of androgenetic alopecia

    NARCIS (Netherlands)

    A. van der Donk (Jos)

    1992-01-01

    textabstractThe main objective of the studies described in this thesis is to study the psychosocial problems of men and women with androgenetic alopecia who applied for treatment. In chapter 2, the psychological characteristics of 59 men with androgenetic alopecia from a sample of the general

  18. Family psychosocial risk screening guided by the Pediatric Psychosocial Preventative Health Model (PPPHM) using the Psychosocial Assessment Tool (PAT).

    Science.gov (United States)

    Kazak, Anne E; Schneider, Stephanie; Didonato, Stephen; Pai, Ahna L H

    2015-05-01

    Although families of children with cancer and other serious medical conditions have documented psychosocial needs, the systematic identification of needs and delivery of evidence-based care remain challenges. Screening for multifaceted family psychosocial risk is a means by which psychosocial treatment needs for pediatric patients and their families can be identified in an effective and inclusive manner. The Pediatric Psychosocial Preventative Health Model (PPPHM) is a model that can guide systematic assessment of family psychosocial risk. The Psychosocial Assessment Tool (PAT) is a brief parent report screener of psychosocial risk based on the PPPHM that can be used for families of infants through adolescents. The PPPHM and the PAT are described in this paper, along with a summary of data supporting systematic risk assessment. The PPPHM outlines three tiers of family psychosocial risk - Universal (low), Targeted (medium), and Clinical (high). The PAT is a validated measure of psychosocial risk. Scores on the PAT, derived from multiple sites and disease conditions, map on to the PPPHM with indications that one-half to two-thirds of families score at the Universal level of risk based on the PAT. The PAT is a unique screener of psychosocial risk, both in terms of its breadth and underlying model (PPPHM), and its length and format. As an example of a means by which families can be screened early in the treatment process, PAT scores and corresponding PPPHM levels can provide direction for the delivery of evidence-based psychosocial care.

  19. Insights into the Mechanisms Involved in the Expression and Regulation of Extracellular Matrix Proteins in Diabetic Nephropathy.

    Science.gov (United States)

    Hu, C; Sun, L; Xiao, L; Han, Y; Fu, X; Xiong, X; Xu, X; Liu, Y; Yang, S; Liu, F; Kanwar, Y S

    2015-01-01

    Diabetic Nephropathy (DN) is believed to be a major microvascular complication of diabetes. The hallmark of DN includes deposition of Extracellular Matrix (ECM) proteins, such as, collagen, laminin and fibronectin in the mesangium and renal tubulo-interstitium of the glomerulus and basement membranes. Such an increased expression of ECM leads to glomerular and tubular basement membranes thickening and increase of mesangial matrix, ultimately resulting in glomerulosclerosis and tubulointerstitial fibrosis. The characteristic morphologic glomerular mesangial lesion has been described as Kimmelstiel-Wilson nodule, and the process at times is referred to as diabetic nodular glomerulosclerosis. Thus, the accumulation of ECM proteins plays a critical role in the development of DN. The relevant mechanism(s) involved in the increased ECM expression and their regulation in the kidney in diabetic state has been extensively investigated and documented in the literature. Nevertheless, there are certain other mechanisms that may yet be conclusively defined. Recent studies demonstrated that some of the new signaling pathways or molecules including, Notch, Wnt, mTOR, TLRs and small GTPase may play a pivotal role in the modulation of ECM regulation and expression in DN. Such modulation could be operational for instance Notch through Notch1/Jagged1 signaling, Wnt by Wnt/β- catenin pathway and mTOR via PI3-K/Akt/mTOR signaling pathways. All these pathways may be critical in the modulation of ECM expression and tubulo-interstitial fibrosis. In addition, TLRs, mainly the TLR2 and TLR4, by TLR2- dependent and TGF-β-dependent conduits, may modulate ECM expression and generate a fibrogenic response. Small GTPase like Rho, Ras and Rab family by targeting relevant genes may also influence the accumulation of ECM proteins and renal fibrosis in hyperglycemic states. This review summarizes the recent information about the role and mechanisms by which these molecules and signaling pathways

  20. Psychosocial aspects of athletic injuries as perceived by athletic trainers.

    Science.gov (United States)

    Clement, Damien; Granquist, Megan D; Arvinen-Barrow, Monna M

    2013-01-01

    Despite the Psychosocial Strategies and Referral content area, athletic trainers (ATs) generally lack confidence in their ability to use this information. The current study's primary purpose was to determine (a) perceived psychological responses and coping behaviors athletes may present to ATs, (b) psychosocial strategies ATs currently use with their athletes, (c) psychosocial strategies ATs deem important to learn more about, and (d) ATs' current practices in referring athletes to counseling or sport psychology services. Mixed-methods study. Online survey containing both quantitative and qualitative items. A total of 215 ATs (86 male, 129 female), representing a response rate of 22.50%. The Athletic Training and Sport Psychology Questionnaire. Stress/anxiety (4.24 ± 0.82), anger (3.70 ± 0.96), and treatment adherence problems (3.62 ± 0.94) were rated as the primary psychological responses athletes may present upon injury. Adherence and having a positive attitude were identified as key determinants in defining athletes' successful coping with their injuries. The top 3 selected psychosocial strategies were keeping the athlete involved with the team (4.57 ± 0.73), using short-term goals (4.45 ± 0.67), and creating variety in rehabilitation exercises (4.32 ± 0.75). The top 3 rated psychosocial strategies ATs deem important to learn more about were understanding motivation (4.29 ± 0.89), using effective communication (4.24 ± 0.91), and setting realistic goals (4.22 ± 0.97). Of the sample, only 59 (27.44%) ATs reported referring an athlete for counseling services, and 37 (84.09%) of those who had access to a sport psychologist (n = 44) reported referring for sport psychology services. These results not only highlight ATs' current use of psychosocial strategies but also their desires to increase their current knowledge and understanding of these strategies while caring for injured athletes.

  1. Hematopoietic stem cell involvement in BCR-ABL1-positive ALL as potential mechanism of resistance to blinatumomab therapy.

    Science.gov (United States)

    Nagel, Inga; Bartels, Marius; Duell, Johannes; Oberg, Hans-Heinrich; Ussat, Sandra; Bruckmueller, Henrike; Ottmann, Oliver; Pfeifer, Heike; Trautmann, Heiko; Gökbuget, Nicola; Caliebe, Almuth; Kabelitz, Dieter; Kneba, Michael; Horst, Heinz-August; Hoelzer, Dieter; Topp, Max S; Cascorbi, Ingolf; Siebert, Reiner; Brüggemann, Monika

    2017-08-21

    The bispecific T-cell engager blinatumomab targeting CD19 can induce complete remission in relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, some patients ultimately relapse with loss of CD19-antigen on leukemic cells which has been established as a novel escape mechanism to CD19-specific immunotherapies. Here, we provide evidence that CD19-negative relapse after CD19-directed therapy in BCP-ALL may be due to selection of preexisting CD19-negative malignant progenitor cells. We present two BCR-ABL1-fusion-positive BCP-ALL patients with CD19-negative myeloid lineage relapse after blinatumomab therapy and show BCR-ABL1-positivity in their hematopoietic stem cell (HSC)/progenitor/myeloid compartments at initial diagnosis by fluorescence in situ hybridization after cell sorting. Using the same approach in 25 additional diagnostic samples of patients with BCR-ABL1-positive BCP-ALL, HSC involvement was identified in 40% of the patients. Patients with major-BCR-ABL1 transcript encoding P210(BCR-ABL1) mainly showed HSC involvement (6/8), whereas in most of the patients with minor-BCR-ABL1 transcript encoding P190(BCR-ABL1) only the CD19-positive leukemia compartments were BCR-ABL1-positive (9/12) (p=0.02). Our data are of clinical importance, because they indicate that not only CD19-positive cells, but also CD19-negative precursors should be targeted to avoid CD19-negative relapses in patients with BCR-ABL1-positive ALL. Copyright © 2017 American Society of Hematology.

  2. Mechanisms Involved in Acquisition of blaNDM Genes by IncA/C2 and IncFIIY Plasmids.

    Science.gov (United States)

    Wailan, Alexander M; Sidjabat, Hanna E; Yam, Wan Keat; Alikhan, Nabil-Fareed; Petty, Nicola K; Sartor, Anna L; Williamson, Deborah A; Forde, Brian M; Schembri, Mark A; Beatson, Scott A; Paterson, David L; Walsh, Timothy R; Partridge, Sally R

    2016-07-01

    blaNDM genes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying a blaNDM gene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of the blaNDM region found on Acinetobacter plasmids. pKP1-NDM-1 and pEC2-NDM-3, from Klebsiella pneumoniae and Escherichia coli, respectively, were identified as type 1 IncA/C2 plasmids with almost identical backbones. Different regions carrying blaNDM are inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1 may have been involved in the acquisition of blaNDM-3 by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, from Enterobacter cloacae and E. coli, respectively, have similar IncFIIY backbones, but different regions carrying blaNDM are found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition of blaNDM-6 by pEC4-NDM-6 and the rmtC 16S rRNA methylase gene by IncFIIY plasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquired blaNDM genes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission of blaNDM genes among species of the Enterobacteriaceae family. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. Amino acid residues involved in the catalytic mechanism of NAD-dependent glutamate dehydrogenase from Halobacterium salinarum.

    Science.gov (United States)

    Pérez-Pomares, F; Ferrer, J; Camacho, M; Pire, C; LLorca, F; Bonete, M J

    1999-02-01

    The pH dependence of kinetic parameters for a competitive inhibitor (glutarate) was determined in order to obtain information on the chemical mechanism for NAD-dependent glutamate dehydrogenase from Halobacterium salinarum. The maximum velocity is pH dependent, decreasing at low pHs giving a pK value of 7.19+/-0.13, while the V/K for l-glutamate at 30 degrees C decreases at low and high pHs, yielding pK values of 7.9+/-0.2 and 9.8+/-0.2, respectively. The glutarate pKis profile decreases at high pHs, yielding a pK of 9. 59+/-0.09 at 30 degrees C. The values of ionization heat calculated from the change in pK with temperature are: 1.19 x 10(4), 5.7 x 10(3), 7 x 10(3), 6.6 x 10(3) cal mol-1, for the residues involved. All these data suggest that the groups required for catalysis and/or binding are lysine, histidine and tyrosine. The enzyme shows a time-dependent loss in glutamate oxidation activity when incubated with diethyl pyrocarbonate (DEPC). Inactivation follows pseudo-first-order kinetics with a second-order rate constant of 53 M-1min-1. The pKa of the titratable group was pK1=6.6+/-0.6. Inactivation with ethyl acetimidate also shows pseudo-first-order kinetics as well as inactivation with TNM yielding second-order constants of 1.2 M-1min-1 and 2.8 M-1min-1, and pKas of 8.36 and 9.0, respectively. The proposed mechanism involves hydrogen binding of each of the two carboxylic groups to tyrosyl residues; histidine interacts with one of the N-hydrogens of the l-glutamate amino group. We also corroborate the presence of a conservative lysine that has a remarkable ability to coordinate a water molecule that would act as general base.

  4. Mechanism of ghrelin-induced gastric contractions in Suncus murinus (house musk shrew): involvement of intrinsic primary afferent neurons.

    Science.gov (United States)

    Mondal, Anupom; Aizawa, Sayaka; Sakata, Ichiro; Goswami, Chayon; Oda, Sen-ichi; Sakai, Takafumi

    2013-01-01

    Here, we have reported that motilin can induce contractions in a dose-dependent manner in isolated Suncus murinus (house musk shrew) stomach. We have also shown that after pretreatment with a low dose of motilin (10(-10) M), ghrelin also induces gastric contractions at levels of 10(-10) M to 10(-7) M. However, the neural mechanism of ghrelin action in the stomach has not been fully revealed. In the present study, we studied the mechanism of ghrelin-induced contraction in vitro using a pharmacological method. The responses to ghrelin in the stomach were almost completely abolished by hexamethonium and were significantly suppressed by the administration of phentolamine, prazosin, ondansetron, and naloxone. Additionally, N-nitro-l-arginine methylester significantly potentiated the contractions. Importantly, the mucosa is essential for ghrelin-induced, but not motilin-induced, gastric contractions. To evaluate the involvement of intrinsic primary afferent neurons (IPANs), which are multiaxonal neurons that pass signals from the mucosa to the myenteric plexus, we examined the effect of the IPAN-related pathway on ghrelin-induced contractions and found that pretreatment with adenosine and tachykinergic receptor 3 antagonists (SR142801) significantly eliminated the contractions and GR113808 (5-hydroxytryptamine receptor 4 antagonist) almost completely eliminated it. The results indicate that ghrelin stimulates and modulates suncus gastric contractions through cholinergic, adrenergic, serotonergic, opioidergic neurons and nitric oxide synthases in the myenteric plexus. The mucosa is also important for ghrelin-induced gastric contractions, and IPANs may be the important interneurons that pass the signal from the mucosa to the myenteric plexus.

  5. The pressor effect of angiotensin-(1-7 in the rat rostral ventrolateral medulla involves multiple peripheral mechanisms

    Directory of Open Access Journals (Sweden)

    Rita C. Oliveira

    2013-01-01

    Full Text Available OBJECTIVE: In the present study, the peripheral mechanism that mediates the pressor effect of angiotensin-(1-7 in the rostral ventrolateral medulla was investigated. METHOD: Angiotensin-(1-7 (25 pmol was bilaterally microinjected in the rostral ventrolateral medulla near the ventral surface in urethane-anesthetized male Wistar rats that were untreated or treated (intravenously with effective doses of selective autonomic receptor antagonists (atenolol, prazosin, methyl-atropine, and hexamethonium or a vasopressin V1 receptor antagonist [d(CH25 -Tyr(Me-AVP] given alone or in combination. RESULTS: Unexpectedly, the pressor response produced by angiotensin-(1-7 (16 ± 2 mmHg, n = 12, which was not associated with significant changes in heart rate, was not significantly altered by peripheral treatment with prazosin, the vasopressin V1 receptor antagonist, hexamethonium or methyl-atropine. Similar results were obtained in experiments that tested the association of prazosin and atenolol; methyl-atropine and the vasopressin V1 antagonist or methyl-atropine and prazosin. Peripheral treatment with the combination of prazosin, atenolol and the vasopressin V1 antagonist abolished the pressor effect of glutamate; however, this treatment produced only a small decrease in the pressor effect of angiotensin-(1-7 at the rostral ventrolateral medulla. The combination of hexamethonium with the vasopressin V1 receptor antagonist or the combination of prazosin, atenolol, the vasopressin V1 receptor antagonist and methyl-atropine was effective in blocking the effect of angiotensin-(1-7 at the rostral ventrolateral medulla. CONCLUSION: These results indicate that angiotensin-(1-7 triggers a complex pressor response at the rostral ventrolateral medulla that involves an increase in sympathetic tonus, release of vasopressin and possibly the inhibition of a vasodilatory mechanism.

  6. Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action.

    Directory of Open Access Journals (Sweden)

    Fernanda Fonseca-Silva

    2016-02-01

    Full Text Available The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. The lack of affordable therapy has necessitated the urgent development of new drugs that are efficacious, safe, and more accessible to patients. Natural products are a major source for the discovery of new and selective molecules for neglected diseases. In this paper, we evaluated the effect of apigenin on Leishmania amazonensis in vitro and in vivo and described the mechanism of action against intracellular amastigotes of L. amazonensis.Apigenin reduced the infection index in a dose-dependent manner, with IC50 values of 4.3 μM and a selectivity index of 18.2. Apigenin induced ROS production in the L. amazonensis-infected macrophage, and the effects were reversed by NAC and GSH. Additionally, apigenin induced an increase in the number of macrophages autophagosomes after the infection, surrounding the parasitophorous vacuole, suggestive of the involvement of host autophagy probably due to ROS generation induced by apigenin. Furthermore, apigenin treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers.In conclusion, our study suggests that apigenin exhibits leishmanicidal effects against L. amazonensis-infected macrophages. ROS production, as part of the mechanism of action, could occur through the increase in host autophagy and thereby promoting parasite death. Furthermore, our data suggest that apigenin is effective in the treatment of L. amazonensis-infected BALB/c mice by oral administration, without altering serological toxicity markers. The selective in vitro activity of apigenin, together with excellent theoretical predictions of oral availability, clear decreases in parasite load and lesion size, and no observed compromises to the overall health of the infected mice encourage us to supports

  7. Mechanism of ghrelin-induced gastric contractions in Suncus murinus (house musk shrew: involvement of intrinsic primary afferent neurons.

    Directory of Open Access Journals (Sweden)

    Anupom Mondal

    Full Text Available Here, we have reported that motilin can induce contractions in a dose-dependent manner in isolated Suncus murinus (house musk shrew stomach. We have also shown that after pretreatment with a low dose of motilin (10(-10 M, ghrelin also induces gastric contractions at levels of 10(-10 M to 10(-7 M. However, the neural mechanism of ghrelin action in the stomach has not been fully revealed. In the present study, we studied the mechanism of ghrelin-induced contraction in vitro using a pharmacological method. The responses to ghrelin in the stomach were almost completely abolished by hexamethonium and were significantly suppressed by the administration of phentolamine, prazosin, ondansetron, and naloxone. Additionally, N-nitro-l-arginine methylester significantly potentiated the contractions. Importantly, the mucosa is essential for ghrelin-induced, but not motilin-induced, gastric contractions. To evaluate the involvement of intrinsic primary afferent neurons (IPANs, which are multiaxonal neurons that pass signals from the mucosa to the myenteric plexus, we examined the effect of the IPAN-related pathway on ghrelin-induced contractions and found that pretreatment with adenosine and tachykinergic receptor 3 antagonists (SR142801 significantly eliminated the contractions and GR113808 (5-hydroxytryptamine receptor 4 antagonist almost completely eliminated it. The results indicate that ghrelin stimulates and modulates suncus gastric contractions through cholinergic, adrenergic, serotonergic, opioidergic neurons and nitric oxide synthases in the myenteric plexus. The mucosa is also important for ghrelin-induced gastric contractions, and IPANs may be the important interneurons that pass the signal from the mucosa to the myenteric plexus.

  8. Increased aerobic glycolysis through beta2 stimulation is a common mechanism involved in lactate formation during shock states.

    Science.gov (United States)

    Levy, Bruno; Desebbe, Olivier; Montemont, Chantal; Gibot, Sebastien

    2008-10-01

    During septic shock, muscle produces lactate by way of an exaggerated NaK-adenosine triphosphatase (ATPase)-stimulated aerobic glycolysis associated with epinephrine stimulation possibly through beta2 adrenoreceptor involvement. It therefore seems logical that a proportion of hyperlactatemia in low cardiac output states would be also related to this mechanism. Thus, in low-flow and normal-to-high-flow models of shock, we investigate (1) whether muscle produces lactate and (2) whether muscle lactate production is linked to beta2 adrenergic stimulation and Na+K+-ATPase. We locally modulated the adrenergic pathway and Na+K+-ATPase activity in male Wistar rats' skeletal muscle using microdialysis with nonselective and selective beta blockers and ouabain in different models of rodent shock (endotoxin, peritonitis, and hemorrhage). Blood flow at the probe site was evaluated by ethanol clearance. We measured the difference between muscle lactate and blood lactate concentration, with a positive gradient indicating muscle lactate or pyruvate production. Epinephrine levels were elevated in all shock groups. All models were associated with hypotension and marked hyperlactatemia. Muscle lactate concentrations were consistently higher than arterial levels, with a mean gradient of 2.5+/-0.3 in endotoxic shock, 2.1+/-0.2 mM in peritonitis group, and 0.9+/-0.2 mM in hemorrhagic shock (Pshock, 210+/-30 microM in peritonitis group, and 90+/-10 microM in hemorrhagic shock (Pshock mechanism. This demonstrates that lactate production during shock states is related, at least in part, to increased NaK-ATPase activity under beta2 stimulation. In shock state associated with a reduced or maintained blood flow, an important proportion of muscle lactate release is regulated by a beta2 receptor stimulation and not secondary to a reduced oxygen availability.

  9. Underlying mechanism of ASIC1a involved in acidosis-induced cytotoxicity in rat C6 glioma cells

    Institute of Scientific and Technical Information of China (English)

    Xie-chuan WENG; Jian-quan ZHENG; Jin LI; Wen-bin XIAO

    2007-01-01

    Aim:To investigate the underlying mechanism of acid-sensing ion channel (ASIC) la involved in the acidosis-induced cytotoxicity of rat C6 glioma cells. Methods:The stable ASICla-silenced C6 cells built with the RNA interference technology were confirmed by RT-PCR and Western blot analysis. Intracellular calcium ([Ca2+]i) in both the wild-type rat C6 glioma cells and the ASIC I a-silenced C6 cells were analyzed before and after acid application/exposure with the calcium imaging experiment. Results:The rapid extracellular pH drop induced the increase of [Ca2+]i in the wild-type C6 cells,but not in the ASICla-silenced C6 cells. During the prolonged acid exposure,[Ca2+]i was lower in the ASICla-silenced C6 cells than that in the control cells. Conclusion:The resultant toxicity of [Ca2+]i might contribute to the acidosis-induced cytotoxicity.

  10. Effects of benzo(a)pyrene on the skeletal development of Sebastiscus marmoratus embryos and the molecular mechanism involved

    Energy Technology Data Exchange (ETDEWEB)

    He Chengyong [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); Zuo Zhenghong [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China); Shi Xiao; Li Ruixia; Chen Donglei; Huang Xin; Chen Yixin [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); Wang Chonggang, E-mail: cgwang@xmu.edu.cn [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China)

    2011-01-25

    Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, which have been known to be carcinogenic and teratogenic. However, the skeletal development toxicity of PAHs and the mechanism involved remain unclear. In fishes, the neurocranial and craniofacial skeleton develop as cartilage. The signaling molecules of hedgehog (Hh) family play crucial roles in regulating skeletal development. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to benzo(a)pyrene (BaP) for 7 days at environmental levels (0.05, 0.5 and 5 nmol/L) which resulted in craniofacial skeleton deformities. BaP exposure reduced the cell proliferation activity in the craniofacial skeleton as detected by quantitative PCR and in situ hybridization. The expression of Sonic hedgehog (Shh), rather than Indian hedgehog (Ihh), was down-regulated in the craniofacial skeleton in the 0.5 and 5 nmol/L groups. Consistent with the Shh results, the expression of Ptch1 and Gli2 was decreased by BaP exposure and BMP4 was presented on changes in the 0.5 and 5 nmol/L groups. These results suggested that BaP could impair the expression and function of Shh signaling pathway, perturbing the proliferation of chondrocytes and so disturbing craniofacial skeletal development.

  11. Potential mechanisms involved in resistant phenotype of MCF-7 breast carcinoma cells to ionizing radiation induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yanling [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate School of Chinese Academy of Sciences, Beijing 100039 (China); Zhang Hong [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China)], E-mail: zhangh@impcas.ac.cn; Li Ning [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate School of Chinese Academy of Sciences, Beijing 100039 (China); Wang Xiaohu [Department of Radiotherapy, Gansu Tumor Hospital, Lanzhou 730050 (China); Hao Jifang [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Zhao Weiping [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate School of Chinese Academy of Sciences, Beijing 100039 (China)

    2009-03-15

    In the present study, we investigated the mechanisms of apoptosis resistance and the roles of the phosphorylation of BRCA1, p21, the Bax/Bcl-2 protein ratio and cell cycle arrest in IR-induced apoptosis in MCF-7 cells. X-irradiation, in particular at low dose (1 Gy), but not carbon ion irradiation, had a significant antiproliferative effect on the growth of MCF-7 cells. 1 Gy X-irradiation resulted in G1 and G2 phase arrest, but 4 Gy induced a significant G1 block. In contrast, carbon ion irradiation resulted in a significant accumulation in the G2 phase. Concomitant with the phosphorylation of H2AX induced by DNA damage, carbon ion irradiation resulted in an approximately 1.9-2.8-fold increase in the phosphorylation of BRCA1 on serine residue 1524, significantly greater than that detected for X-irradiation. Carbon ion irradiation caused a dramatic increase in p21 expression and drastic decrease in Bax expression compared with X-irradiation. The data implicated that phosphorylation of BRCA1 on serine residue 1524 might, at least partially, induce p21 expression but repress Bax expression. Together, our results suggested that the phosphorylation of BRCA1 at Ser-1524 might contribute to the G2 phase arrest and might be an upstream signal involved in preventing apoptosis signal via upregulation of p21 and downregulation of the Bax/Bcl-2 ratio.

  12. Uptake and phloem transport of glucose-fipronil conjugate in Ricinus communis involve a carrier-mediated mechanism.

    Science.gov (United States)

    Wu, Han-Xiang; Yang, Wen; Zhang, Zhi-Xiang; Huang, Ting; Yao, Guang-Kai; Xu, Han-Hong

    2012-06-20

    Some compounds containing glucose are absorbed via the monosaccharide transporters of the plasma membrane. A glucose-fipronil conjugate, N-[3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazol-5-yl]-1-(β-d-glucopyranosyl)-1H-1,2,3-triazole-4-methanamine (GTF), has been synthesized in our previous work. GTF exhibits moderate phloem mobility in Ricinus communis. In the current paper, we demonstrate that the uptake of GTF by Ricinus seedling cotyledon discs is partly mediated by an active carrier system (K(m)1 = 0.17 mM; V(max)1 = 2.2 nmol cm(-2) h(-1)). Four compounds [d-glucose, sucrose, phloridzin, and carbonyl cyanide m-chlorophenylhydrazone (CCCP)] were examined for their effect on GTF uptake. Phloridzin as well as CCCP markedly inhibit GTF uptake, and d-glucose weakly competes with it. The phloem transport of GTF in Ricinus seedlings is found to involve an active carrier-mediated mechanism that effectively contributes to the GTF phloem loading. The results prove that adding a glucose core is a reasonable and feasible approach to confer phloem mobility to fipronil by utilizing plant monosaccharide transporters.

  13. Gut microbiota-involved mechanisms in enhancing systemic exposure of ginsenosides by coexisting polysaccharides in ginseng decoction

    Science.gov (United States)

    Zhou, Shan-Shan; Xu, Jun; Zhu, He; Wu, Jie; Xu, Jin-Di; Yan, Ru; Li, Xiu-Yang; Liu, Huan-Huan; Duan, Su-Min; Wang, Zhuo; Chen, Hu-Biao; Shen, Hong; Li, Song-Lin

    2016-03-01

    Oral decoctions of traditional Chinese medicines (TCMs) serve for therapeutic and prophylactic management of diseases for centuries. Small molecules and polysaccharides are the dominant chemicals co-occurred in the TCM decoction. Small molecules are well-studied by multidisciplinary elaborations, whereas the role of polysaccharides remains largely elusive. Here we explore a gut microbiota-involved mechanism by which TCM polysaccharides restore the homeostasis of gut microbiota and consequently promote the systemic exposure of concomitant small molecules in the decoction. As a case study, ginseng polysaccharides and ginsenosides in Du-Shen-Tang, the decoction of ginseng, were investigated on an over-fatigue and acute cold stress model. The results indicated that ginseng polysaccharides improved intestinal metabolism and absorption of certain ginsenosides, meanwhile reinstated the perturbed holistic gut microbiota, and particularly enhanced the growth of Lactobacillus spp. and Bacteroides spp., two major metabolic bacteria of ginsenosides. By exploring the synergistic actions of polysaccharides with small molecules, these findings shed new light on scientization and rationalization of the classic TCM decoctions in human health care.

  14. Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved.

    Science.gov (United States)

    Bastide, Nadia M; Pierre, Fabrice H F; Corpet, Denis E

    2011-02-01

    Red meat and processed meat intake is associated with a risk of colorectal cancer, a major cause of death in affluent countries. Epidemiological and experimental evidence supports the hypothesis that heme iron present in meat promotes colorectal cancer. This meta-analysis of prospective cohort studies of colon cancer reporting heme intake included 566,607 individuals and 4,734 cases of colon cancer. The relative risk of colon cancer was 1.18 (95% CI: 1.06-1.32) for subjects in the highest category of heme iron intake compared with those in the lowest category. Epidemiological data thus show a suggestive association between dietary heme and risk of colon cancer. The analysis of experimental studies in rats with chemically-induced colon cancer showed that dietary hemoglobin and red meat consistently promote aberrant crypt foci, a putative precancer lesion. The mechanism is not known, but heme iron has a catalytic effect on (i) the endogenous formation of carcinogenic N-nitroso compounds and (ii) the formation of cytotoxic and genotoxic aldehydes by lipoperoxidation. A review of evidence supporting these hypotheses suggests that both pathways are involved in heme iron toxicity.

  15. Mechanisms involved in vitamin D mediated intestinal calcium absorption and in non-classical actions of vitamin D.

    Science.gov (United States)

    Christakos, Sylvia; Dhawan, Puneet; Ajibade, Dare; Benn, Bryan S; Feng, Jingjing; Joshi, Sneha S

    2010-07-01

    Recent studies in our laboratory using calbindin-D9k null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inducible epithelial calcium channel TRPV6 provide evidence for calbindin-D9k and TRPV6 independent regulation of active intestinal calcium absorption. These findings suggest that in the knock out (KO) mice there is compensation by another calcium channel or protein and that other novel factors are involved in 1,25(OH)2D3 mediated active intestinal calcium absorption. In addition, 1,25(OH)2D3 mediated paracellular transport of calcium may have contributed to the normalization of serum calcium in the null mutant mice. 1,25(OH)2D3 downregulates cadherin-17 and upregulates claudin-2 and claudin-12 in the intestine, suggesting that 1,25(OH)2D3, by regulating these epithelial cell junction proteins, can route calcium through the paracellular path. With regard to non-classical actions, 1,25(OH)2D3 has been reported to inhibit the proliferation of a number of malignant cells and to regulate adaptive as well as innate immunity. This article will review new developments related to the function and regulation of vitamin D target proteins in classical and non-classical vitamin D target tissues that have provided novel insight into mechanisms of vitamin D action.

  16. Clinical trial involving sufferers and non-sufferers of cervicogenic headache (CGH): potential mechanisms of action of photobiomodulation (Conference Presentation)

    Science.gov (United States)

    Liebert, Ann D.; Bicknell, Brian

    2017-02-01

    Photobiomodulation (PBM) is an effective tool for the management of spinal pain including inflammation of facet joints. Apart from cervical and lumbar joint pain the upper cervical spine facet joint inflammation can result in the CGH (traumatic or atraumatic in origin). This condition affects children, adults and elders and is responsible for 19% of chronic headache and up to 33% of patients in pain clinics. The condition responds well to physiotherapy, facet joint injection, radiofrequency neurotomy and surgery at a rate of 75%. The other 25% being unresponsive to treatment with no identified features of unresponsiveness. In other conditions of chronic unresponsive cervical pain have responded to photobiomodulation at a level of 80% in the short and medium term. A clinical trial was therefore conducted on a cohort of atraumatic patients from the ages of 5-93 (predominantly Neurologist referred / familial sufferers 2/3 generations vertically and laterally) who had responded to a course of PBM and physiotherapy. The CGH sufferers and their non CGH suffering relatives over these generations were then compared for features that distinguish the two groups. Fifty parameters were tested (anthropmetric, movement and neural tension tests included) and there was a noted difference in tandem stance between the groups (.04 significance with repeated measures). As this impairment is common to benign ataxia and migrainous vertigo and in these conditions there is an ion channelopathy (especially potassium channelopathy). A postulated mechanism of action of PBM would involve modulation of ion channels and this is discussed in this presentation.

  17. Plant-plant-microbe mechanisms involved in soil-borne disease suppression on a maize and pepper intercropping system.

    Directory of Open Access Journals (Sweden)

    Min Yang

    Full Text Available BACKGROUND: Intercropping systems could increase crop diversity and avoid vulnerability to biotic stresses. Most studies have shown that intercropping can provide relief to crops against wind-dispersed pathogens. However, there was limited data on how the practice of intercropping help crops against soil-borne Phytophthora disease. PRINCIPAL FINDINGS: Compared to pepper monoculture, a large scale intercropping study of maize grown between pepper rows reduced disease levels of the soil-borne pepper Phytophthora blight. These reduced disease levels of Phytophthora in the intercropping system were correlated with the ability of maize plants to form a "root wall" that restricted the movement of Phytophthora capsici across rows. Experimentally, it was found that maize roots attracted the zoospores of P. capsici and then inhibited their growth. When maize plants were grown in close proximity to each other, the roots produced and secreted larger quantities of 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H-one (DIMBOA and 6-methoxy-2-benzoxazolinone (MBOA. Furthermore, MBOA, benzothiazole (BZO, and 2-(methylthio-benzothiazole (MBZO were identified in root exudates of maize and showed antimicrobial activity against P. capsici. CONCLUSIONS: Maize could form a "root wall" to restrict the spread of P. capsici across rows in maize and pepper intercropping systems. Antimicrobe compounds secreted by maize root were one of the factors that resulted in the inhibition of P. capsici. These results provide new insights into plant-plant-microbe mechanisms involved in intercropping systems.

  18. The Deceptively Simple N170 Reflects Network Information Processing Mechanisms Involving Visual Feature Coding and Transfer Across Hemispheres

    Science.gov (United States)

    Ince, Robin A. A.; Jaworska, Katarzyna; Gross, Joachim; Panzeri, Stefano; van Rijsbergen, Nicola J.; Rousselet, Guillaume A.; Schyns, Philippe G.

    2016-01-01

    A key to understanding visual cognition is to determine “where”, “when”, and “how” brain responses reflect the processing of the specific visual features that modulate categorization behavior—the “what”. The N170 is the earliest Event-Related Potential (ERP) that preferentially responds to faces. Here, we demonstrate that a paradigmatic shift is necessary to interpret the N170 as the product of an information processing network that dynamically codes and transfers face features across hemispheres, rather than as a local stimulus-driven event. Reverse-correlation methods coupled with information-theoretic analyses revealed that visibility of the eyes influences face detection behavior. The N170 initially reflects coding of the behaviorally relevant eye contralateral to the sensor, followed by a causal communication of the other eye from the other hemisphere. These findings demonstrate that the deceptively simple N170 ERP hides a complex network information processing mechanism involving initial coding and subsequent cross-hemispheric transfer of visual features. PMID:27550865

  19. Mechanisms involved in the hydrothermal growth of ultra-thin and high aspect ratio ZnO nanowires

    Science.gov (United States)

    Demes, Thomas; Ternon, Céline; Morisot, Fanny; Riassetto, David; Legallais, Maxime; Roussel, Hervé; Langlet, Michel

    2017-07-01

    Hydrothermal synthesis of ZnO nanowires (NWs) with tailored dimensions, notably high aspect ratios (AR) and small diameters, is a major concern for a wide range of applications and still represents a challenging and recurring issue. In this work, an additive-free and reproducible hydrothermal procedure has been developed to grow ultra-thin and high AR ZnO NWs on sol-gel deposited ZnO seed layers. Controlling the substrate temperature and using a low reagent concentration (1 mM) has been found to be essential for obtaining such NWs. We show that the NW diameter remains constant at about 20-25 nm with growth time contrary to the NW length that can be selectively increased leading to NWs with ARs up to 400. On the basis of investigated experimental conditions along with thermodynamic and kinetic considerations, a ZnO NW growth mechanism has been developed which involves the formation and growth of nuclei followed by NW growth when the nuclei reach a critical size of about 20-25 nm. The low reagent concentration inhibits NW lateral growth leading to ultra-thin and high AR NWs. These NWs have been assembled into electrically conductive ZnO nanowire networks, which opens attractive perspectives toward the development of highly sensitive low-cost gas- or bio-sensors.

  20. Involvement of oxidative stress in the mechanism of p,p'-DDT-induced nephrotoxicity in adult rats.

    Science.gov (United States)

    Marouani, Neila; Hallegue, Dorsaf; Sakly, Mohsen; Benkhalifa, Moncef; Ben Rhouma, Khémais; Tebourbi, Olfa

    2017-07-01

    The 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (p,p'-DDT) is an organochlorine pesticide that persists in the environment and has a risk to human health. We investigated whether p,p'-DDT-induces nephrotoxicity in rats and whether oxidative stress and apoptosis are involved in the pathogenesis of this process. Male rats received the pesticide at doses of 50 and 100 mg/kg for 10 days. Renal damage was evaluated by histopathological examination and serum markers. The oxidative stress was evaluated by lipid peroxidation (LPO), metallothioneins (MTs) and protein carbonyl levels. Antioxidant enzymes were assessed by determination of superoxide dismutase (SOD) and catalase (CAT) activities. Glutathione-dependent enzymes and reducing power in kidney were evaluated by glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) activities. Renal tubular cells apoptosis was assessed through the TUNEL assay. After 10 days of treatment, an increase of serum creatinine and urea levels occurred, LPO and protein carbonyl levels were increased, while MTs level, SOD and CAT activities were decreased. Besides, the GPx, GR, GST, and GSH activities were decreased. Histological alterations in kidney tissue and intense apoptosis in renal tubular cells were observed. These results suggest that DDT sub-acute treatment causes oxidative stress and apoptosis, which may be the chief mechanisms of DDT-induced nephrotoxicity.

  1. The general practitioner as the first contacted health professional by patients with psychosocial problems: a European study.

    NARCIS (Netherlands)

    Boerma, W.G.W.; Verhaak, P.F.M.

    1999-01-01

    Background: there are considerable differences between and within countries in the involvement of general practitioners (GPs) in psychosocial care. This study aimed to describe the self-perceived role of GPs in 30 European countries as the first contacted professional for patients with psychosocial

  2. Newt tail regeneration: a model for gravity-dependent morphogenesis and clues to the molecular mechanisms involved.

    Science.gov (United States)

    Radugina, Elena A.; Almeida, Eduardo; Grigoryan, Eleonora

    factors and are expressed during development, we hypothesized they may play a role newt tail regenerative morphogenesis under altered g-levels. Specifically there is increasing evidence for HSPs expression changes as a result of hyper-and microgravity. HSPs are also expressed throughout regeneration, rather than just after surgery. To test this hypothesis we performed heat shock on intact and regenerating newts and collected tail tissues. In these experiments we observed that some tails had uplifted tips while others mimicked hook-like regenerates at 1g or 2g. These findings suggest that heat shock, and HSPs induction, may be involved in the mechanism responsible for gravity effects on morphogenesis, or at least interact with them. Current work underway is focused on analyzing the expression of mRNA and localization of proteins for two members of the group, Hsp70 and Hsp90. In summary, we developed and characterized a new practical animal model in which gravity mechanostimulation at 1g, versus unloading in aquaria, causes prominent effects on newt tail regenerative morphogenesis. This model can be achieved without the use of a centrifuge, significantly simplifying its research applications. Initial results using this model suggest that induction of HSPs may be involved in gravity regulation of newt tail regenerative morphogenesis. Further research based on this simple model may help to unravel mechanisms of gravity influence relevant not only to newt tail regeneration, but also to a broad range of other biological processes in amphibian models.

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

    OpenAIRE

    CHISNOIU, ANDREA MARIA; PICOS, ALINA MONICA; POPA, SEVER; CHISNOIU, PETRE DANIEL; LASCU, LIANA; PICOS, ANDREI; CHISNOIU, RADU

    2015-01-01

    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...

  4. Gender based violence and psychosocial intervention at Quito. Weaving narratives to construct new meanings

    Directory of Open Access Journals (Sweden)

    Paz Guarderas

    2014-11-01

    Full Text Available Very few studies have been done in Ecuador on psychosocial interventions involving gender violence. This article, based on research carried out in Quito with people who have experienced this type of violence, is intended to contribute to the debate on the subject. Through narrative production methodology, we hope to construct new meanings of psychosocial intervention and gender violence. The participants offer conceptions of gender violence that go beyond aspects usually taken into account in the creation of laws and services. They point out that current psychosocial intervention in response to gender violence tends to homogenize women, providing services that reduce these situations to woman/victim-man/perpetrator scenarios.

  5. Psycho-social reflections on craniofacial morphogenesis.

    Science.gov (United States)

    Partridge, James

    2010-05-01

    Psychologists are now increasingly involved in understanding the challenges faced by people who experience facial disfigurements from many causes (congenital, traumatic, oncological, iatrogenic, neurological, ophthalmological or dermatological). This article describes how the author has combined the lessons of his personal recovery after severe facial burns with the rigorous science of psychological research to enable improved psycho-social support and interventions to be developed, through a UK not-for-profit (Changing Faces) and in formal health care services. It suggests that against the background of a culture that is less-than-positive about disfigurement, anyone who experiences it needs access to a range of support, advice, counselling and social skills training to enable them to live full, confident lives.

  6. Genetic mechanisms involved in the evolution of the cephalopod camera eye revealed by transcriptomic and developmental studies

    Directory of Open Access Journals (Sweden)

    Ogura Atsushi

    2011-06-01

    Full Text Available Abstract Background Coleoid cephalopods (squids and octopuses have evolved a camera eye, the structure of which is very similar to that found in vertebrates and which is considered a classic example of convergent evolution. Other molluscs, however, possess mirror, pin-hole, or compound eyes, all of which differ from the camera eye in the degree of complexity of the eye structures and neurons participating in the visual circuit. Therefore, genes expressed in the cephalopod eye after divergence from the common molluscan ancestor could be involved in eye evolution through association with the acquisition of new structural components. To clarify the genetic mechanisms that contributed to the evolution of the cephalopod camera eye, we applied comprehensive transcriptomic analysis and conducted developmental validation of candidate genes involved in coleoid cephalopod eye evolution. Results We compared gene expression in the eyes of 6 molluscan (3 cephalopod and 3 non-cephalopod species and selected 5,707 genes as cephalopod camera eye-specific candidate genes on the basis of homology searches against 3 molluscan species without camera eyes. First, we confirmed the expression of these 5,707 genes in the cephalopod camera eye formation processes by developmental array analysis. Second, using molecular evolutionary (dN/dS analysis to detect positive selection in the cephalopod lineage, we identified 156 of these genes in which functions appeared to have changed after the divergence of cephalopods from the molluscan ancestor and which contributed to structural and functional diversification. Third, we selected 1,571 genes, expressed in the camera eyes of both cephalopods and vertebrates, which could have independently acquired a function related to eye development at the expression level. Finally, as experimental validation, we identified three functionally novel cephalopod camera eye genes related to optic lobe formation in cephalopods by in situ

  7. Metabotropic glutamate receptor 7 modulates the rewarding effects of cocaine in rats: involvement of a ventral pallidal GABAergic mechanism.

    Science.gov (United States)

    Li, Xia; Li, Jie; Peng, Xiao-Qing; Spiller, Krista; Gardner, Eliot L; Xi, Zheng-Xiong

    2009-06-01

    The metabotropic glutamate receptor 7 (mGluR7) has received much attention as a potential target for the treatment of epilepsy, major depression, and anxiety. In this study, we investigated the possible involvement of mGluR7 in cocaine reward in animal models of drug addiction. Pretreatment with the selective mGluR7 allosteric agonist N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082; 1-20 mg/kg, i.p.) dose-dependently inhibited cocaine-induced enhancement of electrical brain-stimulation reward and intravenous cocaine self-administration under both fixed-ratio and progressive-ratio reinforcement conditions, but failed to alter either basal or cocaine-enhanced locomotion or oral sucrose self-administration, suggesting a specific inhibition of cocaine reward. Microinjections of AMN082 (1-5 microg/microl per side) into the nucleus accumbens (NAc) or ventral pallidum (VP), but not dorsal striatum, also inhibited cocaine self-administration in a dose-dependent manner. Intra-NAc or intra-VP co-administration of 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP, 5 microg/microl per side), a selective mGluR7 allosteric antagonist, significantly blocked AMN082's action, suggesting an effect mediated by mGluR7 in these brain regions. In vivo microdialysis demonstrated that cocaine (10 mg/kg, i.p.) priming significantly elevated extracellular DA in the NAc or VP, while decreasing extracellular GABA in VP (but not in NAc). AMN082 pretreatment selectively blocked cocaine-induced changes in extracellular GABA, but not in DA, in both naive rats and cocaine self-administration rats. These data suggest: (1) mGluR7 is critically involved in cocaine's acute reinforcement; (2) GABA-, but not DA-, dependent mechanisms in the ventral striatopallidal pathway appear to underlie AMN082's actions; and (3) AMN082 or other mGluR7-selective agonists may be useful in the treatment of cocaine addiction.

  8. Psychosocial Interventions in Depressive Disorders

    Directory of Open Access Journals (Sweden)

    Ceyda Basogul

    2015-03-01

    Full Text Available In the last ten years, improvements in effective psychosocial interventions in the prevention and treatment of depression are remarkable. The World Health Organization stated that major depression affects children, adults and the elderly and is the leading cause of approximately 12% of all disabilities around the World. Medical expenses, loss of workforce, suicide risk, the risk of relapse or recurrence are taken into account, depression is an issue that needs to be handled with utmost care for health care workers especially psychiatric nurses. The purpose of this literature review is to examine psychosocial interventions and effectiveness of these interventions for depressive disorders shows a gradual increase in prevalence in worlwide. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(1: 1-15

  9. Psychosocial rehabilitation in developing countries.

    Science.gov (United States)

    Rangaswamy, Thara; Sujit, John

    2012-10-01

    Psychosocial rehabilitation (PSR) is an essential component in the management of schizophrenia. It is especially relevant in the improvement of functioning and the quality of life of these individuals. The scarcity of mental health personnel and lack of training in many low and middle income countries (LAMIC) has led to low priority being accorded to PSR. This paper describes some of the PSR initiatives in LAMIC, especially those undertaken after disasters, home-based interventions and community-based rehabilitation programmes.

  10. Adult attachment and psychosocial functioning

    OpenAIRE

    Pielage, Suzanne Brenda

    2006-01-01

    In the trilogy Attachment, Separation and Loss (1969, 1973, 1980), Bowlby theorized that early experiences with caregivers affect the quality of individuals’ later (romantic) relationships and, consequently, their mental health. The current thesis set out to examine the relationships between adult attachment and psychosocial functioning, predominately in the realm of close relationships. In the first part of the thesis, the focus lay on the assessment of the adult attachment construct. In Cha...

  11. Antimanic-like activity of candesartan in mice: Possible involvement of antioxidant, anti-inflammatory and neurotrophic mechanisms.

    Science.gov (United States)

    de Souza Gomes, Júlia Ariana; de Souza, Greicy Coelho; Berk, Michael; Cavalcante, Lígia Menezes; de Sousa, Francisca Cléa F; Budni, Josiane; de Lucena, David Freitas; Quevedo, João; Carvalho, André F; Macêdo, Danielle

    2015-11-01

    Activation of the brain angiotensin II type 1 receptor (AT1R) triggers pro-oxidant and pro-inflammatory mechanisms which are involved in the neurobiology of bipolar disorder (BD). Candesartan (CDS) is an AT1 receptor antagonist with potential neuroprotective properties. Herein we investigated CDS effects against oxidative, neurotrophic inflammatory and cognitive effects of amphetamine (AMPH)-induced mania. In the reversal protocol adult mice were given AMPH 2 mg/kg i.p. or saline and between days 8 and 14 received CDS 0.1, 0.3 or 1 mg/kg orally, lithium (Li) 47.5 mg/kg i.p., or saline. In the prevention treatment, mice were pretreated with CDS, Li or saline prior to AMPH. Locomotor activity and working memory performance were assessed. Glutathione (GSH), thiobarbituric acid-reactive substance (TBARS) and TNF-α levels were evaluated in the hippocampus (HC) and cerebellar vermis (CV). Brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase 3-beta (GSK-3beta) levels were measured in the HC. CDS and Li prevented and reversed the AMPH-induced increases in locomotor activity. Only CDS prevented and reversed AMPH-induced working memory deficits. CDS prevented AMPH-induced alterations in GSH (HC and CV), TBARS (HC and CV), TNF-α (HC and CV) and BDNF (HC) levels. Li prevented alterations in BDNF and phospho-Ser9-GSK3beta. CDS reversed AMPH-induced alterations in GSH (HC and CV), TBARS (HC), TNF-α (CV) and BDNF levels. Li reversed AMPH-induced alterations in TNF-α (HC and CV) and BDNF (HC) levels. CDS is effective in reversing and preventing AMPH-induced behavioral and biochemical alterations, providing a rationale for the design of clinical trials investigating CDS׳s possible therapeutic effects.

  12. The asymmetric binding of PGC-1α to the ERRα and ERRγ nuclear receptor homodimers involves a similar recognition mechanism.

    Directory of Open Access Journals (Sweden)

    Maria Takacs

    Full Text Available BACKGROUND: PGC-1α is a crucial regulator of cellular metabolism and energy homeostasis that functionally acts together with the estrogen-related receptors (ERRα and ERRγ in the regulation of mitochondrial and metabolic gene networks. Dimerization of the ERRs is a pre-requisite for interactions with PGC-1α and other coactivators, eventually leading to transactivation. It was suggested recently (Devarakonda et al that PGC-1α binds in a strikingly different manner to ERRγ ligand-binding domains (LBDs compared to its mode of binding to ERRα and other nuclear receptors (NRs, where it interacts directly with the two ERRγ homodimer subunits. METHODS/PRINCIPAL FINDINGS: Here, we show that PGC-1α receptor interacting domain (RID binds in an almost identical manner to ERRα and ERRγ homodimers. Microscale thermophoresis demonstrated that the interactions between PGC-1α RID and ERR LBDs involve a single receptor subunit through high-affinity, ERR-specific L3 and low-affinity L2 interactions. NMR studies further defined the limits of PGC-1α RID that interacts with ERRs. Consistent with these findings, the solution structures of PGC-1α/ERRα LBDs and PGC-1α/ERRγ LBDs complexes share an identical architecture with an asymmetric binding of PGC-1α to homodimeric ERR. CONCLUSIONS/SIGNIFICANCE: These studies provide the molecular determinants for the specificity of interactions between PGC-1α and the ERRs, whereby negative cooperativity prevails in the binding of the coactivators to these receptors. Our work indicates that allosteric regulation may be a general mechanism controlling the binding of the coactivators to homodimers.

  13. The Ang II-induced growth of vascular smooth muscle cells involves a phospholipase D-mediated signaling mechanism.

    Science.gov (United States)

    Freeman, E J

    2000-02-15

    Angiotensin (Ang) II acts as a mitogen in vascular smooth muscle cells (VSMC) via the activation of multiple signaling cascades, including phospholipase C, tyrosine kinase, and mitogen-activated protein kinase pathways. However, increasing evidence supports signal-activated phospholipases A(2) and D (PLD) as additional mechanisms. Stimulation of PLD results in phosphatidic acid (PA) formation, and PA has been linked to cell growth. However, the direct involvement of PA or its metabolite diacylglycerol (DAG) in Ang II-induced growth is unclear. PLD activity was measured in cultured rat VSMC prelabeled with [(3)H]oleic acid, while the incorporation of [(3)H]thymidine was used to monitor growth. We have previously reported the Ang II-dependent, AT(1)-coupled stimulation of PLD and growth in VSMC. Here, we show that Ang II (100 nM) and exogenous PLD (0.1-100 units/mL; Streptomyces chromofuscus) stimulated thymidine incorporation (43-208% above control). PA (100 nM-1 microM) also increased thymidine incorporation to 135% of control. Propranolol (100 nM-10 microM), which inhibits PA phosphohydrolase, blocked the growth stimulated by Ang II, PLD, or PA by as much as 95%, an effect not shared by other beta-adrenergic antagonists. Propranolol also increased the production of PA in the presence of Ang II by 320% and reduced DAG and arachidonic acid (AA) accumulation. The DAG lipase inhibitor RHC-80267 (1-10 microM) increased Ang II-induced DAG production, while attenuating thymidine incorporation and release of AA. Thus, it appears that activation of PLD, formation of PA, conversion of PA to DAG, and metabolism of DAG comprise an important signaling cascade in Ang II-induced growth of VSMC.

  14. Mechanisms involved in the anti-inflammatory action of a polysulfated fraction from Gracilaria cornea in rats.

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    Chistiane Oliveira Coura

    Full Text Available The anti-inflammatory mechanisms of the sulfated polysaccharidic fraction obtained from red marine alga Gracilaria cornea (Gc-FI were investigated using a paw edema model induced in rats by different inflammatory agents (carrageenan, dextran, serotonin, bradykinin, compound 48/80 or L-arginine. Gc-FI at the doses of 3, 9 or 27 mg/kg, subcutaneously--s.c., significantly inhibited rat paw edema induced by carrageenan and dextran, as confirmed by myeloperoxidase and Evans' blue assessments, respectively. Gc-FI (9 mg/kg, s.c. inhibited rat paw edema induced by histamine, compound 48/80 and L-arginine. Additionally, Gc-FI (9 mg/kg, s.c. inhibited Cg-induced edema in animals with intact mast cells but did not inhibit that with degranulated mast cells by compound 48/80, revealing a protective role on mast cell membranes. Gc-FI down-regulated the IL-1β, TNF-α and COX-2 mRNA and protein levels compared with those of the carrageenan group, based on qRT-PCR and immunohistochemistry analyses. After inhibition with ZnPP IX, a specific heme oxygenase-1 (HO-1 inhibitor, the anti-inflammatory effect of Gc-FI was not observed in Cg-induced paw edema, suggesting that the anti-inflammatory effect of Gc-FI is, in part, dependent on the integrity of the HO-1 pathway. Gc-FI can target a combination of multiple points involved in inflammatory phenomena.

  15. Mechanisms involved in the anti-inflammatory action of a polysulfated fraction from Gracilaria cornea in rats.

    Science.gov (United States)

    Coura, Chistiane Oliveira; Souza, Ricardo Basto; Rodrigues, José Ariévilo Gurgel; Vanderlei, Edfranck de Sousa Oliveira; de Araújo, Ianna Wivianne Fernandes; Ribeiro, Natássia Albuquerque; Frota, Annyta Fernandes; Ribeiro, Kátia Alves; Chaves, Hellíada Vasconcelos; Pereira, Karuza Maria Alves; da Cunha, Rodrigo Maranguape Silva; Bezerra, Mirna Marques; Benevides, Norma Maria Barros

    2015-01-01

    The anti-inflammatory mechanisms of the sulfated polysaccharidic fraction obtained from red marine alga Gracilaria cornea (Gc-FI) were investigated using a paw edema model induced in rats by different inflammatory agents (carrageenan, dextran, serotonin, bradykinin, compound 48/80 or L-arginine). Gc-FI at the doses of 3, 9 or 27 mg/kg, subcutaneously--s.c., significantly inhibited rat paw edema induced by carrageenan and dextran, as confirmed by myeloperoxidase and Evans' blue assessments, respectively. Gc-FI (9 mg/kg, s.c.) inhibited rat paw edema induced by histamine, compound 48/80 and L-arginine. Additionally, Gc-FI (9 mg/kg, s.c.) inhibited Cg-induced edema in animals with intact mast cells but did not inhibit that with degranulated mast cells by compound 48/80, revealing a protective role on mast cell membranes. Gc-FI down-regulated the IL-1β, TNF-α and COX-2 mRNA and protein levels compared with those of the carrageenan group, based on qRT-PCR and immunohistochemistry analyses. After inhibition with ZnPP IX, a specific heme oxygenase-1 (HO-1) inhibitor, the anti-inflammatory effect of Gc-FI was not observed in Cg-induced paw edema, suggesting that the anti-inflammatory effect of Gc-FI is, in part, dependent on the integrity of the HO-1 pathway. Gc-FI can target a combination of multiple points involved in inflammatory phenomena.

  16. Mast cells phagocyte Candida albicans and produce nitric oxide by mechanisms involving TLR2 and Dectin-1.

    Science.gov (United States)

    Pinke, Karen Henriette; Lima, Heliton Gustavo de; Cunha, Fernando Queiroz; Lara, Vanessa Soares

    2016-02-01

    Candida albicans (C. albicans) is a fungus commonly found in the human mucosa, which may cause superficial and systemic infections, especially in immunosuppression. Until now, the main actors in the defense against this fungus are the epithelial cells, neutrophils, macrophages/monocytes and dendritic cells. However, mast cells are strategically located to play a first line of anti-Candida defense and it has appropriate mechanisms to do it. As with other cells, the recognition of C. albicans occurs meanly via TLR2 and Dectin-1. We assess the TLR2/Dectin-1 involvement in phagocytosis and production of nitric oxide (NO) and reactive oxygen species (ROS) by mast cells challenged with C. albicans. Bone marrow-derived mast cells (MC) from wild type (Wt) or knockout (TLR2-/-) mice C57BL/6 were subjected to in vitro Dectin-1 blockade. After challenged with FITC-labeled C. albicans or zymosan, phagocytosis was analyzed by microscopy. The intracellular production of NO and ROS was measured by DAF-FM diacetate and CellROX Deep/Red Reagent kits. The nitrite formation and hydrogen peroxide release were analyzed by Griess reaction and Amplex Red Hydrogen Peroxide/Peroxidase Assay Kit. Wt/MC phagocytose C. albicans with production of intracellular NO, but not ROS. Moreover, increased levels of nitrite were also observed. The absence and/or blockade of TLR2/Dectin-1 caused significant decreased in C. albicans phagocytosis and NO production. Our results showed that mast cells are able to phagocytose and produce NO against C. albicans via TLR2/Dectin-1. Therefore, mast cells could be important during the course of Candida infection and as a therapeutic target.

  17. Mecanismos moleculares implicados en las enfermedades cardiovasculares aterotrombóticas Molecular mechanisms involved in atherothrombotic cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Judith Borrero Sánchez

    2012-09-01

    Full Text Available El síndrome coronario agudo es un problema de salud y constituye la primera causa de muerte en el mundo desarrollado y en Cuba. Esta enfermedad, que incluye infarto de miocardio, angina de pecho y muerte súbita, causa más muertes cada año que el resto de las enfermedades combinadas. El factor causal de mayor relevancia del infarto del miocardio, radica en la formación y evolución crónica de un ateroma, o eventos que son favorecidos por el estrés oxidativo, las citocinas proinflamatorias, la trombina y el no control de los factores de riesgo. La presente revisión se realizó con el propósito de explicar los mecanismos moleculares y la influencia de los factores de riesgo implicados en la fisiopatología de estas enfermedades. Se concluyó que las especies reactivas del oxígeno y el estrés oxidativo, desempeñan un papel importante en la fisiopatología de estas afecciones cardiovasculares, de relevancia para el diagnóstico y la terapéutica.Acute coronary syndrome is a health problem and is the leading cause of death in Europe, North America, and Cuba. This disease, which includes heart attack, angina and sudden death, causes more deaths each year than all other diseases combined. The most important causal factor of myocardial infarction lies in the formation and chronic evolution of atheroma, or events that are favored by oxidative stress, proinflammatory cytokines, thrombin and no control of risk factors. This review was conducted in order to explain the molecular mechanisms and the influence of the risk factors involved in the pathophysiology of these diseases. It was concluded that reactive oxygen species and oxidative stress play an important role in the pathophysiology of such cardiovascular disorders, of relevance for its diagnosis and therapy.

  18. Slimmer or fertile? Pharmacological mechanisms involved in reduced sperm quality and fertility in rats exposed to the anorexigen sibutramine.

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    Cibele S Borges

    Full Text Available Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin

  19. Psychosocial work environment and prediction of quality of care indicators in one Canadian health center.

    Science.gov (United States)

    Paquet, Maxime; Courcy, François; Lavoie-Tremblay, Mélanie; Gagnon, Serge; Maillet, Stéphanie

    2013-05-01

    Few studies link organizational variables and outcomes to quality indicators. This approach would expose operant mechanisms by which work environment characteristics and organizational outcomes affect clinical effectiveness, safety, and quality indicators. What are the predominant psychosocial variables in the explanation of organizational outcomes and quality indicators (in this case, medication errors and length of stay)? The primary objective of this study was to link the fields of evidence-based practice to the field of decision making, by providing an effective model of intervention to improve safety and quality. The study involved healthcare workers (n = 243) from 13 different care units of a university affiliated health center in Canada. Data regarding the psychosocial work environment (10 work climate scales, effort/reward imbalance, and social support) was linked to organizational outcomes (absenteeism, turnover, overtime), to the nurse/patient ratio and quality indicators (medication errors and length of stay) using path analyses. The models produced in this study revealed a contribution of some psychosocial factors to quality indicators, through an indirect effect of personnel- or human resources-related variables, more precisely: turnover, absenteeism, overtime, and nurse/patient ratio. Four perceptions of work environment appear to play an important part in the indirect effect on both medication errors and length of stay: apparent social support from supervisors, appreciation of the workload demands, pride in being part of one's work team, and effort/reward balance. This study reveals the importance of employee perceptions of the work environment as an indirect predictor of quality of care. Working to improve these perceptions is a good investment for loyalty and attendance. In general, better personnel conditions lead to fewer medication errors and shorter length of stay. © Sigma Theta Tau International.

  20. Socio-demographic characteristics and psychosocial consequences of sickle cell disease: the case of patients in a public hospital in Ghana.

    Science.gov (United States)

    Adzika, Vincent A; Glozah, Franklin N; Ayim-Aboagye, Desmond; Ahorlu, Collins S K

    2017-01-31

    Sickle cell disease (SCD) is of major public health concern globally, with majority of patients living in Africa. Despite its relevance, there is a dearth of research to determine the socio-demographic distribution and psychosocial impact of SCD in Ghana. The objective of this study was to examine the socio-demographic distribution and psychosocial consequences of SCD among patients in Ghana and to assess their quality of life and coping mechanisms. A cross-sectional research design was used that involved the completion of questionnaires on socio-demographic characteristics, quality of life, coping mechanisms, anxiety and depression. Participants were 387 male and female patients attending a sickle cell clinic in a public hospital. Results showed that majority of the patients were single, female, less than 39 years old and had attained secondary school level of education or less. Also, patients were more satisfied by the presence of love, friends and relatives as well as home, community and neighbourhood environment. While pains of varied nature and severity were the major reasons for attending hospital in SCD condition, going to the hospital as well as having faith in God was the most frequently reported mechanisms for coping with an unbearable SCD attacks. Results of multiple regression analysis showed that some socio-demographic and quality of life indicators had strong associations with anxiety and/or depression. It is recommended that a holistic intervention strategy incorporating psychosocial dimensions should be considered in the treatment and management of SCD.

  1. Identification of mechanisms involved in the relaxation of rabbit cavernous smooth muscle by a new nitric oxide donor ruthenium compound

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    João Batista Gadelha de Cerqueira

    2012-10-01

    Full Text Available PURPOSE: The aim of this study was to evaluate the relaxation in vitro of cavernous smooth muscle induced by a new NO donor of the complex nitrosil-ruthenium, named trans-[Ru(NH34(caffeine(NO]C13 (Rut-Caf and sodium nitroprusside (SNP. MATERIALS AND METHODS: The tissues, immersed in isolated bath systems, were pre-contracted with phenilephrine (PE (1 µM and then concentration-response curves (10-12 - 10-4 M were obtained. To clarify the mechanism of action involved, it was added to the baths ODQ (10 µM, 30 µM, oxyhemoglobin (10 µM, L-cysteine (100 µM, hydroxicobalamine (100 µM, glibenclamide, iberotoxin and apamine. Tissue samples were frozen in liquid nitrogen to measure the amount of cGMP and cAMP produced. RESULTS: The substances provoked significant relaxation of the cavernous smooth muscle. Both Rut-Caf and SNP determined dose-dependent relaxation with similar potency (pEC50 and maximum effect (Emax. The substances showed activity through activation of the soluble guanylyl cyclase (sGC, because the relaxations were inhibited by ODQ. Oxyhemoglobin significantly diminished the relaxation effect of the substances. L-cysteine failed to modify the relaxations caused by the agents. Hydroxicobalamine significantly diminished the relaxation effect of Rut-Caf. Glibenclamide significantly increased the efficacy of Rut-Caf (pEC50 4.09 x 7.09. There were no alterations of potency or maximum effect of the substances with the addition of the other ion channel blockers. Rut-Caf induced production of significant amounts of cGMP and cAMP during the relaxation process. CONCLUSIONS: In conclusion, Rut-Caf causes relaxation of smooth muscle of corpus cavernosum by means of activation of sGC with intracellular production of cGMP and cAMP; and also by release of NO in the intracellular environment. Rut-Caf releases the NO free radical and it does not act directly on the potassium ion channels.

  2. Thermodynamic analysis of ionizable groups involved in the catalytic mechanism of human matrix metalloproteinase 7 (MMP-7).

    Science.gov (United States)

    Takeharu, Hitoshi; Yasukawa, Kiyoshi; Inouye, Kuniyo

    2011-12-01

    Human matrix metalloproteinase 7 (MMP-7) exhibits a broad bell-shaped pH-dependence with the acidic and alkaline pK(e) (pK(e1) and pK(e2)) values of about 4 and 10. In this study, we estimated the ionizable groups involved in its catalytic mechanism by thermodynamic analysis. pK(a) of side chains of L-Asp, L-Glu, L-His, L-Cys, L-Tyr, L-Lys, and L-Arg at 25-45°C were determined by the pH titration of amino-acid solutions, from which their enthalpy changes, ∆H°, of deprotonation were calculated. pK(e1) and pK(e2) of MMP-7 at 15-45°C were determined in the hydrolysis of (7-methoxycoumarin-4-yl)acetyl-L-Pro-L-Leu-Gly-L-Leu-[N(3)-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl]-L-Ala-L-Arg-NH(2), from which ∆H(o) for pK(e1) and pK(e2) was calculated. The ∆H(o) for pK(e1) (-20.6±6.1kJmol(-1)) was similar to that for L-Glu (-23.6±5.8kJmol(-1)), and the ∆H(o) for pK(e2) (89.9±4.0kJmol(-1)) was similar to those for L-Arg (87.6±5.5kJmol(-1)) and L-Lys (70.4±4.4kJmol(-1)). The mutation of the active-site residue Glu198 into Ala completely abolished the activity, suggesting that Glu198 is the ionizable group for pK(e1). On the other hand, no arginine or lysine residues are found in the active site of MMP-7. We proposed a possibility that a protein-bound water is the ionizable group for pK(e2).

  3. Study of the mechanisms involved in the vasorelaxation induced by (−)-epigallocatechin-3-gallate in rat aorta

    Science.gov (United States)

    Álvarez, Ezequiel; Campos-Toimil, Manuel; Justiniano-Basaran, Hélène; Lugnier, Claire; Orallo, Francisco

    2005-01-01

    This study investigated several mechanisms involved in the vasorelaxant effects of (−)-epigallocatechin-3-gallate (EGCG). EGCG (1 μM–1 mM) concentration dependently relaxed, after a transient increase in tension, contractions induced by noradrenaline (NA, 1 μM), high extracellular KCl (60 mM), or phorbol 12-myristate 13-acetate (PMA, 1 μM) in intact rat aortic rings. In a Ca2+-free solution, EGCG (1 μM–1 mM) relaxed 1 μM PMA-induced contractions, without previous transient contraction. However, EGCG (1 μM–1 mM) did not affect the 1 μM okadaic acid-induced contractions. Removal of endothelium and/or pretreatment with glibenclamide (10 μM), tetraethylammonium (2 mM) or charybdotoxin (100 nM) plus apamin (500 nM) did not modify the vasorelaxant effects of EGCG. In addition, EGCG noncompetitively antagonized the contractions induced by NA (in 1.5 mM Ca2+-containing solution) and Ca2+ (in depolarizing Ca2+-free high KCl 60 mM solution). In rat aortic smooth muscle cells (RASMC), EGCG (100 μM) reduced increases in cytosolic free Ca2+ concentration ([Ca2+]i) induced by angiotensin II (ANG II, 100 nM) and KCl (60 mM) in 1.5 mM CaCl2-containing solution and by ANG II (100 nM) in the absence of extracellular Ca2+. In RASMC, EGCG (100 μM) did not modify basal generation of cAMP or cGMP, but significantly reversed the inhibitory effects of NA (1 μM) and high KCl (60 mM) on cAMP and cGMP production. EGCG inhibited the enzymatic activity of all the cyclic nucleotide PDE isoenzymes present in vascular tissue, being more effective on PDE2 (IC50∼17) and on PDE1 (IC50∼25). Our results suggest that the vasorelaxant effects of EGCG in rat aorta are mediated, at least in part, by an inhibition of PDE activity, and the subsequent increase in cyclic nucleotide levels in RASMC, which, in turn, can reduce agonist- or high KCl concentration-induced increases in [Ca2+]i. PMID:16299547

  4. Low prosocial attachment, involvement with drug-using peers, and adolescent drug use: a longitudinal examination of mediational mechanisms.

    Science.gov (United States)

    Henry, Kimberly L

    2008-06-01

    The process of disengagement from prosocial entities (e.g., family and school) and either simultaneous or subsequent engagement with antisocial entities (e.g., friends who use drugs) is a critical contributor to adolescent drug use and delinquency. This study provides a series of formal mediation tests to demonstrate the relationship between poor family attachment, poor school attachment, involvement with friends who use drugs, and a student's own use of drugs. Results indicate that poor family attachment exerts its effect on drug use through poor school attachment and involvement with friends who use drugs. In addition, poor school attachment exerts its effect on drug use through involvement with friends who use drugs. The results of this study corroborate theories that suggest disengagement from prosocial entities is associated with involvement with antisocial entities and eventual involvement in drug use. Implications for prevention strategies are discussed.

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

    Science.gov (United States)

    CHISNOIU, ANDREA MARIA; PICOS, ALINA MONICA; POPA, SEVER; CHISNOIU, PETRE DANIEL; LASCU, LIANA; PICOS, ANDREI; CHISNOIU, RADU

    2015-01-01

    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

  6. Psychosocial predictors of non-adherence to chronic medication: systematic review of longitudinal studies

    Science.gov (United States)

    Zwikker, Hanneke E; van den Bemt, Bart J; Vriezekolk, Johanna E; van den Ende, Cornelia H; van Dulmen, Sandra

    2014-01-01

    Objectives Several cross-sectional studies suggest that psychosocial factors are associated with non-adherence to chronic preventive maintenance medication (CPMM); however, results from longitudinal associations have not yet been systematically summarized. Therefore, the objective of this study was to systematically synthesize evidence of longitudinal associations between psychosocial predictors and CPMM non-adherence. Materials and methods PUBMED, EMBASE, CINAHL, and PsychINFO databases were searched for studies meeting our inclusion criteria. The reference lists and the ISI Web of Knowledge of the included studies were checked. Studies were included if they had an English abstract, involved adult populations using CPMM living in Western countries, and if they investigated associations between psychosocial predictors and medication non-adherence using longitudinal designs. Data were extracted according to a literature-based extraction form. Study quality was independently judged by two researchers using a framework comprising six bias domains. Studies were considered to be of high quality if ≥four domains were free of bias. Psychosocial predictors for non-adherence were categorized into five pre-defined categories: beliefs/cognitions; coping styles; social influences and social support; personality traits; and psychosocial well-being. A qualitative best evidence synthesis was performed to synthesize evidence of longitudinal associations between psychosocial predictors and CPMM non-adherence. Results Of 4,732 initially-identified studies, 30 (low-quality) studies were included in the systematic review. The qualitative best evidence synthesis demonstrated limited evidence for absence of a longitudinal association between CPMM non-adherence and the psychosocial categories. The strength of evidence for the review’s findings is limited by the low quality of included studies. Conclusion The results do not provide psychosocial targets for the development of new

  7. A psychosocial perspective on the glossectomy experience.

    Science.gov (United States)

    Pettygrove, W B

    1985-02-01

    This analysis of the glossectomy experience based on Goffman's concepts of the preservation of self and of stigma management suggests several helpful responses for speech-language pathologists and other clinicians. Attention to psychosocial dimensions of recovery. In the face of life-threatening illness and necessarily radical treatment, the patient and others may trivialize or overlook psychosocial needs. The importance of specific social behaviors--talking on a telephone or eating in a restaurant--can only be understood in terms of the patient's own self-definition. The psychological impact is more than frustration at lost or inadequate functioning. It may be profound grief, a response to threats to aspects of self-definition most valued by the patient. Help in the presentation and preservation of self. While helping to improve speech intelligibility by reinforcing different compensatory mechanisms, clinicians can assist with other compensations in social performance. More attention to nonverbal cues, including dress and physical appearance, may be helpful. Increased use of written communication can facilitate social interactions and reinforce the sense of linguistic competence until intelligibility and fluency are regained. From the perspective of Goffman's analyses, the individual who selectively manipulates social cues to counteract a stigma need not feel "fake." The intent of more conscious manipulations is not to invent a new self or to fool others but to preserve the integrity of the self. More information about stereotypes may help the glossectomee cope with others' inappropriate reactions and evaluate the relative importance of stigmas in different social interactions (e.g., stereotypes expressed by one's employer or family members deserve more attention than those expressed by strangers).(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Psychosocial healing and post-conflict social reconstruction in the former Yugoslavia.

    Science.gov (United States)

    Gutlove, Paula; Thompson, Gordon

    2004-01-01

    Post-conflict reconstruction encompasses social, physical and political reconstruction. Social reconstruction entails rebuilding the human interactions that allow a society to function. This involves the healing of psychological and social wounds of individuals and society. Psychosocial healing is a process to promote psychological and social health of individuals, families and community groups. The Medical Network for Social Reconstruction in the Former Yugoslavia has pioneered a broad range of psychosocial healing programmes including community-integration programmes, development of volunteer action, and training of professional and lay people to take part in psychosocial healing. These programmes have demonstrated that psychosocial healing can be an effective way to heal post-conflict societal trauma and contribute to rebuilding society with an improved quality of life.

  9. Molecular mechanisms involved in the inhibition of MDA-MB-435 breast cancer cells by phenolic acids from the red-flesh peach BY00P6653

    Science.gov (United States)

    A wide variety of fruits and vegetables extracts have been shown to protect against cancer cell growth in vitro. Increasing evidence suggests that phenolics compounds found in fruits and vegetables may have anticancer properties. However, the molecular mechanisms involved in the anti-proliferative...

  10. Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2 leading to cell depolarization and calcium influx

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Bechmann, Louise Ellegaard; Hartmann, Bolette

    2015-01-01

    , but the mechanisms involved are not well understood. Here, we show that rats express NT in the gut and that glucose gavage stimulates secretion similarly to oral glucose in humans. Therefore, we conducted experiments on isolated perfused rat small intestine with a view to characterize the cellular pathways...

  11. Salvianolic Acid B inhibits platelet adhesion under conditions of flow by a mechanism involving the collagen receptor alpha 2 beta 1

    NARCIS (Netherlands)

    Wu, Ya Ping; Zhao, Xiao Min; Pan, Shao Dong; Guo, De An; Wei, Ran; Han, Ji Ju; Kainoh, Mie; Xia, Zuo Li; de Groot, Philip G.; Lisman, Ton

    2008-01-01

    Salvianolic acid B (SAB) is a component of Danshen, a herb widely used in Chinese medicine, and was previously shown to exert a number of biological activities including inhibition of platelet function, but the exact mechanisms involved are unclear. SAB dose-dependently inhibited platelet deposition

  12. Psychosocial adjustment to recurrent cancer.

    Science.gov (United States)

    Mahon, S M; Cella, D F; Donovan, M I

    1990-01-01

    This descriptive study of the perceptions and needs of people with recurrent malignancies asks three questions: How do patients describe the meaning of a recurrence of cancer? Do individuals perceive the diagnosis of recurrence and the initial diagnosis of cancer differently? What are the key psychosocial problems associated with recurrent cancer? The theoretical framework was based on Lazarus and Folkman's theory of stress, appraisal, and coping. Subjects completed the Impact of Event Scale (IES), the Psychosocial Adjustment to Illness Scale--Self-Report (PAIS), and a semistructured qualitative interview. The interview elicited perceptions of the event of recurrence and differences between the diagnosis of recurrence and the initial diagnosis. The convenience sample included 40 patients diagnosed with recurrent cancer within the last 30 days. Many subjects (78%) reported that the recurrence was more upsetting than the initial diagnosis. Scores on both the IES and the PAIS were high when compared to normative samples of patients with cancer suggesting that this sample of patients experienced a lot of psychological distress as well as problems at home, work, and in their social lives. These concerns often were unknown to caregivers. Although more research is needed, the authors propose that, with more accurate assessment, more effective intervention could be implemented and the quality of life improved for patients with recurrent cancer.

  13. Psychosocial aspects in cardiac rehabilitation

    DEFF Research Database (Denmark)

    Pogosova, N. V.; Saner, H.; Pedersen, S. S.

    2015-01-01

    A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health- related quality ......, the success of CR may critically depend on the interdependence of the body and mind and this interaction needs to be reflected through the assessment and management of PSRFs in line with robust scientific evidence, by trained staff, integrated within the core CR team.......A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health- related quality...... questions, standardised questionnaires, or structured clinical interviews. Psychotherapy and medication can be considered to alleviate any PSRF-related symptoms and to enhance HRQoL, but the evidence for a definite beneficial effect on cardiac endpoints is inconclusive. A multimodal behavioural intervention...

  14. Psychosocial aspects in cardiac rehabilitation

    DEFF Research Database (Denmark)

    Pogosova, Nana; Saner, Hugo; Pedersen, Susanne S.

    2015-01-01

    A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health-related quality o......, the success of CR may critically depend on the interdependence of the body and mind and this interaction needs to be reflected through the assessment and management of PSRFs in line with robust scientific evidence, by trained staff, integrated within the core CR team.......A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health-related quality...... questions, standardised questionnaires, or structured clinical interviews. Psychotherapy and medication can be considered to alleviate any PSRF-related symptoms and to enhance HRQoL, but the evidence for a definite beneficial effect on cardiac endpoints is inconclusive. A multimodal behavioural intervention...

  15. Psychosocial risk factors and heart failure hospitalization

    DEFF Research Database (Denmark)

    Rod, Naja Hulvej; Andersen, Ingelise; Prescott, Eva

    2011-01-01

    Prospective studies on the role of psychosocial factors in heart failure development are virtually nonexistent. The authors aimed to address the effect of psychosocial factors on the risk of heart failure hospitalization in men and women free of cardiovascular disease. In 1991-1993, the 8,670 par...

  16. Pregnancy intention, demographic differences, and psychosocial health.

    Science.gov (United States)

    Maxson, Pamela; Miranda, Marie Lynn

    2011-08-01

    We explore the psychosocial, demographic, and maternal characteristics across wanted, mistimed, and unwanted pregnancies. Data from 1321 women from a prospective cohort study of pregnant women in Durham, NC, are analyzed. Psychosocial correlates were obtained through prenatal surveys; electronic medical records were used to ascertain maternal health and pregnancy outcomes. Sixty-two percent of the women indicated an unintended pregnancy, with 44% (578) mistimed and 18% (245) unwanted. Only 38% of the pregnancies were characterized as wanted. Women with unwanted and with mistimed pregnancies were similar demographically, but they differed significantly on psychosocial profiles and maternal characteristics. Women with mistimed and with wanted pregnancies differed in demographics and psychosocial profiles. Wanted pregnancies had the healthiest, mistimed an intermediate, and unwanted the poorest psychosocial profile. Women with unwanted pregnancies had the highest depression, perceived stress, and negative paternal support scores (ppsychosocial profiles had higher odds of being in the unwanted category. Controlling for psychosocial and demographic variables, perceived stress and positive paternal support remained significant predictors of belonging to the unwanted and mistimed groups. Fully characterizing pregnancy intention and its relationship to psychosocial profiles may provide a basis for identifying women with highest risk during pregnancy and early motherhood. Women with unwanted and mistimed pregnancies may appear similar demographically but are different psychosocially. Women with unwanted pregnancies have multiple risk factors and would benefit from targeted interventions.

  17. Psychosocial and Family Functioning in Spina Bifida

    Science.gov (United States)

    Holmbeck, Grayson N.; Devine, Katie A.

    2010-01-01

    A developmentally oriented bio-neuropsychosocial model is introduced to explain the variation in family functioning and psychosocial adjustment in youth and young adults with spina bifida (SB). Research on the family functioning and psychosocial adjustment of individuals with SB is reviewed. The findings of past research on families of youth with…

  18. Psychosocial and Family Functioning in Spina Bifida

    Science.gov (United States)

    Holmbeck, Grayson N.; Devine, Katie A.

    2010-01-01

    A developmentally oriented bio-neuropsychosocial model is introduced to explain the variation in family functioning and psychosocial adjustment in youth and young adults with spina bifida (SB). Research on the family functioning and psychosocial adjustment of individuals with SB is reviewed. The findings of past research on families of youth with…

  19. Psychosocial care to patients with Malignant Melanoma

    DEFF Research Database (Denmark)

    Thorup, Charlotte Brun

    Psychosocial care to patients with Malignant Melanoma Intensions: The intension of this project is to link new knowledge with the nurses experience based knowledge within the psychosocial care to patients, who have been diagnosed with Malignant Melanoma (MM), thereby improving the care...

  20. Habitus and the Psychosocial: Bourdieu with Feelings

    Science.gov (United States)

    Reay, Diane

    2015-01-01

    This paper explores the potential of habitus to provide a window on the psychosocial. The paper works with a notion of psychosocial study as inquiry into the mutual constitution of the individual and the social relations within which they are enmeshed. At the same time it attempts to deepen and enrich notions of habitus. Although the strong focus…

  1. Psychosocial causes and consequences of pathological gaming

    NARCIS (Netherlands)

    Lemmens, J.S.; Valkenburg, P.M.; Peter, J.

    2011-01-01

    Pathological use of computer and video games has been associated with indicators of psychosocial well-being, such as loneliness, low self-esteem, low social competence, and low life satisfaction. However, few studies have decisively demonstrated whether these indicators of psychosocial well-being

  2. Explorations in Knowing: Thinking Psychosocially about Legitimacy

    Science.gov (United States)

    Chappell, Anne; Ernest, Paul; Ludhra, Geeta; Mendick, Heather

    2014-01-01

    In this paper, we look at what engaging with psychoanalysis, through psychosocial accounts of subjectivity, has contributed to our struggles for legitimacy and security within our ways of knowing. The psychosocial, with its insistence on the unconscious and the irrational, features as both a source of security and of insecurity. We use three…

  3. Work-related psychosocial factors and the development of ischemic heart disease: a systematic review

    DEFF Research Database (Denmark)

    Eller, Nanna H; Netterstrøm, Bo; Gyntelberg, Finn

    2009-01-01

    The literature on the relationship between work-related psychosocial factors and the development of ischemic heart disease (IHD) was systematically reviewed: 33 articles presented 51 analyses of studies involving male participants, 18 analyses involving female participants, and 8 analyses with both...

  4. The Wicked Character of Psychosocial Risks

    DEFF Research Database (Denmark)

    Jespersen, Anne Helbo; Hasle, Peter; Nielsen, Klaus Tranetoft

    2016-01-01

    regulation, and particularly the enforcement in the form of inspection and audits of certified occupational health and safety management systems, face challenges in assessing psychosocial risks and the strategies used by regulators to overcome these challenges. While regulation has become more effective......Psychosocial risks constitute a significant problem in most workplaces, and they are generally considered more difficult to regulate than many other occupational health and safety risks. This article investigates the challenges of regulating psychosocial risks in the workplace. The difficulties lie...... in the particular nature of psychosocial risks: their complexity, uncertainty, value, and power divergences. Psychosocial risks therefore resemble ‘wicked problems’, typically characterized by unclear cause-effect relationships and uncertain solutions. We use the ‘wicked problems’ concept to show how workplace...

  5. Association between psychosocial disorders and oral health

    Directory of Open Access Journals (Sweden)

    Amita Aditya

    2015-01-01

    Full Text Available It is a fact that mind and body share an intimate relationship. There are many ways in which mental and physical health impact each other. Psychosocial factors play a part in the pathogenesis of physical health, and oral health is no exception. Chronic and painful oral symptoms lead to psychosocial disorder and at the same time, some patients with psychosocial disorders experience painful oral and facial symptoms. Several investigators have concluded that psychosocial factors play an important role in the pathogenesis of an array of oral problems, ranging from poor oral hygiene to chronic pain disorders, such as temporomandibular joint disorders, burning mouth syndrome, and atypical pain. This review aims at the in-depth analysis of the correlation between psychosocial disorders and various oral symptoms.

  6. Cutting the Loops of Depression: a System Dynamics Representation of the Feedback Mechanisms Involved in Depression Development

    NARCIS (Netherlands)

    Herrera, D.; Bleijenbergh, I.L.

    2016-01-01

    Depression is a complex illness that involves the instability of biological and psychological structures in an individual. These disturbances make a depressed person to be affected in the personal relationships within his social circles and to be unable to fulfill normal daily activities as expected

  7. Psychosocial factors in peptic ulcer and inflammatory bowel disease.

    Science.gov (United States)

    Levenstein, Susan

    2002-06-01

    Over the past decade, while gastroenterologists' interest in mind-body interactions in organic disorders dwindled, stronger evidence has linked psychosocial factors with the incidence and recurrence of peptic ulcer and with the course of inflammatory bowel disease. Psychological-behavioral approaches to treatment continue to be disappointing. Psychosocial factors may affect ulcer by increasing duodenal acid load, altering local circulation or motility, intensifying Helicobacter pylori infection, stimulating corticosteroid secretion, and affecting health risk behaviors; possible mechanisms for inflammatory bowel disease include immune deregulation, gut permeability changes, and poor medication adherence. Both belong to the growing category of diseases thought to have an infectious component: for peptic ulcer the bacterium Helicobacter pylori, for inflammatory bowel disease an exaggerated immune response to gut bacteria. Peptic ulcer and inflammatory bowel disease, which present unique interactions among psychological, immunologic, endocrine, infectious, and behavioral factors, are splendid paradigms of the biopsychosocial model.

  8. Psychosocial work dimensions, personality, and body mass index: sex differences.

    Science.gov (United States)

    Blanch, Angel; Aluja, Anton

    2013-08-01

    The association between psychosocial work dimensions (i.e. demand and control) and obesity has been found to be inconclusive, indicating that individual differences factors might also contribute to explain the variability in BMI. The interaction between work dimensions and personality variables in a group of male and female workers (N = 506), and its associations with BMI were analyzed with a cross-sectional study with self-report data. Hierarchical regression analyses were used to predict the BMI levels from work and individual differences variables and their interactions for males and females. The main effects of personality variables were not significant, physical workload interacted with neuroticism for males, whereas control interacted with activity for females. Psychosocial work dimensions and personality traits were related to BMI for men and women. These outcomes reinforce the notion that different models might account for the explanatory mechanisms of BMI in regard to sex.

  9. Psychosocial work dimensions, personality, and body mass index: Sex differences

    Directory of Open Access Journals (Sweden)

    Angel Blanch

    2013-08-01

    Full Text Available Objectives: The association between psychosocial work dimensions (i.e. demand and control and obesity has been found to be inconclusive, indicating that individual differences factors might also contribute to explain the variability in BMI. Materials and Methods: The interaction between work dimensions and personality variables in a group of male and female workers (N = 506, and its associations with BMI were analyzed with a cross-sectional study with self-report data. Hierarhical regression analyses were used to predict the BMI levels from work and individual differences variables and their interactions for males and females. Results: The main effects of personality variables were not significant, physical workload interacted with neuroticism for males, whereas control interacted with activity for females. Conclusions: Psychosocial work dimensions and personality traits were related to BMI for men and women. These outcomes reinforce the notion that different models might account for the explanatory mechanisms of BMI in regard to sex.

  10. Autophosphorylation of [alpha]CaMKII is Differentially Involved in New Learning and Unlearning Mechanisms of Memory Extinction

    Science.gov (United States)

    Kimura, Ryoichi; Silva, Alcino J.; Ohno, Masuo

    2008-01-01

    Accumulating evidence indicates the key role of [alpha]-calcium/calmodulin-dependent protein kinase II ([alpha]CaMKII) in synaptic plasticity and learning, but it remains unclear how this kinase participates in the processing of memory extinction. Here, we investigated the mechanism by which [alpha]CaMKII may mediate extinction by using…

  11. Promoting Psychosocial Adjustment and Stress Management in First-Year College Students: The Benefits of Engagement in a Psychosocial Wellness Seminar

    Science.gov (United States)

    Conley, Colleen S.; Travers, Lea V.; Bryant, Fred B.

    2013-01-01

    Objective/Methods: This research evaluates the effectiveness of a psychosocial wellness seminar for first-year college students, from 2009 to 2011, using an 8-month prospective quasi-experimental design. Participants/Results: Compared with controls ("n" = 22) involved in an alternative seminar, intervention participants ("n" =…

  12. Altered Gene Expression of RNF34 and PACAP Possibly Involved in Mechanism of Exercise-Induced Analgesia for Neuropathic Pain in Rats.

    Science.gov (United States)

    Yamaoka, Shintaro; Oshima, Yusuke; Horiuchi, Hideki; Morino, Tadao; Hino, Masayuki; Miura, Hiromasa; Ogata, Tadanori

    2017-09-13

    Despite the availability of several modalities of treatment, including surgery, pharmacological agents, and nerve blocks, neuropathic pain is often unresponsive and sometimes progresses to intractable chronic pain. Although exercise therapy is a candidate for treatment of neuropathic pain, the mechanism underlying its efficacy has not been elucidated. To clarify the molecular mechanism for pain relief induced by exercise, we measured Rnf34 and Pacap mRNA levels in the spinal cord dorsal horn of SNL rats, a model of neuropathic pain. SNL model rats exhibited stable mechanical hyperalgesia for at least 6 weeks. When the rats were forced to exercise on a treadmill, mechanical and thermal hyperalgesia were significantly ameliorated compared with the non-exercise group. Accordingly, gene expression level of Rnf34 and Pacap were also significantly altered in the time course analysis after surgery. These results suggest that exercise therapy possibly involves pain relief in SNL rats by suppressing Rnf34 and Pacap expression in the spinal cord.

  13. Psychosocial interventions for premature ejaculation

    Directory of Open Access Journals (Sweden)

    Tamara Melnik

    Full Text Available BACKGROUND: Premature ejaculation (PE is a very common sexual dysfunction among patients, and with varying prevalence estimates ranging from 3% to 20%. Although psychological issues are present in most patients with premature PE, as a cause or as a consequence, research on the effects of psychological approaches for PE has in general not been controlled or randomised and is lacking in long-term follow up. OBJECTIVE: To assess the efficacy of psychosocial interventions for PE. CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW: Trials were searched in computerized general and specialized databases, such as: MEDLINE by PubMed (1966 to 2010; PsycINFO (1974 to 2010; EMBASE (1980 to 2010; LILACS (1982 to 2010; the Cochrane Central Register of Controlled Trials (Cochrane Library, 2010; and by checking bibliographies, and contacting manufacturers and researchers. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials evaluating psychosocial interventions compared with different psychosocial interventions, pharmacological interventions, waiting list, or no treatment for PE. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, and outcomes was extracted by at least two independent reviewers using a standard form. The primary outcome measure for comparing the effects of psychosocial interventions to waiting list and standard medications was improvement in IELT (i.e., time from vaginal penetration to ejaculation. The secondary outcome was change in validated PE questionnaires. MAIN RESULTS: In one study behavioral therapy (BT was significantly better than waiting list for duration of intercourse (MD (mean difference 407.90 seconds, 95% CI 302.42 to 513.38, and couples' sexual satisfaction (MD -26.10, CI -50.48 to -1.72. BT was also significantly better for a new functional-sexological treatment (FS (MD 412.00 seconds, 95% CI 305.88 to 518.12, change over time in subjective perception of duration of intercourse (Women: MD 2

  14. Child Marriages and Psychosocial Outcomes

    Directory of Open Access Journals (Sweden)

    Evrim Aktepe

    2017-12-01

    Full Text Available One of the most frequent forms of child abuse worldwide is child marriage. Underage marriages are going on to keep their commonness in countries such as Turkey although frequencies of them are decreasing in the world. Child marriage generally refers to the marriage of a child who is under 18 years of age. Because the majority of these marriages are performed without the conscious consent of the child, they are also defined as “early and forced marriages. Child marriages seperate children from their families and friends, expose them to domestic violence, jeopardize their development and the opportunities in educational, social and occupational areas. Early marriages may lead to psychologi-cal problems as well as depression and suicide. The aim of this article is to evaluate the frequency and causes of early marriage and its psychosocial consequences. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2017; 9(4.000: 410-420

  15. Mechanism-based Inactivation by Aromatization of the Transaminase BioA Involved in Biotin Biosynthesis in Mycobaterium tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Ce; Geders, Todd W.; Park, Sae Woong; Wilson, Daniel J.; Boshoff, Helena I.; Abayomi, Orishadipe; Barry, III, Clifton E.; Schnappinger, Dirk; Finzel, Barry C.; Aldrich, Courtney C. (Weill-Med); (UMM); (NIAID)

    2011-11-16

    BioA catalyzes the second step of biotin biosynthesis, and this enzyme represents a potential target to develop new antitubercular agents. Herein we report the design, synthesis, and biochemical characterization of a mechanism-based inhibitor (1) featuring a 3,6-dihydropyrid-2-one heterocycle that covalently modifies the pyridoxal 5'-phosphate (PLP) cofactor of BioA through aromatization. The structure of the PLP adduct was confirmed by MS/MS and X-ray crystallography at 1.94 {angstrom} resolution. Inactivation of BioA by 1 was time- and concentration-dependent and protected by substrate. We used a conditional knock-down mutant of M. tuberculosis to demonstrate the antitubercular activity of 1 correlated with BioA expression, and these results provide support for the designed mechanism of action.

  16. Docking Studies in Target Proteins Involved in Antibacterial Action Mechanisms: Extending the Knowledge on Standard Antibiotics to Antimicrobial Mushroom Compounds

    Directory of Open Access Journals (Sweden)

    Maria José Alves

    2014-01-01

    Full Text Available In the present work, the knowledge on target proteins of standard antibiotics was extended to antimicrobial mushroom compounds. Docking studies were performed for 34 compounds in order to evaluate their affinity to bacterial proteins that are known targets for some antibiotics with different mechanism of action: inhibitors of cell wall synthesis, inhibitors of protein synthesis, inhibitors of nucleic acids synthesis and antimetabolites. After validation of the molecular docking approach, virtual screening of all the compounds was performed against penicillin binding protein 1a (PBP1a, alanine racemase (Alr, d-alanyl-d-alanine synthetase (Ddl, isoleucyl-tRNA sinthetase (IARS, DNA gyrase subunit B, topoisomerase IV (TopoIV, dihydropteroate synthetase (DHPS and dihydrofolate reductase (DHFR using AutoDock4. Overall, it seems that for the selected mushroom compounds (namely, enokipodins, ganomycins and austrocortiluteins the main mechanism of the action is the inhibition of cell wall synthesis, being Alr and Ddl probable protein targets.

  17. Role of psychosocial care on ICU trauma

    Directory of Open Access Journals (Sweden)

    Usha Chivukula

    2014-01-01

    Full Text Available Context: Patients treated in intensive care units (ICU though receive the best medical attention are found to suffer from trauma typically attributed to the ICU environment. Biopsychosocial approach in ICUs is found to minimize ICU trauma. Aims: This study investigates the role of psychosocial care on patients in ICU after coronary artery bypass graft (CABG. Settings and Design: The study included 250 post-operative CABG patients from five corporate hospitals. The combination of between subject and correlation design was used. Materials and Methods: The ICU psychosocial care scale (ICUPCS and ICU trauma scale (ICUTS were used to measure the psychosocial care and trauma. Statistical Analysis: ANOVA and simple and multiple regression were applied. Results: Hospitals significantly differed in psychosocial care provided in ICUs. Higher the psychosocial care in ICU, lower was the ICU trauma experienced and vice versa. Psychosocial care was a significant major predictor of ICU trauma. Conclusions: The study suggests emphasis on psychosocial aspects in ICU care for optimizing prognosis.

  18. Determination of rate constants for the uptake process involving SO{sub 2} and an aerosol particle. A quantum mechanics/molecular mechanics and quantum statistical investigation

    Energy Technology Data Exchange (ETDEWEB)

    Madsen, Marianne Sloth [Department of Chemistry, H.C. Orsted Institute, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen O (Denmark); Danish Meteorological Institute, Lyngbyvej 100, DK-2100 Copenhagen O (Denmark)], E-mail: msm@dmi.dk; Gross, Allan [Department of Chemistry, H.C. Orsted Institute, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen O (Denmark); Danish Meteorological Institute, Lyngbyvej 100, DK-2100 Copenhagen O (Denmark); Falsig, Hanne [Department of Chemistry, H.C. Orsted Institute, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen O (Denmark); Kongsted, Jacob [Department of Theoretical Chemistry, Chemical Center, University of Lund, P.O. Box 124, S-22100 Lund (Sweden); Osted, Anders; Mikkelsen, Kurt V. [Department of Chemistry, H.C. Orsted Institute, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen O (Denmark); Christiansen, Ove [Department of Chemistry, University of Aarhus, Langelandsgade 140, DK-8000 Aarhus C (Denmark)

    2008-06-02

    We present a combined quantum mechanics/molecular mechanics and quantum statistical investigation of the interactions between a molecule (SO{sub 2}) and an aerosol particle including rate constants for the uptake process. A coupled cluster/molecular mechanics method including explicit polarization is used along with a quantum statistical method for calculating sticking coefficients. The importance of the polarization of the classical subsystem (the aerosol particle), the size of the classical subsystem and the size of one-electron basis sets are studied. The interaction energy is divided into van der Waals, electrostatic and polarization contributions. Relevant binding sites for the evaluation of the sticking coefficient are identified. These are classified into three groups according to the strength of the molecule-aerosol particle interaction energy. The identification of binding sites provides relevant information used in the quantum statistical method and thereby knowledge of the magnitude of the sticking coefficients for the different binding sites along with the total rates for the uptake processes between the aerosol particle and the SO{sub 2} molecule.

  19. Mechanism of HCV's resistance to IFN-α in cell culture involves expression of functional IFN-α receptor 1

    Directory of Open Access Journals (Sweden)

    Lamaze Christophe

    2011-07-01

    Full Text Available Abstract The mechanisms underlying the Hepatitis C virus (HCV resistance to interferon alpha (IFN-α are not fully understood. We used IFN-α resistant HCV replicon cell lines and an infectious HCV cell culture system to elucidate the mechanisms of IFN-α resistance in cell culture. The IFN-α resistance mechanism of the replicon cells were addressed by a complementation study that utilized the full-length plasmid clones of IFN-α receptor 1 (IFNAR1, IFN-α receptor 2 (IFNAR2, Jak1, Tyk2, Stat1, Stat2 and the ISRE- luciferase reporter plasmid. We demonstrated that the expression of the full-length IFNAR1 clone alone restored the defective Jak-Stat signaling as well as Stat1, Stat2 and Stat3 phosphorylation, nuclear translocation and antiviral response against HCV in all IFN-α resistant cell lines (R-15, R-17 and R-24 used in this study. Moreover RT-PCR, Southern blotting and DNA sequence analysis revealed that the cells from both R-15 and R-24 series of IFN-α resistant cells have 58 amino acid deletions in the extracellular sub domain 1 (SD1 of IFNAR1. In addition, cells from the R-17 series have 50 amino acids deletion in the sub domain 4 (SD4 of IFNAR1 protein leading to impaired activation of Tyk2 kinase. Using an infectious HCV cell culture model we show here that viral replication in the infected Huh-7 cells is relatively resistant to exogenous IFN-α. HCV infection itself induces defective Jak-Stat signaling and impairs Stat1 and Stat2 phosphorylation by down regulation of the cell surface expression of IFNAR1 through the endoplasmic reticulum (ER stress mechanisms. The results of this study suggest that expression of cell surface IFNAR1 is critical for the response of HCV to exogenous IFN-α.

  20. Enhancement of pulmonary tumour seeding by human coagulation factors II, IX, X--an investigation into the possible mechanisms involved.

    OpenAIRE

    Purushotham, A D; McCulloch, P.; George, W. D.

    1991-01-01

    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 sacr...

  1. Insights into the dual activation mechanism involving bifunctional cinchona alkaloid thiourea organocatalysts: an NMR and DFT study.

    Science.gov (United States)

    Zhu, Jun-Ling; Zhang, Yong; Liu, Chong; Zheng, An-Min; Wang, Wei

    2012-11-02

    In-depth understanding of the activation mechanism in asymmetric organocatalysis is of great importance for rational development of highly efficient catalytic systems. In this Article, the mechanism for the direct vinylogous Michael reaction of α,β-unsaturated γ-butyrolactam (Nu) and chalcone (EI) catalyzed by the bifunctional cinchona alkaloid thiourea organocatalyst (Cat) was studied with a combination of experimental (NMR) and theoretical (DFT) approaches, through which a new dual activation pathway was found. The key feature of this new dual activation mechanism (Pathway C) is that one N-H(A) of the thiourea moiety and the N-H of the protonated amine in Cat simultaneously activate Nu, while the other N-H(B) of the thiourea moiety activates EI. Both the NMR measurement and the DFT calculation identified that the interaction of Cat with Nu is stronger than that with EI in the catalyst-substrate complexes. Kinetic studies via variable-temperature NMR measurements indicated that, with the experimental activation energy E(a) of 10.2 kcal/mol, the reaction is all first-order in Nu, EI, and Cat. The DFT calculation further revealed that the C-C bond formation is both the rate-determining and the stereoselectivity-controlling steps. In agreement with the experimental data, the energy barrier for the rate-determining step along Pathway C was calculated as 8.8 kcal/mol. The validity of Pathway C was further evidenced by the calculated enantioselectivity (100% ee) and diastereoselectivity (60:1 dr), which are in excellent match with the experimental data (98% ee and >30:1 dr, respectively). Mechanistic study on the Michael addition of nitromethane to chalcone catalyzed by the Catalyst I further identified the generality of this new dual activation mechanism in cinchona alkaloid thiourea organocatalysis.

  2. Insights into the epigenetic mechanisms involving histone lysine methylation and demethylation in ischemia induced damage and repair has therapeutic implication.

    Science.gov (United States)

    Chakravarty, Sumana; Jhelum, Priya; Bhat, Unis Ahmad; Rajan, Wenson D; Maitra, Swati; Pathak, Salil S; Patel, Anant B; Kumar, Arvind

    2017-01-01

    Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. Therapeutic interventions to minimize ischemia-induced neural damage are limited due to poor understanding of molecular mechanisms mediating complex pathophysiology in stroke. Recently, epigenetic mechanisms mostly histone lysine (K) acetylation and deacetylation have been implicated in ischemic brain damage and have expanded the dimensions of potential therapeutic intervention to the systemic/local administration of histone deacetylase inhibitors. However, the role of other epigenetic mechanisms such as histone lysine methylation and demethylation in stroke-induced damage and subsequent recovery process is elusive. Here, we established an Internal Carotid Artery Occlusion (ICAO) model in CD1 mouse that resulted in mild to moderate level of ischemic damage to the striatum, as suggested by magnetic resonance imaging (MRI), TUNEL and histopathological staining along with an evaluation of neurological deficit score (NDS), grip strength and rotarod performance. The molecular investigations show dysregulation of a number of histone lysine methylases (KMTs) and few of histone lysine demethylases (KDMs) post-ICAO with significant global attenuation in the transcriptionally repressive epigenetic mark H3K9me2 in the striatum. Administration of Dimethyloxalylglycine (DMOG), an inhibitor of KDM4 or JMJD2 class of histone lysine demethylases, significantly ameliorated stroke-induced NDS by restoring perturbed H3K9me2 levels in the ischemia-affected striatum. Overall, these results highlight the novel role of epigenetic regulatory mechanisms controlling the epigenetic mark H3K9me2 in mediating the stroke-induced striatal damage and subsequent repair following mild to moderate cerebral ischemia.

  3. Imidazoline receptors in the heart: a novel target and a novel mechanism of action that involves atrial natriuretic peptides

    Directory of Open Access Journals (Sweden)

    S. Mukaddam-Daher

    2004-08-01

    Full Text Available Chronic stimulation of sympathetic nervous activity contributes to the development and maintenance of hypertension, leading to left ventricular hypertrophy (LVH, arrhythmias and cardiac death. Moxonidine, an imidazoline antihypertensive compound that preferentially activates imidazoline receptors in brainstem rostroventrolateral medulla, suppresses sympathetic activation and reverses LVH. We have identified imidazoline receptors in the heart atria and ventricles, and shown that atrial I1-receptors are up-regulated in spontaneously hypertensive rats (SHR, and ventricular I1-receptors are up-regulated in hamster and human heart failure. Furthermore, cardiac I1-receptor binding decreased after chronic in vivo exposure to moxonidine. These studies implied that cardiac I1-receptors are involved in cardiovascular regulation. The presence of I1-receptors in the heart, the primary site of production of natriuretic peptides, atrial natriuretic peptide (ANP and brain natriuretic peptide (BNP, cardiac hormones implicated in blood pressure control and cardioprotection, led us to propose that ANP may be involved in the actions of moxonidine. In fact, acute iv administration of moxonidine (50 to 150 µg/rat dose-dependently decreased blood pressure, stimulated diuresis and natriuresis and increased plasma ANP and its second messenger, cGMP. Chronic SHR treatment with moxonidine (0, 60 and 120 µg kg-1 h-1, sc for 4 weeks dose-dependently decreased blood pressure, resulted in reversal of LVH and decreased ventricular interleukin 1ß concentration after 4 weeks of treatment. These effects were associated with a further increase in already elevated ANP and BNP synthesis and release (after 1 week, and normalization by 4 weeks. In conclusion, cardiac imidazoline receptors and natriuretic peptides may be involved in the acute and chronic effects of moxonidine.

  4. Physiological Mechanisms Only Tell Half Story: Multiple Biological Processes are involved in Regulating Freezing Tolerance of Imbibed Lactuca sativa Seeds.

    Science.gov (United States)

    Jaganathan, Ganesh K; Han, Yingying; Li, Weijie; Song, Danping; Song, Xiaoyan; Shen, Mengqi; Zhou, Qiang; Zhang, Chenxue; Liu, Baolin

    2017-03-13

    The physiological mechanisms by which imbibed seeds survive freezing temperatures in their natural environment have been categorized as freezing avoidance by supercooling and freezing tolerance by extracellular freeze-desiccation, but the biochemical and molecular mechanisms conferring seed freezing tolerance is unexplored. In this study, using imbibed Lactuca sativa seeds we show that fast cooled seeds (60 °C h(-1)) suffered significantly higher membrane damage at temperature between -20 °C and -10 °C than slow cooled (3 °Ch(-1)) seeds (P  0.05). However, both SOD activity and accumulation of free proline were induced significantly after slow cooling to -20 °C compared with fast cooling. RNA-seq demonstrated that multiple pathways were differentially regulated between slow and fast cooling. Real-time verification of some differentially expressed genes (DEGs) revealed that fast cooling caused mRNA level changes of plant hormone and ubiquitionation pathways at higher sub-zero temperature, whilst slow cooling caused mRNA level change of those pathways at lower sub-zero ttemperatures. Thus, we conclude that imbibed seed tolerate low temperature not only by physiological mechanisms but also by biochemical and molecular changes.

  5. Involvement of two different mechanisms in trigeminal ganglion-evoked vasodilatation in the cat lower lip: role of experimental conditions.

    Science.gov (United States)

    Date, H; Kato, M; Izumi, H

    2000-03-15

    The present study was designed to examine the vasodilator mechanisms elicited by electrical stimulation of trigeminal ganglion (TG) in cat lower lip of the cats. When vago-sympathectomized cats were fixed into a stereotaxic frame by means of ear-bars, etc., the lip blood flow (LBF) increase evoked by lingual nerve (LN) stimulation (parasympathetic reflex response) was almost abolished in 15 out of 34 animals, but unaffected in the other 19. With the animal in the stereotaxic frame, electrical stimulation at sites within the TG evoked an LBF increase whether or not the LN stimulation-induced reflex response was intact. However, hexamethonium abolished the TG stimulation-induced LBF increase in animals whose brainstem parasympathetic reflex was intact, but reduced it by only 50% in animals whose reflex was impaired. This difference was seen in all experiments in which the electrode site was within the TG proper, regardless of its exact position. Although the underlying mechanism is unclear, these data suggest that when the TG is stimulated the LBF increase is entirely mediated via the parasympathetic reflex mechanism in animals whose brainstem reflex is intact, and that an antidromic vasodilatation occurs only in animals whose brainstem parasympathetic reflex is impaired.

  6. Pharmacological Characterization of the Mechanisms Involved in Delayed Calcium Deregulation in SH-SY5Y Cells Challenged with Methadone

    Directory of Open Access Journals (Sweden)

    Sergio Perez-Alvarez

    2012-01-01

    Full Text Available Previously, we have shown that SH-SY5Y cells exposed to high concentrations of methadone died due to a necrotic-like cell death mechanism related to delayed calcium deregulation (DCD. In this study, we show that, in terms of their Ca2+ responses to 0.5 mM methadone, SH-SY5Y cells can be pooled into four different groups. In a broad pharmacological survey, the relevance of different Ca2+-related mechanisms on methadone-induced DCD was investigated including extracellular calcium, L-type Ca2+ channels, μ-opioid receptor, mitochondrial inner membrane potential, mitochondrial ATP synthesis, mitochondrial Ca2+/2Na+-exchanger, reactive oxygen species, and mitochondrial permeability transition. Only those compounds targeting mitochondria such as oligomycin, FCCP, CGP 37157, and cyclosporine A were able to amend methadone-induced Ca2+ dyshomeostasis suggesting that methadone induces DCD by modulating the ability of mitochondria to handle Ca2+. Consistently, mitochondria became dramatically shorter and rounder in the presence of methadone. Furthermore, analysis of oxygen uptake by isolated rat liver mitochondria suggested that methadone affected mitochondrial Ca2+ uptake in a respiratory substrate-dependent way. We conclude that methadone causes failure of intracellular Ca2+ homeostasis, and this effect is associated with morphological and functional changes of mitochondria. Likely, this mechanism contributes to degenerative side effects associated with methadone treatment.

  7. Timely activation of budding yeast APCCdh1 involves degradation of its inhibitor, Acm1, by an unconventional proteolytic mechanism.

    Directory of Open Access Journals (Sweden)

    Michael Melesse

    Full Text Available Regulated proteolysis mediated by the ubiquitin proteasome system is a fundamental and essential feature of the eukaryotic cell division cycle. Most proteins with cell cycle-regulated stability are targeted for degradation by one of two related ubiquitin ligases, the Skp1-cullin-F box protein (SCF complex or the anaphase-promoting complex (APC. Here we describe an unconventional cell cycle-regulated proteolytic mechanism that acts on the Acm1 protein, an inhibitor of the APC activator Cdh1 in budding yeast. Although Acm1 can be recognized as a substrate by the Cdc20-activated APC (APCCdc20 in anaphase, APCCdc20 is neither necessary nor sufficient for complete Acm1 degradation at the end of mitosis. An APC-independent, but 26S proteasome-dependent, mechanism is sufficient for complete Acm1 clearance from late mitotic and G1 cells. Surprisingly, this mechanism appears distinct from the canonical ubiquitin targeting pathway, exhibiting several features of ubiquitin-independent proteasomal degradation. For example, Acm1 degradation in G1 requires neither lysine residues in Acm1 nor assembly of polyubiquitin chains. Acm1 was stabilized though by conditional inactivation of the ubiquitin activating enzyme Uba1, implying some requirement for the ubiquitin pathway, either direct or indirect. We identified an amino terminal predicted disordered region in Acm1 that contributes to its proteolysis in G1. Although ubiquitin-independent proteasome substrates have been described, Acm1 appears unique in that its sensitivity to this mechanism is strictly cell cycle-regulated via cyclin-dependent kinase (Cdk phosphorylation. As a result, Acm1 expression is limited to the cell cycle window in which Cdk is active. We provide evidence that failure to eliminate Acm1 impairs activation of APCCdh1 at mitotic exit, justifying its strict regulation by cell cycle-dependent transcription and proteolytic mechanisms. Importantly, our results reveal that strict cell

  8. The Crystal Structure and Mechanism of an Unusual Oxidoreductase, GilR, Involved in Gilvocarcin V Biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Noinaj, Nicholas; Bosserman, Mary A.; Schickli, M. Alexandra; Piszczek, Grzegorz; Kharel, Madan K.; Pahari, Pallab; Buchanan, Susan K.; Rohr, Jürgen (NIH); (Kentucky)

    2012-11-26

    GilR is a recently identified oxidoreductase that catalyzes the terminal step of gilvocarcin V biosynthesis and is a unique enzyme that establishes the lactone core of the polyketide-derived gilvocarcin chromophore. Gilvocarcin-type compounds form a small distinct family of anticancer agents that are involved in both photo-activated DNA-alkylation and histone H3 cross-linking. High resolution crystal structures of apoGilR and GilR in complex with its substrate pregilvocarcin V reveals that GilR belongs to the small group of a relatively new type of the vanillyl-alcohol oxidase flavoprotein family characterized by bicovalently tethered cofactors. GilR was found as a dimer, with the bicovalently attached FAD cofactor mediated through His-65 and Cys-125. Subsequent mutagenesis and functional assays indicate that Tyr-445 may be involved in reaction catalysis and in mediating the covalent attachment of FAD, whereas Tyr-448 serves as an essential residue initiating the catalysis by swinging away from the active site to accommodate binding of the 6R-configured substrate and consequently abstracting the proton of the hydroxyl residue of the substrate hemiacetal 6-OH group. These studies lay the groundwork for future enzyme engineering to broaden the substrate specificity of this bottleneck enzyme of the gilvocarcin biosynthetic pathway for the development of novel anti-cancer therapeutics.

  9. Structures and molecular mechanisms for common 15q13.3 microduplications involving CHRNA7: benign or pathological?

    Science.gov (United States)

    Szafranski, Przemyslaw; Schaaf, Christian P; Person, Richard E; Gibson, Ian B; Xia, Zhilian; Mahadevan, Sangeetha; Wiszniewska, Joanna; Bacino, Carlos A; Lalani, Seema; Potocki, Lorraine; Kang, Sung-Hae; Patel, Ankita; Cheung, Sau Wai; Probst, Frank J; Graham, Brett H; Shinawi, Marwan; Beaudet, Arthur L; Stankiewicz, Pawel

    2010-07-01

    We have investigated four approximately 1.6-Mb microduplications and 55 smaller 350-680-kb microduplications at 15q13.2-q13.3 involving the CHRNA7 gene that were detected by clinical microarray analysis. Applying high-resolution array-CGH, we mapped all 118 chromosomal breakpoints of these microduplications. We also sequenced 26 small microduplication breakpoints that were clustering at hotspots of nonallelic homologous recombination (NAHR). All four large microduplications likely arose by NAHR between BP4 and BP5 LCRs, and 54 small microduplications arose by NAHR between two CHRNA7-LCR copies. We identified two classes of approximately 1.6-Mb microduplications and five classes of small microduplications differing in duplication size, and show that they duplicate the entire CHRNA7. We propose that size differences among small microduplications result from preexisting heterogeneity of the common BP4-BP5 inversion. Clinical data and family histories of 11 patients with small microduplications involving CHRNA7 suggest that these microduplications might be associated with developmental delay/mental retardation, muscular hypotonia, and a variety of neuropsychiatric disorders. However, we conclude that these microduplications and their associated potential for increased dosage of the CHRNA7-encoded alpha 7 subunit of nicotinic acetylcholine receptors are of uncertain clinical significance at present. Nevertheless, if they prove to have a pathological effects, their high frequency could make them a common risk factor for many neurobehavioral disorders.

  10. Psychosocial aspects of rehabilitation in sports.

    Science.gov (United States)

    Covassin, Tracey; Beidler, Erica; Ostrowski, Jennifer; Wallace, Jessica

    2015-04-01

    When an athlete is injured, the primary focus of the sports medicine team is to treat the physical effects of the injury. However, many injured athletes experience negative psychological responses that should also be addressed throughout the rehabilitation process. Sports medicine professions should use psychosocial skills to help decrease the negative consequences of the injury, such as fear of reinjury, anxiety, depression, and adherence to rehabilitation. These psychosocial skills include goal setting, imagery, relaxation techniques, motivation, and self-talk. This article addresses the negative consequences of injury, psychosocial skills used to aid in the rehabilitation process, and clinical implications of the psychological aspects of rehabilitation in sport.

  11. Psychosocial Needs of Relatives of Trauma Patients.

    Science.gov (United States)

    Verharen, Lisbeth; Mintjes, Joke; Kaljouw, Marian; Melief, Willem; Schilder, Lies; van der Laan, Geert

    2015-08-01

    In trauma care, the patient is the primary focus of attention. However, patients' relatives also need attention, for two main reasons. First, the support of relatives is an important factor in the convalescence of patients. Second, the trauma means a serious disruption of not only the life of patients, but also that of their relatives. The purpose of this study was to explore the needs of relatives of trauma patients, to what extent these needs are met by the support of social workers, and how relatives benefit from this support. The study was conducted in hospitals in The Netherlands. Needs were measured using the Dutch version of the Critical Care Family Needs Inventory. Results of in-depth interviews were used to develop a questionnaire to explore the type of social worker support and to what extent relatives benefit from this support. Findings show that trauma patients' relatives have a need for information, access to the patient and hospital staff, and psychosocial assistance. In most cases social workers supported relatives and relatives benefited from the support. To ensure that trauma patients' relatives receive the support they need, social workers should be involved in trauma care as the standard of good care.

  12. Rapid and Localized Mechanical Stimulation and Adhesion Assay: TRPM7 Involvement in Calcium Signaling and Cell Adhesion.

    Science.gov (United States)

    Nishitani, Wagner Shin; Alencar, Adriano Mesquita; Wang, Yingxiao

    2015-01-01

    A cell mechanical stimulation equipment, based on cell substrate deformation, and a more sensitive method for measuring adhesion of cells were developed. A probe, precisely positioned close to the cell, was capable of a vertical localized mechanical stimulation with a temporal frequency of 207 Hz, and strain magnitude of 50%. This setup was characterized and used to probe the response of Human Umbilical Endothelial Vein Cells (HUVECs) in terms of calcium signaling. The intracellular calcium ion concentration was measured by the genetically encoded Cameleon biosensor, with the Transient Receptor Potential cation channel, subfamily M, member 7 (TRPM7) expression inhibited. As TRPM7 expression also regulates adhesion, a relatively simple method for measuring adhesion of cells was also developed, tested and used to study the effect of adhesion alone. Three adhesion conditions of HUVECs on polyacrylamide gel dishes were compared. In the first condition, the substrate is fully treated with Sulfo-SANPAH crosslinking and fibronectin. The other two conditions had increasingly reduced adhesion: partially treated (only coated with fibronectin, with no use of Sulfo-SANPAH, at 5% of the normal amount) and non-treated polyacrylamide gels. The cells showed adhesion and calcium response to the mechanical stimulation correlated to the degree of gel treatment: highest for fully treated gels and lowest for non-treated ones. TRPM7 inhibition by siRNA on HUVECs caused an increase in adhesion relative to control (no siRNA treatment) and non-targeting siRNA, but a decrease to 80% of calcium response relative to non-targeting siRNA which confirms the important role of TRPM7 in mechanotransduction despite the increase in adhesion.

  13. Involvement of spinal glutamate transporter-1 in the development of mechanical allodynia and hyperalgesia associated with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Shi J

    2016-11-01

    Full Text Available Jinshan Shi,1,* Ke Jiang,2,* Zhaoduan Li,3 1Department of Anesthesiology, Guizhou Provincial People’s Hospital, 2Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 3Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Little is known about the effects of the development of type 2 diabetes on glutamate homeostasis in the spinal cord. Therefore, we quantified the extracellular levels of glutamate in the spinal cord of Zucker diabetic fatty (ZDF rats using in vivo microdialysis. In addition, protein levels of glutamate transporter-1 (GLT-1 in the spinal cord of ZDF rats were measured using Western blot. Finally, the effects of repeated intrathecal injections of ceftriaxone, which was previously shown to enhance GLT-1 expression, on the development of mechanical allodynia and hyperalgesia as well as on basal extracellular level of glutamate and the expression of GLT-1 in the spinal cord of ZDF rats were evaluated. It was found that ZDF rats developed mechanical hyperalgesia and allodynia, which were associated with increased basal extracellular levels of glutamate and attenuated levels of GLT-1 expression in the spinal cord, particularly in the dorsal horn. Furthermore, repeated intrathecal administrations of ceftriaxone dose-dependently prevented the development of mechanical hyperalgesia and allodynia in ZDF rats, which were correlated with enhanced GLT-1 expression without altering the basal glutamate levels in the spinal cord of ZDF rats. Overall, the results suggested that impaired glutamate reuptake in the spinal cord may contribute to the development of neuropathic pains in type 2 diabetes. Keywords: diabetes, peripheral neuropathy, spinal cord, Zucker diabetic fatty rats, glutamate, glutamate transporter-1

  14. Rapid and Localized Mechanical Stimulation and Adhesion Assay: TRPM7 Involvement in Calcium Signaling and Cell Adhesion.

    Directory of Open Access Journals (Sweden)

    Wagner Shin Nishitani

    Full Text Available A cell mechanical stimulation equipment, based on cell substrate deformation, and a more sensitive method for measuring adhesion of cells were developed. A probe, precisely positioned close to the cell, was capable of a vertical localized mechanical stimulation with a temporal frequency of 207 Hz, and strain magnitude of 50%. This setup was characterized and used to probe the response of Human Umbilical Endothelial Vein Cells (HUVECs in terms of calcium signaling. The intracellular calcium ion concentration was measured by the genetically encoded Cameleon biosensor, with the Transient Receptor Potential cation channel, subfamily M, member 7 (TRPM7 expression inhibited. As TRPM7 expression also regulates adhesion, a relatively simple method for measuring adhesion of cells was also developed, tested and used to study the effect of adhesion alone. Three adhesion conditions of HUVECs on polyacrylamide gel dishes were compared. In the first condition, the substrate is fully treated with Sulfo-SANPAH crosslinking and fibronectin. The other two conditions had increasingly reduced adhesion: partially treated (only coated with fibronectin, with no use of Sulfo-SANPAH, at 5% of the normal amount and non-treated polyacrylamide gels. The cells showed adhesion and calcium response to the mechanical stimulation correlated to the degree of gel treatment: highest for fully treated gels and lowest for non-treated ones. TRPM7 inhibition by siRNA on HUVECs caused an increase in adhesion relative to control (no siRNA treatment and non-targeting siRNA, but a decrease to 80% of calcium response relative to non-targeting siRNA which confirms the important role of TRPM7 in mechanotransduction despite the increase in adhesion.

  15. Adenovirus Recruits Dynein by an Evolutionary Novel Mechanism Involving Direct Binding to pH-Primed Hexon

    Directory of Open Access Journals (Sweden)

    Julian Scherer

    2011-08-01

    Full Text Available Following receptor-mediated uptake into endocytic vesicles and escape from the endosome, adenovirus is transported by cytoplasmic dynein along microtubules to the perinuclear region of the cell. How motor proteins are recruited to viruses for their own use has begun to be investigated only recently. We review here the evidence for a role for dynein and other motor proteins in adenovirus infectivity. We also discuss the implications of recent studies on the mechanism of dynein recruitment to adenovirus for understanding the relationship between pathogenic and physiological cargo recruitment and for the evolutionary origins of dynein-mediated adenovirus transport.

  16. Huang Qi Jian Zhong Pellet Attenuates TNBS-Induced Colitis in Rats via Mechanisms Involving Improvement of Energy Metabolism

    OpenAIRE

    Duan-Yong Liu; Chun-Shui Pan; Yu-Ying Liu; Xiao-Hong Wei; Chang-Man Zhou; Kai Sun; Ke He; Chong Li; Li Yan; Jing-Yu Fan; Chuan-She Wang; Toshifumi Hibi; Hong-Ning Liu; Jing-Yan Han

    2013-01-01

    Huang Qi Jian Zhong Pellet (HQJZ) is a famous Chinese medicine formula for treatment of various gastrointestinal tract diseases. This study investigated the role of HQJZ in 2,4,6-trinitrobenzene sulfonic acid- (TNBS-) induced colitis and its underlying mechanism. Colonic mucosal injury was induced by TNBS in the Sprague-Dawley rats. In the HQJZ treatment group, HQJZ was administered (2 g/kg) for 14 days starting from day 1 after TNBS infusion. Colonic mucosal injury occurred obviously 1 day a...

  17. The β-amyloid protein induces S100β expression in rat hippocampus through a mechanism that involves IL-1

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To explore the effect of β-amyloid protein (Aβ) on S100β expression in rat hippocampus and its mechanisms. Methods At 7 days after bilateral stereotaxis injection of different dose of fibrillar Aβ 25-35 and interluekin-1 receptor antagonist (IL-1ra) into the rat CA1 region, the learning and memory abilities of rats were tested with passive avoidance task. Amyloid deposition was detected by using Congo red staining technique. Nissl staining and immunohistochemical techniques were used to analyze th...

  18. Apparent anti-Woodward-Hoffmann addition to a nickel bis(dithiolene) complex: the reaction mechanism involves reduced, dimetallic intermediates.

    Science.gov (United States)

    Dang, Li; Shibl, Mohamed F; Yang, Xinzheng; Harrison, Daniel J; Alak, Aiman; Lough, Alan J; Fekl, Ulrich; Brothers, Edward N; Hall, Michael B

    2013-04-01

    Nickel dithiolene complexes have been proposed as electrocatalysts for alkene purification. Recent studies of the ligand-based reactions of Ni(tfd)2 (tfd = S2C2(CF3)2) and its anion [Ni(tfd)2](-) with alkenes (ethylene and 1-hexene) showed that in the absence of the anion, the reaction proceeds most rapidly to form the intraligand adduct, which decomposes by releasing a substituted dihydrodithiin. However, the presence of the anion increases the rate of formation of the stable cis-interligand adduct, and decreases the rate of dihydrodithiin formation and decomposition. In spite of both computational and experimental studies, the mechanism, especially the role of the anion, remained somewhat elusive. We are now providing a combined experimental and computational study that addresses the mechanism and explains the role of the anion. A kinetic study (global analysis) for the reaction of 1-hexene is reported, which supports the following mechanism: (1) reversible intraligand addition, (2) oxidation of the intraligand addition product prior to decomposition, and (3) interligand adduct formation catalyzed by Ni(tfd)2(-). Density functional theory (DFT) calculations were performed on the Ni(tfd)2/Ni(tfd)2(-)/ethylene system to shed light on the selectivity of adduct formation in the absence of anion and on the mechanism in which Ni(tfd)2(-) shifts the reaction from intraligand addition to interligand addition. Computational results show that in the neutral system the free energy of activation for intraligand addition is lower than that for interligand addition, in agreement with the experimental results. The computations predict that the anion enhances the rate of the cis-interligand adduct formation by forming a dimetallic complex with the neutral complex. The [(Ni(tfd)2)2](-) dimetallic complex then coordinates ethylene and isomerizes to form a Ni,S-bound ethylene complex, which then rapidly isomerizes to the stable interligand adduct but not to the intraligand adduct

  19. Diazepam neuroprotection in excitotoxic and oxidative stress involves a mitochondrial mechanism additional to the GABAAR and hypothermic effects.

    Science.gov (United States)

    Sarnowska, Anna; Beresewicz, Małgorzata; Zabłocka, Barbara; Domańska-Janik, Krystyna

    2009-01-01

    The aim of the present investigation was to analyze the molecular mechanism(s) of diazepam neuroprotection in two models of selective neuronal death in CA1 sector of hippocampus: in vivo following transient gerbil brain ischemia and in vitro in rat hippocampal brain slices subjected to glutamatergic (100 microM NMDA) or oxidative (30 microM tertbutyl-hydroksyperoxide (TBH)) stress. In the in vivo model the diazepam treatment (two doses of 10mg/kg i.p. 30 and 90 min after the insult) resulted in more than 60% of CA1 hippocampal neurons surviving the insult comparing with 15% in untreated animals. To test whether the protective effect of diazepam was due to the postulated drug-induced hypothermia we followed the fluxes of body temperature during postischemic reperfusion: diazepam reduced temperature from 36.6+/-1 degrees C to 33.4+/-2 degrees C. Equivalent hypothermia induced and maintained in animals after ischemia did not prevent neuronal cell loss to the same extent as diazepam did (42.8+/-9.2% and 72.4+/-14.5% of live neurons, respectively). In vitro, under constant temperature conditions, diazepam exerted neuroprotective effects following a "U-shaped" dose-response curve, with concentration efficacy window of 0.5-10 microM. Five micro-molar diazepam showed significant protection by reducing over 50% the number of (dead) propidium iodide labeled cells even in the presence of GABA(A) receptor antagonist bicuculline. Next, we have shown that diazepam reduced the efflux of cytochrome c out of mitochondria both in compromised CA1 neurons in vitro and in isolated mitochondria treated with 30 microM THB. Our results suggest that the neuroprotective action of diazepam relies on additional mechanism(s) and not solely on its hypothermic effect. We suggest that diazepam evokes neuroprotection through its central receptors located on the GABA(A) receptor complex and, possibly, through its peripheral receptor, the translocator protein TSPO (previously called the peripheral

  20. Exploring the Mechanisms of Pathogenesis in Prostate Cancer Involving TMPRSS2-ERG (Or ETV1) Gene Rearrangement

    Science.gov (United States)

    2009-01-01

    Esther Baena, PhD; Zhe Li, PhD. Conclusion: We planned to use both a series of mouse models and biochemical approaches to study the mechanisms of...Apr 1, 2006). 9. S. A. Tomlins et al., Science 310, 644 (Oct 28, 2005). 10. J. Wang , Y. Cai, C. Ren, M. Ittmann, Cancer Res 66, 8347 (Sep 1, 2006...Cancer Res 68, 3584 (May 15, 2008). 23. S. Wang et al., Cancer Cell 4, 209 (Sep, 2003). 24. Y. Y. Kisanuki et al., Dev Biol 230, 230 (Feb 15, 2001

  1. Transcriptome profiling of Pinus radiata juvenile wood with contrasting stiffness identifies putative candidate genes involved in microfibril orientation and cell wall mechanics

    Directory of Open Access Journals (Sweden)

    Wu Harry X

    2011-10-01

    Full Text Available Abstract Background The mechanical properties of wood are largely determined by the orientation of cellulose microfibrils in secondary cell walls. Several genes and their allelic variants have previously been found to affect microfibril angle (MFA and wood stiffness; however, the molecular mechanisms controlling microfibril orientation and mechanical strength are largely uncharacterised. In the present study, cDNA microarrays were used to compare gene expression in developing xylem with contrasting stiffness and MFA in juvenile Pinus radiata trees in order to gain further insights into the molecular mechanisms underlying microfibril orientation and cell wall mechanics. Results Juvenile radiata pine trees with higher stiffness (HS had lower MFA in the earlywood and latewood of each ring compared to low stiffness (LS trees. Approximately 3.4 to 14.5% out of 3, 320 xylem unigenes on cDNA microarrays were differentially regulated in juvenile wood with contrasting stiffness and MFA. Greater variation in MFA and stiffness was observed in earlywood compared to latewood, suggesting earlywood contributes most to differences in stiffness; however, 3-4 times more genes were differentially regulated in latewood than in earlywood. A total of 108 xylem unigenes were differentially regulated in juvenile wood with HS and LS in at least two seasons, including 43 unigenes with unknown functions. Many genes involved in cytoskeleton development and secondary wall formation (cellulose and lignin biosynthesis were preferentially transcribed in wood with HS and low MFA. In contrast, several genes involved in cell division and primary wall synthesis were more abundantly transcribed in LS wood with high MFA. Conclusions Microarray expression profiles in Pinus radiata juvenile wood with contrasting stiffness has shed more light on the transcriptional control of microfibril orientation and the mechanical properties of wood. The identified candidate genes provide an

  2. Assessment of psychosocial risks faced by workers in Almería-type greenhouses, using the Mini Psychosocial Factor method.

    Science.gov (United States)

    Montoya-García, M E; Callejón-Ferre, A J; Pérez-Alonso, J; Sánchez-Hermosilla, J

    2013-03-01

    This work reports the use of the Mini Psychosocial Factor (MPF) method for assessing the psychosocial risks faced by agricultural workers in the greenhouses of Almería (Spain) with the aim of improving their health. The variables Rhythm, Mobbing, Relationships, Health, Recognition, Autonomy, Emotional Involvement, Support, Compensation, Control, Demands, and Mental Load were recorded using a pre-validated questionnaire containing 15 questions. The sex, age, and nationality of the respondents (n = 310) were also recorded, as were the type of greenhouse in which each worked, the size of the greenhouse, and the crop grown. The results showed psychosocial risks to exist for the workers. Multiple correspondence analysis, however, showed that moderate risks can be offset by new prevention programmes that improve Spanish legislation in terms of workers' salaries, worker-employer social days, work timetables to facilitate family life, and training courses. This could improve the work environment and health of Almería's greenhouse workers as well as their productivity. Copyright © 2012 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  3. A global approach of the mechanism involved in the biosynthesis of gold colloids using micro-algae

    Science.gov (United States)

    Dahoumane, Si Amar; Yéprémian, Claude; Djédiat, Chakib; Couté, Alain; Fiévet, Fernand; Coradin, Thibaud; Brayner, Roberta

    2014-10-01

    The use of micro-algae for the production of noble metal nanoparticles has drawn much attention recently. This paper aims to address some questions raised by our earlier publications and some recent reports from other groups, among which the biological pathways involved in the bioreduction of noble metal cations into nanoparticles and the design of stable colloids. TEM micrographs, taken at the early stage of contact between cells and salt solutions, show undoubtedly that the biomineralization process occurs within the thylakoidal membranes, which are the organelles responsible for photosynthesis. We strongly believe that the available enzymes and their cofactors (enzymatic machinery) are the key molecules that allow such reduction, promoting therefore the formation of nanoparticles. In addition, by comparing the characteristics of gold colloids made by polysaccharides-producing and non-producing micro-algae strains, we demonstrate that the stability of those colloids is ensured predominantly by those biopolymers. These macrobiomolecules control partly the size and the shape of NPs.

  4. Chronic psychosocial stress induces visceral hyperalgesia in mice.

    Science.gov (United States)

    Tramullas, Mónica; Dinan, Timothy G; Cryan, John F

    2012-05-01

    Experimental and clinical evidence has shown that chronic stress plays an important role in the onset and/or exacerbation of symptoms of functional gastrointestinal disorders. Here, we aimed to investigate whether exposure to a chronic and temporally unpredictable psychosocial stressor alters visceral and somatic nociception as well as anxiety-related behaviour. In male C57BL/6J mice, chronic stress was induced by repeated exposure to social defeat (SD, 2 h) and overcrowding (OC, 24 h) during 19 consecutive days. Visceral and somatic nociception was evaluated by colorectal distension and a hot plate, respectively. The social interaction test was used to assess social anxiety. Mice exposed to psychosocial stress developed visceral hyperalgesia and somatic hypoalgesia 24 h following the last stress session. SD/OC mice also exhibited social anxiety-like behaviour. All these changes were also associated with physiological alterations, measured as a decreased faecal pellet output and hypothalamic-pituitary-adrenal (HPA) axis disruption. Taken together, these data confirm that this mouse model of chronic psychosocial stress may be useful for studies on the pathophysiological mechanisms underlying such stress-associated disorders and to further test potential therapies.

  5. Roles of rifampicin in drug-drug interactions: underlying molecular mechanisms involving the nuclear pregnane X receptor

    Directory of Open Access Journals (Sweden)

    Raymond Kenneth

    2006-02-01

    Full Text Available Abstract Rifampicin, an important drug in the treatment of tuberculosis, is used extensively despite its broad effects on drug-drug interactions, creating serious problems. The clinical importance of such interactions includes autoinduction leading to suboptimal or failed treatment. The concomitantly administered effects of rifampicin on other drugs can result in their altered metabolism or transportation that are metabolised by cytochromes P450 or transported by p-glycoprotein in the gastrointestinal tract and liver. This review paper summarises recent findings with emphases on the molecular mechanisms used to explain these broad drug-drug interactions. In general, rifampicin can act on a pattern: rifampicin activates the nuclear pregnane X receptor that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. This pattern of action may explain many of the rifampicin inducing drug-drug interactions. However, effects through other mechanisms have also been reported and these make any explanation of such drug-drug interactions more complex.

  6. RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins Involved in a Posttranscriptional Iron Regulatory Mechanism

    Science.gov (United States)

    Figueroa-Angulo, Elisa E.; Calla-Choque, Jaeson S.; Mancilla-Olea, Maria Inocente; Arroyo, Rossana

    2015-01-01

    Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs) that interact with an iron responsive element (IRE) located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis. PMID:26703754

  7. A novel COX-independent mechanism of sulindac sulfide involves cleavage of epithelial cell adhesion molecule protein.

    Science.gov (United States)

    Liggett, Jason L; Min, Kyung-Won; Smolensky, Dmitriy; Baek, Seung Joon

    2014-08-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively used over the counter to treat headaches and inflammation as well as clinically to prevent cancer among high-risk groups. The inhibition of cyclooxygenase (COX) activity by NSAIDs plays a role in their anti-tumorigenic properties. NSAIDs also have COX-independent activity which is not fully understood. In this study, we report a novel COX-independent mechanism of sulindac sulfide (SS), which facilitates a previously uncharacterized cleavage of epithelial cell adhesion molecule (EpCAM) protein. EpCAM is a type I transmembrane glycoprotein that has been implemented as an over-expressed oncogene in many cancers including colon, breast, pancreas, and prostate. We found EpCAM to be down-regulated by SS in a manner that is independent of COX activity, transcription regulation, de novo protein synthesis, and proteasomal degradation pathway. Our findings clearly demonstrate that SS drives cleavage of the extracellular portion of EpCAM near the N-terminus. This SS driven cleavage is blocked by a deleting amino acids 55-81 as well as simply mutating arginine residues at positions 80 and 81 to alanine of EpCAM. Proteolysis of EpCAM by SS may provide a novel mechanism by which NSAIDs affect anti-tumorigenesis at the post-translational level.

  8. Compensatory mechanism involving the knee joint of the intact limb during gait in unilateral below-knee amputees.

    Science.gov (United States)

    Beyaert, C; Grumillier, C; Martinet, N; Paysant, J; André, J-M

    2008-08-01

    This study evaluated the asymmetry of knee kinetics during uncomfortable gait induced by prosthesis misalignment to further demonstrate the compensatory function of the knee joint of the intact limb during gait. Three-dimensional gait analysis including knee kinematics and kinetics at the beginning of stance phase was conducted in 15 healthy subjects and 17 unilateral trans-tibial amputees (TTA) walking at self-selected speed in three conditions of prosthetic alignment: initial alignment (IA); initial alignment altered either by 6 degrees of internal rotation (IR) or by 6 degrees of external rotation (ER) applied on the pylon. Patients reported best comfort of gait in IA condition and discomfort mainly in IR condition. Maximum knee flexion and knee total work at power phases K0-K2 were significantly higher in intact limbs compared to prosthetic and control limbs. In intact limbs, these variables had significantly higher values (+10-35%, pknee kinetics of the prosthetic limb, which suggests a protective mechanism. Knee kinetics of the intact limb did alter, which suggests a compensatory mechanism.

  9. Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism.

    Science.gov (United States)

    Guo, Jingjing; Zhou, Huan-Xiang

    2016-08-31

    Small ubiquitin-related modifiers (SUMOs) are conjugated to proteins to regulate a variety of cellular processes. SENPs are cysteine proteases with a catalytic center located within a channel between two subdomains that catalyzes SUMO C-terminal cleavage for processing of SUMO precursors and de-SUMOylation of target proteins. The β-grasp domain of SUMOs binds to an exosite cleft, and allosterically activates SENPs via an unknown mechanism. Our molecular dynamics simulations showed that binding of the β-grasp domain induces significant conformational and dynamic changes in SENP1, including widening of the exosite cleft and quenching of nanosecond dynamics in all but a distal region. A dock-and-coalesce mechanism emerges for SENP-catalyzed SUMO cleavage: the wedging of the β-grasp domain enables the docking of the proximal portion of the C-terminus and the strengthened cross-channel motional coupling initiates inter-subdomain correlated motions to allow for the distal portion to coalesce around the catalytic center.

  10. 社会心理因素与龋病及其机制的研究进展%Research progress on the mechanisms for the social psychosocial factors and dental caries

    Institute of Scientific and Technical Information of China (English)

    张蓓蓓; 赵丽娟

    2013-01-01

    With modern medical mode to biological—psychological—social model transformation, the effect of the social psychological factors on etiology of dental caries has been constantly highlighted. The social psychological fac-tors can increase the sensitivity of dental caries in the way of increasing the amount of the hormone and immuno-transmitter, reducing immune defenses by the nerve—endocrine—immune network, such as reducing production of saliva, changing the velocity of flow and the components of saliva. The result induces or increases the etiology of dental caries. In this article the research progress about social psychological factors on dental caries so that oral doctors can realize the effect of psychosocial factors on dental caries to improve prevention and treatment level to these diseases.%  随着现代医学模式向生物—心理—社会模式的转变,社会心理因素在龋病发病中的作用日益受到关注。社会心理因素可通过机体的神经—内分泌—免疫网络增加激素和免疫递质的释放,降低免疫防御能力,降低唾液的流速和流量,改变口腔内原有的生物学特征,增加机体对龋病的敏感性,从而引发或加重龋病。本文就社会心理因素,社会心理因素与龋病的关系,社会心理因素的致龋机制等研究进展作一综述。

  11. Scientific Evidence in the Study and Treatment of Addictive Behaviours in Psychosocial Intervention. Journal on Equality and Quality of Life

    Directory of Open Access Journals (Sweden)

    Itziar Iruarrizaga Díez

    2010-02-01

    Full Text Available In Spain, the importance and relevance of substance dependence and other addictive behaviours has generated great interest among the scientific community. Since its creation in 1992, Psychosocial Intervention. Journal on Equality and Quality of Life has transmitted the needs and training demands of psychologists, paying special attention to those aspects related to prevention, health outcomes and psychosocial factors involved in the onset and maintenance of drug addiction, psychosocial intervention and the treatment of addictive behaviours. As an introduction to this report on the Scientific evidence in the study and treatment of addictive behaviours, all topics covered by this journal throughout the years will be addressed.

  12. Modeling of Glycerol-3-Phosphate Transporter Suggests a Potential ‘Tilt’ Mechanism involved in its Function

    Science.gov (United States)

    Tsigelny, Igor F.; Greenberg, Jerry; Kouznetsova, Valentina; Nigam, Sanjay K.

    2009-01-01

    Many major facilitator superfamily (MFS) transporters have similar 12-transmembrane α-helical topologies with two six-helix halves connected by a long loop. In humans, these transporters participate in key physiological processes and are also, as in the case of members of the organic anion transporter (OAT) family, of pharmaceutical interest. Recently, crystal structures of two bacterial representatives of the MFS family — the glycerol-3-phosphate transporter (GlpT) and lac-permease (LacY) — have been solved and, because of assumptions regarding the high structural conservation of this family, there is hope that the results can be applied to mammalian transporters as well. Based on crystallography, it has been suggested that a major conformational “switching” mechanism accounts for ligand transport by MFS proteins. This conformational switch would then allow periodic changes in the overall transporter configuration, resulting in its cyclic opening to the periplasm or cytoplasm. Following this lead, we have modeled a possible “switch” mechanism in GlpT, using the concept of rotation of protein domains as in the DynDom program17 and membranephilic constraints predicted by the MAPAS program.23 We found that the minima of energies of intersubunit interactions support two alternate positions consistent with their transport properties. Thus, for GlpT, a “tilt” of 9°–10° rotation had the most favorable energetics of electrostatic interaction between the two halves of the transporter; moreover, this confirmation was sufficient to suggest transport of the ligand across the membrane. We conducted steered molecular dynamics simulations of the GlpT-ligand system to explore how glycerol-3-phosphate would be handled by the “tilted” structure, and obtained results generally consistent with experimental mutagenesis data. While biochemical data remain most consistent with a single-site alternating access model, our results raise the possibility that, while

  13. Myelinated Afferents Are Involved in Pathology of the Spontaneous Electrical Activity and Mechanical Hyperalgesia of Myofascial Trigger Spots in Rats

    Directory of Open Access Journals (Sweden)

    Fei Meng

    2015-01-01

    Full Text Available Myofascial trigger points (MTrPs are common causes for chronic pain. Myelinated afferents were considered to be related with muscular pain, and our clinical researches indicated they might participate in the pathology of MTrPs. Here, we applied myofascial trigger spots (MTrSs, equal to MTrPs in human of rats to further investigate role of myelinated afferents. Modified pyridine-silver staining revealed more nerve endings at MTrSs than non-MTrSs (P0.05. 30 min after the injection, MPTs at MTrSs were significantly lower than those of non-MTrSs (P<0.01. Therefore, we concluded that proliferated myelinated afferents existed at MTrSs, which were closely related to pathology of SEA and mechanical hyperalgesia of MTrSs.

  14. Multiple insecticide resistance mechanisms involving metabolic changes and insensitive target sites selected in anopheline vectors of malaria in Sri Lanka

    Directory of Open Access Journals (Sweden)

    Karunaratne SHP Parakrama

    2008-08-01

    Full Text Available Abstract Background The current status of insecticide resistance and the underlying resistance mechanisms were studied in the major vector of malaria, Anopheles culicifacies, and the secondary vector, Anopheles subpictus in five districts (Anuradhapura, Kurunegala, Moneragala, Puttalam and Trincomalee of Sri Lanka. Eight other anophelines, Anopheles annularis, Anopheles barbirostris, Anopheles jamesii, Anopheles nigerrimus, Anopheles peditaeniatus, Anopheles tessellatus, Anopheles vagus and Anopheles varuna from Anuradhapura district were also tested. Methods Adult females were exposed to the WHO discriminating dosages of DDT, malathion, fenitrothion, propoxur, λ-cyhalothrin, cyfluthrin, cypermethrin, deltamethrin, permethrin and etofenprox. The presence of metabolic resistance by esterase, glutathione S-transferase (GST and monooxygenase-based mechanisms, and the sensitivity of the acetylcholinesterase target site were assessed using synergists, and biochemical, and metabolic techniques. Results All the anopheline species had high DDT resistance. All An. culicifacies and An. subpictus populations were resistant to malathion, except An. culicifacies from Kurunegala, where there was no malathion carboxylesterase activity. Kurunegala and Puttalam populations of An. culicifacies were susceptible to fenitrothion. All the An. culicifacies populations were susceptible to carbamates. Both species were susceptible to the discriminating dosages of cypermethrin and cyfluthrin, but had different levels of resistance to other pyrethroids. Of the 8 other anophelines, only An. nigerrimus and An. peditaeniatus were resistant to all the insecticides tested, probably due to their high exposure to the insecticides used in agriculture. An. vagus showed some resistance to permethrin. Esterases, GSTs and monooxygenases were elevated in both An. culicifacies and An. subpictus. AChE was most sensitive to insecticides in Kurunegala and Trincomalee An. culicifacies

  15. From simple receptors to complex multimodal percepts: A first global picture on the mechanisms involved in perceptual binding

    Directory of Open Access Journals (Sweden)

    Rosemarie eVelik

    2012-07-01

    Full Text Available The binding problem in perception is concerned with answering the question how information from millions of sensory receptors, processed by millions of neurons working in parallel, can be merged into a unified percept. Binding in perception reaches from the lowest levels of feature binding up to the levels of multimodal binding of information coming from the different sensor modalities and also from other functional systems. The last 40 years of research have shown that the binding problem cannot be solved easily. Today, it is considered as one of the key questions to brain understanding. To date, various solutions have been suggested to the binding problem including: (1 combination coding, (2 binding by synchrony, (3 population coding, (4 binding by attention, (5 binding by knowledge, expectation, and memory, (6 hardwired versus on-demand binding, (7 bundling and binding of features, (8 the feature-integration theory of attention, (9 synchronization through top-down processes. Each of those hypotheses addresses important aspects of binding. However, each of them also suffers from certain weak points and can never give a complete explanation. This article gives a brief overview of the so far suggested solutions of perceptual binding and then shows that those are actually not mutually exclusive but can complement each other. A computationally verified model is presented which shows that, most likely, the different described mechanisms of binding act (1 at different hierarchical levels and (2 in different stages of perceptual knowledge acquisition. The model furthermore considers and explains a number of inhibitory filter mechanisms that suppress the activation of inappropriate or currently irrelevant information.

  16. Mechanisms involved in the depolarization of cutaneous afferents produced by segmental and descending inputs in the cat spinal cord.

    Science.gov (United States)

    Jiménez, I; Rudomin, P; Solodkin, M

    1987-01-01

    The relative contribution of specific and unspecific (potassium) components involved in the generation of primary afferent depolarization (PAD) of cutaneous fibres was analyzed in the spinal cord of the anesthetized cat. To this end we examined the correlation between the intraspinal threshold changes of single afferent fibres in the sural nerve produced by segmental and descending inputs and the negative DC potential shifts produced by these same stimuli at the site of excitability testing, the latter taken as indicators of the changes in extracellular concentration of potassium ions. Stimulation of the ipsilateral brain-stem reticular formation and of the contralateral red nucleus with 100-200 Hz trains reduced very effectively the intraspinal threshold of sural nerve fibres ending in the dorsal horn practically without producing any negative DC potential shifts at the site of excitability testing. However, negative DC potential shifts were produced more ventrally, in the intermediate nucleus and/or motor nucleus. Stimulation of the sural and superficial peroneus nerves with pulses at 2 Hz and strengths below 2 xT, also reduced the intraspinal threshold of single SU fibres without producing significant DC potential changes at the site of excitability testing. On the other hand, 100 Hz trains with strengths above 2 xT produced negative DC potential shifts and a proportional reduction of the intraspinal threshold of the SU fibres. The PAD of sural fibres produced by stimulation of rubro-spinal and reticulo-spinal fibres as well as by stimulation of sensory nerves with low frequency trains was unaffected or slightly increased, by i.v. injection of strychnine (0.2 mg/kg), but was readily abolished 5-10 min after the i.v. injection of picrotoxin (2 mg/kg). The results suggest that activation of reticulo-spinal and rubro-spinal fibres, as well as stimulation of cutaneous nerves with low frequencies and low strengths, produce PAD of cutaneous fibres involving activation

  17. A unique mechanism of nuclear division in Giardia lamblia involves components of the ventral disk and the nuclear envelope.

    Science.gov (United States)

    Solari, Alberto J; Rahn, Monica I; Saura, Alicia; Lujan, Hugo D

    2003-12-01

    The fine structure of the binucleate, parasitic protist Giardia lamblia during interphase and divisional stages was studied by serial thin sectioning and three-dimensional reconstructions. The earlier sign of nuclear division is the development of a few peripheral areas of densely packed chromatin directly attached to the inner nuclear envelope. An intracytoplasmic sheet of ventral disk components grows from the cell periphery towards one of the nuclei, apparently constricting this nucleus, which becomes located at a ventral bulge. After the basal bodies become duplicated, a full nuclear division occurs in trophozoites, giving two pairs of parent-daughter nuclei. This full division occurs in a dorsal-ventral direction, with the resulting nuclear pairs located at the sides of the two sets of basal bodies. A new ventral disk is formed from the disk-derived sheets in the cell harboring the four nuclei. Cytokinesis is polymorphic, but at early stages is dorsal-to-dorsal. Encysting trophozoites show the development of Golgi cisternae stacks and dense, specific secretory granules. 3-D reconstructions show that cysts contain a single pair of incompletely strangled nuclei. The dividing Giardia lacks a typical, microtubular spindle either inside or outside the nuclei. The nuclear envelope seems to be the only structure involved in the final division of the parent-daughter nuclei.

  18. Tong Xie Yao Fang relieves irritable bowel syndrome in rats via mechanisms involving regulation of 5-hydroxytryptamine and substance P.

    Science.gov (United States)

    Yin, Yue; Zhong, Lei; Wang, Jian-Wei; Zhao, Xue-Ying; Zhao, Wen-Jing; Kuang, Hai-Xue

    2015-04-21

    To investigate whether the Chinese medicine Tong Xie Yao Fang (TXYF) improves dysfunction in an irritable bowel syndrome (IBS) rat model. Thirty baby rats for IBS modeling were separated from mother rats (1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine (5-HT) and substance P (SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity. Defecation frequency was 1.8 ± 1.03 in normal rats and 4.5 ± 1.58 in IBS model rats (P colon transit function was significantly increased (256.88 ± 20.32 vs 93.36 ± 17.28, P colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS.

  19. Molecular mechanisms involved in TFF3 peptide-mediated modulation of the E-cadherin/catenin cell adhesion complex.

    Science.gov (United States)

    Meyer zum Büschenfelde, Dirk; Hoschützky, Heinz; Tauber, Rudolf; Huber, Otmar

    2004-05-01

    TFF3 is a member of the TFF-domain peptide family which is constitutively expressed in mucous epithelial tissues where it acts as a motogenic factor and plays an important role during epithelial restitution after wounding and during inflammation. In contrast to these beneficial functions, TFFs were also reported to be involved in cell scattering and tumor invasion. These changes in epithelial cell morphology and motility are associated with a modulation of cell contacts. In this respect, we here investigated the E-cadherin/catenin cell adhesion complex in FLAG-hTFF3-transfected HT29/B6 and MDCK cells. In hTFF3-transfected cells the amount of E-cadherin is reduced with a concomitant reduction of alpha- and beta-catenin levels. On one hand, E-cadherin expression is lowered at the transcriptional level as shown by multiplex RT-PCR analysis. This decrease does not depend on differences in the promoter methylation status as shown by methylation-specific PCR. On the other hand, pulse-chase experiments showed a reduction in the E-cadherin half-life in hTFF3-transfected cells reflecting increased E-cadherin degradation. In summary, hTFF3 induces transcriptional and posttranslational processes resulting in a modulation of E-cadherin-mediated cell-cell contacts that may play an important role in the paradoxical benefical and pathogenic function of TFF peptides.

  20. Psychosocial rehabilitation and democratic development in Nepal

    DEFF Research Database (Denmark)

    Triantafillou, Peter; Sassene, Michel

    2011-01-01

    interventions have made critics proclaim that Western psychosocial expertise subjects the bereaved of the Third World to repressive administrative power by objectifying and colonizing their minds. Meanwhile, advocates of psychosocial rehabilitation maintain that such criticisms fail to appreciate the ability...... of local healing strategies to actually empower torture victims through rehabilitation programmes. Inspired by Michel Foucault's concept of government, this article argues that both these assessments of torture rehabilitation overlook forms of power that work through the constitution of subjectivities...

  1. Psychosocial aspects of 'mixedness' in Scandinavia

    DEFF Research Database (Denmark)

    Singla, Rashmi

    The increasing number of interethnic married couples and their children in Scandinavia, challenges the stereotypes about us and others. However, these are relatively unresearched, invisible social categories against the backdrop of societal hegemonic homogeneity. This paper covers some psychosoci...... regarding the complex negotiation processes of identity through both ‘celebratory’ and ‘critique’ perspectives to ‘mixedness’, are presented along with implications for psychosocial support– and intervention services....

  2. Psychosocial Complications of Coronary Artery Disease

    OpenAIRE

    Karimi-Moonaghi, Hossein; Mojalli, Mohammad; Khosravan, Shahla

    2014-01-01

    Background: Cardiovascular diseases are the leading causes of death around the world. The coronary artery disease (CAD) is one of the most common diseases in this category, which can be the trigger to various psychosocial complications. We believe that inadequate attention has been paid to this issue. Objectives: The purpose of the present study was to explore the psychosocial complications of CAD from the Iranian patients’ perspective. Patients and Methods: A qualitative design based on the ...

  3. [Psychotherapeutic and psychosocial interventions and endophenotypes in bipolar disorders].

    Science.gov (United States)

    Correard, N; Elissalde, S N; Azorin, J-M; Fakra, E; Belzeaux, R

    2012-12-01

    Diseases with complex determinism, bipolar disorders, involve at the same time environmental and genetic factors of vulnerability. The characterization of these vulnerabilities would allow a better knowledge of their etiology and envisage the development of therapeutics, more specialized, even preventive. The research in genetic psychiatry allowed to highlight endophenotype candidates associated to bipolar disorders. They are endogenous clinical or biological features, biologically more elementary than phenotypes and more directly bound to the physiological consequences of genes and their polymorphisms. Targeting some of them with specific psychotherapy and psychosocial interventions could reduce the consequences of their expression and so have an action on the course of the disease and also preventive.

  4. Nandrolone and stanozolol induce Leydig cell tumor proliferation through an estrogen-dependent mechanism involving IGF-I system.

    Science.gov (United States)

    Chimento, Adele; Sirianni, Rosa; Zolea, Fabiana; De Luca, Arianna; Lanzino, Marilena; Catalano, Stefania; Andò, Sebastiano; Pezzi, Vincenzo

    2012-05-01

    Several substances such as anabolic androgenic steroids (AAS), peptide hormones like insulin-like growth factor-I (IGF-I), aromatase inhibitors and estrogen antagonists are offered via the Internet, and are assumed without considering the potential deleterious effects that can be caused by their administration. In this study we aimed to determine if nandrolone and stanozolol, two commonly used AAS, could have an effect on Leydig cell tumor proliferation and if their effects could be potentiated by the concomitant use of IGF-I. Using a rat Leydig tumor cell line, R2C cells, as experimental model we found that nandrolone and stanozolol caused a dose-dependent induction of aromatase expression and estradiol (E2) production. When used in combination with IGF-I they were more effective than single molecules in inducing aromatase expression. AAS exhibited estrogenic activity and induced rapid estrogen receptor (ER)-dependent pathways involving IGF1R, AKT, and ERK1/2 phosphorylation. Inhibitors for these kinases decreased AAS-dependent aromatase expression. Up-regulated aromatase levels and related E2 production increased cell proliferation as a consequence of increased cyclin E expression. The observation that ER antagonist ICI182,780 was also able to significantly reduce ASS- and AAS + IGF-induced cell proliferation, confirmed a role for estrogens in AAS-dependent proliferative effects. Taken together these data clearly indicate that the use of high doses of AAS, as it occurs in doping practice, enhances Leydig cell proliferation, increasing the risk of tumor development. This risk is higher when AAS are used in association with IGF-I. To our knowledge this is the first report directly associating AAS and testicular cancer.

  5. Genome-Wide Analyses Suggest Mechanisms Involving Early B-Cell Development in Canine IgA Deficiency

    Science.gov (United States)

    Frankowiack, Marcel; Kierczak, Marcin; Bergvall, Kerstin; Axelsson, Erik; Tintle, Linda; Marti, Eliane; Roosje, Petra; Leeb, Tosso; Hedhammar, Åke; Hammarström, Lennart; Lindblad-Toh, Kerstin

    2015-01-01

    Immunoglobulin A deficiency (IgAD) is the most common primary immune deficiency disorder in both humans and dogs, characterized by recurrent mucosal tract infections and a predisposition for allergic and other immune mediated diseases. In several dog breeds, low IgA levels have been observed at a high frequency and with a clinical resemblance to human IgAD. In this study, we used genome-wide association studies (GWAS) to identify genomic regions associated with low IgA levels in dogs as a comparative model for human IgAD. We used a novel percentile groups-approach to establish breed-specific cut-offs and to perform analyses in a close to continuous manner. GWAS performed in four breeds prone to low IgA levels (German shepherd, Golden retriever, Labrador retriever and Shar-Pei) identified 35 genomic loci suggestively associated (p IgA levels. In German shepherd, three genomic regions (candidate genes include KIRREL3 and SERPINA9) were genome-wide significantly associated (p IgA levels. A ~20kb long haplotype on CFA28, significantly associated (p = 0.0005) to IgA levels in Shar-Pei, was positioned within the first intron of the gene SLIT1. Both KIRREL3 and SLIT1 are highly expressed in the central nervous system and in bone marrow and are potentially important during B-cell development. SERPINA9 expression is restricted to B-cells and peaks at the time-point when B-cells proliferate into antibody-producing plasma cells. The suggestively associated regions were enriched for genes in Gene Ontology gene sets involving inflammation and early immune cell development. PMID:26225558

  6. Intraocular Pressure and the Mechanisms Involved in Resistance of the Aqueous Humor Flow in the Trabecular Meshwork Outflow Pathways.

    Science.gov (United States)

    Tamm, Ernst R; Braunger, Barbara M; Fuchshofer, Rudolf

    2015-01-01

    Intraocular pressure (IOP), the critical risk factor for glaucoma, is generated and maintained by the aqueous humor circulation system. Aqueous humor is secreted from the epithelial layers of the ciliary body and exits the eye through the trabecular meshwork or the uveoscleral outflow pathways. IOP builds up in response to a resistance to aqueous humor flow in the trabecular outflow pathways. The trabecular outflow resistance is localized in the inner wall region, which comprises the juxtacanalicular connective tissue (JCT) and the inner wall endothelium of Schlemm's canal (SC). Outflow resistance in this region is lowered through the relaxation of contractile myofibroblast-like cells in trabecular meshwork and the adjacent scleral spur, or the contraction of the ciliary muscle. In primary open-angle glaucoma, the most frequent form of glaucoma, outflow resistance of the inner wall region is typically higher than normal. There is evidence that the increase in resistance is related to characteristic biological changes in the resident cells of the JCT, which more and more acquire the structural and functional characteristics of contractile myofibroblasts. The changes involve an augmentation of their actin cytoskeleton and of their surrounding fibrillary extracellular matrix, which connects to JCT cells via integrins. This scenario leads to an overall stiffening of the inner wall region, and is modulated by transforming growth factor-β/connective tissue growth factor signaling. Essentially comparable changes appear to occur in SC endothelial cells. Stiffening of JCT and SC cells is very likely a critical causative factor for the increase in trabecular outflow resistance in POAG.

  7. Effect of selenium on control of postharvest gray mould of tomato fruit and the possible mechanisms involved

    Directory of Open Access Journals (Sweden)

    Zhilin eWu

    2016-01-01

    Full Text Available Selenium (Se has important benefits for crop growth and stress tolerance at low concentrations. However, there is very little information on antimicrobial effect of selenium against the economically important fungus Botrytis cinerea. In the present study, using sodium selenite as Se source, we investigated the effect of Se salts on spore germination and mycelial growth of the fungal pathogen in vitro and gray mould control in harvested tomato fruit. Se treatment at 24 mg/L significantly inhibited spore germination of the fungal pathogen and effectively controlled gray mould in harvested tomato fruit. Se treatment at 24 mg/L seems to induce the generation of intracellular reactive oxygen species in the fungal spores. The membrane integrity damage was observed with fluorescence microscopy following staining with propidium iodide after treatment of the spores with Se. These results suggest that Se has the potential for controlling gray mould rot of tomato fruits and might be useful in integrated control against gray mould disease of postharvest fruits and vegetables caused by B. cinerea. The mechanisms by which Se decreased gray mould decay of tomato fruit may be directly related to the severe damage to the conidia plasma membrane and loss of cytoplasmic materials from the hyphae.

  8. PLAG1 alterations in lipoblastoma: involvement in varied mesenchymal cell types and evidence for alternative oncogenic mechanisms.

    Science.gov (United States)

    Gisselsson, D; Hibbard, M K; Dal Cin, P; Sciot, R; Hsi, B L; Kozakewich, H P; Fletcher, J A

    2001-09-01

    Lipoblastomas are rare soft tissue tumors that occur primarily in young children. They typically contain variably differentiated adipocytes, primitive mesenchymal cells, myxoid matrix, and fibrous trabeculae. Abnormalities in chromosome 8, leading to rearrangements of the PLAG1 gene, were demonstrated recently in four lipoblastomas. In the present report, we determine the frequency of PLAG1 alterations in 16 lipoblastomas from children aged 13 years or younger, and we also evaluate the stages of lipoblastoma differentiation at which PLAG1 genomic alterations are found. Eleven lipoblastomas (69%), including those with either classic or lipoma-like histology, had rearrangements of the 8q12 PLAG1 region. Another three lipoblastomas had polysomy for chromosome 8 in the absence of PLAG1 rearrangement. Only two cases (13%) lacked a chromosome 8 abnormality. Notably, the lipoblastomas with chromosome 8 polysomy had up to five copies of chromosome 8 as an isolated cytogenetic finding in an otherwise diploid cell. We also demonstrate that PLAG1 alterations are found in a spectrum of mesenchymal cell types in lipoblastomas, including lipoblasts, mature adipocytes, primitive mesenchymal cells, and fibroblast-like cells. This finding is consistent with neoplastic origin in a primitive mesenchymal precursor and with variable differentiation to a mature adipocyte end-point. Hence, our studies provide biological validation for the clinical observation that lipoblastomas can evolve into mature, lipoma-like, lesions. They also suggest that PLAG1 dosage alterations caused by polysomy 8 might represent an alternative oncogenic mechanism in lipoblastoma.

  9. Common mechanisms involved in Alzheimer's disease and type 2 diabetes: a key role of chronic bacterial infection and inflammation.

    Science.gov (United States)

    Miklossy, Judith; McGeer, Patrick L

    2016-04-01

    Strong epidemiologic evidence and common molecular mechanisms support an association between Alzheimer's disease (AD) and type 2-diabetes. Local inflammation and amyloidosis occur in both diseases and are associated with periodontitis and various infectious agents. This article reviews the evidence for the presence of local inflammation and bacteria in type 2 diabetes and discusses host pathogen interactions in chronic inflammatory disorders. Chlamydophyla pneumoniae, Helicobacter pylori and spirochetes are demonstrated in association with dementia and brain lesions in AD and islet lesions in type 2 diabetes. The presence of pathogens in host tissues activates immune responses through Toll-like receptor signaling pathways. Evasion of pathogens from complement-mediated attack results in persistent infection, inflammation and amyloidosis. Amyloid beta and the pancreatic amyloid called amylin bind to lipid bilayers and produce Ca(2+) influx and bacteriolysis. Similarly to AD, accumulation of amylin deposits in type 2 diabetes may result from an innate immune response to chronic bacterial infections, which are known to be associated with amyloidosis. Further research based on an infectious origin of both AD and type 2 diabetes may lead to novel treatment strategies.

  10. Enhancement of pulmonary tumour seeding by human coagulation factors II, IX, X--an investigation into the possible mechanisms involved.

    Science.gov (United States)

    Purushotham, A D; McCulloch, P; George, W D

    1991-09-01

    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 microcirculation. In a second experiment, rat factor complex II, IX, X was prepared, and Mtln3 cells were then injected in female Fisher 344 rats alone or in combination with either human factor complex or rat factor complex. Following sacrifice, the number of pulmonary nodules in animals receiving cells with rat factor complex was similar to that in animals receiving human factor complex, and significantly higher than that in the control (P less than 0.001, ANOVA and Mann-Whitney), indicating that the observed enhancement of pulmonary seeding is unrelated to the xenogeneic properties of the human factor complex.

  11. Swarming mechanisms in the yellow fever mosquito: aggregation pheromones are involved in the mating behavior of Aedes aegypti.

    Science.gov (United States)

    Fawaz, Emadeldin Y; Allan, Sandra A; Bernier, Ulrich R; Obenauer, Peter J; Diclaro, Joseph W

    2014-12-01

    Mosquitoes of various species mate in swarms comprised of tens of thousands of flying males. In this study, we examined Aedes aegypti swarming behavior and identified associated chemical cues. Novel evidence is provided that Ae. aegypti females aggregate by means of olfactory cues, such as aggregation pheromones. Isolation of Ae. aegypti aggregation pheromones was achieved by aeration of confined mosquitoes and collection of associated volatiles by glass filters. The collected volatiles were identified through gas chromatography mass spectrometry (GCMS). Three aggregation pheromones were collected and identified as 2,6,6-trimethylcyclohex-2-ene-1,4-dione (ketoisophorone) (CAS# 1125-21-9, t(R) = 18.75), 2,2,6-trimethylcyclohexane-1,4-dione (the saturated analog of ketoisophorone) (CAS# 20547-99-3, t(R) = 20.05), and 1-(4-ethylphenyl) ethanone (CAS# 937-30-4, t(R) = 24.22). Our biological studies revealed that the identified compounds stimulated mosquito behavior under laboratory conditions. The mechanism of mosquito swarm formation is discussed in light of our behavioral study findings. A preliminary field trial demonstrated the potential application of the isolated aggregation pheromones in controlling Ae. aegypti. © 2014 The Society for Vector Ecology.

  12. Design and evaluation of doxorubicin-containing microbubbles for ultrasound-triggered doxorubicin delivery: cytotoxicity and mechanisms involved.

    Science.gov (United States)

    Lentacker, Ine; Geers, Bart; Demeester, Joseph; De Smedt, Stefaan C; Sanders, Niek N

    2010-01-01

    Drug delivery with microbubbles and ultrasound is gaining more and more attention in the drug delivery field due to its noninvasiveness, local applicability, and proven safety in ultrasonic imaging techniques. In this article, we tried to improve the cytotoxicity of doxorubicin (DOX)-containing liposomes by preparing DOX-liposome-containing microbubbles for drug delivery with therapeutic ultrasound. In this way, the DOX release and uptake can be restricted to ultrasound-treated areas. Compared to DOX-liposomes, DOX-loaded microbubbles killed at least two times more melanoma cells after exposure to ultrasound. After treatment of the melanoma cells with DOX-liposome-loaded microbubbles and ultrasound, DOX was mainly present in the nuclei of the cancer cells, whereas it was mainly detected in the cytoplasm of cells treated with DOX-liposomes. Exposure of cells to DOX-liposome-loaded microbubbles and ultrasound caused an almost instantaneous cellular entry of the DOX. At least two mechanisms were identified that explain the fast uptake of DOX and the superior cell killing of DOX-liposome-loaded microbubbles and ultrasound. First, exposure of DOX-liposome-loaded microbubbles to ultrasound results in the release of free DOX that is more cytotoxic than DOX-liposomes. Second, the cellular entry of the released DOX is facilitated due to sonoporation of the cell membranes. The in vitro results shown in this article indicate that DOX-liposome-loaded microbubbles could be a very interesting tool to obtain an efficient ultrasound-controlled DOX delivery in vivo.

  13. Cordycepin Decreases Compound Action Potential Conduction of Frog Sciatic Nerve In Vitro Involving Ca2+-Dependent Mechanisms

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    Li-Hua Yao

    2015-01-01

    Full Text Available Cordycepin has been widely used in oriental countries to maintain health and improve physical performance. Compound nerve action potential (CNAP, which is critical in signal conduction in the peripheral nervous system, is necessary to regulate physical performance, including motor system physiological and pathological processes. Therefore, regulatory effects of cordycepin on CNAP conduction should be elucidated. In this study, the conduction ability of CNAP in isolated frog sciatic nerves was investigated. Results revealed that cordycepin significantly decreased CNAP amplitude and conductive velocity in a reversible and concentration-dependent manner. At 50 mg/L cordycepin, CNAP amplitude and conductive velocity decreased by 62.18 ± 8.06% and 57.34% ± 6.14% compared with the control amplitude and conductive velocity, respectively. However, the depressive action of cordycepin on amplitude and conductive velocity was not observed in Ca2+-free medium or in the presence of Ca2+ channel blockers (CdCl2/LaCl3. Pretreatment with L-type Ca2+ channel antagonist (nifedipine/deltiazem also blocked cordycepin-induced responses; by contrast, T-type and P-type Ca2+ channel antagonists (Ni2+ failed to block such responses. Therefore, cordycepin decreased the conduction ability of CNAP in isolated frog sciatic nerves via L-type Ca2+ channel-dependent mechanism.

  14. Antisense oligonucleotide targeting Livin induces apoptosis of human bladder cancer cell via a mechanism involving caspase 3

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    Weili Zhang

    2010-06-01

    Full Text Available Abstract Background and Aim in recent years, Livin, a new member of IAPs family, is found to be a key molecule in cancers. Researchers consider Livin may become a new target for tumor therapy; however, the role of it in bladder cancer is still unclear. The purpose of this article is to investigate Antisense Oligonucleotide (ASODN of Livin on treating bladder cancer cell and underlying mechanisms. Methods Phosphorathioate modifying was used to synthesize antisense oligonucleotides targeting Livin, followed by transfection into human bladder cancer cell 5637. After transfection, Livin mRNA and protein level, cell proliferation and apoptosis changes, caspase3 level and its effect on human bladder cancer transplantable tumor in nude mice were measured. Result results showed Livin ASODN effectively inhibited Livin expression and tumor cell proliferation, and these effects probably through enhanced caspase3 activity and apoptosis of tumor cells. In nude mice transplantable tumor model, Livin expressions were inhibited meanwhile caspase3 expression was increased. Tumor growth slowed down and apoptosis was enhanced. Conclusion Our data suggest that Livin plays an important role in inhibiting apoptosis of bladder cancer cells. Livin ASODN may promote cell apoptosis, inhibit bladder cancer growth, and become one of the methods of gene therapy for bladder cancer.

  15. Arsenate tolerance mechanism of Oenothera odorata from a mine population involves the induction of phytochelatins in roots.

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    Kim, Dae-Yeon; Park, Hyun; Lee, Sang-Hwan; Koo, Namin; Kim, Jeong-Gyu

    2009-04-01

    We investigated the arsenate tolerance mechanisms of Oenothera odorata by comparing two populations [i.e., one population from the mine site (MP) and the other population from an uncontaminated site (UP)] via the exposure of hydroponic solution containing arsenate (i.e., 0-50 microM). The MP plants were significantly more tolerant to arsenate than UP plants. The UP plants accumulated more As in their shoots and roots than did the MP plants. The UP plants translocated up to 21 microg g(-1) of As into shoots, whereas MP plants translocated less As (up to 4.5 microg g(-1)) to shoots over all treatments. The results of lipid peroxidation indicated that MP plants were less damaged by oxidative stress than were UP plants. Phytochelatin (PC) content correlated linearly with root As concentration in the MP (i.e., [PCs](root)=1.69x[As](root), r(2)=0.945) and UP (i.e., [PCs](root)=0.89x[As](root), r(2)=0.979) plants. This relationship means that increased PC to As ratio may be associated with increased tolerance. Our results suggest that PC induction in roots plays a critical role in As tolerance of O. odorata.

  16. A Tribolium castaneum whole-embryo culture protocol for studying the molecular mechanisms and morphogenetic movements involved in insect development.

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    Macaya, Constanza C; Saavedra, Patricio E; Cepeda, Rodrigo E; Nuñez, Viviana A; Sarrazin, Andres F

    2016-01-01

    The development of the red flour beetle Tribolium castaneum is more representative of arthropods than the evolutionarily derived fly, Drosophila melanogaster. Thus, Tribolium is becoming an emerging organism model for studying the evolution of the mechanisms that control embryonic development in arthropods. In this regard, diverse genetic and molecular tools are currently available for Tribolium, as well as imaging and embryonic techniques. Recently, we developed a method for culturing embryos in order to study specific stages during Tribolium development. In this report, we present a detailed and "easy-to-follow" protocol for embryo handling and dissection, extending the use of whole-embryo culture to functional analysis by performing in vivo pharmacological manipulations. This experimental accessibility allowed us to study the relevance of microtubules in axis elongation, using nocodazole and taxol drugs to interfere with microtubule networks, followed by length measurement analysis. Additionally, we demonstrated that embryo handling had no effect on the development of Tribolium embryos, and we checked viability after dissection and bisection and during incubation using propidium iodide. The embryo culture protocol we describe here can be applied to study diverse developmental processes in Tribolium. We expect that this protocol can be adapted and applied to other arthropods.

  17. The β-amyloid protein induces S100β expression in rat hippocampus through a mechanism that involves IL-1

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To explore the effect of β-amyloid protein (Aβ) on S100β expression in rat hippocampus and its mechanisms. Methods At 7 days after bilateral stereotaxis injection of different dose of fibrillar Aβ 25-35 and interluekin-1 receptor antagonist (IL-1ra) into the rat CA1 region, the learning and memory abilities of rats were tested with passive avoidance task. Amyloid deposition was detected by using Congo red staining technique. Nissl staining and immunohistochemical techniques were used to analyze the number of neurons, and GFAP and the S100β expression in hippocampal CA1 region , respectively. Results After fibrillar Aβ injection, the step-through latency of rats was significantly shortened compared to that of the control group. The GFAP positive astrocytes were found surrounding amyloid deposition. Neuronal loss occurred in the pyramidal cell layer of CA1 region. The number of S100β positive cells in Aβ-treated group was significantly increased compared with that in the control group. After IL-1ra injection, the number of S100β positive cells was significantly decreased. Conclusion Intrahippocampal injection of Aβ 25-35 could cause similar pathologic changes of Alzheimer's disease. Aβ 25-35 was capable of up-regulating S100β expression in a dose-dependent manner. The injection of IL-1ra could attenuate the effect of Aβ on S100β expression.

  18. Predator exposure/psychosocial stress animal model of post-traumatic stress disorder modulates neurotransmitters in the rat hippocampus and prefrontal cortex.

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    C Brad Wilson

    Full Text Available Post-Traumatic Stress Disorder (PTSD can develop in response to a traumatic event involving a threat to life. To date, no diagnostic biomarkers have been identified for PTSD. Recent research points toward physiological abnormalities in the hypothalamic-pituitary-adrenal (HPA axis, sympathoadrenal medullary and immune system that may be implicated in the disorder. The modulation of neurotransmitters is another possible mechanism, but their role in the progression of PTSD is poorly understood. Low serotonin (5-HT may be a factor, but it may not be the only neurotransmitter affected as modulation affects levels of other neurotransmitters. In this study, we hypothesized the predator exposure/psychosocial stress rodent model of PTSD may alter levels of 5-HT and other neurotransmitters in the rat hippocampus and prefrontal cortex (PFC. Male Sprague-Dawley rats were used in this experiment. We induced PTSD via a predator exposure/psychosocial stress model, whereby rats were placed in a cage with a cat for 1 hour on days 1 and 11 of the 31-day experiment. Rats also received psychosocial stress via daily cage cohort changes. On day 32, the rats were sacrificed and the brains dissected to remove the hippocampus and PFC. Norepinephrine (NE, 5-Hydroxyindoleacetic acid (5-HIAA, homovanillic acid (HVA, dopamine (DA, and 3,4-Dihydroxyphenylacetic acid (DOPAC, and 5-HT levels in the hippocampus and PFC were measured with high-performance liquid chromatography (HPLC. In the hippocampus, 5-HT and HVA were lower, while NE and DOPAC were higher, in the PTSD group vs. controls. In the PFC, only 5-HT was lower, while NE, DA, and DOPAC were higher, in the PTSD group vs. controls. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also examined and confirmed our findings. These results demonstrate that the predator exposure/psychosocial stress model of PTSD produces neurotransmitter changes similar to those seen in human patients and may

  19. Estradiol levels modulate brain activity and negative responses to psychosocial stress across the menstrual cycle.

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    Albert, Kimberly; Pruessner, Jens; Newhouse, Paul

    2015-09-01

    Although ovarian hormones are thought to have a potential role in the well-known sex difference in mood and anxiety disorders, the mechanisms through which ovarian hormone changes contribute to stress regulation are not well understood. One mechanism by which ovarian hormones might impact mood regulation is by mediating the effect of psychosocial stress, which often precedes depressive episodes and may have mood consequences that are particularly relevant in women. In the current study, brain activity and mood response to psychosocial stress was examined in healthy, normally cycling women at either the high or low estradiol phase of the menstrual cycle. Twenty eight women were exposed to the Montreal Imaging Stress Task (MIST), with brain activity determined through functional magnetic resonance imaging, and behavioral response assessed with subjective mood and stress measures. Brain activity responses to psychosocial stress differed between women in the low versus high estrogen phase of the menstrual cycle: women with high estradiol levels showed significantly less deactivation in limbic regions during psychosocial stress compared to women with low estradiol levels. Additionally, women with higher estradiol levels also had less subjective distress in response to the MIST than women with lower estradiol levels. The results of this study suggest that, in normally cycling premenopausal women, high estradiol levels attenuate the brain activation changes and negative mood response to psychosocial stress. Normal ovarian hormone fluctuations may alter the impact of psychosocially stressful events by presenting periods of increased vulnerability to psychosocial stress during low estradiol phases of the menstrual cycle. This menstrual cycle-related fluctuation in stress vulnerability may be relevant to the greater risk for affective disorder or post-traumatic stress disorder in women. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Psychosocial stress and asthma morbidity.

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    Yonas, Michael A; Lange, Nancy E; Celedón, Juan C

    2012-04-01

    The objective of this review is to provide an overview and discussion of recent epidemiologic and mechanistic studies of stress in relation to asthma incidence and morbidity. Recent findings suggest that stress, whether at the individual (i.e. epigenetics, perceived stress), family (i.e. prenatal maternal stress, early-life exposure, or intimate partner violence) or community (i.e. neighborhood violence; neighborhood disadvantage) level, influences asthma and asthma morbidity. Key recent findings regarding how psychosocial stress may influence asthma through Posttraumatic Stress Disorder, prenatal and postnatal maternal/caregiver stress, and community violence and deprivation are highlighted. New research illustrates the need to further examine, characterize, and address the influence of social and environmental factors (i.e. psychological stress) on asthma. Further, research and innovative methodologies are needed to characterize the relationship and pathways associated with stress at multiple levels to more fully understand and address asthma morbidity, and to design potential interventions, especially to address persistent disparities in asthma in ethnic minorities and economically disadvantaged communities.

  1. Evaluation of the analgesic effect of aqueous extract of Brugmansia suaveolens flower in mice: possible mechanism involved.

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    Muccillo-Baisch, Ana Luiza; Parker, Alexander Garcia; Cardoso, Gianni Peraza; Cezar-Vaz, Marta Regina; Soares, Maria Cristina Flores

    2010-04-01

    The study was conducted to test the aqueous extract of Brugmansia suaveolens (AEBs) flowers for their antinociceptive effects in mice. In the hot plate test, a significant increase in reaction time for two doses of AEBs at 60, 90, 120, and 150 min after treatment was noted. Pretreatment of animals with naloxone (5 mg/kg, intraperitoneally [IP]) left the antinociceptive effect of AEBs at a dose of 100 mg/kg unaffected at 60, 90, 120, and 150 min after treatment and at a dose of 300 mg/kg at 30 min but not at 90, 120, and 150 min. In the writhing test, the AEBs significantly inhibited acetic acid-induced abdominal constriction and was equally potent at both doses. Pretreatment with naloxone (5 mg/kg, IP) left the antinociceptive effect of both doses of AEBs unaffected. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg, IP) caused a significant change in the number of abdominal constrictions but did not change the antinociceptive effect of AEBs. Pretreatment of animals with methylene blue also did not change the effect of AEBs on the number of writhing movements in mice. Flumazenil (5 mg/kg, IP) antagonized the antinociceptive effects of diazepam and also reversed the antinociceptive effect of AEBs. AEBs showed a depressant effect on the central nervous system, and the treatment of mice with pentobarbital combined with AEBs increased the animals' sleeping time in a dose-dependent manner. These results suggest that the antinociceptive activity of AEBs may be related in part to benzodiazepine receptors, although peripheral mechanisms cannot be excluded.

  2. Phytochemicals in regulating fatty acid β-oxidation: Potential underlying mechanisms and their involvement in obesity and weight loss.

    Science.gov (United States)

    Rupasinghe, H P Vasantha; Sekhon-Loodu, Satvir; Mantso, Theodora; Panayiotidis, Mihalis I

    2016-09-01

    Excessive accumulation of fat as the result of more energy intake and less energy expenditure is known as obesity. Lipids are essential components in the human body and are vital for maintaining homeostasis and physiological as well as cellular metabolism. Fatty acid synthesis and catabolism (by fatty acid oxidation) are normal part of basic fuel metabolism in animals. Fatty acids are degraded in the mitochondria by a biochemical process called β-oxidation in which two-carbon fragments are produced in each cycle. The increase in fatty acid β-oxidation is negatively correlated with body mass index. Although healthy life style, avoiding Western diet, dieting and strenuous exercise are the commonly used methods to lose weight, they are not considered a permanent solution in addition to risk attenuation of basal metabolic rate (BMR). Pharmacotherapy offers benefits of weight loss by altering the satiety and lowering absorption of fat from the food; however, its side effects may outweigh the benefits of weight loss. Alternatively, dietary phytochemicals and natural health products offer great potential as an efficient weight loss strategy by modulating lipid metabolism and/or increasing BMR and thermogenesis. Specifically, polyphenols such as citrus flavonoids, green tea epigallocatechin gallate, resveratrol, capsaicin and curcumin, have been reported to increase lipolysis and induce fatty acid β-oxidation through modulation of hormone sensitive lipase, acetyl-coA carboxylase, carnitine acyl transferase and peroxisome proliferator-activated receptor gamma coactivator-1. In this review article, we discuss selected phytochemicals in relation to their integrated functionalities and specific mechanisms for weight loss. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Sarcoplasmic phospholamban protein is involved in the mechanisms of postresuscitation myocardial dysfunction and the cardioprotective effect of nitrite during resuscitation.

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    Yu Huang

    Full Text Available OBJECTIVES: Sarcoplasmic reticulum (SR Ca(2+-handling proteins play an important role in myocardial dysfunction after acute ischemia/reperfusion injury. We hypothesized that nitrite would improve postresuscitation myocardial dysfunction by increasing nitric oxide (NO generation and that the mechanism of this protection is related to the modulation of SR Ca(2+-handling proteins. METHODS: We conducted a randomized prospective animal study using male Sprague-Dawley rats. Cardiac arrest was induced by intravenous bolus of potassium chloride (40 µg/g. Nitrite (1.2 nmol/g or placebo was administered when chest compression was started. No cardiac arrest was induced in the sham group. Hemodynamic parameters were monitored invasively for 90 minutes after the return of spontaneous circulation (ROSC. Echocardiogram was performed to evaluate cardiac function. Myocardial samples were harvested 5 minutes and 1 hour after ROSC. RESULTS: Myocardial function was significantly impaired in the nitrite and placebo groups after resuscitation, whereas cardiac function (i.e., ejection fraction and fractional shortening was significantly greater in the nitrite group than in the placebo group. Nitrite administration increased the level of nitric oxide in the myocardium 5 min after resuscitation compared to the other two groups. The levels of phosphorylated phospholamban (PLB were decreased after resuscitation, and nitrite increased the phosphorylation of phospholamban compared to the placebo. No significant differences were found in the expression of sarcoplasmic reticulum Ca(2+ ATPase (SERCA2a and ryanodine receptors (RyRs. CONCLUSIONS: postresuscitation myocardial dysfunction is associated with the impairment of PLB phosphorylation. Nitrite administered during resuscitation improves postresuscitation myocardial dysfunction by preserving phosphorylated PLB protein during resuscitation.

  4. Mechanisms involved in abdominal nociception induced by either TRPV1 or TRPA1 stimulation of rat peritoneum.

    Science.gov (United States)

    Trevisan, Gabriela; Rossato, Mateus F; Hoffmeister, Carin; Oliveira, Sara M; Silva, Cássia R; Matheus, Filipe C; Mello, Gláucia C; Antunes, Edson; Prediger, Rui D S; Ferreira, Juliano

    2013-08-15

    Abdominal pain is a frequent symptom of peritoneal cavity irritation, but little is known about the role of the receptors for irritant substances, transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1), in this painful condition. Thus, we investigated the abdominal nociception caused by peritoneal stimulation with TRPV1 (capsaicin) and TRPA1 (allyl isothiocyanate, AITC) agonists and their mechanisms in rats. The intraperitoneal (i.p.) injection of either capsaicin or AITC (0.03-10 mg/kg) induced short-term (up to 20 min) and dose-dependent abdominal nociception, and also produced c-fos expression in spinal afferents of the dorsal horn. TRPV1 antagonism prevented (94 ± 4% inhibition) nociception induced by capsaicin but not by AITC. In contrast, the TRPA1 antagonism almost abolished AITC-induced nociception (95 ± 2% inhibition) without altering the capsaicin response. Moreover, nociception induced by either capsaicin or AITC was reduced by the desensitisation of TRPV1-positive sensory fibres with resiniferatoxin (73 ± 18 and 76 ± 15% inhibitions, respectively) and by the NK1 receptor antagonist aprepitant (56 ± 5 and 53 ± 8% inhibitions, respectively). Likewise, the i.p. injections of capsaicin or AITC increased the content of substance P in the peritoneal fluid. Nevertheless, neither the mast cell membrane stabiliser cromoglycate, nor the H1 antagonist promethazine, nor depletion of peritoneal macrophages affected abdominal nociception induced either by capsaicin or AITC. Accordingly, neither capsaicin nor AITC increased the histamine content in the peritoneal fluid or provoked peritoneal mast cell degranulation in vitro. Collectively, our findings suggest that TRPV1 and TRPA1 stimulation in the peritoneum produces abdominal nociception that is mediated by sensory fibres activation.

  5. Regulation of the CDP-choline pathway by sterol regulatory element binding proteins involves transcriptional and post-transcriptional mechanisms.

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    Ridgway, Neale D; Lagace, Thomas A

    2003-06-15

    The synthesis of phosphatidylcholine (PtdCho) by the CDP-choline pathway is under the control of the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CCT). Sterol regulatory element binding proteins (SREBPs) have been proposed to regulate CCT at the transcriptional level, or via the synthesis of lipid activators or substrates of the CDP-choline pathway. To assess the contributions of these two mechanisms, we examined CCTalpha expression and PtdCho synthesis by the CDP-choline pathway in cholesterol and fatty acid auxotrophic CHO M19 cells inducibly expressing constitutively active nuclear forms of SREBP1a or SREBP2. Induction of either SREBP resulted in increased expression of mRNAs for sterol-regulated genes, elevated fatty acid and cholesterol synthesis (>10-50-fold) and increased PtdCho synthesis (2-fold). CCTalpha mRNA was increased 2-fold by enforced expression of SREBP1a or SREBP2. The resultant increase in CCTalpha protein and activity (2-fold) was restricted primarily to the soluble fraction of cells, and increased CCTalpha activity in vivo was not detected. Inhibition of the synthesis of fatty acids or their CoA esters by cerulenin or triacsin C respectively following SREBP induction effectively blocked the accompanying elevation in PtdCho synthesis. Thus PtdCho synthesis was driven by increased synthesis of fatty acids or a product thereof. These data show that transcriptional activation of CCTalpha is modest relative to that of other SREBP-regulated genes, and that stimulation of PtdCho synthesis by SREBPs in CHO cells is due primarily to increased fatty acid synthesis.

  6. Structural and Molecular Mechanism of CdpR Involved in Quorum-Sensing and Bacterial Virulence in Pseudomonas aeruginosa.

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    Jingru Zhao

    2016-04-01

    Full Text Available Although quorum-sensing (QS systems are important regulators of virulence gene expression in the opportunistic human pathogen Pseudomonas aeruginosa, their detailed regulatory mechanisms have not been fully characterized. Here, we show that deletion of PA2588 resulted in increased production of pyocyanin and biofilm, as well as enhanced pathogenicity in a mouse model. To gain insights into the function of PA2588, we performed a ChIP-seq assay and identified 28 targets of PA2588, including the intergenic region between PA2588 and pqsH, which encodes the key synthase of Pseudomonas quinolone signal (PQS. Though the C-terminal domain was similar to DNA-binding regions of other AraC family members, structural studies revealed that PA2588 has a novel fold at the N-terminal region (NTR, and its C-terminal HTH (helix-turn-helix domain is also unique in DNA recognition. We also demonstrated that the adaptor protein ClpS, an essential regulator of ATP-dependent protease ClpAP, directly interacted with PA2588 before delivering CdpR to ClpAP for degradation. We named PA2588 as CdpR (ClpAP-degradation and pathogenicity Regulator. Moreover, deletion of clpP or clpS/clpA promotes bacterial survival in a mouse model of acute pneumonia infection. Taken together, this study uncovered that CdpR is an important QS regulator, which can interact with the ClpAS-P system to regulate the expression of virulence factors and pathogenicity.

  7. Two non-target mechanisms are involved in glyphosate-resistant horseweed (Conyza canadensis L. Cronq.) biotypes.

    Science.gov (United States)

    González-Torralva, Fidel; Rojano-Delgado, Antonia M; Luque de Castro, María D; Mülleder, Norbert; De Prado, Rafael

    2012-11-15

    The physiological and biochemical bases for glyphosate resistance and susceptibility in horseweed (Conyza canadensis L. Cronq.) populations collected from Córdoba, Huelva, Málaga, Jaén and Seville in southern Spain were investigated. Screening 25 populations treated with glyphosate (238gacidequivalentha(-1)) at the rosette stage (BBCH 14-15) revealed reductions in fresh weight (fw) of 9-99%. The resistant biotype (R C004) was 6.1 times more resistant than the susceptible biotype (S). Shikimate accumulation in both biotypes increased until 72h after treatment (HAT), and then continued to increase (to 61.2%) in the S biotype, but decreased by 40% in the R (C004) biotype. Differential glyphosate spray retention and foliar uptake of applied (14)C-glyphosate between the R (C004) and S biotype had no effect on resistance to this herbicide. Quantitative and qualitative tests showed greater (14)C-glyphosate mobility in the S biotype than in the R (C004) biotype. Glyphosate was metabolized faster in the R (C004) biotype than in the S biotype. The herbicide disappeared completely from the R (C004) biotype by conversion into glyoxylate, sarcosine and aminomethylphosphonic acid within 96 HAT. On the other hand, 41.43nmolg(-1)fw of all glyphosate applied remained in the S biotype and glyoxylate was its only non-toxic metabolite. These results suggest that glyphosate resistance in horseweed is due to two different non-target mechanisms, namely: (a) impaired glyphosate translocation and (b) glyphosate metabolism to other compounds.

  8. Mechanism of Hyperinsulinism in Short-chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency Involves Activation of Glutamate Dehydrogenase*

    Science.gov (United States)

    Li, Changhong; Chen, Pan; Palladino, Andrew; Narayan, Srinivas; Russell, Laurie K.; Sayed, Samir; Xiong, Guoxiang; Chen, Jie; Stokes, David; Butt, Yasmeen M.; Jones, Patricia M.; Collins, Heather W.; Cohen, Noam A.; Cohen, Akiva S.; Nissim, Itzhak; Smith, Thomas J.; Strauss, Arnold W.; Matschinsky, Franz M.; Bennett, Michael J.; Stanley, Charles A.

    2010-01-01

    The mechanism of insulin dysregulation in children with hyperinsulinism associated with inactivating mutations of short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) was examined in mice with a knock-out of the hadh gene (hadh−/−). The hadh−/− mice had reduced levels of plasma glucose and elevated plasma insulin levels, similar to children with SCHAD deficiency. hadh−/− mice were hypersensitive to oral amino acid with decrease of glucose level and elevation of insulin. Hypersensitivity to oral amino acid in hadh−/− mice can be explained by abnormal insulin responses to a physiological mixture of amino acids and increased sensitivity to leucine stimulation in isolated perifused islets. Measurement of cytosolic calcium showed normal basal levels and abnormal responses to amino acids in hadh−/− islets. Leucine, glutamine, and alanine are responsible for amino acid hypersensitivity in islets. hadh−/− islets have lower intracellular glutamate and aspartate levels, and this decrease can be prevented by high glucose. hadh−/− islets also have increased [U-14C]glutamine oxidation. In contrast, hadh−/− mice have similar glucose tolerance and insulin sensitivity compared with controls. Perifused hadh−/− islets showed no differences from controls in response to glucose-stimulated insulin secretion, even with addition of either a medium-chain fatty acid (octanoate) or a long-chain fatty acid (palmitate). Pull-down experiments with SCHAD, anti-SCHAD, or anti-GDH antibodies showed protein-protein interactions between SCHAD and GDH. GDH enzyme kinetics of hadh−/− islets showed an increase in GDH affinity for its substrate, α-ketoglutarate. These studies indicate that SCHAD deficiency causes hyperinsulinism by activation of GDH via loss of inhibitory regulation of GDH by SCHAD. PMID:20670938

  9. Murine neural stem cells model Hunter disease in vitro: glial cell-mediated neurodegeneration as a possible mechanism involved.

    Science.gov (United States)

    Fusar Poli, E; Zalfa, C; D'Avanzo, F; Tomanin, R; Carlessi, L; Bossi, M; Nodari, L Rota; Binda, E; Marmiroli, P; Scarpa, M; Delia, D; Vescovi, A L; De Filippis, L

    2013-11-07

    Mucopolysaccharidosis type II (MPSII or Hunter Syndrome) is a lysosomal storage disorder caused by the deficit of iduronate 2-sulfatase (IDS) activity and characterized by progressive systemic and neurological impairment. As the early mechanisms leading to neuronal degeneration remain elusive, we chose to examine the properties of neural stem cells (NSCs) isolated from an animal model of the disease in order to evaluate whether their neurogenic potential could be used to recapitulate the early phases of neurogenesis in the brain of Hunter disease patients. Experiments here reporte