WorldWideScience

Sample records for important mechanism involved

  1. Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.

    Science.gov (United States)

    Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P

    2012-08-01

    Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

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

    International Nuclear Information System (INIS)

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

    1998-01-01

    '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-fold

  3. Parental Involvement as a Important Factor for Successful Education

    Directory of Open Access Journals (Sweden)

    Maša Đurišić

    2017-09-01

    Full Text Available To comply with the system of integrated support for their students’, schools need to build partnership with parents and develop mutual responsibility for childrens’ success in the educational system. In this way, parental involement are increased, parents’ effort to support schools are encouraged, and they are directly making a positive impact to a successful educational system. Considering the importance of parents’ participation and involvement in school activities, in this paper, we will analyse the positive effects of parental involvement, summarize leading principles for the successful partnership of parents and school and present six factors (Parenting, Communicating, Volunteering, Learning at home, Decision-making and Collaborating with the community and six models (Protective Model, Expert Model, Transmission Model, Curriculum-Enrichment Model, Consumer Model and Partnership Model of parental involvement. In addition, we will draw conclusions and make recommendations that are important for planning programs that are focused on the improvement of parent involvement.

  4. Altered DNA methylation: a secondary mechanism involved in carcinogenesis.

    Science.gov (United States)

    Goodman, Jay I; Watson, Rebecca E

    2002-01-01

    This review focuses on the role that DNA methylation plays in the regulation of normal and aberrant gene expression and on how, in a hypothesis-driven fashion, altered DNA methylation may be viewed as a secondary mechanism involved in carcinogenesis. Research aimed at discerning the mechanisms by which chemicals can transform normal cells into frank carcinomas has both theoretical and practical implications. Through an increased understanding of the mechanisms by which chemicals affect the carcinogenic process, we learn more about basic biology while, at the same time, providing the type of information required to make more rational safety assessment decisions concerning their actual potential to cause cancer under particular conditions of exposure. One key question is: does the mechanism of action of the chemical in question involve a secondary mechanism and, if so, what dose may be below its threshold?

  5. THE MECHANISM OF IMPLEMENTATION OF THE POLICYOF IMPORT SUBSTITUTION IN THE ARKHANGELSK REGION

    Directory of Open Access Journals (Sweden)

    N. Didenko

    2015-01-01

    Full Text Available In modern conditions of development of the world economy and the processes of globalization increasingly raises the question of the independence of the region from products that are necessary for the viability of the population purchased from third-party States. One of the ways of development of the region is the strategy of active import substitution. In this work, we studied the methods of implementation of the active import substitution strategy. We propose a variant of development of the mechanism of intensifi cation of active import substitution, which includes targeted comprehensive program, containing the plan of activities aimed at creating competitive advantages of enterprises involved in import substitution.

  6. Relative importance of nitrate and sulfate aerosol production mechanisms in urban atmospheres

    International Nuclear Information System (INIS)

    Middleton, P.; Kiang, C.S.

    1979-01-01

    The relative importance of the various sulfate and nitrate aerosol production mechanisms is calculated for different atmospheric conditions. The calculation scheme used to determine the rates of nitrate and sulfate production, based on the concept that vapor transfer to the aerosols and nitrate and sulfate formation within the aerosols are coupled kinetic processes, considers sulfate formation by ozone and hydrogen peroxide oxidation and catalytic oxidation in the presence of soot, iron and manganese of sulfite solutions and sulfuric acid condensation and nitrate formation by the liquid-phase oxidation of dissolved nitrogen oxides for different initial gas concentrations and particle compositions and sizes. It is found that sulfate production is higher under daytime conditions, primarily proceeding by mechanisms involving sulfuric acid and hydrogen peroxide, while at night oxidation processes on the surface of the aerosol film are more important. Nitrate tends to decrease nighttime sulfate production due to an increase in aerosol acidity and nitrate production is found to be higher under nighttime conditions and in the winter

  7. The Importance of Patient Involvement in Stroke Rehabilitation

    DEFF Research Database (Denmark)

    Kristensen, Hanne Kaae; Tistad, Malin; Koch, Lena von

    2016-01-01

    OBJECTIVE: To investigate the perceived needs for health services by persons with stroke within the first year after rehabilitation, and associations between perceived impact of stroke, involvement in decisions regarding care/treatment, and having health services needs met. METHOD: Data...... was collected, through a mail survey, from patients with stroke who were admitted to a university hospital in 2012 and had received rehabilitation after discharge from the stroke unit. The rehabilitation lasted an average of 2 to 4.6 months. The Stroke Survivor Needs Survey Questionnaire was used to assess....... CONCLUSIONS: The results highlight the importance of involving patients in making decisions on stroke rehabilitation, as it appears to be associated with meeting their health services needs....

  8. The mechanisms involved at the cell level

    International Nuclear Information System (INIS)

    Leblanc, G.; Pourcher, Th.; Perron, B.; Guillain, F.; Quemeneur, E.; Fritsch, P.

    2003-01-01

    The mechanisms responsible at the cell level for inducing toxic reactions after contamination are as yet only imperfectly known. Work still needs to be done for both contaminants that have a biological role, such as iodine, and those that do not, such as cadmium, uranium and plutonium. In particular, these mechanisms bring into play, in biological membranes, carriers which are the physiological partners responsible for material exchange with the environment or inside the body. As they lack absolute selectivity, these carriers, which are involved in the assimilation and accumulation of vital mineral elements, also have the ability to transport toxic elements and isotopes. (authors)

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

    Science.gov (United States)

    Bridges, Christy C.; Zalups, Rudolfs K.

    2016-01-01

    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. PMID:27422290

  10. An overview of potential molecular mechanisms involved in VSMC phenotypic modulation.

    Science.gov (United States)

    Zhang, Ming-Jie; Zhou, Yi; Chen, Lei; Wang, Yan-Qin; Wang, Xu; Pi, Yan; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

    2016-02-01

    The fully differentiated medial vascular smooth muscle cells (VSMCs) of mature vessels keep quiescent and contractile. However, VSMC can exhibit the plasticity in phenotype switching from a differentiated and contractile phenotype to a dedifferentiated state in response to alterations in local environmental cues, which is called phenotypic modulation or switching. Distinguishing from its differentiated state expressing more smooth muscle (SM)-specific/selective proteins, the phenotypic modulation in VSMC is characterized by an increased rate of proliferation, migration, synthesis of extracellular matrix proteins and decreased expression of SM contractile proteins. Although it has been well demonstrated that phenotypic modulation of VSMC contributes to the occurrence and progression of many proliferative vascular diseases, little is known about the details of the molecular mechanisms of VSMC phenotypic modulation. Growing evidence suggests that variety of molecules including microRNAs, cytokines and biochemical factors, membrane receptors, ion channels, cytoskeleton and extracellular matrix play important roles in controlling VSMC phenotype. The focus of the present review is to provide an overview of potential molecular mechanisms involved in VSMC phenotypic modulation in recent years. To clarify VSMC differentiation and phenotypic modulation mechanisms will contribute to producing cell-based therapeutic interventions for aberrant VSMC differentiation-related diseases.

  11. The Importance of Patient Involvement in Stroke Rehabilitation

    Science.gov (United States)

    2016-01-01

    Objective To investigate the perceived needs for health services by persons with stroke within the first year after rehabilitation, and associations between perceived impact of stroke, involvement in decisions regarding care/treatment, and having health services needs met. Method Data was collected, through a mail survey, from patients with stroke who were admitted to a university hospital in 2012 and had received rehabilitation after discharge from the stroke unit. The rehabilitation lasted an average of 2 to 4.6 months. The Stroke Survivor Needs Survey Questionnaire was used to assess the participants' perceptions of involvement in decisions on care or treatment and needs for health services in 11 problem areas: mobility, falls, incontinence, pain, fatigue, emotion, concentration, memory, speaking, reading, and sight. The perceived impact of stroke in eight areas was assessed using the Stroke Impact Scale (SIS) 3.0. Eleven logistic regression models were created to explore associations between having health services needs met in each problem area respectively (dependent variable) and the independent variables. In all models the independent variables were: age, sex, SIS domain corresponding to the dependent variable, or stroke severity in cases when no corresponding SIS domain was identified, and involvement in decisions on care and treatment. Results The 63 participants who returned the questionnaires had a mean age of 72 years, 33 were male and 30 were female. Eighty percent had suffered a mild stroke. The number of participants who reported problems varied between 51 (80%, mobility) and 24 (38%, sight). Involvement in decisions on care and treatment was found to be associated with having health services needs met in six problem areas: falls, fatigue, emotion, memory, speaking, and reading. Conclusions The results highlight the importance of involving patients in making decisions on stroke rehabilitation, as it appears to be associated with meeting their health

  12. Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression.

    Science.gov (United States)

    Verduijn, J; Milaneschi, Y; Schoevers, R A; van Hemert, A M; Beekman, A T F; Penninx, B W J H

    2015-09-29

    involved in MDD's etiology. These same mechanisms, however, are less important in clinical progression from first to later MDD episodes and toward chronicity.

  13. Psychoeducational preparation of children for surgery: the importance of parental involvement.

    Science.gov (United States)

    Li, Ho Cheung William; Lopez, Violeta; Lee, Tin Loi Isabel

    2007-01-01

    To examine the effects of therapeutic play intervention on outcomes of children undergoing day surgery, and to highlight the importance of parental involvement in the psychoeducational preparation of children for surgery. A randomized controlled trial, two group pre-test and repeated post-test, between subjects design was employed. Hong Kong Chinese children (7-12 years of age; n=203) admitted for elective surgery in a day surgery unit, along with their parents during a 13-month period, were invited to participate in the study. By using a simple complete randomization method, 97 of children with their parents were assigned to the experimental group receiving therapeutic play intervention, and 106 children with their parents were assigned to the control group receiving routine information preparation. The results showed that both children and their parents in the experimental group reported lower state anxiety scores in pre- and post-operative periods. Children in the experimental group exhibited fewer instances of negative emotional behaviors and parents in the experimental group reported greater satisfaction. The results, however, find no differences in children's post-operative pain between the two groups. The study provides empirical evidence to support the effectiveness of using therapeutic play intervention and the importance of parental involvement in the psychoeducational preparation of children for surgery. The findings heighten the awareness of the importance of integrating therapeutic play and parental involvement as essential components of holistic and quality nursing care to prepare children for surgery.

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

    International Nuclear Information System (INIS)

    Brenes, J.C.; Broiz, A.C.; Bassi, G.S.; Schwarting, R.K.W.; Brandão, M.L.

    2012-01-01

    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 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

  15. 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.

  16. 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

  17. Education on invasive mechanical ventilation involving intensive care nurses: a systematic review.

    Science.gov (United States)

    Guilhermino, Michelle C; Inder, Kerry J; Sundin, Deborah

    2018-03-26

    Intensive care unit nurses are critical for managing mechanical ventilation. Continuing education is essential in building and maintaining nurses' knowledge and skills, potentially improving patient outcomes. The aim of this study was to determine whether continuing education programmes on invasive mechanical ventilation involving intensive care unit nurses are effective in improving patient outcomes. Five electronic databases were searched from 2001 to 2016 using keywords such as mechanical ventilation, nursing and education. Inclusion criteria were invasive mechanical ventilation continuing education programmes that involved nurses and measured patient outcomes. Primary outcomes were intensive care unit mortality and in-hospital mortality. Secondary outcomes included hospital and intensive care unit length of stay, length of intubation, failed weaning trials, re-intubation incidence, ventilation-associated pneumonia rate and lung-protective ventilator strategies. Studies were excluded if they excluded nurses, patients were ventilated for less than 24 h, the education content focused on protocol implementation or oral care exclusively or the outcomes were participant satisfaction. Quality was assessed by two reviewers using an education intervention critical appraisal worksheet and a risk of bias assessment tool. Data were extracted independently by two reviewers and analysed narratively due to heterogeneity. Twelve studies met the inclusion criteria for full review: 11 pre- and post-intervention observational and 1 quasi-experimental design. Studies reported statistically significant reductions in hospital length of stay, length of intubation, ventilator-associated pneumonia rates, failed weaning trials and improvements in lung-protective ventilation compliance. Non-statistically significant results were reported for in-hospital and intensive care unit mortality, re-intubation and intensive care unit length of stay. Limited evidence of the effectiveness of

  18. 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

  19. Mechanisms and factors involved in hip injuries during frontal crashes.

    Science.gov (United States)

    Yoganandan, N; Pintar, F A; Gennarelli, T A; Maltese, M R; Eppinger, R H

    2001-11-01

    This study was conducted to collect data and gain insights relative to the mechanisms and factors involved in hip injuries during frontal crashes and to study the tolerance of hip injuries from this type of loading. Unembalmed human cadavers were seated on a standard automotive seat (reinforced) and subjected to knee impact test to each lower extremity. Varying combinations of flexion and adduction/abduction were used for initial alignment conditions and pre-positioning. Accelerometers were fixed to the iliac wings and twelfth thoracic vertebral spinous process. A 23.4-kg padded pendulum impacted the knee at velocities ranging from 4.3 to 7.6 m/s. The impacting direction was along the anteroposterior axis, i.e., the global X-axis, in the body-fixed coordinate system. A load cell on the front of the pendulum recorded the impact force. Peak impact forces ranged from 2,450 to 10,950 N. The rate of loading ranged from 123 to 7,664 N/msec. The impulse values ranged from 12.4 to 31.9 Nsec. Injuries were not apparent in three tests. Eight tests resulted in trauma. Fractures involving the pelvis including the acetabulum and proximal femur occurred in five out of the eight tests, and distal femoral bone fracture occurred in one test. These results underscore the importance of leg pre-positioning and the orientation of the impacting axis to produce specific types of trauma to the pelvic region of the lower extremity.

  20. 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.

  1. Arbuscular mycorrhizal fungi for the biocontrol of plant-parasitic nematodes: a review of the mechanisms involved

    Directory of Open Access Journals (Sweden)

    Nele eSchouteden

    2015-11-01

    Full Text Available 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 towards future field applications of AMF against PPN. The scientific community has entered an exciting era that provide 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.

  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. PMID:26635750

  3. 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.

  4. Neurobiological mechanisms involved in sleep bruxism.

    Science.gov (United States)

    Lavigne, G J; Kato, T; Kolta, A; Sessle, B J

    2003-01-01

    Sleep bruxism (SB) is reported by 8% of the adult population and is mainly associated with rhythmic masticatory muscle activity (RMMA) characterized by repetitive jaw muscle contractions (3 bursts or more at a frequency of 1 Hz). The consequences of SB may include tooth destruction, jaw pain, headaches, or the limitation of mandibular movement, as well as tooth-grinding sounds that disrupt the sleep of bed partners. SB is probably an extreme manifestation of a masticatory muscle activity occurring during the sleep of most normal subjects, since RMMA is observed in 60% of normal sleepers in the absence of grinding sounds. The pathophysiology of SB is becoming clearer, and there is an abundance of evidence outlining the neurophysiology and neurochemistry of rhythmic jaw movements (RJM) in relation to chewing, swallowing, and breathing. The sleep literature provides much evidence describing the mechanisms involved in the reduction of muscle tone, from sleep onset to the atonia that characterizes rapid eye movement (REM) sleep. Several brainstem structures (e.g., reticular pontis oralis, pontis caudalis, parvocellularis) and neurochemicals (e.g., serotonin, dopamine, gamma aminobutyric acid [GABA], noradrenaline) are involved in both the genesis of RJM and the modulation of muscle tone during sleep. It remains unknown why a high percentage of normal subjects present RMMA during sleep and why this activity is three times more frequent and higher in amplitude in SB patients. It is also unclear why RMMA during sleep is characterized by co-activation of both jaw-opening and jaw-closing muscles instead of the alternating jaw-opening and jaw-closing muscle activity pattern typical of chewing. The final section of this review proposes that RMMA during sleep has a role in lubricating the upper alimentary tract and increasing airway patency. The review concludes with an outline of questions for future research.

  5. 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.

  6. The importance of the strain rate and creep on the stress corrosion cracking mechanisms and models

    International Nuclear Information System (INIS)

    Aly, Omar F.; Mattar Neto, Miguel; Schvartzman, Monica M.A.M.

    2011-01-01

    Stress corrosion cracking is a nuclear, power, petrochemical, and other industries equipment and components (like pressure vessels, nozzles, tubes, accessories) life degradation mode, involving fragile fracture. The stress corrosion cracking failures can produce serious accidents, and incidents which can put on risk the safety, reliability, and efficiency of many plants. These failures are of very complex prediction. The stress corrosion cracking mechanisms are based on three kinds of factors: microstructural, mechanical and environmental. Concerning the mechanical factors, various authors prefer to consider the crack tip strain rate rather than stress, as a decisive factor which contributes to the process: this parameter is directly influenced by the creep strain rate of the material. Based on two KAPL-Knolls Atomic Power Laboratory experimental studies in SSRT (slow strain rate test) and CL (constant load) test, for prediction of primary water stress corrosion cracking in nickel based alloys, it has done a data compilation of the film rupture mechanism parameters, for modeling PWSCC of Alloy 600 and discussed the importance of the strain rate and the creep on the stress corrosion cracking mechanisms and models. As derived from this study, a simple theoretical model is proposed, and it is showed that the crack growth rate estimated with Brazilian tests results with Alloy 600 in SSRT, are according with the KAPL ones and other published literature. (author)

  7. Risk Perception of Plastic Pollution: Importance of Stakeholder Involvement and Citizen Science

    DEFF Research Database (Denmark)

    Syberg, Kristian; Hansen, Steffen Foss; Christensen, Thomas Budde

    2017-01-01

    , the public, and policy makers and elaborate on how the eight risk drivers have influenced this process. Plastic pollution has several of the characteristics that can enhance people’s perception of the risk as being important and which has generated great awareness of the problem. The chapter finally...... discusses how risk perception can be improved by greater stakeholder involvement and utilization of citizen science and thereby improve the foundation for timely and efficient societal measures....

  8. 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.

  9. 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.

  10. 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.

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

    International Nuclear Information System (INIS)

    Wang, Jun; Cao, Hui; Wang, Hongjie; Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli; Xiang, Ming

    2015-01-01

    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 + CD25 + Foxp3 + 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

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

    International Nuclear Information System (INIS)

    Kaneuji, Takeshi; Ariyoshi, Wataru; Okinaga, Toshinori; Toshinaga, Akihiro; Takahashi, Tetsu; Nishihara, Tatsuji

    2011-01-01

    Highlights: → Effect of compressive force on osteoblasts were examined. → Compressive force induced OPG expression and suppressed osteoclastogenesis. → 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 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-κB 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 IκBα, 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 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-κB) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt/Ca 2+ pathway.

  13. 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

  14. The Atmospherically Important Reaction of Hydroxyl Radicals with Methyl Nitrate: A Theoretical Study Involving the Calculation of Reaction Mechanisms, Enthalpies, Activation Energies, and Rate Coefficients.

    Science.gov (United States)

    Ng, Maggie; Mok, Daniel K W; Lee, Edmond P F; Dyke, John M

    2017-09-07

    A theoretical study, involving the calculation of reaction enthalpies, activation energies, mechanisms, and rate coefficients, was made of the reaction of hydroxyl radicals with methyl nitrate, an important process for methyl nitrate removal in the earth's atmosphere. Four reaction channels were considered: formation of H 2 O + CH 2 ONO 2 , CH 3 OOH + NO 2 , CH 3 OH + NO 3 , and CH 3 O + HNO 3 . For all channels, geometry optimization and frequency calculations were performed at the M06-2X/6-31+G** level, while relative energies were improved at the UCCSD(T*)-F12/CBS level. The major channel is found to be the H abstraction channel, to give the products H 2 O + CH 2 ONO 2 . The reaction enthalpy (ΔH 298 K RX ) of this channel is computed as -17.90 kcal mol -1 . Although the other reaction channels are also exothermic, their reaction barriers are high (>24 kcal mol -1 ), and therefore these reactions do not contribute to the overall rate coefficient in the temperature range considered (200-400 K). Pathways via three transition states were identified for the H abstraction channel. Rate coefficients were calculated for these pathways at various levels of variational transition state theory including tunneling. The results obtained are used to distinguish between two sets of experimental rate coefficients, measured in the temperature range of 200-400 K, one of which is approximately an order of magnitude greater than the other. This comparison, as well as the temperature dependence of the computed rate coefficients, shows that the lower experimental values are favored. The implications of the results to atmospheric chemistry are discussed.

  15. Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injury

    Science.gov (United States)

    Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injuryHenriquez, A.1, Snow, S.2, Miller, D1.,Schladweiler, M.2 and Kodavanti, U2.1 Curriculum in Toxicology, UNC, Chapel Hill, NC. 2 EPHD/NHEERL, US EPA, RTP, Durham, NC. ...

  16. Importance of Silicon and Mechanisms of Biosilica Formation in Plants

    Science.gov (United States)

    Siti Nor Akmar, Abdullah; Rafii, Mohd Y.; Tengoua, F. F.; Nurul Mayzaitul Azwa, Jamaludin; Shabanimofrad, M.

    2015-01-01

    Silicon (Si) is one of the most prevalent macroelements, performing an essential function in healing plants in response to environmental stresses. The purpose of using Si is to induce resistance to distinct stresses, diseases, and pathogens. Additionally, Si can improve the condition of soils, which contain toxic levels of heavy metals along with other chemical elements. Silicon minimizes toxicity of Fe, Al, and Mn, increases the availability of P, and enhances drought along with salt tolerance in plants through the formation of silicified tissues in plants. However, the concentration of Si depends on the plants genotype and organisms. Hence, the physiological mechanisms and metabolic activities of plants may be affected by Si application. Peptides as well as amino acids can effectively create polysilicic species through interactions with different species of silicate inside solution. The carboxylic acid and the alcohol groups of serine and asparagine tend not to engage in any significant role in polysilicates formation, but the hydroxyl group side chain can be involved in the formation of hydrogen bond with Si(OH)4. The mechanisms and trend of Si absorption are different between plant species. Furthermore, the transportation of Si requires an energy mechanism; thus, low temperatures and metabolic repressors inhibit Si transportation. PMID:25685787

  17. Importance of Silicon and Mechanisms of Biosilica Formation in Plants

    Directory of Open Access Journals (Sweden)

    Mahbod Sahebi

    2015-01-01

    Full Text Available Silicon (Si is one of the most prevalent macroelements, performing an essential function in healing plants in response to environmental stresses. The purpose of using Si is to induce resistance to distinct stresses, diseases, and pathogens. Additionally, Si can improve the condition of soils, which contain toxic levels of heavy metals along with other chemical elements. Silicon minimizes toxicity of Fe, Al, and Mn, increases the availability of P, and enhances drought along with salt tolerance in plants through the formation of silicified tissues in plants. However, the concentration of Si depends on the plants genotype and organisms. Hence, the physiological mechanisms and metabolic activities of plants may be affected by Si application. Peptides as well as amino acids can effectively create polysilicic species through interactions with different species of silicate inside solution. The carboxylic acid and the alcohol groups of serine and asparagine tend not to engage in any significant role in polysilicates formation, but the hydroxyl group side chain can be involved in the formation of hydrogen bond with Si(OH4. The mechanisms and trend of Si absorption are different between plant species. Furthermore, the transportation of Si requires an energy mechanism; thus, low temperatures and metabolic repressors inhibit Si transportation.

  18. Transmitting Sport Values: The Importance of Parental Involvement in Children’s Sport Activity

    Directory of Open Access Journals (Sweden)

    Francesca Danioni

    2017-03-01

    Full Text Available The transmission of positive values between parents and children is generally considered to be the hallmark of successful socialization. As this issue has been widely discussed but surprisingly little researched - especially with reference to core sport values - in this study we aimed to: 1 analyze adolescent athletes’ acceptance of the sport values their parents want to transmit to them (i.e., parental socialization values and 2 examine the relationship between parental involvement in children’s sportive activity and adolescents’ acceptance of their parents’ socialization values. One hundred and seventy-two Italian adolescents (48.3% male, 51.7% female who regularly practice team sports were asked to fill out a questionnaire which included the Youth Sport Values Questionnaire – 2 and the Parental Involvement in Sport Questionnaire. The dyadic correlations revealed that young athletes are in general willing to accept their parents’ socialization values in regards to sport. Moreover, from the relative weight analysis (a relatively new data analysis strategy, it emerged that parental involvement characterized by praise and understanding is the most important predictor of adolescents’ willingness to accept their parents’ sport values. Implications of these results and further expansion of the study are discussed.

  19. Bifidobacterium breve MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect

    Science.gov (United States)

    MURATA, Kozue; TOMOSADA, Yohsuke; VILLENA, Julio; CHIBA, Eriko; SHIMAZU, Tomoyuki; ASO, Hisashi; IWABUCHI, Noriyuki; XIAO, Jin-zhong; SAITO, Tadao; KITAZAWA, Haruki

    2014-01-01

    Bifidobacterium breve MCC-117 is able to significantly reduce the expression of inflammatory cytokines in porcine intestinal epithelial (PIE) cells and to improve IL-10 levels in CD4+CD25high Foxp3+ lymphocytes in response to heat-stable enterotoxigenic Escherichia coli (ETEC) pathogen-associated molecular patterns (PAMPs), while the immunoregulatory effect of B. adolescentis ATCC15705 was significantly lower than that observed for the MCC-117 strain. Considering the different capacities of the two bifidobacterium strains to activate toll-like receptor (TLR)-2 and their differential immunoregulatory activities in PIE and immune cells, we hypothesized that comparative studies with both strains could provide important information regarding the molecular mechanism(s) involved in the anti-inflammatory activity of bifidobacteria. In this work, we demonstrated that the anti-inflammatory effect of B. breve MCC-117 was achieved by a complex interaction of multiple negative regulators of TLRs as well as inhibition of multiple signaling pathways. We showed that B. breve MCC-117 reduced heat-stable ETEC PAMP-induced NF-κB, p38 MAPK and PI3 K activation and expression of pro-inflammatory cytokines in PIE cells. In addition, we demonstrated that B. breve MCC-117 may activate TLR2 synergistically and cooperatively with one or more other pattern recognition receptors (PRRs), and that interactions may result in a coordinated sum of signals that induce the upregulation of A20, Bcl-3, Tollip and SIGIRR. Upregulation of these negative regulators could have an important physiological impact on maintaining or reestablishing homeostatic TLR signals in PIE cells. Therefore, in the present study, we gained insight into the molecular mechanisms involved in the immunoregulatory effect of B. breve MCC-117. PMID:24936377

  20. The Importance of Father Involvement in Early Childhood Programs

    Science.gov (United States)

    Ancell, Katherine S.; Bruns, Deborah A.; Chitiyo, Jonathan

    2018-01-01

    Active family involvement in Early Childhood Special Education (ECSE) is regarded as a beneficial factor in young children's learning and development. One definition of family involvement is the active role parents take in their child's development and the knowledge and participation they share with professionals who are part of the child's daily…

  1. Absorption of Carotenoids and Mechanisms Involved in Their Health-Related Properties.

    Science.gov (United States)

    Cervantes-Paz, Braulio; Victoria-Campos, Claudia I; Ornelas-Paz, José de Jesús

    Carotenoids participate in the normal metabolism and function of the human body. They are involved in the prevention of several diseases, especially those related to the inflammation syndrome. Their main mechanisms of action are associated to their potent antioxidant activity and capacity to regulate the expression of specific genes and proteins. Recent findings suggest that carotenoid metabolites may explain several processes where the participation of their parent carotenoids was unclear. The health benefits of carotenoids strongly depend on their absorption and transformation during gastrointestinal digestion. The estimation of the 'bioaccessibility' of carotenoids through in vitro models have made possible the evaluation of the effect of a large number of factors on key stages of carotenoid digestion and intestinal absorption. The bioaccessibility of these compounds allows us to have a clear idea of their potential bioavailability, a term that implicitly involves the biological activity of these compounds.

  2. Mechanisms involved in metformin action in the treatment of polycystic ovary syndrome.

    Science.gov (United States)

    Motta, A B

    2009-01-01

    The N, N' dimethyl-biguanide : Metformin is an antidiabetic drug that increases glucose utilization in insulin-sensitive tissues. As Polycystic Ovary Syndrome (PCOS) and diabetes share some altered parameters-such as abnormal glucose: insulin ratio, altered lipidic metabolism and insulin-resistance syndrome- the use of metformin has become increasingly accepted and widespread in the treatment of PCOS. Currently, metformin is used to induce ovulation and during early pregnancy in PCOS patients, however, a complete knowledge of the metformin action has not been achieved yet. This review describes beyond the classical reproductive action of metformin and explores other benefits of the drug. In addition, the present work discusses the molecular mechanisms involved further than the classical pathway that involves the AMP-activated protein kinase.

  3. Clustering mechanism of oxocarboxylic acids involving hydration reaction: Implications for the atmospheric models

    Science.gov (United States)

    Liu, Ling; Kupiainen-Määttä, Oona; Zhang, Haijie; Li, Hao; Zhong, Jie; Kurtén, Theo; Vehkamäki, Hanna; Zhang, Shaowen; Zhang, Yunhong; Ge, Maofa; Zhang, Xiuhui; Li, Zesheng

    2018-06-01

    The formation of atmospheric aerosol particles from condensable gases is a dominant source of particulate matter in the boundary layer, but the mechanism is still ambiguous. During the clustering process, precursors with different reactivities can induce various chemical reactions in addition to the formation of hydrogen bonds. However, the clustering mechanism involving chemical reactions is rarely considered in most of the nucleation process models. Oxocarboxylic acids are common compositions of secondary organic aerosol, but the role of oxocarboxylic acids in secondary organic aerosol formation is still not fully understood. In this paper, glyoxylic acid, the simplest and the most abundant atmospheric oxocarboxylic acid, has been selected as a representative example of oxocarboxylic acids in order to study the clustering mechanism involving hydration reactions using density functional theory combined with the Atmospheric Clusters Dynamic Code. The hydration reaction of glyoxylic acid can occur either in the gas phase or during the clustering process. Under atmospheric conditions, the total conversion ratio of glyoxylic acid to its hydration reaction product (2,2-dihydroxyacetic acid) in both gas phase and clusters can be up to 85%, and the product can further participate in the clustering process. The differences in cluster structures and properties induced by the hydration reaction lead to significant differences in cluster formation rates and pathways at relatively low temperatures.

  4. Family involvement and helping behavior in teams

    NARCIS (Netherlands)

    Brummelhuis, L.L. ten; Lippe, A.G. van der; Kluwer, E.S.

    2010-01-01

    Helping behavior at work has become increasingly important, with organizations making more and more use of cooperative work practices. The difficulty is that employees are facing growing demands beyond the workplace. This study investigates the mechanisms by which family involvement ( family

  5. Family involvement and helping behaviour in teams

    NARCIS (Netherlands)

    Brummelhuis, L.L. ten; Lippe, T. van der; Kluwer, E.S.

    2010-01-01

    Helping behavior at work has become increasingly important, with organizations making more and more use of cooperative work practices. The difficulty is that employees are facing growing demands beyond the workplace. This study investigates the mechanisms by which family involvement (family

  6. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

    OpenAIRE

    Lozano-Cuenca, J.; González-Hernández, A.; López-Canales, O.A.; Villagrana-Zesati, J.R.; Rodríguez-Choreão, J.D.; Morín-Zaragoza, R.; Castillo-Henkel, E.F.; López-Canales, J.S.

    2017-01-01

    Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10?9?10?5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-...

  7. Immature psychological defense mechanisms are associated with greater personal importance of junk food, alcohol, and television.

    Science.gov (United States)

    Costa, Rui Miguel; Brody, Stuart

    2013-10-30

    Immature psychological defense mechanisms are psychological processes that play an important role in suppressing emotional awareness and contribute to psychopathology. In addition, unhealthy food, television viewing, and alcohol consumption can be among the means to escape self-awareness. In contrast, engaging in, and responding fully to specifically penile-vaginal intercourse (PVI) is associated with indices of better emotional regulation, including less use of immature defense mechanisms. There was a lack of research on the association of immature defense mechanisms with personal importance of junk food, alcohol, television, PVI, and noncoital sex. In an online survey, 334 primarily Scottish women completed the Defense Style Questionnaire (DSQ-40), and rated the personal importance of junk food, alcohol, television, PVI, and noncoital sex. Immature defense mechanisms correlated with importance of junk food, alcohol, and television. Importance of PVI correlated with mature defenses, and less use of some component immature defenses. Importance of alcohol correlated with importance of junk food, television, and noncoital sex. Importance of junk food was correlated with importance of television and noncoital sex. The findings are discussed in terms of persons with poorer self-regulatory abilities having more interest in junk food, television, and alcohol, and less interest in PVI. © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Tokamak engineering mechanics

    International Nuclear Information System (INIS)

    Song, Yuntao; Wu, Weiyue; Du, Shijun

    2014-01-01

    Provides a systematic introduction to tokamaks in engineering mechanics. Includes design guides based on full mechanical analysis, which makes it possible to accurately predict load capacity and temperature increases. Presents comprehensive information on important design factors involving materials. Covers the latest advances in and up-to-date references on tokamak devices. Numerous examples reinforce the understanding of concepts and provide procedures for design. Tokamak Engineering Mechanics offers concise and thorough coverage of engineering mechanics theory and application for tokamaks, and the material is reinforced by numerous examples. Chapter topics include general principles, static mechanics, dynamic mechanics, thermal fluid mechanics and multiphysics structural mechanics of tokamak structure analysis. The theoretical principle of the design and the methods of the analysis for various components and load conditions are presented, while the latest engineering technologies are also introduced. The book will provide readers involved in the study of mechanical/fusion engineering with a general understanding of tokamak engineering mechanics.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

    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. - 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.

  10. 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.

  11. Involvement of translation and transcription processes into neurophysiological mechanisms of long-term memory reconsolidation.

    Science.gov (United States)

    Kozyrev, S A; Nikitin, V P

    2013-03-01

    We studied the involvement of translation and transcription processes into behavioral and neuronal mechanisms of reconsolidation of the long-term memory of the conditioned taste aversion in edible snails. Injection of cycloheximide (an inhibitor of protein synthesis) to the snails in 48 h after training combined with subsequent reminder and presentation of the conditional stimulus resulted in the development of persistent amnesia and depression of the responses of the defensive behavior command neurons LPl1 and RPl1 to the conditional stimulus. Injection of mRNA synthesis inhibitors actinomycin D or DRB (5,6-dichloro-1-β-D-ribofuranosylbenzimidasole) in 48 h after conditioning with subsequent reminding procedure produced no effects on memory retention and on the responses of the command neurons to the conditional stimulus. The study suggests that the proteins translated from previously synthesized and stored mRNA were involved in the mechanisms of reconsolidation of the memory responsible for conditioned taste aversion.

  12. Measures for Administration of the Import of Mechanical and Electronic Products

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ The Measures for the Administration of the Import of Mechanical and Electronic Products co-formulated by the Ministry of Commerce,the General Administration of Customs and the General Administration of Quality Supervision,Inspection and Quarantine,was hereby promul-gated,which entered into force as of May 1,2008.

  13. How the Quantity of Agricultural Mechanics Training Received at the Secondary Level Impact Teacher Perceived Importance of Agricultural Mechanics Skills

    Science.gov (United States)

    Rasty, John; Anderson, Ryan G.; Paulsen, Thomas H.

    2017-01-01

    Preservice teacher candidates in agricultural education have expressed concerns with teaching agricultural mechanics content yet the number of required courses in agricultural mechanics has dwindled. To determine the root of current teachers' perceptions, it is important to look at the developmental experiences that have led to those perceptions.…

  14. Hierarchy of mechanisms involved in generating Na/K-ATPase polarity in MDCK epithelial cells

    NARCIS (Netherlands)

    Mays, R.W.; Siemers, K.A.; Fritz, B.A.; Lowe, A.W.; van Meer, G.; Nelson, W.J.

    1995-01-01

    We have studied mechanisms involved in generating a polarized distribution of Na/K-ATPase in the basal-lateral membrane of two clones of MDCK II cells. Both clones exhibit polarized distributions of marker proteins of the apical and basal-lateral membranes, including Na/K-ATPase, at steady state.

  15. 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.

  16. Numerical and Experimental Study of Mechanisms Involved in Boiling Histotripsy.

    Science.gov (United States)

    Pahk, Ki Joo; Gélat, Pierre; Sinden, David; Dhar, Dipok Kumar; Saffari, Nader

    2017-12-01

    The aim of boiling histotripsy is to mechanically fractionate tissue as an alternative to thermal ablation for therapeutic applications. In general, the shape of a lesion produced by boiling histotripsy is tadpole like, consisting of a head and a tail. Although many studies have demonstrated the efficacy of boiling histotripsy for fractionating solid tumors, the exact mechanisms underpinning this phenomenon are not yet well understood, particularly the interaction of a boiling vapor bubble with incoming incident shockwaves. To investigate the mechanisms involved in boiling histotripsy, a high-speed camera with a passive cavitation detection system was used to observe the dynamics of bubbles produced in optically transparent tissue-mimicking gel phantoms exposed to the field of a 2.0-MHz high-intensity focused ultrasound (HIFU) transducer. We observed that boiling bubbles were generated in a localized heated region and cavitation clouds were subsequently induced ahead of the expanding bubble. This process was repeated with HIFU pulses and eventually resulted in a tadpole-shaped lesion. A simplified numerical model describing the scattering of the incident ultrasound wave by a vapor bubble was developed to help interpret the experimental observations. Together with the numerical results, these observations suggest that the overall size of a lesion induced by boiling histotripsy is dependent on the sizes of (i) the heated region at the HIFU focus and (ii) the backscattered acoustic field by the original vapor bubble. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

  17. 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

    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

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

    NARCIS (Netherlands)

    Conde de la Rosa, Laura; Schoemaker, Marieke H.; Vrenken, Titia E.; Buist-Homan, Manon; Havinga, Rick; Jansen, Peter L. M.; Moshage, Han

    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

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

    Science.gov (United States)

    Vidal-Dupiol, Jeremie; Adjeroud, Mehdi; Roger, Emmanuel; Foure, Laurent; Duval, David; Mone, Yves; Ferrier-Pages, Christine; Tambutte, Eric; Tambutte, Sylvie; Zoccola, Didier; Allemand, Denis; Mitta, Guillaume

    2009-08-04

    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. In our experimental procedure, one set of Pocillopora damicornis nubbins was subjected to a gradual increase of water temperature from 28 degrees C to 32 degrees C over 15 days. A second control set kept at constant temperature (28 degrees 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. Under thermal stress

  20. Microarray Analysis of the Molecular Mechanism Involved in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Cheng Tan

    2018-01-01

    Full Text Available Purpose. This study aimed to investigate the underlying molecular mechanisms of Parkinson’s disease (PD by bioinformatics. Methods. Using the microarray dataset GSE72267 from the Gene Expression Omnibus database, which included 40 blood samples from PD patients and 19 matched controls, differentially expressed genes (DEGs were identified after data preprocessing, followed by Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analyses. Protein-protein interaction (PPI network, microRNA- (miRNA- target regulatory network, and transcription factor- (TF- target regulatory networks were constructed. Results. Of 819 DEGs obtained, 359 were upregulated and 460 were downregulated. Two GO terms, “rRNA processing” and “cytoplasm,” and two KEGG pathways, “metabolic pathways” and “TNF signaling pathway,” played roles in PD development. Intercellular adhesion molecule 1 (ICAM1 was the hub node in the PPI network; hsa-miR-7-5p, hsa-miR-433-3p, and hsa-miR-133b participated in PD pathogenesis. Six TFs, including zinc finger and BTB domain-containing 7A, ovo-like transcriptional repressor 1, GATA-binding protein 3, transcription factor dp-1, SMAD family member 1, and quiescin sulfhydryl oxidase 1, were related to PD. Conclusions. “rRNA processing,” “cytoplasm,” “metabolic pathways,” and “TNF signaling pathway” were key pathways involved in PD. ICAM1, hsa-miR-7-5p, hsa-miR-433-3p, hsa-miR-133b, and the abovementioned six TFs might play important roles in PD development.

  1. Involvement of spinal NR2B-containing NMDA receptors in oxaliplatin-induced mechanical allodynia in rats

    Directory of Open Access Journals (Sweden)

    Yano Takahisa

    2011-01-01

    Full Text Available Abstract Background Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. The chronic neuropathy is a dose-limiting toxicity. We previously reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats. In the present study, we investigated the involvement of NR2B-containing N-methyl-D-aspartate (NMDA receptors in oxaliplatin-induced mechanical allodynia in rats. Results Repeated administration of oxaliplatin (4 mg/kg, i.p., twice a week caused mechanical allodynia in the fourth week, which was reversed by intrathecal injection of MK-801 (10 nmol and memantine (1 μmol, NMDA receptor antagonists. Similarly, selective NR2B antagonists Ro25-6981 (300 nmol, i.t. and ifenprodil (50 mg/kg, p.o. significantly attenuated the oxaliplatin-induced pain behavior. In addition, the expression of NR2B protein and mRNA in the rat spinal cord was increased by oxaliplatin on Day 25 (late phase but not on Day 5 (early phase. Moreover, we examined the involvement of nitric oxide synthase (NOS as a downstream target of NMDA receptor. L-NAME, a non-selective NOS inhibitor, and 7-nitroindazole, a neuronal NOS (nNOS inhibitor, significantly suppressed the oxaliplatin-induced pain behavior. The intensity of NADPH diaphorase staining, a histochemical marker for NOS, in the superficial layer of spinal dorsal horn was obviously increased by oxaliplatin, and this increased intensity was reversed by intrathecal injection of Ro25-6981. Conclusion These results indicated that spinal NR2B-containing NMDA receptors are involved in the oxaliplatin-induced mechanical allodynia.

  2. 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.

  3. Evidence for the involvement of MC4 receptors in the central mechanisms of opioid antinociception

    NARCIS (Netherlands)

    Starowicz, Katarzyna

    2005-01-01

    The data described in this thesis extend general knowledge of the involvement of the MC4 receptor in mechanisms of analgesia. The following aspects outlined below constitute novel information. Firstly, the MC4R localization in the DRG is demonstrated. The MC4 receptor was assumed to exist

  4. Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth.

    Science.gov (United States)

    Commandeur, Arno E; Styer, Aaron K; Teixeira, Jose M

    2015-01-01

    , rodent xenograft, naturally mutant, and genetically modified models used to study possible molecular mechanisms of leiomyoma development and growth are described. Particular emphasis is placed on known links to fibrosis, hypertrophy, and hyperplasia and genes that are potentially important in these processes. Menstrual cycle-related injury and repair and coinciding hormonal cycling appears to affect myometrial stem cells that, at a certain stage of fibroid development, often obtain cytogenetic aberrations and mutations of Mediator complex subunit 12 (MED12). Mammalian target of rapamycin (mTOR), a master regulator of proliferation, is activated in many of these tumors, possibly by mechanisms that are similar to some human fibrosis syndromes and/or by mutation of upstream tumor suppressor genes. Animal models of the disease support some of these dysregulated pathways in fibroid etiology or pathogenesis, but none are definitive. All of this suggests that there are likely several key mechanisms involved in the disease that, in addition to increasing the complexity of uterine fibroid pathobiology, offer possible approaches for patient-specific therapies. A final model that incorporates many of these reported mechanisms is presented with a discussion of their implications for leiomyoma clinical practice. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Parvoviral nuclear import: bypassing the host nuclear-transport machinery.

    Science.gov (United States)

    Cohen, Sarah; Behzad, Ali R; Carroll, Jeffrey B; Panté, Nelly

    2006-11-01

    The parvovirus Minute virus of mice (MVM) is a small DNA virus that replicates in the nucleus of its host cells. However, very little is known about the mechanisms underlying parvovirus' nuclear import. Recently, it was found that microinjection of MVM into the cytoplasm of Xenopus oocytes causes damage to the nuclear envelope (NE), suggesting that the nuclear-import mechanism of MVM involves disruption of the NE and import through the resulting breaks. Here, fluorescence microscopy and electron microscopy were used to examine the effect of MVM on host-cell nuclear structure during infection of mouse fibroblast cells. It was found that MVM caused dramatic changes in nuclear shape and morphology, alterations of nuclear lamin immunostaining and breaks in the NE of infected cells. Thus, it seems that the unusual nuclear-import mechanism observed in Xenopus oocytes is in fact used by MVM during infection of host cells.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  8. 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.

  9. Mechanisms important to later stages of streamer system development

    Science.gov (United States)

    Lehtinen, N. G.; Carlson, B.; Kochkin, P.; Østgaard, N.

    2017-12-01

    Typical streamer modeling focuses on the propagation of the streamer head and thus neglects processes such as electron detachment, electron energy relaxation, and thermalization of the electron energy distribution. These mechanisms, however, may become important at later stages of streamer system development, in particular following streamer collisions. We present a model of a later-stage streamer system development which includes these processes. A linear analysis suggests that these processes under some conditions can lead to new effects, such as excitation of waves similar to striations in the positive column of a glow discharge. Such instabilities do not occur if these mechanisms are neglected under the same conditions, although previous modeling suggested existence of wave-like phenomena during the streamer propagation [Luque et al, 2016, doi:10.1002/2015JA022234]. In the sea-level pressure air, the obtained striation-like waves may manifest as very high frequency range (>10 MHz) oscillations in plasma parameters and may have been detected in the electrode current and electromagnetic radiation measurements during laboratory spark experiments. We discuss whether the longitudinal electric field in such waves can efficiently transfer energy to charged particles, because such a process may play a role in production of x-rays.

  10. Investigations into the involvement of NMDA mechanisms in recognition memory.

    Science.gov (United States)

    Warburton, E Clea; Barker, Gareth R I; Brown, Malcom W

    2013-11-01

    This review will focus on evidence showing that NMDA receptor neurotransmission is critical for synaptic plasticity processes within brain regions known to be necessary for the formation of object recognition memories. The aim will be to provide evidence concerning NMDA mechanisms related to recognition memory processes and show that recognition memory for objects, places or associations between objects and places depends on NMDA neurotransmission within the perirhinal cortex, temporal association cortex medial prefrontal cortex and hippocampus. Administration of the NMDA antagonist AP5, selectively into each of these brain regions has revealed that the extent of the involvement NMDA receptors appears dependent on the type of information required to solve the recognition memory task; thus NMDA receptors in the perirhinal cortex are crucial for the encoding of long-term recognition memory for objects, and object-in-place associations, but not for short-term recognition memory or for retrieval. In contrast the hippocampus and medial prefrontal cortex are required for both long-term and short-term recognition memory for places or associations between objects and places, or for recognition memory tasks that have a temporal component. Such studies have therefore confirmed that the multiple brain regions make distinct contributions to recognition memory but in addition that more than one synaptic plasticity process must be involved. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Mechanisms involved in the chemical inhibition of the Eosin-sensitized photooxidation of trypsin

    Energy Technology Data Exchange (ETDEWEB)

    Rizzuto, F.; Spikes, J.D.

    1975-01-01

    A large series of compounds was screened for ability to protect trypsin from eosin-sensitized photodynamic inactivation. Eosin-sensitized photooxidation reactions of this type typically proceed via the triplet state of the dye and often involve singlet state oxygen as the oxidizing entity. In order to determine the mechanisms by which trypsin is protected from photoinactivation, a number of good protective agents (inhibitors) and some non-protective agents were selected for more detailed flash photolysis studies. Good inhibitors such as p-phenylenediamine, n-propyl gallate, serotonin creatinine sulfate and p-toluenediamine competed efficiently with oxygen and with trypsin for reaction with the triplet state of eosin. The inhibitors were shown to quench triplet eosin to the ground state and/or reduce triplet eosin to form the semireduced eosin radical and an oxidized form of the inhibitor. In the latter case, oxidized inhibitor could react by a reverse electron transfer reaction with the semireduced eosin radical to regenerate ground state eosin and the inhibitor. The good inhibitors also competed effectively with trypsin for oxidation by semioxidized eosin, thus giving another possible protective mechanism. Non-inhibitors such as halogen ions and the paramagnetic ions Co/sup + +/, Cu/sup + +/ and Mn/sup + +/ reacted only slowly with triplet and with semioxidized eosin. The primary pathway for the eosin-sensitized photooxidation of trypsin at pH 8.0 involved singlet oxygen, although semioxidized eosin may also participate.

  12. The mechanisms involved at the cell level; Les mecanismes mis en jeu au niveau cellulaire

    Energy Technology Data Exchange (ETDEWEB)

    Leblanc, G.; Pourcher, Th.; Perron, B. [Nice Univ., Dir. des Sciences du Vivant, Dept. de Biologie Joliot-Curie, 06 (France); Guillain, F. [CEA Grenoble, Dir. des Sciences du Vivant, 38 (France); Quemeneur, E. [CEA Marcoule, Dir. des Sciences du Vivant, 30 (France); Fritsch, P. [CEA Bruyeres le Chatel, Dir. des Sciences du Vivant, 91 (France)

    2003-07-01

    The mechanisms responsible at the cell level for inducing toxic reactions after contamination are as yet only imperfectly known. Work still needs to be done for both contaminants that have a biological role, such as iodine, and those that do not, such as cadmium, uranium and plutonium. In particular, these mechanisms bring into play, in biological membranes, carriers which are the physiological partners responsible for material exchange with the environment or inside the body. As they lack absolute selectivity, these carriers, which are involved in the assimilation and accumulation of vital mineral elements, also have the ability to transport toxic elements and isotopes. (authors)

  13. Predictive Mechanisms Are Not Involved the Same Way during Human-Human vs. Human-Machine Interactions: A Review

    Directory of Open Access Journals (Sweden)

    Aïsha Sahaï

    2017-10-01

    Full Text Available Nowadays, interactions with others do not only involve human peers but also automated systems. Many studies suggest that the motor predictive systems that are engaged during action execution are also involved during joint actions with peers and during other human generated action observation. Indeed, the comparator model hypothesis suggests that the comparison between a predicted state and an estimated real state enables motor control, and by a similar functioning, understanding and anticipating observed actions. Such a mechanism allows making predictions about an ongoing action, and is essential to action regulation, especially during joint actions with peers. Interestingly, the same comparison process has been shown to be involved in the construction of an individual's sense of agency, both for self-generated and observed other human generated actions. However, the implication of such predictive mechanisms during interactions with machines is not consensual, probably due to the high heterogeneousness of the automata used in the experimentations, from very simplistic devices to full humanoid robots. The discrepancies that are observed during human/machine interactions could arise from the absence of action/observation matching abilities when interacting with traditional low-level automata. Consistently, the difficulties to build a joint agency with this kind of machines could stem from the same problem. In this context, we aim to review the studies investigating predictive mechanisms during social interactions with humans and with automated artificial systems. We will start by presenting human data that show the involvement of predictions in action control and in the sense of agency during social interactions. Thereafter, we will confront this literature with data from the robotic field. Finally, we will address the upcoming issues in the field of robotics related to automated systems aimed at acting as collaborative agents.

  14. Peroxisome protein import: a complex journey.

    Science.gov (United States)

    Baker, Alison; Lanyon-Hogg, Thomas; Warriner, Stuart L

    2016-06-15

    The import of proteins into peroxisomes possesses many unusual features such as the ability to import folded proteins, and a surprising diversity of targeting signals with differing affinities that can be recognized by the same receptor. As understanding of the structure and function of many components of the protein import machinery has grown, an increasingly complex network of factors affecting each step of the import pathway has emerged. Structural studies have revealed the presence of additional interactions between cargo proteins and the PEX5 receptor that affect import potential, with a subtle network of cargo-induced conformational changes in PEX5 being involved in the import process. Biochemical studies have also indicated an interdependence of receptor-cargo import with release of unloaded receptor from the peroxisome. Here, we provide an update on recent literature concerning mechanisms of protein import into peroxisomes. © 2016 The Author(s).

  15. Parental Involvement as a Important Factor for Successful Education

    Science.gov (United States)

    Ðurišic, Maša; Bunijevac, Mila

    2017-01-01

    To comply with the system of integrated support for their students, schools need to build partnership with parents and develop mutual responsibility for children's success in the educational system. In this way, parental involvement are increased, parents' effort to support schools are encouraged, and they are directly making a positive impact to…

  16. Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability

    OpenAIRE

    Wan, Ruiqian; Weigand, Letitia A.; Bateman, Ryan; Griffioen, Kathleen; Mendelowitz, David; Mattson, Mark P.

    2014-01-01

    Autonomic control of heart rate is mediated by cardioinhibitory parasympathetic cholinergic neurons located in the brainstem and stimulatory sympathetic noradrenergic neurons. During embryonic development the survival and cholinergic phenotype of brainstem autonomic neurons is promoted by brain-derived neurotrophic factor (BDNF). We now provide evidence that BDNF regulates heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Mice with a BDNF haplo...

  17. 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 ...

  18. Extracellular Molecules Involved in Cancer Cell Invasion

    International Nuclear Information System (INIS)

    Stivarou, Theodora; Patsavoudi, Evangelia

    2015-01-01

    Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion

  19. Biogenesis of mitochondrial carrier proteins: molecular mechanisms of import into mitochondria.

    Science.gov (United States)

    Ferramosca, Alessandra; Zara, Vincenzo

    2013-03-01

    Mitochondrial metabolite carriers are hydrophobic proteins which catalyze the flux of several charged or hydrophilic substrates across the inner membrane of mitochondria. These proteins, like most mitochondrial proteins, are nuclear encoded and after their synthesis in the cytosol are transported into the inner mitochondrial membrane. Most metabolite carriers, differently from other nuclear encoded mitochondrial proteins, are synthesized without a cleavable presequence and contain several, poorly characterized, internal targeting signals. However, an interesting aspect is the presence of a positively charged N-terminal presequence in a limited number of mitochondrial metabolite carriers. Over the last few years the molecular mechanisms of import of metabolite carrier proteins into mitochondria have been thoroughly investigated. This review summarizes the present knowledge and discusses recent advances on the import and sorting of mitochondrial metabolite carriers. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. 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.

  1. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Central neuropeptide Y plays an important role in mediating the adaptation mechanism against chronic stress in male rats.

    Science.gov (United States)

    Yang, Yu; Babygirija, Reji; Zheng, Jun; Shi, Bei; Sun, Weinan; Zheng, Xiaojiao; Zhang, Fan; Cao, Yu

    2018-02-07

    Exposure to continuous life stress often causes gastrointestinal (GI) symptoms. Studies have shown that neuropeptide Y (NPY) counteracts the biological actions of corticotrophin-releasing factor (CRF), and is involved in the termination of the stress response. However, in chronic repeated restraint stress (CRS) conditions, the actions of NPY on GI motility remain controversial. To evaluate the role of NPY in mediation of the adaptation mechanism and GI motility in CRS conditions, a CRS rat model was set up. Central CRF and NPY expression levels were analyzed, serum corticosterone and NPY concentrations were measured, and GI motor function was evaluated. The NPY Y1 receptor antagonist BIBP-3226 was centrally administered before stress loading, and on days, 1-5, of repeated stress, the central CRF and the serum corticosterone concentrations were measured. In addition, gastric and colonic motor functions were evaluated. The elevated central CRF expression and corticosterone concentration caused by acute stress began to fall after 3 days of stress loading, while central NPY expression and serum NPY began to increase. GI dysmotility also returned to a normal level. Pretreatment with BIBP-3226 abolished the adaptation mechanism, and significantly increased CRF expression and the corticosterone concentration, which resulted in delayed gastric emptying and accelerated fecal pellet output. Inhibited gastric motility and enhanced distal colonic motility were also recorded. CRS-produced adaptation, over-expressed central CRF, and GI dysmotility observed in acute restraint stress were restored to normal levels. Central NPY via the Y1 receptor plays an important role in mediating the adaptation mechanism against chronic stress. Copyright © 2018 Endocrine Society.

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

    Science.gov (United States)

    Wang, Huizheng; Zhang, Kai; Zhu, Jie; Song, Weiwei; Zhao, Li; Zhang, Xiuguo

    2013-01-01

    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. 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. The data in our study reveal the regulatory mechanism of an (R)-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  4. 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.

  5. Healthcare Technology Management (HTM) of mechanical ventilators by clinical engineers.

    Science.gov (United States)

    Yoshioka, Jun; Nakane, Masaki; Kawamae, Kaneyuki

    2014-01-01

    Mechanical ventilator failures expose patients to unacceptable risks, and maintaining mechanical ventilator safety is an important issue. We examined the usefulness of maintaining mechanical ventilators by clinical engineers (CEs) using a specialized calibrator. These evaluations and the ability to make in-house repairs proved useful for obviating the need to rent ventilators which, in turn, might prove faulty themselves. The CEs' involvement in maintaining mechanical ventilators is desirable, ensures prompt service, and, most importantly, enhances safe management of mechanical ventilators.

  6. Adolescents' Involvement in Cyber Bullying and Perceptions of School: The Importance of Perceived Peer Acceptance for Female Adolescents.

    Science.gov (United States)

    Betts, Lucy R; Spenser, Karin A; Gardner, Sarah E

    2017-01-01

    Young people are spending increasing amounts of time using digital technology and, as such, are at great risk of being involved in cyber bullying as a victim, bully, or bully/victim. Despite cyber bullying typically occurring outside the school environment, the impact of being involved in cyber bullying is likely to spill over to school. Fully 285 11- to 15-year-olds (125 male and 160 female, M age  = 12.19 years, SD  = 1.03) completed measures of cyber bullying involvement, self-esteem, trust, perceived peer acceptance, and perceptions of the value of learning and the importance of school. For young women, involvement in cyber bullying as a victim, bully, or bully/victim negatively predicted perceptions of learning and school, and perceived peer acceptance mediated this relationship. The results indicated that involvement in cyber bullying negatively predicted perceived peer acceptance which, in turn, positively predicted perceptions of learning and school. For young men, fulfilling the bully/victim role negatively predicted perceptions of learning and school. Consequently, for young women in particular, involvement in cyber bullying spills over to impact perceptions of learning. The findings of the current study highlight how stressors external to the school environment can adversely impact young women's perceptions of school and also have implications for the development of interventions designed to ameliorate the effects of cyber bullying.

  7. The importance of institutional mechanisms for exercising gender equality

    Directory of Open Access Journals (Sweden)

    Pajvančić Marijana

    2014-01-01

    Full Text Available In the contemporary democratic societies, equality between men and women is one of the fundamental human rights as well as the key moral and legal value. In order to be exercised, this right must be legally recognized and efficiently exercised in all aspects of human life: political, economic, social and cultural. Experience has shown that an effective exercise of gender equality calls for integrating the gender perspective into all public policies, at all levels and in all decision-making processes. The necessary prerequisite is a proper institutional and legal framework. The institutional framework in the field of gender equality includes institutions operating within the legislative and the executive branch, as well as those involved in the protection of gender equality. The jurisdiction of the institutional mechanism within the legislative branch is defined in general terms and it does not reflect the multi-sectoral nature of activities covered by this operative body. The Gender Equality Council and the Gender Equality Agency, which were operative until the year 2014, differed in their composition and membership selection method, and they had different positions in the structure of executive authorities; the content and scope of their jurisdiction was not clearly defined, nor were they vested with sufficient and relevant powers. For that reason, it is essential to establish a new structure of institutional mechanisms within the executive branch as soon as possible. In that course, it should be ascertained that these institutions have direct communication with the government, and their competences have to be regulated adequately and precisely. In order to ensure that the normative and other measures and activities produce good results, it is necessary to provide and sustain an inter-sectoral approach to gender equality and create systemic presumptions and adequate procedures which will provide for utmost coordination and cooperation of all

  8. Review of important rock mechanics studies required for underground high level nuclear waste repository program

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, S.; Cho, W. J

    2007-01-15

    Disposal concept adapting room and pillar method, which is a confirmed technique in mining and tunnel construction for long time, has advantages at cost, safety, technical feasibility, flexibility, and international cooperation point of views. Then the important rock mechanics principals and in situ and laboratory tests for understanding the behavior of rock, buffer, and backfill as well as their interactions will be reviewed. The accurate understanding of them is important for developing a safe disposal concept and successful operation of underground repository for permanent disposal of radioactive wastes. First of all, In this study, current status of rock mechanics studies for HLW disposal in foreign countries such as Sweden, USA, Canada, Finland, Japan, and France were reviewed. After then the in situ and laboratory tests for site characterization were summarized. Furthermore, rock mechanics studies required during the whole procedure for the disposal project from repository design to the final closure will be reviewed systematically. This study will help for developing a disposal system including site selection, repository design, operation, maintenance, and closure of a repository in deep underground rock. By introducing the required rock mechanics tests at different stages, it would be helpful from the planning stage to the operation stage of a radioactive waste disposal project.

  9. Review of important rock mechanics studies required for underground high level nuclear waste repository program

    International Nuclear Information System (INIS)

    Kwon, S.; Cho, W. J.

    2007-01-01

    Disposal concept adapting room and pillar method, which is a confirmed technique in mining and tunnel construction for long time, has advantages at cost, safety, technical feasibility, flexibility, and international cooperation point of views. Then the important rock mechanics principals and in situ and laboratory tests for understanding the behavior of rock, buffer, and backfill as well as their interactions will be reviewed. The accurate understanding of them is important for developing a safe disposal concept and successful operation of underground repository for permanent disposal of radioactive wastes. First of all, In this study, current status of rock mechanics studies for HLW disposal in foreign countries such as Sweden, USA, Canada, Finland, Japan, and France were reviewed. After then the in situ and laboratory tests for site characterization were summarized. Furthermore, rock mechanics studies required during the whole procedure for the disposal project from repository design to the final closure will be reviewed systematically. This study will help for developing a disposal system including site selection, repository design, operation, maintenance, and closure of a repository in deep underground rock. By introducing the required rock mechanics tests at different stages, it would be helpful from the planning stage to the operation stage of a radioactive waste disposal project

  10. 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.

  11. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats.

    Science.gov (United States)

    Lozano-Cuenca, J; González-Hernández, A; López-Canales, O A; Villagrana-Zesati, J R; Rodríguez-Choreão, J D; Morín-Zaragoza, R; Castillo-Henkel, E F; López-Canales, J S

    2017-08-07

    Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7.5-10-5 M). The present outcome was not modified by 10-6 M atropine (an antagonist of muscarinic acetylcholine receptors), 3.1×10-7 M glibenclamide (an ATP-sensitive K+ channel blocker), 10-3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker), 10-5 M indomethacin (a prostaglandin synthesis inhibitor), 10-5 M clotrimazole (a cytochrome P450 inhibitor) or 10-5 M cycloheximide (a general protein synthesis inhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (Pclobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

  12. Extracellular Molecules Involved in Cancer Cell Invasion

    Directory of Open Access Journals (Sweden)

    Theodora Stivarou

    2015-01-01

    Full Text Available Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  13. Family involvement and helping behaviour in teams

    OpenAIRE

    Brummelhuis, L.L. ten; Lippe, T. van der; Kluwer, E.S.

    2010-01-01

    Helping behavior at work has become increasingly important, with organizations making more and more use of cooperative work practices. The difficulty is that employees are facing growing demands beyond the workplace. This study investigates the mechanisms by which family involvement (family structure, family tasks, family support) affects helping behavior in teams. Based on a sample of 495 team members, the results show that having a supportive partner and performing care tasks increase helpi...

  14. Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols.

    Directory of Open Access Journals (Sweden)

    Juliana B R Corrêa Soares

    Full Text Available BACKGROUND: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel remains the main drug used for schistosomiasis treatment, and reliance on the single therapy has been prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz within the S. mansoni gut is a major heme detoxification route with lipid droplets involved in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of three antimalarial compounds, quinine (QN, quinidine (QND and quinacrine (QCR in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. METHODOLOGY/PRINCIPAL FINDINGS: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN, and QND (75 mg/kg/day from the 11(th to 17(th day after infection caused significant decreases in worm burden (39%-61% and egg production (42%-98%. Hz formation was significantly inhibited (40%-65% in female worms recovered from QN- and QND-treated mice and correlated with reduction in the female worm burden. We also observed that QN treatment promoted remarkable ultrastructural changes in male and female worms, particularly in the gut epithelium and reduced the granulomatous reaction to parasite eggs trapped in the liver. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. CONCLUSIONS: The overall significant reduction in several disease burden parameters by the antimalarial quinoline methanols indicates that interference with Hz formation in S. mansoni represents an important mechanism of schistosomicidal action of these compounds and points out the heme crystallization process as a

  15. Trust-Building in Electronic Markets: Relative Importance and Interaction Effects of Trust-Building Mechanisms

    Science.gov (United States)

    Tams, Stefan

    We examine the relative and complementary effectiveness of trust-building strategies in online environments. While prior research has examined various antecedents to trust, we investigated two trust-building mechanisms more in depth: Web site trust and vendor reputation. We tried to understand the relative effectiveness of these two important mechanisms to provide online businesses with a clear recommendation of how to establish trust in an effective and efficient manner. Drawing from the literature on trust, we proposed vendor reputation to be more effective than Web site trust. Moreover, we examined a potential complementary effect of these mechanisms so as to provide online businesses with a deeper understanding of how to derive superior trust. We hypothesize a small such effect. The study proposes a laboratory experiment to test the model.

  16. Justice mechanisms and the question of legitimacy: the example of Rwanda's multi-layered justice mechanisms

    NARCIS (Netherlands)

    Oomen, B.; Ambos, K.; Large, J.; Wierda, M.

    2009-01-01

    Legitimacy, this contribution argues, plays a key role in connecting transitional justice mechanisms to sustainable peace, and strengthening people's perceptions of legitimacy should be of concern to all those involved in these institutions. Here, it is important to take an empirical, people-based

  17. Proteomics of Fusarium oxysporum race 1 and race 4 reveals enzymes involved in carbohydrate metabolism and ion transport that might play important roles in banana Fusarium wilt.

    Science.gov (United States)

    Sun, Yong; Yi, Xiaoping; Peng, Ming; Zeng, Huicai; Wang, Dan; Li, Bo; Tong, Zheng; Chang, Lili; Jin, Xiang; Wang, Xuchu

    2014-01-01

    Banana Fusarium wilt is a soil-spread fungal disease caused by Fusarium oxysporum. In China, the main virulence fungi in banana are F. oxysporum race 1 (F1, weak virulence) and race 4 (F4, strong virulence). To date, no proteomic analyses have compared the two races, but the difference in virulence between F1 and F4 might result from their differentially expressed proteins. Here we report the first comparative proteomics of F1 and F4 cultured under various conditions, and finally identify 99 protein species, which represent 59 unique proteins. These proteins are mainly involved in carbohydrate metabolism, post-translational modification, energy production, and inorganic ion transport. Bioinformatics analysis indicated that among the 46 proteins identified from F4 were several enzymes that might be important for virulence. Reverse transcription PCR analysis of the genes for 15 of the 56 proteins revealed that their transcriptional patterns were similar to their protein expression patterns. Taken together, these data suggest that proteins involved in carbohydrate metabolism and ion transport may be important in the pathogenesis of banana Fusarium wilt. Some enzymes such as catalase-peroxidase, galactosidase and chitinase might contribute to the strong virulence of F4. Overexpression or knockout of the genes for the F4-specific proteins will help us to further understand the molecular mechanism of Fusarium-induced banana wilt.

  18. Genes involved in sex pheromone biosynthesis of Ephestia cautella, an important food storage pest, are determined by transcriptome sequencing

    KAUST Repository

    Antony, Binu; Soffan, Alan; Jakše, Jernej; Alfaifi, Sulieman; Sutanto, Koko D.; Aldosari, Saleh A.; Aldawood, Abdulrahman S.; Pain, Arnab

    2015-01-01

    Our study provides important background information on the enzymes involved in pheromone biosynthesis. This information will be useful for the in vitro production of E. cautella sex pheromones and may provide potential targets for disrupting the pheromone-based communication system of E. cautella to prevent infestations.

  19. 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.

  20. Comparison of a two-body threshold (π,2π) reaction mechanism with the usual one-body mechanism in the deuteron

    International Nuclear Information System (INIS)

    Rockmore, R.

    1984-01-01

    A two-body threshold (π +- ,π +- π -+ ) reaction mechanism is suggested in direct analogy with pion absorption. The mechanism involves boson rescattering via Δ excitation. The relative importance of this mechanism and the ordinary one-body mechanism in nuclei is studied in the particular case of S-wave deuteron targets. The contribution of the two-body mechanism to the threshold reaction cross section is found to be less than 1% of the simple one-body estimate

  1. 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 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.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.The data in our study reveal the regulatory mechanism of an (R-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  2. Nuclear import mechanism for myocardin family members and their correlation with vascular smooth muscle cell phenotype.

    Science.gov (United States)

    Nakamura, Seiji; Hayashi, Ken'ichiro; Iwasaki, Kazuhiro; Fujioka, Tomoaki; Egusa, Hiroshi; Yatani, Hirofumi; Sobue, Kenji

    2010-11-26

    Myocardin (Mycd), which is essential for the differentiation of the smooth muscle cell lineage, is constitutively located in the nucleus, although its family members, myocardin-related transcription factors A and B (MRTF-A/B), mostly reside in the cytoplasm and translocate to the nucleus in response to Rho signaling. The mechanism for their nuclear import is unclear. Here we investigated the mechanism for the nuclear import of Mycd family members and demonstrated any correlation between such mechanism and the phenotype of vascular smooth muscle cells (VSMCs). In cultured VSMCs, the knockdown of importin β1 inhibited the nuclear import of Mycd and MRTF-A/B. Their NH(2)-terminal basic domain was identified as a binding site for importin α/β1 by in vitro analyses. However, Mycd had a higher affinity for importin α/β1 than did MRTF-A/B, even in the absence of G-actin, and Mycd affinity for importin α1/β1 was stronger than for any other importin α/β1 heterodimers. The binding of Mycd to importin α/β1 was insensitive to G-actin, whereas that of MRTF-A/B was differently inhibited by G-actin. In dedifferentiated VSMCs, the levels of importins α1 and β1 were reduced concomitant with down-regulation of Mycd, serum response factor, and smooth muscle cell markers. By contrast, in differentiated VSMCs, their expressions were up-regulated. Thus, the nuclear import of Mycd family members in VSMCs depends on importin α/β1, and their relative affinities for importin α/β1 heterodimers determine Mycd nuclear import. The expression of Mycd nuclear import machineries is related to the expression levels of VSMC phenotype-dependent smooth muscle cell markers.

  3. The corticotropin-releasing hormone network and the hypothalamic-pituitary-adrenal axis: molecular and cellular mechanisms involved.

    Science.gov (United States)

    Bonfiglio, Juan José; Inda, Carolina; Refojo, Damián; Holsboer, Florian; Arzt, Eduardo; Silberstein, Susana

    2011-01-01

    Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive response to stress. Hyperactive and/or dysregulated CRH circuits are involved in neuroendocrinological disturbances and stress-related mood disorders such as anxiety and depression. This review describes the main physiological features of the CRH network and summarizes recent relevant information concerning the molecular mechanism of CRH action obtained from signal transduction studies using cells and wild-type and transgenic mice lines. Special focus is placed on the MAPK signaling pathways triggered by CRH through the CRH receptor 1 that plays an essential role in CRH action in pituitary corticotrophs and in specific brain structures. Recent findings underpin the concept of specific CRH-signaling pathways restricted to specific anatomical areas. Understanding CRH action at molecular levels will not only provide insight into the precise CRH mechanism of action, but will also be instrumental in identifying novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. Copyright © 2011 S. Karger AG, Basel.

  4. Justice mechanisms and the question of legitimacy: the example of Rwanda's multi-layered justice mechanisms

    OpenAIRE

    Oomen, B.; Ambos, K.; Large, J.; Wierda, M.

    2009-01-01

    Legitimacy, this contribution argues, plays a key role in connecting transitional justice mechanisms to sustainable peace, and strengthening people's perceptions of legitimacy should be of concern to all those involved in these institutions. Here, it is important to take an empirical, people-based approach to legitimacy, with regard for its dynamic quality. This approach should focus on all three dimensions of legitimacy: the input into transitional justice mechanisms, the popular adherence t...

  5. 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.

  6. Radiation protection following nuclear power accidents: a survey of putative mechanisms involved in the radioprotective actions of taurine during and after radiation exposure.

    Directory of Open Access Journals (Sweden)

    Olav Christophersen

    2012-02-01

    Full Text Available There are several animal experiments showing that high doses of ionizing radiation lead to strongly enhanced leakage of taurine from damaged cells into the extracellular fluid, followed by enhanced urinary excretion. This radiation-induced taurine depletion can itself have various harmful effects (as will also be the case when taurine depletion is due to other causes, such as alcohol abuse or cancer therapy with cytotoxic drugs, but taurine supplementation has been shown to have radioprotective effects apparently going beyond what might be expected just as a consequence of correcting the harmful consequences of taurine deficiency per se. The mechanisms accounting for the radioprotective effects of taurine are, however, very incompletely understood. In this article an attempt is made to survey various mechanisms that potentially might be involved as parts of the explanation for the overall beneficial effect of high levels of taurine that has been found in experiments with animals or isolated cells exposed to high doses of ionizing radiation. It is proposed that taurine may have radioprotective effects by a combination of several mechanisms: 1 during the exposure to ionizing radiation by functioning as an antioxidant, but perhaps more because it counteracts the prooxidant catalytic effect of iron rather than functioning as an important scavenger of harmful molecules itself, 2 after the ionizing radiation exposure by helping to reduce the intensity of the post-traumatic inflammatory response, and thus reducing the extent of tissue damage that develops because of severe inflammation rather than as a direct effect of the ionizing radiation per se, 3 by functioning as a growth factor helping to enhance the growth rate of leukocytes and leukocyte progenitor cells and perhaps also of other rapidly proliferating cell types, such as enterocyte progenitor cells, which may be important for immunological recovery and perhaps also for rapid repair of various

  7. Involvement of endothelin and ET(A) endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation.

    Science.gov (United States)

    Fujita, Masahide; Andoh, Tsugunobu; Saiki, Ikuo; Kuraishi, Yasushi

    2008-02-01

    We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ET(A)-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but not the ET(B)-receptor antagonist BQ-788 (1 and 3 nmol/site), inhibited mechanical allodynia in mice with grown melanoma. In naive mice, an intraplantar injection of tumor extract (1 and 3 mg/site), which was prepared from the grown melanoma in the paw, produced mechanical allodynia, which was inhibited by BQ-123 and BQ-788 at doses of 3 and 10 nmol/site. An intraplantar injection of ET-1 (1 and 10 pmol/site) elicited licking behavior, which was increased in the melanoma-bearing hind paw. BQ-123 (3 and 10 nmol/site) inhibited licking induced by ET-1 (10 pmol/site). The level of mRNA of ET(A), but not ET(B), receptor, was significantly increased in the dorsal root ganglia on the inoculated side. Cultured B16-BL6 cells contained ET, and the melanoma mass increased the concentration of ET as it grew bigger. These results suggest that ET-1 and ET(A) receptor are at least partly involved in the induction of pain induced by melanoma cell inoculation.

  8. Identification of a tripartite import signal in the Ewing Sarcoma protein (EWS)

    International Nuclear Information System (INIS)

    Shaw, Debra J.; Morse, Robert; Todd, Adrian G.; Eggleton, Paul; Lorson, Christian L.; Young, Philip J.

    2009-01-01

    The Ewing Sarcoma (EWS) protein is a ubiquitously expressed RNA processing factor that localises predominantly to the nucleus. However, the mechanism through which EWS enters the nucleus remains unclear, with differing reports identifying three separate import signals within the EWS protein. Here we have utilized a panel of truncated EWS proteins to clarify the reported nuclear localisation signals. We describe three C-terminal domains that are important for efficient EWS nuclear localization: (1) the third RGG-motif; (2) the last 10 amino acids (known as the PY-import motif); and (3) the zinc-finger motif. Although these three domains are involved in nuclear import, they are not independently capable of driving the efficient import of a GFP-moiety. However, collectively they form a complex tripartite signal that efficiently drives GFP-import into the nucleus. This study helps clarify the EWS import signal, and the identification of the involvement of both the RGG- and zinc-finger motifs has wide reaching implications.

  9. Identification of a tripartite import signal in the Ewing Sarcoma protein (EWS)

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, Debra J.; Morse, Robert; Todd, Adrian G. [Clinical Neurobiology, IBCS, Peninsula College of Medicine and Dentistry, Exeter EX1 2LU (United Kingdom); Eggleton, Paul [Inflammation and Musculoskeletal Disease, IBCS, Peninsula College of Medicine and Dentistry, Exeter EX1 2LU (United Kingdom); MRC Immunochemistry Unit, University of Oxford, Oxford OX1 3QU (United Kingdom); Lorson, Christian L. [Department of Veterinary Pathobiology, Bond Life Sciences Center, 1201 Rollins Road, University of Missouri, Columbia, MO 65211 (United States); Young, Philip J., E-mail: philip.young@pms.ac.uk [Clinical Neurobiology, IBCS, Peninsula College of Medicine and Dentistry, Exeter EX1 2LU (United Kingdom)

    2009-12-25

    The Ewing Sarcoma (EWS) protein is a ubiquitously expressed RNA processing factor that localises predominantly to the nucleus. However, the mechanism through which EWS enters the nucleus remains unclear, with differing reports identifying three separate import signals within the EWS protein. Here we have utilized a panel of truncated EWS proteins to clarify the reported nuclear localisation signals. We describe three C-terminal domains that are important for efficient EWS nuclear localization: (1) the third RGG-motif; (2) the last 10 amino acids (known as the PY-import motif); and (3) the zinc-finger motif. Although these three domains are involved in nuclear import, they are not independently capable of driving the efficient import of a GFP-moiety. However, collectively they form a complex tripartite signal that efficiently drives GFP-import into the nucleus. This study helps clarify the EWS import signal, and the identification of the involvement of both the RGG- and zinc-finger motifs has wide reaching implications.

  10. Physical activity and bone: The importance of the various mechanical stimuli for bone mineral density. A review

    Directory of Open Access Journals (Sweden)

    Bente Morseth

    2011-08-01

    Full Text Available Numerous studies have reported benefits of regular physical activity on bone mineral density (BMD. The effects of physical activity on BMD are primarily linked to the mechanisms of mechanical loading, but the understanding of the precise mechanism behind the association is incomplete. The aim of this paper was to review the main findings concerning sources and types of mechanical stimuli in relation to BMD. Mechanical forces that act on bone are generated from impact with the ground (ground-reaction forces and from skeletal muscle contractions (muscle forces or muscle-joint forces, but the relative importance of these two sources has not been elucidated. Both muscle-joint forces and gravitational forces seem to be able to induce bone adaptation independently, and there may be differences in the importance of loading sources at different skeletal sites. The nature of the stimuli is affected by the type, intensity, frequency, and duration of the activity. The activity should be dynamic, not static, and the magnitude and rate of the stimuli should be high. In accordance with this, cross-sectional studies report highest BMD in athletes of high-impact activities such as dancing, soccer, volleyball, basketball, squash, speed skating, gymnastics, hockey, and step-aerobics. Endurance activities such as orienteering, skiing, and triathlon seem to be beneficial to a lesser degree, whereas low-impact activities such as swimming and cycling are associated with lower BMD than controls. Both the intensity and frequency of the activity should be varied and increased beyond the habitual level. Duration of the activity seems to be less important, and a few loading cycles seem to be sufficient.

  11. General mechanism involved in subwavelength optics of conducting microstructures: charge-oscillation-induced light emission and interference.

    Science.gov (United States)

    Huang, Xian-Rong; Peng, Ru-Wen

    2010-04-01

    Interactions between light and conducting microstructures or nanostructures can result in a variety of novel phenomena, but their underlying mechanisms have not been completely understood. From calculations of surface charge density waves on conducting gratings and by comparing them with classical surface plasmons, we revealed a general yet concrete picture regarding the coupling of light to free electron oscillation on structured conducting surfaces that can lead to oscillating subwavelength charge patterns (i.e., structured surface plasmons). New wavelets emitted from these light sources then destructively interfere to form evanescent waves. This principle, usually combined with other mechanisms, is mainly a geometrical effect that can be universally involved in light scattering from all periodic and non-periodic structures containing free electrons. This picture may provide clear guidelines for developing conductor-based nano-optical devices.

  12. Transcriptome analysis of Polygonum minus reveals candidate genes involved in important secondary metabolic pathways of phenylpropanoids and flavonoids

    Directory of Open Access Journals (Sweden)

    Kok-Keong Loke

    2017-02-01

    Full Text Available Background Polygonum minus is an herbal plant in the Polygonaceae family which is rich in ethnomedicinal plants. The chemical composition and characteristic pungent fragrance of Polygonum minus have been extensively studied due to its culinary and medicinal properties. There are only a few transcriptome sequences available for species from this important family of medicinal plants. The limited genetic information from the public expressed sequences tag (EST library hinders further study on molecular mechanisms underlying secondary metabolite production. Methods In this study, we performed a hybrid assembly of 454 and Illumina sequencing reads from Polygonum minus root and leaf tissues, respectively, to generate a combined transcriptome library as a reference. Results A total of 34.37 million filtered and normalized reads were assembled into 188,735 transcripts with a total length of 136.67 Mbp. We performed a similarity search against all the publicly available genome sequences and found similarity matches for 163,200 (86.5% of Polygonum minus transcripts, largely from Arabidopsis thaliana (58.9%. Transcript abundance in the leaf and root tissues were estimated and validated through RT-qPCR of seven selected transcripts involved in the biosynthesis of phenylpropanoids and flavonoids. All the transcripts were annotated against KEGG pathways to profile transcripts related to the biosynthesis of secondary metabolites. Discussion This comprehensive transcriptome profile will serve as a useful sequence resource for molecular genetics and evolutionary research on secondary metabolite biosynthesis in Polygonaceae family. Transcriptome assembly of Polygonum minus can be accessed at http://prims.researchfrontier.org/index.php/dataset/transcriptome.

  13. RNA-binding proteins involved in post-transcriptional regulation in bacteria

    Directory of Open Access Journals (Sweden)

    Elke eVan Assche

    2015-03-01

    Full Text Available Post-transcriptional regulation is a very important mechanism to control gene expression in changing environments. In the past decade, a lot of interest has been directed towards the role of small RNAs in bacterial post-transcriptional regulation. However, small RNAs are not the only molecules controlling gene expression at this level, RNA-binding proteins play an important role as well. CsrA and Hfq are the two best studied bacterial proteins of this type, but recently, additional proteins involved in post-transcriptional control have been identified. This review focuses on the general working mechanisms of post-transcriptionally active RNA-binding proteins, which include (i adaptation of the susceptibility of mRNAs and sRNAs to RNases, (ii modulating the accessibility of the ribosome binding site of mRNAs, (iii recruiting and assisting in the interaction of mRNAs with other molecules and (iv regulating transcription terminator / antiterminator formation, and gives an overview of both the well-studied and the newly identified proteins that are involved in post-transcriptional regulatory processes. Additionally, the post-transcriptional mechanisms by which the expression or the activity of these proteins is regulated, are described. For many of the newly identified proteins, however, mechanistic questions remain. Most likely, more post-transcriptionally active proteins will be identified in the future.

  14. Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress.

    Science.gov (United States)

    Guzman, David Calderón; Olguín, Hugo Juárez; García, Ernestina Hernández; Peraza, Armando Valenzuela; de la Cruz, Diego Zamora; Soto, Monica Punzo

    2017-01-01

    Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR. This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes. The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.

  15. 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...

  16. Mechanisms involved in the p62-73 idiopeptide-modulated delay of lupus nephritis in SNF(1) mice.

    Science.gov (United States)

    Nyland, J F; Stoll, M L; Jiang, F; Feng, F; Gavalchin, J

    2012-12-01

    The F(1) progeny of the (SWR × NZB) cross develop a lupus-like disease with high serum titers of autoantibodies, and increased frequency and severity of immune complex-mediated glomerulonephritis in females. In previous work, we found that an idiotypic peptide corresponding to aa62-73 (p62-73) of the heavy chain variable region of autoantibody 540 (Id(LN)F(1)) induced the proliferation of p62-73 idiotype-reactive T cell clones. Further, monthly immunization of pre-nephritic SNF(1) female mice with p62-73 resulted in decreased nephritis and prolonged life spans. Here we show that this treatment modulated proliferative responses to Id(LN)F(1) antigen, including a reduction in the population of idiopeptide-presenting antigen-presenting cells (APCs), as early as two weeks after immunization (10 weeks of age). Th1-type cytokine production was increased at 12 weeks of age. The incidence and severity of nephritis was reduced by 14 weeks compared to controls. Clinical indicators of nephritis, specifically histological evidence of glomerulonephritis and urine protein levels, were reduced by 20 weeks. Together these data suggest that events involved in the mechanism(s) whereby p62-73 immunization delayed nephritis occurred early after immunization, and involved modulation of APCs, B and T cell populations.

  17. Healthcare Technology Management (HTM) of mechanical ventilators by clinical engineers

    OpenAIRE

    Yoshioka, Jun; Nakane, Masaki; Kawamae, Kaneyuki

    2014-01-01

    Mechanical ventilator failures expose patients to unacceptable risks, and maintaining mechanical ventilator safety is an important issue. We examined the usefulness of maintaining mechanical ventilators by clinical engineers (CEs) using a specialized calibrator. These evaluations and the ability to make in-house repairs proved useful for obviating the need to rent ventilators which, in turn, might prove faulty themselves. The CEs' involvement in maintaining mechanical ventilators is desirable...

  18. The importance of male partner involvement for women's acceptability and adherence to female-initiated HIV prevention methods in Zimbabwe.

    Science.gov (United States)

    Montgomery, Elizabeth T; van der Straten, Ariane; Chidanyika, Agnes; Chipato, Tsungai; Jaffar, Shabbar; Padian, Nancy

    2011-07-01

    Enlisting male partner involvement is perceived as an important component of women's successful uptake of female-initiated HIV prevention methods. We conducted a longitudinal study among a cohort of 955 Zimbabwean women participating in a clinical trial of the effectiveness of a female-initiated HIV prevention method (the diaphragm and lubricant gel) to: (a) describe the extent to which women involved their male partners in the decision to use the study products, and (b) measure the effect perceived male partner support had on their acceptability and consistent use of these methods. Reported levels of male partner involvement in discussions and decisions regarding: joining the study, study activities, the outcome of HIV/STI test results, and product use were very high. In multivariate analyses, regular disclosure of study product use and partner approval for the diaphragm and gel were significantly associated with women's acceptability and consistent use of the products; an essential component for determining efficacy of investigational prevention methods. These results support the need for more sophisticated measurement of how couples interact to make decisions that impact study participation and investigational product use as well as more rigorous adaptations and evaluations of existing strategies to involve male partners in female-initiated HIV prevention trials.

  19. Radiation-induced genomic instability: Are epigenetic mechanisms the missing link?

    Energy Technology Data Exchange (ETDEWEB)

    Aypar, Umut; Morgan, William F.; Baulch, Janet E.

    2011-02-01

    Purpose: This review examines the evidence for the hypothesis that epigenetics are involved in the initiation and perpetuation of radiation-induced genomic instability (RIGI). Conclusion: In addition to the extensively studied targeted effects of radiation, it is now apparent that non-targeted delayed effects such as RIGI are also important post-irradiation outcomes. In RIGI, unirradiated progeny cells display phenotypic changes at delayed times after radiation of the parental cell. RIGI is thought to be important in the process of carcinogenesis, however, the mechanism by which this occurs remains to be elucidated. In the genomically unstable clones developed by Morgan and colleagues, radiation-induced mutations, double-strand breaks, or changes in mRNA levels alone could not account for the initiation or perpetuation of RIGI. Since changes in the DNA sequence could not fully explain the mechanism of RIGI, inherited epigenetic changes may be involved. Epigenetics are known to play an important role in many cellular processes and epigenetic aberrations can lead to carcinogenesis. Recent studies in the field of radiation biology suggest that the changes in methylation patterns may be involved in RIGI. Together these clues have led us to hypothesize that epigenetics may be the missing link in understanding the mechanism behind RIGI.

  20. DHA involvement in neurotransmission process

    Directory of Open Access Journals (Sweden)

    Vancassel Sylvie

    2007-05-01

    Full Text Available The very high enrichment of the nervous system in the polyunsaturated fatty acids, arachidonic (AA, 20: 4n-6 and docosahexaenoic acids (DHA, 22: 6n-3, is dependant of the dietary availability of their respective precursors, linoleic (18: 2n-6 and_-linolenic acids (18: 3n-3. Inadequate amounts of DHA in brain membranes have been linked to a wide variety of abnormalities ranging from visual acuity and learning irregularities, to psychopathologies. However, the molecular mechanisms involved remain unknown. Several years ago, we hypothesized that a modification of DHA contents of neuronal membranes by dietary modulation could change the neurotransmission function and then underlie inappropriate behavioural response. We showed that, in parallel to a severe loss of brain DHA concomitant to a compensatory substitution by 22:5n-6, the dietary lack of α-linolenic acid during development induced important changes in the release of neurotransmitters (dopamine, serotonin, acetylcholine in cerebral areas specifically involved in learning, memory and reward processes. Data suggested alteration of presynaptic storage process and dysregulations of reciprocal functional interactions between monoaminergic and cholinergic pathways. Moreover, we showed that recovery of these neurochemical changes was possible when the deficient diet was switched to a diet balanced in n-3 and n-6 PUFA before weaning. The next step is to understand the mechanism involved. Particularly, we focus on the study of the metabolic cooperation between the endothelial cell, the astrocyte and the neuron which regulate synaptic transmission.These works could contribute to the understanding of the link between some neuropsychiatric disorders and the metabolism of n-3 PUFA, through their action on neurotransmission.

  1. The relative importance of the adsorption and partitioning mechanisms in hydrophilic interaction liquid chromatography.

    Science.gov (United States)

    Gritti, Fabrice; Höltzel, Alexandra; Tallarek, Ulrich; Guiochon, Georges

    2015-01-09

    We propose an original model of effective diffusion along packed beds of mesoporous particles for HILIC developed by combining Torquatos model for heterogeneous beds (external eluent+particles), Landauers model for porous particles (solid skeleton+internal eluent), and the time-averaged model for the internal eluent (bulk phase+diffuse water (W) layer+rigid W layer). The new model allows to determine the analyte concentration in rigid and diffuse W layer from the experimentally determined retention factor and intra-particle diffusivity and thus to distinguish the retentive contributions from adsorption and partitioning. We apply the model to investigate the separation of toluene (TO, as a non-retained compound), nortriptyline (NT), cytosine (CYT), and niacin (NA) on an organic ethyl/inorganic silica hybrid adsorbent. Elution conditions are varied through the choice of a third solvent (W, ethanol, tetrahydrofuran (THF), acetonitrile (ACN), or n-hexane) in a mobile phase (MP) of ACN/aqueous acetate buffer (pH 5)/third solvent (90/5/5, v/v/v). Whereas NA and CYT retention factors increase monotonously from W to n-hexane as third solvent, NT retention reaches its maximum with polar aprotic third solvents. The involved equilibrium constants for adsorption and partitioning, however, do not follow the same trends as the overall retention factors. NT retention is dominated by partitioning and NA retention by adsorption, while CYT retention is controlled by adsorption rather than partitioning. Our results reveal that the relative importance of adsorption and partitioning mechanisms depends in a complex way from analyte properties and experimental parameters and cannot be predicted generally. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Importance of weak minerals on earthquake mechanics

    Science.gov (United States)

    Kaneki, S.; Hirono, T.

    2017-12-01

    The role of weak minerals such as smectite and talc on earthquake mechanics is one of the important issues, and has been debated for recent several decades. Traditionally weak minerals in fault have been reported to weaken fault strength causing from its low frictional resistance. Furthermore, velocity-strengthening behavior of such weak mineral (talc) is considered to responsible for fault creep (aseismic slip) in the San Andreas fault. In contrast, recent studies reported that large amount of weak smectite in the Japan Trench could facilitate gigantic seismic slip during the 2011 Tohoku-oki earthquake. To investigate the role of weak minerals on rupture propagation process and magnitude of slip, we focus on the frictional properties of carbonaceous materials (CMs), which is the representative weak materials widely distributed in and around the convergent boundaries. Field observation and geochemical analyses revealed that graphitized CMs-layer is distributed along the slip surface of a fossil plate-subduction fault. Laboratory friction experiments demonstrated that pure quartz, bulk mixtures with bituminous coal (1 wt.%), and quartz with layered coal samples exhibited almost similar frictional properties (initial, yield, and dynamic friction). However, mixtures of quartz (99 wt.%) and layered graphite (1 wt.%) showed significantly lower initial and yield friction coefficient (0.31 and 0.50, respectively). Furthermore, the stress ratio S, defined as (yield stress-initial stress)/(initial stress-dynamic stress), increased in layered graphite samples (1.97) compared to quartz samples (0.14). Similar trend was observed in smectite-rich fault gouge. By referring the reported results of dynamic rupture propagation simulation using S ratio of 1.4 (typical value for the Japan Trench) and 2.0 (this study), we confirmed that higher S ratio results in smaller slip distance by approximately 20 %. On the basis of these results, we could conclude that weak minerals have lower

  3. 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.

  4. Chemotherapeutics-resistance "arms" race: An update on mechanisms involved in resistance limiting EGFR inhibitors in lung cancer.

    Science.gov (United States)

    Singh, Pankaj Kumar; Silakari, Om

    2017-10-01

    Clinical reports suggest that EGFR-mutated lung cancer usually respond significantly towards small molecule tyrosine kinase inhibitors. Same studies also report the eventual development of acquired resistance within a median time interval of 9 to 14months. One of the major mechanisms involved in this acquired resistance was found to be a secondary point mutation at gate-keeper residue, EGFR T790M. However, there are other recent studies which disclose the role of few other novel key players such as, ZEB1, TOPK etc., in the development of tolerance towards the EGFR TKI's, along with other commonly known mechanisms, such as amplification of signalling pathways such as, c-MET, Erbb2, AXL, additional acquired secondary mutations (PIK3CA, BRAF), or phenotypic transformation (small cell or epithelial to mesenchymal transitions). Interestingly, a recent study showed development of resistance via another point mutation, C797S, in case of tumors which were previously resistant and were administered agents capable of overcoming T790M gatekeeper mutation based resistance. Thus, raising serious concern over the direction of drug development involving tyrosine kinases such as EGFR. Current approaches focussing on development of third generation inhibitors, dual inhibitors or inhibitors of HSP90 have shown significant activity but do not answer the long term question of resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. On the fluid mechanics of bilabial plosives

    NARCIS (Netherlands)

    Pelorson, X.; Hofmans, G.C.J.; Ranucci, M.; Bosch, R.C.M.

    1997-01-01

    In this paper we present a review of some fluid mechanical phenomena involved in bilabial plosive sound production. As a basis for further discussion, firstly an in vivo experimental set-up is described. The order of magnitude of some important geometrical and fluid dynamical quantities is

  6. Heterogeneity of reward mechanisms.

    Science.gov (United States)

    Lajtha, A; Sershen, H

    2010-06-01

    The finding that many drugs that have abuse potential and other natural stimuli such as food or sexual activity cause similar chemical changes in the brain, an increase in extracellular dopamine (DA) in the shell of the nucleus accumbens (NAccS), indicated some time ago that the reward mechanism is at least very similar for all stimuli and that the mechanism is relatively simple. The presently available information shows that the mechanisms involved are more complex and have multiple elements. Multiple brain regions, multiple receptors, multiple distinct neurons, multiple transmitters, multiple transporters, circuits, peptides, proteins, metabolism of transmitters, and phosphorylation, all participate in reward mechanisms. The system is variable, is changed during development, is sex-dependent, and is influenced by genetic differences. Not all of the elements participate in the reward of all stimuli. Different set of mechanisms are involved in the reward of different drugs of abuse, yet different mechanisms in the reward of natural stimuli such as food or sexual activity; thus there are different systems that distinguish different stimuli. Separate functions of the reward system such as anticipation, evaluation, consummation and identification; all contain function-specific elements. The level of the stimulus also influences the participation of the elements of the reward system, there are possible reactions to even below threshold stimuli, and excessive stimuli can change reward to aversion involving parts of the system. Learning and memory of past reward is an important integral element of reward and addictive behavior. Many of the reward elements are altered by repeated or chronic stimuli, and chronic exposure to one drug is likely to alter the response to another stimulus. To evaluate and identify the reward stimulus thus requires heterogeneity of the reward components in the brain.

  7. Involvement of protein kinase C in the mechanism of action of Escherichia coli heat-stable enterotoxin (STa) in a human colonic carcinoma cell line, COLO-205

    International Nuclear Information System (INIS)

    Gupta, Dyuti Datta; Saha, Subhrajit; Chakrabarti, Manoj K.

    2005-01-01

    The present study was undertaken to determine the involvement of calcium-protein kinase C pathway in the mechanism of action of Escherichia coli heat stable enterotoxin (STa) apart from STa-induced activation of guanylate cyclase in human colonic carcinoma cell line COLO-205, which was used as a model cultured cell line to study the mechanism of action of E. coli STa. In response to E. coli STa, protein kinase C (PKC) activity was increased in a time-dependent manner with its physical translocation from cytosol to membrane. Inhibition of the PKC activity in membrane fraction and inhibition of its physical translocation in response to IP 3 -mediated calcium release inhibitor dantrolene suggested the involvement of intracellular store depletion in the regulation of PKC activity. Among different PKC isoforms, predominant involvement of calcium-dependent protein kinase C (PKCα) was specified using isotype-specific pseudosubstrate, which showed pronounce enzyme activity. Inhibition of enzyme activity by PKCα-specific inhibitor Goe6976 and immunoblott study employing isotype-specific antibody further demonstrated the involvement of calcium-dependent isoform of PKC in the mechanism of action of E. coli STa. Moreover, inhibition of guanylate cyclase activity by PKCα-specific inhibitor Goe6976 suggested the involvement of PKCα in the regulation of guanylate cyclase activity

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Interdependence, issue importance, and the 2009 Russia-Ukraine gas conflict

    International Nuclear Information System (INIS)

    Lee, Yusin

    2017-01-01

    The primary aim of this paper is to explain the 2009 Russia-Ukraine gas conflict. In particular, it attempts to identify the causal mechanisms between their interdependence in the gas sphere and the gas conflict. The paper first shows that existing theories in the study of international relations have limitations in accounting for that conflict. Therefore, a theoretical framework drawing insights from Armstrong's model on dependence-political compliance and Crescenzi's exit model is proposed to explain it. Relying on this framework, this paper demonstrates that the 2009 Russia-Ukraine gas conflict took place through two critical causal mechanisms. In the contexts of the 2008 global financial crisis and Ukraine's anti-Russian policy, Russia and Ukraine both considered issues involved in the gas trade such as debts, prices, transit tariffs, and Ukraine's pipeline system to be very important. Therefore, when Russia issued demands with economic threats, Ukraine refused to comply. - Highlights: • This paper explains the 2009 Russia-Ukraine gas conflict. • It shows the causal mechanisms between their interdependent gas relations and the conflict. • The conflict took place through two critical causal mechanisms. • Russia and Ukraine considered the issues involved in the gas trade to be critical. • Thus, when Russia issued demands with economic threats, Ukraine refused to comply.

  11. A novel two-step mechanism for removal of a mitochondrial signal sequence involves the mAAA complex and the putative rhomboid protease Pcp1.

    Science.gov (United States)

    Esser, Karlheinz; Tursun, Baris; Ingenhoven, Martin; Michaelis, Georg; Pratje, Elke

    2002-11-08

    The yeast protein cytochrome c peroxidase (Ccp1) is nuclearly encoded and imported into the mitochondrial intermembrane space, where it is involved in degradation of reactive oxygen species. It is known, that Ccp1 is synthesised as a precursor with a N-terminal pre-sequence, that is proteolytically removed during transport of the protein. Here we present evidence for a new processing pathway, involving novel signal peptidase activities. The mAAA protease subunits Yta10 (Afg3) and Yta12 (Rca1) were identified both to be essential for the first processing step. In addition, the Pcp1 (Ygr101w) gene product was found to be required for the second processing step, yielding the mature Ccp1 protein. The newly identified Pcp1 protein belongs to the rhomboid-GlpG superfamily of putative intramembrane peptidases. Inactivation of the protease motifs in mAAA and Pcp1 blocks the respective steps of proteolysis. A model of coupled Ccp1 transport and N-terminal processing by the mAAA complex and Pcp1 is discussed. Similar processing mechanisms may exist, because the mAAA subunits and the newly identified Pcp1 protein belong to ubiquitous protein families.

  12. Cell-surface metalloprotease ADAM12 is internalized by a clathrin- and Grb2-dependent mechanism

    DEFF Research Database (Denmark)

    Hansen, Dorte Stautz; Leyme, Anthony; Grandal, Michael Vibo

    2012-01-01

    ADAM12 (A Disintegrin And Metalloprotease 12), a member of the ADAMs family of transmembrane proteins, is involved in ectodomain shedding, cell-adhesion and signaling, with important implications in cancer. Therefore, mechanisms that regulate the levels and activity of ADAM12 at the cell-surface ......ADAM12 (A Disintegrin And Metalloprotease 12), a member of the ADAMs family of transmembrane proteins, is involved in ectodomain shedding, cell-adhesion and signaling, with important implications in cancer. Therefore, mechanisms that regulate the levels and activity of ADAM12 at the cell...

  13. Involvement of adrenergic and serotonergic nervous mechanisms in allethrin-induced tremors in mice.

    Science.gov (United States)

    Nishimura, M; Obana, N; Yagasaki, O; Yanagiya, I

    1984-05-01

    Oral or intravenous administration of allethrin, a synthetic derivative of the pirethrin-based insecticides, produces neurotoxic symptoms consisting of mild salivation, hyperexcitability, tremors and convulsions which result in death. Intracerebroventricular injection of allethrin to mouse at about one-nineth the dose of intravenous administration, produced qualitatively identical but less prominent symptoms, indicating that at least some of the symptoms may be originated in the central nervous system. To investigate the mechanism of action of the compound, we studied the ability of agents which alter neurotransmission to prevent or potentiate the effect of convulsive doses of technical grade (15.5% cis, 84.5% trans) allethrin. Intraperitoneal pretreatment with drugs which block noradrenergic receptors or norepinephrine synthesis, such as pentobarbital, chlorpromazine, phentolamine, phenoxybenzamine and reserpine, depressed the tremor induced by allethrin. The inhibitory effect of reserpine was reversed by phenylephrine. Both the serotonergic blocker, methysergide, and the serotonin depletor, rho-chlorphenylalanine, potentiated the effect of allethrin. The potentiating effect of methysergide was antagonized by 5-hydroxytryptamine. However, intracerebroventricular administration of methysergide was ineffective in potentiating the effect of allethrin. alpha 2- and beta-adrenoceptor blockers, muscarinic antagonists, GABA mimenergics and morphine had no effect. These results suggest that allethrin produces its neurotoxic responses in mice by acting on the brain and spinal levels. Furthermore, adrenergic excitatory and serotonergic inhibitory mechanisms may be involved in the neural pathway through which the allethrin-induced tremor is evoked.

  14. Pyrazinamide: the importance of uncovering the mechanisms of action in mycobacteria.

    Science.gov (United States)

    Stehr, Matthias; Elamin, Ayssar A; Singh, Mahavir

    2015-05-01

    Pyrazinamide (PZA) is still one of the key drugs used in current therapeutic regimens for tuberculosis (TB). Despite its importance for TB therapy, the mode of action of PZA remains unknown. PZA has to be converted to its active form pyrazinoic acid (POA) by the nicotinamidase PncA and is then excreted by an unknown efflux pump. At acidic conditions, POA is protonated to HPOA and is reabsorbed into the cell where it causes cellular damage. For a long time, it has been thought that PZA/POA has no defined target of action, but recent studies have shown that both PZA and POA have several different targets interfering with diverse biochemical pathways, especially in the NAD(+) and energy metabolism. PZA resistance seems to depend not only on a defective pyrazinamidase but is also rather a result of the interplay of many different enzyme targets and transport mechanisms.

  15. Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Song-Ze, E-mail: dingsongze@hotmail.com [Department of Internal Medicine, Henan Provincial People’s Hospital, Zhengzhou University, Wei-Wu Road, Zhengzhou, Henan 450000 (China); Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Yang, Yu-Xiu; Li, Xiu-Ling [Department of Internal Medicine, Henan Provincial People’s Hospital, Zhengzhou University, Wei-Wu Road, Zhengzhou, Henan 450000 (China); Michelli-Rivera, Audrey [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Han, Shuang-Yin [Department of Internal Medicine, Henan Provincial People’s Hospital, Zhengzhou University, Wei-Wu Road, Zhengzhou, Henan 450000 (China); Wang, Lei; Pratheeshkumar, Poyil; Wang, Xin; Lu, Jian; Yin, Yuan-Qin; Budhraja, Amit; Hitron, Andrew J. [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States)

    2013-05-15

    Hexavalent chromium [Cr(VI)] is an important human carcinogen associated with pulmonary diseases and lung cancer. Exposure to Cr(VI) induces DNA damage, cell morphological change and malignant transformation in human lung epithelial cells. Despite extensive studies, the molecular mechanisms remain elusive, it is also not known if Cr(VI)-induced transformation might accompany with invasive properties to facilitate metastasis. We aimed to study Cr(VI)-induced epithelial–mesenchymal transition (EMT) and invasion during oncogenic transformation in lung epithelial cells. The results showed that Cr(VI) at low doses represses E-cadherin mRNA and protein expression, enhances mesenchymal marker vimentin expression and transforms the epithelial cell into fibroblastoid morphology. Cr(VI) also increases cell invasion and promotes colony formation. Further studies indicated that Cr(VI) uses multiple mechanisms to repress E-cadherin expression, including activation of E-cadherin repressors such as Slug, ZEB1, KLF8 and enhancement the binding of HDAC1 in E-cadherin gene promoter, but DNA methylation is not responsible for the loss of E-cadherin. Catalase reduces Cr(VI)-induced E-cadherin and vimentin protein expression, attenuates cell invasion in matrigel and colony formation on soft agar. These results demonstrate that exposure to a common human carcinogen, Cr(VI), induces EMT and invasion during oncogenic transformation in lung epithelial cells and implicate in cancer metastasis and prevention. - Graphical abstract: Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanisms in lung epithelial cells. - Highlights: • We study if Cr(VI) might induce EMT and invasion in epithelial cells. • Cr(VI) induces EMT by altering E-cadherin and vimentin expression. • It also increases cell invasion and promotes oncogenic transformation. • Catalase reduces Cr(VI)-induced EMT, invasion and

  16. Iron-Induced Damage in Cardiomyopathy: Oxidative-Dependent and Independent Mechanisms

    Directory of Open Access Journals (Sweden)

    Elena Gammella

    2015-01-01

    Full Text Available The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies.

  17. 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.

  18. Towards a Better Understanding of the Molecular Mechanisms Involved in Sunlight-Induced Melanoma

    Directory of Open Access Journals (Sweden)

    Williams Mandy

    2005-01-01

    Full Text Available Although much less prevalent than its nonmelanoma skin cancer counterparts, cutaneous malignant melanoma (CMM is the most lethal human skin cancer. Epidemiological and biological studies have established a strong link between lifetime exposure to ultraviolet (UV light, particularly sunburn in childhood, and the development of melanoma. However, the specific molecular targets of this environmental carcinogen are not known. Data obtained from genetic and molecular studies over the last few years have identified the INK4a/ARF locus as the “gatekeeper” melanoma suppressor, encoding two tumour suppressor proteins in human, p16 INK4a and p14 ARF . Recent developments in molecular biotechnology and research using laboratory animals have made a significant gene breakthrough identifying the components of the p16 INK4a /Rb pathway as the principal and rate-limiting targets of UV radiation actions in melanoma formation. This review summarizes the current knowledge of the molecular mechanisms involved in melanoma development and its relationship to sunlight UV radiation.

  19. Importance of Bacterial Replication and Alveolar Macrophage-Independent Clearance Mechanisms during Early Lung Infection with Streptococcus pneumoniae

    Science.gov (United States)

    Camberlein, Emilie; Cohen, Jonathan M.; José, Ricardo; Hyams, Catherine J.; Callard, Robin; Chimalapati, Suneeta; Yuste, Jose; Edwards, Lindsey A.; Marshall, Helina; van Rooijen, Nico; Noursadeghi, Mahdad

    2015-01-01

    Although the importance of alveolar macrophages for host immunity during early Streptococcus pneumoniae lung infection is well established, the contribution and relative importance of other innate immunity mechanisms and of bacterial factors are less clear. We have used a murine model of S. pneumoniae early lung infection with wild-type, unencapsulated, and para-amino benzoic acid auxotroph mutant TIGR4 strains to assess the effects of inoculum size, bacterial replication, capsule, and alveolar macrophage-dependent and -independent clearance mechanisms on bacterial persistence within the lungs. Alveolar macrophage-dependent and -independent (calculated indirectly) clearance half-lives and bacterial replication doubling times were estimated using a mathematical model. In this model, after infection with a high-dose inoculum of encapsulated S. pneumoniae, alveolar macrophage-independent clearance mechanisms were dominant, with a clearance half-life of 24 min compared to 135 min for alveolar macrophage-dependent clearance. In addition, after a high-dose inoculum, successful lung infection required rapid bacterial replication, with an estimated S. pneumoniae doubling time of 16 min. The capsule had wide effects on early lung clearance mechanisms, with reduced half-lives of 14 min for alveolar macrophage-independent and 31 min for alveolar macrophage-dependent clearance of unencapsulated bacteria. In contrast, with a lower-dose inoculum, the bacterial doubling time increased to 56 min and the S. pneumoniae alveolar macrophage-dependent clearance half-life improved to 42 min and was largely unaffected by the capsule. These data demonstrate the large effects of bacterial factors (inoculum size, the capsule, and rapid replication) and alveolar macrophage-independent clearance mechanisms during early lung infection with S. pneumoniae. PMID:25583525

  20. Mechanisms involved in growth inhibition induced by clofibrate in hepatoma cells

    International Nuclear Information System (INIS)

    Muzio, Giuliana; Maggiora, Marina; Trombetta, Antonella; Martinasso, Germana; Reffo, Patrizia; Colombatto, Sebastiano; Canuto, Rosa Angela

    2003-01-01

    Low concentrations of some peroxisome proliferators have been found to decrease apoptosis in rat liver cells, whereas higher but pharmacological concentrations have been found to inhibit cell proliferation or to induce apoptosis in human and rat hepatoma cells. The highly deviated JM2 rat hepatoma cell line was used to examine the mechanisms underlying the inhibitory effect on cell proliferation. Clofibrate chiefly inhibited cell proliferation in these cells. Parallel to the decrease in cell proliferation there was an increase of peroxisome proliferator activated receptor (PPAR) gamma and of protein phosphatase 2A, whose importance was confirmed, respectively, by using antisense oliginucleotides (AS-ODN) or okadaic acid. The increase of protein phosphatase 2A induced by PPARgamma caused a decrease of MAPK, an intracellular signaling transduction pathway, as shown by evaluation of Erk1,2 and c-myc. In light of these results, clofibrate, like conventional synthetic ligands of PPARgamma, may be regarded as a possible prototype anti-tumour drug

  1. Craniofacial Pain: Brainstem Mechanisms

    Directory of Open Access Journals (Sweden)

    Barry J Sessle

    1996-01-01

    Full Text Available This article reviews recent research advances in animals that have identified critical neural elements in the brainstem receiving and transmitting craniofacial nociceptive inputs, as well as some of the mechanisms involved in the modulation and plasticity of nociceptive transmission. Nociceptive neurones in the trigeminal (V brainstem sensory nuclear complex can be classified as nociceptive-specific (NS or wide dynamic range (WDR. Some of these neurones respond exclusively to sensory inputs evoked by stimulation of facial skin or oral mucosa and have features suggesting that they are critical neural elements involved in the ability to localize an acute superficial pain and sense its intensity and duration. Many of the V brainstem nociceptive neurones, however, receive convergent inputs from afferents supplying deep craniofacial tissues (eg, dural vessel, muscle and skin or mucosa. These neurones are likely involved in deep pain, including headache, because few nociceptive neurones receive inputs exclusively from afferents supplying these tissues. These extensive convergent input patterns also appear to be important factors in pain spread and referral, and in central mechanisms underlying neuroplastic changes in V neuronal properties that may occur with injury and inflammation. For example, application of the small fibre excitant and inflammatory irritant mustard oil into the temporomandibular joint, masseter or tongue musculature induces a prolonged but reversible enhancement of responses to cutaneous and deep afferent inputs of most WDR and NS neurones. These effects may be accompanied by increased electromyographic activity reflexly induced in the masticatory muscles by mustard oil, and involve endogenous N-methyl-D-aspartate and opioid neurochemical mechanisms. Such peripherally induced modulation of brainstem nociceptive neuronal properties reflects the functional plasticity of the central V system, and may be involved in the development of

  2. Global climate regulation and border adjustment mechanisms: the case of carbon importers inclusion in the european trading scheme

    International Nuclear Information System (INIS)

    2008-06-01

    The creation of an inclusion mechanism applied to imports whose production process increases significantly the global climate risk is looked upon as a solution to a collective-action problem. Such a mechanism would provide those States that will sign the next United Nations Convention on Climate Change with a potential remedy if and when gaps between quantified objects, to which all are committed, entail significant competition distortions. Whether this mechanism assumes the form of an external carbon tax or consists in including importers in the European system of CO 2 quota exchanges, it would surely respond to the re-distributive need generated by global warming, provided that the proceeds are used to help bring industrial production in developing countries up to standard. These restrictive measures aimed at preserving the planet are probably compatible with the extraordinary regimes applied by the WTO, which already uses exogenous non-trade norms to arbitrate conflicts. This would validate further the legitimacy of authority transfers onto the WTO, whose scope of legal authority increases constantly, along with that of conflicts that stem from collective preferences. (author)

  3. Agriculturally important microbial biofilms: Present status and future prospects.

    Science.gov (United States)

    Velmourougane, Kulandaivelu; Prasanna, Radha; Saxena, Anil Kumar

    2017-07-01

    Microbial biofilms are a fascinating subject, due to their significant roles in the environment, industry, and health. Advances in biochemical and molecular techniques have helped in enhancing our understanding of biofilm structure and development. In the past, research on biofilms primarily focussed on health and industrial sectors; however, lately, biofilms in agriculture are gaining attention due to their immense potential in crop production, protection, and improvement. Biofilms play an important role in colonization of surfaces - soil, roots, or shoots of plants and enable proliferation in the desired niche, besides enhancing soil fertility. Although reports are available on microbial biofilms in general; scanty information is published on biofilm formation by agriculturally important microorganisms (bacteria, fungi, bacterial-fungal) and their interactions in the ecosystem. Better understanding of agriculturally important bacterial-fungal communities and their interactions can have several implications on climate change, soil quality, plant nutrition, plant protection, bioremediation, etc. Understanding the factors and genes involved in biofilm formation will help to develop more effective strategies for sustainable and environment-friendly agriculture. The present review brings together fundamental aspects of biofilms, in relation to their formation, regulatory mechanisms, genes involved, and their application in different fields, with special emphasis on agriculturally important microbial biofilms. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Identification of Inhibitors of Biological Interactions Involving Intrinsically Disordered Proteins

    Directory of Open Access Journals (Sweden)

    Daniela Marasco

    2015-04-01

    Full Text Available Protein–protein interactions involving disordered partners have unique features and represent prominent targets in drug discovery processes. Intrinsically Disordered Proteins (IDPs are involved in cellular regulation, signaling and control: they bind to multiple partners and these high-specificity/low-affinity interactions play crucial roles in many human diseases. Disordered regions, terminal tails and flexible linkers are particularly abundant in DNA-binding proteins and play crucial roles in the affinity and specificity of DNA recognizing processes. Protein complexes involving IDPs are short-lived and typically involve short amino acid stretches bearing few “hot spots”, thus the identification of molecules able to modulate them can produce important lead compounds: in this scenario peptides and/or peptidomimetics, deriving from structure-based, combinatorial or protein dissection approaches, can play a key role as hit compounds. Here, we propose a panoramic review of the structural features of IDPs and how they regulate molecular recognition mechanisms focusing attention on recently reported drug-design strategies in the field of IDPs.

  5. 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

  6. Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in rats

    Directory of Open Access Journals (Sweden)

    Katagiri Ayano

    2012-03-01

    Full Text Available Abstract Background It has been reported that the P2Y12 receptor (P2Y12R is involved in satellite glial cells (SGCs activation, indicating that P2Y12R expressed in SGCs may play functional roles in orofacial neuropathic pain mechanisms. However, the involvement of P2Y12R in orofacial neuropathic pain mechanisms is still unknown. We therefore studied the reflex to noxious mechanical or heat stimulation of the tongue, P2Y12R and glial fibrillary acidic protein (GFAP immunohistochemistries in the trigeminal ganglion (TG in a rat model of unilateral lingual nerve crush (LNC to evaluate role of P2Y12R in SGC in lingual neuropathic pain. Results The head-withdrawal reflex thresholds to mechanical and heat stimulation of the lateral tongue were significantly decreased in LNC-rats compared to sham-rats. These nocifensive effects were apparent on day 1 after LNC and lasted for 17 days. On days 3, 9, 15 and 21 after LNC, the mean relative number of TG neurons encircled with GFAP-immunoreactive (IR cells significantly increased in the ophthalmic, maxillary and mandibular branch regions of TG. On day 3 after LNC, P2Y12R expression occurred in GFAP-IR cells but not neuronal nuclei (NeuN-IR cells (i.e. neurons in TG. After 3 days of successive administration of the P2Y12R antagonist MRS2395 into TG in LNC-rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly decreased coincident with a significant reversal of the lowered head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue compared to vehicle-injected rats. Furthermore, after 3 days of successive administration of the P2YR agonist 2-MeSADP into the TG in naïve rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly increased and head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue were significantly decreased in a dose-dependent manner compared to vehicle-injected rats

  7. The importance and role of the corporate governance mechanism in increasing the level of management efficiency

    Directory of Open Access Journals (Sweden)

    Đorđević Slaviša

    2012-01-01

    Full Text Available There is inherent conflict of interests between owners and managers. They try to solve it in different ways. In this paper we have tried to briefly introduce the most important internal mechanisms of corporate governance (monitoring by the board of directors, incentive system for managers, internal audit and the importance of institutional investors. The financial scandals that included the world-famous corporations as well as current world economic crisis suggests that the protection of owners should continue to work to improve existing or new solutions that will improve the level of corporate governance.

  8. Evidence for the Involvement of Spinal Cord-Inhibitory and Cytokines-Modulatory Mechanisms in the Anti-Hyperalgesic Effect of Hecogenin Acetate, a Steroidal Sapogenin-Acetylated, in Mice

    Directory of Open Access Journals (Sweden)

    Jullyana S.S. Quintans

    2014-06-01

    Full Text Available Hecogenin is a steroidal sapogenin largely drawn from the plants of the genus Agave, commonly known as ‘sisal’, and is one of the important precursors used by the pharmaceutical industry for the synthesis of steroid hormones. Hecogenin acetate (HA is a steroidal sapogenin-acetylated that produces antinociceptive activity. Thus, we evaluate the antihyperalgesic profile of HA in mice in inflammatory models, as well as its possible involvement with c-fos expression on spinal cord area and cytokines to produces analgesic profile. Acute pretreatment with HA (5, 10, or 20 mg/kg; i.p. inhibited the development of mechanical hyperalgesia induced by carrageenan, TNF-α, dopamine and PGE2. Additionally, the immunofluorescence data demonstrated that acute pretreatment with HA, at all doses tested, significantly inhibited Fos-like expression in the spinal cord dorsal horn normally observed after carrageenan-inflammation. Moreover, HA did not affect the motor performance of the mice as tested in the Rota rod test. This antinociceptive profile seems to be related, at least in part, to a reduction of pro-inflammatory cytokines, as IL-1β. The present results suggest that HA attenuates mechanical hyperalgesia by blocking the neural transmission of pain at the spinal cord levels and by cytokines-inhibitory mechanisms.

  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. Survival in amyotrophic lateral sclerosis with home mechanical ventilation: the impact of systematic respiratory assessment and bulbar involvement.

    Science.gov (United States)

    Farrero, Eva; Prats, Enric; Povedano, Mónica; Martinez-Matos, J Antonio; Manresa, Frederic; Escarrabill, Joan

    2005-06-01

    To analyze (1) the impact of a protocol of early respiratory evaluation of the indications for home mechanical ventilation (HMV) in patients with amyotrophic lateral sclerosis (ALS), and (2) the effects of the protocol and of bulbar involvement on the survival of patients receiving noninvasive ventilation (NIV). Retrospective study in a tertiary care referral center. HMV was indicated in 86 patients with ALS, with 22 patients (25%) presenting with intolerance to treatment associated with bulbar involvement. Treatment with HMV had been initiated in 15 of 64 patients prior to initiating the protocol (group A) and in the remaining 49 patients after protocol initiation (group B). In group A, the majority of patients began treatment with HMV during an acute episode requiring ICU admission (p = 0.001) and tracheal ventilation (p = 0.025), with a lower percentage of patients beginning HMV treatment without respiratory insufficiency (p = 0.013). No significant differences in survival rates were found between groups A and B among patients treated with NIV. Greater survival was observed in group B (p = 0.03) when patients with bulbar involvement were excluded (96%). Patients without bulbar involvement at the start of therapy with NIV presented a significantly better survival rate (p = 0.03). Multivariate analysis showed bulbar involvement to be an independent prognostic factor for survival (relative risk, 1.6; 95% confidence interval, 1.01 to 2.54; p = 0.04). No significant differences in survival were observed between patients with bulbar involvement following treatment with NIV and those with intolerance, except for the subgroup of patients who began NIV treatment with hypercapnia (p = 0.0002). Early systematic respiratory evaluation in patients with ALS is necessary to improve the results of HMV. Further studies are required to confirm the benefits of NIV treatment in patients with bulbar involvement, especially in the early stages.

  11. Endocytosis of HERG is clathrin-independent and involves arf6.

    Directory of Open Access Journals (Sweden)

    Rucha Karnik

    Full Text Available The hERG potassium channel is critical for repolarisation of the cardiac action potential. Reduced expression of hERG at the plasma membrane, whether caused by hereditary mutations or drugs, results in long QT syndrome and increases the risk of ventricular arrhythmias. Thus, it is of fundamental importance to understand how the density of this channel at the plasma membrane is regulated. We used antibodies to an extracellular native or engineered epitope, in conjunction with immunofluorescence and ELISA, to investigate the mechanism of hERG endocytosis in recombinant cells and validated the findings in rat neonatal cardiac myocytes. The data reveal that this channel undergoes rapid internalisation, which is inhibited by neither dynasore, an inhibitor of dynamin, nor a dominant negative construct of Rab5a, into endosomes that are largely devoid of the transferrin receptor. These results support a clathrin-independent mechanism of endocytosis and exclude involvement of dynamin-dependent caveolin and RhoA mechanisms. In agreement, internalised hERG displayed marked overlap with glycosylphosphatidylinositol-anchored GFP, a clathrin-independent cargo. Endocytosis was significantly affected by cholesterol extraction with methyl-β-cyclodextrin and inhibition of Arf6 function with dominant negative Arf6-T27N-eGFP. Taken together, we conclude that hERG undergoes clathrin-independent endocytosis via a mechanism involving Arf6.

  12. The mechanism and properties of acid-coagulated milk gels

    Directory of Open Access Journals (Sweden)

    Chanokphat Phadungath

    2005-03-01

    Full Text Available Acid-coagulated milk products such as fresh acid-coagulated cheese varieties and yogurt areimportant dairy food products. However, little is known regarding the mechanisms involved in gel formation, physical properties of acid gels, and the effects of processing variables such as heat treatment and gelation temperature on the important physical properties of acid milk gels. This paper reviews the modern concepts of possible mechanisms involved in the formation of particle milk gel aggregation, along with recent developments including the use of techniques such as dynamic low amplitude oscillatory rheology to observe the gel formation process, and confocal laser scanning microscopy to monitor gel microstructure.

  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. Endogenous reward mechanisms and their importance in stress reduction, exercise and the brain.

    Science.gov (United States)

    Esch, Tobias; Stefano, George B

    2010-06-30

    Stress can facilitate disease processes and causes strain on the health care budgets. It is responsible or involved in many human ailments of our time, such as cardiovascular illnesses, particularly related to the psychosocial stressors of daily life, including work. Besides pharmacological or clinical medical treatment options, behavioral stress reduction is much-needed. These latter approaches rely on an endogenous healing potential via life-style modification. Hence, research has suggested different ways and approaches to self-treat stress or buffer against stressors and their impacts. These self-care-centred approaches are sometimes referred to as mind-body medicine or multi-factorial stress management strategies. They consist of various cognitive behavioral techniques, as well as relaxation exercises and nutritional counselling. However, a critical and consistent element of modern effective stress reduction strategies are exercise practices. With regard to underlying neurobiological mechanisms of stress relief, reward and motivation circuitries that are imbedded in the limbic regions of the brain are responsible for the autoregulatory and endogenous processing of stress. Exercise techniques clearly have an impact upon these systems. Thereby, physical activities have a potential to increase mood, i.e., decrease psychological distress by pleasure induction. For doing so, neurobiological signalling molecules such as endogenous morphine and coupled nitric oxide pathways get activated and finely tuned. Evolutionarily, the various activities and autoregulatory pathways are linked together, which can also be demonstrated by the fact that dopamine is endogenously converted into morphine which itself leads to enhanced nitric oxide release by activation of constitutive nitric oxide synthase enzymes. These molecules and mechanisms are clearly stress-reducing.

  15. Involvement of the nitric oxide in melatonin-mediated protection against injury.

    Science.gov (United States)

    Fan, Wenguo; He, Yifan; Guan, Xiaoyan; Gu, Wenzhen; Wu, Zhi; Zhu, Xiao; Huang, Fang; He, Hongwen

    2018-05-01

    Melatonin is a hormone mainly synthesized by the pineal gland in vertebrates and known well as an endogenous regulator of circadian and seasonal rhythms. It has been demonstrated that melatonin is involved in many physiological and pathophysiological processes showing antioxidant, anti-apoptotic and anti-inflammatory properties. Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions. Accumulating evidence has clearly revealed that melatonin regulates NO/NOS system through multiple mechanisms that may influence physiological and pathophysiological processes. This article reviews the latest evidence for the effects of melatonin on NO/NOS regulation in different organs and disease conditions, the potential cellular mechanisms by which melatonin is involved in organ protection are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. 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.

  17. Myositis non-inflammatory mechanisms: An up-dated review.

    Science.gov (United States)

    Manole, Emilia; Bastian, Alexandra E; Butoianu, Niculina; Goebel, Hans H

    2017-01-01

    Idiopathic inflammatory myopathies (IIM) represent a heterogeneous group of rare muscular diseases, with no clearly known causes. IIM frequently have an incomplete response to treatment due to the difficulty in distinguishing between IIM forms, and due to neglect their non-inflammatory causes. Important data concerning non-immune mechanisms in IIM pathology have been recently accumulated. There is a correlation between inflammatory and non-inflammatory mechanisms, but their involvement in IIM pathogenesis is still unknown. Here we review some of the most important data regarding the non-immune IIM pathology, highlighting possible future therapeutic targets: endoplasmic reticulum stress, ATP metabolism, ROS generation, autophagy, and microRNAs disturbances.

  18. Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms.

    Science.gov (United States)

    Tonacchera, M; Vitti, P; Agretti, P; Ceccarini, G; Perri, A; Cavaliere, R; Mazzi, B; Naccarato, A G; Viacava, P; Miccoli, P; Pinchera, A; Chiovato, L

    1999-11-01

    The molecular biology of follicular cell growth in thyroid nodules is still poorly understood. Because gain-of-function (activating) mutations of the thyroid-stimulating hormone receptor (TShR) and/or Gs alpha genes may confer TSh-independent growth advantage to neoplastic thyroid cells, we searched for somatic mutations of these genes in a series of hyperfunctioning and nonfunctioning follicular thyroid adenomas specifically selected for their homogeneous gross anatomy (single nodule in an otherwise normal thyroid gland). TShR gene mutations were identified by direct sequencing of exons 9 and 10 of the TShR gene in genomic DNA obtained from surgical specimens. Codons 201 and 227 of the Gs alpha gene were also analyzed. At histology, all hyperfunctioning nodules and 13 of 15 nonfunctioning nodules were diagnosed as follicular adenomas. Two nonfunctioning thyroid nodules, although showing a prevalent microfollicular pattern of growth, had histological features indicating malignant transformation (a minimally invasive follicular carcinoma and a focal papillary carcinoma). Activating mutations of the TShR gene were found in 12 of 15 hyperfunctioning follicular thyroid adenomas. In one hyperfunctioning adenoma, which was negative for TShR mutations, a mutation in codon 227 of the Gs alpha gene was identified. At variance with hyperfunctioning thyroid adenomas, no mutation of the TShR or Gs alpha genes was detected in nonfunctioning thyroid nodules. In conclusion, our findings clearly define a different molecular pathogenetic mechanism in hyperfunctioning and nonfunctioning follicular thyroid adenomas. Activation of the cAMP cascade, which leads to proliferation but maintains differentiation of follicular thyroid cells, typically occurs in hyperfunctioning thyroid adenomas. Oncogenes other than the TShR and Gs alpha genes are probably involved in nonfunctioning follicular adenomas.

  19. Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity

    International Nuclear Information System (INIS)

    Cattani, Daiane; Oliveira Cavalli, Liz Vera Lúcia de; Heinz Rieg, Carla Elise; Domingues, Juliana Tonietto; Dal-Cim, Tharine; Tasca, Carla Inês; Mena Barreto Silva, Fátima Regina; Zamoner, Ariane

    2014-01-01

    Graphical abstract: - Highlights: • Roundup ® induces Ca 2+ influx through L-VDCC and NMDA receptor activation. • The mechanisms underlying Roundup ® neurotoxicity involve glutamatergic excitotoxicity. • Kinase pathways participate in Roundup ® -induced neural toxicity. • Roundup ® alters glutamate uptake, release and metabolism in hippocampal cells. - Abstract: Previous studies demonstrate that glyphosate exposure is associated with oxidative damage and neurotoxicity. Therefore, the mechanism of glyphosate-induced neurotoxic effects needs to be determined. The aim of this study was to investigate whether Roundup ® (a glyphosate-based herbicide) leads to neurotoxicity in hippocampus of immature rats following acute (30 min) and chronic (pregnancy and lactation) pesticide exposure. Maternal exposure to pesticide was undertaken by treating dams orally with 1% Roundup ® (0.38% glyphosate) during pregnancy and lactation (till 15-day-old). Hippocampal slices from 15 day old rats were acutely exposed to Roundup ® (0.00005–0.1%) during 30 min and experiments were carried out to determine whether glyphosate affects 45 Ca 2+ influx and cell viability. Moreover, we investigated the pesticide effects on oxidative stress parameters, 14 C-α-methyl-amino-isobutyric acid ( 14 C-MeAIB) accumulation, as well as glutamate uptake, release and metabolism. Results showed that acute exposure to Roundup ® (30 min) increases 45 Ca 2+ influx by activating NMDA receptors and voltage-dependent Ca 2+ channels, leading to oxidative stress and neural cell death. The mechanisms underlying Roundup ® -induced neurotoxicity also involve the activation of CaMKII and ERK. Moreover, acute exposure to Roundup ® increased 3 H-glutamate released into the synaptic cleft, decreased GSH content and increased the lipoperoxidation, characterizing excitotoxicity and oxidative damage. We also observed that both acute and chronic exposure to Roundup ® decreased 3 H-glutamate uptake and

  20. POVMs: a small but important step beyond standard quantum mechanics

    NARCIS (Netherlands)

    Muynck, de W.M.; Nieuwenhuizen, T.M.; Spicka, V.; Mehmani, B.; et al., xx

    2007-01-01

    It is the purpose of the present contribution to demonstrate that the generalization of the concept of a quantum mechanical oservable from the Hermitian operator of standard quantum mechanics to a positive operator-valued measure is not a peripheral issue, allegedly to be understood in terms of a

  1. [Labor accidents involving the eyes: assessment of occupational risks involving nursing workers].

    Science.gov (United States)

    de Almeida, Cristiana Brasil; Pagliuca, Lorita Marlena Freitag; Leite, Ana Lourdes Almeida e Silva

    2005-01-01

    The study aimed at identifying nursing workers who were victims of eye accidents and the type of accident; describing the measures taken and proposing Health Education methods. A descriptive and exploratory study was carried out at a public maternity hospital from September 2002 to January 2003. Data were collected through direct observation of the environment and interviews with workers. Subjects were ten professionals (one nurse, two technicians and seven nursing auxiliaries) who were victims of work accidents involving the eye. The accidents were grouped according to the type of material that caused the trauma: chemical substances (4), medication (3), mechanical trauma (1), scalp (1) and urine (1). The results reveal that hospital workers are vulnerable to labor accidents because the environment presents biological, chemical and physical risks. An important step to prevent the occurrence of new accidents would be the prevention of human mistakes through permanent training and the use of protection glasses.

  2. Involvement of pterygoid venous plexus in patulous eustachian tube symptoms.

    Science.gov (United States)

    Oshima, Takeshi; Ogura, Masaki; Kikuchi, Toshiaki; Hori, Yoko; Mugikura, Shunji; Higano, Shuichi; Takahashi, Shoki; Kawase, Tetsuaki; Kobayashi, Toshimitsu

    2007-07-01

    The pterygoid venous plexus (PVP) is an important factor in the mechanism of eustachian tube (ET) closure under conditions that can cause increased venous pressure in the head, such as during neck compression and postural change from the sitting/standing to the recumbent position. The symptoms of patulous ET are usually improved by neck compression or postural change (from sitting/standing to recumbent position). Venous congestion around the ET and/or gravitational change may be involved in the changing degree of symptoms, but its mechanism is not understood. This study investigated whether the PVP is involved. The dimensions of soft tissues surrounding ET were measured on magnetic resonance images before and after neck compression. The lateral pterygoid muscle became enlarged after neck compression. Simultaneously, the volume of venous plexus observed between the medial pterygoid muscle and tensor veli palatini muscle was increased. Such enlargement was probably due to blood pooling in the PVP, resulting in protrusion of the ET anterior wall to the luminal side, and decreased ET patency.

  3. Meiotic restitution mechanisms involved in the formation of 2n pollen in Agave tequilana Weber and Agave angustifolia Haw.

    Science.gov (United States)

    Gómez-Rodríguez, Víctor Manuel; Rodríguez-Garay, Benjamín; Barba-Gonzalez, Rodrigo

    2012-01-01

    A cytological analysis of the microsporogenesis was carried out in the Agave tequilana and A. angustifolia species. Several abnormalities such as chromosomal bridges, lagging chromosomes, micronuclei, monads, dyads and triads were found. The morphological analysis of the pollen, together with the above-mentioned 2n microspores, allowed us to confirm the presence of 2n pollen as well as its frequency. In both A. tequilana and A. angustifolia two different mechanisms were observed: the first mechanism, a failure in the cytokinesis in meiosis II caused the formation of dyads with two 2n cells and triads containing two n cells and one 2n cell; the second mechanism, involves an abnormal spindle, which caused the formation of triads with two n cells and one 2n cell. Likewise, the presence of monads was detected in both species, these, might be caused by a failure of the cytokinesis in both meiotic divisions. This is the first report about the presence of a Second Division Restitution mechanism (SDR) which causes the formation of 2n pollen in the genus Agave. The genetic implications of the presence of 2n pollen in the genus Agave are discussed.

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

    International Nuclear Information System (INIS)

    Massi, Paola; Valenti, Marta; Solinas, Marta; Parolaro, Daniela

    2010-01-01

    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

  5. 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 [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.

  6. 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.

  7. Mechanisms Design

    DEFF Research Database (Denmark)

    Restrepo-Giraldo, John Dairo

    2006-01-01

    Most products and machines involve some kind of controlled movement. From window casements to DVD players, from harbor cranes to the shears to prune your garden, all these machines require mechanisms to move. This course intends to provide the analytical and conceptual tools to design such mechan......Most products and machines involve some kind of controlled movement. From window casements to DVD players, from harbor cranes to the shears to prune your garden, all these machines require mechanisms to move. This course intends to provide the analytical and conceptual tools to design...... using criteria such as size, performance parameters, operation environment, etc. Content: Understanding Mechanisms Design (2 weeks) Definitions, mechanisms representations, kinematic diagrams, the four bar linkage, mobility, applications of mechanisms, types of mechanisms, special mechanisms, the design......: equations for various mechanisms. At the end of this module you will be able to analyze existing mechanisms and to describe their movement. Designing mechanisms (7 weeks) Type synthesis and dimensional synthesis, function generation, path generation, three precision points in multi-loop mechanisms...

  8. Mitochondrial damage: An important mechanism of ambient PM2.5 exposure-induced acute heart injury in rats

    International Nuclear Information System (INIS)

    Li, Ruijin; Kou, Xiaojing; Geng, Hong; Xie, Jingfang; Tian, Jingjing; Cai, Zongwei; Dong, Chuan

    2015-01-01

    Highlights: • PM 2.5 induces heart mitochondrial morphological damage of rats. • Mitochondrial fission/fusion gene expression is important regulation mechanism. • Proinflammatoy cytokine level changes are accompanied with mitochondrial damage. • Alterations in oxidative stress and calcium homeostasis are focused on. - Abstract: Epidemiological studies suggested that ambient fine particulate matter (PM 2.5 ) exposure was associated with cardiovascular disease. However, the underlying mechanism, especially the mitochondrial damage mechanism, of PM 2.5 -induced heart acute injury is still unclear. In this study, the alterations of mitochondrial morphology and mitochondrial fission/fusion gene expression, oxidative stress, calcium homeostasis and inflammation in hearts of rats exposed to PM 2.5 with different dosages (0.375, 1.5, 6.0 and 24.0 mg/kg body weight) were investigated. The results indicated that the PM 2.5 exposure induced pathological changes and ultra-structural damage in hearts such as mitochondrial swell and cristae disorder. Furthermore, PM 2.5 exposure significantly increased specific mitochondrial fission/fusion gene (Fis1, Mfn1, Mfn2, Drp1 and OPA1) expression in rat hearts. These changes were accompanied by decreases of activities of superoxide dismutase (SOD), Na + K + -ATPase and Ca 2+ -ATPase and increases of levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) as well as levels of pro-inflammatory mediators including TNF-α, IL-6 and IL-1β in rat hearts. The results implicate that mitochondrial damage, oxidative stress, cellular homeostasis imbalance and inflammation are potentially important mechanisms for the PM 2.5 -induced heart injury, and may have relations with cardiovascular disease

  9. Financial mechanisms and social safety-oriented model of development of the Russian economy (based on import substitution and innovation

    Directory of Open Access Journals (Sweden)

    T. I. Ovchinnikova

    2016-01-01

    Full Text Available In article features of import substitution in the socially oriented model determined as economy with the high level of the state income redistribution of subjects of managing and developed on this basis of system of social protection are considered. Import substitution is considered from the traditional point of view – creation of new productions and technologies which are implemented at the expense of own and borrowed funds of investors. The financial mechanisms for implementation of innovations promoting import substitution are offered: industry plans and road maps as availability of reference points for creation of rational amounts of the budget payments and financial resources of the entities necessary for upgrade of productions, and also the directions of financial resources for implementation of specific most important national priorities and innovative investment projects. The volume of investment into the fixed capital correlated to its cost considerably grew from 3.5% in 2003 to 11.6% in 2009, but value of this indicator isn't enough as degree of depreciation of fixed assets in economy of the region constituted 44.9% in 2009. Direct foreign investments prevail: in Krasnoyarsk Krai their share constituted in 2009 – 45.4%, Krasnodar Region – 40.5%, the Nizhny Novgorod Region – 84.5%. In the Voronezh region such entities as KBHA, Federal State Unitary Enterprise State Research and Production Space Center branch of M. V. Khrunichev the Voronezh Mechanical Plant, JSC Sozvezdiye Concern having the high technologies making safety of the country and especially needing investments function. In plans of urgent strategy of social and economic development of the Voronezh region it is supposed to increase specific weight of innovative products of such entities and to increase the level of innovative activity till 2020. The socially oriented model considering import substitution domestic technologies and products needs strengthening of the

  10. Interfacial Mechanics Analysis of a Brittle Coating–Ductile Substrate System Involved in Thermoelastic Contact

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    2017-02-01

    Full Text Available In this paper, interfacial stress analysis for a brittle coating/ductile substrate system, which is involved in a sliding contact with a rigid ball, is presented. By combining interface mechanics theory and the image point method, stress and displacement responses within a coated material for normal load, tangential load, and thermal load are obtained; further, the Green’s functions are established. The effects of coating thickness, friction coefficient, and a coating’s thermoelastic properties on the interfacial shear stress, τxz, and transverse stress, σxx, distributions are discussed in detail. A phenomenon, where interfacial shear stress tends to be relieved by frictional heating, is found in the case of a coating material’s thermal expansion coefficient being less than a substrate material’s thermal expansion coefficient. Additionally, numerical results show that distribution of interfacial stress can be altered and, therefore, interfacial damage can be modified by adjusting a coating’s structural parameters and thermoelastic properties.

  11. Energy transfer in a mechanically trapped exciplex.

    Science.gov (United States)

    Klosterman, Jeremy K; Iwamura, Munetaka; Tahara, Tahei; Fujita, Makoto

    2009-07-15

    Host-guest complexes involving M(6)L(4) coordination cages can display unusual photoreactivity, and enclathration of the very large fluorophore bisanthracene resulted in an emissive, mechanically trapped intramolecular exciplex. Mechanically linked intramolecular exciplexes are important for understanding the dependence of energy transfer on donor-acceptor distance, orientation, and electronic coupling but are relatively unexplored. Steady-state and picosecond time-resolved fluorescence measurements have revealed that selective excitation of the encapsulated guest fluorophore results in efficient energy transfer from the excited guest to an emissive host-guest exciplex state.

  12. Insertion of molecular oxygen into a palladium(II) methyl bond: a radical chain mechanism involving palladium(III) intermediates.

    Science.gov (United States)

    Boisvert, Luc; Denney, Melanie C; Hanson, Susan Kloek; Goldberg, Karen I

    2009-11-04

    The reaction of (bipy)PdMe(2) (1) (bipy = 2,2'-bipyridine) with molecular oxygen results in the formation of the palladium(II) methylperoxide complex (bipy)PdMe(OOMe) (2). The identity of the product 2 has been confirmed by independent synthesis. Results of kinetic studies of this unprecedented oxygen insertion reaction into a palladium alkyl bond support the involvement of a radical chain mechanism. Reproducible rates, attained in the presence of the radical initiator 2,2'-azobis(2-methylpropionitrile) (AIBN), reveal that the reaction is overall first-order (one-half-order in both [1] and [AIBN], and zero-order in [O(2)]). The unusual rate law (half-order in [1]) implies that the reaction proceeds by a mechanism that differs significantly from those for organic autoxidations and for the recently reported examples of insertion of O(2) into Pd(II) hydride bonds. The mechanism for the autoxidation of 1 is more closely related to that found for the autoxidation of main group and early transition metal alkyl complexes. Notably, the chain propagation is proposed to proceed via a stepwise associative homolytic substitution at the Pd center of 1 with formation of a pentacoordinate Pd(III) intermediate.

  13. On the Importance of "Front-Side Mechanics" in Athletics Sprinting.

    Science.gov (United States)

    Haugen, Thomas; Danielsen, Jørgen; Alnes, Leif Olav; McGhie, David; Sandbakk, Øyvind; Ettema, Gertjan

    2018-05-16

    Practitioners have, for many years, argued that athletic sprinters should optimize front-side mechanics (leg motions occurring in front of the extended line through the torso) and minimize back-side mechanics. This study aimed to investigate if variables related to front- and back-side mechanics can be distinguished from other previously highlighted kinematic variables (spatiotemporal variables and variables related to segment configuration and velocities at touchdown) in how they statistically predict performance. A total of 24 competitive sprinters (age: 23.1 [3.4] y, height: 1.81 [0.06] m, body mass: 75.7 [5.6] kg, and 100-m personal best: 10.86 [0.22] s) performed two 20-m starts from block and 2 to 3 flying sprints over 20 m. Kinematics were recorded in 3D using a motion tracking system with 21 cameras at a 250 Hz sampling rate. Several front- and back-side variables, including thigh (r = .64) and knee angle (r = .51) at lift-off and maximal thigh extension (r = .66), were largely correlated (P mechanics were crucial for sprint performance among the investigated sprinters.

  14. Endocytosis of hERG Is Clathrin-Independent and Involves Arf6

    Science.gov (United States)

    Abuarab, Nada; Smith, Andrew J.; Hardy, Matthew E. L.; Elliott, David J. S.; Sivaprasadarao, Asipu

    2013-01-01

    The hERG potassium channel is critical for repolarisation of the cardiac action potential. Reduced expression of hERG at the plasma membrane, whether caused by hereditary mutations or drugs, results in long QT syndrome and increases the risk of ventricular arrhythmias. Thus, it is of fundamental importance to understand how the density of this channel at the plasma membrane is regulated. We used antibodies to an extracellular native or engineered epitope, in conjunction with immunofluorescence and ELISA, to investigate the mechanism of hERG endocytosis in recombinant cells and validated the findings in rat neonatal cardiac myocytes. The data reveal that this channel undergoes rapid internalisation, which is inhibited by neither dynasore, an inhibitor of dynamin, nor a dominant negative construct of Rab5a, into endosomes that are largely devoid of the transferrin receptor. These results support a clathrin-independent mechanism of endocytosis and exclude involvement of dynamin-dependent caveolin and RhoA mechanisms. In agreement, internalised hERG displayed marked overlap with glycosylphosphatidylinositol-anchored GFP, a clathrin-independent cargo. Endocytosis was significantly affected by cholesterol extraction with methyl-β-cyclodextrin and inhibition of Arf6 function with dominant negative Arf6-T27N-eGFP. Taken together, we conclude that hERG undergoes clathrin-independent endocytosis via a mechanism involving Arf6. PMID:24392021

  15. Father-involvement in a refugee sample: relations between posttraumatic stress and caregiving.

    Science.gov (United States)

    van Ee, Elisa; Sleijpen, Marieke; Kleber, Rolf J; Jongmans, Marian J

    2013-12-01

    Despite increased attention to the role of fathers within families, there is still a dearth of studies on the impact of trauma on father-involvement. This study investigates the quantity of father-involvement and the influence of posttraumatic stress on the quality of involvement in a refugee and asylum seeker population. Eighty refugees and asylum seekers and their young children (aged 18-42 months) were recruited. Measures included assessment of parental trauma (Harvard Trauma Questionnaire), quantity and quality of involvement (quantity of caregiving and Emotional Availability Scales), and perception of the father-child relationship (interview). The results show that fathers were less involved in caregiving tasks and play activities than mothers. No parental gender differences were found on each of the Emotional Availability Scales. Traumatic stress symptoms negatively affected the perception and the actual quality of parent-child interaction (sensitivity, structuring, nonhostility). Nevertheless, almost all fathers described their relationship with their child as good and their child as very important to them. As the quality of father-involvement is of importance to the development of the child, traumatized fathers are as much in need of clinical intervention as mothers. Despite the impact of posttraumatic stress, refugee fathers clearly are involved in the lives of their children. Mechanisms such as a deliberate withdrawal when stressed and compensation might enable affected fathers to step into the interaction when needed, raise the quality of involvement with their child, and diminish the negative impact of stress resulting from trauma and migration. © FPI, Inc.

  16. Epigenetic modifications: An important mechanism in diabetic disturbances.

    Science.gov (United States)

    Rorbach-Dolata, Anna; Kubis, Adriana; Piwowar, Agnieszka

    2017-11-29

    In the search for explanations of diabetes pathomechanisms, especially the development of its vascular complications (micro- and macrovascular ), although current, good metabolic control of diabetes, attention was drawn to the role of epigenetic inheritance associated with epigenetic modifications of histone proteins and DNA in hyperglycemia conditions. This study showed the significant role of DNA methylation and histone epigenetic modifications (a different nature and a different degree) in the transmission of information that is not connected with gene inheritance but concerns the persistent changes induced by hyperglycemia..Attention was paid to the role of DNA methylation of pancreatic cells in the pathogenesis of type 1 diabetes, but also type 2. The important role of DNA methylation changes in a so-called intrauterine growth restriction (IUGR) as reason of subsequent development of diabetes was particularly emphasized. In the pathogenesis of type 2 diabetes and its complications, especially microvascular complications, the greatest share and importance of epigenetic modifications on mitochondrial DNA metylation are the most important. The multidirectionality Complicaand complexity of epigenetic modifications of histone proteins indicate their importance in the development of diabetic disturbances. An especially important role is attributed to methylation and acetylation of histone proteins, in particular on arginine and lysine, whose changes occur most frequently. Moreover, epigenetic modifications of the enzymes, especially methylases, responsible for these processes are the underlying. It has been indicated that the identification of epigenetic differences within the DNA or histone proteins may be a useful prognostic biomarker of susceptibility to the disease development in the future. Moreover, they may become a potential target for future therapeutic interventions for clinical disorders in diabetes.

  17. Managing delayed projects. Cernavoda NPP - Romania. Importance of NGO involvement

    International Nuclear Information System (INIS)

    Rotaru, I.

    2003-01-01

    In Romania there is a diversity of civil societies with respect to the attitude towards nuclear power. Among the dedicated societies supporting nuclear power development there are: the Romanian Atomic Forum (Ratomet), affiliated to the European Atomic Forum; the Romanian Nuclear Power Association (Arden), affiliated to the European Nuclear Society; the Romanian Radioprotection Society (SR Rp), affiliated to the Radiation Protection Association. The main dedicated activities of above mentioned Non-governmental Organizations (Ng) are: establishing contacts and organizing meeting with Romanian political decision making factors, mass media representatives, institutional entities, civil society ect.; orienting and co-coordinating activities of Romanian companies involved in production and services for nuclear energy; serving as contact point for relevant international communication and business relation; creating internal working groups for certain theme or sub-domain and suggested solution for a particular issue, including experts even from outside of the association; performing lobby activities ect

  18. Solving the cardiac hypertrophy riddle: The angiotensin II-mechanical stress connection.

    Science.gov (United States)

    Zablocki, Daniela; Sadoshima, Junichi

    2013-11-08

    A series of studies conducted 20 years ago, documenting the cardiac hypertrophy phenotype and its underlying signaling mechanism induced by angiotensin II (Ang II) and mechanical stress, showed a remarkable similarity between the effect of the Gαq agonist and that of mechanical forces on cardiac hypertrophy. Subsequent studies confirmed the involvement of autocrine/paracrine mechanisms, including stretch-induced release of Ang II in load-induced cardiac hypertrophy. Recent studies showed that the Ang II type 1 (AT1) receptor is also directly activated by mechanical forces, suggesting that AT1 receptors play an important role in mediating load-induced cardiac hypertrophy through both ligand- and mechanical stress-dependent mechanisms.

  19. Importance of intrahepatic mechanisms to gluconeogenesis from alanine during exercise and recovery

    International Nuclear Information System (INIS)

    Wasserman, D.H.; Williams, P.E.; Lacy, D.B.; Green, D.R.; Cherrington, A.D.

    1988-01-01

    These studies were performed to assess the importance of intrahepatic mechanisms to gluconeogenesis in the dog during 150 min of treadmill exercise and 90 min of recovery. Sampling catheters were implanted in an artery and portal and hepatic veins 16 days before experimentation. Infusions of [U- 14 C]alanine, [3- 3 H]glucose, and indocyanine green were used to assess gluconeogenesis. During exercise, a decline in arterial and portal vein plasma alanine and in hepatic blood flow led to a decrease in hepatic alanine delivery. During recovery, hepatic blood flow was restored to basal, causing an increase in hepatic alanine delivery beyond exercise rates but still below resting rates. Hepatic fractional alanine extraction increased from 0.26 +/- 0.02 at rest to 0.64 +/- 0.03 during exercise and remained elevated during recovery. Net hepatic alanine uptake was 2.5 +/- 0.2 mumol.kg-1.min-1 at rest and remained unchanged during exercise but was increased during recovery. The conversion rate of [ 14 C]alanine to glucose had increased by 248 +/- 38% by 150 min of exercise and had increased further during recovery. The efficiency with which alanine was channeled into glucose in the liver was accelerated to a rate of 338 +/- 55% above basal by 150 min of exercise but declined slightly during recovery. In conclusion, 1) gluconeogenesis from alanine is accelerated during exercise, due to an increase in the hepatic fractional extraction of the amino acid and through intrahepatic mechanisms that more efficiently channel it into glucose

  20. Bell trajectories for revealing quantum control mechanisms

    International Nuclear Information System (INIS)

    Dennis, Eric; Rabitz, Herschel

    2003-01-01

    The dynamics induced while controlling quantum systems by optimally shaped laser pulses have often been difficult to understand in detail. A method is presented for quantifying the importance of specific sequences of quantum transitions involved in the control process. The method is based on a ''beable'' formulation of quantum mechanics due to John Bell that rigorously maps the quantum evolution onto an ensemble of stochastic trajectories over a classical state space. Detailed mechanism identification is illustrated with a model seven-level system. A general procedure is presented to extract mechanism information directly from closed-loop control experiments. Application to simulated experimental data for the model system proves robust with up to 25% noise

  1. 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.

  2. Formation mechanisms of trichloromethyl-containing compounds in the terrestrial environment

    DEFF Research Database (Denmark)

    Breider, Florian; Albers, Christian Nyrop

    2015-01-01

    Natural trichloromethyl compounds present in the terrestrial environment are important contributors to chlorine in the lower atmosphere and may be also a cause for concern when high concentrations are detected in soils and groundwater. During the last decade our knowledge of the mechanisms involved...... of trichloromethyl compounds and then to compare these mechanisms with the much more comprehensive literature on the reactions occurring during chemical chlorination of organic material. It turns out that the reaction mechanisms during chemical chlorination are likely to be similar to those occurring naturally...

  3. Reaction mechanisms in heavy ion fusion

    Directory of Open Access Journals (Sweden)

    Lubian J.

    2011-10-01

    Full Text Available We discuss the reaction mechanisms involved in heavy ion fusion. We begin with collisions of tightly bound systems, considering three energy regimes: energies above the Coulomb barrier, energies just below the barrier and deep sub-barrier energies. We show that channel coupling effects may influence the fusion process at above-barrier energies, increasing or reducing the cross section predicted by single barrier penetration model. Below the Coulomb barrier, it enhances the cross section, and this effect increases with the system’s size. It is argued that this behavior can be traced back to the increasing importance of Coulomb coupling with the charge of the collision partners. The sharp drop of the fusion cross section observed at deep sub-barrier energies is addressed and the theoretical approaches to this phenomenon are discussed. We then consider the reaction mechanisms involved in fusion reactions of weakly bound systems, paying particular attention to the calculations of complete and incomplete fusion available in the literature.

  4. Involvement of thiol-based mechanisms in plant development.

    Science.gov (United States)

    Rouhier, Nicolas; Cerveau, Delphine; Couturier, Jérémy; Reichheld, Jean-Philippe; Rey, Pascal

    2015-08-01

    Increasing knowledge has been recently gained regarding the redox regulation of plant developmental stages. The current state of knowledge concerning the involvement of glutathione, glutaredoxins and thioredoxins in plant development is reviewed. The control of the thiol redox status is mainly ensured by glutathione (GSH), a cysteine-containing tripeptide and by reductases sharing redox-active cysteines, glutaredoxins (GRXs) and thioredoxins (TRXs). Indeed, thiol groups present in many regulatory proteins and metabolic enzymes are prone to oxidation, ultimately leading to post-translational modifications such as disulfide bond formation or glutathionylation. This review focuses on the involvement of GSH, GRXs and TRXs in plant development. Recent studies showed that the proper functioning of root and shoot apical meristems depends on glutathione content and redox status, which regulate, among others, cell cycle and hormone-related processes. A critical role of GRXs in the formation of floral organs has been uncovered, likely through the redox regulation of TGA transcription factor activity. TRXs fulfill many functions in plant development via the regulation of embryo formation, the control of cell-to-cell communication, the mobilization of seed reserves, the biogenesis of chloroplastic structures, the metabolism of carbon and the maintenance of cell redox homeostasis. This review also highlights the tight relationships between thiols, hormones and carbon metabolism, allowing a proper development of plants in relation with the varying environment and the energy availability. GSH, GRXs and TRXs play key roles during the whole plant developmental cycle via their antioxidant functions and the redox-regulation of signaling pathways. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Mechanisms of otoconia and otolith development.

    Science.gov (United States)

    Lundberg, Yunxia Wang; Xu, Yinfang; Thiessen, Kevin D; Kramer, Kenneth L

    2015-03-01

    Otoconia are bio-crystals that couple mechanic forces to the sensory hair cells in the utricle and saccule, a process essential for us to sense linear acceleration and gravity for the purpose of maintaining bodily balance. In fish, structurally similar bio-crystals called otoliths mediate both balance and hearing. Otoconia abnormalities are common and can cause vertigo and imbalance in humans. However, the molecular etiology of these illnesses is unknown, as investigators have only begun to identify genes important for otoconia formation in recent years. To date, in-depth studies of selected mouse otoconial proteins have been performed, and about 75 zebrafish genes have been identified to be important for otolith development. This review will summarize recent findings as well as compare otoconia and otolith development. It will provide an updated brief review of otoconial proteins along with an overview of the cells and cellular processes involved. While continued efforts are needed to thoroughly understand the molecular mechanisms underlying otoconia and otolith development, it is clear that the process involves a series of temporally and spatially specific events that are tightly coordinated by numerous proteins. Such knowledge will serve as the foundation to uncover the molecular causes of human otoconia-related disorders. © 2014 Wiley Periodicals, Inc.

  6. Circuit mechanisms of sensorimotor learning

    Science.gov (United States)

    Makino, Hiroshi; Hwang, Eun Jung; Hedrick, Nathan G.; Komiyama, Takaki

    2016-01-01

    SUMMARY The relationship between the brain and the environment is flexible, forming the foundation for our ability to learn. Here we review the current state of our understanding of the modifications in the sensorimotor pathway related to sensorimotor learning. We divide the process in three hierarchical levels with distinct goals: 1) sensory perceptual learning, 2) sensorimotor associative learning, and 3) motor skill learning. Perceptual learning optimizes the representations of important sensory stimuli. Associative learning and the initial phase of motor skill learning are ensured by feedback-based mechanisms that permit trial-and-error learning. The later phase of motor skill learning may primarily involve feedback-independent mechanisms operating under the classic Hebbian rule. With these changes under distinct constraints and mechanisms, sensorimotor learning establishes dedicated circuitry for the reproduction of stereotyped neural activity patterns and behavior. PMID:27883902

  7. Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

    Science.gov (United States)

    Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

    2016-10-01

    As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. 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......‐scanning extended X‐ray absorption fine structure spectroscopy enabled the time‐dependent evolution of the starting compound, the intermediates and the product to be monitored over the full reaction period. The reaction starts with fast chlorine substitution and partial reduction during the dissolution...

  9. The ectomycorrhizal fungus Paxillus involutus converts organic matter in plant litter using a trimmed brown-rot mechanism involving Fenton chemistry

    DEFF Research Database (Denmark)

    Rineau, Francois; Roth, Doris; Shah, Firoz

    2012-01-01

    chemistry similar to that of brown-rot fungi. The set of enzymes expressed by Pa. involutus during the degradation of the organic matter was similar to the set of enzymes involved in the oxidative degradation of wood by brown-rot fungi. However, Pa. involutus lacked transcripts encoding extracellular...... the mycorrhizal fungi. To capture the nitrogen, the fungi must at least partly disrupt the recalcitrant organic matterprotein complexes within which the nitrogen is embedded. This disruption process is poorly characterized. We used spectroscopic analyses and transcriptome profiling to examine the mechanism...... by which the ectomycorrhizal fungus Paxillus involutus degrades organic matter when acquiring nitrogen from plant litter. The fungus partially degraded polysaccharides and modified the structure of polyphenols. The observed chemical changes were consistent with a hydroxyl radical attack, involving Fenton...

  10. Infant sleep and paternal involvement in infant caregiving during the first 6 months of life.

    Science.gov (United States)

    Tikotzky, Liat; Sadeh, Avi; Glickman-Gavrieli, Tamar

    2011-01-01

    The goals of this study were to assess: (a) the involvement of fathers and mothers in overall and nighttime infant caregiving; (b) the links between paternal involvement in infant care and infant sleep patterns during the first 6 months. Fifty-six couples recruited during their first pregnancy, participated in the study. After delivery (1 and 6 months), both parents completed a questionnaire assessing the involvement of fathers relative to mothers in infant caregiving. Infant sleep was assessed using actigraphy and sleep diaries. Mothers were significantly more involved than fathers in daytime and nighttime caregiving. A higher involvement of fathers in overall infant care predicted and was associated with fewer infant night-wakings and with shorter total sleep time after controlling for breastfeeding. The findings highlight the importance of including fathers in developmental sleep research. Future studies should explore mechanisms underlying the relations between paternal involvement and infant sleep.

  11. Physiological Importance and Mechanisms of Protein Hydrolysate Absorption

    Science.gov (United States)

    Zhanghi, Brian M.; Matthews, James C.

    Understanding opportunities to maximize the efficient digestion and assimilation by production animals of plant- and animal-derived protein products is critical for farmers, nutritionists, and feed manufacturers to sustain and expand the affordable production of high quality animal products for human consumption. The challenge to nutritionists is to match gastrointestinal tract load to existing or ­inducible digestive and absorptive capacities. The challenge to feed manufacturers is to develop products that are efficient substrates for digestion, absorption, and/or both events. Ultimately, the efficient absorption of digesta proteins depends on the mediated passage (transport) of protein hydrosylate products as dipeptides and unbound amino acids across the lumen- and blood-facing membranes of intestinal absorptive cells. Data testing the relative efficiency of supplying protein as hydrolysates or specific dipeptides versus as free amino acids, and the response of animals in several physiological states to feeding of protein hydrolysates, are presented and reviewed in this chapter. Next, data describing the transport mechanisms responsible for absorbing protein hydrolysate digestion products, and the known and putative regulation of these mechanisms by their substrates (small peptides) and hormones are presented and reviewed. Several conclusions are drawn regarding the efficient use of protein hydrolysate-based diets for particular physiological states, the economically-practical application of which likely will depend on technological advances in the manufacture of protein hydrolysate products.

  12. 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.

  13. General extrapolation model for an important chemical dose-rate effect

    International Nuclear Information System (INIS)

    Gillen, K.T.; Clough, R.L.

    1984-12-01

    In order to extrapolate material accelerated aging data, methodologies must be developed based on sufficient understanding of the processes leading to material degradation. One of the most important mechanisms leading to chemical dose-rate effects in polymers involves the breakdown of intermediate hydroperoxide species. A general model for this mechanism is derived based on the underlying chemical steps. The results lead to a general formalism for understanding dose rate and sequential aging effects when hydroperoxide breakdown is important. We apply the model to combined radiation/temperature aging data for a PVC material and show that this data is consistent with the model and that model extrapolations are in excellent agreement with 12-year real-time aging results from an actual nuclear plant. This model and other techniques discussed in this report can aid in the selection of appropriate accelerated aging methods and can also be used to compare and select materials for use in safety-related components. This will result in increased assurance that equipment qualification procedures are adequate

  14. Growth rate regulated genes and their wide involvement in the Lactococcus lactis stress responses

    Directory of Open Access Journals (Sweden)

    Redon Emma

    2008-07-01

    obtained in various growth conditions. It raised the importance of growth rate regulations in bacteria but also participated to the elucidation of the involved mechanism. Though the mechanism controlling growth rate is not yet fully understood in L. lactis, one expected regulatory mechanism has been ruled out, two potential regulators have been pointed out and the involvement of gene location on the chromosome has also been found to be involved in the expression regulation of these growth related genes.

  15. Mitochondrial damage: An important mechanism of ambient PM{sub 2.5} exposure-induced acute heart injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ruijin; Kou, Xiaojing; Geng, Hong; Xie, Jingfang; Tian, Jingjing [Institute of Environmental Science, College of Environmental & Resource Sciences, Shanxi University, Taiyuan (China); Cai, Zongwei, E-mail: zwcai@hkbu.edu.hk [State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR (China); Dong, Chuan, E-mail: dc@sxu.edu.cn [Institute of Environmental Science, College of Environmental & Resource Sciences, Shanxi University, Taiyuan (China)

    2015-04-28

    Highlights: • PM{sub 2.5} induces heart mitochondrial morphological damage of rats. • Mitochondrial fission/fusion gene expression is important regulation mechanism. • Proinflammatoy cytokine level changes are accompanied with mitochondrial damage. • Alterations in oxidative stress and calcium homeostasis are focused on. - Abstract: Epidemiological studies suggested that ambient fine particulate matter (PM{sub 2.5}) exposure was associated with cardiovascular disease. However, the underlying mechanism, especially the mitochondrial damage mechanism, of PM{sub 2.5}-induced heart acute injury is still unclear. In this study, the alterations of mitochondrial morphology and mitochondrial fission/fusion gene expression, oxidative stress, calcium homeostasis and inflammation in hearts of rats exposed to PM{sub 2.5} with different dosages (0.375, 1.5, 6.0 and 24.0 mg/kg body weight) were investigated. The results indicated that the PM{sub 2.5} exposure induced pathological changes and ultra-structural damage in hearts such as mitochondrial swell and cristae disorder. Furthermore, PM{sub 2.5} exposure significantly increased specific mitochondrial fission/fusion gene (Fis1, Mfn1, Mfn2, Drp1 and OPA1) expression in rat hearts. These changes were accompanied by decreases of activities of superoxide dismutase (SOD), Na{sup +}K{sup +}-ATPase and Ca{sup 2+}-ATPase and increases of levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) as well as levels of pro-inflammatory mediators including TNF-α, IL-6 and IL-1β in rat hearts. The results implicate that mitochondrial damage, oxidative stress, cellular homeostasis imbalance and inflammation are potentially important mechanisms for the PM{sub 2.5}-induced heart injury, and may have relations with cardiovascular disease.

  16. Study of mechanism involved in synthesis of graphene oxide and reduced graphene oxide from graphene nanoplatelets

    Science.gov (United States)

    Sharma, Bhasha; Shekhar, Shashank; Malik, Parul; Jain, Purnima

    2018-06-01

    Graphene, a wonder material has inspired quest among researchers due to its numerous applications and exceptional properties. This paper highlights the mechanism and chemistry behind the fabrication of graphene oxide by using phosphoric acid. Chemical functionalization is of prime importance which avoids agglomeration of nanoparticles to attain inherent properties. As non-homogeneous dispersion limits its utilization due to interfacial interactions which restrict reactive sites to produce intercalated network. Thus, chemically functionalized graphene leads to stable dispersion and enhances thermal, mechanical and electrical properties of the resultant polymer composite materials. Solubility of graphene in aqueous solution is the major issue because graphene is hydrophobic, to rectify this oxygen containing hydrophilic groups must be introduced to make it compatible and this can be attained by covalent functionalization. Among all nanofiller GO has shown average particle size i.e. 95 nm and highest surface charge density. The characteristic changes were estimated using Raman spectra.

  17. Mechanics of human voice production and control.

    Science.gov (United States)

    Zhang, Zhaoyan

    2016-10-01

    As the primary means of communication, voice plays an important role in daily life. Voice also conveys personal information such as social status, personal traits, and the emotional state of the speaker. Mechanically, voice production involves complex fluid-structure interaction within the glottis and its control by laryngeal muscle activation. An important goal of voice research is to establish a causal theory linking voice physiology and biomechanics to how speakers use and control voice to communicate meaning and personal information. Establishing such a causal theory has important implications for clinical voice management, voice training, and many speech technology applications. This paper provides a review of voice physiology and biomechanics, the physics of vocal fold vibration and sound production, and laryngeal muscular control of the fundamental frequency of voice, vocal intensity, and voice quality. Current efforts to develop mechanical and computational models of voice production are also critically reviewed. Finally, issues and future challenges in developing a causal theory of voice production and perception are discussed.

  18. Isolation and characterization of Lotus japonicus genes involved in iron and zinc homeostasis

    DEFF Research Database (Denmark)

    Cvitanich, Cristina; Jensen, Winnie; Sandal, Niels Nørgaard

    . Legumes are frequently grown in soil with limited nutrient availability. Plants use finely tuned mechanisms to keep appropriated levels of iron and zinc in each of their organs. Several genes involved in iron and zinc homeostasis have been described in yeast, and a few orthologs have been studied...... in plants. We have used these sequences to search for L. japonicus ESTs and genomic loci that are likely to be involved in iron and zinc metabolism. We have identified sequences corresponding to ferritins, ferric reductases, metal transport proteins of the ZIP family, and cation transporters of the NRAMP......The goal of this project is to find ways to improve the nutritional value of legumes by identifying genes and proteins important for iron and zinc regulation in the model legume Lotus japonicus. Legumes are important staples in the developing world and are a major source of nutrients in many areas...

  19. Bioinformatics Analysis Reveals Genes Involved in the Pathogenesis of Ameloblastoma and Keratocystic Odontogenic Tumor.

    Science.gov (United States)

    Santos, Eliane Macedo Sobrinho; Santos, Hércules Otacílio; Dos Santos Dias, Ivoneth; Santos, Sérgio Henrique; Batista de Paula, Alfredo Maurício; Feltenberger, John David; Sena Guimarães, André Luiz; Farias, Lucyana Conceição

    2016-01-01

    Pathogenesis of odontogenic tumors is not well known. It is important to identify genetic deregulations and molecular alterations. This study aimed to investigate, through bioinformatic analysis, the possible genes involved in the pathogenesis of ameloblastoma (AM) and keratocystic odontogenic tumor (KCOT). Genes involved in the pathogenesis of AM and KCOT were identified in GeneCards. Gene list was expanded, and the gene interactions network was mapped using the STRING software. "Weighted number of links" (WNL) was calculated to identify "leader genes" (highest WNL). Genes were ranked by K-means method and Kruskal-Wallis test was used (Preview data was used to corroborate the bioinformatics data. CDK1 was identified as leader gene for AM. In KCOT group, results show PCNA and TP53 . Both tumors exhibit a power law behavior. Our topological analysis suggested leader genes possibly important in the pathogenesis of AM and KCOT, by clustering coefficient calculated for both odontogenic tumors (0.028 for AM, zero for KCOT). The results obtained in the scatter diagram suggest an important relationship of these genes with the molecular processes involved in AM and KCOT. Ontological analysis for both AM and KCOT demonstrated different mechanisms. Bioinformatics analyzes were confirmed through literature review. These results may suggest the involvement of promising genes for a better understanding of the pathogenesis of AM and KCOT.

  20. QTL analysis of frost damage in pea suggests different mechanisms involved in frost tolerance.

    Science.gov (United States)

    Klein, Anthony; Houtin, Hervé; Rond, Céline; Marget, Pascal; Jacquin, Françoise; Boucherot, Karen; Huart, Myriam; Rivière, Nathalie; Boutet, Gilles; Lejeune-Hénaut, Isabelle; Burstin, Judith

    2014-06-01

    Avoidance mechanisms and intrinsic resistance are complementary strategies to improve winter frost tolerance and yield potential in field pea. The development of the winter pea crop represents a major challenge to expand plant protein production in temperate areas. Breeding winter cultivars requires the combination of freezing tolerance as well as high seed productivity and quality. In this context, we investigated the genetic determinism of winter frost tolerance and assessed its genetic relationship with yield and developmental traits. Using a newly identified source of frost resistance, we developed a population of recombinant inbred lines and evaluated it in six environments in Dijon and Clermont-Ferrand between 2005 and 2010. We developed a genetic map comprising 679 markers distributed over seven linkage groups and covering 947.1 cM. One hundred sixty-one quantitative trait loci (QTL) explaining 9-71 % of the phenotypic variation were detected across the six environments for all traits measured. Two clusters of QTL mapped on the linkage groups III and one cluster on LGVI reveal the genetic links between phenology, morphology, yield-related traits and frost tolerance in winter pea. QTL clusters on LGIII highlighted major developmental gene loci (Hr and Le) and the QTL cluster on LGVI explained up to 71 % of the winter frost damage variation. This suggests that a specific architecture and flowering ideotype defines frost tolerance in winter pea. However, two consistent frost tolerance QTL on LGV were independent of phenology and morphology traits, showing that different protective mechanisms are involved in frost tolerance. Finally, these results suggest that frost tolerance can be bred independently to seed productivity and quality.

  1. Lean Customer Involvement : A Multiple Case Study on the Effects of Kanban on Customer Involvement

    OpenAIRE

    Lundheim, Henning

    2012-01-01

    Customer involvement is an important, but challenging part of software development. Delays and failures can often be attributed to a lack of customer involvement. Different development methodologies provide different strategies for customer involvement, all with their own challenges. Kanban is a new development methodology quickly gaining popularity in the software development community. This thesis aims to answer the question: How does Kanban influence customer involvement? The main prob...

  2. Molecular mechanisms of toxicity of important food-borne phytotoxins

    NARCIS (Netherlands)

    Rietjens, I.M.C.M.; Martena, M.J.; Boersma, M.G.; Spiegelenberg, W.; Alink, G.M.

    2005-01-01

    At present, there is an increasing interest for plant ingredients and their use in drugs, for teas, or in food supplements. The present review describes the nature and mechanism of action of the phytochemicals presently receiving increased attention in the field of food toxicology. This relates to

  3. Studies of collision mechanisms in electron capture by slow multiply charged ions

    International Nuclear Information System (INIS)

    Gilbody, H B; McCullough, R W

    2004-01-01

    We review measurements based on translational energy spectroscopy which are being used to identify and assess the relative importance of the various collision mechanisms involved in one-electron capture by slow multiply charged ions in collisions with simple atoms and molecules

  4. Compilation of information on uncertainties involved in deposition modeling

    International Nuclear Information System (INIS)

    Lewellen, W.S.; Varma, A.K.; Sheng, Y.P.

    1985-04-01

    The current generation of dispersion models contains very simple parameterizations of deposition processes. The analysis here looks at the physical mechanisms governing these processes in an attempt to see if more valid parameterizations are available and what level of uncertainty is involved in either these simple parameterizations or any more advanced parameterization. The report is composed of three parts. The first, on dry deposition model sensitivity, provides an estimate of the uncertainty existing in current estimates of the deposition velocity due to uncertainties in independent variables such as meteorological stability, particle size, surface chemical reactivity and canopy structure. The range of uncertainty estimated for an appropriate dry deposition velocity for a plume generated by a nuclear power plant accident is three orders of magnitude. The second part discusses the uncertainties involved in precipitation scavenging rates for effluents resulting from a nuclear reactor accident. The conclusion is that major uncertainties are involved both as a result of the natural variability of the atmospheric precipitation process and due to our incomplete understanding of the underlying process. The third part involves a review of the important problems associated with modeling the interaction between the atmosphere and a forest. It gives an indication of the magnitude of the problem involved in modeling dry deposition in such environments. Separate analytics have been done for each section and are contained in the EDB

  5. Biological pathways and genetic mechanisms involved in social functioning.

    Science.gov (United States)

    Ordoñana, Juan R; Bartels, Meike; Boomsma, Dorret I; Cella, David; Mosing, Miriam; Oliveira, Joao R; Patrick, Donald L; Veenhoven, Ruut; Wagner, Gert G; Sprangers, Mirjam A G

    2013-08-01

    To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research. A search of Web of Science and PubMed databases was conducted using combinations of the following keywords: genetics, twins, heritability, social functioning, social adjustment, social interaction, and social dysfunction. Variability in the definitions and measures of social functioning was extensive. Moderate to high heritability was reported for social functioning and related concepts, including prosocial behavior, loneliness, and extraversion. Disorders characterized by impairments in social functioning also show substantial heritability. Genetic variants hypothesized to be involved in social functioning are related to the network of brain structures and processes that are known to affect social cognition and behavior. Better knowledge and understanding about the impact of genetic factors on social functioning is needed to help us to attain a more comprehensive view of health-related quality-of-life (HRQOL) and will ultimately enhance our ability to identify those patients who are vulnerable to poor social functioning.

  6. Mechanism of protein import across the chloroplast envelope.

    Science.gov (United States)

    Chen, K; Chen, X; Schnell, D J

    2000-01-01

    The development and maintenance of chloroplasts relies on the contribution of protein subunits from both plastid and nuclear genomes. Most chloroplast proteins are encoded by nuclear genes and are post-translationally imported into the organelle across the double membrane of the chloroplast envelope. Protein import into the chloroplast consists of two essential elements: the specific recognition of the targeting signals (transit sequences) of cytoplasmic preproteins by receptors at the outer envelope membrane and the subsequent translocation of preproteins simultaneously across the double membrane of the envelope. These processes are mediated via the co-ordinate action of protein translocon complexes in the outer (Toc apparatus) and inner (Tic apparatus) envelope membranes.

  7. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

    Directory of Open Access Journals (Sweden)

    J. Lozano-Cuenca

    Full Text Available Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10–9–10–5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10–7.5–10–5 M. The present outcome was not modified by 10–6 M atropine (an antagonist of muscarinic acetylcholine receptors, 3.1×10–7 M glibenclamide (an ATP-sensitive K+ channel blocker, 10–3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker, 10–5 M indomethacin (a prostaglandin synthesis inhibitor, 10–5 M clotrimazole (a cytochrome P450 inhibitor or 10–5 M cycloheximide (a general protein synthesis inhibitor. Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05 by 10–5 M L-NAME (a direct inhibitor of nitric oxide synthase, 10–7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase, 10–6 M KT 5823 (an inhibitor of protein kinase G, 10–2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker and 10–7 M apamin plus 10–7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively, and was blocked by 8×10–2 M potassium (a high concentration and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

  8. Microorganisms involved in MIC

    Energy Technology Data Exchange (ETDEWEB)

    Sorensen, K. [Danish Technological Institute (Denmark)

    2011-07-01

    Microbiologically influenced corrosion (MIC) is a widespread problem that is difficult to detect and assess because of its complex mechanism. This paper presents the involvement of microorganisms in MIC. Some of the mechanisms that cause MIC include hydrogen consumption, production of acids, anode-cathode formation and electron shuttling. A classic bio-corrosive microorganism in the oil and gas industry is sulphate-reducing prokaryotes (SRP). Methanogens also increase corrosion rates in metals. Some of the phylogenetic orders detected while studying SRP and methanogens are archaeoglobales, clostridiales, methanosarcinales and methanothermococcus. There were some implications, such as growth of SRP not being correlated with growth of methanogens; methanogens were included in MIC risk assessment. A few examples are used to display how microorganisms are involved in topside corrosion and microbial community in producing wells. From the study, it can be concluded that, MIC risk assessment includes system data and empirical knowledge of the distribution and number of microorganisms in the system.

  9. Immune mechanisms in fish skin against monogeneans--a model.

    Science.gov (United States)

    Buchmann, K

    1999-01-01

    Host responses against skin inhabiting monogeneans are commonly observed but the responsible immune mechanisms in the fish skin are sufficiently described. Based on recent knowledge of fish immunity and skin response mechanisms in mammals a model for the skin immunity in fish to monogenean infections is proposed. Important cellular components of the model are the epithelial cells, the mucous cells and leucocytes. The release of cytokines, e.g., IL-1, following mechanical or chemical injury of the epithelial cells, initiates a series of events leading to decrease of the ectoparasite population. Cytokines (e.g., IL-1, TNF, INF) are suggested to affect secretions from mucous cell and attract neutrophils and macrophages. Leukotrienes are probably involved in the inflammatory reactions. The subsequent production of humoral substances (among others complement factors and peptides) could be responsible for the antiparasitic response in the later stages of infection. Although non-specific factors dominate the response, the involvement of specific antibodies and lymphocytes cannot be excluded.

  10. Complications of mechanical ventilation

    Directory of Open Access Journals (Sweden)

    Drašković Biljana

    2011-01-01

    Full Text Available Mechanical ventilation of the lungs, as an important therapeutic measure, cannot be avoided in critically ill patients. However, when machines take over some of vital functions there is always a risk of complications and accidents. Complications associated with mechanical ventilation can be divided into: 1 airway-associated complications; 2 complications in the response of patients to mechanical ventilation; and 3 complications related to the patient’s response to the device for mechanical ventilation. Complications of artificial airway may be related to intubation and extubation or the endotracheal tube. Complications of mechanical ventilation, which arise because of the patient’s response to mechanical ventilation, may primarily cause significant side effects to the lungs. During the last two decades it was concluded that mechanical ventilation can worsen or cause acute lung injury. Mechanical ventilation may increase the alveolar/capillary permeability by overdistension of the lungs (volutrauma, it can exacerbate lung damage due to the recruitment/derecruitment of collapsed alveoli (atelectrauma and may cause subtle damages due to the activation of inflammatory processes (biotrauma. Complications caused by mechanical ventilation, beside those involving the lungs, can also have significant effects on other organs and organic systems, and can be a significant factor contributing to the increase of morbidity and mortality in critically ill of mechanically ventilated patients. Complications are fortunately rare and do not occur in every patient, but due to their seriousness and severity they require extensive knowledge, experience and responsibility by health-care workers.

  11. Insecticide Resistance and Metabolic Mechanisms Involved in Larval and Adult Stages of Aedes aegypti Insecticide-Resistant Reference Strains from Cuba.

    Science.gov (United States)

    Bisset, Juan Andrés; Rodríguez, María Magdalena; French, Leydis; Severson, David W; Gutiérrez, Gladys; Hurtado, Daymi; Fuentes, Ilario

    2014-12-01

    Studies were conducted to compare levels of insecticide resistance and to determine the metabolic resistance mechanisms in larval and adult stages of Aedes aegypti from Cuba. Three insecticide-resistant reference strains of Ae. aegypti from Cuba were examined. These strains were derived from a Santiago de Cuba strain isolated in 1997; it was previously subjected to a strong selection for resistance to temephos (SAN-F6), deltamethrin (SAN-F12), and propoxur (SAN-F13) and routinely maintained in the laboratory under selection pressure up to the present time, when the study was carried out. In addition, an insecticide-susceptible strain was used for comparison. The insecticide resistance in larvae and adults was determined using standard World Health Organization methodologies. Insecticide resistance mechanisms were determined by biochemical assays. The esterases (α EST and β EST) and mixed function oxidase (MFO) activities were significantly higher in adults than in the larvae of the three resistant strains studied. The association of resistance level with the biochemical mechanism for each insecticide was established for each stage. The observed differences between larval and adult stages of Ae. aegypti in their levels of insecticide resistance and the biochemical mechanisms involved should be included as part of monitoring and surveillance activities in Ae. aegypti vector control programs.

  12. Public interest group involvement

    International Nuclear Information System (INIS)

    Shelley, P.

    1986-01-01

    Including public interest groups in the siting process for nuclear waste disposal facilities is of great importance. Controversial sitings often result in litigation, but involving public interest groups early in the process will lessen the change of this. They act as surrogates for the general public and should be considered as members of the team. It is important to remember though, that all public interest groups are different. In choosing public panels such as public advisory committees, members should not be chosen on the basis of some quota. Opposition groups should not be excluded. Also, it is important to put the right person in charge of the committee. The goal of public involvement is to identify the conflicts. This must be done during the decision process, because conflicts must be known before they can be eliminated. Regarding litigation, it is important to ease through and around legal battles. If the siting process has integrity and a good faith effort has been shown, the court should uphold the effort. In addition, it is important to be negotiable and to eliminate shortcuts

  13. Dual Headquarters Involvement in Multibusiness Firms

    DEFF Research Database (Denmark)

    Nell, Phillip Christopher; Kappen, Philip; Dellestrand, Henrik

    The strategy literature has shown that headquarters involve themselves into subsidiary operations to add value. Yet, little is known about the extent to which multiple headquarters do so. Therefore, we investigate antecedents of corporate and divisional headquarters’ involvement in innovation...... development projects of subsidiaries. Analyses of 85 innovation development projects reveal that dual innovation importance (innovation that is important for the division and the rest of the firm), and dual dual embeddedness (innovating subsidiary is embedded both within the division and in the rest...... of the firm) lead to greater dual headquarters involvement, especially when the innovation development network is large. The results contribute to the literature on complex parenting and theory of selective headquarters involvement....

  14. Effect of food azo dye tartrazine on learning and memory functions in mice and rats, and the possible mechanisms involved.

    Science.gov (United States)

    Gao, Yonglin; Li, Chunmei; Shen, Jingyu; Yin, Huaxian; An, Xiulin; Jin, Haizhu

    2011-08-01

    Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in mice and rats. Animals were administered different doses of tartrazine for a period of 30 d and were evaluated by open-field test, step-through test, and Morris water maze test, respectively. Furthermore, the biomarkers of the oxidative stress and pathohistology were also measured to explore the possible mechanisms involved. The results indicated that tartrazine extract significantly enhanced active behavioral response to the open field, increased the escape latency in Morris water maze test and decreased the retention latency in step-through tests. The decline in the activities of catalase, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) as well as a rise in the level of malonaldehyde (MDA) were observed in the brain of tartrazine-treated rats, and these changes were associated with the brain from oxidative damage. The dose levels of tartrazine in the present study produced a few adverse effects in learning and memory functions in animals. The mechanisms might be attributed to promoting lipid peroxidation products and reactive oxygen species, inhibiting endogenous antioxidant defense enzymes and the brain tissue damage. Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. Since the last assessment carried out by the Joint FAO/WHO Expert Committee on Food Additives in 1964, many new studies have been conducted. However, there is a little information about the effects on learning and memory performance. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in animals and its possible mechanism involved. Based on our results, we believe that more extensive assessment of food additives in current use is warranted. © 2011 Institute of Food

  15. The Radical Pair Mechanism and the Avian Chemical Compass: Quantum Coherence and Entanglement

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yiteng [Purdue Univ., West Lafayette, IN (United States); Kais, Sabre [Purdue Univ., West Lafayette, IN (United States); Berman, Gennady Petrovich [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-02-02

    We review the spin radical pair mechanism which is a promising explanation of avian navigation. This mechanism is based on the dependence of product yields on 1) the hyperfine interaction involving electron spins and neighboring nuclear spins and 2) the intensity and orientation of the geomagnetic field. One surprising result is that even at ambient conditions quantum entanglement of electron spins can play an important role in avian magnetoreception. This review describes the general scheme of chemical reactions involving radical pairs generated from singlet and triplet precursors; the spin dynamics of the radical pairs; and the magnetic field dependence of product yields caused by the radical pair mechanism. The main part of the review includes a description of the chemical compass in birds. We review: the general properties of the avian compass; the basic scheme of the radical pair mechanism; the reaction kinetics in cryptochrome; quantum coherence and entanglement in the avian compass; and the effects of noise. We believe that the quantum avian compass can play an important role in avian navigation and can also provide the foundation for a new generation of sensitive and selective magnetic-sensing nano-devices.

  16. Paralimbic system and striatum are involved in motivational behavior.

    Science.gov (United States)

    Nishimura, Masahiko; Yoshii, Yoshihiko; Watanabe, Jobu; Ishiuchi, Shogo

    2009-10-28

    Goal-directed rewarded behavior and goal-directed non-rewarded behavior are concerned with motivation. However, the neural substrates involved in goal-directed non-rewarded behaviors are unknown. Using functional magnetic resonance imaging, we investigated the brain activities of healthy individuals during a novel tool use (turning a screwdriver) to elucidate the relationship between the brain mechanism relevant to goal-directed non-rewarded behavior and motivation. We found that our designed behavioral task evoked activities in the orbitofrontal cortex, striatum, anterior insula, lateral prefrontal cortex, and anterior cingulate cortex compared with a meaningless task. These results suggest that activation in these cerebral regions play important roles in motivational behavior without tangible rewards.

  17. Gouty involvement of the patella and extensor mechanism of the knee mimicking aggressive neoplasm. A case series.

    Science.gov (United States)

    Kester, Christopher; Wallace, Matthew T; Jelinek, James; Aboulafia, Albert

    2018-06-01

    Gout is a common inflammatory crystal deposition disease that occurs in many joints throughout the body. Active gout is most often associated with painful synovitis causing searing joint pains, but gout can also produce large masses of space-occupying deposits called tophi. Tophi are most frequently seen in juxta-articular locations with or without bony erosion and are often misdiagnosed as degenerative joint disease. Soft tissue deposits and tendon involvement are also known manifestations of gout, but can present with indeterminate and alarming findings on imaging. We present three cases of tophaceous gout mimicking aggressive neoplasms in the extensor mechanism of the knee. All cases presented as extensor tendon masses eroding into the patella, with imaging findings initially concerning for primary musculoskeletal malignancy.

  18. A Molecular Dynamics (MD) and Quantum Mechanics/Molecular Mechanics (QM/MM) Study on Ornithine Cyclodeaminase (OCD): A Tale of Two Iminiums

    Science.gov (United States)

    Ion, Bogdan F.; Bushnell, Eric A. C.; De Luna, Phil; Gauld, James W.

    2012-01-01

    Ornithine cyclodeaminase (OCD) is an NAD+-dependent deaminase that is found in bacterial species such as Pseudomonas putida. Importantly, it catalyzes the direct conversion of the amino acid L-ornithine to L-proline. Using molecular dynamics (MD) and a hybrid quantum mechanics/molecular mechanics (QM/MM) method in the ONIOM formalism, the catalytic mechanism of OCD has been examined. The rate limiting step is calculated to be the initial step in the overall mechanism: hydride transfer from the L-ornithine’s Cα–H group to the NAD+ cofactor with concomitant formation of a Cα=NH2 + Schiff base with a barrier of 90.6 kJ mol−1. Importantly, no water is observed within the active site during the MD simulations suitably positioned to hydrolyze the Cα=NH2 + intermediate to form the corresponding carbonyl. Instead, the reaction proceeds via a non-hydrolytic mechanism involving direct nucleophilic attack of the δ-amine at the Cα-position. This is then followed by cleavage and loss of the α-NH2 group to give the Δ1-pyrroline-2-carboxylate that is subsequently reduced to L-proline. PMID:23202934

  19. A Molecular Dynamics (MD and Quantum Mechanics/Molecular Mechanics (QM/MM Study on Ornithine Cyclodeaminase (OCD: A Tale of Two Iminiums

    Directory of Open Access Journals (Sweden)

    James W. Gauld

    2012-10-01

    Full Text Available Ornithine cyclodeaminase (OCD is an NAD+-dependent deaminase that is found in bacterial species such as Pseudomonas putida. Importantly, it catalyzes the direct conversion of the amino acid L-ornithine to L-proline. Using molecular dynamics (MD and a hybrid quantum mechanics/molecular mechanics (QM/MM method in the ONIOM formalism, the catalytic mechanism of OCD has been examined. The rate limiting step is calculated to be the initial step in the overall mechanism: hydride transfer from the L-ornithine’s Cα–H group to the NAD+ cofactor with concomitant formation of a Cα=NH2+ Schiff base with a barrier of 90.6 kJ mol−1. Importantly, no water is observed within the active site during the MD simulations suitably positioned to hydrolyze the Cα=NH2+ intermediate to form the corresponding carbonyl. Instead, the reaction proceeds via a non-hydrolytic mechanism involving direct nucleophilic attack of the δ-amine at the Cα-position. This is then followed by cleavage and loss of the α-NH2 group to give the Δ1-pyrroline-2-carboxylate that is subsequently reduced to L-proline.

  20. The progestin etonogestrel enhances the respiratory response to metabolic acidosis in newborn rats. Evidence for a mechanism involving supramedullary structures.

    Science.gov (United States)

    Loiseau, Camille; Osinski, Diane; Joubert, Fanny; Straus, Christian; Similowski, Thomas; Bodineau, Laurence

    2014-05-01

    Central congenital hypoventilation syndrome is a neuro-respiratory disease characterized by the dysfunction of the CO2/H(+) chemosensitive neurons of the retrotrapezoid nucleus/parafacial respiratory group. A recovery of CO2/H(+) chemosensitivity has been observed in some central congenital hypoventilation syndrome patients coincidental with contraceptive treatment by a potent progestin, desogestrel (Straus et al., 2010). The mechanisms of this progestin effect remain unknown, although structures of medulla oblongata, midbrain or diencephalon are known to be targets for progesterone. In the present study, on ex vivo preparations of central nervous system of newborn rats, we show that acute exposure to etonogestrel (active metabolite of desogestrel) enhanced the increased respiratory frequency induced by metabolic acidosis via a mechanism involving supramedullary structures located in pontine, mesencephalic or diencephalic regions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. 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

  2. Endocrine-disrupting Chemicals: Review of Toxicological Mechanisms Using Molecular Pathway Analysis

    Science.gov (United States)

    Yang, Oneyeol; Kim, Hye Lim; Weon, Jong-Il; Seo, Young Rok

    2015-01-01

    Endocrine disruptors are known to cause harmful effects to human through various exposure routes. These chemicals mainly appear to interfere with the endocrine or hormone systems. As importantly, numerous studies have demonstrated that the accumulation of endocrine disruptors can induce fatal disorders including obesity and cancer. Using diverse biological tools, the potential molecular mechanisms related with these diseases by exposure of endocrine disruptors. Recently, pathway analysis, a bioinformatics tool, is being widely used to predict the potential mechanism or biological network of certain chemicals. In this review, we initially summarize the major molecular mechanisms involved in the induction of the above mentioned diseases by endocrine disruptors. Additionally, we provide the potential markers and signaling mechanisms discovered via pathway analysis under exposure to representative endocrine disruptors, bisphenol, diethylhexylphthalate, and nonylphenol. The review emphasizes the importance of pathway analysis using bioinformatics to finding the specific mechanisms of toxic chemicals, including endocrine disruptors. PMID:25853100

  3. Intercellular Ca2+ Waves: Mechanisms and Function

    Science.gov (United States)

    Sanderson, Michael J.

    2012-01-01

    Intercellular calcium (Ca2+) waves (ICWs) represent the propagation of increases in intracellular Ca2+ through a syncytium of cells and appear to be a fundamental mechanism for coordinating multicellular responses. ICWs occur in a wide diversity of cells and have been extensively studied in vitro. More recent studies focus on ICWs in vivo. ICWs are triggered by a variety of stimuli and involve the release of Ca2+ from internal stores. The propagation of ICWs predominately involves cell communication with internal messengers moving via gap junctions or extracellular messengers mediating paracrine signaling. ICWs appear to be important in both normal physiology as well as pathophysiological processes in a variety of organs and tissues including brain, liver, retina, cochlea, and vascular tissue. We review here the mechanisms of initiation and propagation of ICWs, the key intra- and extracellular messengers (inositol 1,4,5-trisphosphate and ATP) mediating ICWs, and the proposed physiological functions of ICWs. PMID:22811430

  4. Verifiably Truthful Mechanisms

    DEFF Research Database (Denmark)

    Branzei, Simina; Procaccia, Ariel D.

    2015-01-01

    the computational sense). Our approach involves three steps: (i) specifying the structure of mechanisms, (ii) constructing a verification algorithm, and (iii) measuring the quality of verifiably truthful mechanisms. We demonstrate this approach using a case study: approximate mechanism design without money...

  5. Neural mechanisms of emotional regulation and decision making

    OpenAIRE

    Gospic, Katarina

    2011-01-01

    Emotions influence our perception and decision making. It is of great importance to understand the neurophysiology behind these processes as they influence human core functions. Moreover, knowledge within this field is required in order to develop new medical therapies for pathological conditions that involve dysregulation of emotions. In this thesis the neural mechanisms of emotional regulation and decision making were investigated using different pharmacological manipul...

  6. Parental Involvement in Children's Education : A Gendered Perspective

    OpenAIRE

    Stanikzai, Razia

    2013-01-01

    The importance of parental involvement as an enabling factor in children’s education is well evidenced. Teachers have a critical role in facilitating or hindering parents’ involvement in their children’s learning. The research project provides an analysis of what teachers view as parents’ role in their children’s education with an emphasis on gender-differentiated involvement. It also discusses the barriers to parents’ involvement as well as explores whether teachers understand the importance...

  7. Glucan: mechanisms involved in its radioprotective effect

    International Nuclear Information System (INIS)

    Patchen, M.L.; D'Alesandro, M.M.; Brook, I.; Blakely, W.F.; MacVittie, T.J.

    1987-01-01

    It has generally been accepted that most biologically derived agents that are radioprotective in the hemopoietic-syndrome dose range (eg, endotoxin, Bacillus Calmette Guerin, Corynebacterium parvum, etc) exert their beneficial properties by enhancing hemopoietic recovery and hence, by regenerating the host's ability to resist life-threatening opportunistic infections. However, using glucan as a hemopoietic stimulant/radioprotectant, we have demonstrated that host resistance to opportunistic infection is enhanced in these mice even prior to the detection of significant hemopoietic regeneration. This early enhanced resistance to microbial invasion in glucan-treated irradiated mice could be correlated with enhanced and/or prolonged macrophage (but not granulocyte) function. These results suggest that early after irradiation glucan may mediate its radioprotection by enhancing resistance to microbial invasion via mechanisms not necessarily predicated on hemopoietic recovery. In addition, preliminary evidence suggests that glucan can also function as an effective free-radical scavenger. Because macrophages have been shown to selectively phagocytize and sequester glucan, the possibility that these specific cells may be protected by virtue of glucan's scavenging ability is also suggested

  8. Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1997 annual progress report

    International Nuclear Information System (INIS)

    Bull, R.J.

    1997-01-01

    'The Pacific Northwest National Lab. was awarded ten (10) Environmental Management Science Program (EMSP) research grants in Fiscal Year 1996. This section gives a summary of how each grant is addressing significant DOE cleanup issues, including those at the Hanford Site. The technical progress made to date in each of these research projects is addressed in more detail in the individual progress reports contained in this document. This research is primarily focused in three areas-Tank Waste Remediation, Soil and Groundwater Cleanup, and Health Effects.'

  9. Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1997 annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Bull, R.J.

    1997-06-01

    'The Pacific Northwest National Lab. was awarded ten (10) Environmental Management Science Program (EMSP) research grants in Fiscal Year 1996. This section gives a summary of how each grant is addressing significant DOE cleanup issues, including those at the Hanford Site. The technical progress made to date in each of these research projects is addressed in more detail in the individual progress reports contained in this document. This research is primarily focused in three areas-Tank Waste Remediation, Soil and Groundwater Cleanup, and Health Effects.'

  10. Mechanisms of Silver Nanoparticle Toxicity

    DEFF Research Database (Denmark)

    Foldbjerg, Rasmus

    nanometers. At this size, materials begin to exhibit unique properties that affect physical, chemical, and biological behavior. However, the same characteristics which make nanomaterials attractive for exploitation in new products have led to concerns that nanomaterials may pose a risk for humans...... to their anti-microbial properties, high electrical conductivity, and optical properties. Information about the mechanisms involved in the cytotoxicity of Ag NPs is important in order to evaluate the potential hazards posed by these particles. Several studies have suggested oxidative stress to play a major role...... by transcriptional profiling and to investigate cellular processes such as oxidative stress, apoptosis, cell cycle and DNA damage, which may be involved in carcinogenesis. For this purpose, Ag NP suspensions were prepared from a commercial powder or synthesized in-house. The Ag NPs were characterized...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Identification of a transporter Slr0982 involved in ethanol tolerance in cyanobacterium Synechocystis sp. PCC 6803

    Directory of Open Access Journals (Sweden)

    Yanan eZhang

    2015-05-01

    Full Text Available Cyanobacteria have been engineered to produce ethanol through recent synthetic biology efforts. However, one major challenge to the cyanobacterial systems for high-efficiency ethanol production is their low tolerance to the ethanol toxicity. With a major goal to identify novel transporters involved in ethanol tolerance, we constructed gene knockout mutants for 58 transporter-encoding genes of Synechocystis sp. PCC 6803 and screened their tolerance change under ethanol stress. The efforts allowed discovery of a mutant of slr0982 gene encoding an ATP-binding cassette transporter which grew poorly in BG11 medium supplemented with 1.5% (v/v ethanol when compared with the wild type, and the growth loss could be recovered by complementing slr0982 in the ∆slr0982 mutant, suggesting that slr0982 is involved in ethanol tolerance in Synechocystis. To decipher the tolerance mechanism involved, a comparative metabolomic and network-based analysis of the wild type and the ethanol-sensitive ∆slr0982 mutant was performed. The analysis allowed the identification of four metabolic modules related to slr0982 deletion in the ∆slr0982 mutant, among which metabolites like sucrose and L-pyroglutamic acid which might be involved in ethanol tolerance, were found important for slr0982 deletion in the ∆slr0982 mutant. This study reports on the first transporter related to ethanol tolerance in Synechocystis, which could be a useful target for further tolerance engineering. In addition, metabolomic and network analysis provides important findings for better understanding of the tolerance mechanism to ethanol stress in Synechocystis.

  13. Single turnover studies of oxidative halophenol dehalogenation by horseradish peroxidase reveal a mechanism involving two consecutive one electron steps: toward a functional halophenol bioremediation catalyst.

    Science.gov (United States)

    Sumithran, Suganya; Sono, Masanori; Raner, Gregory M; Dawson, John H

    2012-12-01

    Horseradish peroxidase (HRP) catalyzes the oxidative para-dechlorination of the environmental pollutant/carcinogen 2,4,6-trichlorophenol (2,4,6-TCP). A possible mechanism for this reaction is a direct oxygen atom transfer from HRP compound I (HRP I) to trichlorophenol to generate 2,6-dichloro 1,4-benzoquinone, a two-electron transfer process. An alternative mechanism involves two consecutive one-electron transfer steps in which HRP I is reduced to compound II (HRP II) and then to the ferric enzyme as first proposed by Wiese et al. [F.W. Wiese, H.C. Chang, R.V. Lloyd, J.P. Freeman, V.M. Samokyszyn, Arch. Environ. Contam. Toxicol. 34 (1998) 217-222]. To probe the mechanism of oxidative halophenol dehalogenation, the reactions between 2,4,6-TCP and HRP compounds I or II have been investigated under single turnover conditions (i.e., without excess H(2)O(2)) using rapid scan stopped-flow spectroscopy. Addition of 2,4,6-TCP to HRP I leads rapidly to HRP II and then more slowly to the ferric resting state, consistent with a mechanism involving two consecutive one-electron oxidations of the substrate via a phenoxy radical intermediate. HRP II can also directly dechlorinate 2,4,6-TCP as judged by rapid scan stopped-flow and mass spectrometry. This observation is particularly significant since HRP II can only carry out one-electron oxidations. A more detailed understanding of the mechanism of oxidative halophenol dehalogenation will facilitate the use of HRP as a halophenol bioremediation catalyst. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Human nucleoporins promote HIV-1 docking at the nuclear pore, nuclear import and integration.

    Directory of Open Access Journals (Sweden)

    Francesca Di Nunzio

    Full Text Available The nuclear pore complex (NPC mediates nucleo-cytoplasmic transport of macromolecules and is an obligatory point of passage and functional bottleneck in the replication of some viruses. The Human Immunodeficiency Virus (HIV has evolved the required mechanisms for active nuclear import of its genome through the NPC. However the mechanisms by which the NPC allows or even assists HIV translocation are still unknown. We investigated the involvement of four key nucleoporins in HIV-1 docking, translocation, and integration: Nup358/RanBP2, Nup214/CAN, Nup98 and Nup153. Although all induce defects in infectivity when depleted, only Nup153 actually showed any evidence of participating in HIV-1 translocation through the nuclear pore. We show that Nup358/RanBP2 mediates docking of HIV-1 cores on NPC cytoplasmic filaments by interacting with the cores and that the C-terminus of Nup358/RanBP2 comprising a cyclophilin-homology domain contributes to binding. We also show that Nup214/CAN and Nup98 play no role in HIV-1 nuclear import per se: Nup214/CAN plays an indirect role in infectivity read-outs through its effect on mRNA export, while the reduction of expression of Nup98 shows a slight reduction in proviral integration. Our work shows the involvement of nucleoporins in diverse and functionally separable steps of HIV infection and nuclear import.

  15. 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.

  16. Density functional theory and quantum mechanics/molecular mechanics study of cysteine protease inhibition by nitrile-based inhibitors.

    Directory of Open Access Journals (Sweden)

    Sam P De Visser

    2013-12-01

    Full Text Available Cysteine protease enzymes are important for human physiology and catalyze key protein degradation pathways. These enzymes react via a nucleophilic reaction mechanism that involves a cysteine residue and the proton of a proximal histidine. Particularly efficient inhibitors of these enzymes are nitrile-based, however, the details of the catalytic reaction mechanism currently are poorly understood. To gain further insight into the inhibition of these molecules, we have performed a combined density functional theory and quantum mechanics/molecular mechanics study on the reaction of a nitrile-based inhibitor with the enzyme active site amino acids. We show here that small perturbations to the inhibitor structure can have dramatic effects on the catalysis and inhibition processes. Thus, we investigated a range of inhibitor templates and show that specific structural changes reduce the inhibitory efficiency by several orders of magnitude. Moreover, as the reaction takes place on a polar surface, we find strong differences between the DFT and QM/MM calculated energetics. In particular, the DFT model led to dramatic distortions from the starting structure and the convergence to a structure that would not fit the enzyme active site. In the subsequent QM/MM study we investigated the use of mechanical versus electronic embedding on the kinetics, thermodynamics and geometries along the reaction mechanism. We find minor effects on the kinetics of the reaction but large geometric and thermodynamics differences as a result of inclusion of electronic embedding corrections. The work here highlights the importance of model choice in the investigation of this biochemical reaction mechanism.

  17. Mechanisms and secondary factors involved in the induction of radiation transformation in vitro

    International Nuclear Information System (INIS)

    Little, J.B.

    1983-01-01

    The long term of this research program was to gain information concerning the mechanisms that determine the carcinogenic effects of ionizing radiation, particularly high LET radiation exposure. The experimental approach involves parallel studies of the induction of malignant transformation in BALB/3T3 cells and of specific gene mutations in human lymphoblastoid cells. Emphasis was on the biologic effects of internally incorporated Auger electron emitting radionuclides and the initiation of studies to determine the effects of low dose-rate neutron exposure. Auger electron irradiation sever as a model for high LET-type radiation effects and as an experimental tool for studying the effects of radiation at specific sites within the cell. Auger-emitting radiosotopes are commonly used in clinical nuclear medicine, rendering them a potential hazard to human populations. We examined the influence of cellular localization of Auger-emitting radionuclides and the spectrum of energy distribution in DNA on their mutagenic, cytogenetic, and transformational effects. The effects of 125 I (an energetic beta emitter) were compared. We studied the induction of cytogenetic changes by 125 I exposure of the cell membrane, as well as its potential to promote (enhance) transformation initiated by low dose external x-ray exposure. We will investigate the Relative Biological Effectiveness for mutagenesis and transformation of low doses of fast neutrons delivered continuously at variable low dose-rates. 34 refs., 1 tab

  18. Interphase lymphoid cell death: its importance in the genesis of radiation disease and molecular mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Poverennyj, A M; Ryabchenko, N I

    1987-09-01

    An analysis of the data on the effect of lymphoid cells on the proliferation and differentiation of hemopoietic stem cells has led to a conclusion that radiation injury of lymphocytes plays an important role in the pathogenesis of the cerebrospinal syndrome. The molecular mechanisms of lymphocyte interphase death were considered. It was shown that due to some peculiarities in the energy supply of these' cells the appearance of breaks in DNA causes the development of biochemical processes resulting in a decrease in NAD, an increase in the activity of nucleases, a decrease in ATP, and the accumulation of active metabolites of glycolysis. There reactions result in an increase in the disintegration of DNA, chromatin and pyknosis of lymphocyte nuclei.

  19. Pharmacologic pre- and postconditioning for stroke: Basic mechanisms and translational opportunity

    Directory of Open Access Journals (Sweden)

    Elga Esposito

    2015-01-01

    Full Text Available Beyond reperfusion therapies, there are still no widely effective therapies for ischemic stroke. Although much progress has been made to define the molecular pathways involved, targeted neuroprotective strategies have often failed in clinical trials. An emerging hypothesis suggests that focusing on single targets and mechanisms may not work since ischemic stroke triggers multiple pathways in multiple cell types. In this review, we briefly survey and assess the opportunities that may be afforded by pre- and postconditioning therapies, with particular attention to pharmacologic pre- and postconditioning. Pharmacologic conditioning may be defined as the use of chemical agents either before or shortly after stroke onset to trigger mechanisms of endogenous tolerance that are thought to involve evolutionarily conserved signals that offer broad protection against ischemia. Importantly, many of the pharmacologic agents may also have been previously used in humans, thus providing hope for translating basic mechanisms into clinical applications.

  20. On the Beneficial Role of Silicon to Organisms : A Case Study on the Importance of Silicon Chemistry to Metal Accumulation in Yeast

    NARCIS (Netherlands)

    Brasser, H.J.; Krijger, G.C.; Wolterbeek, H.T.

    2008-01-01

    Silicon is involved in numerous important structural and functional roles in a wide range of organisms, including diatoms, plants, and humans, but clear mechanisms have been discovered only in diatoms and sponges. Silicate availability influences metal concentrations within various cell- and

  1. Tension (re)builds: Biophysical mechanisms of embryonic wound repair.

    Science.gov (United States)

    Zulueta-Coarasa, Teresa; Fernandez-Gonzalez, Rodrigo

    2017-04-01

    Embryonic tissues display an outstanding ability to rapidly repair wounds. Epithelia, in particular, serve as protective layers that line internal organs and form the skin. Thus, maintenance of epithelial integrity is of utmost importance for animal survival, particularly at embryonic stages, when an immune system has not yet fully developed. Rapid embryonic repair of epithelial tissues is conserved across species, and involves the collective migration of the cells around the wound. The migratory cell behaviours associated with wound repair require the generation and transmission of mechanical forces, not only for the cells to move, but also to coordinate their movements. Here, we review the forces involved in embryonic wound repair. We discuss how different force-generating structures are assembled at the molecular level, and the mechanisms that maintain the balance between force-generating structures as wounds close. Finally, we describe the mechanisms that cells use to coordinate the generation of mechanical forces around the wound. Collective cell movements and their misregulation have been associated with defective tissue repair, developmental abnormalities and cancer metastasis. Thus, we propose that understanding the role of mechanical forces during embryonic wound closure will be crucial to develop therapeutic interventions that promote or prevent collective cell movements under pathological conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Mechanism for translocation of fluoroquinolones across lipid membranes

    DEFF Research Database (Denmark)

    Cramariuc, O.; Rog, T.; Javanainen, M.

    2012-01-01

    Classical atom-scale molecular dynamics simulations, constrained free energy calculations, and quantum mechanical (QM) calculations are employed to study the diffusive translocation of ciprofloxacin (CPFX) across lipid membranes. CPFX is considered here as a representative of the fluoroquinolone...... antibiotics class. Neutral and zwitterionic CPFX coexist at physiological pH, with the latter being predominant. Simulations reveal that only the neutral form permeates the bilayer, and it does so through a novel mechanism that involves dissolution of concerted stacks of zwitterionic ciprofloxacins....... Subsequent QM analysis of the observed molecular stacking shows the important role of partial charge neutralization in the stacks, highlighting how the zwitterionic form of the drug is neutralized for translocation. The findings propose a translocation mechanism in which zwitterionic CPFX molecules approach...

  3. Mechanisms involved in the evasion of the host defence by Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Kharazmi, A

    1991-01-01

    Pseudomonas aeruginosa, an extracellular opportunistic pathogen, utilizes two major mechanisms to evade the host defence system. One of these mechanisms is the production of a large number of extracellular products, such as proteases, toxins, and lipases. The two proteases, alkaline protease and ...

  4. Mechanical engineering education

    CERN Document Server

    Davim, J Paulo

    2012-01-01

    Mechanical Engineering is defined nowadays as a discipline "which involves the application of principles of physics, design, manufacturing and maintenance of mechanical systems". Recently, mechanical engineering has also focused on some cutting-edge subjects such as nanomechanics and nanotechnology, mechatronics and robotics, computational mechanics, biomechanics, alternative energies, as well as aspects related to sustainable mechanical engineering.This book covers mechanical engineering higher education with a particular emphasis on quality assurance and the improvement of academic

  5. IDEA and Family Involvement

    Directory of Open Access Journals (Sweden)

    Mehmet Emin Öztürk

    2017-01-01

    Full Text Available Individuals with Disabilities Education Act (IDEA gives many rights to parents with special needs in terms of involvement and participation. Given the importance of family involvement in the special education process, and federal legislation that increasingly mandated and supported such involvement over time, considerable research has focused on the multiple ways that relationships between schools and families in the special education decision making process have played out. Educational professionals should create a positive climate for CLD families so that they feel more comfortable and therefore are able to participate more authentically and meaningfully.

  6. Monoamine involvement in the antidepressant-like effect induced by P2 blockade.

    Science.gov (United States)

    Diniz, Cassiano R A F; Rodrigues, Murilo; Casarotto, Plínio C; Pereira, Vítor S; Crestani, Carlos C; Joca, Sâmia R L

    2017-12-01

    Depression is a common mental disorder that affects millions of individuals worldwide. Available monoaminergic antidepressants are far from ideal since they show delayed onset of action and are ineffective in approximately 40% of patients, thus indicating the need of new and more effective drugs. ATP signaling through P2 receptors seems to play an important role in neuropathological mechanisms involved in depression, since their pharmacological or genetic inactivation induce antidepressant-like effects in the forced swimming test (FST). However, the mechanisms involved in these effects are not completely understood. The present work investigated monoamine involvement in the antidepressant-like effect induced by non-specific P2 receptor antagonist (PPADS) administration. First, the effects of combining sub-effective doses of PPADS with sub-effective doses of fluoxetine (FLX, selective serotonin reuptake inhibitor) or reboxetine (RBX, selective noradrenaline reuptake inhibitor) were investigated in mice submitted to FST. Significant antidepressant-like effect was observed when subeffective doses of PPADS was combined with subeffective doses of either FLX or RBX, with no significant locomotor changes. Next, the effects of depleting serotonin and noradrenaline levels, by means of PCPA (p-Chlorophenylalanine) or DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) pretreatment, respectively, was investigated. Both, PCPA and DSP-4 pretreatment partially attenuated PPADS-induced effects in FST, without inducing relevant locomotor changes. Our results suggest that the antidepressant-like effect of PPADS involves modulation of serotonin and noradrenaline levels in the brain. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Who Involves Whom?

    Science.gov (United States)

    Ward, Clifford

    1979-01-01

    The author reviews the development of a parents' group at the Bradford Grange School (Manchester, United Kingdom) for ESN (educationally subnormal) children. Problems with the initial parents' group are pointed out, successful approaches are considered, and the importance of parent involvement is stressed. (SBH)

  8. Key Mechanisms for Employee-Driven Innovation in Governmental Client Organisations

    DEFF Research Database (Denmark)

    Sørensen, Henrik; Wandahl, Søren; Faber, Lene

    2018-01-01

    the mechanisms of organisational trust, innovation safety, organisational practices, cultural settings and the recognition and rewards structure to motivate employees. The decision-making procedures should be transparent especially to the idea-owner and the employees involved, and the implementation and putting......In order to ensure that knowledge and ideas are transformed into innovative contributions, a systematic approach is important. The aim of this research was to identify the specific mechanisms that are key to implementing an innovation process model when conducting Employee-driven Innovation...... into practice should be fast progressed phases in the innovation process....

  9. Mechanical properties of low-density polyethylene filled by graphite nanoplatelets

    DEFF Research Database (Denmark)

    Carotenuto, G.; De Nicola, S.; Palomba, M.

    2012-01-01

    The mechanical properties of GNP/LDPE nanocomposites (graphite nanoplatelets/low density polyethylene) have been investigated, in order to establish the effect of nanoscale reinforcement within the polymer matrix. Results show that the presence of the filler does not involve a change...... in the microscopic structure of the polymer. However, on a macroscopic scale, GNPs limit the mobility of the polymer chains, resulting in an increase in stiffness for the final composite. Orientation of GNPs within the LDPE matrix is also an important issue that affects mechanical properties and it has been...

  10. Parent Involvement in Homework: A Research Synthesis

    Science.gov (United States)

    Patall, Erika A.; Cooper, Harris; Robinson, Jorgianne Civey

    2008-01-01

    New emphasis is being placed on the importance of parent involvement in children's education. In a synthesis of research on the effects of parent involvement in homework, a meta-analysis of 14 studies that manipulated parent training for homework involvement reveals that training parents to be involved in their child's homework results in (a)…

  11. High throughput phenotypic selection of Mycobacterium tuberculosis mutants with impaired resistance to reactive oxygen species identifies genes important for intracellular growth.

    Directory of Open Access Journals (Sweden)

    Olga Mestre

    Full Text Available Mycobacterium tuberculosis has the remarkable capacity to survive within the hostile environment of the macrophage, and to resist potent antibacterial molecules such as reactive oxygen species (ROS. Thus, understanding mycobacterial resistance mechanisms against ROS may contribute to the development of new anti-tuberculosis therapies. Here we identified genes involved in such mechanisms by screening a high-density transposon mutant library, and we show that several of them are involved in the intracellular lifestyle of the pathogen. Many of these genes were found to play a part in cell envelope functions, further strengthening the important role of the mycobacterial cell envelope in protection against aggressions such as the ones caused by ROS inside host cells.

  12. The changing U.S. financial system : some implications for the monetary transmission mechanism

    OpenAIRE

    Gordon H. Sellon

    2002-01-01

    An important part of monetary policy is the monetary transmission mechanism, the process by which monetary policy actions influence the economy. While the transmission mechanism involves a number of channels, including exchange rates, bank credit, and asset prices, most economists consider interest rates to be the principal avenue by which monetary policy affects economic activity.> In recent decades, significant changes in the structure of financial markets and institutions in the United Sta...

  13. Redundant mechanisms are involved in suppression of default cell fates during embryonic mesenchyme and notochord induction in ascidians.

    Science.gov (United States)

    Kodama, Hitoshi; Miyata, Yoshimasa; Kuwajima, Mami; Izuchi, Ryoichi; Kobayashi, Ayumi; Gyoja, Fuki; Onuma, Takeshi A; Kumano, Gaku; Nishida, Hiroki

    2016-08-01

    During embryonic induction, the responding cells invoke an induced developmental program, whereas in the absence of an inducing signal, they assume a default uninduced cell fate. Suppression of the default fate during the inductive event is crucial for choice of the binary cell fate. In contrast to the mechanisms that promote an induced cell fate, those that suppress the default fate have been overlooked. Upon induction, intracellular signal transduction results in activation of genes encoding key transcription factors for induced tissue differentiation. It is elusive whether an induced key transcription factor has dual functions involving suppression of the default fates and promotion of the induced fate, or whether suppression of the default fate is independently regulated by other factors that are also downstream of the signaling cascade. We show that during ascidian embryonic induction, default fates were suppressed by multifold redundant mechanisms. The key transcription factor, Twist-related.a, which is required for mesenchyme differentiation, and another independent transcription factor, Lhx3, which is dispensable for mesenchyme differentiation, sequentially and redundantly suppress the default muscle fate in induced mesenchyme cells. Similarly in notochord induction, Brachyury, which is required for notochord differentiation, and other factors, Lhx3 and Mnx, are likely to suppress the default nerve cord fate redundantly. Lhx3 commonly suppresses the default fates in two kinds of induction. Mis-activation of the autonomously executed default program in induced cells is detrimental to choice of the binary cell fate. Multifold redundant mechanisms would be required for suppression of the default fate to be secure. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Tokamak engineering mechanics

    CERN Document Server

    Song, Yuntao; Du, Shijun

    2013-01-01

    Tokamak Engineering Mechanics offers concise and thorough coverage of engineering mechanics theory and application for tokamaks, and the material is reinforced by numerous examples. Chapter topics include general principles, static mechanics, dynamic mechanics, thermal fluid mechanics and multiphysics structural mechanics of tokamak structure analysis. The theoretical principle of the design and the methods of the analysis for various components and load conditions are presented, while the latest engineering technologies are also introduced. The book will provide readers involved in the study

  15. Drugs Involved in Dyslipidemia and Obesity Treatment: Focus on Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Sofia Dias

    2018-01-01

    Full Text Available Metabolic syndrome can be defined as a state of disturbed metabolic homeostasis characterized by visceral obesity, atherogenic dyslipidemia, arterial hypertension, and insulin resistance. The growing prevalence of metabolic syndrome will certainly contribute to the burden of cardiovascular disease. Obesity and dyslipidemia are main features of metabolic syndrome, and both can present with adipose tissue dysfunction, involved in the pathogenic mechanisms underlying this syndrome. We revised the effects, and underlying mechanisms, of the current approved drugs for dyslipidemia and obesity (fibrates, statins, niacin, resins, ezetimibe, and orlistat; sibutramine; and diethylpropion, phentermine/topiramate, bupropion and naltrexone, and liraglutide on adipose tissue. Specifically, we explored how these drugs can modulate the complex pathways involved in metabolism, inflammation, atherogenesis, insulin sensitivity, and adipogenesis. The clinical outcomes of adipose tissue modulation by these drugs, as well as differences of major importance for clinical practice between drugs of the same class, were identified. Whether solutions to these issues will be found in further adjustments and combinations between drugs already in use or necessarily in new advances in pharmacology is not known. To better understand the effect of drugs used in dyslipidemia and obesity on adipose tissue not only is challenging for physicians but could also be the next step to tackle cardiovascular disease.

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

    Science.gov (United States)

    Vandenburgh, Herman H.

    1993-01-01

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

  17. Omics Approach to Identify Factors Involved in Brassica Disease Resistance.

    Science.gov (United States)

    Francisco, Marta; Soengas, Pilar; Velasco, Pablo; Bhadauria, Vijai; Cartea, Maria E; Rodríguez, Victor M

    2016-01-01

    Understanding plant's defense mechanisms and their response to biotic stresses is of fundamental meaning for the development of resistant crop varieties and more productive agriculture. The Brassica genus involves a large variety of economically important species and cultivars used as vegetable source, oilseeds, forage and ornamental. Damage caused by pathogens attack affects negatively various aspects of plant growth, development, and crop productivity. Over the last few decades, advances in plant physiology, genetics, and molecular biology have greatly improved our understanding of plant responses to biotic stress conditions. In this regard, various 'omics' technologies enable qualitative and quantitative monitoring of the abundance of various biological molecules in a high-throughput manner, and thus allow determination of their variation between different biological states on a genomic scale. In this review, we have described advances in 'omic' tools (genomics, transcriptomics, proteomics and metabolomics) in the view of conventional and modern approaches being used to elucidate the molecular mechanisms that underlie Brassica disease resistance.

  18. Molecular mechanisms of induced-mutations

    International Nuclear Information System (INIS)

    Kato, Takeshi

    1985-01-01

    The outcome of recent studies on mechanisms of induced-mutations is outlined with particular emphasis on the dependence of recA gene function in Escherichia coli. Genes involved in spontaneous mutation and x-ray- and chemical-induced mutation and genes involved in adaptive response are presented. As for SOS mutagenesis, SOS-induced regulation mechanisms and mutagenic routes are described. Furthermore, specificity of mutagens themselves are discussed in relation to mechanisms of base substitution, frameshift, and deletion mutagenesis. (Namekawa, K.)

  19. Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both transcription and DNA licensing.

    Science.gov (United States)

    Zhang, Ruowen; Wu, Jiahui; Ferrandon, Sylvain; Glowacki, Katie J; Houghton, Janet A

    2016-12-06

    The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter. Pretreatment of HT29 cells with α-amanitin reduced GANT61-induced γH2AX foci. Co-localization of GLI1 and BrdU foci, inhibited by GANT61, indicated GLI1 and DNA replication to be linked. By co-immunoprecipitation and confocal microscopy, GLI1 co-localized with the DNA licensing factors ORC4, CDT1, and MCM2. Significant co-localization of GLI1 and ORC4 was inhibited by GANT61, and enrichment of ORC4 occurred at the GLI binding site in the FOXM1 promoter. CDT1 was found to be a transcription target of GLI1. Overexpression of CDT1 in HT29 and SW480 cells reduced GANT61-induced cell death, gH2AX foci, and cleavage of caspase-3. Data demonstrate involvement of transcription and of DNA replication licensing factors by non-transcriptional and transcriptional mechanisms in the GLI-dependent mechanism of action of GANT61.

  20. Mechanical properties of fracture zones

    International Nuclear Information System (INIS)

    Leijon, B.

    1993-05-01

    Available data on mechanical characteristics of fracture zones are compiled and discussed. The aim is to improve the basis for adequate representation of fracture zones in geomechanical models. The sources of data researched are primarily borehole investigations and case studies in rock engineering, involving observations of fracture zones subjected to artificial load change. Boreholes only yield local information about the components of fracture zones, i.e. intact rock, fractures and various low-strength materials. Difficulties are therefore encountered in evaluating morphological and mechanical properties of fracture zones from borehole data. Although often thought of as macroscopically planar features, available field data consistently show that fracture zones are characterized by geometrical irregularities such as thickness variations, surface undulation and jogs. These irregularities prevail on all scales. As a result, fracture zones are on all scales characterized by large, in-plane variation of strength- and deformational properties. This has important mechanical consequences in terms of non-uniform stress transfer and complex mechanisms of shear deformation. Field evidence for these findings, in particular results from the underground research laboratory in Canada and from studies of induced fault slip in deep mines, is summarized and discussed. 79 refs

  1. IBRD AND ITS INVOLVEMENT IN MODERNISING AND IMPROVING THE FUNCTIONALITY OF PENSION SYSTEMS

    Directory of Open Access Journals (Sweden)

    Cristina Rosu

    2014-12-01

    Full Text Available In our research we review the International Bank for Reconstruction and Development’s (IBRD most important contributions to the functionality of the pension systems around the world. The pension systems design constitutes an important premise for the adequate functioning of these systems. In international practice, there is a wide variety of principles and mechanisms which can constitute the foundation of pension systems, the most common being materialized in the multi-pillar pension system, promoted by the IBRD. Its involvement in modernizing and improving the functionality of pension systems has reached also many other aspects such as evaluation of the national pension systems’ performance, financial assistance to governments with the aim of meeting the objectives corresponding to pension systems, scientific, technical and informational support. We conclude that IBRD’s involvement in modernizing and improving the functionality of pension systems has determined a significant transformation of the national pension systems, especially in Latin America and Eastern and Central Europe. However, its well-known multi-pillar model is not free of criticism as a result of the various analytical errors.

  2. 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.

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

    International Nuclear Information System (INIS)

    López-Canales, J.S.; Lozano-Cuenca, J.; Muãoz-Islas, E.; Aguilar-Carrasco, J.C.; López-Canales, O.A.; López-Mayorga, R.M.; Castillo-Henkel, E.F.; Valencia-Hernández, I.; Castillo-Henkel, C.

    2015-01-01

    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 2+ -activated K + channels were involved in this effect

  4. Molecular mechanisms of aging and immune system regulation in Drosophila.

    Science.gov (United States)

    Eleftherianos, Ioannis; Castillo, Julio Cesar

    2012-01-01

    Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span.

  5. Possible involvement of GABAergic mechanism in protective effect of melatonin against sleep deprivation-induced behaviour modification and oxidative damage in mice.

    Science.gov (United States)

    Kumar, Anil; Singh, Anant

    2009-08-01

    Sleep is an important physiological process responsible for the maintenance of physical, mental and emotional health of a living being. Sleep deprivation is considered risky for several pathological diseases such as anxiety and motor and cognitive dysfunctions. Sleep deprivation has recently been reported to cause oxidative damage. This study has been designed to explore the possible involvement of the GABAergic mechanism in protective effects of melatonin against 72-h sleep deprivation-induced behaviour modification and oxidative damage in mice. Mice were sleep-deprived for a period of 72 h using the grid over water suspended method. Animals were divided into groups of 6-8 animals each. Melatonin (5 and 10 mg/kg), flumazenil (0.5 mg/kg), picrotoxin (0.5 mg/kg) and muscimol (0.05 mg/kg) were administered for 5 days starting 2 days before 72-h sleep deprivation. Various behavioural tests (plus maze, zero maze, mirror chamber, actophotometer) and body weight assessment followed by oxidative stress parameters (malondialdehyde level, glutathione, catalase, nitrite and protein) were carried out. The 72-h sleep deprivation caused significant anxiety-like behaviour, weight loss, impaired locomotor activity and oxidative damage as compared with naïve (without sleep deprivation). Treatment with melatonin (5 mg/kg and 10 mg/kg, ip) significantly improved locomotor activity, weight loss and antianxiety effect as compared with control (sleep-deprived). Biochemically, melatonin treatment significantly restored reduced glutathione, catalase activity, attenuated lipid peroxidation and nitrite level as compared with control animals (72-h sleep-deprived). Flumazenil (0.5 mg/kg) and picrotoxin (0.5 mg/kg) pretreatments with a lower dose of melatonin (5 mg/kg) significantly antagonized the protective effect of melatonin. However, muscimol (0.05 mg/kg) pretreatment with melatonin (5 mg/kg, ip) potentiated the protective effect of melatonin which was significant as compared with their

  6. Patient empowerment and involvement in telemedicine

    DEFF Research Database (Denmark)

    Konge Nielsen, Marie; Johannessen, Helle

    2018-01-01

    Basic ideas of empowerment and user involvement in relation to telemedicine are presented, as is a case implying user resistance to telemedicine. Four logics of empowerment are employed to identify the underlying rationale of specific cases of telemedicine. The article concludes, that although...... telemedicine is acknowledged as relevant, the approach to it is often too mechanical to imply empowerment of the patient. Some patient groups may not feel safe by using telemedicine, and user involvement and empowerment will not be possible....

  7. Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer

    Directory of Open Access Journals (Sweden)

    Yiwen Fang

    2016-02-01

    Full Text Available Long non-coding RNAs (lncRNAs play important roles in cancer. They are involved in chromatin remodeling, as well as transcriptional and post-transcriptional regulation, through a variety of chromatin-based mechanisms and via cross-talk with other RNA species. lncRNAs can function as decoys, scaffolds, and enhancer RNAs. This review summarizes the characteristics of lncRNAs, including their roles, functions, and working mechanisms, describes methods for identifying and annotating lncRNAs, and discusses future opportunities for lncRNA-based therapies using antisense oligonucleotides.

  8. Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes.

    Directory of Open Access Journals (Sweden)

    Mohammad F Saeed

    2010-09-01

    Full Text Available Zaire ebolavirus (ZEBOV, a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new

  9. A paracrine mechanism involving renal tubular cells, adipocytes and macrophages promotes kidney stone formation in a simulated metabolic syndrome environment.

    Science.gov (United States)

    Zuo, Li; Tozawa, Keiichi; Okada, Atsushi; Yasui, Takahiro; Taguchi, Kazumi; Ito, Yasuhiko; Hirose, Yasuhiko; Fujii, Yasuhiro; Niimi, Kazuhiro; Hamamoto, Shuzo; Ando, Ryosuke; Itoh, Yasunori; Zou, Jiangang; Kohri, Kenjiro

    2014-06-01

    We developed an in vitro system composed of renal tubular cells, adipocytes and macrophages to simulate metabolic syndrome conditions. We investigated the molecular communication mechanism of these cells and their involvement in kidney stone formation. Mouse renal tubular cells (M-1) were cocultured with adipocytes (3T3-L1) and/or macrophages (RAW264.7). Calcium oxalate monohydrate crystals were exposed to M-1 cells after 48-hour coculture and the number of calcium oxalate monohydrate crystals adherent to the cells was quantified. The expression of cocultured medium and M-1 cell inflammatory factors was analyzed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. The inflammatory markers MCP-1, OPN and TNF-α were markedly up-regulated in cocultured M-1 cells. OPN expression increased in M-1 cells cocultured with RAW264.7 cells while MCP-1 and TNF-α were over expressed in M-1 cells cocultured with 3T3-L1 cells. Coculturing M-1 cells simultaneously with 3T3-L1 and RAW264.7 cells resulted in a significant increase in calcium oxalate monohydrate crystal adherence to M-1 cells. Inflammatory cytokine changes were induced by coculturing renal tubular cells with adipocytes and/or macrophages without direct contact, indicating that crosstalk between adipocytes/macrophages and renal tubular cells was mediated by soluble factors. The susceptibility to urolithiasis of patients with metabolic syndrome might be due to aggravated inflammation of renal tubular cells triggered by a paracrine mechanism involving these 3 cell types. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. Screening of biologically important Zn2 + by a chemosensor with fluorescent turn on-off mechanism

    Science.gov (United States)

    Khan, Tanveer A.; Sheoran, Monika; Nikhil Raj M., Venkata; Jain, Surbhi; Gupta, Diksha; Naik, Sunil G.

    2018-01-01

    Reported herein the synthesis, characterization and biologically important zinc ion binding propensity of a weakly fluorescent chemosensor, 4-methyl-2,6-bis((E)-(2-(4-phenylthiazol-2-yl)hydrazono)methyl)phenol (1). 1H NMR spectroscopic titration experiment reveals the binding knack of 1 to the essential Zn2 +. The photo-physical studies of 1 exhibit an enhancement in the fluorescence by several folds upon binding with the zinc ions attributed to PET-off process, with a binding constant value of 5.22 × 103 M- 1. 1 exhibits an excellent detection range for Zn2 + with lower detection limit value of 2.31 × 10- 8 M. The selectivity of 1 was studied with various mono and divalent metal cations and it was observed that most cations either quenches the fluorescence or remains unchanged except for Cd2 +, which shows a slight enhancement in fluorescence intensity of 1. The ratiometric displacement of Cd2 + ions by Zn2 + ions shows an excellent selectivity towards in-situ detection of Zn2 + ions. Photo-physical studies also support the reversible binding of 1 to Zn2 + ions having on and off mechanism in presence of EDTA. Such recognition of the biologically important zinc ions finds potential application in live cell imaging.

  11. Non-strictly black body spectrum from the tunnelling mechanism

    International Nuclear Information System (INIS)

    Corda, Christian

    2013-01-01

    The tunnelling mechanism is widely used to explain Hawking radiation. However, in many cases the analysis used to obtain the Hawking temperature only involves comparing the emission probability for an outgoing particle with the Boltzmann factor. Banerjee and Majhi improved this approach by explicitly finding a black body spectrum associated with black holes. Their result, obtained using a reformulation of the tunnelling mechanism, is in contrast to that of Parikh and Wilczek, who found an emission probability that is compatible with a non-strictly thermal spectrum. Using the recently identified effective state for a black hole, we solve this contradiction via a slight modification of the analysis by Banerjee and Majhi. The final result is a non-strictly black body spectrum from the tunnelling mechanism. We also show that for an effective temperature, we can express the corresponding effective metric using Hawking’s periodicity arguments. Potential important implications for the black hole information puzzle are discussed. -- Highlights: •We review an important result by Banerjee and Majhi on the tunnelling mechanism in the framework of Hawking radiation. •This result is in contrast to another result reported by Parikh and Wilczek. •We introduce the effective state of a black hole. •We explain the contrast via a slight modification of the analysis by Banerjee and Majhi. •We discuss potential important implications for the black hole information puzzle

  12. Cosmosiin Increases ADAM10 Expression via Mechanisms Involving 5’UTR and PI3K Signaling

    Directory of Open Access Journals (Sweden)

    Zhuo Min

    2018-06-01

    Full Text Available The α-secretase “a disintegrin and metalloproteinase domain-containing protein” (ADAM10 is involved in the processing of amyloid precursor protein (APP. Upregulation of ADAM10 precludes the generation of neurotoxic β-amyloid protein (Aβ and represents a plausible therapeutic strategy for Alzheimer’s disease (AD. In this study, we explored compounds that can potentially promote the expression of ADAM10. Therefore, we performed high-throughput small-molecule screening in SH-SY5Y (human neuroblastoma cells that stably express a luciferase reporter gene driven by the ADAM10 promoter, including a portion of its 5’-untranslated region (5’UTR. This has led to the discovery of cosmosiin (apigenin 7-O-β-glucoside. Here, we report that in human cell lines (SH-SY5Y and HEK293, cosmosiin proportionally increased the levels of the immature and mature forms of the ADAM10 protein without altering its mRNA level. This effect was attenuated by translation inhibitors or by deleting the 5’UTR of ADAM10, suggesting that a translational mechanism was responsible for the increased levels of ADAM10. Luciferase deletion assays revealed that the first 144 nucleotides of the 5’UTR were necessary for mediating the cosmosiin-induced enhancement of ADAM10 expression in SH-SY5Y cells. Cosmosiin failed to increase the levels of the ADAM10 protein in murine cells, which lack native expression of the ADAM10 transcript containing the identified 5’UTR element. The potential signaling pathway may involve phosphatidylinositide 3-kinase (PI3K because pharmacological inhibition of PI3K attenuated the effect of cosmosiin on the expression of the ADAM10 protein. Finally, cosmosiin attenuated Aβ generation because the levels of Aβ40/42 in HEK-APP cells were significantly reduced after cosmosiin treatment. Collectively, we found that the first 144 nucleotides of the ADAM10 5’UTR, and PI3K signaling, are involved in cosmosiin-induced enhancement of the expression

  13. Neurobiochemical mechanisms of a ketogenic diet in refractory epilepsy

    Directory of Open Access Journals (Sweden)

    Patricia Azevedo de Lima

    2014-12-01

    Full Text Available A ketogenic diet is an important therapy used in the control of drug-refractory seizures. Many studies have shown that children and adolescents following ketogenic diets exhibit an over 50% reduction in seizure frequency, which is considered to be clinically relevant. These benefits are based on a diet containing high fat (approximately 90% fat for 24 months. This dietary model was proposed in the 1920s and has produced variable clinical responses. Previous studies have shown that the mechanisms underlying seizure control involve ketone bodies, which are produced by fatty acid oxidation. Although the pathways involved in the ketogenic diet are not entirely clear, the main effects of the production of ketone bodies appear to be neurotransmitter modulation and antioxidant effects on the brain. This review highlights the impacts of the ketogenic diet on the modulation of neurotransmitters, levels of biogenic monoamines and protective antioxidant mechanisms of neurons. In addition, future perspectives are proposed.

  14. Getting involved in research.

    Science.gov (United States)

    Banner, Davina; Grant, Lyle G

    2011-01-01

    The need for quality nursing research to promote evidence-based practice and optimize patient care is well recognized. This is particularly pertinent in cardiovascular nursing, where cardiovascular disease continues to be the leading cause of morbidity and mortality worldwide (World Health Organization, 2007). Across the spectrum of academic, clinical, and health care administration nursing roles, research remains fundamental to bridging theory, practice, and education (LoBiondo-Wood, Haber, Cameron, & Singh, 2009). Despite recognition of the importance of nursing research, the gap between research and practice continues to be an ongoing issue (Funk, Tornquist, & Champagne, 1995; Pettengill, Gillies, & Clark, 1994; Rizzuto, Bostrom, Suterm, & Chenitz, 1994; Rolfe, 1998). Nurses are appropriately situated to contribute to research that improves clinical outcomes and health service delivery. However, the majority of nurses in clinical practice do not have a significant research component structured into their nursing role. In this research column, the authors outline the importance of nurses being engaged in research and present some different levels of involvement that nurses may assume. A continuum of nursing research involvement includes asking researchable questions, being a savvy consumer of research evidence, finding your own level of research involvement, and aspiring to lead.

  15. Understanding the Value of Volunteer Involvement

    Science.gov (United States)

    Terry, Bryan; Harder, Amy; Pracht, Dale

    2011-01-01

    Volunteers can be an important resource of many nonprofit organizations. The ability to meet the mission, goals and objectives of nonprofit organizations often depends upon the effectiveness of volunteer involvement in direct service delivery or indirect program support. Volunteer involvement utilizes financial and non-financial resources of an…

  16. 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.

  17. Noncanonical Hamiltonian mechanics

    International Nuclear Information System (INIS)

    Litteljohn, R.G.

    1986-01-01

    Noncanonical variables in Hamiltonian mechanics were first used by Lagrange in 1808. In spite of this, most work in Hamiltonian mechanics has been carried out in canonical variables, up to this day. One reason for this is that noncanonical coordinates are seldom needed for mechanical problems based on Lagrangians of the form L = T - V, where T is the kinetic energy and V is the potential energy. Of course, such Lagrangians arise naturally in celestial mechanics, and as a result they form the paradigms of nineteenth-century mechanics and have become enshrined in all the mechanics textbooks. Certain features of modern problems, however, lead to the use of noncanonical coordinates. Among these are issues of gauge invariance and singular Lagrange a Poisson structures. In addition, certain problems, like the flow of magnetic-field lines in physical space, are naturally formulated in terms of noncanonical coordinates. None of these features is present in the nineteenth-century paradigms of mechanics, but they do arise in problems involving particle motion in the presence of magnetic fields. For example, the motion of a particle in an electromagnetic wave is an important one in plasma physics, but the usual Hamiltonian formulation is gauge dependent. For this problem, noncanonical approaches based on Lagrangians in phase space lead to powerful computational techniques which are gauge invariant. In the limit of strong magnetic fields, particle motion becomes 'guiding-center motion'. Guiding-center motion is also best understood in terms of noncanonical coordinates. Finally the flow of magnetic-field lines through physical space is a Hamiltonian system which is best understood with noncanonical coordinates. No doubt many more systems will arise in the future for which these noncanonical techniques can be applied. (author)

  18. Mechanisms and Effectivity of Sulfate Reducing Bioreactors ...

    Science.gov (United States)

    Mining-influenced water (MIW) is the main environmental challenges associated with the mining industry. Passive MIW remediation can be achieved through microbial activity in sulfate-reducing bioreactors (SRBRs), but their actual removal rates depend on different factors, one of which is the substrate composition. Chitinous materials have demonstrated high metal removal rates, particularly for the two recalcitrant MIW contaminants Zn and Mn, but their removal mechanisms need further study. We studied Cd, Fe, Zn, and Mn removal in bioactive and abiotic SRBRs to elucidate the metal removal mechanisms and the differences in metal and sulfate removal rates using a chitinous material as substrate. We found that sulfate-reducing bacteria are effective in increasing metal and sulfate removal rates and duration of operation in SRBRs, and that the main mechanism involved was metal precipitation as sulfides. The solid residues provided evidence of the presence of sulfides in the bioactive column, more specifically ZnS, according to XPS analysis. The feasibility of passive treatments with a chitinous substrate could be an important option for MIW remediation. Mining influenced water (MIW) remediation is still one of the top priorities for the agency because it addresses the most important environmental problem associated with the mining industry and that affects thousands of communities in the U.S. and worldwide. In this paper, the MIW bioremediation mechanisms are studied

  19. Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?

    Directory of Open Access Journals (Sweden)

    Francesca Marini

    2016-08-01

    Full Text Available Osteoporosis is a complex multifactorial disorder of the skeleton. Genetic factors are important in determining peak bone mass and structure, as well as the predisposition to bone deterioration and fragility fractures. Nonetheless, genetic factors alone are not sufficient to explain osteoporosis development and fragility fracture occurrence. Indeed, epigenetic factors, representing a link between individual genetic aspects and environmental influences, are also strongly suspected to be involved in bone biology and osteoporosis. Recently, alterations in epigenetic mechanisms and their activity have been associated with aging. Also, bone metabolism has been demonstrated to be under the control of epigenetic mechanisms. Runt-related transcription factor 2 (RUNX2, the master transcription factor of osteoblast differentiation, has been shown to be regulated by histone deacetylases and microRNAs (miRNAs. Some miRNAs were also proven to have key roles in the regulation of Wnt signalling in osteoblastogenesis, and to be important for the positive or negative regulation of both osteoblast and osteoclast differentiation. Exogenous and environmental stimuli, influencing the functionality of epigenetic mechanisms involved in the regulation of bone metabolism, may contribute to the development of osteoporosis and other bone disorders, in synergy with genetic determinants. The progressive understanding of roles of epigenetic mechanisms in normal bone metabolism and in multifactorial bone disorders will be very helpful for a better comprehension of disease pathogenesis and translation of this information into clinical practice. A deep understanding of these mechanisms could help in the future tailoring of proper individual treatments, according to precision medicine’s principles.

  20. Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?

    Science.gov (United States)

    Marini, Francesca; Cianferotti, Luisella; Brandi, Maria Luisa

    2016-08-12

    Osteoporosis is a complex multifactorial disorder of the skeleton. Genetic factors are important in determining peak bone mass and structure, as well as the predisposition to bone deterioration and fragility fractures. Nonetheless, genetic factors alone are not sufficient to explain osteoporosis development and fragility fracture occurrence. Indeed, epigenetic factors, representing a link between individual genetic aspects and environmental influences, are also strongly suspected to be involved in bone biology and osteoporosis. Recently, alterations in epigenetic mechanisms and their activity have been associated with aging. Also, bone metabolism has been demonstrated to be under the control of epigenetic mechanisms. Runt-related transcription factor 2 (RUNX2), the master transcription factor of osteoblast differentiation, has been shown to be regulated by histone deacetylases and microRNAs (miRNAs). Some miRNAs were also proven to have key roles in the regulation of Wnt signalling in osteoblastogenesis, and to be important for the positive or negative regulation of both osteoblast and osteoclast differentiation. Exogenous and environmental stimuli, influencing the functionality of epigenetic mechanisms involved in the regulation of bone metabolism, may contribute to the development of osteoporosis and other bone disorders, in synergy with genetic determinants. The progressive understanding of roles of epigenetic mechanisms in normal bone metabolism and in multifactorial bone disorders will be very helpful for a better comprehension of disease pathogenesis and translation of this information into clinical practice. A deep understanding of these mechanisms could help in the future tailoring of proper individual treatments, according to precision medicine's principles.

  1. IL-13 may be involved in the development of CAD via different mechanisms under different conditions in a Chinese Han population.

    Science.gov (United States)

    Zha, Ling-Feng; Nie, Shao-Fang; Chen, Qian-Wen; Liao, Yu-Hua; Zhang, Hong-Song; Dong, Jiang-Tao; Xie, Tian; Wang, Fan; Tang, Ting-Ting; Xia, Ni; Xu, Cheng-Qi; Zhou, Ying-Chao; Zeng, Zhi-Peng; Jiao, Jiao; Wang, Peng-Yun; Wang, Qing K; Tu, Xin; Cheng, Xiang

    2018-04-18

    Interleukin-13 (IL-13) has important functions in atherosclerosis, but its role in coronary artery disease (CAD) is unclear. Here, we studied the genetic role of IL-13 in CAD in a Chinese Han population using tag SNPs covering the whole IL13 gene (i.e., rs1881457, rs2069744 and rs20541) and a two-stage cohort containing 1863 CAD cases and 1841 controls. Traditional risk factors for CAD, such as age, BMI, and other factors, were used as covariates in logistic regression analysis. In the total population, we found that two haplotypes of IL13 (ATG and ATA, ordered rs1881457 C -rs2069744 T -rs20541 A ) significantly contributed to the risk of CAD with adjusted p values less than 0.05 (p adj  = 0.019 and p adj  = 0.042, respectively). In subgroup population analyses, the variant rs1881457 C was found to significantly contribute to a nearly two fold increase in the risk of CAD in men (p adj  = 0.023, OR = 1.91, 95% CI: 1.09-3.33). The variant rs1881457 C also significantly contributed to a nearly twofold risk of late-onset CAD (p adj  = 0.024, OR = 1.93, 95% CI: 1.09-3.42). In conclusion, IL13 might be involved in CAD via different mechanisms under different conditions in the Chinese Han population.

  2. [Pulmonary involvement in connective tissue disease].

    Science.gov (United States)

    Bartosiewicz, Małgorzata

    2016-01-01

    The connective tissue diseases are a variable group of autoimmune mediated disorders characterized by multiorgan damage. Pulmonary complications are common, usually occur after the onset of joint symptoms, but can also be initially presenting complaint. The respiratory system may be involved in all its component: airways, vessels, parenchyma, pleura and respiratory muscles. Lung involvement is an increasing cause of morbidity and mortality in the connective tissue diseases. Clinical course is highly variable - can range from mild to rapidly progressive, some processes are reversible, while others are irreversible. Thus, the identification of reversible disease , and separately progressive disease, are important clinical issues. The frequency, clinical presentation, prognosis and responce to therapy are different, depending on the pattern of involvement as well as on specyfic diagnostic method used to identify it. High- resolution computed tompography plays an important role in identifying patients with respiratory involvement. Pulmonary function tests are a sensitive tool detecting interstitial lung disease. In this article, pulmonary lung involvement accompanying most frequently apperaing connective tissue diseases - rheumatoid arthritis, systemic sclerosis, lupus erythematosus, polymyositis/dermatomyositis, Sjögrens syndrome and mixed connective tissue disaese are reviewed.

  3. Current Theory on the Cerebral Mechanisms of Hypoxic PRE- and Postconditioning.

    Science.gov (United States)

    Rybnikova, E A; Samoilov, M O

    2016-01-01

    An exposure of the organism to several episodes of mild hypoxia results in the development of brain hypoxic/ischemic tolerance, as well as cross-tolerance to the stressful factors of psychoemotional nature. Such kind of preconditioning by mild hypoxia functions as “alarm signalization” by I.P. Pavlov, preparing the organism and, in particularly, brain to the forthcoming harmful event. Dose-dependent action of hypoxia on the brain can be considered as one particular case of the general phenomenon termed hormesis, or neurohormesis. Endogenous defense processes launched by the hypoxic preconditioning and leading to the development of cerebral tolerance are associated with activation of intracellular signal cascades, transcriptional factors, regulatory proteins and expression of pro-adaptive genes and their products in the susceptible brain regions. Important mechanism of systemic adaptation induced by hypoxic preconditioning includes modifications of pituitary-adrenal axis aimed at enhancement of its adaptive resources. All these components are involved in the neuroprotective processes in three sequential phases - initiation, induction, and expression. Important role belongs also to epigenetic mechanisms controlling the activity of pro-adaptive genes. In contrast to the preconditioning, hypoxic postconditioning is comparatively novel phenomenon and therefore its mechanisms are less studied. The involvement of hypoxia-inducible factor HIF-1, and non-specific protective processes as up-regulation of anti-apoptotic factors and neurotrophines.

  4. Effective Information Technology Governance Mechanisms: An Australian Study

    Directory of Open Access Journals (Sweden)

    Syaiful Ali

    2006-01-01

    Full Text Available Growing importance of information technology (IT, as a strategic factor for organizations in achieving their objectives, have raised the concern of organizations in establishing and implementing effective IT governance. This study seeks to empirically examine the individual IT governance mechanisms that influence the overall effectiveness of IT governance. The data were obtained by using web based survey from 176 members of ISACA (Information Systems and Audit Control Association Australia. This study examines the influences of six proposed IT governance mechanisms on the overall effectiveness of IT governance. Using Factor Analysis and Multiple Regression techniques, the current study finds significant positive relationships between the overall level of effective IT governance and the following four IT governance mechanisms: the existence of ethics/ culture of compliance in IT, corporate communication systems, an IT strategy committee, and the involvement of senior management in IT.

  5. 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.

  6. Genes involved in sex pheromone biosynthesis of Ephestia cautella, an important food storage pest, are determined by transcriptome sequencing

    KAUST Repository

    Antony, Binu

    2015-07-18

    . Phylogenetic trees were constructed for desaturases, FARs and FATs, and transcripts that clustered with the ∆14, ∆12 and ∆9 desaturases, PG-specific FARs and potential candidate FATs, respectively, were identified. Transcripts encoding putative pheromone degrading enzymes, and candidate pheromone carrier and receptor proteins expressed in the E. cautella PG, were also identified. Conclusions Our study provides important background information on the enzymes involved in pheromone biosynthesis. This information will be useful for the in vitro production of E. cautella sex pheromones and may provide potential targets for disrupting the pheromone-based communication system of E. cautella to prevent infestations.

  7. A Review on the Study of the Generation of (Nanoparticles Aerosols during the Mechanical Solicitation of Materials

    Directory of Open Access Journals (Sweden)

    Neeraj Shandilya

    2014-01-01

    Full Text Available This paper focuses on presenting the forefront of the interdisciplinary studies conceived towards the generation of the wear particles aerosol when materials are subjected to mechanical stresses. Various wear mechanisms and instrumentation involved during stress application and aerosolization of wear particles, as well as particles characterization, measurement, and modeling techniques are presented through the investigation of a series of contextual works which are emphasized on the identification of these aspects. The review is motivated from the fact that understanding mechanisms involved in wear-induced particle generation, both at nano- and at microscale, is important for many applications that involve surfaces sliding over each other due to various potential health aspects. An attempt has been made to explain how the information based on this broad spectrum of subjects discovered in this contribution can be used and improved in order to produce a more resilient, rational, and versatile knowledge base which has been found lacking in the present literature during its survey. The area of study is highly multidisciplinary since it involves aerosol, particle, and material sciences.

  8. 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

  9. Improved mechanical properties of retorted carrots by ultrasonic pre-treatments.

    Science.gov (United States)

    Day, Li; Xu, Mi; Øiseth, Sofia K; Mawson, Raymond

    2012-05-01

    The use of ultrasound pre-processing treatment, compared to blanching, to enhance mechanical properties of non-starchy cell wall materials was investigated using carrot as an example. The mechanical properties of carrot tissues were measured by compression and tensile testing after the pre-processing treatment prior to and after retorting. Carrot samples ultrasound treated for 10 min at 60 °C provided a higher mechanical strength (P<0.05) to the cell wall structure than blanching for the same time period. With the addition of 0.5% CaCl(2) in the pre-treatment solution, both blanching and ultrasound treatment showed synergistic effect on enhancing the mechanical properties of retorted carrot pieces. At a relatively short treatment time (10 min at 60 °C) with the use of 0.5% CaCl(2), ultrasound treatment achieved similar enhancement to the mechanical strength of retorted carrots to blanching for a much longer time period (i.e. 40 min). The mechanism involved appears to be related to the stress responses present in all living plant matter. However, there is a need to clarify the relative importance of the potential stress mechanisms in order to get a better understanding of the processing conditions likely to be most effective. The amount of ultrasound treatment required is likely to involve low treatment intensities and there are indications from the structural characterisation and mechanical property analyses that the plant cell wall tissues were more elastic than that accomplished using low temperature long time blanching. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  10. Adolescents’ Involvement in Cyber Bullying and Perceptions of School: The Importance of Perceived Peer Acceptance for Female Adolescents

    OpenAIRE

    Betts, Lucy R.; Spenser, Karin A.; Gardner, Sarah E.

    2017-01-01

    Young people are spending increasing amounts of time using digital technology and, as such, are at great risk of being involved in cyber bullying as a victim, bully, or bully/victim. Despite cyber bullying typically occurring outside the school environment, the impact of being involved in cyber bullying is likely to spill over to school. Fully 285 11- to 15-year-olds (125 male and 160 female, M age = 12.19 years, SD = 1.03) completed measures of cyber bullying involvement, self-esteem, trust,...

  11. The importance of a hot-sequential mechanism in triplet-state formation by charge recombination in reaction centers of bacterial photosynthesis

    International Nuclear Information System (INIS)

    Saito, K.; Mukai, K.; Sumi, H.

    2006-01-01

    In photosynthesis, pigment-excitation energies in the antenna system produced by light harvesting are transferred among antenna pigments toward the core antenna, where they are captured by the reaction center and initially fixed in the form of a charge separation. Primary charge separation between an oxidized special pair (P + ) and a reduced bacteriopheohytin (H - ) is occasionally intervened by recombination, and a spin-triplet state ( 3 P*) is formed on P in the bacterial reaction center. The 3 P* state is harmful to bio-organisms, inducing the formation of the highly damaging singlet oxygen species. Therefore, understanding the 3 P*-formation mechanism is important. The 3 P* formation is mediated by a state |m> of intermediate charge separation between P and the accessory chlorophyll, which is located between P and H. It will be shown theoretically in the present work that at room temperature, not only the mechanism of superexchange by quantum-mechanical virtual mediation at |m>, but also a hot-sequential mechanism contributes to the mediation. In the latter, although |m> is produced as a real state, the final state 3 P* is quickly formed during thermalization of phonons in the protein matrix in |m>. In the former, the final state is formed more quickly before dephasing-thermalization of phonons in |m>. 3 P* is unistep formed from the charge-separated state in the both mechanisms

  12. Key Mechanisms for Employee-Driven Innovation in Governmental Client Organisations

    DEFF Research Database (Denmark)

    Sørensen, Henrik; Faber, Lene; Wandahl, Søren

    2018-01-01

    the mechanisms of organisational trust, innovation safety, organisational practices, cultural settings and the recognition and rewards structure to motivate employees. The decision-making procedures should be transparent especially to the idea-owner and the employees involved, and the implementation and putting......In order to ensure that knowledge and ideas are transformed into innovative contributions, a systematic approach is important. The aim of this research was to identify the specific mechanisms that are key to implementing an innovation process model when conducting Employee-driven Innovation...... in a governmental client organisation. The methodological approach was an exploratory case study of a governmental client organisation within the Danish construction industry. The units of analysis were groups of employees and managers within the case organisation. The primary mechanisms identified were...

  13. Determining the relative importance of the mechanisms of behavior change within Alcoholics Anonymous: a multiple mediator analysis.

    Science.gov (United States)

    Kelly, John F; Hoeppner, Bettina; Stout, Robert L; Pagano, Maria

    2012-02-01

    Evidence indicates that Alcoholics Anonymous (AA) participation reduces relapse risk but less is known about the mechanisms through which AA confers this benefit. Initial studies indicate self-efficacy, negative affect, adaptive social networks and spiritual practices are mediators of this effect, but because these have been tested in isolation, their relative importance remains elusive. This study tested multiple mediators simultaneously to help determine the most influential pathways. Prospective, statistically controlled, naturalistic investigation examined the extent to which these previously identified mechanisms mediated AA attendance effects on alcohol outcomes controlling for baseline outcome values, mediators, treatment, and other confounders. Nine clinical sites within the United States. Adults (n = 1726) suffering from alcohol use disorder (AUD) initially enrolled in a randomized study with two arms: aftercare (n = 774); and out-patient (n = 952) comparing three out-patient treatments (Project MATCH). AA attendance during treatment; mediators at 9 months; and outcomes [percentage of days abstinent (PDA) and drinks per drinking day (DDD)] at 15 months. Among out-patients the effect of AA attendance on alcohol outcomes was explained primarily by adaptive social network changes and increases in social abstinence self-efficacy. Among more impaired aftercare patients, in addition to mediation through adaptive network changes and increases in social self-efficacy, AA lead to better outcomes through increasing spirituality/religiosity and by reducing negative affect. The degree to which mediators explained the relationship between AA and outcomes ranged from 43% to 67%. While Alcoholics Anonymous facilitates recovery by mobilizing several processes simultaneously, it is changes in social factors which appear to be of primary importance. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

  14. Molecular mechanisms involved in the inhibition of tumor cells proliferation exposed to elevated concentrations of the epidermal growth factor

    International Nuclear Information System (INIS)

    Guillen, Isabel A; Berlanga, Jorge; Camacho, Hanlet

    2013-01-01

    The EGF promotes inhibition of cell proliferation in vitro and in vivo models depending on its concentration, application schema and the type of tumor cells on which it acts. Our research hypothesis was based on the fact that the EGF varies the expression of genes involved in a negative regulation of tumor cell lines proliferation carrying high levels of its receptor (EGFR). Our objectives were, to obtain information about the effect of EGF on tumor cell proliferation in vitro and in vivo models and, know the gene expression patterns of a group of genes involved in cancer signaling pathways and EGFR. The results showed that EGF at nanomolar concentrations inhibits the tumor cells proliferation bearing high levels of EGFR and, promotes the survival of treated animals, establishing a direct relationship between the inhibition of cell proliferation, high concentrations of EGF and, high amount of EGFR in the cells. The differential gene expression profile showed a variation in a group of genes which exert a powerful control over the cell cycle progression, gene transcription and apoptosis. It was concluded that the inhibition of tumor cell proliferation by the action of EGF is due to activation of molecular mechanisms controlling cell cycle progression. This work won the Annual Award of the Cuban Academy of Sciences in 2012

  15. Mechanisms for cytoplasmic organization: an overview.

    Science.gov (United States)

    Pagliaro, L

    2000-01-01

    One of the basic characteristics of life is the intrinsic organization of cytoplasm, yet we know surprisingly little about the manner in which cytoplasmic macromolecules are arranged. It is clear that cytoplasm is not the homogeneous "soup" it was once envisioned to be, but a comprehensive model for cytoplasmic organization is not available in modern cell biology. The premise of this volume is that phase separation in cytoplasm may play a role in organization at the subcellular level. Other mechanisms for non-membrane-bounded intracellular organization have previously been proposed. Some of these will be reviewed in this chapter. Multiple mechanisms, involving phase separation, specific intracellular targeting, formation of macromolecular complexes, and channeling, all could well contribute to cytoplasmic organization. Temporal and spatial organization, as well as composition, are likely to be important in defining the characteristics of cytoplasm.

  16. Mechanisms of telomere loss and their consequences for chromosome instability

    International Nuclear Information System (INIS)

    Muraki, Keiko; Nyhan, Kristine; Han, Limei; Murnane, John P.

    2012-01-01

    The ends of chromosomes in mammals, called telomeres, are composed of a 6-bp repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs) at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.

  17. Mechanisms of telomere loss and their consequences for chromosome instability

    Directory of Open Access Journals (Sweden)

    Keiko eMuraki

    2012-10-01

    Full Text Available The ends of chromosomes in mammals, called telomeres, are composed of a 6 base pair repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.

  18. Mechanisms of telomere loss and their consequences for chromosome instability

    Energy Technology Data Exchange (ETDEWEB)

    Muraki, Keiko; Nyhan, Kristine; Han, Limei; Murnane, John P., E-mail: jmurnane@radonc.ucsf.edu [Department of Radiation Oncology, University of California at San Francisco, San Francisco, CA (United States)

    2012-10-04

    The ends of chromosomes in mammals, called telomeres, are composed of a 6-bp repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs) at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.

  19. Prebiotics: Definition and protective mechanisms.

    Science.gov (United States)

    Valcheva, Rosica; Dieleman, Levinus A

    2016-02-01

    The increase in chronic metabolic and immunologic disorders in the modern society is linked to major changes in the dietary patterns. These chronic conditions are associated with intestinal microbiota dysbiosis where important groups of carbohydrate fermenting, short-chain fatty acids-producing bacteria are reduced. Dietary prebiotics are defined as a selectively fermented ingredients that result in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health. Application of prebiotics may then restore the gut microbiota diversity and activity. Unlike the previously accepted prebiotics definition, where a limited number of bacterial species are involved in the prebiotic activity, new data from community-wide microbiome analysis demonstrated a broader affect of the prebiotics on the intestinal microbiota. These new findings require a revision of the current definition. In addition, prebiotics may exert immunomodulatory effects through microbiota-independent mechanisms that will require future investigations involving germ-free animal disease models. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. IBT-based quantitative proteomics identifies potential regulatory proteins involved in pigmentation of purple sea cucumber, Apostichopus japonicus.

    Science.gov (United States)

    Xing, Lili; Sun, Lina; Liu, Shilin; Li, Xiaoni; Zhang, Libin; Yang, Hongsheng

    2017-09-01

    Sea cucumbers are an important economic species and exhibit high yield value among aquaculture animals. Purple sea cucumbers are very rare and beautiful and have stable hereditary patterns. In this study, isobaric tags (IBT) were first used to reveal the molecular mechanism of pigmentation in the body wall of the purple sea cucumber. We analyzed the proteomes of purple sea cucumber in early pigmentation stage (Pa), mid pigmentation stage (Pb) and late pigmentation stage (Pc), resulting in the identification of 5580 proteins, including 1099 differentially expressed proteins in Pb: Pa and 339 differentially expressed proteins in Pc: Pb. GO and KEGG analyses revealed possible differentially expressed proteins, including"melanogenesis", "melanosome", "melanoma", "pigment-biosynthetic process", "Epidermis development", "Ras-signaling pathway", "Wnt-signaling pathway", "response to UV light", and "tyrosine metabolism", involved in pigment synthesis and regulation in purple sea cucumbers. The large number of differentially expressed proteins identified here should be highly useful in further elucidating the mechanisms underlying pigmentation in sea cucumbers. Furthermore, these results may also provide the base for further identification of proteins involved in resistance mechanisms against melanoma, albinism, UV damage, and other diseases in sea cucumbers. Copyright © 2017. Published by Elsevier Inc.

  1. Metal-Oxide Film Conversions Involving Large Anions

    Energy Technology Data Exchange (ETDEWEB)

    Pretty, S.; Zhang, X.; Shoesmith, D.W.; Wren, J.C. [The University of Western Ontario, Chemistry Department, 1151 Richmond St., N6A 5B7, London, Ontario (Canada)

    2008-07-01

    The main objective of my research is to establish the mechanism and kinetics of metal-oxide film conversions involving large anions (I{sup -}, Br{sup -}, S{sup 2-}). Within a given group, the anions will provide insight on the effect of anion size on the film conversion, while comparison of Group 6 and Group 7 anions will provide insight on the effect of anion charge. This research has a range of industrial applications, for example, hazardous radioiodine can be immobilized by reaction with Ag to yield AgI. From the perspective of public safety, radioiodine is one of the most important fission products from the uranium fuel because of its large fuel inventory, high volatility, and radiological hazard. Additionally, because of its mobility, the gaseous iodine concentration is a critical parameter for safety assessment and post-accident management. A full kinetic analysis using electrochemical techniques has been performed on the conversion of Ag{sub 2}O to (1) AgI and (2) AgBr. (authors)

  2. Metal-Oxide Film Conversions Involving Large Anions

    International Nuclear Information System (INIS)

    Pretty, S.; Zhang, X.; Shoesmith, D.W.; Wren, J.C.

    2008-01-01

    The main objective of my research is to establish the mechanism and kinetics of metal-oxide film conversions involving large anions (I - , Br - , S 2- ). Within a given group, the anions will provide insight on the effect of anion size on the film conversion, while comparison of Group 6 and Group 7 anions will provide insight on the effect of anion charge. This research has a range of industrial applications, for example, hazardous radioiodine can be immobilized by reaction with Ag to yield AgI. From the perspective of public safety, radioiodine is one of the most important fission products from the uranium fuel because of its large fuel inventory, high volatility, and radiological hazard. Additionally, because of its mobility, the gaseous iodine concentration is a critical parameter for safety assessment and post-accident management. A full kinetic analysis using electrochemical techniques has been performed on the conversion of Ag 2 O to (1) AgI and (2) AgBr. (authors)

  3. The most important parasites in Serbia involving the foodborne route of transmission

    Science.gov (United States)

    Petrović, J. M.; Prodanov-Radulović, J. Z.; Vasilev, S. D.

    2017-09-01

    Food can be an important route for transmission of parasites to humans. Compared to other foodborne pathogens in Serbia, foodborne (or potentially foodborne) parasites do not get the attention they undoubtedly deserve. The aim of this article is to give an overview of the most important parasitic pathogens that can be transmitted by food, and that cause disease in humans: Echinococcus, Trichinella, Taenia solium and Toxoplasma gondii. For each of these pathogens, the severity of human diseases they cause, incidence, mortality and case fatality rate among humans in Serbia as well as their prevalence in animal species in Serbia are described. Some of the described foodborne parasites can induce severe disease symptoms in humans associated with high case fatality rates, while others can cause massive outbreaks. All of the aforementioned parasites occur throughout Serbia and cause both severe public health problems and substantial economic losses in livestock production. In conclusion, the control measures of foodborne parasites certainly need to include education of farmers and improvement of veterinary sanitary measures in animal farming and animal waste control.

  4. IUTAM Symposium on progress in the theory and numerics of configurational mechanics

    CERN Document Server

    2009-01-01

    Configurational mechanics has attracted much attention from various research fields over the recent years/decades and has developed into a versatile tool that can be applied to a variety of problems. Since Eshelby's seminal works a general notion of configurational mechanics has evolved and has successfully been applied to many problems involving various types of defects in continuous media. The most prominent application is the use of configurational forces in fracture mechanics. However, as configurational mechanics is related to arbitrary material inhomogeneities it has also very successfully been applied to many materials science and engineering problems such as phase transitions and inelastic deformations. Also, the modeling of materials with micro-structure evolution is an important field, in which configurational mechanics can provide a better understanding of processes going on within the material. Besides these mechanical, physical, and chemical applications, ideas from configurational mechanics are ...

  5. An Overview of Long Noncoding RNAs Involved in Bone Regeneration from Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Shuping Peng

    2018-01-01

    Full Text Available Bone regeneration is very important for the recovery of some diseases including osteoporosis and bone fracture trauma. It is a multiple-step- and multiple-gene-involved complex process, including the matrix secretion and calcium mineralization by osteoblasts differentiated from mesenchymal stem cells (MSCs and the absorption of calcium and phosphorus by osteoclasts differentiated from hematopoietic stem cells. Long noncoding RNAs (lncRNAs are a family of transcripts longer than 200 nt without or with very low protein-coding potential. Recent studies have demonstrated that lncRNAs are widely involved in the regulation of lineage commitment and differentiation of stem cells through multiple mechanisms. In this review, we will summarize the roles and molecular mechanism of lncRNAs including H19, MALAT1, MODR, HOTAIR, DANCR, MEG3, HoxA-AS3, and MIAT in osteogenesis ossification; lncRNA ZBED3-AS1 and CTA-941F9.9, DANCR, and HIT in chondrogenic differentiation; and lncRNA DANCR in osteoclast differentiation. These findings will facilitate the development and application of novel molecular drugs which regulate the balance of bone formation and absorption.

  6. Cellular and Molecular Mechanisms in Perioperative Hepatic Protection: A Review of Current Interventions

    Directory of Open Access Journals (Sweden)

    Zahra Talebi

    2017-05-01

    Full Text Available Liver is one of the most important organs needing great concern during the perioperative period. There are a number of different mechanisms that interact with liver cells and might affect their integrity and cell live. Though these mechanisms are not all the same, there is a great common point: all affect the metabolic pathways of the liver. Ischemia, anesthetic drug effects and other perioperative insults may affect the liver. Disturbance in an organ’s blood flow is an inherent part of diverse surgical procedures, which leads to lack of oxygen and nutrient supply. These ischemic periods can be particularly long in case of liver surgeries, such as resection of large hepatic tumors, management of hepatic trauma and liver transplant. Once the blood flow and oxygen supply are restored, the interruption of blood flow affects the oxygen dependent cells in liver, which require mitochondrial oxidative phosphorylation for their metabolism. Molecular mechanisms such as Redox status, ionic interchange disturbances as well as different mediators and cells like KC, SEC, dendritic cells, leukocytes, and lymphocytes, are involved in the process ultimately leading to cell death by apoptosis and necrosis. This review provides an overview on the cellular and molecular mechanisms involved in liver injuries, categorizing these mechanisms in 3 different classes: preoperative mechanisms, intraoperative mechanisms and postoperative mechanisms. Each of them are discussed in a different part of the manuscript

  7. Nucleocytoplasmic trafficking of Nipah virus W protein involves multiple discrete interactions with the nuclear import and export machinery

    International Nuclear Information System (INIS)

    Audsley, Michelle D.; Jans, David A.; Moseley, Gregory W.

    2016-01-01

    Paramyxoviruses replicate in the cytoplasm with no obvious requirement to interact with the nucleus. Nevertheless, the W protein of the highly lethal bat-borne paramyxovirus Nipah virus (NiV) is known to undergo specific targeting to the nucleus, mediated by a single nuclear localisation signal (NLS) within the C-terminal domain. Here, we report for the first time that additional sites modulate nucleocytoplasmic localisation of W. We show that the N-terminal domain interacts with importin α1 and contributes to nuclear accumulation of W, indicative of a novel N-terminal NLS. We also find that W undergoes exportin-1 mediated nuclear export, dependent on a leucine at position 174. Together, these data enable significant revision of the generally accepted model of W trafficking, with implications for understanding of the mechanisms of NiV immune evasion. - Highlights: • A new model for Nipah virus W protein nucleocytoplasmic trafficking is proposed. • Nipah W protein is shown to undergo active nuclear export via exportin-1. • Nipah W nuclear import is mediated by multiple nuclear localisation signals.

  8. Involvement of Mζ-Like Protein Kinase in the Mechanisms of Conditioned Food Aversion Memory Reconsolidation in the Helix lucorum.

    Science.gov (United States)

    Solntseva, S V; Kozyrev, S A; Nikitin, V P

    2015-06-01

    We studied the involvement of Mζ-like protein kinase (PKMζ) into mechanisms of conditioned food aversion memory reconsolidation in Helix lucorum. Injections PKMζ inhibitor ZIP in a dose of 5 mg/kg on day 2 or 10 after learning led to memory impairment and amnesia development. Injections of the inhibitor in doses of 1.5 or 2.5 mg/kg had no effect. Repeated training on day 11 after induction of amnesia resulted in the formation of memory on the same type of food aversion similar to first training. The number of combinations of conditional (food) and reinforcing (electrical shock) stimuli was similar during initial and repeated training. We hypothesize that the inhibition of Mζ-like protein kinase erases the memory trace and a new memory is formed during repeated training.

  9. Patient involvement in Danish health care

    DEFF Research Database (Denmark)

    Vrangbaek, Karsten

    2015-01-01

    PURPOSE: The purpose of this paper is to investigate different types of patient involvement in Denmark, and to discuss the potential implications of pursuing several strategies for patient involvement simultaneously. DESIGN/METHODOLOGY/APPROACH: The paper presents a preliminary framework for anal......PURPOSE: The purpose of this paper is to investigate different types of patient involvement in Denmark, and to discuss the potential implications of pursuing several strategies for patient involvement simultaneously. DESIGN/METHODOLOGY/APPROACH: The paper presents a preliminary framework...... for analysis of patient involvement in health care. This framework is used to analyze key governance features of patient involvement in Denmark based on previous research papers and reports describing patient involvement in Danish health care. FINDINGS: Patient involvement is important in Denmark...... be identified when pursuing the strategies at the same time. RESEARCH LIMITATIONS/IMPLICATIONS: Because of the chosen research approach, the research results may lack generalizability. Therefore, researchers are encouraged to test the proposed framework further. PRACTICAL IMPLICATIONS: The paper includes...

  10. Wallerian degeneration slow mouse neurons are protected against cell death caused by mechanisms involving mitochondrial electron transport dysfunction.

    Science.gov (United States)

    Tokunaga, Shinji; Araki, Toshiyuki

    2012-03-01

    Ischemia elicits a variety of stress responses in neuronal cells, which result in cell death. wld(S) Mice bear a mutation that significantly delays Wallerian degeneration. This mutation also protects all neuronal cells against other types of stresses resulting in cell death, including ischemia. To clarify the types of stresses that neuronal cell bodies derived from wld(S) mice are protected from, we exposed primary cultured neurons derived from wld(S) mice to various components of hypoxic stress. We found that wld(S) mouse neurons are protected against cellular injury induced by reoxygenation following hypoxic stress. Furthermore, we found that wld(S) mouse neurons are protected against functional impairment of the mitochondrial electron transport chain. These data suggest that Wld(S) protein expression may provide protection against neuronal cell death caused by mechanisms involving mitochondrial electron transport dysfunction. Copyright © 2011 Wiley Periodicals, Inc.

  11. User interface and patient involvement.

    Science.gov (United States)

    Andreassen, Hege Kristin; Lundvoll Nilsen, Line

    2013-01-01

    Increased patient involvement is a goal in contemporary health care, and of importance to the development of patient oriented ICT. In this paper we discuss how the design of patient-user interfaces can affect patient involvement. Our discussion is based on 12 semi-structured interviews with patient users of a web-based solution for patient--doctor communication piloted in Norway. We argue ICT solutions offering a choice of user interfaces on the patient side are preferable to ensure individual accommodation and a high degree of patient involvement. When introducing web-based tools for patient--health professional communication a free-text option should be provided to the patient users.

  12. Addressing Measurement Issues Related to Bullying Involvement

    Science.gov (United States)

    Casper, Deborah M.; Meter, Diana J.; Card, Noel A.

    2015-01-01

    In this article, we address measurement issues related to select aspects of bullying involvement with the goal of moving psychometrically sound measurement practices toward applied bullying research. We first provide a nontechnical introduction to psychometric considerations in measuring bullying involvement, highlighting the importance of…

  13. What's important to a game?

    DEFF Research Database (Denmark)

    Debus, Michael S.; Grabarczyk, Pawel

    2017-01-01

    , as well as visual representation, of the model suggests an equal importance of these three dimensions. We claim that such symmetry is unattainable. Through the exploration of the three dimensions relationships to one another, we will show that the mechanical system has a higher importance to games than...

  14. Mechanical, dielectric, and physicochemical properties of impregnating resin based on unsaturated polyesterimides

    Science.gov (United States)

    Fetouhi, Louiza; Petitgas, Benoit; Dantras, Eric; Martinez-Vega, Juan

    2017-10-01

    This work aims to characterize the dielectric and the mechanical properties of a resin based on an unsaturated polyesterimide diluted in methacrylate reactive diluents used in the impregnation of rotating machines. The broadband dielectric spectrometry and the dynamic mechanical analysis were used to quantify the changes in dielectric and mechanical properties of the network PEI resin, as a function of temperature and frequency. The network characterizations highlight the presence of two main relaxations, α and α', confirmed by the differential scanning calorimetry analysis, showing the complexity of the chemical composition of this resin. The dielectric spectroscopy shows a significant increase in the dielectric values due to an increase of the material conductivity, while the mechanical spectroscopy shows an important decrease of the polymer rigidity and viscosity expressed by an important decrease in the storage modulus. The PEI resin shows a high reactivity when it is submitted in successive heating ramps, which involves in a post-cross-linking reaction. Contribution to the topical issue "Electrical Engineering Symposium (SGE 2016)", edited by Adel Razek

  15. 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.

  16. Genes Involved in the Endoplasmic Reticulum N-Glycosylation Pathway of the Red Microalga Porphyridium sp.: A Bioinformatic Study

    Directory of Open Access Journals (Sweden)

    Oshrat Levy-Ontman

    2014-02-01

    Full Text Available N-glycosylation is one of the most important post-translational modifications that influence protein polymorphism, including protein structures and their functions. Although this important biological process has been extensively studied in mammals, only limited knowledge exists regarding glycosylation in algae. The current research is focused on the red microalga Porphyridium sp., which is a potentially valuable source for various applications, such as skin therapy, food, and pharmaceuticals. The enzymes involved in the biosynthesis and processing of N-glycans remain undefined in this species, and the mechanism(s of their genetic regulation is completely unknown. In this study, we describe our pioneering attempt to understand the endoplasmic reticulum N-Glycosylation pathway in Porphyridium sp., using a bioinformatic approach. Homology searches, based on sequence similarities with genes encoding proteins involved in the ER N-glycosylation pathway (including their conserved parts were conducted using the TBLASTN function on the algae DNA scaffold contigs database. This approach led to the identification of 24 encoded-genes implicated with the ER N-glycosylation pathway in Porphyridium sp. Homologs were found for almost all known N-glycosylation protein sequences in the ER pathway of Porphyridium sp.; thus, suggesting that the ER-pathway is conserved; as it is in other organisms (animals, plants, yeasts, etc..

  17. MFS Transporters and GABA Metabolism Are Involved in the Self-Defense Against DON in Fusarium graminearum

    Directory of Open Access Journals (Sweden)

    Qinhu Wang

    2018-04-01

    Full Text Available Trichothecene mycotoxins, such as deoxynivalenol (DON produced by the fungal pathogen, Fusarium graminearum, are not only important for plant infection but are also harmful to human and animal health. Trichothecene targets the ribosomal protein Rpl3 that is conserved in eukaryotes. Hence, a self-defense mechanism must exist in DON-producing fungi. It is reported that TRI (trichothecene biosynthesis 101 and TRI12 are two genes responsible for self-defense against trichothecene toxins in Fusarium. In this study, however, we found that simultaneous disruption of TRI101 and TRI12 has no obvious influence on DON resistance upon exogenous DON treatment in F. graminearum, suggesting that other mechanisms may be involved in self-defense. By using RNA-seq, we identified 253 genes specifically induced in DON-treated cultures compared with samples from cultures treated or untreated with cycloheximide, a commonly used inhibitor of eukaryotic protein synthesis. We found that transporter genes are significantly enriched in this group of DON-induced genes. Of those genes, 15 encode major facilitator superfamily transporters likely involved in mycotoxin efflux. Significantly, we found that genes involved in the metabolism of gamma-aminobutyric acid (GABA, a known inducer of DON production in F. graminearum, are significantly enriched among the DON-induced genes. The GABA biosynthesis gene PROLINE UTILIZATION 2-2 (PUT2-2 is downregulated, while GABA degradation genes are upregulated at least twofold upon treatment with DON, resulting in decreased levels of GABA. Taken together, our results suggest that transporters influencing DON efflux are important for self-defense and that GABA mediates the balance of DON production and self-defense in F. graminearum.

  18. Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress.

    Science.gov (United States)

    Zhang, Qiang; Liu, Jianing; Chen, Shulan; Liu, Jing; Liu, Lijuan; Liu, Guirong; Wang, Fang; Jiang, Wenxin; Zhang, Caixia; Wang, Shuangyu; Yuan, Xiao

    2016-04-01

    It is well recognized that mandibular growth, which is caused by a variety of functional appliances, is considered to be the result of both neuromuscular and skeletal adaptations. Accumulating evidence has demonstrated that apoptosis plays an important role in the adaptation of skeletal muscle function. However, the underlying mechanism of apoptosis that is induced by stretch continues to be incompletely understood. Endoplasmic reticulum stress (ERS), a newly defined signaling pathway, initiates apoptosis. This study seeks to determine if caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress in myoblast and its underlying mechanism. Apoptosis was assessed by Hochest staining, DAPI staining and annexin V binding and PI staining. ER chaperones, such as GRP78, CHOP and caspase-12, were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Furthermore, caspase-12 inhibitor was used to value the mechanism of the caspase-12 pathway. Apoptosis of myoblast, which is subjected to cyclic stretch, was observed in a time-dependent manner. We found that GRP78 mRNA and protein were significantly increased and CHOP and caspase-12 were activated in myoblast that was exposed to cyclic stretch. Caspase-12 inhibition reduced stretch-induced apoptosis, and caspase-12 activated caspase-3 to induce apoptosis. We concluded that caspase-12 played an important role in stretch-induced apoptosis that is associated by endoplasmic reticulum stress by activating caspase-3.

  19. Mechanisms of callose deposition in rice regulated by exogenous abscisic acid and its involvement in rice resistance to Nilaparvata lugens Stål (Hemiptera: Delphacidae).

    Science.gov (United States)

    Liu, Jinglan; Du, Haitao; Ding, Xu; Zhou, Yaodong; Xie, Pengfei; Wu, Jincai

    2017-12-01

    Callose is a plant cell wall polysaccharide controlled by β-1,3-glucanase and synthase. Abscisic acid (ABA) is an important plant hormone. Exogenous ABA promotes rice resistance to pests. Whether exogenous ABA could reduce the decline in rice yield after brown planthopper (Nilaparvata lugens Stål; BPH) feeding is an important question, however, the mechanisms behind rice resistance induced by ABA remain obscure. Electronic penetration graph (EPG) recording indicated a significant increase in rice resistance to BPH, and the number of BPH eggs decreased significantly upon application of exogenous ABA. As the concentration of ABA increased, the reduction in rice yield decreased significantly after BPH feeding. Further studies showed that β-1,3-glucanase activity was significantly lower, but synthase activity was higher after ABA treatment than in controls. Our results demonstrated that exogenous ABA suppressed β-1,3-glucanase and induced synthase activity, and promoted callose deposition. This is an important defense mechanism that prevents BPH from ingesting phloem sap. These studies provide support for an insect-resistance mechanism after ABA treatment and provide a reference for the integrated management of other piercing-sucking pests. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  20. How can stakeholder involvement be improved?

    International Nuclear Information System (INIS)

    2015-12-01

    Radioactive waste management is embedded in broader societal issues such as environment, risk management, sustainability, energy and health policy. In all these fields, there is an increasing demand for public involvement, participation or engagement. Guidance for public authorities also generally encourages greater involvement of the public. Involvement may take different forms at different phases and can include sharing information, consulting, dialoguing or deliberating on decisions with relevant stakeholders. Stakeholder involvement should be seen as a meaningful part of formulating and implementing public policy. There is no single technique for organising engagement. Initiatives should respond to their context and to stakeholders' particular needs. As the number of stakeholder involvement approaches and publications describing them continues to grow, new opportunities are opening up through social media, which has become an important tool for stakeholder involvement in recent years

  1. Measures and mechanisms of common ground: backchannels, conversational repair, and interactive alignmentin free and task-oriented social interactions

    DEFF Research Database (Denmark)

    Fusaroli, Riccardo; Tylén, Kristian; Madsen, Katrine Garly

    A crucial aspect of everyday conversational interactions is our ability to establish and maintain common ground. Understanding the relevant mechanisms involved in such social coordination remains an important challenge for cognitive science. While common ground is often discussed in very general ...

  2. A Neural Circuit Mechanism for the Involvements of Dopamine in Effort-Related Choices: Decay of Learned Values, Secondary Effects of Depletion, and Calculation of Temporal Difference Error

    Science.gov (United States)

    2018-01-01

    Abstract Dopamine has been suggested to be crucially involved in effort-related choices. Key findings are that dopamine depletion (i) changed preference for a high-cost, large-reward option to a low-cost, small-reward option, (ii) but not when the large-reward option was also low-cost or the small-reward option gave no reward, (iii) while increasing the latency in all the cases but only transiently, and (iv) that antagonism of either dopamine D1 or D2 receptors also specifically impaired selection of the high-cost, large-reward option. The underlying neural circuit mechanisms remain unclear. Here we show that findings i–iii can be explained by the dopaminergic representation of temporal-difference reward-prediction error (TD-RPE), whose mechanisms have now become clarified, if (1) the synaptic strengths storing the values of actions mildly decay in time and (2) the obtained-reward-representing excitatory input to dopamine neurons increases after dopamine depletion. The former is potentially caused by background neural activity–induced weak synaptic plasticity, and the latter is assumed to occur through post-depletion increase of neural activity in the pedunculopontine nucleus, where neurons representing obtained reward exist and presumably send excitatory projections to dopamine neurons. We further show that finding iv, which is nontrivial given the suggested distinct functions of the D1 and D2 corticostriatal pathways, can also be explained if we additionally assume a proposed mechanism of TD-RPE calculation, in which the D1 and D2 pathways encode the values of actions with a temporal difference. These results suggest a possible circuit mechanism for the involvements of dopamine in effort-related choices and, simultaneously, provide implications for the mechanisms of TD-RPE calculation. PMID:29468191

  3. Polypyrrole for Artificial Muscles: Ionic Mechanisms

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2006-01-01

    the matrix of a polymer electrode – thereby causing volume expansion which can be converted into work. Solvent molecules are able to penetrate the polymer too. A precise description of the nature of these ionic and solvent movements is therefore important for understanding and improving the performance....... This work examines the influence of solvent, ionic species and electrolyte concentration on the fundamental question about the ionic mechanism involved: Is the actuation process driven by anion motion, cation motion, or a mixture of the two? In addition: What is the extent of solvent motion? The discussion...... is centered on polypyrrole (PPy), which is the material most used and studied. The tetraethyl ammonium cation (TEA) is shown to be able to move in and out of PPy(DBS) polymer films, in contrast to expectations. There is a switching between ionic mechanisms during cycling in TEACl electrolyte....

  4. On chaos in quantum mechanics: The two meanings of sensitive dependence

    International Nuclear Information System (INIS)

    Ingraham, R.L.; Luna Acosta, G.A.

    1993-08-01

    Sensitive dependence on initial conditions, the most important signature of chaos, can mean failure of Lyapunov stability, the primary meaning adopted in dynamical systems theory, or the presence of positive Lyapunov exponents, the meaning favored in physics. These are not equivalent in general. We show that there is sensitive dependence in quantum mechanics in the sense of violation of Lyapunov stability for maps of the state vector like involving unbounded operators A. This is true even for bounded quantum systems, where the corresponding Lyapunov exponents are all zero. Experiments to reveal this sensitive dependence, a definite though unfamiliar prediction of quantum mechanics, should be devised. It may also invalidate the usual assumption of linear response theory in quantum statistical mechanics in some cases. (author) 13 refs

  5. GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia.

    Science.gov (United States)

    Stepanović-Petrović, Radica M; Tomić, Maja A; Vucković, Sonja M; Kocev, Nikola; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

    2008-01-01

    The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline (GABA(A) receptor antagonist) on these effects of antiepileptic drugs. Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: (1) the development of hyperalgesia induced by Con A; (2) the effects of carbamazepine/oxcarbazepine on Con A-induced hyperalgesia, and (3) the effects of bicuculline on the carbamazepine/oxcarbazepine antihyperalgesia. Intraperitoneally injected bicuculline (0.5-1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine (27 mg/kg, i.p.) and oxcarbazepine (80 mg/kg, i.p.). When applied intraplantarly, bicuculline (0.14 mg/paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine (0.14 mg/paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test. These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA(A) receptor activation. Copyright 2008 S. Karger AG, Basel.

  6. 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.

  7. Gastroprotective and ulcer healing effects of hydroethanolic extract of leaves of Caryocar coriaceum: Mechanisms involved in the gastroprotective activity.

    Science.gov (United States)

    de Lacerda Neto, Luis Jardelino; Ramos, Andreza Guedes Barbosa; Santos Sales, Valterlucio; de Souza, Severino Denicio Gonçalves; Dos Santos, Antonia Thassya Lucas; de Oliveira, Larissa Rolim; Kerntopf, Marta Regina; de Albuquerque, Thais Rodrigues; Coutinho, Henrique Douglas Melo; Quintans-Júnior, Lucindo Jose; Wanderley, Almir Gonçalves; de Menezes, Irwin Rose Alencar

    2017-01-05

    This work aimed to determine the chemical fingerprint of hydroethanolic extract of leaves of Caryocar coriaceum (HELCC) and the gastroprotective activity. The chemical fingerprint of HELCC was analyzed by HPLC-DAD, to quantify total phenols and flavonoids were carried out by Folin-Ciocalteu reagent and aluminum chloride assay, while in vitro antioxidant activity was evaluated by the DPPH method. The methods used to determine pharmacological activity were: gastroprotective screening test in classical models of induced acute and chronic gastric lesions and physical barrier test. Further assays were performed to demonstrate the involvement of NO, prostaglandins, ATP-dependent potassium channels, TRPV, noradrenergic α2 receptors, histamines, and opioids. The DPPH method demonstrated the antioxidant activity of the extract, in vitro, explained by the presence of polyphenols and flavonoids. Oral administration of the extract, previously dissolved in deionized water, at a dose of 100 mg/kg decreased the lesions induced by indomethacin, acidified ethanol, ethanol and acetic acid by 75.0, 72.8, 69.4 and 86.2% respectively. It was demonstrated that opioid receptors, α 2 -adrenergic receptors and primary afferent neurons sensitive to capsaicin were involved in the mechanism of gastric protection, in addition to the contribution of NO and prostaglandins. The results show that extract is a promising candidate for the treatment of gastric ulcers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Parent involvement and student academic performance: a multiple mediational analysis.

    Science.gov (United States)

    Topor, David R; Keane, Susan P; Shelton, Terri L; Calkins, Susan D

    2010-01-01

    Parent involvement in a child's education is consistently found to be positively associated with a child's academic performance. However, there has been little investigation of the mechanisms that explain this association. The present study examines two potential mechanisms of this association: the child's perception of cognitive competence and the quality of the student-teacher relationship. This study used a sample of 158 seven-year-old participants, their mothers, and their teachers. Results indicated a statistically significant association between parent involvement and a child's academic performance, over and above the impact of the child's intelligence. A multiple mediation model indicated that the child's perception of cognitive competence fully mediated the relation between parent involvement and the child's performance on a standardized achievement test. The quality of the student-teacher relationship fully mediated the relation between parent involvement and teacher ratings of the child's classroom academic performance. Limitations, future research directions, and implications for public policy initiatives are discussed.

  9. Mitochondrial-related gene expression profiles suggest an important role of PGC-1alpha in the compensatory mechanism of endemic dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    He, Shu-Lan [Key Laboratory of Environment and Gene Related Diseases, Xi' an Jiaotong University, Ministry Education, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Trace Elements and Endemic Diseases, Xi' an Jiaotong University, Ministry of Health, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Tan, Wu-Hong, E-mail: tanwh@mail.xjtu.edu.cn [Key Laboratory of Environment and Gene Related Diseases, Xi' an Jiaotong University, Ministry Education, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Trace Elements and Endemic Diseases, Xi' an Jiaotong University, Ministry of Health, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Zhang, Zeng-Tie; Zhang, Feng [Key Laboratory of Environment and Gene Related Diseases, Xi' an Jiaotong University, Ministry Education, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Trace Elements and Endemic Diseases, Xi' an Jiaotong University, Ministry of Health, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Qu, Cheng-Juan [Institute of Biomedicine, University of Eastern Finland, Kuopio (Finland); Lei, Yan-Xia; Zhu, Yan-He [Key Laboratory of Environment and Gene Related Diseases, Xi' an Jiaotong University, Ministry Education, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Trace Elements and Endemic Diseases, Xi' an Jiaotong University, Ministry of Health, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Yu, Han-Jie [Department of Biotechnology, Northwest University, Xi' an, Shaanxi 710069 (China); Xiang, You-Zhang [Shandong Institute for prevention and Treatment of Endemic Disease, Jinan, Shandong 250014 (China); and others

    2013-10-15

    Keshan disease (KD) is an endemic dilated cardiomyopathy with unclear etiology. In this study, we compared mitochondrial-related gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from 16 KD patients and 16 normal controls in KD areas. Total RNA was isolated, amplified, labeled and hybridized to Agilent human 4×44k whole genome microarrays. Mitochondrial-related genes were screened out by the Third-Generation Human Mitochondria-Focused cDNA Microarray (hMitChip3). Quantitative real-time PCR, immunohistochemical and biochemical parameters related mitochondrial metabolism were conducted to validate our microarray results. In KD samples, 34 up-regulated genes (ratios≥2.0) were detected by significance analysis of microarrays and ingenuity systems pathway analysis (IPA). The highest ranked molecular and cellular functions of the differentially regulated genes were closely related to amino acid metabolism, free radical scavenging, carbohydrate metabolism, and energy production. Using IPA, 40 significant pathways and four significant networks, involved mainly in apoptosis, mitochondrion dysfunction, and nuclear receptor signaling were identified. Based on our results, we suggest that PGC-1alpha regulated energy metabolism and anti-apoptosis might play an important role in the compensatory mechanism of KD. Our results may lead to the identification of potential diagnostic biomarkers for KD in PBMCs, and may help to understand the pathogenesis of KD. Highlights: • Thirty-four up-regulated genes were detected in KD versus health controls. • Forty pathways and four networks were detected in KD. • PGC-1alpha regulated energy metabolism and anti-apoptosis in KD.

  10. Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection

    Directory of Open Access Journals (Sweden)

    Claudio M. Mastroianni

    2014-05-01

    Full Text Available Chronic hepatitis C virus (HCV infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV. Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV.

  11. Involving Employees in Strategy innovation

    DEFF Research Database (Denmark)

    Friis, Ole Uhrskov; Koch, Christian

    2011-01-01

    Strategy as a practice and continuous innovation approaches are combined to conceptualise dilemmas of short versus long term and to analyse a case of employee participation as a particular example of strategy innovation. The case is a medium size textile company developing its strategy involving ...... and Balanced Score Card consultancy, an ‘open space’ workshop and organized strategy projects. Especially the latter two are important in facilitating the employee involvement. The case however also exhibit enterprise situated praxis’s like mitigation of taboos....

  12. eLearning course may shorten the duration of mechanical restraint among psychiatric inpatients: a cluster-randomized trial.

    Science.gov (United States)

    Kontio, Raija; Pitkänen, Anneli; Joffe, Grigori; Katajisto, Jouko; Välimäki, Maritta

    2014-10-01

    The management of psychiatric inpatients exhibiting severely disturbed and aggressive behaviour is an important educational topic. Well structured, IT-based educational programmes (eLearning) often ensure quality and may make training more affordable and accessible. The aim of this study was to explore the impact of an eLearning course for personnel on the rates and duration of seclusion and mechanical restraint among psychiatric inpatients. In a cluster-randomized intervention trial, the nursing personnel on 10 wards were randomly assigned to eLearning (intervention) or training-as-usual (control) groups. The eLearning course comprised six modules with specific topics (legal and ethical issues, behaviour-related factors, therapeutic relationship and self-awareness, teamwork and integrating knowledge with practice) and specific learning methods. The rates (incidents per 1000 occupied bed days) and durations of the coercion incidents were examined before and after the course. A total of 1283 coercion incidents (1143 seclusions [89%] and 140 incidents involving the use of mechanical restraints [11%]) were recorded on the study wards during the data collection period. On the intervention wards, there were no statistically significant changes in the rates of seclusion and mechanical restraint. However, the duration of incidents involving mechanical restraints shortened from 36.0 to 4.0 h (median) (P eLearning course, the duration of incidents involving the use of mechanical restraints decreased. However, more studies are needed to ensure that the content of the course focuses on the most important factors associated with the seclusion-related elements. The eLearning course deserves further development and further studies. The duration of coercion incidents merits attention in future research.

  13. Mechanical and mechanobiological influences on bone fracture repair : identifying important cellular characteristics

    NARCIS (Netherlands)

    Isaksson, H.E.

    2007-01-01

    Fracture repair is a complex and multifactorial process, which involves a well-programmed series of cellular and molecular events that result in a combination of intramembranous and endochondral bone formation. The vast majority of fractures is treated successfully. They heal through ‘secondary

  14. 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.

  15. Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses.

    Science.gov (United States)

    Won, Hyejung; Mah, Won; Kim, Eunjoon

    2013-01-01

    Autism spectrum disorder (ASD) is a group of developmental disabilities characterized by impairments in social interaction and communication and restricted and repetitive interests/behaviors. Advances in human genomics have identified a large number of genetic variations associated with ASD. These associations are being rapidly verified by a growing number of studies using a variety of approaches, including mouse genetics. These studies have also identified key mechanisms underlying the pathogenesis of ASD, many of which involve synaptic dysfunctions, and have investigated novel, mechanism-based therapeutic strategies. This review will try to integrate these three key aspects of ASD research: human genetics, animal models, and potential treatments. Continued efforts in this direction should ultimately reveal core mechanisms that account for a larger fraction of ASD cases and identify neural mechanisms associated with specific ASD symptoms, providing important clues to efficient ASD treatment.

  16. The Haemophilus ducreyi LspA1 protein inhibits phagocytosis by using a new mechanism involving activation of C-terminal Src kinase.

    Science.gov (United States)

    Dodd, Dana A; Worth, Randall G; Rosen, Michael K; Grinstein, Sergio; van Oers, Nicolai S C; Hansen, Eric J

    2014-05-20

    Haemophilus ducreyi causes chancroid, a sexually transmitted infection. A primary means by which this pathogen causes disease involves eluding phagocytosis; however, the molecular basis for this escape mechanism has been poorly understood. Here, we report that the LspA virulence factors of H. ducreyi inhibit phagocytosis by stimulating the catalytic activity of C-terminal Src kinase (Csk), which itself inhibits Src family protein tyrosine kinases (SFKs) that promote phagocytosis. Inhibitory activity could be localized to a 37-kDa domain (designated YL2) of the 456-kDa LspA1 protein. The YL2 domain impaired ingestion of IgG-opsonized targets and decreased levels of active SFKs when expressed in mammalian cells. YL2 contains tyrosine residues in two EPIYG motifs that are phosphorylated in mammalian cells. These tyrosine residues were essential for YL2-based inhibition of phagocytosis. Csk was identified as the predominant mammalian protein interacting with YL2, and a dominant-negative Csk rescued phagocytosis in the presence of YL2. Purified Csk phosphorylated the tyrosines in the YL2 EPIYG motifs. Phosphorylated YL2 increased Csk catalytic activity, resulting in positive feedback, such that YL2 can be phosphorylated by the same kinase that it activates. Finally, we found that the Helicobacter pylori CagA protein also inhibited phagocytosis in a Csk-dependent manner, raising the possibility that this may be a general mechanism among diverse bacteria. Harnessing Csk to subvert the Fcγ receptor (FcγR)-mediated phagocytic pathway represents a new bacterial mechanism for circumventing a crucial component of the innate immune response and may potentially affect other SFK-involved cellular pathways. Phagocytosis is a critical component of the immune system that enables pathogens to be contained and cleared. A number of bacterial pathogens have developed specific strategies to either physically evade phagocytosis or block the intracellular signaling required for

  17. 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.

  18. Molecular mechanism of X-ray-induced p53-dependent apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Hisako [Tokyo Metropolitan Inst. of Medical Center (Japan)

    1999-03-01

    Radiation-induced cell death has been classified into the interphase- and mitotic-ones, both of which apoptosis involving. This review described the molecular mechanism of the apoptosis, focusing on its p53-dependent process. It is known that there are genes regulating cell death either negatively or positively and the latter is involved in apoptosis. As an important factor in the apoptosis, p53 has become remarkable since it was shown that X-ray-induced apoptosis required RNA and protein syntheses in thymocytes and those cells of p53 gene-depleted mouse were shown to be resistant to gamma-ray-induced apoptosis. Radiation sensitivity of MOLT-4 cells derived from human T cell leukemia, exhibiting the typical X-ray-induced p53-dependent apoptosis, depends on the levels of p53 mRNA and protein. p53 is a gene suppressing tumor and also a transcription factor. Consequently, mutation of p53 conceivably leads to the failure of cell cycle regulation, which allows damaged cells to divide without both repair and exclusion due to loss of the apoptotic mechanism, and finally results in carcinogenesis. The radiation effect occurs in the order of the cell damage, inhibition of p53-Mdm2 binding, accumulation of p53, activation of mdm2 transcription, Mdm2 accumulation, p53-protein degradation and recovery to the steady state level. Here, the cystein protease (caspases) plays an important role as a disposing mechanism for cells scheduled to die. However, many are unknown to be solved in future. (K.H.) 119 refs.

  19. Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin

    International Nuclear Information System (INIS)

    Ouadah-Boussouf, Nafia; Babin, Patrick J.

    2016-01-01

    One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. - Highlights: • The environmental contaminant tributyltin (TBT) may promote obesity development. • TBT may induce adipocyte hypertrophy through a PPARγ independent mechanism. • RXR/RXR and RXR/LXR dimers are potential in vivo effectors of TBT in zebrafish.

  20. Pharmacological evaluation of the mechanisms involved in increased adiposity in zebrafish triggered by the environmental contaminant tributyltin

    Energy Technology Data Exchange (ETDEWEB)

    Ouadah-Boussouf, Nafia; Babin, Patrick J., E-mail: p.babin@gpp.u-bordeaux1.fr

    2016-03-01

    One proposed contributing factor to the rise in overweight and obesity is exposure to endocrine disrupting chemicals. Tributyltin chloride (TBT), an organotin, induces adipogenesis in cell culture models and may increases adipose mass in vivo in vertebrate model organisms. It has been hypothesized that TBT acts via the peroxisome proliferator activated receptor (PPAR)γ-dependent pathway. However, the mechanisms involved in the effects of TBT exposure on in vivo adipose tissue metabolism remain unexplored. Semitransparent zebrafish larvae, with their well-developed white adipose tissue, offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte biology and whole-organism adiposity in a vertebrate model. Within hours, zebrafish larvae, treated at environmentally-relevant nanomolar concentrations of TBT, exhibited a remarkable increase in adiposity linked to adipocyte hypertrophy. Under the experimental conditions used, we also demonstrated that zebrafish larvae adipose tissue proved to be highly responsive to selected human nuclear receptor agonists and antagonists. Retinoid X receptor (RXR) homodimers and RXR/liver X receptor heterodimers were suggested to be in vivo effectors of the obesogenic effect of TBT on zebrafish white adipose tissue. RXR/PPARγ heterodimers may be recruited to modulate adiposity in zebrafish but were not a necessary requirement for the short term in vivo TBT obesogenic effect. Together, the present results suggest that TBT may induce the promotion of triacylglycerol storage in adipocytes via RXR-dependent pathways without necessary using PPAR isoforms. - Highlights: • The environmental contaminant tributyltin (TBT) may promote obesity development. • TBT may induce adipocyte hypertrophy through a PPARγ independent mechanism. • RXR/RXR and RXR/LXR dimers are potential in vivo effectors of TBT in zebrafish.

  1. Borderline personality disorder symptoms and criminal justice system involvement: The roles of emotion-driven difficulties controlling impulsive behaviors and physical Aggression.

    Science.gov (United States)

    Moore, Kelly E; Tull, Matthew T; Gratz, Kim L

    2017-07-01

    Borderline personality disorder (BPD) is associated with elevated risk for a variety of risky behaviors, including criminal behaviors. Yet, limited research has examined the relation of BPD to criminal justice (CJ) involvement, or the mechanisms underlying this relation. This study examined the role of two mechanisms, emotion-driven difficulties controlling impulsive behaviors and physical aggression, in the relation between BPD symptom severity and CJ involvement among 118 patients in residential substance abuse treatment (76% male; 62% African-American). Participants completed measures of BPD symptom severity, CJ contact, diversity of CJ charges, emotion-driven impulse control difficulties, physical aggression, and covariates (substance use severity and antisocial personality disorder symptoms). BPD symptom severity was associated with CJ contact through emotion-driven difficulties controlling impulsive behaviors, and with diversity of CJ charges through emotion-driven difficulties controlling impulsive behaviors and physical aggression; however, the indirect relations to diversity of CJ charges became non-significant when covariates were included. Results highlight the important role of emotion-driven difficulties controlling impulsive behaviors in criminal behaviors among individuals with BPD symptoms, as well as the potential clinical utility of targeting this mechanism to prevent CJ involvement and/or recidivism. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. The Perceived Importance of HR duties to Danish line managers

    DEFF Research Database (Denmark)

    Brandl, Julia; Madsen, Mona Toft; Madsen, Henning

    2009-01-01

    Today, HR scholars widely acknowledge that realising HRM requires the involvement of all managers and that the personal motivation of line managers plays an important role in their successful involvement. Yet, previous research has neglected to study how line managers rate the importance of parti...

  3. Mechanisms involved in the intestinal digestion and absorption of dietary vitamin A.

    Science.gov (United States)

    Harrison, E H; Hussain, M M

    2001-05-01

    Dietary retinyl esters are hydrolyzed in the intestine by the pancreatic enzyme, pancreatic triglyceride lipase (PTL), and intestinal brush border enzyme, phospholipase B. Recent work on the carboxylester lipase (CEL) knockout mouse suggests that CEL may not be involved in dietary retinyl ester digestion. The possible roles of the pancreatic lipase-related proteins (PLRP) 1 and 2 and other enzymes require further investigation. Unesterified retinol is taken up by the enterocytes, perhaps involving both diffusion and protein-mediated facilitated transport. Once in the cell, retinol is complexed with cellular retinol-binding protein type 2 (CRBP2) and the complex serves as a substrate for reesterification of the retinol by the enzyme lecithin:retinol acyltransferase (LRAT). Retinol not bound to CRBP2 is esterified by acyl-CoA acyltransferase (ARAT). The retinyl esters are incorporated into chylomicrons, intestinal lipoproteins that transport other dietary lipids such as triglycerides, phospholipids, and cholesterol. Chylomicrons containing newly absorbed retinyl esters are then secreted into the lymph.

  4. Intra- and Intercellular Quality Control Mechanisms of Mitochondria

    Directory of Open Access Journals (Sweden)

    Yoshimitsu Kiriyama

    2017-12-01

    Full Text Available Mitochondria function to generate ATP and also play important roles in cellular homeostasis, signaling, apoptosis, autophagy, and metabolism. The loss of mitochondrial function results in cell death and various types of diseases. Therefore, quality control of mitochondria via intra- and intercellular pathways is crucial. Intracellular quality control consists of biogenesis, fusion and fission, and degradation of mitochondria in the cell, whereas intercellular quality control involves tunneling nanotubes and extracellular vesicles. In this review, we outline the current knowledge on the intra- and intercellular quality control mechanisms of mitochondria.

  5. Molecular characterization of a genomic region in a Lactococcus bacteriophage that is involved in its sensitivity to the phage defense mechanism AbiA.

    OpenAIRE

    Dinsmore, P K; Klaenhammer, T R

    1997-01-01

    A spontaneous mutant of the lactococcal phage phi31 that is insensitive to the phage defense mechanism AbiA was characterized in an effort to identify the phage factor(s) involved in sensitivity of phi31 to AbiA. A point mutation was localized in the genome of the AbiA-insensitive phage (phi31A) by heteroduplex analysis of a 9-kb region. The mutation (G to T) was within a 738-bp open reading frame (ORF245) and resulted in an arginine-to-leucine change in the predicted amino acid sequence of t...

  6. Evaluation of Purinergic Mechanism for the Treatment of Voiding Dysfunction: A Study in Conscious Spinal Cord-injured Rats

    Directory of Open Access Journals (Sweden)

    Shing-Hwa Lu

    2007-10-01

    Conclusion: These results indicate that purinergic mechanisms, presumably involving P2X3 or P2X2/3 receptors on bladder C-fiber afferent nerves, play an important role in the detrusor hyperreflexia that occurs after spinal cord injury in rats.

  7. Detoxification and sensing mechanisms are of similar importance for Cd resistance in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Sarah A. Winter

    2016-10-01

    Full Text Available The present study employed mass spectrometry (ICP-MS to measure the internal cadmium concentrations (Cdint in Caenorhabditis elegans to determine Cd uptake from a Cd-containing environment as well as Cd release under Cd-free conditions. To analyze the functional role of several ATP binding cassette (ABC transporters (e.g., HMT-1 and MRP-1 and phytochelatin synthase (PCS, we compared wild-type (WT and different mutant strains of C. elegans. As a pre-test on selected mutant strains, several time-resolved experiments were performed to determine the survival rate and avoidance behavior of C. elegans under Cd stress, which confirmed the already known Cd sensitivity of the deletion mutants mrp-1Δ, pcs-1Δ, and hmt-1Δ. In addition, these experiments revealed flight reactions under Cd stress to be almost completely absent in mrp-1Δ mutants. The ICP-MS studies showed Cd uptake to be significantly higher in mrp-1Δ and WT than in hmt-1Δ. As Cd is ingested with food, food refusal due to very early Cd stress and its perception was likely the reason for the reduced Cd uptake of hmt-1Δ. Cd release (detoxification was found to be maximal in mrp-1Δ, minimal in hmt-1Δ, and intermediate in WT. High mortality under Cd stress, food refusal, and minimal Cd release in the case of hmt-1Δ suggest a vital importance of the HMT-1/PCS-1 detoxification system for the survival of C. elegans under Cd stress. High mortality under Cd stress, absence of an avoidance behavior, missing food refusal, and maximal Cd release in the case of mrp-1Δ indicate that MRP-1 is less important for Cd detoxification under severe stress, but is probably important for Cd perception. Accordingly, our results suggest that the survival of WT under Cd stress (or possibly other forms of metal stress primarily depends on the function of the HMT-1/PCS-1 detoxification system and the presence of a sensing mechanism to control the uptake of Cd (or other metals, which keeps internal Cd (or metal

  8. Detoxification and sensing mechanisms are of similar importance for Cd resistance in Caenorhabditis elegans.

    Science.gov (United States)

    Winter, Sarah A; Dölling, Ramona; Knopf, Burkhard; Mendelski, Martha N; Schäfers, Christoph; Paul, Rüdiger J

    2016-10-01

    The present study employed mass spectrometry (ICP-MS) to measure the internal cadmium concentrations (Cd int ) in Caenorhabditis elegans to determine Cd uptake from a Cd-containing environment as well as Cd release under Cd-free conditions. To analyze the functional role of several ATP binding cassette (ABC) transporters (e.g., HMT-1 and MRP-1) and phytochelatin synthase (PCS), we compared wild-type (WT) and different mutant strains of C. elegans . As a pre-test on selected mutant strains, several time-resolved experiments were performed to determine the survival rate and avoidance behavior of C. elegans under Cd stress, which confirmed the already known Cd sensitivity of the deletion mutants mrp-1 Δ, pcs-1 Δ, and hmt-1 Δ. In addition, these experiments revealed flight reactions under Cd stress to be almost completely absent in mrp-1 Δ mutants. The ICP-MS studies showed Cd uptake to be significantly higher in mrp-1 Δ and WT than in hmt-1 Δ. As Cd is ingested with food, food refusal due to very early Cd stress and its perception was likely the reason for the reduced Cd uptake of hmt-1 Δ. Cd release (detoxification) was found to be maximal in mrp-1 Δ, minimal in hmt-1 Δ, and intermediate in WT. High mortality under Cd stress, food refusal, and minimal Cd release in the case of hmt-1 Δ suggest a vital importance of the HMT-1/PCS-1 detoxification system for the survival of C. elegans under Cd stress. High mortality under Cd stress, absence of an avoidance behavior, missing food refusal, and maximal Cd release in the case of mrp-1 Δ indicate that MRP-1 is less important for Cd detoxification under severe stress, but is probably important for Cd perception. Accordingly, our results suggest that the survival of WT under Cd stress (or possibly other forms of metal stress) primarily depends on the function of the HMT-1/PCS-1 detoxification system and the presence of a sensing mechanism to control the uptake of Cd (or other metals), which keeps internal Cd (or

  9. [Research progress on mechanical performance evaluation of artificial intervertebral disc].

    Science.gov (United States)

    Li, Rui; Wang, Song; Liao, Zhenhua; Liu, Weiqiang

    2018-03-01

    The mechanical properties of artificial intervertebral disc (AID) are related to long-term reliability of prosthesis. There are three testing methods involved in the mechanical performance evaluation of AID based on different tools: the testing method using mechanical simulator, in vitro specimen testing method and finite element analysis method. In this study, the testing standard, testing equipment and materials of AID were firstly introduced. Then, the present status of AID static mechanical properties test (static axial compression, static axial compression-shear), dynamic mechanical properties test (dynamic axial compression, dynamic axial compression-shear), creep and stress relaxation test, device pushout test, core pushout test, subsidence test, etc. were focused on. The experimental techniques using in vitro specimen testing method and testing results of available artificial discs were summarized. The experimental methods and research status of finite element analysis were also summarized. Finally, the research trends of AID mechanical performance evaluation were forecasted. The simulator, load, dynamic cycle, motion mode, specimen and test standard would be important research fields in the future.

  10. ZFPIP/Zfp462 is involved in P19 cell pluripotency and in their neuronal fate

    International Nuclear Information System (INIS)

    Masse, Julie; Piquet-Pellorce, Claire; Viet, Justine; Guerrier, Daniel; Pellerin, Isabelle; Deschamps, Stephane

    2011-01-01

    The nuclear zinc finger protein ZFPIP/Zfp462 is an important factor involved in cell division during the early embryonic development of vertebrates. In pluripotent P19 cells, ZFPIP/Zfp462 takes part in cell proliferation, likely via its role in maintaining chromatin structure. To further define the function of ZFPIP/Zfp462 in the mechanisms of pluripotency and cell differentiation, we constructed a stable P19 cell line in which ZFPIP/Zfp462 knockdown is inducible. We report that ZFPIP/Zfp462 was vital for mitosis and self-renewal in pluripotent P19 cells. Its depletion induced substantial decreases in the expression of the pluripotency genes Nanog, Oct4 and Sox2 and was associated with the transient expression of specific neuronal differentiation markers. We also demonstrated that ZFPIP/Zfp462 expression appears to be unnecessary after neuronal differentiation is induced in P19 cells. Taken together, our results strongly suggest that ZFPIP/Zfp462 is a key chromatin factor involved in maintaining P19 pluripotency and in the early mechanisms of neural differentiation but that it is dispensable in differentiated P19 cells.

  11. Involvement of hyaluronidases in colorectal cancer

    International Nuclear Information System (INIS)

    Bouga, Helen; Tsouros, Isidoros; Bounias, Dimitrios; Kyriakopoulou, Dora; Stavropoulos, Michael S; Papageorgakopoulou, Nikoletta; Theocharis, Dimitrios A; Vynios, Demitrios H

    2010-01-01

    Hyaluronidases belong to a class of enzymes that degrade, predominantly, hyaluronan. These enzymes are known to be involved in physiological and pathological processes, such as tumor growth, infiltration and angiogenesis, but their exact role in tumor promotion or suppression is not clear yet. Advanced colorectal cancer is associated with elevated amounts of hyaluronan of varying size. The aim of the present study was therefore to illuminate the importance of hyaluronidases in colon carcinoma progression. The patients' samples (macroscopically normal and cancerous) were subjected to sequential extraction with PBS, 4 M GdnHCl and 4 M GdnHCl - 1% Triton X-100. The presence of the various hyaluronidases in the extracts was examined by zymography and western blotting. Their expression was also examined by RT-PCR. Among hyaluronidases examined, Hyal-1, -2, -3 and PH-20 were detected. Their activity was higher in cancerous samples. Hyal-1 and Hyal-2 were overexpressed in cancerous samples, especially in advanced stages of cancer. Both isoforms were mainly extracted with PBS. Hyal-3 was observed only in the third extract of advanced stages of cancer. PH-20 was abundant in all three extracts of all stages of cancer. The expression of only Hyal-1 and PH-20 was verified by RT-PCR. A high association of hyaluronidases in colorectal cancer was observed. Each hyaluronidase presented different tissue distribution, which indicated the implication of certain isoforms in certain cancer stages. The results provided new evidence on the mechanisms involved in the progression of colorectal cancer

  12. A novel mechanism important for the alignment of microtubules.

    Science.gov (United States)

    Wightman, Raymond; Turner, Simon R

    2008-04-01

    Using a live-cell imaging approach to study individual micro-tubules, we have compared microtubule behavior between net-like and aligned cortical arrays. In contrast to previous studies, a steep angled collision between the growing end of a microtubule and a preexisting microtubule was found to favor crossover. Frequencies of microtubule crossovers, bundling and catastrophes are similar regardless of whether the cell exhibited a net-like or aligned microtubule array. In the predominantly aligned array of petiole cells, severing occurs at the sites of microtubule crossovers and serves to remove unaligned microtubules and to increase microtubule density. Severing was observed to be rare in net-like arrays. Microtubule severing is carried out by the katanin enzyme. In this addendum, we present new insights into the possible mechanism of crossing over and preliminary data looking at organization of the array in a katanin mutant.

  13. 5-lipoxygenase activation is involved in the mechanisms of chronic hepatic injury in a rat model of chronic aluminum overload exposure

    Energy Technology Data Exchange (ETDEWEB)

    Mai, Shaoshan [Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016 (China); He, Qin [Department of Heptobiliary Surgery, 1st Affiliated Hospital, Chongqing Medical University, Chongqing 400016 (China); Wang, Hong; Hu, Xinyue; Luo, Ying; Yang, Yang; Kuang, Shengnan; Tian, Xiaoyan; Ma, Jie [Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016 (China); Yang, Junqing, E-mail: 1139627371@qq.com [Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016 (China)

    2016-08-15

    We previously confirmed that rats overloaded with aluminum exhibited hepatic function damage and increased susceptibility to hepatic inflammation. However, the mechanism of liver toxicity by chronic aluminum overload is poorly understood. In this study, we investigated changes in the 5-lipoxygenase (5-LO) signaling pathway and its effect on liver injury in aluminum-overloaded rats. A rat hepatic injury model of chronic aluminum injury was established via the intragastric administration of aluminum gluconate (Al{sup 3+} 200 mg/kg per day, 5 days a week for 20 weeks). The 5-LO inhibitor, caffeic acid (10 and 30 mg/kg), was intragastrically administered 1 h after aluminum administration. Hematoxylin and eosin staining was used to visualize pathological changes in rat liver tissue. A series of biochemical indicators were measured with biochemistry assay or ELISAs. Immunochemistry and RT-PCR methods were used to detect 5-LO protein and mRNA expression in the liver, respectively. Caffeic acid administration protected livers against histopathological injury, decreased plasma ALT, AST, and ALP levels, decreased TNF-α, IL-6, IL-1β and LTs levels, increased the reactive oxygen species content, and down-regulated the mRNA and protein expressions of 5-LO in aluminum overloaded rats. Our results indicate that 5-lipoxygenase activation is mechanistically involved in chronic hepatic injury in a rat model of chronic aluminum overload exposure and that the 5-LO signaling pathway, which associated with inflammation and oxidative stress, is a potential therapeutic target for chronic non-infection liver diseases. - Highlights: • 5-LO signaling contributes to mechanisms of hepatotoxicity of aluminum overload. • Oxidative and inflammatory reaction involve in chonic aluminum hepatotoxicity. • 5-LO inhibitor has a protective effect on aluminum-overload liver injury. • 5-LO signaling is a potential therapeutic target for non-infection liver diseases.

  14. Mechanisms involved in repairing the lesions induced in pBR 322 by PUVA treatment (8-Methoxypsoralen + ultraviolet A light)

    International Nuclear Information System (INIS)

    Bauluz, C.

    1988-01-01

    This work deals with the genotoxic effects derived from damaging pBR322 DNA through PUVA treatment (8-Methoxypsoralen plusUVA light), both with respect to the lethality and mutagenicity of the lesions produced by the treatment. The mechanisms involved in the repair of the plasmid lesions have been investigated by transforming several strains of E. coli differing in their DNA-repair capacities. The frequency, distribution and type of mutations occurring in a restriction fragment of the damaged plasmid were determined in order to establish the mutagenic features of the PUVA treatment. Damages produced bY PUVA habe a strong lethal effect on plasmid survival; however, partial recovery is possible through some of the bacterial DNA repair pathways, namely Excision repair, SOS-repair and a third mechanism which appears to be independent from the analised genes and is detected at high density of lesions per plasmid molecule. PUVA treatment produces a high increase in plasmid mutagenesis; however, the contribution of such an increase to the whole plasmid survival is negligible. Only punctual mutations were detected and consisted mainly in base-pair substitutions. Some mutation-prone regions were sound inside the investigated DNA fragment, a though their existence is more likely to be related with the structure acquired by the damaged DNA than with the type of damaging agent. (Author)

  15. NRC Information No. 87-24: Operational experience involving losses of electrical inverters

    International Nuclear Information System (INIS)

    Rossi, C.E.

    1992-01-01

    The NRC case study report identified three potential failure mechanisms for inverters. One of these involves relatively high ambient temperature and/or humidity within inverter enclosures. This condition appears to result in accelerated aging of components that form a part of the inverter circuitry causing a significant reduction in component life expectancy and inverter loss. Another mechanism for inverter failure involves the electrical interconnecting and physical arrangements for the inverter circuitry components. In some installations, these arrangements are such that when certain components fail, other components also may fail or degrade. The third failure mechanism involves voltage spikes and perturbations. Many of the electrical loads in a plant have inductive characteristics. During plant operations that involve energizing and deenergizing these loads, voltage spikes and perturbations are generated. The solid-state devices in the inverter circuitry are sensitive to these voltage spikes, and this has resulted in component failure, blown fuses, and inverter losses. Additionally, secondary voltage perturbations caused by lighting strikes or switching surges can have an adverse effect on inverter operation

  16. Service Users' Involvement and Engagement in Interprofessional Care.

    Science.gov (United States)

    Kaini, B K

    2016-01-01

    Interprofessional care is joint working between health care professionals by pooling their skills, knowledge and expertise, to make joint decisions and learn from each other for the benefits of service users and healthcare professionals. Service users involvement is considered as one of the important aspects of planning, management and decision making process in the delivery of health care to service users. Service users' involvement is not the same as public involvement and partnership arrangements in health care. The active involvement and engagement of service users in health care positively contributes to improve quality of care, to promote better health and to shape the future of health services. Service users are always at the centre of health care professionals' values, work ethics and roles. Moreover, service users centred interprofessional team collaboration is very important to deliver effective health services.

  17. Bohmian mechanics, open quantum systems and continuous measurements

    CERN Document Server

    Nassar, Antonio B

    2017-01-01

    This book shows how Bohmian mechanics overcomes the need for a measurement postulate involving wave function collapse. The measuring process plays a very important role in quantum mechanics. It has been widely analyzed within the Copenhagen approach through the Born and von Neumann postulates, with later extension due to Lüders. In contrast, much less effort has been invested in the measurement theory within the Bohmian mechanics framework. The continuous measurement (sharp and fuzzy, or strong and weak) problem is considered here in this framework. The authors begin by generalizing the so-called Mensky approach, which is based on restricted path integral through quantum corridors. The measuring system is then considered to be an open quantum system following a stochastic Schrödinger equation. Quantum stochastic trajectories (in the Bohmian sense) and their role in basic quantum processes are discussed in detail. The decoherence process is thereby described in terms of classical trajectories issuing from th...

  18. 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.

  19. Mechanisms involved in alternariol-induced cell cycle arrest

    International Nuclear Information System (INIS)

    Solhaug, A.; Vines, L.L.; Ivanova, L.; Spilsberg, B.; Holme, J.A.; Pestka, J.; Collins, A.; Eriksen, G.S.

    2012-01-01

    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 μM almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 μM) 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 μM 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.

  20. Bullying Prevention and the Parent Involvement Model

    Science.gov (United States)

    Kolbert, Jered B.; Schultz, Danielle; Crothers, Laura M.

    2014-01-01

    A recent meta-analysis of bullying prevention programs provides support for social-ecological theory, in which parent involvement addressing child bullying behaviors is seen as important in preventing school-based bullying. The purpose of this manuscript is to suggest how Epstein and colleagues' parent involvement model can be used as a…

  1. Biologically important conformational features of DNA as interpreted by quantum mechanics and molecular mechanics computations of its simple fragments.

    Science.gov (United States)

    Poltev, V; Anisimov, V M; Dominguez, V; Gonzalez, E; Deriabina, A; Garcia, D; Rivas, F; Polteva, N A

    2018-02-01

    Deciphering the mechanism of functioning of DNA as the carrier of genetic information requires identifying inherent factors determining its structure and function. Following this path, our previous DFT studies attributed the origin of unique conformational characteristics of right-handed Watson-Crick duplexes (WCDs) to the conformational profile of deoxydinucleoside monophosphates (dDMPs) serving as the minimal repeating units of DNA strand. According to those findings, the directionality of the sugar-phosphate chain and the characteristic ranges of dihedral angles of energy minima combined with the geometric differences between purines and pyrimidines determine the dependence on base sequence of the three-dimensional (3D) structure of WCDs. This work extends our computational study to complementary deoxydinucleotide-monophosphates (cdDMPs) of non-standard conformation, including those of Z-family, Hoogsteen duplexes, parallel-stranded structures, and duplexes with mispaired bases. For most of these systems, except Z-conformation, computations closely reproduce experimental data within the tolerance of characteristic limits of dihedral parameters for each conformation family. Computation of cdDMPs with Z-conformation reveals that their experimental structures do not correspond to the internal energy minimum. This finding establishes the leading role of external factors in formation of the Z-conformation. Energy minima of cdDMPs of non-Watson-Crick duplexes demonstrate different sequence-dependence features than those known for WCDs. The obtained results provide evidence that the biologically important regularities of 3D structure distinguish WCDs from duplexes having non-Watson-Crick nucleotide pairing.

  2. Epigenetic mechanisms of alcoholism and stress-related disorders.

    Science.gov (United States)

    Palmisano, Martina; Pandey, Subhash C

    2017-05-01

    Stress-related disorders, such as anxiety, early life stress, and posttraumatic stress disorder appear to be important factors in promoting alcoholism, as alcohol consumption can temporarily attenuate the negative affective symptoms of these disorders. Several molecules involved in signaling pathways may contribute to the neuroadaptation induced during alcohol dependence and stress disorders, and among these, brain-derived neurotrophic factor (BDNF), corticotropin releasing factor (CRF), neuropeptide Y (NPY) and opioid peptides (i.e., nociceptin and dynorphin) are involved in the interaction of stress and alcohol. In fact, alterations in the expression and function of these molecules have been associated with the pathophysiology of stress-related disorders and alcoholism. In recent years, various studies have focused on the epigenetic mechanisms that regulate chromatin architecture, thereby modifying gene expression. Interestingly, epigenetic modifications in specific brain regions have been shown to be associated with the neurobiology of psychiatric disorders, including alcoholism and stress. In particular, the enzymes responsible for chromatin remodeling (i.e., histone deacetylases and methyltransferases, DNA methyltransferases) have been identified as common molecular mechanisms for the interaction of stress and alcohol and have become promising therapeutic targets to treat or prevent alcoholism and associated emotional disorders. Published by Elsevier Inc.

  3. Statistical mechanical analysis of LMFBR fuel cladding tubes

    International Nuclear Information System (INIS)

    Poncelet, J.-P.; Pay, A.

    1977-01-01

    The most important design requirement on fuel pin cladding for LMFBR's is its mechanical integrity. Disruptive factors include internal pressure from mixed oxide fuel fission gas release, thermal stresses and high temperature creep, neutron-induced differential void-swelling as a source of stress in the cladding and irradiation creep of stainless steel material, corrosion by fission products. Under irradiation these load-restraining mechanisms are accentuated by stainless steel embrittlement and strength alterations. To account for the numerous uncertainties involved in the analysis by theoretical models and computer codes statistical tools are unavoidably requested, i.e. Monte Carlo simulation methods. Thanks to these techniques, uncertainties in nominal characteristics, material properties and environmental conditions can be linked up in a correct way and used for a more accurate conceptual design. (Auth.)

  4. Mechanism for iron control of the Vibrio fischeri luminescence system: involvement of cyclic AMP and cyclic AMP receptor protein and modulation of DNA level.

    Science.gov (United States)

    Dunlap, P V

    1992-07-01

    Iron controls luminescence in Vibrio fischeri by an indirect but undefined mechanism. To gain insight into that mechanism, the involvement of cyclic AMP (cAMP) and cAMP receptor protein (CRP) and of modulation of DNA levels in iron control of luminescence were examined in V. fischeri and in Escherichia coli containing the cloned V. fischeri lux genes on plasmids. For V. fischeri and E. coli adenylate cyclase (cya) and CRP (crp) mutants containing intact lux genes (luxR luxICDABEG), presence of the iron chelator ethylenediamine-di(o-hydroxyphenyl acetic acid) (EDDHA) increased expression of the luminescence system like in the parent strains only in the cya mutants in the presence of added cAMP. In the E. coli strains containing a plasmid with a Mu dl(lacZ) fusion in luxR, levels of beta-galactosidase activity (expression from the luxR promoter) and luciferase activity (expression from the lux operon promoter) were both 2-3-fold higher in the presence of EDDHA in the parent strain, and for the mutants this response to EDDHA was observed only in the cya mutant in the presence of added cAMP. Therefore, cAMP and CRP are required for the iron restriction effect on luminescence, and their involvement in iron control apparently is distinct from the known differential control of transcription from the luxR and luxICDABEG promoters by cAMP-CRP. Furthermore, plasmid and chromosomal DNA levels were higher in E. coli and V. fischeri in the presence of EDDHA. The higher DNA levels correlated with an increase in expression of chromosomally encoded beta-galactosidase in E. coli and with a higher level of autoinducer in cultures of V. fischeri. These results implicate cAMP-CRP and modulation of DNA levels in the mechanism of iron control of the V. fischeri luminescence system.

  5. A importância do gene p53 na carcinogênese humana The importance of the p53 gene in human carcinogenesis

    Directory of Open Access Journals (Sweden)

    Agnes C. Fett-Conte

    2002-04-01

    Full Text Available Existem várias razões que justificam o título de "guardião do genoma" do gene P53. Seu envolvimento, direto ou indireto, tem sido observado na etiopatogenia de praticamente todas as neoplasias humanas, incluindo as leucemias e linfomas. Conhecer seus mecanismos de ação é fundamental para compreender os aspectos moleculares da carcinogênese. O presente trabalho apresenta uma revisão sobre as características deste gene e sua importância no diagnóstico, prognóstico e terapêutica, o que faz dele um alvo em potencial das estratégias de terapia gênica.There are several reasons which justify the name of 'guardian of the genome' given to the P53 gene. Its involvement either directly or indirectly has been observed in the pathology of practically all human neoplasias, including leukemia and lymphomas. Knowledge of its mechanisms of action is fundamental to understand molecular aspects of carcinogenesis. This work presents a revision of the characteristics of this gene and its importance in the diagnosis, prognosis and treatment and why this makes it a potential target for gene therapy strategies.

  6. The mechanism of chitosan degradation by gamma and e-beam irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Gryczka, U. [Institute of Nuclear Chemistry and Technology, ul. Dorodna 16, P.O. Box 97, 03-195 Warsaw (Poland)], E-mail: urszulagryczka@wp.pl; Dondi, D. [General Chemistry Department, University of Pavia, Viale Taramelli 12, 27100 Pavia (Italy); Chmielewski, A.G.; Migdal, W. [Institute of Nuclear Chemistry and Technology, ul. Dorodna 16, P.O. Box 97, 03-195 Warsaw (Poland); Buttafava, A.; Faucitano, A. [General Chemistry Department, University of Pavia, Viale Taramelli 12, 27100 Pavia (Italy)

    2009-07-15

    The mechanism of the radiolytic degradation of chitosan under vacuum and under air is investigated in the dose range 30-300 kGy by EPR spectroscopy coupled with FTIR and gel permeation chromatography (GPC) analysis. A decrease of the number average molecular weights by a factor of 3-4 was monitored in the dose range from 0 to 300 kGy. A deconvolution of the EPR spectra is proposed leading to the identification of intermediate radicals and to a radiolysis mechanism which validity is assessed with respect to free radical and radiation chemistry knowledge of carbohydrate systems. An important result is the EPR identification of stable nitroxyl radicals in the samples irradiated in presence of oxygen. This detection is a proof of the involvement of the amino group in the radiolysis mechanism and prompts the expectation of other related products as hydroxylamine ethers. A practical implication of such observation concerns possible toxicity effects. However, on the base of the low-concentration level of the nitroxyl detected, such risk is considered of negligible importance.

  7. Examining Understandings of Parent Involvement in Early Childhood Programs

    Science.gov (United States)

    Hilado, Aimee V.; Kallemeyn, Leanne; Phillips, Lauren

    2013-01-01

    The importance of parent involvement in children's development and learning is increasingly recognized in the research literature and in federal and state policies; however, no unified definition of parent involvement exists. This study examined different understandings and definitions of parent involvement in a sample of administrators of…

  8. Postamputation pain: studies on mechanisms.

    Science.gov (United States)

    Nikolajsen, Lone

    2012-10-01

    Amputation is followed by both painful and non-painful phantom phenomena in a large number of amputees. Non-painful phantom sensations rarely pose any clinical problem, but 60-80% of all amputees also experience painful sensations (i.e. phantom pain) located to the missing limb. The severity of phantom pain usually decreases with time, but severe pain persists in 5-10% of patients. Pain in the residual limb (i.e. stump pain) is another consequence of amputation. Both stump and phantom pain can be very difficult to treat. Treatment guidelines used for other neuropathic pain conditions are probably the best approximation, especially for the treatment of stump pain. The aim of the present doctoral thesis was to explore some of the mechanisms underlying pain after amputation. Ten studies were carried out (I-X). My PhD thesis from 1998 dealt with pain before the amputation and showed that preamputation pain increases the risk of phantom pain after amputation (I). A perioperative epidural blockade, however, did not reduce the incidence of pain or abnormal sensory phenomena after amputation (II, III). The importance of sensitization before amputation for the subsequent development of pain is supported by study IV, in which pressure pain thresholds obtained at the limb before amputation were inversely related to stump and phantom pain after 1 week. Afferent input from the periphery is likely to contribute to postamputation pain as sodium channels were upregulated in human neuromas (VI), although neuroma removal did not always alleviate phantom pain (V). Sensitization of neurons in the spinal cord also seems to be involved in pain after amputation as phantom pain was reduced by ketamine, an NMDA-receptor antagonist. Another NMDA-receptor antagonist, memantine, and gabapentin, a drug working by binding to the δ2α-subunit of voltage-gated calcium channels, had no effect on phantom pain (VII-IX). Supraspinal factors are also important for pain after amputation as

  9. Underlying mechanism in the water chemistry of nuclear systems

    International Nuclear Information System (INIS)

    Walton, G.N.

    1978-01-01

    The equilibrium between dissolved hydrogen and oxygen in the molecular decomposition of water, and the equilibrium between hydrogen ions and hydroxyl ions in the ionic dissociation of water, both constitute important underlying mechanisms in the corrosion behaviour of water. The two equilibria, and the rates of the reactions involved in water and steam, will be compared and contrasted as a function of temperature, pressure and radiation. The effects of the equilibria on the hydrolysis and solubility of ferrous and ferric ions, and the ions of other metals, will be discussed in relation to the control of conditions in the coolant circuits of nuclear reactors. A third mechanism to discussed is the electrochemical exchange reactions that can contribute to the contamination of circuits. (author)

  10. "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.

  11. Increasing Importance of Balamuthia mandrillaris

    OpenAIRE

    Matin, Abdul; Siddiqui, Ruqaiyyah; Jayasekera, Samantha; Khan, Naveed Ahmed

    2008-01-01

    Balamuthia mandrillaris is an emerging protozoan parasite, an agent of granulomatous amoebic encephalitis involving the central nervous system, with a case fatality rate of >98%. This review presents our current understanding of Balamuthia infections, their pathogenesis and pathophysiology, and molecular mechanisms associated with the disease, as well as virulence traits of Balamuthia that may be potential targets for therapeutic interventions and/or for the development of preventative measures.

  12. 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.

  13. Is red wine a SAFE sip away from cardioprotection? Mechanisms involved in resveratrol- and melatonin-induced cardioprotection.

    Science.gov (United States)

    Lamont, Kim T; Somers, Sarin; Lacerda, Lydia; Opie, Lionel H; Lecour, Sandrine

    2011-05-01

    Epidemiological studies suggest that regular moderate consumption of red wine confers cardioprotection but the mechanisms involved in this effect remain unclear. Recent studies demonstrate the presence of melatonin in wine. We propose that melatonin, at a concentration found in red wine, confers cardioprotection against ischemia-reperfusion injury. Furthermore, we investigated whether both melatonin and resveratrol protect via the activation of the newly discovered survivor activating factor enhancement (SAFE) prosurvival signaling pathway that involves the activation of tumor necrosis factor alpha (TNFα) and the signal transducer and activator of transcription 3 (STAT3). Isolated perfused male mouse (wild type, TNFα receptor 2 knockout mice, and cardiomyocyte-specific STAT3-deficient mice) or rat hearts (Wistars) were subjected to ischemia-reperfusion. Resveratrol (2.3 mg/L) or melatonin (75 ng/L) was perfused for 15 min with a 10-min washout period prior to an ischemia-reperfusion insult. Infarct size was measured at the end of the protocol, and Western blot analysis was performed to evaluate STAT3 activation prior to the ischemic insult. Both resveratrol and melatonin, at concentrations found in red wine, significantly reduced infarct size compared with control hearts in wild-type mouse hearts (25 ± 3% and 25 ± 3% respectively versus control 69 ± 3%, P < 0.001) but failed to protect in TNF receptor 2 knockout or STAT3-deficient mice. Furthermore, perfusion with either melatonin or resveratrol increased STAT3 phosphorylation prior to ischemia by 79% and 50%, respectively (P < 0.001 versus control). Our data demonstrate that both melatonin and resveratrol, as found in red wine, protect the heart in an experimental model of myocardial infarction via the SAFE pathway. © 2011 John Wiley & Sons A/S.

  14. Molecular mechanisms of cognitive dysfunction following traumatic brain injury

    Science.gov (United States)

    Walker, Kendall R.; Tesco, Giuseppina

    2013-01-01

    Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration. PMID:23847533

  15. Molecular mechanisms of cognitive dysfunction following traumatic brain injury.

    Science.gov (United States)

    Walker, Kendall R; Tesco, Giuseppina

    2013-01-01

    Traumatic brain injury (TBI) results in significant disability due to cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. The role of TBI in chronic neurodegeneration and the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and most recently chronic traumatic encephalopathy (CTE) is of particular importance. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. In this review, we present experimental evidence of the known secondary injury mechanisms which contribute to neuronal cell loss, axonal injury, and synaptic dysfunction and hence cognitive impairment both acutely and chronically following TBI. In particular we focus on the mechanisms linking TBI to the development of two forms of dementia: AD and CTE. We provide evidence of potential molecular mechanisms involved in modulating Aβ and Tau following TBI and provide evidence of the role of these mechanisms in AD pathology. Additionally we propose a mechanism by which Aβ generated as a direct result of TBI is capable of exacerbating secondary injury mechanisms thereby establishing a neurotoxic cascade that leads to chronic neurodegeneration.

  16. Modeling mechanical and thermo-mechanical erosion by flowing lava at Raglan, Cape Smith Belt, New Québec, Canada

    Science.gov (United States)

    Cataldo, V.; Williams, D. A.; Lesher, C. M.

    2015-12-01

    The 1.5-D Williams et al. model of thermal erosion by turbulent lava was recently applied to the Athabasca Valles lava channel on Mars, in an attempt to establish the importance of thermal erosion in excavating this ~80-100 m deep outflow channel. The modeled erosion depths (0.4-7.5 m) are far less than the depth of the channel which, combined with the short duration of the eruption, suggests that mechanical erosion may have had a greater role. Several studies suggest that mechanical erosion by lava is more important in channel-tube formation than previously thought, under certain circumstances. How would we be able to distinguish between mechanical and thermal erosion? By investigating model results when substrate properties change, as we move from a consolidated, mechanically strong substrate to a partially consolidated or unconsolidated, mechanically weaker substrate. The Proterozoic Raglan komatiitic basalt lava channel of the Cape Smith Belt, New Québec, Canada is a complex erosional environment involving invasive erosion of both sediment and gabbro substrates - which makes it a critical test case. The lava eroded an upper layer of soft sediment, with erosion at the tops, bottoms, and sides of the conduit, through underlying gabbro, and then burrowed laterally into underlying sediment, a scenario requiring a two-dimensional modeling approach. Using the available field data, we will simulate two-dimensional thermomechanical and mechanical erosion interfaces on all sides of a turbulent lava flow by creating a finite-element mesh. The mesh will be defined by the geometry of the lava flow at those lava conduits for which data on lava and substrate composition, lava thickness, slope of the ground, conduit area and volume, and lava flow length are available. Ultimately, this model will be applied to lunar sinuous rilles and martian lava channels for which the use of a two-dimensional approach is needed.

  17. Development of the Neptune Deepwater Port: The Importance of Key Stakeholder Involvement and Benefits

    Energy Technology Data Exchange (ETDEWEB)

    Silver, Marc

    2010-09-15

    In 2005, a subsidiary of GDF SUEZ began developing the Neptune LNG Deepwater Port off the coast of Massachusetts. The project met with minimal opposition and maintained a very aggressive timeline. The reasons? Productive involvement with key stakeholders and well-defined benefits. This paper outlines the systematic approach to stakeholder outreach and mitigation planning that Neptune LNG LLC took to garner project acceptance. Details of the pre-planning phase, the stakeholder outreach phase, and the project mitigation phase are all discussed. The result was a major energy project that took less than 3.5 years to permit and 1.5 years to build.

  18. Disagreement in Parental Reports of Father Involvement

    Science.gov (United States)

    Charles, Pajarita; Spielfogel, Jill; Gorman-Smith, Deborah; Schoeny, Michael; Henry, David; Tolan, Patrick

    2016-01-01

    Despite agreement on the value of father involvement in children’s lives, research has been limited due to the exclusion of fathers in studies, questionable validity of mothers’ reports on father involvement, and simple measures of fathering behavior. Our study extends previous research by comparing reports of father involvement using robust, multidimensional father involvement measures. Data from 113 fathers and 126 mothers reporting on 221 children were used to assess father involvement. Results indicate that fathers reported significantly higher levels of involvement than mothers reported. Findings from hierarchical linear models suggest that race/ethnicity and mothers’ reports of positive relationship quality were associated with smaller discrepancies in reports of father involvement, whereas nonmarried partnerships, older children, father residence, and biological status predicted larger discrepancies. Our study demonstrates the importance of obtaining father involvement reports directly from fathers and why father involvement should be assessed as a multidimensional construct to examine fathering behavior. PMID:29515272

  19. Investigation of incidents of terrorism involving commercial aircraft.

    Science.gov (United States)

    Clark, M A; Wagner, G N; Wright, D G; Ruehle, C J; McDonnell, E W

    1989-07-01

    Deaths resulting from terrorism involving aircraft have occurred incident to hijackings as well as bombings. Passengers or groups of passengers have been chosen by terrorists as the recipients of violence based on citizenship, religion, and political beliefs. They have usually been segregated from other passengers and subsequently mistreated and/or murdered. Thorough documentation of the injuries of victims is essential to the investigation of such atrocities; a medicolegal autopsy correlated with a scene investigation is of paramount importance. Aircraft bombings can create extremely sensitive political situations and public demands for quick resolution. The autopsy of victims in such circumstances, if properly conducted, can yield invaluable trace evidence leading to the identification of the explosive device. The examination of any surviving victims as well as the aircraft is also critical in reconstructing the event. Deaths occurring as the result of in-flight aircraft bombings can produce injuries by five different mechanisms, viz. blast, shrapnel, decompression, impact with the aircraft, and ground impact.

  20. 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.

  1. 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.

  2. Respiratory muscle involvement in sarcoidosis.

    Science.gov (United States)

    Schreiber, Tina; Windisch, Wolfram

    2018-07-01

    In sarcoidosis, muscle involvement is common, but mostly asymptomatic. Currently, little is known about respiratory muscle and diaphragm involvement and function in patients with sarcoidosis. Reduced inspiratory muscle strength and/or a reduced diaphragm function may contribute to exertional dyspnea, fatigue and reduced health-related quality of life. Previous studies using volitional and non-volitional tests demonstrated a reduced inspiratory muscle strength in sarcoidosis compared to control subjects, and also showed that respiratory muscle function may even be significantly impaired in a subset of patients. Areas covered: This review examines the evidence on respiratory muscle involvement and its implications in sarcoidosis with emphasis on pathogenesis, diagnosis and treatment of respiratory muscle dysfunction. The presented evidence was identified by a literature search performed in PubMed and Medline for articles about respiratory and skeletal muscle function in sarcoidosis through to January 2018. Expert commentary: Respiratory muscle involvement in sarcoidosis is an underdiagnosed condition, which may have an important impact on dyspnea and health-related quality of life. Further studies are needed to understand the etiology, pathogenesis and extent of respiratory muscle involvement in sarcoidosis.

  3. Strategy Innovation with Employee Involvement

    DEFF Research Database (Denmark)

    Friis, Ole Uhrskov; Koch, Christian

    2015-01-01

    The purpose of this article is to investigate how employees can be involved in strategy innovation processes and how new strategy practices (new tools and procedures) are used to change strategy praxis in order to sustain value creation. In the strategizing actions, we found that even...... if the managers still dominate, some processes of direct involvement of employees occur, in particular when employees are asked to supplement overall strategic goals and when they directly shape several sub-strategies. Strategy practices found include strategy planning, an open space workshop and organised...... strategy projects. Especially the latter two are important in facilitating the employee involvement. The case, however, also exhibits enterprise-situated praxises related to unplanned events, like the mitigation of taboos....

  4. Formation Mechanism of Spherical TiC in Ni-Ti-C System during Combustion Synthesis.

    Science.gov (United States)

    Zhu, Guoliang; Wang, Wei; Wang, Rui; Zhao, Chuanbao; Pan, Weitao; Huang, Haijun; Du, Dafan; Wang, Donghong; Shu, Da; Dong, Anping; Sun, Baode; Jiang, Sheng; Pu, Yilong

    2017-08-29

    The formation mechanism of TiC particles in a Ni-Ti-C system were revealed by using differential thermal analysis (DTA), XRD, and SEM to identify the reaction products in different temperature ranges. The results indicated that the synthesis mechanism of TiC in Ni-Ti-C system was complex; several reactions were involved in the combustion synthesis of TiC-Ni composite. The Ni-Ti intermediate phases play important roles during the formation of TiC. Moreover, the influence of heating rate on the size range of TiC was also discussed.

  5. Quantum Mechanics - Fundamentals and Applications to Technology

    Science.gov (United States)

    Singh, Jasprit

    1996-10-01

    Explore the relationship between quantum mechanics and information-age applications This volume takes an altogether unique approach to quantum mechanics. Providing an in-depth exposition of quantum mechanics fundamentals, it shows how these concepts are applied to most of today's information technologies, whether they are electronic devices or materials. No other text makes this critical, essential leap from theory to real-world applications. The book's lively discussion of the mathematics involved fits right in with contemporary multidisciplinary trends in education: Once the basic formulation has been derived in a given chapter, the connection to important technological problems is summarily described. The many helpful features include * Twenty-eight application-oriented sections that focus on lasers, transistors, magnetic memories, superconductors, nuclear magnetic resonance (NMR), and other important technology-driving materials and devices * One hundred solved examples, with an emphasis on numerical results and the connection between the physics and its applications * End-of-chapter problems that ground the student in both fundamental and applied concepts * Numerous figures and tables to clarify the various topics and provide a global view of the problems under discussion * Over two hundred illustrations to highlight problems and text A book for the information age, Quantum Mechanics: Fundamentals and Applications to Technology promises to become a standard in departments of electrical engineering, applied physics, and materials science, as well as physics. It is an excellent text for senior undergraduate and graduate students, and a helpful reference for practicing scientists, engineers, and chemists in the semiconductor and electronic industries.

  6. Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms

    DEFF Research Database (Denmark)

    Nestoras, Konstantinos; Mohammed, Asma Hadi; Schreurs, Ann-Sofie

    2010-01-01

    The correct levels of deoxyribonucleotide triphosphates and their relative abundance are important to maintain genomic integrity. Ribonucleotide reductase (RNR) regulation is complex and multifaceted. RNR is regulated allosterically by two nucleotide-binding sites, by transcriptional control, and...

  7. Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses

    Directory of Open Access Journals (Sweden)

    Hyejung eWon

    2013-08-01

    Full Text Available Autism spectrum disorder (ASD is a group of developmental disabilities characterized by impairments in social interaction and communication and restricted and repetitive inter-ests/behaviors. Advances in human genomics have identified a large number of genetic varia-tions associated with ASD. These associations are being rapidly verified by a growing number of studies using a variety of approaches, including mouse genetics. These studies have also identified key mechanisms underlying the pathogenesis of ASD, many of which involve synaptic dysfunctions, and have investigated novel, mechanism-based therapeutic strategies. This review will try to integrate these three key aspects of ASD research: human genetics, animal models, and potential treatments. Continued efforts in this direction should ultimately reveal core mechanisms that account for a larger fraction of ASD cases and identify neural mechanisms associated with specific ASD symptoms, providing important clues to efficient ASD treatment.

  8. Similarities and differences in neuroplasticity mechanisms between brain gliomas and nonlesional epilepsy.

    Science.gov (United States)

    Bourdillon, Pierre; Apra, Caroline; Guénot, Marc; Duffau, Hugues

    2017-12-01

    To analyze the conceptual and practical implications of a hodotopic approach in neurosurgery, and to compare the similarities and the differences in neuroplasticity mechanisms between low-grade gliomas and nonlesional epilepsy. We review the recent data about the hodotopic organization of the brain connectome, alongside the organization of epileptic networks, and analyze how these two structures interact, suggesting therapeutic prospects. Then we focus on the mechanisms of neuroplasticity involved in glioma natural course and after glioma surgery. Comparing these mechanisms with those in action in an epileptic brain highlights their differences, but more importantly, gives an original perspective to the consequences of surgery on an epileptic brain and what could be expected after pathologic white matter removal. The organization of the brain connectome and the neuroplasticity is the same in all humans, but different pathologic mechanisms are involved, and specific therapeutic approaches have been developed in epilepsy and glioma surgery. We demonstrate that the "connectome" point of view can enrich epilepsy care. We also underscore how theoretical and practical tools commonly used in epilepsy investigations, such as invasive electroencephalography, can be of great help in awake surgery in general. Putting together advances in understanding of connectomics and neuroplasticity, leads to significant conceptual improvements in epilepsy surgery. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  9. Study on the Mechanical and Interfacial Property of Injection Molded Fiber Reinforced Thermoplastics

    OpenAIRE

    王, 存涛

    2014-01-01

    Fiber reinforced polymer (FRP) composites have been used widely in the land transportation, aerospace, marine structures and characteristically conservative infrastructure construction industries and generally, the interface plays very important role in the properties of FRP materials. Therefore, this research studied the mechanical and interfacial property involved in the non-weld samples, weld samples and adhesive samples of insert moldings. Green composites as one of environment-friendly m...

  10. Importance of MRI in the diagnosis of vertebral involvement in generalized cystic lymphangiomatosis

    Energy Technology Data Exchange (ETDEWEB)

    Renjen, Pooja; Kovanlikaya, Arzu; Brill, Paula W. [New York Presbyterian Hospital/Weill Cornell Medical Center, Department of Radiology, New York, NY (United States); Narula, Navneet [New York Presbyterian Hospital/Weill Cornell Medical Center, Department of Pathology, New York, NY (United States)

    2014-11-15

    A 9-year-old boy presented with the sudden onset of pleuritic chest pain and on CT was found to have a large pleural effusion, mediastinal fluid, splenic lesions and multiple apparently sclerotic vertebral bodies. Subsequent MRI showed that those vertebral bodies that appeared sclerotic were in fact normal, and the vertebral bodies initially interpreted as normal had an abnormal T1 and T2 hyperintense signal on MRI and were relatively lucent on CT. MRI also demonstrated abnormal heterogeneous T2 hyperintense paraspinal tissue and several multicystic soft tissue masses. Biopsy of two adjacent vertebral bodies, one relatively sclerotic and one lucent, demonstrated findings of bony remodeling without a specific diagnosis. Biopsy of an infiltrative mediastinal mass confirmed the diagnosis of generalized cystic lymphangiomatosis. MRI should be included in the assessment of vertebral involvement in this condition because CT and biopsy findings may be nonspecific. (orig.)

  11. Community Involvement in TB Research

    NARCIS (Netherlands)

    M. van der Werf (Marloes); S.G. Heumann (Silke); E.M.H. Mitchell

    2011-01-01

    textabstractWhile communities at risk have been both drivers and partners in HIV research, their important role in TB research is yet to be fully realized. Involvement of communities in tuberculosis care and prevention is currently on the international agenda. This creates opportunities and

  12. Multiscale modelling of DNA mechanics

    International Nuclear Information System (INIS)

    Dršata, Tomáš; Lankaš, Filip

    2015-01-01

    Mechanical properties of DNA are important not only in a wide range of biological processes but also in the emerging field of DNA nanotechnology. We review some of the recent developments in modeling these properties, emphasizing the multiscale nature of the problem. Modern atomic resolution, explicit solvent molecular dynamics simulations have contributed to our understanding of DNA fine structure and conformational polymorphism. These simulations may serve as data sources to parameterize rigid base models which themselves have undergone major development. A consistent buildup of larger entities involving multiple rigid bases enables us to describe DNA at more global scales. Free energy methods to impose large strains on DNA, as well as bead models and other approaches, are also briefly discussed. (topical review)

  13. Crosstalk between Apoptosis and Autophagy: Molecular Mechanisms and Therapeutic Strategies in Cancer

    Directory of Open Access Journals (Sweden)

    Abdelouahid El-Khattouti

    2013-01-01

    Full Text Available Both apoptosis and autophagy are highly conserved processes that besides their role in the maintenance of the organismal and cellular homeostasis serve as a main target of tumor therapeutics. Although their important roles in the modulation of tumor therapeutic strategies have been widely reported, the molecular actions of both apoptosis and autophagy are counteracted by cancer protective mechanisms. While apoptosis is a tightly regulated process that is implicated in the removal of damaged or unwanted cells, autophagy is a cellular catabolic pathway that is involved in lysosomal degradation and recycling of proteins and organelles, and thereby is considered an important survival/protective mechanism for cancer cells in response to metabolic stress or chemotherapy. Although the relationship between autophagy and cell death is very complicated and has not been characterized in detail, the molecular mechanisms that control this relationship are considered to be a relevant target for the development of a therapeutic strategy for tumor treatment. In this review, we focus on the molecular mechanisms of apoptosis, autophagy, and those of the crosstalk between apoptosis and autophagy in order to provide insight into the molecular mechanisms that may be essential for the balance between cell survival and death as well as their role as targets for the development of novel therapeutic approaches.

  14. Transcriptome analysis reveals key differentially expressed genes involved in wheat grain development

    Directory of Open Access Journals (Sweden)

    Yonglong Yu

    2016-04-01

    Full Text Available Wheat seed development is an important physiological process of seed maturation and directly affects wheat yield and quality. In this study, we performed dynamic transcriptome microarray analysis of an elite Chinese bread wheat cultivar (Jimai 20 during grain development using the GeneChip Wheat Genome Array. Grain morphology and scanning electron microscope observations showed that the period of 11–15 days post-anthesis (DPA was a key stage for the synthesis and accumulation of seed starch. Genome-wide transcriptional profiling and significance analysis of microarrays revealed that the period from 11 to 15 DPA was more important than the 15–20 DPA stage for the synthesis and accumulation of nutritive reserves. Series test of cluster analysis of differential genes revealed five statistically significant gene expression profiles. Gene ontology annotation and enrichment analysis gave further information about differentially expressed genes, and MapMan analysis revealed expression changes within functional groups during seed development. Metabolic pathway network analysis showed that major and minor metabolic pathways regulate one another to ensure regular seed development and nutritive reserve accumulation. We performed gene co-expression network analysis to identify genes that play vital roles in seed development and identified several key genes involved in important metabolic pathways. The transcriptional expression of eight key genes involved in starch and protein synthesis and stress defense was further validated by qRT-PCR. Our results provide new insight into the molecular mechanisms of wheat seed development and the determinants of yield and quality.

  15. The knottin-like Blufensin family regulates genes involved in nuclear import and the secretory pathway in barley-powdery mildew interactions

    Science.gov (United States)

    Xu, Weihui; Meng, Yan; Surana, Priyanka; Fuerst, Greg; Nettleton, Dan; Wise, Roger P.

    2015-01-01

    Plants have evolved complex regulatory mechanisms to control a multi-layered defense response to microbial attack. Both temporal and spatial gene expression are tightly regulated in response to pathogen ingress, modulating both positive and negative control of defense. BLUFENSINs, small knottin-like peptides in barley, wheat, and rice, are highly induced by attack from fungal pathogens, in particular, the obligate biotrophic fungus, Blumeria graminis f. sp. hordei (Bgh), causal agent of barley powdery mildew. Previous research indicated that Blufensin1 (Bln1) functions as a negative regulator of basal defense mechanisms. In the current report, we show that BLN1 and BLN2 can both be secreted to the apoplast and Barley stripe mosaic virus (BSMV)-mediated overexpression of Bln2 increases susceptibility of barley to Bgh. Bimolecular fluorescence complementation (BiFC) assays signify that BLN1 and BLN2 can interact with each other, and with calmodulin. We then used BSMV-induced gene silencing to knock down Bln1, followed by Barley1 GeneChip transcriptome analysis, to identify additional host genes influenced by Bln1. Analysis of differential expression revealed a gene set enriched for those encoding proteins annotated to nuclear import and the secretory pathway, particularly Importin α1-b and Sec61 γ subunits. Further functional analysis of these two affected genes showed that when silenced, they also reduced susceptibility to Bgh. Taken together, we postulate that Bln1 is co-opted by Bgh to facilitate transport of disease-related host proteins or effectors, influencing the establishment of Bgh compatibility on its barley host. PMID:26089830

  16. The relationship between online campaigning and political involvement

    NARCIS (Netherlands)

    Kruikemeier, S.; van Noort, G.; Vliegenthart, R.; de Vreese, C.H.

    2016-01-01

    Purpose-The purpose of this paper is to examine the causal relationship between interactive and personal campaigning on social media and political involvement, and the mechanisms that explain the effects. Specifically, this study examines whether personal and interactive communication on Twitter

  17. 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

  18. Timely Activation of Budding Yeast APCCdh1 Involves Degradation of Its Inhibitor, Acm1, by an Unconventional Proteolytic Mechanism

    Science.gov (United States)

    Melesse, Michael; Choi, Eunyoung; Hall, Hana; Walsh, Michael J.; Geer, M. Ariel; Hall, Mark C.

    2014-01-01

    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-cycle expression profiles

  19. Effect of Selenium on Control of Postharvest Gray Mold of Tomato Fruit and the Possible Mechanisms Involved

    Science.gov (United States)

    Wu, Zhilin; Yin, Xuebin; Bañuelos, Gary S.; Lin, Zhi-Qing; Zhu, Zhu; Liu, Ying; Yuan, Linxi; Li, Miao

    2016-01-01

    Selenium (Se) has important benefits for crop growth and stress tolerance at low concentrations. However, there is very little information on antimicrobial effect of Se 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 mold control in harvested tomato fruit. Se treatment at 24 mg/L significantly inhibited spore germination of the fungal pathogen and effectively controlled gray mold 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 mold rot of tomato fruits and might be useful in integrated control against gray mold disease of postharvest fruits and vegetables caused by B. cinerea. The mechanisms by which Se decreased gray mold 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. PMID:26779128

  20. 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.

  1. Barriers to School Involvement: Are Immigrant Parents Disadvantaged?

    Science.gov (United States)

    Turney, Kristin; Kao, Grace

    2009-01-01

    Parental involvement at school offers unique opportunities for parents, and this school-based involvement has important implications for children's academic and behavioral outcomes. The authors used data from the Early Childhood Longitudinal Study-Kindergarten Cohort (National Center for Education Statistics, 2001) to examine race and immigrant…

  2. Business Involvement in Schools: Separating Wheat from Chaff.

    Science.gov (United States)

    Molnar, Alex

    1990-01-01

    Given the importance of educating for democratic citizenship, the involvement of individual business people with policymaking bodies and task forces is highly desirable. However, schools should limit business involvement to civic-minded contributions free of marketing or advertising hype. To do otherwise betrays the spirit of educational…

  3. Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review.

    Science.gov (United States)

    Gaudry, Stéphane; Messika, Jonathan; Ricard, Jean-Damien; Guillo, Sylvie; Pasquet, Blandine; Dubief, Emeline; Boukertouta, Tanissia; Dreyfuss, Didier; Tubach, Florence

    2017-12-01

    Intensivists' clinical decision making pursues two main goals for patients: to decrease mortality and to improve quality of life and functional status in survivors. Patient-important outcomes are gaining wide acceptance in most fields of clinical research. We sought to systematically review how well patient-important outcomes are reported in published randomized controlled trials (RCTs) in critically ill patients. Literature search was conducted to identify eligible trials indexed from January to December 2013. Articles were eligible if they reported an RCT involving critically ill adult patients. We excluded phase II, pilot and physiological crossover studies. We assessed study characteristics. All primary and secondary outcomes were collected, described and classified using six categories of outcomes including patient-important outcomes (involving mortality at any time on the one hand and quality of life, functional/cognitive/neurological outcomes assessed after ICU discharge on the other). Of the 716 articles retrieved in 2013, 112 RCTs met the inclusion criteria. Most common topics were mechanical ventilation (27%), sepsis (19%) and nutrition (17%). Among the 112 primary outcomes, 27 (24%) were patient-important outcomes (mainly mortality, 21/27) but only six (5%) were patient-important outcomes besides mortality assessed after ICU discharge (functional disability = 4; quality of life = 2). Among the 598 secondary outcomes, 133 (22%) were patient-important outcomes (mainly mortality, 92/133) but only 41 (7%) were patient-important outcomes besides mortality assessed after ICU discharge (quality of life = 20, functional disability = 14; neurological/cognitive performance = 5; handicap = 1; post-traumatic stress = 1). Seventy-three RCTs (65%) reported at least one patient-important outcome but only 11 (10%) reported at least one patient-important outcome besides mortality assessed after ICU discharge. Patient-important outcomes are rarely primary

  4. Parental involvement and educational achievement

    NARCIS (Netherlands)

    Driessen, G.; Smit, F.; Sleegers, P.

    2005-01-01

    Parental involvement is seen as an important strategy for the advancement of the quality of education. The ultimate objective of this is to expand the social and cognitive capacities of pupils. In addition, special attention is paid to the children of low-educated and ethnic minority parents.

  5. DHA involvement in neurotransmission process

    OpenAIRE

    Vancassel Sylvie; Aïd Sabah; Denis Isabelle; Guesnet Philippe; Lavialle Monique

    2007-01-01

    The very high enrichment of the nervous system in the polyunsaturated fatty acids, arachidonic (AA, 20: 4n-6) and docosahexaenoic acids (DHA, 22: 6n-3), is dependant of the dietary availability of their respective precursors, linoleic (18: 2n-6) and_-linolenic acids (18: 3n-3). Inadequate amounts of DHA in brain membranes have been linked to a wide variety of abnormalities ranging from visual acuity and learning irregularities, to psychopathologies. However, the molecular mechanisms involved ...

  6. Does Playing Sports Video Games Predict Increased Involvement in Real-Life Sports Over Several Years Among Older Adolescents and Emerging Adults?

    Science.gov (United States)

    Adachi, Paul J C; Willoughby, Teena

    2016-02-01

    Given the extreme popularity of video games among older adolescents and emerging adults, the investigation of positive outcomes of video game play during these developmental periods is crucial. An important direction for research in this area is the investigation of a link between sports video game play and involvement in real-life sports among youth. Yet, this association has not been examined in the long-term among older adolescents and emerging adults, and thus represents an exciting new area for discovery. The primary goal of the current study, therefore, was to examine the long-term association between sports video game play and involvement in real-life sports clubs among older adolescents and emerging adults. In addition, we examined whether self-esteem was an underlying mechanism of this longitudinal association. We surveyed older adolescents and emerging adults (N = 1132; 70.6 % female; M age = 19.06 years, range of 17-25 years at the first assessment) annually over 3 years about their video game play, self-esteem, and involvement in real-life sports. We found a long-term predictive effect of sports video game play on increased involvement in real-life sports over the 3 years. Furthermore, we demonstrated that self-esteem was an underlying mechanism of this long-term association. Our findings make an important contribution to an emerging body of literature on the positive outcomes of video game play, as they suggest that sports video game play may be an effective tool to promote real-life sports participation and physical activity among older adolescents and emerging adults.

  7. Sexual polyploidization in plants--cytological mechanisms and molecular regulation.

    Science.gov (United States)

    De Storme, Nico; Geelen, Danny

    2013-05-01

    In the plant kingdom, events of whole genome duplication or polyploidization are generally believed to occur via alterations of the sexual reproduction process. Thereby, diploid pollen and eggs are formed that contain the somatic number of chromosomes rather than the gametophytic number. By participating in fertilization, these so-called 2n gametes generate polyploid offspring and therefore constitute the basis for the establishment of polyploidy in plants. In addition, diplogamete formation, through meiotic restitution, is an essential component of apomixis and also serves as an important mechanism for the restoration of F1 hybrid fertility. Characterization of the cytological mechanisms and molecular factors underlying 2n gamete formation is therefore not only relevant for basic plant biology and evolution, but may also provide valuable cues for agricultural and biotechnological applications (e.g. reverse breeding, clonal seeds). Recent data have provided novel insights into the process of 2n pollen and egg formation and have revealed multiple means to the same end. Here, we summarize the cytological mechanisms and molecular regulatory networks underlying 2n gamete formation, and outline important mitotic and meiotic processes involved in the ectopic induction of sexual polyploidization. © 2013 Ghent University. New Phytologist © 2013 New Phytologist Trust.

  8. Phenomena and parameters important to burnup credit

    International Nuclear Information System (INIS)

    Parks, C.V.; Dehart, M.D.; Wagner, J.C.

    2001-01-01

    Since the mid-1980s, a significant number of studies have been directed at understanding the phenomena and parameters important to implementation of burnup credit in out-of-reactor applications involving pressurized-water- reactor (PWR) spent fuel. The efforts directed at burnup credit involving boiling-water-reactor (BWR) spent fuel have been more limited. This paper reviews the knowledge and experience gained from work performed in the United States and other countries in the study of burnup credit. Relevant physics and analysis phenomenon are identified, and an assessment of their importance to burnup credit implementation for transport and dry cask storage is given. (author)

  9. Transcriptome Sequence Analysis of an Ornamental Plant, Ananas comosus var. bracteatus, Revealed the Potential Unigenes Involved in Terpenoid and Phenylpropanoid Biosynthesis

    OpenAIRE

    Ma, Jun; Kanakala, S.; He, Yehua; Zhang, Junli; Zhong, Xiaolan

    2015-01-01

    Background Ananas comosus var. bracteatus (Red Pineapple) is an important ornamental plant for its colorful leaves and decorative red fruits. Because of its complex genome, it is difficult to understand the molecular mechanisms involved in the growth and development. Thus high-throughput transcriptome sequencing of Ananas comosus var. bracteatus is necessary to generate large quantities of transcript sequences for the purpose of gene discovery and functional genomic studies. Results The Anana...

  10. Convergent and divergent pathways decoding hierarchical additive mechanisms in treating cerebral ischemia-reperfusion injury.

    Science.gov (United States)

    Zhang, Ying-Ying; Li, Hai-Xia; Chen, Yin-Ying; Fang, Hong; Yu, Ya-Nan; Liu, Jun; Jing, Zhi-Wei; Wang, Zhong; Wang, Yong-Yan

    2014-03-01

    Cerebral ischemia is considered to be a highly complex disease resulting from the complicated interplay of multiple pathways. Disappointedly, most of the previous studies were limited to a single gene or a single pathway. The extent to which all involved pathways are translated into fusing mechanisms of a combination therapy is of fundamental importance. We report an integrative strategy to reveal the additive mechanism that a combination (BJ) of compound baicalin (BA) and jasminoidin (JA) fights against cerebral ischemia based on variation of pathways and functional communities. We identified six pathways of BJ group that shared diverse additive index from 0.09 to 1, which assembled broad cross talks from seven pathways of BA and 16 pathways of JA both at horizontal and vertical levels. Besides a total of 60 overlapping functions as a robust integration background among the three groups based on significantly differential subnetworks, additive mechanism with strong confidence by networks altered functions. These results provide strong evidence that the additive mechanism is more complex than previously appreciated, and an integrative analysis of pathways may suggest an important paradigm for revealing pharmacological mechanisms underlying drug combinations. © 2013 John Wiley & Sons Ltd.

  11. Mechanisms of mechanical strain memory in airway smooth muscle.

    Science.gov (United States)

    Kim, Hak Rim; Hai, Chi-Ming

    2005-10-01

    We evaluated the hypothesis that mechanical deformation of airway smooth muscle induces structural remodeling of airway smooth muscle cells, thereby modulating mechanical performance in subsequent contractions. This hypothesis implied that past experience of mechanical deformation was retained (or "memorized") as structural changes in airway smooth muscle cells, which modulated the cell's subsequent contractile responses. We termed this phenomenon mechanical strain memory. Preshortening has been found to induce attenuation of both force and isotonic shortening velocity in cholinergic receptor-activated airway smooth muscle. Rapid stretching of cholinergic receptor-activated airway smooth muscle from an initial length to a final length resulted in post-stretch force and myosin light chain phosphorylation that correlated significantly with initial length. Thus post-stretch muscle strips appeared to retain memory of the initial length prior to rapid stretch (mechanical strain memory). Cytoskeletal recruitment of actin- and integrin-binding proteins and Erk 1/2 MAPK appeared to be important mechanisms of mechanical strain memory. Sinusoidal length oscillation led to force attenuation during oscillation and in subsequent contractions in intact airway smooth muscle, and p38 MAPK appeared to be an important mechanism. In contrast, application of local mechanical strain to cultured airway smooth muscle cells induced local actin polymerization and cytoskeletal stiffening. It is conceivable that deep inspiration-induced bronchoprotection may be a manifestation of mechanical strain memory such that mechanical deformation from past breathing cycles modulated the mechanical performance of airway smooth muscle in subsequent cycles in a continuous and dynamic manner.

  12. A BDNF sensitive mechanism is involved in the fear memory resulting from the interaction between stress and the retrieval of an established trace.

    Science.gov (United States)

    Giachero, Marcelo; Bustos, Silvia G; Calfa, Gaston; Molina, Victor A

    2013-04-15

    The present study investigates the fear memory resulting from the interaction of a stressful experience and the retrieval of an established fear memory trace. Such a combination enhanced both fear expression and fear retention in adult Wistar rats. Likewise, midazolam intra-basolateral amygdala (BLA) infusion prior to stress attenuated the enhancement of fear memory thus suggesting the involvement of a stress-induced reduction of the GABAergic transmission in BLA in the stress-induced enhancing effect. It has been suggested that, unlike the immediate-early gene Zif268 which is related to the reconsolidation process, the expression of hippocampal brain-derived neurotrophic factor (BDNF) is highly correlated with consolidation. We therefore evaluate the relative contribution of these two neurobiological processes to the fear memory resulting from the above-mentioned interaction. Intra-dorsal hippocampus (DH) infusions of either the antisense Zif268 or the inhibitor of the protein degradation (Clasto-Lactacystin β-Lactone), suggested to be involved in the retrieval-dependent destabilization process, did not affect the resulting contextual memory. In contrast, the knockdown of hippocampal BDNF mitigated the stress-induced facilitating influence on fear retention. In addition, the retrieval experience elevated BDNF level in DH at 60 min after recall exclusively in stressed animals. These findings suggest the involvement of a hippocampal BDNF sensitive mechanism in the stress-promoting influence on the fear memory following retrieval.

  13. 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

  14. Quantum mechanics & the big world

    NARCIS (Netherlands)

    Wezel, Jasper van

    2007-01-01

    Quantum Mechanics is one of the most successful physical theories of the last century. It explains physical phenomena from the smallest to the largest lengthscales. Despite this triumph, quantum mechanics is often perceived as a mysterious theory, involving superposition states that are alien to our

  15. Clathrin- and caveolin-independent entry of human papillomavirus type 16--involvement of tetraspanin-enriched microdomains (TEMs).

    Science.gov (United States)

    Spoden, Gilles; Freitag, Kirsten; Husmann, Matthias; Boller, Klaus; Sapp, Martin; Lambert, Carsten; Florin, Luise

    2008-10-02

    Infectious entry of human papillomaviruses into their host cells is an important step in the viral life cycle. For cell binding these viruses use proteoglycans as initial attachment sites. Subsequent transfer to a secondary receptor molecule seems to be involved in virus uptake. Depending on the papillomavirus subtype, it has been reported that entry occurs by clathrin- or caveolin-mediated mechanisms. Regarding human papillomavirus type 16 (HPV16), the primary etiologic agent for development of cervical cancer, clathrin-mediated endocytosis was described as infectious entry pathway. Using immunofluorescence and infection studies we show in contrast to published data that infectious entry of HPV16 occurs in a clathrin- and caveolin-independent manner. Inhibition of clathrin- and caveolin/raft-dependent endocytic pathways by dominant-negative mutants and siRNA-mediated knockdown, as well as inhibition of dynamin function, did not impair infection. Rather, we provide evidence for involvement of tetraspanin-enriched microdomains (TEMs) in HPV16 endocytosis. Following cell attachment, HPV16 particles colocalized with the tetraspanins CD63 and CD151 on the cell surface. Notably, tetraspanin-specific antibodies and siRNA inhibited HPV16 cell entry and infection, confirming the importance of TEMs for infectious endocytosis of HPV16. Tetraspanins fulfill various roles in the life cycle of a number of important viral pathogens, including human immunodeficiency virus (HIV) and hepatitis C virus (HCV). However, their involvement in endocytosis of viral particles has not been proven. Our data indicate TEMs as a novel clathrin- and caveolin-independent invasion route for viral pathogens and especially HPV16.

  16. STAKEHOLDER INVOLVEMENT IN THE HEALTH TECHNOLOGY ASSESSMENT PROCESS IN LATIN AMERICA.

    Science.gov (United States)

    Pichon-Riviere, Andres; Soto, Natalie; Augustovski, Federico; Sampietro-Colom, Laura

    2018-06-11

    Latin American countries are taking important steps to expand and strengthen universal health coverage, and health technology assessment (HTA) has an increasingly prominent role in this process. Participation of all relevant stakeholders has become a priority in this effort. Key issues in this area were discussed during the 2017 Latin American Health Technology Assessment International (HTAi) Policy Forum. The Forum included forty-one participants from Latin American HTA agencies; public, social security, and private insurance sectors; and the pharmaceutical and medical device industry. A background paper and presentations by invited experts and Forum members supported discussions. This study presents a summary of these discussions. Stakeholder involvement in HTA remains inconsistently implemented in the region and few countries have established formal processes. Participants agreed that stakeholder involvement is key to improve the HTA process, but the form and timing of such improvements must be adapted to local contexts. The legitimization of both HTA and decision-making processes was identified as one of the main reasons to promote stakeholder involvement; but to be successful, the entire system of assessment and decision making must be properly staffed and organized, and certain basic conditions must be met, including transparency in the HTA process and a clear link between HTA and decision making. Participants suggested a need for establishing clear rules of participation in HTA that would protect HTA producers and decision makers from potentially distorting external influences. Such rules and mechanisms could help foster trust and credibility among stakeholders, supporting actual involvement in HTA processes.

  17. 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.

  18. Involvement of Sodium Nitroprusside (SNP in the Mechanism That Delays Stem Bending of Different Gerbera Cultivars

    Directory of Open Access Journals (Sweden)

    Aung H. Naing

    2017-11-01

    Full Text Available Longevity of cut flowers of many gerbera cultivars (Gerbera jamesonii is typically short because of stem bending; hence, stem bending that occurs during the early vase life period is a major problem in gerbera. Here, we investigated the effects of sodium nitroprusside (SNP on the delay of stem bending in the gerbera cultivars, Alliance, Rosalin, and Bintang, by examining relative fresh weight, bacterial density in the vase solution, transcriptional analysis of a lignin biosynthesis gene, antioxidant activity, and xylem blockage. All three gerbera cultivars responded to SNP by delaying stem bending, compared to the controls; however, the responses were dose- and cultivar-dependent. Among the treatments, SNP at 20 mg L-1 was the best to delay stem bending in Alliance, while dosages of 10 and 5 mg L-1 were the best for Rosalin and Bintang, respectively. However, stem bending in Alliance and Rosalin was faster than in Bintang, indicating a discrepancy influenced by genotype. According to our analysis of the role of SNP in the delay of stem bending, the results revealed that SNP treatment inhibited bacterial growth and xylem blockage, enhanced expression levels of a lignin biosynthesis gene, and maintained antioxidant activities. Therefore, it is suggested that the cause of stem bending is associated with the above-mentioned parameters and SNP is involved in the mechanism that delays stem bending in the different gerbera cultivars.

  19. Analyzing Parental Involvement Dimensions in Early Childhood Education

    Science.gov (United States)

    Kurtulmus, Zeynep

    2016-01-01

    The importance of parental involvement in children's academic and social development has been widely accepted. For children's later school success, the first years are crucial. Majority of the research focuses on enhancing and supporting parental involvement in educational settings. The purpose of this study was to analyze dimensions of parental…

  20. Deciphering the mechanisms involved in Portulaca oleracea (C4) response to drought: metabolic changes including crassulacean acid-like metabolism induction and reversal upon re-watering.

    Science.gov (United States)

    D'Andrea, Rodrigo Matías; Andreo, Carlos Santiago; Lara, María Valeria

    2014-11-01

    Portulaca oleracea is a C(4) plant; however, under drought it can change its carbon fixation metabolism into a crassulacean acid metabolism (CAM)-like one. While the C(3) -CAM shift is well known, the C(4) -CAM transition has only been described in Portulaca. Here, a CAM-like metabolism was induced in P. oleracea by drought and then reversed by re-watering. Physiological and biochemical approaches were undertaken to evaluate the drought and recovery responses. In CAM-like plants, chlorophyll fluorescence parameters were transitory affected and non-radiative energy dissipation mechanisms were induced. Induction of flavonoids, betalains and antioxidant machinery may be involved in photosynthetic machinery protection. Metabolic analysis highlights a clear metabolic shift, when a CAM-like metabolism is induced and then reversed. Increases in nitrogenous compounds like free amino acids and urea, and of pinitol could contribute to withstand drought. Reciprocal variations in arginase and urease in drought-stressed and in re-watered plants suggest urea synthesis is strictly regulated. Recovery of C(4) metabolism was accounted by CO(2) assimilation pattern and malate levels. Increases in glycerol and in polyamines would be of importance of re-watered plants. Collectively, in P. oleracea multiple strategies, from induction of several metabolites to the transitory development of a CAM-like metabolism, participate to enhance its adaptation to drought. © 2014 Scandinavian Plant Physiology Society.

  1. Ace inhibitors and cardiovascular regulation : the importance of autocrine and paracrine mechanisms

    NARCIS (Netherlands)

    Wijngaarden, Jan van

    1992-01-01

    As demonstrated in a large number of clinical studies, angiotensin converting enzyme (ACE) inhibitors are of great value for the treatment of cardiovascular disorders. Although the clinical merits of these drugs are now well recognized, their mechanism of action is not yet completely understood. The

  2. Fluid mechanics as a driver of tissue-scale mechanical signaling in organogenesis.

    Science.gov (United States)

    Gilbert, Rachel M; Morgan, Joshua T; Marcin, Elizabeth S; Gleghorn, Jason P

    2016-12-01

    Organogenesis is the process during development by which cells self-assemble into complex, multi-scale tissues. Whereas significant focus and research effort has demonstrated the importance of solid mechanics in organogenesis, less attention has been given to the fluid forces that provide mechanical cues over tissue length scales. Fluid motion and pressure is capable of creating spatial gradients of forces acting on cells, thus eliciting distinct and localized signaling patterns essential for proper organ formation. Understanding the multi-scale nature of the mechanics is critically important to decipher how mechanical signals sculpt developing organs. This review outlines various mechanisms by which tissues generate, regulate, and sense fluid forces and highlights the impact of these forces and mechanisms in case studies of normal and pathological development.

  3. Review of thermodinamic and mechanical properties of hydrogen-transition metal systems

    International Nuclear Information System (INIS)

    Mathias, H.; Katz, Y.

    1978-04-01

    A large body of fundamental and empirical knowledge has been acquired during many years of research concerning the interactions between hydrogen and metals, the location of hydrogen in metal structures, its mobility in metals and its influence on mechanical properties of metals. Much progress has been made in the understanding of related phenomena, and various theories have been proposed, but considerable disagreement still exist about basic mechanisms involved. The growing interest in these subjects and their important role in science and technology are well documented by many reviews and symposia. A general survey of these topics with reference to experimental results and theories related to thermodynamic and mechanical properties of hydrogen-transition metal systems, such as H-Pd, H-Ti, H-Fe etc. is given in the present review. Special emphasis is given to hydrogen embrittlement of metals

  4. Involvement of Programmed Cell Death in Neurotoxicity of Metallic Nanoparticles: Recent Advances and Future Perspectives

    Science.gov (United States)

    Song, Bin; Zhou, Ting; Liu, Jia; Shao, LongQuan

    2016-11-01

    The widespread application of metallic nanoparticles (NPs) or NP-based products has increased the risk of exposure to NPs in humans. The brain is an important organ that is more susceptible to exogenous stimuli. Moreover, any impairment to the brain is irreversible. Recently, several in vivo studies have found that metallic NPs can be absorbed into the animal body and then translocated into the brain, mainly through the blood-brain barrier and olfactory pathway after systemic administration. Furthermore, metallic NPs can cross the placental barrier to accumulate in the fetal brain, causing developmental neurotoxicity on exposure during pregnancy. Therefore, metallic NPs become a big threat to the brain. However, the mechanisms underlying the neurotoxicity of metallic NPs remain unclear. Programmed cell death (PCD), which is different from necrosis, is defined as active cell death and is regulated by certain genes. PCD can be mainly classified into apoptosis, autophagy, necroptosis, and pyroptosis. It is involved in brain development, neurodegenerative disorders, psychiatric disorders, and brain injury. Given the pivotal role of PCD in neurological functions, we reviewed relevant articles and tried to summarize the recent advances and future perspectives of PCD involvement in the neurotoxicity of metallic NPs, with the purpose of comprehensively understanding the neurotoxic mechanisms of NPs.

  5. Protein import into isolated pea root leucoplasts

    OpenAIRE

    Chu, Chiung-Chih; Li, Hsou-min

    2015-01-01

    Leucoplasts are important organelles for the synthesis and storage of starch, lipids and proteins. However, molecular mechanism of protein import into leucoplasts and how it differs from that of import into chloroplasts remain unknown. We used pea seedlings for both chloroplast and leucoplast isolations to compare within the same species. We further optimized the isolation and import conditions to improve import efficiency and to permit a quantitative comparison between the two plastid types....

  6. The mechanisms of intractable asthma

    Directory of Open Access Journals (Sweden)

    Stephen T Holgate

    1996-01-01

    Full Text Available Overwhelming evidence now points to asthma as a chronic inflammatory disease involving the airways. The T lymphocyte takes primacy in driving the inflammatory response through upregulation of cytokines, specifically those encoded in the IL-4 gene cluster: IL-4 and IL-13 (IgE isotype switching; IL-3, IL-5 and GM-CSF (eosinophil and basophil recruitment; and IL-9 (mast cell maturation. Additional cytokines of importance include TNFa and a range of related C-x-C and C-C cytokines. Although allergens are involved in initiating the Th-2 T-cell response, other factors are likely to operate that expand and maintain the inflammatory reaction. These include a potential role for superantigens and autoimmune mechanisms as well as the recruitment of accessory cytokine producing cells, especially mast cells and eosinophils. Leucocytes recruited from the microvasculature through interactions with specific adhesion molecules release an array of mediators, which in addition to causing bronchoconstriction also lead to damage to the epithelium and underlying structures. Neutral proteases from mast cells, metalloproteases from eosinophils and an array of mediators from the formed elements of the airway all contribute to the tissue destruction remodelling process. It was concluded that asthma is a dynamic disease process involving an interplay between inflammation and repair processes and that the differing proportions of these could account for the various disease phenotypes associated with severity and progression.

  7. Identification of genes involved in low aminoglycoside-induced SOS response in Vibrio cholerae: a role for transcription stalling and Mfd helicase.

    Science.gov (United States)

    Baharoglu, Zeynep; Babosan, Anamaria; Mazel, Didier

    2014-02-01

    Sub-inhibitory concentrations (sub-MIC) of antibiotics play a very important role in selection and development of resistances. Unlike Escherichia coli, Vibrio cholerae induces its SOS response in presence of sub-MIC aminoglycosides. A role for oxidized guanine residues was observed, but the mechanisms of this induction remained unclear. To select for V. cholerae mutants that do not induce low aminoglycoside-mediated SOS induction, we developed a genetic screen that renders induction of SOS lethal. We identified genes involved in this pathway using two strategies, inactivation by transposition and gene overexpression. Interestingly, we obtained mutants inactivated for the expression of proteins known to destabilize the RNA polymerase complex. Reconstruction of the corresponding mutants confirmed their specific involvement in induction of SOS by low aminoglycoside concentrations. We propose that DNA lesions formed on aminoglycoside treatment are repaired through the formation of single-stranded DNA intermediates, inducing SOS. Inactivation of functions that dislodge RNA polymerase leads to prolonged stalling on these lesions, which hampers SOS induction and repair and reduces viability under antibiotic stress. The importance of these mechanisms is illustrated by a reduction of aminoglycoside sub-MIC. Our results point to a central role for transcription blocking at DNA lesions in SOS induction, so far underestimated.

  8. Endothelial atheroprotective and anti-inflammatory mechanisms.

    Science.gov (United States)

    Berk, B C; Abe, J I; Min, W; Surapisitchat, J; Yan, C

    2001-12-01

    Atherosclerosis preferentially occurs in areas of turbulent flow and low fluid shear stress, whereas laminar flow and high shear stress are atheroprotective. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF), have been shown to stimulate expression of endothelial cell (EC) genes that may promote atherosclerosis. Recent data suggest that steady laminar flow decreases EC apoptosis and blocks TNF-mediated EC activation. EC apoptosis is likely important in the process termed "plaque erosion" that leads to platelet aggregation. Steady laminar flow inhibits EC apoptosis by preventing cell cycle entry, by increasing antioxidant mechanisms (e.g., superoxide dismutase), and by stimulating nitric oxide-dependent protective pathways that involve enzymes PI3-kinase and Akt. Conversely, our laboratory has identified nitric oxide-independent mechanisms that limit TNF signal transduction. TNF regulates gene expression in EC, in part, by stimulating mitogen-activated protein kinases (MAPK) which phosphorylate transcription factors. We hypothesized that fluid shear stress modulates TNF effects on EC by inhibiting TNF-mediated activation of MAP kinases. To test this hypothesis, we determined the effects of steady laminar flow (shear stress = 12 dynes/cm2) on TNF-stimulated activity of two MAP kinases: extracellular signal regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK). Flow alone stimulated ERK1/2 activity, but decreased JNK activity compared to static controls. TNF (10 ng/ml) alone activated both ERK1/2 and JNK maximally at 15 minutes in human umbilical vein EC (HUVEC). Pre-exposing HUVEC for 10 minutes to flow inhibited TNF activation of JNK by 46%, but it had no significant effect on ERK1/2 activation. Incubation of EC with PD98059, a specific mitogen-activated protein kinase kinase inhibitor, blocked the flow-mediated inhibition of TNF activation of JNK. Flow-mediated inhibition of JNK was unaffected by 0.1 mM L-nitroarginine, 100 pM 8-bromo

  9. Molecular mechanisms involved in the production of chromosomal aberrations. I

    International Nuclear Information System (INIS)

    Natarajan, A.T.; Obe, G.

    1978-01-01

    Chinese hamster ovary cells (CHO) were X-irradiated in G2 stage of the cell cycle and immediately treated, in the presence of inactivated Sendai virus, with Neurospora endonuclease (E.C. 3.1.4.), an enzyme which is specific for cleaving single-stranded DNA. With this treatment, the frequencies of all types of chromosome aberrations increased when compared to X-irradiated controls. These results are interpreted as due to the conversion of some of the X-ray induced single-stranded DNA breaks into double-strand breaks by this enzyme. Similar enhancement due to this enzyme was found following treatment with methyl methanesulfonate (MMS) and bleomycin, but not following UV and mitomycin C. Addition of Micrococcus endonuclease and Neurospora endonuclease to the cells did not alter the frequencies of aberrations induced by UV. The introduction of enzymes with specific DNA-repair function offers possibilities to probe into the molecular events involved in the formation of structural chromosome aberrations induced by different classes of physical and chemical mutagens. (Auth.)

  10. Phagocytosis in Teleosts. Implications of the New Cells Involved

    Directory of Open Access Journals (Sweden)

    María Ángeles Esteban

    2015-12-01

    Full Text Available Phagocytosis is the process by which cells engulf some solid particles to form internal vesicles known as phagosomes. Phagocytosis is in fact a specific form of endocytosis involving the vesicular interiorization of particles. Phagocytosis is essentially a defensive reaction against infection and invasion of the body by foreign substances and, in the immune system, phagocytosis is a major mechanism used to remove pathogens and/or cell debris. For these reasons, phagocytosis in vertebrates has been recognized as a critical component of the innate and adaptive immune responses to pathogens. Furthermore, more recent studies have revealed that phagocytosis is also crucial for tissue homeostasis and remodeling. Professional phagocytes in teleosts are monocyte/macrophages, granulocytes and dendritic cells. Nevertheless, in recent years phagocytic properties have also been attributed to teleost lymphocytes and thrombocytes. The possible implications of such cells on this important biological process, new factors affecting phagocytosis, evasion of phagocytosis or new forms of phagocytosis will be considered and discussed.

  11. Experimental and computational evidence of halogen bonds involving astatine

    Science.gov (United States)

    Guo, Ning; Maurice, Rémi; Teze, David; Graton, Jérôme; Champion, Julie; Montavon, Gilles; Galland, Nicolas

    2018-03-01

    The importance of halogen bonds—highly directional interactions between an electron-deficient σ-hole moiety in a halogenated compound and an acceptor such as a Lewis base—is being increasingly recognized in a wide variety of fields from biomedicinal chemistry to materials science. The heaviest halogens are known to form stronger halogen bonds, implying that if this trend continues down the periodic table, astatine should exhibit the highest halogen-bond donating ability. This may be mitigated, however, by the relativistic effects undergone by heavy elements, as illustrated by the metallic character of astatine. Here, the occurrence of halogen-bonding interactions involving astatine is experimentally evidenced. The complexation constants of astatine monoiodide with a series of organic ligands in cyclohexane solution were derived from distribution coefficient measurements and supported by relativistic quantum mechanical calculations. Taken together, the results show that astatine indeed behaves as a halogen-bond donor—a stronger one than iodine—owing to its much more electrophilic σ-hole.

  12. Analysis of Amino Acid Residues of Potential Importance for Phosphati-dylserine Specificity of P4-type ATPase ATP8A2

    DEFF Research Database (Denmark)

    Mogensen, Louise; Vestergaard, Anna Lindeløv; Mikkelsen, Stine

    The asymmetric structure of the plasma membrane is maintained through internalization of phos-pholipids by the family of P4-ATPases by a poorly characterized mechanism. Studies in yeast point towards a non-classical pathway involving important residues of a two-gate mechanism [1]. Glycine-230...... 302 of ATP8A2 with alanine (N302A), tyrosine (N302Y) and serine (N302S). Furthermore, a triple mutant of ATP8A2 (Q95GQ96AN302S) was studied to reveal any cooperativity between the two gates, as observed in yeast [1]. The affinities of the mutants for phosphatidylserine and phosphatidylethanolamine...

  13. Importance of Country-of-Origin on Different Product Categories Purchase Decision

    Directory of Open Access Journals (Sweden)

    Krupka Zoran

    2017-12-01

    Full Text Available Country of origin is an important factor in product evaluation process as well as for purchase decision. Its importance depends on the amount of information consumers have about the product and product category. This paper investigates the importance of coutry of origin in purchase decision-making process for three different product categories: high risk and high level of consumer involvement in purchasing process (car, medium risk and midium level of consumer involvement in purchasing process (TV, and low risk and low level of consumer involvement in purchasing process (confectionery products. Also, this paper investigates importance of country of manufacturing for purchase decision-making process in relation to country of origin’s importance. Research was conducted on 215 respondents from Belgium and Republic of Croatia. Results have shown that country of origin is important only for car purchase, but not for TV and confectionery products. For all product categories, country of origin has been shown to be more important in the decision-making process than country of manufacturing.

  14. Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms.

    Science.gov (United States)

    Kloosterman, Wigard P; Tavakoli-Yaraki, Masoumeh; van Roosmalen, Markus J; van Binsbergen, Ellen; Renkens, Ivo; Duran, Karen; Ballarati, Lucia; Vergult, Sarah; Giardino, Daniela; Hansson, Kerstin; Ruivenkamp, Claudia A L; Jager, Myrthe; van Haeringen, Arie; Ippel, Elly F; Haaf, Thomas; Passarge, Eberhard; Hochstenbach, Ron; Menten, Björn; Larizza, Lidia; Guryev, Victor; Poot, Martin; Cuppen, Edwin

    2012-06-28

    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. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Molecular mechanisms of toxicity of important food-borne phytotoxins.

    Science.gov (United States)

    Rietjens, Ivonne M C M; Martena, Martijn J; Boersma, Marelle G; Spiegelenberg, Wim; Alink, Gerrit M

    2005-02-01

    At present, there is an increasing interest for plant ingredients and their use in drugs, for teas, or in food supplements. The present review describes the nature and mechanism of action of the phytochemicals presently receiving increased attention in the field of food toxicology. This relates to compounds including aristolochic acids, pyrrolizidine alkaloids, beta-carotene, coumarin, the alkenylbenzenes safrole, methyleugenol and estragole, ephedrine alkaloids and synephrine, kavalactones, anisatin, St. John's wort ingredients, cyanogenic glycosides, solanine and chaconine, thujone, and glycyrrhizinic acid. It can be concluded that several of these phytotoxins cause concern, because of their bioactivation to reactive alkylating intermediates that are able to react with cellular macromolecules causing cellular toxicity, and, upon their reaction with DNA, genotoxicity resulting in tumors. Another group of the phytotoxins presented is active without the requirement for bioactivation and, in most cases, these compounds appear to act as neurotoxins interacting with one of the neurotransmitter systems. Altogether, the examples presented illustrate that natural does not equal safe and that in modern society adverse health effects, upon either acute or chronic exposure to phytochemicals, can occur as a result of use of plant- or herb-based foods, teas, or other extracts.

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

    International Nuclear Information System (INIS)

    Huang, Lixing; Wang, Chonggang; Zhang, Youyu; Wu, Meifang; Zuo, Zhenghong

    2013-01-01

    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

  17. Divided care and the Third Way: user involvement in statutory and voluntary sector cancer services.

    Science.gov (United States)

    Tritter, J Q; Barley, V; Daykin, N; Evans, Simon; McNeill, Judith; Rimmer, James; Sanidas, M; Turton, Pat

    2003-07-01

    In health care, as in much of the public sphere, the voluntary sector is playing an increasingly large role in the funding, provision and delivery of services and nowhere is this more apparent than in cancer care. Simultaneously the growth of privatisation, marketisation and consumerism has engendered a rise in the promotion of 'user involvement' in health care. These changes in the organisation and delivery of health care, in part inspired by the 'Third Way' and the promotion of public and citizen participation, are particularly apparent in the British National Health Service. This paper presents initial findings from a three-year study of user involvement in cancer services. Using both case study and survey data, we explore the variation in the definition, aims, usefulness and mechanisms for involving users in the evaluation and development of cancer services across three Health Authorities in South West England. The findings have important implications for understanding shifts in power, autonomy and responsibility between patients, carers, clinicians and health service managers. The absence of any common definition of user involvement or its purpose underlines the limited trust between the different actors in the system and highlights the potentially negative impact of a Third Way health service.

  18. Mechanisms of radiation-induced neoplastic cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table.

  19. Mechanisms of radiation-induced neoplastic cell transformation

    International Nuclear Information System (INIS)

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table

  20. Photoprotection in Plants Optical Screening-based Mechanisms

    CERN Document Server

    Solovchenko, Alexei

    2010-01-01

    Optical screening of excessive and potentially harmful solar radiation is an important photoprotective mechanism, though it has received much less attention in comparison with other systems preventing photooxidative damage to photoautotrophic organisms. This photoprotection in the form of screening appears to be especially important for juvenile and senescing plants as well as under environmental stresses—i.e. in situations where the efficiency of enzymatic ROS elimination, DNA repair and other ‘classical’ photoprotective systems could be impaired. This book represents an attempt to develop an integral view of optical screening-based photoprotection in microalgae and higher plants. Towards this end, the key groups of pigments involved in the screening of ultraviolet and visible components of solar radiation in microalgae and higher plants, and the patterns of their accumulation and distribution within plant cells and tissues, are described. Special attention is paid to the manifestations of screening pi...

  1. Genotoxic potential of montmorillonite clay mineral and alteration in the expression of genes involved in toxicity mechanisms in the human hepatoma cell line HepG2.

    Science.gov (United States)

    Maisanaba, Sara; Hercog, Klara; Filipic, Metka; Jos, Ángeles; Zegura, Bojana

    2016-03-05

    Montmorillonite, also known as Cloisite(®)Na(+) (CNa(+)), is a natural clay with a wide range of well-documented and novel applications, such as pharmaceutical products or food packaging. Although considered a low toxic product, the expected increased exposure to CNa(+) arises concern on the potential consequences on human and environmental health especially as its genotoxicity has scarcely been investigated so far. Thus, we investigated, for the first time, the influence of non-cytotoxic concentrations of CNa(+) (15.65, 31.25 and 62.5 μg/mL) on genomic instability of human hepatoma cell line (HepG2) by determining the formation of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) with the Cytokinesis block micronucleus cytome assay. Further on we studied the influence of CNa(+) on the expression of several genes involved in toxicity mechanisms using the real-time quantitative PCR. The results showed that CNa(+) increased the number of MNi, while the numbers of NBUDs and NPBs were not affected. In addition it deregulated genes in all the groups studied, mainly after longer time of exposure. These findings provide the evidence that CNa(+) is potentially genotoxic. Therefore further studies that will elucidate the molecular mechanisms involved in toxic activity of CNa(+) are needed for hazard identification and human safety assessment. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Rock mechanics and the economics of cut-and-fill mining

    Energy Technology Data Exchange (ETDEWEB)

    Almgren, G.

    1980-05-15

    The application of rock mechanics to mining has great economic potential. Factors such as loss of ore, rock-dilution, possibilities of machanization and rock support are all influenced by the degree of rock mechanics involvement. In particular loss of ore is limited by the correct dimensioning of pillars and remnants. Rock-dilution, depending upon caving, can in the same way be mastered by the right dimensions of stopes and pillars and of rock supporting. Possibilities of mechanization depend upon sizes of drifts and stopes, stope availabilities and access to the stopes, all depending upon a considered rock mechanic investigation. Also shut-downs in the stopes owing to caving can be affected in the same way. Consequences on the mining economy for cut-and-fil mining are illustrated concerning loss of ore, rock-dilution, mechanization levels and rock support. The biggest influence can be made on rock-dilution and mechanization. Under special circumstances loss of ore can be of the same magnitude, namely if the ore production per year is directly influenced by the loss of ore and can not be compensated by other mining activities. Rock support is of less economic importance compared with rock-dilution and mechanization, presupposed no less of ore-production.

  3. Involvement of Endoplasmic Reticulum Stress in Capsaicin-Induced Apoptosis of Human Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Shengzhang Lin

    2013-01-01

    Full Text Available Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in both in vitro and in vivo systems, as well as the possible mechanisms involved. In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990 with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153, a marker of the endoplasmic-reticulum-stress- (ERS- mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover, in vivo studies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78, phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK, and phosphoeukaryotic initiation factor-2α (phospho-eIF2α, activating transcription factor 4 (ATF4 and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin.

  4. Importance of Country-of-Origin on Different Product Categories Purchase Decision

    OpenAIRE

    Krupka Zoran; Arežina Darija

    2017-01-01

    Country of origin is an important factor in product evaluation process as well as for purchase decision. Its importance depends on the amount of information consumers have about the product and product category. This paper investigates the importance of coutry of origin in purchase decision-making process for three different product categories: high risk and high level of consumer involvement in purchasing process (car), medium risk and midium level of consumer involvement in purchasing proce...

  5. Quantitative description of the regional mechanics of the left atria by electroanatomical mapping

    International Nuclear Information System (INIS)

    Kuklik, Pawel; Molaee, Payman; Brooks, Anthony G; John, Bobby; Worthley, Stephen G; Sanders, Prashanthan

    2010-01-01

    The left atrium is a complex chamber, which plays an integral role in the maintenance of physiologic hemodynamic and electrical stability of the heart and is involved in many disease states, most commonly atrial fibrillation. Preserving regions of the left atrium that contribute the greatest to atrial mechanical function during curative strategies for atrial fibrillation are important. We present here a new application of the CARTO electroanatomical mapping system in the assessment of the left atria mechanical function. Electroanatomical data were collected in course of the electrophysiological procedure in 11 control patients and 12 patients with paroxysmal atrial fibrillation. The three-dimensional geometry of the left atria was reconstructed in 10 ms intervals and segmented into distinct regions. For each segment, a regional ejection fraction was calculated. We found that anterior, septal and lateral segments have significantly greater regional ejection fraction than atria roof, inferior and posterior segments. Therefore, we hypothesize that in order to minimize the impact on atrial mechanical function, an important determinant of thromboembolic risk, damage should be minimized to these atrial regions

  6. Involvement of Auxin and Brassinosteroid in Dwarfism of Autotetraploid Apple (Malus × domestica).

    Science.gov (United States)

    Ma, Yue; Xue, Hao; Zhang, Lei; Zhang, Feng; Ou, Chunqing; Wang, Feng; Zhang, Zhihong

    2016-05-24

    The plant height is an important trait in fruit tree. However, the molecular mechanism on dwarfism is still poorly understood. We found that colchicine-induced autotetraploid apple plants (Malus × domestica) exhibited a dwarf phenotype. The vertical length of cortical parenchyma cells was shorter in autotetraploids than in diploids, by observing paraffin sections. Hormone levels of indoleacetic acid (IAA) and brassinosteroid (BR) were significantly decreased in 3- and 5-year-old autotetraploid plants. Digital gene expression (DGE) analysis showed that the differentially expressed genes were mainly involved in IAA and BR pathways. microRNA390 was significantly upregulated according to microarray analysis. Exogenous application of IAA and BR promoted stem elongation of both apple plants grown in medium. The results show that dwarfing in autotetraploid apple plants is most likely regulated by IAA and BR. The dwarf phenotype of autotetraploid apple plants could be due to accumulation of miR390 after genome doubling, leading to upregulation of apple trans-acting short-interfering RNA 3 (MdTAS3) expression, which in turn downregulates the expression of MdARF3. Overall, this leads to partial interruption of the IAA and BR signal transduction pathway. Our study provides important insights into the molecular mechanisms underlying dwarfism in autopolyploid apple plants.

  7. Beyond the therapeutic shackles of the monoamines: New mechanisms in bipolar disorder biology.

    Science.gov (United States)

    Data-Franco, João; Singh, Ajeet; Popovic, Dina; Ashton, Melanie; Berk, Michael; Vieta, Eduard; Figueira, M L; Dean, Olivia M

    2017-01-04

    Multiple novel biological mechanisms putatively involved in the etiology of bipolar disorders are being explored. These include oxidative stress, altered glutamatergic neurotransmission, mitochondrial dysfunction, inflammation, cell signaling, apoptosis and impaired neurogenesis. Important clinical translational potential exists for such mechanisms to help underpin development of novel therapeutics - much needed given limitations of current therapies. These new mechanisms also help improve our understanding of how current therapeutics might exert their effects. Lithium, for example, appears to have antioxidant, immunomodulatory, signaling, anti-apoptotic and neuroprotective properties. Similar properties have been attributed to other mood stabilizers such as valproate, lamotrigine, and quetiapine. Perhaps of greatest translational value has been the recognition of such mechanisms leading to the emergence of novel therapeutics for bipolar disorders. These include the antioxidant N-acetylcysteine, the anti-inflammatory celecoxib, and ketamine - with effects on the glutamatergic system and microglial inhibition. We review these novel mechanisms and emerging therapeutics, and comment on next steps in this space. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Applications in solid mechanics

    DEFF Research Database (Denmark)

    Ølgaard, Kristian Breum; Wells, Garth N.

    2012-01-01

    Problems in solid mechanics constitute perhaps the largest field of application of finite element methods. The vast majority of solid mechanics problems involve the standard momentum balance equation, posed in a Lagrangian setting, with different models distinguished by the choice of nonlinear...... or linearized kinematics, and the constitutive model for determining the stress. For some common models, the constitutive relationships are rather complex. This chapter addresses a number of canonical solid mechanics models in the context of automated modeling, and focuses on some pertinent issues that arise...

  9. Revelations from the Nematode Caenorhabditis elegans on the Complex Interplay of Metal Toxicological Mechanisms

    Directory of Open Access Journals (Sweden)

    Ebany J. Martinez-Finley

    2011-01-01

    Full Text Available Metals have been definitively linked to a number of disease states. Due to the widespread existence of metals in our environment from both natural and anthropogenic sources, understanding the mechanisms of their cellular detoxification is of upmost importance. Organisms have evolved cellular detoxification systems including glutathione, metallothioneins, pumps and transporters, and heat shock proteins to regulate intracellular metal levels. The model organism, Caenorhabditis elegans (C. elegans, contains these systems and provides several advantages for deciphering the mechanisms of metal detoxification. This review provides a brief summary of contemporary literature on the various mechanisms involved in the cellular detoxification of metals, specifically, antimony, arsenic, cadmium, copper, manganese, mercury, and depleted uranium using the C. elegans model system for investigation and analysis.

  10. Submillisecond Elastic Recoil Reveals Molecular Origins of Fibrin Fiber Mechanics

    Science.gov (United States)

    Hudson, Nathan E.; Ding, Feng; Bucay, Igal; O’Brien, E. Timothy; Gorkun, Oleg V.; Superfine, Richard; Lord, Susan T.; Dokholyan, Nikolay V.; Falvo, Michael R.

    2013-01-01

    Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering. These results have inspired a variety of molecular models for fibrin’s elasticity, ranging from reversible protein unfolding to rubber-like elasticity. An important property that has not been explored is the timescale of elastic recoil, a parameter that is critical for fibrin’s mechanical function and places a temporal constraint on molecular models of fiber elasticity. Using high-frame-rate imaging and atomic force microscopy-based nanomanipulation, we measured the recoil dynamics of individual fibrin fibers and found that the recoil was orders of magnitude faster than anticipated from models involving protein refolding. We also performed steered discrete molecular-dynamics simulations to investigate the molecular origins of the observed recoil. Our results point to the unstructured αC regions of the otherwise structured fibrin molecule as being responsible for the elastic recoil of the fibers. PMID:23790375

  11. Learn new mechanisms from life

    International Nuclear Information System (INIS)

    Ji Qing; Luo Mingyan; Tong Xiaolin; Zhang Bo; Zhang Hui

    2005-01-01

    On the basis of the important experimental results of molecular motors, it was pointed out that the moving process of molecular motors is a coupling biological process of chemical-electrical-mechanical processes. This clever mechanism of energy conversion on the molecular level with several processes coupled together had never been observed before. The understanding of this new mechanism is an important step towards the understanding of life and an important content of what we can learn from life. The authors introduced here the status of the investigations on the mechanism for the force generation of kinesin and the studies of the authors in this field. (authors)

  12. Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism

    Directory of Open Access Journals (Sweden)

    Xinmiao Yan

    2016-03-01

    Full Text Available Pyrrolizidine Alkaloids (PAs are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1 and glutathione peroxidase 1 (GPX1 targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

  13. Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism.

    Science.gov (United States)

    Yan, Xinmiao; Kang, Hong; Feng, Jun; Yang, Yiyan; Tang, Kailin; Zhu, Ruixin; Yang, Li; Wang, Zhengtao; Cao, Zhiwei

    2016-03-07

    Pyrrolizidine Alkaloids (PAs) are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH) metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types) in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1) and glutathione peroxidase 1 (GPX1) targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

  14. Relativistic quantum mechanics

    International Nuclear Information System (INIS)

    Ollitrault, J.Y.

    1998-12-01

    These notes form an introduction to relativistic quantum mechanics. The mathematical formalism has been reduced to the minimum in order to enable the reader to calculate elementary physical processes. The second quantification and the field theory are the logical followings of this course. The reader is expected to know analytical mechanics (Lagrangian and Hamiltonian), non-relativistic quantum mechanics and some basis of restricted relativity. The purpose of the first 3 chapters is to define the quantum mechanics framework for already known notions about rotation transformations, wave propagation and restricted theory of relativity. The next 3 chapters are devoted to the application of relativistic quantum mechanics to a particle with 0,1/5 and 1 spin value. The last chapter deals with the processes involving several particles, these processes require field theory framework to be thoroughly described. (A.C.)

  15. Characterizing Density and Complexity of Imported Cargos

    Energy Technology Data Exchange (ETDEWEB)

    Birrer, Nathaniel [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Divin, Charles [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Glenn, Steven [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Martz, Harry [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-08-01

    X-ray inspection systems are used to detect radiological and nuclear threats in imported cargo. In order to better understand performance of these systems, system imaging capabilities and the characteristics of imported cargo need to be determined. This project involved calculation of the modulation transfer function as a metric of system imaging performance and a study of the density and inhomogeneity of imported cargos, which have been shown to correlate with human analysts, threat detection performance.

  16. [Neurohumoral mechanisms for vasovagal syncopes. Part I].

    Science.gov (United States)

    Gajek, Jacek; Zyśko, Dorota

    2003-04-01

    Vasovagal syncope is defined as a reflex loss of consciousness related to reaction to various stimuli as orthostatic stress, pain or emotions connected with loss of muscle postural tone. The aetiology of this disorder is still unknown. The imbalance between the parts of autonomic nervous system and other homeostasis-related systems as renin-angiotensin-aldosterone system, peptides as endothelin, neuropeptide Y, vasopressin, adrenomedullin and cAMP, adenosine and AMP can play an important role in the development of vasovagal syncope. In the first part of the paper the authors describe the mechanisms involved in the development of vasovagal reaction, pathophysiology of the head-up tilt test and the role of autonomic nervous system.

  17. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, ...

  18. A novel mechanism of E2F1 regulation via nucleocytoplasmic shuttling: determinants of nuclear import and export.

    Science.gov (United States)

    Ivanova, Iordanka A; Vespa, Alisa; Dagnino, Lina

    2007-09-01

    E2F1 is a transcription factor central for cell survival, proliferation, and repair following genomic insult. Depending on the cell type and conditions, E2F1 can induce apoptosis in transformed cells, behaving as a tumour suppressor, or impart growth advantages favouring tumour formation. The pleiotropic functions of E2F1 are a likely consequence of its ability to transcriptionally control a wide variety of target genes, and require tight regulation of its activity at multiple levels. Although sequestration of proteins to particular cellular compartments is a well-established regulatory mechanism, virtually nothing is known about its contribution to modulation of E2F1 target gene expression. We have examined the subcellular trafficking of E2F1 and, contrary to the widely held notion that this factor is constitutively nuclear, we now demonstrate that it is subjected to continuous nucleocytoplasmic shuttling. We have also defined two nuclear localization domains and a nuclear export region, which mediates CRM1-dependent transit out of the nucleus. The predominant subcellular location of E2F1 is likely determined by the balance between the activity of nuclear import and export domains, and can be modulated by differentiation stimuli in epidermal cells. Thus, we have identified a hitherto unrecognized mechanism to control E2F1 function through modulation of its subcellular localization.

  19. Classical treatments of quantum mechanical effects in collisions of weakly bound complexes

    International Nuclear Information System (INIS)

    Lopez, Jose G.; McCoy, Anne B.

    2005-01-01

    Classical and quantum simulations of Ne + Ar 2 collision dynamics are performed in order to investigate where quantum mechanical effects are most important and where classical simulations provide good descriptions of the dynamics. It is found that when Ar 2 is in a low-lying vibrational state, the differences between the results of quantum and quasiclassical simulations are profound. However, excellent agreement between the results of the quantum and classical simulations can be achieved when the initial conditions for the classical trajectories are sampled from the quantum phase space distribution given by the Wigner function. These effects are largest when collisions occur under constrained geometries or when Ar 2 is in its ground vibrational state. The results of this work suggest that sampling the initial conditions using the Wigner function provides a straightforward way to incorporate the most important quantum mechanical effects in simulations of collisions involving very cold weakly bound complexes

  20. Classical fracture mechanics methods

    International Nuclear Information System (INIS)

    Schwalbe, K.H.; Heerens, J.; Landes, J.D.

    2007-01-01

    Comprehensive Structural Integrity is a reference work which covers all activities involved in the assurance of structural integrity. It provides engineers and scientists with an unparalleled depth of knowledge in the disciplines involved. The new online Volume 11 is dedicated to the mechanical characteristics of materials. This paper contains the chapter 11.02 of this volume and is structured as follows: Test techniques; Analysis; Fracture behavior; Fracture toughness tests for nonmetals

  1. The role of Customer Involvement in Library E-services

    DEFF Research Database (Denmark)

    Scupola, Ada; Nikolajsen, H. W.

    2009-01-01

    We investigate customer involvement in the development of e-service within research Libraries. By revisiting earlier research on innovation processes as well as newer research on new product and new service development we derive a conceptual model on different actors that are important in the pro......We investigate customer involvement in the development of e-service within research Libraries. By revisiting earlier research on innovation processes as well as newer research on new product and new service development we derive a conceptual model on different actors that are important...

  2. Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-Jun-N-terminal kinase signaling.

    Science.gov (United States)

    Eshraghi, Adrien A; Gupta, Chhavi; Van De Water, Thomas R; Bohorquez, Jorge E; Garnham, Carolyn; Bas, Esperanza; Talamo, Victoria Maria

    2013-03-01

    To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM-111. An animal model of cochlear implantation. Guinea pigs' hearing thresholds were measured by auditory brainstem response (ABR) before and after cochlear implantation in four groups: EIT; pretreated with hyaluronate gel 30 minutes before EIT (EIT+Gel); pretreated with hyaluronate gel/AM-111 30 minutes before EIT (EIT+AM-111); and unoperated contralateral ears as controls. Neurofilament, synapsin, and fluorescein isothiocyanate (FITC)-phalloidin staining for hair cell counts were performed at 90 days post-EIT. Immunostaining for 4-hydroxy-2-nonenal (HNE), activated caspase-3, CellROX, and phospho-c-Jun were performed at 24 hours post-EIT. ABR thresholds increased post-EIT in the cochleae of EIT only and EIT+Gel treated animals. There was no significant increase in hearing thresholds in cochleae from either EIT+AM-111 treated or unoperated control ears. AM-111 protection of organ of Corti sensory elements (i.e., hair cells [HCs], supporting cells [SCs], nerve fibers, and synapses) was documented at 3 months post-EIT. Immunostaining of 24-hour post-EIT specimens demonstrated increased levels of HNE in HCs and SCs; increased levels of CellROX and activation of caspase-3 was observed only in SCs, and phosphorylation of c-Jun occurred only in HCs of the EIT-only and EIT+Gel specimens. There was no immunostaining for either HNE, CellROX, caspase-3, or phospho-c-Jun in the organ of Corti specimens from AM-111 treated cochleae. Molecular mechanisms involved in programmed cell death of HCs are different than the ones involved in programmed cell death of SCs. Local delivery of AM-111 provided a significant level of protection against EIT-induced hearing losses, HC losses, and damage to neural elements. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  3. Mechanisms involved in the differential recovery of CD4 and CD8 T-lymphocytes after local irradiation in mice

    International Nuclear Information System (INIS)

    De Ruysscher, D; Waer, M.; Vandeputte, M.; Van der Schueren, E.

    1990-01-01

    The mechanisms involved in the differential recovery of CD4 (helper/inducer phenotype) and CD8 (Cytotoxic/suppressor phenotype) T-lymphocytes after fractionated local irradiation were investigated. In mice, a better recovery of CD4 cells than of CD8 cells was found, while the reverse has been described in humans. Differences in radiosensivitity between CD4 and CD8 mouse splenocytes could not be found. No sequestration of CD8 cells in irradiated tissues could be demonstrated. Irradiation of the thymus did not influence the observed immune changes. Altered thymic production of CD4 and CD8 cells could be excluded by intrathymic injection of FITC (fluorescein isothiocyanate). Hindlimb and tail irradiation did suggest that the differential recovery of CD4 and CD8 T-lymphocytes after local irradiation is determined by extrathymic factors in man and mice, and that the observed differences in immune recovery between man and mice are due to defective thymic function in the former and normal function in the latter. (author). 12 refs.; 5 figs.; 2 tabs

  4. Clathrin- and caveolin-independent entry of human papillomavirus type 16--involvement of tetraspanin-enriched microdomains (TEMs.

    Directory of Open Access Journals (Sweden)

    Gilles Spoden

    Full Text Available BACKGROUND: Infectious entry of human papillomaviruses into their host cells is an important step in the viral life cycle. For cell binding these viruses use proteoglycans as initial attachment sites. Subsequent transfer to a secondary receptor molecule seems to be involved in virus uptake. Depending on the papillomavirus subtype, it has been reported that entry occurs by clathrin- or caveolin-mediated mechanisms. Regarding human papillomavirus type 16 (HPV16, the primary etiologic agent for development of cervical cancer, clathrin-mediated endocytosis was described as infectious entry pathway. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence and infection studies we show in contrast to published data that infectious entry of HPV16 occurs in a clathrin- and caveolin-independent manner. Inhibition of clathrin- and caveolin/raft-dependent endocytic pathways by dominant-negative mutants and siRNA-mediated knockdown, as well as inhibition of dynamin function, did not impair infection. Rather, we provide evidence for involvement of tetraspanin-enriched microdomains (TEMs in HPV16 endocytosis. Following cell attachment, HPV16 particles colocalized with the tetraspanins CD63 and CD151 on the cell surface. Notably, tetraspanin-specific antibodies and siRNA inhibited HPV16 cell entry and infection, confirming the importance of TEMs for infectious endocytosis of HPV16. CONCLUSIONS/SIGNIFICANCE: Tetraspanins fulfill various roles in the life cycle of a number of important viral pathogens, including human immunodeficiency virus (HIV and hepatitis C virus (HCV. However, their involvement in endocytosis of viral particles has not been proven. Our data indicate TEMs as a novel clathrin- and caveolin-independent invasion route for viral pathogens and especially HPV16.

  5. Nuclear import of glucokinase in pancreatic beta-cells is mediated by a nuclear localization signal and modulated by SUMOylation.

    Science.gov (United States)

    Johansson, Bente Berg; Fjeld, Karianne; Solheim, Marie Holm; Shirakawa, Jun; Zhang, Enming; Keindl, Magdalena; Hu, Jiang; Lindqvist, Andreas; Døskeland, Anne; Mellgren, Gunnar; Flatmark, Torgeir; Njølstad, Pål Rasmus; Kulkarni, Rohit N; Wierup, Nils; Aukrust, Ingvild; Bjørkhaug, Lise

    2017-10-15

    The localization of glucokinase in pancreatic beta-cell nuclei is a controversial issue. Although previous reports suggest such a localization, the mechanism for its import has so far not been identified. Using immunofluorescence, subcellular fractionation and mass spectrometry, we present evidence in support of glucokinase localization in beta-cell nuclei of human and mouse pancreatic sections, as well as in human and mouse isolated islets, and murine MIN6 cells. We have identified a conserved, seven-residue nuclear localization signal ( 30 LKKVMRR 36 ) in the human enzyme. Substituting the residues KK 31,32 and RR 35,36 with AA led to a loss of its nuclear localization in transfected cells. Furthermore, our data indicates that SUMOylation of glucokinase modulates its nuclear import, while high glucose concentrations do not significantly alter the enzyme nuclear/cytosolic ratio. Thus, for the first time, we provide data in support of a nuclear import of glucokinase mediated by a redundant mechanism, involving a nuclear localization signal, and which is modulated by its SUMOylation. These findings add new knowledge to the functional role of glucokinase in the pancreatic beta-cell. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Signal transduction pathways involved in mechanotransduction in bone cells

    International Nuclear Information System (INIS)

    Liedert, Astrid; Kaspar, Daniela; Blakytny, Robert; Claes, Lutz; Ignatius, Anita

    2006-01-01

    Several in vivo and in vitro studies with different loading regimens showed that mechanical stimuli have an influence on proliferation and differentiation of bone cells. Prerequisite for this influence is the transduction of mechanical signals into the cell, a phenomenon that is termed mechanotransduction, which is essential for the maintenance of skeletal homeostasis in adults. Mechanoreceptors, such as the integrins, cadherins, and stretch-activated Ca 2+ channels, together with various signal transduction pathways, are involved in the mechanotransduction process that ultimately regulates gene expression in the nucleus. Mechanotransduction itself is considered to be regulated by hormones, the extracellular matrix of the osteoblastic cells and the mode of the mechanical stimulus

  7. Glutamate-induced apoptosis in neuronal cells is mediated via caspase-dependent and independent mechanisms involving calpain and caspase-3 proteases as well as apoptosis inducing factor (AIF and this process is inhibited by equine estrogens

    Directory of Open Access Journals (Sweden)

    Bhavnani Bhagu R

    2006-06-01

    Full Text Available Abstract Background Glutamate, a major excitatory amino acid neurotransmitter, causes apoptotic neuronal cell death at high concentrations. Our previous studies have shown that depending on the neuronal cell type, glutamate-induced apoptotic cell death was associated with regulation of genes such as Bcl-2, Bax, and/or caspase-3 and mitochondrial cytochrome c. To further delineate the intracellular mechanisms, we have investigated the role of calpain, an important calcium-dependent protease thought to be involved in apoptosis along with mitochondrial apoptosis inducing factor (AIF and caspase-3 in primary cortical cells and a mouse hippocampal cell line HT22. Results Glutamate-induced apoptotic cell death in neuronal cells was associated with characteristic DNA fragmentation, morphological changes, activation of calpain and caspase-3 as well as the upregulation and/or translocation of AIF from mitochondria into cytosol and nuclei. Our results reveal that primary cortical cells and HT22 cells display different patterns of regulation of these genes/proteins. In primary cortical cells, glutamate induces activation of calpain, caspase-3 and translocation of AIF from mitochondria to cytosol and nuclei. In contrast, in HT22 cells, only the activation of calpain and upregulation and translocation of AIF occurred. In both cell types, these processes were inhibited/reversed by 17β-estradiol and Δ8,17β-estradiol with the latter being more potent. Conclusion Depending upon the neuronal cell type, at least two mechanisms are involved in glutamate-induced apoptosis: a caspase-3-dependent pathway and a caspase-independent pathway involving calpain and AIF. Since HT22 cells lack caspase-3, glutamate-induced apoptosis is mediated via the caspase-independent pathway in this cell line. Kinetics of this apoptotic pathway further indicate that calpain rather than caspase-3, plays a critical role in the glutamate-induced apoptosis. Our studies further indicate

  8. Using Airborne Remote Sensing to Increase Situational Awareness in Civil Protection and Humanitarian Relief - the Importance of User Involvement

    Science.gov (United States)

    Römer, H.; Kiefl, R.; Henkel, F.; Wenxi, C.; Nippold, R.; Kurz, F.; Kippnich, U.

    2016-06-01

    Enhancing situational awareness in real-time (RT) civil protection and emergency response scenarios requires the development of comprehensive monitoring concepts combining classical remote sensing disciplines with geospatial information science. In the VABENE++ project of the German Aerospace Center (DLR) monitoring tools are being developed by which innovative data acquisition approaches are combined with information extraction as well as the generation and dissemination of information products to a specific user. DLR's 3K and 4k camera system which allow for a RT acquisition and pre-processing of high resolution aerial imagery are applied in two application examples conducted with end users: a civil protection exercise with humanitarian relief organisations and a large open-air music festival in cooperation with a festival organising company. This study discusses how airborne remote sensing can significantly contribute to both, situational assessment and awareness, focussing on the downstream processes required for extracting information from imagery and for visualising and disseminating imagery in combination with other geospatial information. Valuable user feedback and impetus for further developments has been obtained from both applications, referring to innovations in thematic image analysis (supporting festival site management) and product dissemination (editable web services). Thus, this study emphasises the important role of user involvement in application-related research, i.e. by aligning it closer to user's requirements.

  9. Drug involvement in fatal overdoses

    Directory of Open Access Journals (Sweden)

    Christopher J. Ruhm

    2017-12-01

    Full Text Available Death certificate data from the Multiple Cause of Death (MCOD files were analyzed to better understand the drug categories most responsible for the increase in fatal overdoses occurring between 1999 and 2014. Statistical adjustment methods were used to account for the understatement in reported drug involvement occurring because death certificates frequently do not specify which drugs were involved in the deaths. The frequency of combination drug use introduced additional uncertainty and so a distinction was made between any versus exclusive drug involvement. Many results were sensitive to the starting and ending years chosen for examination. Opioid analgesics played a major role in the increased drug deaths for analysis windows starting in 1999 but other drugs, particularly heroin, became more significant for recent time periods. Combination drug use was important for all time periods and needs to be accounted for when designing policies to slow or reverse the increase in overdose deaths.

  10. Structural and Molecular Mechanism of CdpR Involved in Quorum-Sensing and Bacterial Virulence in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    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.

  11. Mechanical Systems, Classical Models

    CERN Document Server

    Teodorescu, Petre P

    2009-01-01

    This third volume completes the Work Mechanical Systems, Classical Models. The first two volumes dealt with particle dynamics and with discrete and continuous mechanical systems. The present volume studies analytical mechanics. Topics like Lagrangian and Hamiltonian mechanics, the Hamilton-Jacobi method, and a study of systems with separate variables are thoroughly discussed. Also included are variational principles and canonical transformations, integral invariants and exterior differential calculus, and particular attention is given to non-holonomic mechanical systems. The author explains in detail all important aspects of the science of mechanics, regarded as a natural science, and shows how they are useful in understanding important natural phenomena and solving problems of interest in applied and engineering sciences. Professor Teodorescu has spent more than fifty years as a Professor of Mechanics at the University of Bucharest and this book relies on the extensive literature on the subject as well as th...

  12. Family Economic Status and Parental Involvement: Influences of Parental Expectation and Perceived Barriers

    Science.gov (United States)

    Wang, Yiji; Deng, Ciping; Yang, Xiangdong

    2016-01-01

    Parental involvement in children's education is a critical factor associated with children's socio-emotional and educational outcomes. However, low parental involvement occurs more often among economically disadvantaged families. It is unclear what mechanisms may explain the association between family economic status and parents' educational…

  13. Mechanical stimulation induces mTOR signaling via an ERK-independent mechanism: implications for a direct activation of mTOR by phosphatidic acid.

    Directory of Open Access Journals (Sweden)

    Jae Sung You

    Full Text Available Signaling by mTOR is a well-recognized component of the pathway through which mechanical signals regulate protein synthesis and muscle mass. However, the mechanisms involved in the mechanical regulation of mTOR signaling have not been defined. Nevertheless, recent studies suggest that a mechanically-induced increase in phosphatidic acid (PA may be involved. There is also evidence which suggests that mechanical stimuli, and PA, utilize ERK to induce mTOR signaling. Hence, we reasoned that a mechanically-induced increase in PA might promote mTOR signaling via an ERK-dependent mechanism. To test this, we subjected mouse skeletal muscles to mechanical stimulation in the presence or absence of a MEK/ERK inhibitor, and then measured several commonly used markers of mTOR signaling. Transgenic mice expressing a rapamycin-resistant mutant of mTOR were also used to confirm the validity of these markers. The results demonstrated that mechanically-induced increases in p70(s6k T389 and 4E-BP1 S64 phosphorylation, and unexpectedly, a loss in total 4E-BP1, were fully mTOR-dependent signaling events. Furthermore, we determined that mechanical stimulation induced these mTOR-dependent events, and protein synthesis, through an ERK-independent mechanism. Similar to mechanical stimulation, exogenous PA also induced mTOR-dependent signaling via an ERK-independent mechanism. Moreover, PA was able to directly activate mTOR signaling in vitro. Combined, these results demonstrate that mechanical stimulation induces mTOR signaling, and protein synthesis, via an ERK-independent mechanism that potentially involves a direct interaction of PA with mTOR. Furthermore, it appears that a decrease in total 4E-BP1 may be part of the mTOR-dependent mechanism through which mechanical stimuli activate protein synthesis.

  14. Advances in heterocycle synthesis via [3+m]-cycloaddition reactions involving an azaoxyallyl cation as the key intermediate.

    Science.gov (United States)

    Xuan, Jun; Cao, Xia; Cheng, Xiao

    2018-05-17

    Heterocyclic compounds are widely found in many natural isolates and medicinally relevant compounds, as well as some fine chemicals. The development of general and efficient methods for the construction of heterocyclic compounds is one of the most important tasks in synthetic organic chemistry. Along these lines, [3+m]-cycloaddition reactions involving in situ generated azaoxyallyl cations as the 3-atom units have emerged as a powerful method for the synthesis of nitrogen-containing heterocycles. In this feature article, we highlight recent advances in this rapidly growing area, mainly focusing on the reaction design as well as the reaction mechanism.

  15. A successful effort to involve stakeholders in a facility siting decision using LIPS with stakeholder involvement

    International Nuclear Information System (INIS)

    Merkhofer, L.; Conway, R.; Anderson, B.

    1995-01-01

    Local public opposition to federal bureaucratic decisions has resulted in public agencies rethinking the role of stakeholders in decision making. Efforts to include stakeholders directly in the decision-making process are on the increase. Unfortunately, many attempts to involve members of the public in decisions involving complex technical issues have failed. A key problem has been defining a meaningful role for the public in the process of arriving at a technical decision. This paper describes a successful effort by Sandia National Laboratories (SNL) in New Mexico to involve stakeholders in an important technical decision associated with its Environmental Restoration (ER) Project. The decision was where to locate a Corrective Action Management Unit (CAMU), a facility intended to consolidate and store wastes generated from the cleanup of hazardous waste sites. A formal priority setting process known as the Laboratory Integration Prioritization System (LIPS) was adapted to provide an approach for involving the public. Although rarely applied to stakeholder participation, the LIPS process proved surprisingly effective. It produced a consensus over a selected site and enhanced public trust and understanding of Project activities

  16. Mechanism-based classification of pain for physical therapy management in palliative care: A clinical commentary

    Directory of Open Access Journals (Sweden)

    Senthil P Kumar

    2011-01-01

    Full Text Available Pain relief is a major goal for palliative care in India so much that most palliative care interventions necessarily begin first with pain relief. Physical therapists play an important role in palliative care and they are regarded as highly proficient members of a multidisciplinary healthcare team towards management of chronic pain. Pain necessarily involves three different levels of classification-based upon pain symptoms, pain mechanisms and pain syndromes. Mechanism-based treatments are most likely to succeed compared to symptomatic treatments or diagnosis-based treatments. The objective of this clinical commentary is to update the physical therapists working in palliative care, on the mechanism-based classification of pain and its interpretation, with available therapeutic evidence for providing optimal patient care using physical therapy. The paper describes the evolution of mechanism-based classification of pain, the five mechanisms (central sensitization, peripheral neuropathic, nociceptive, sympathetically maintained pain and cognitive-affective are explained with recent evidence for physical therapy treatments for each of the mechanisms.

  17. Basic MR relaxation mechanisms and contrast agent design.

    Science.gov (United States)

    De León-Rodríguez, Luis M; Martins, André F; Pinho, Marco C; Rofsky, Neil M; Sherry, A Dean

    2015-09-01

    The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists, largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities. In this review we detail the many important considerations when pursuing the design and use of MR contrast media. We offer a perspective on the importance of chemical stability, particularly kinetic stability, and how this influences one's thinking about the safety of metal-ligand-based contrast agents. We discuss the mechanisms involved in MR relaxation in the context of probe design strategies. A brief description of currently available contrast agents is accompanied by an in-depth discussion that highlights promising MRI contrast agents in the development of future clinical and research applications. Our intention is to give a diverse audience an improved understanding of the factors involved in developing new types of safe and highly efficient MR contrast agents and, at the same time, provide an appreciation of the insights into physiology and disease that newer types of responsive agents can provide. © 2015 Wiley Periodicals, Inc.

  18. Molecular Mechanisms of Appetite Regulation

    Directory of Open Access Journals (Sweden)

    Ji Hee Yu

    2012-12-01

    Full Text Available The prevalence of obesity has been rapidly increasing worldwide over the last several decades and has become a major health problem in developed countries. The brain, especially the hypothalamus, plays a key role in the control of food intake by sensing metabolic signals from peripheral organs and modulating feeding behaviors. To accomplish these important roles, the hypothalamus communicates with other brain areas such as the brainstem and reward-related limbic pathways. The adipocyte-derived hormone leptin and pancreatic β-cell-derived insulin inform adiposity to the hypothalamus. Gut hormones such as cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1, and oxyntomodulin transfer satiety signals to the brain and ghrelin relays hunger signals. The endocannabinoid system and nutrients are also involved in the physiological regulation of food intake. In this article, we briefly review physiological mechanisms of appetite regulation.

  19. Deleted in malignant brain tumour 1 (DMBT1) is secreted in the oviduct and involved in the mechanism of fertilization in equine and porcine species

    DEFF Research Database (Denmark)

    Ambruosi, Barbara; Accogli, Gianluca; Douet, Cecile

    2013-01-01

    fertilization rate, and that this effect is cancelled by the addition of antibodies, in both porcine and equine species. Moreover, pre-incubation of oocytes with recombinant DMBT1 induces an increase of the monospermic fertilization rate in the pig, confirming an involvement of DMBT1 in the fertilization...... allowed us to identify the DMBT1 protein as well as a DMBT1-like protein in several mammals. Our results strongly suggest an important role of DMBT1 in the process of fertilization.......Oviductal environment affects preparation of gametes for fertilization, fertilization itself, and the subsequent embryo development. The aim of this study is to evaluate the effect of oviductal fluid and the possible involvement of Deleted in Malignant Brain Tumours 1 (DMBT1) on in vitro...

  20. New Mechanisms of Mercury Binding to Peat

    Science.gov (United States)

    Nagy, K. L.; Manceau, A.; Gasper, J. D.; Ryan, J. N.; Aiken, G. R.

    2007-12-01

    Mercury can be immobilized in the aquatic environment by binding to peat, a solid form of natural organic matter. Binding mechanisms can vary in strength and reversibility, and therefore will control concentrations of bioreactive mercury, may explain rates of mercury methylation, and are important for designing approaches to improve water quality using natural wetlands or engineered phytoremediation schemes. In addition, strong binding between mercury and peat is likely to result in the fixation of mercury that ultimately resides in coal. The mechanisms by which aqueous mercury at low concentrations reacts with both dissolved and solid natural organic matter remain incompletely understood, despite recent efforts. We have identified three distinct binding mechanisms of divalent cationic mercury to solid peats from the Florida Everglades using EXAFS spectroscopic data (FAME beamline, European Synchrotron Radiation Facility (ESRF)) obtained on experimental samples as compared to relevant references including mercury-bearing solids and mercury bound to various organic molecules. The proportions of the three molecular configurations vary with Hg concentration, and two new configurations that involve sulfur ligands occur at Hg concentrations up to about 4000 ppm. The binding mechanism at the lowest experimental Hg concentration (60-80 ppm) elucidates published reports on the inhibition of metacinnabar formation in the presence of Hg-bearing solutions and dissolved natural organic matter, and also, the differences in extent of mercury methylation in distinct areas of the Florida Everglades.

  1. Possible Involvement of Hydrosulfide in B12-Dependent Methyl Group Transfer

    Directory of Open Access Journals (Sweden)

    John I. Toohey

    2017-04-01

    Full Text Available Evidence from several fields of investigation lead to the hypothesis that the sulfur atom is involved in vitamin B12-dependent methyl group transfer. To compile the evidence, it is necessary to briefly review the following fields: methylation, the new field of sulfane sulfur/hydrogen sulfide (S°/H2S, hydrosulfide derivatives of cobalamins, autoxidation of hydrosulfide radical, radical S-adenosylmethionine methyl transfer (RSMT, and methionine synthase (MS. Then, new reaction mechanisms for B12-dependent methyl group transfer are proposed; the mechanisms are facile and overcome difficulties that existed in previously-accepted mechanisms. Finally, the theory is applied to the effect of S°/H2S in nerve tissue involving the “hypomethylation theory” that was proposed 50 years ago to explain the neuropathology resulting from deficiency of vitamin B12 or folic acid. The conclusions are consistent with emerging evidence that sulfane sulfur/hydrogen sulfide may be beneficial in treating Alzheimer’s disease.

  2. Parallel analysis and orthogonal identification of N-glycans with different capillary electrophoresis mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Hua-tao [Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore); NUS Environmental Research Institute, 5A Engineering Drive 1, T-Lab Building, Singapore 117411 (Singapore); Su, Min; Rifai, Farida Nur [Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore); Li, Pingjing [NUS Environmental Research Institute, 5A Engineering Drive 1, T-Lab Building, Singapore 117411 (Singapore); Li, Sam F.Y., E-mail: chmlifys@nus.edu.sg [Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore); NUS Environmental Research Institute, 5A Engineering Drive 1, T-Lab Building, Singapore 117411 (Singapore)

    2017-02-08

    The deep involvement of glycans or carbohydrate moieties in biological processes makes glycan patterns an important direction for the clinical and medicine researches. A multiplexing CE mapping method for glycan analysis was developed in this study. By applying different CE separation mechanisms, the potential of combined parallel applications of capillary zone electrophoresis (CZE), micellar electrokinetic chromatography (MEKC) and capillary gel electrophoresis (CGE) for rapid and accurate identification of glycan was investigated. The combination of CZE and MEKC demonstrated enhancing chromatography separation capacity without the compromises of sample pre-treatment and glycan concentration. The separation mechanisms for multiplexing platform were selected based on the orthogonalities of the separation of glycan standards. MEKC method exhibited promising ability for the analysis of small GU value glycans and thus complementing the unavailability of CZE. The method established required only small amount of samples, simple instrument and single fluorescent labelling for sensitive detection. This integrated method can be used to search important glycan patterns appearing in biopharmaceutical products and other glycoproteins with clinical importance. - Highlights: • Cross-validation of analytes in complex samples was done with different CE separation mechanisms. • A simple strategy is used to confirm peak identification and extend capacity of CE separation. • The method uses small amount of sample, simple instrument and single fluorescent labeling. • Selection of mechanisms is based on orthogonalities of GU values of glycan standards. • Micellar electrokinetic chromatography was suitable for analysis of small or highly sialylated glycans.

  3. Parallel analysis and orthogonal identification of N-glycans with different capillary electrophoresis mechanisms

    International Nuclear Information System (INIS)

    Feng, Hua-tao; Su, Min; Rifai, Farida Nur; Li, Pingjing; Li, Sam F.Y.

    2017-01-01

    The deep involvement of glycans or carbohydrate moieties in biological processes makes glycan patterns an important direction for the clinical and medicine researches. A multiplexing CE mapping method for glycan analysis was developed in this study. By applying different CE separation mechanisms, the potential of combined parallel applications of capillary zone electrophoresis (CZE), micellar electrokinetic chromatography (MEKC) and capillary gel electrophoresis (CGE) for rapid and accurate identification of glycan was investigated. The combination of CZE and MEKC demonstrated enhancing chromatography separation capacity without the compromises of sample pre-treatment and glycan concentration. The separation mechanisms for multiplexing platform were selected based on the orthogonalities of the separation of glycan standards. MEKC method exhibited promising ability for the analysis of small GU value glycans and thus complementing the unavailability of CZE. The method established required only small amount of samples, simple instrument and single fluorescent labelling for sensitive detection. This integrated method can be used to search important glycan patterns appearing in biopharmaceutical products and other glycoproteins with clinical importance. - Highlights: • Cross-validation of analytes in complex samples was done with different CE separation mechanisms. • A simple strategy is used to confirm peak identification and extend capacity of CE separation. • The method uses small amount of sample, simple instrument and single fluorescent labeling. • Selection of mechanisms is based on orthogonalities of GU values of glycan standards. • Micellar electrokinetic chromatography was suitable for analysis of small or highly sialylated glycans.

  4. Electroencephalogram oscillations support the involvement of task-unrelated thoughts in the mechanism of boredom: A pilot study.

    Science.gov (United States)

    Miyauchi, Eri; Kawasaki, Masahiro

    2018-06-11

    Boredom is a universal experience; however, the neural mechanisms underlying the phenomenon remain unclear. Previous research suggests that boredom is related to attentional failure and derives a possible explanation for the cognitive processes of boredom as a product of appraisals made about task-unrelated thoughts. There are little published data regarding proposed processes from neuroscientific perspectives. Therefore, the authors aimed to examine whether cognitive processes of boredom with task-unrelated thoughts followed by appraisals of them can be explained by examining oscillatory correlates. Electroencephalography was used to measure changes in neural oscillatory activity during subjective experiences of boredom or dislike in healthy subjects. Using this approach, temporal information of brain activity particular to the boredom experience was acquired. Additionally, the Adult Attention-Deficit Hyperactivity Disorder Self-Report Scale was used to evaluate the effects of attentional deficits in the neural processing of boredom. Tonic increase in theta and transient increases in alpha activity were exhibited before the key press response for experiencing boredom; however, only tonic increases in theta amplitudes were boredom specific. The results of this pilot study suggest that the boredom experience is possibly associated with cognitive processes involved in task-unrelated thoughts, followed by their appraisals to be bored, mediated by alpha and theta activity. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Immunological mechanisms involved in the protection against intestinal taeniosis elicited by oral immunization with Taenia solium calreticulin.

    Science.gov (United States)

    Leon-Cabrera, Sonia; Cruz-Rivera, Mayra; Mendlovic, Fela; Romero-Valdovinos, Mirza; Vaughan, Gilberto; Salazar, Ana María; Avila, Guillermina; Flisser, Ana

    2012-11-01

    Oral immunization with functional recombinant Taenia solium calreticulin (rTsCRT) induces 37% reduction in tapeworm burden in the experimental model of intestinal taeniosis in hamsters. Furthermore, tapeworms recovered from vaccinated animals exhibit diminished length, being frequently found in more posterior parts of the small intestine. The aim of this study was to analyze the immunological mechanisms involved in protection in response to rTsCRT oral immunization. Hamsters were orally immunized with rTsCRT using cholera toxin (CT) as adjuvant, weekly for 4 weeks. Fifteen days after the last boost animals were challenged with four T. solium cysticerci. Reduction in the adult worm recovery and increased transcription of mRNA for IL-4 and IFN-γ in the mucosa of rTsCRT+CT immunized animals were observed. Immunization also induced goblet cell hyperplasia in the mucosa surrounding the implantation site of the parasite. Specific IgG and IgA antibodies in serum and fecal supernatants were detected after the second immunization, being more pronounced after challenge. Our data suggest that oral vaccination with rTsCRT+CT regulates a local expression of IL-4 and IFN-γ, stimulating secretion of IgA that, together with the increase of goblet cells and mucin production, could result in an unfavorable environment for T. solium promoting an impaired tapeworm development. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Study of the mechanisms involved in the laser superficial hardening process of metallic alloys

    International Nuclear Information System (INIS)

    Silva, Edmara Marques Rodrigues da

    2001-01-01

    The laser superficial hardening process of a ferrous alloy (gray cast iron) and of an aluminum-silicon alloy was investigated in this work. These metallic alloys are used in the automobile industry for manufacturing cylinders and pistons, respectively. By application of individual pulses and single tracks, the involved mechanisms during the processing were studied. Variables such as energy density, power density, temporal width, beam diameter on the sample surface, atmosphere of the processing region, overlapping and scanning velocity. The hardened surface was characterized by optical and scanning electronic microscopy, dispersive energy microanalysis, X-ray mapping, X-ray diffraction, and measurements of roughness and Vickers microhardness. Depending on the processing parameters, it is possible to obtain different microstructures. The affected area of gray cast iron, can be hardened by remelting or transformation hardening (total or partial) if the reached temperature is higher or not that of melting temperature. Laser treatment originated new structures such as retained austenite, martensite and, occasionally, eutectic of cellular dendritic structure. Aluminum-silicon alloy does not have phase transformation in solid state, it can be hardened only by remelting. The increase of hardness is a function of the precipitation hardening process, which makes the silicon particles smaller and more disperse in the matrix. Maximal values of microhardness (700-1000 HV) were reached with the laser treatment in gray cast iron samples. The initial microhardness is of 242 HV. For aluminum-silicon alloy, the laser remelting increases the initial microhardness of 128 HV to the range of 160-320 HV. The found results give a new perspective for using the CLA/IPEN's laser in the heat treatment area. Besides providing a higher absorptivity to the materials, compared with the CO 2 laser, and optical fiber access, the superficial hardening with Nd:YAG laser, depending on the level of

  7. Mechanisms of Interaction in Speech Production

    Science.gov (United States)

    Baese-Berk, Melissa; Goldrick, Matthew

    2009-01-01

    Many theories predict the presence of interactive effects involving information represented by distinct cognitive processes in speech production. There is considerably less agreement regarding the precise cognitive mechanisms that underlie these interactive effects. For example, are they driven by purely production-internal mechanisms (e.g., Dell,…

  8. Mechanisms of allograft rejection of corneal endothelium

    International Nuclear Information System (INIS)

    Tagawa, Y.; Silverstein, A.M.; Prendergast, R.A.

    1982-01-01

    The local intraocular graft-vs.-host (GVH) reaction, involving the destruction of the corneal endothelial cells of the rabbit host by sensitized donor lymphoid cells, has been used to study the mechanism of corneal allograft rejection. Pretreatment of donor cells with a specific mouse monoclonal hybridoma anti-T cell antibody and complement suppresses the destructive reaction, suggesting that a