WorldWideScience

Sample records for multiple key roles

  1. Quantum key distribution network for multiple applications

    Science.gov (United States)

    Tajima, A.; Kondoh, T.; Ochi, T.; Fujiwara, M.; Yoshino, K.; Iizuka, H.; Sakamoto, T.; Tomita, A.; Shimamura, E.; Asami, S.; Sasaki, M.

    2017-09-01

    The fundamental architecture and functions of secure key management in a quantum key distribution (QKD) network with enhanced universal interfaces for smooth key sharing between arbitrary two nodes and enabling multiple secure communication applications are proposed. The proposed architecture consists of three layers: a quantum layer, key management layer and key supply layer. We explain the functions of each layer, the key formats in each layer and the key lifecycle for enabling a practical QKD network. A quantum key distribution-advanced encryption standard (QKD-AES) hybrid system and an encrypted smartphone system were developed as secure communication applications on our QKD network. The validity and usefulness of these systems were demonstrated on the Tokyo QKD Network testbed.

  2. Secure image retrieval with multiple keys

    Science.gov (United States)

    Liang, Haihua; Zhang, Xinpeng; Wei, Qiuhan; Cheng, Hang

    2018-03-01

    This article proposes a secure image retrieval scheme under a multiuser scenario. In this scheme, the owner first encrypts and uploads images and their corresponding features to the cloud; then, the user submits the encrypted feature of the query image to the cloud; next, the cloud compares the encrypted features and returns encrypted images with similar content to the user. To find the nearest neighbor in the encrypted features, an encryption with multiple keys is proposed, in which the query feature of each user is encrypted by his/her own key. To improve the key security and space utilization, global optimization and Gaussian distribution are, respectively, employed to generate multiple keys. The experiments show that the proposed encryption can provide effective and secure image retrieval for each user and ensure confidentiality of the query feature of each user.

  3. The key role of extracellular vesicles in the metastatic process.

    Science.gov (United States)

    Zhao, Hongyun; Achreja, Abhinav; Iessi, Elisabetta; Logozzi, Mariantonia; Mizzoni, Davide; Di Raimo, Rossella; Nagrath, Deepak; Fais, Stefano

    2018-01-01

    Extracellular vesicles (EVs), including exosomes, have a key role in the paracrine communication between organs and compartments. EVs shuttle virtually all types of biomolecules such as proteins, lipids, nucleic acids, metabolites and even pharmacological compounds. Their ability to transfer their biomolecular cargo into target cells enables EVs to play a key role in intercellular communication that can regulate cellular functions such as proliferation, apoptosis and migration. This has led to the emergence of EVs as a key player in tumor growth and metastasis through the formation of "tumor niches" in target organs. Recent data have also been shown that EVs may transform the microenvironment of primary tumors thus favoring the selection of cancer cells with a metastatic behavior. The release of EVs from resident non-malignant cells may contribute to the metastatic processes as well. However, cancer EVs may induce malignant transformation in resident mesenchymal stem cells, suggesting that the metastatic process is not exclusively due to circulating tumor cells. In this review, we outline and discuss evidence-based roles of EVs in actively regulating multiple steps of the metastatic process and how we can leverage EVs to impair metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Nuclear energy: a key role despite problems

    International Nuclear Information System (INIS)

    Anderson, E.V.

    1977-01-01

    Nuclear energy is projected to be the fastest growing power source and a key to meeting power demands in spite of the many problems facing the nuclear industry in the form of delays, protests, and cancellations. Pressures for a nuclear moratorium will slow the industry, Mr. Anderson feels, but in the long run nuclear reactors will make up an increasing share of the power generating capacity. The Arthur D. Little Co. projects a fourfold increase between 1975 and 1985 on the basis of 10-year lead times for construction of nuclear power plants. Half the new generating capacity after 1985 will be nuclear. Problems besetting every stage of the nuclear fuel cycle result from debates over proliferation, waste disposal, reactor safety, and environmental damage and lead to controversy over regulations and licensing. U.S. utilities are not ordering reactors, but manufacturers are finding markets in other countries. Financial difficulties have kept domestic utilities from undertaking large investment programs until they can resolve problems of fuel costs and rate structures. New construction is inevitable, however, to meet future electrical requirements. Nuclear companies, which number nearly 1300 manufacturers and service providers, need to develop a better public image by working together to demonstrate their ability to manage the risks and uncertainties

  5. [Multiple roles and health among Korean women].

    Science.gov (United States)

    Cho, Su-Jin; Jang, Soong-Nang; Cho, Sung-Il

    2008-09-01

    Most studies about multiple roles and women's health suggested that combining with paid job, being married and having children was more likely to improve health status than in case of single or traditional roles. We investigated whether there was better health outcome in multiple roles among Korean women coinciding with previous studies of other nations. Data were from the 2005 Korea National Health & Nutritional Examination Survey, a subsample of women aged 25-59 years (N=2,943). Health status was assessed for self-rated poor health, perceived stress and depression, respectively based on one questionnaire item. The age-standardized prevalence of all health outcomes were calculated by role categories and socioeconomic status. Multiple logistic regression was used to assess the association of self rated health, perceived stress, and depression with multiple roles adjusted for age, education, household income, number of children and age of children. Having multiple roles with working role was not associated with better health and psychological wellbeing. Compared to those with traditional roles, employed women more frequently experienced perceived stress, with marital and/or parental roles. Non-working single mothers suffered depression more often than women with traditional roles or other role occupancy. Socioeconomic status indicators were potent independent correlates of self-rated health and perceived stress. Employment of women with other roles did not confer additional health benefit to traditional family responsibility. Juggling of work and family responsibility appeared more stressful than traditional unemployed parental and marital role in Korean women.

  6. Balancing multiple roles through consensus

    DEFF Research Database (Denmark)

    Oshima, Sae

    2014-01-01

    , the stylist and the client negotiate not only the quality of the cut, but also their expected roles. Caring about both the bodies and the minds of customers is an important element in measuring the quality of cosmetological services, a consideration which may oblige stylists to immediately agree with and act...... upon every client request or concern. However, simply yielding to the customer’s opinions can threaten the stylist’s role as a beauty expert, one who possesses their own professional standards. The analysis reveals that the participants frequently transform revision requests/offers into mutual...... decisions through a combination of verbal and bodily actions. In doing so, they harmonize the sometimes conflicting responsibilities of “service provider/patron” and “expert/novice.”...

  7. Gender, multiple roles, role meaning, and mental health.

    Science.gov (United States)

    Simon, R W

    1995-06-01

    This paper examines gender differences in the consequences of combining spouse, parent, and worker roles for mental health. I suggest that work and family roles have different meanings for males and females, and that differences in the meaning of these roles may be partially responsible for why the mental health advantages of holding multiple roles are fewer for women than for men. Based on qualitative analyses of follow-up, in-depth interviews with 40 employed married parents who participated in a community panel study of mental health, I find that sex differences in the perceived relationship between work and family roles may help account for sex differences in distress by contributing to male-female differences in both the extent and nature of work-parent conflicts, attributions of responsibility for marital problems, feelings of guilt, and self-evaluations as parents and spouses. By identifying gender differences in the meaning of roles among individuals who have the same multiple role configuration, and suggesting how these differences can help explain sex differences in well-being; this research may expand existing theories about the mental health consequences of multiple role involvements.

  8. Bax-mediated mitochondrial outer membrane permeabilization (MOMP), distinct from the mitochondrial permeability transition, is a key mechanism in diclofenac-induced hepatocyte injury: Multiple protective roles of cyclosporin A.

    Science.gov (United States)

    Siu, Woen Ping; Pun, Pamela Boon Li; Latchoumycandane, Calivarathan; Boelsterli, Urs A

    2008-03-15

    Diclofenac, a widely used nonsteroidal anti-inflammatory drug, has been associated with rare but severe cases of clinical hepatotoxicity. Diclofenac causes concentration-dependent cell death in human hepatocytes (after 24-48 h) by mitochondrial permeabilization via poorly defined mechanisms. To explore whether the cyclophilin D (CyD)-dependent mitochondrial permeability transition (mPT) and/or the mitochondrial outer membrane permeabilization (MOMP) was primarily involved in mediating cell death, we exposed immortalized human hepatocytes (HC-04) to apoptogenic concentrations of diclofenac (>500 microM) in the presence or absence of inhibitors of upstream mediators. The CyD inhibitor, cyclosporin A (CsA, 2 microM) fully inhibited diclofenac-induced cell injury, suggesting that mPT was involved. However, CyD gene silencing using siRNA left the cells susceptible to diclofenac toxicity, and CsA still protected the CyD-negative cells from lethal injury. Diclofenac induced early (9 h) activation of Bax and Bak and caused mitochondrial translocation of Bax, indicating that MOMP was involved in cell death. Inhibition of Bax protein expression by using siRNA significantly protected HC-04 from diclofenac-induced cell injury. Diclofenac also induced early Bid activation (tBid formation, 6 h), which is an upstream mechanism that initiates Bax activation and mitochondrial translocation. Bid activation was sensitive to the Ca2+ chelator, BAPTA. In conclusion, we found that Bax/Bak-mediated MOMP is a key mechanism of diclofenac-induced lethal cell injury in human hepatocytes, and that CsA can prevent MOMP through inhibition of Bax activation. These data support our concept that the Ca2+-Bid-Bax-MOMP axis is a critical pathway in diclofenac (metabolite)-induced hepatocyte injury.

  9. Bax-mediated mitochondrial outer membrane permeabilization (MOMP), distinct from the mitochondrial permeability transition, is a key mechanism in diclofenac-induced hepatocyte injury: Multiple protective roles of cyclosporin A

    International Nuclear Information System (INIS)

    Siu, W.P.; Pun, Pamela Boon Li; Latchoumycandane, Calivarathan; Boelsterli, Urs A.

    2008-01-01

    Diclofenac, a widely used nonsteroidal anti-inflammatory drug, has been associated with rare but severe cases of clinical hepatotoxicity. Diclofenac causes concentration-dependent cell death in human hepatocytes (after 24-48 h) by mitochondrial permeabilization via poorly defined mechanisms. To explore whether the cyclophilin D (CyD)-dependent mitochondrial permeability transition (mPT) and/or the mitochondrial outer membrane permeabilization (MOMP) was primarily involved in mediating cell death, we exposed immortalized human hepatocytes (HC-04) to apoptogenic concentrations of diclofenac (> 500 μM) in the presence or absence of inhibitors of upstream mediators. The CyD inhibitor, cyclosporin A (CsA, 2 μM) fully inhibited diclofenac-induced cell injury, suggesting that mPT was involved. However, CyD gene silencing using siRNA left the cells susceptible to diclofenac toxicity, and CsA still protected the CyD-negative cells from lethal injury. Diclofenac induced early (9 h) activation of Bax and Bak and caused mitochondrial translocation of Bax, indicating that MOMP was involved in cell death. Inhibition of Bax protein expression by using siRNA significantly protected HC-04 from diclofenac-induced cell injury. Diclofenac also induced early Bid activation (tBid formation, 6 h), which is an upstream mechanism that initiates Bax activation and mitochondrial translocation. Bid activation was sensitive to the Ca 2+ chelator, BAPTA. In conclusion, we found that Bax/Bak-mediated MOMP is a key mechanism of diclofenac-induced lethal cell injury in human hepatocytes, and that CsA can prevent MOMP through inhibition of Bax activation. These data support our concept that the Ca 2+ -Bid-Bax-MOMP axis is a critical pathway in diclofenac (metabolite)-induced hepatocyte injury

  10. Women and multiple roles: myths and reality.

    Science.gov (United States)

    Barnett, Rosalind Chait

    2004-01-01

    Strong beliefs persist about the negative effects of maternal employment on women, their marriages, and their children, in spite of considerable systematic research indicating that, on average, employment has positive effects. The underlying assumption is that the roles of wife and mother are "natural" roles and are therefore performed without undue stress. In contrast, the role of employee is seen as "unnatural" and therefore highly demanding. These beliefs affect clinical practice, fostering a concern among mental health professionals about whether women can handle the demands of multiple roles without serious negative health consequences. It is therefore important to evaluate these beliefs in light of the empirical literature. Such an evaluation is especially critical at this particular time, when demographic trends suggest that the number of employed women with children is increasing, that paid employment will be a central component in most women's life experiences, and that as a society we are highly unlikely to return to the days of the "traditional" family. The need for careful scrutiny is underscored by the current political climate, in which there is much rhetoric implying that maternal employment "causes" many of our social ills--school dropouts, drug abuse, juvenile violence, and divorce.

  11. Multiple Paths to Mathematics Practice in Al-Kashi's Key to Arithmetic

    Science.gov (United States)

    Taani, Osama

    2014-01-01

    In this paper, I discuss one of the most distinguishing features of Jamshid al-Kashi's pedagogy from his Key to Arithmetic, a well-known Arabic mathematics textbook from the fifteenth century. This feature is the multiple paths that he includes to find a desired result. In the first section light is shed on al-Kashi's life and his contributions to mathematics and astronomy. Section 2 starts with a brief discussion of the contents and pedagogy of the Key to Arithmetic. Al-Kashi's multiple approaches are discussed through four different examples of his versatility in presenting a topic from multiple perspectives. These examples are multiple definitions, multiple algorithms, multiple formulas, and multiple methods for solving word problems. Section 3 is devoted to some benefits that can be gained by implementing al-Kashi's multiple paths approach in modern curricula. For this discussion, examples from two teaching modules taken from the Key to Arithmetic and implemented in Pre-Calculus and mathematics courses for preservice teachers are discussed. Also, the conclusions are supported by some aspects of these modules. This paper is an attempt to help mathematics educators explore more benefits from reading from original sources.

  12. Security of public key encryption technique based on multiple chaotic systems

    International Nuclear Information System (INIS)

    Wang Kai; Pei Wenjiang; Zou Liuhua; Cheung Yiuming; He Zhenya

    2006-01-01

    Recently, a new public key encryption technique based on multiple chaotic systems has been proposed [B. Ranjan, Phys. Rev. Lett. 95 (2005) 098702]. This scheme employs m-chaotic systems and a set of linear functions for key exchange over an insecure channel. Security of the proposed algorithm grows as (NP) m , where N, P are the size of the key and the computational complexity of the linear functions respectively. In this Letter, the fundamental weakness of the cryptosystem is pointed out and a successful attack is described. Given the public keys and the initial vector, one can calculate the secret key based on Parseval's theorem. Both theoretical and experimental results show that the attacker can access to the secret key without difficulty. The lack of security discourages the use of such algorithm for practical applications

  13. Cryptanalysis of the public key encryption based on multiple chaotic systems

    International Nuclear Information System (INIS)

    Zhang Linhua

    2008-01-01

    Recently, Ranjan proposed a novel public key encryption technique based on multiple chaotic systems [Phys Lett 2005;95]. Unfortunately, Wang soon gave a successful attack on its special case based on Parseval's theorem [Wang K, Pei W, Zhou L, et al. Security of public key encryption technique based on multiple chaotic system. Phys Lett A, in press]. In this letter, we give an improved example which can avoid the attack and point out that Wang cannot find the essential drawback of the technique. However, further experimental result shows Ruanjan's encryption technique is inefficient, and detailed theoretic analysis shows that the complexity to break the cryptosystem is overestimated

  14. Teachers' Explanations of a Key Developmental Understanding of Multiplicative Reasoning

    Science.gov (United States)

    Rhee, Katherine L.

    2012-01-01

    This qualitative research study explores teachers' understandings of multiplicative reasoning as a key developmental understanding (KDU). A KDU entails knowingly applying the same mathematical concepts within different contexts. A KDU supports an individual to build a connected understanding of mathematics as opposed to only understanding…

  15. Agroecology: the key role of arbuscular mycorrhizas in ecosystem services.

    Science.gov (United States)

    Gianinazzi, Silvio; Gollotte, Armelle; Binet, Marie-Noëlle; van Tuinen, Diederik; Redecker, Dirk; Wipf, Daniel

    2010-11-01

    The beneficial effects of arbuscular mycorrhizal (AM) fungi on plant performance and soil health are essential for the sustainable management of agricultural ecosystems. Nevertheless, since the 'first green revolution', less attention has been given to beneficial soil microorganisms in general and to AM fungi in particular. Human society benefits from a multitude of resources and processes from natural and managed ecosystems, to which AM make a crucial contribution. These resources and processes, which are called ecosystem services, include products like food and processes like nutrient transfer. Many people have been under the illusion that these ecosystem services are free, invulnerable and infinitely available; taken for granted as public benefits, they lack a formal market and are traditionally absent from society's balance sheet. In 1997, a team of researchers from the USA, Argentina and the Netherlands put an average price tag of US $33 trillion a year on these fundamental ecosystem services. The present review highlights the key role that the AM symbiosis can play as an ecosystem service provider to guarantee plant productivity and quality in emerging systems of sustainable agriculture. The appropriate management of ecosystem services rendered by AM will impact on natural resource conservation and utilisation with an obvious net gain for human society.

  16. Role of multiple cusps in tooth fracture.

    Science.gov (United States)

    Barani, Amir; Bush, Mark B; Lawn, Brian R

    2014-07-01

    The role of multiple cusps in the biomechanics of human molar tooth fracture is analysed. A model with four cusps at the bite surface replaces the single dome structure used in previous simulations. Extended finite element modelling, with provision to embed longitudinal cracks into the enamel walls, enables full analysis of crack propagation from initial extension to final failure. The cracks propagate longitudinally around the enamel side walls from starter cracks placed either at the top surface (radial cracks) or from the tooth base (margin cracks). A feature of the crack evolution is its stability, meaning that extension occurs steadily with increasing applied force. Predictions from the model are validated by comparison with experimental data from earlier publications, in which crack development was followed in situ during occlusal loading of extracted human molars. The results show substantial increase in critical forces to produce longitudinal fractures with number of cuspal contacts, indicating a capacity for an individual tooth to spread the load during mastication. It is argued that explicit critical force equations derived in previous studies remain valid, at the least as a means for comparing the capacity for teeth of different dimensions to sustain high bite forces. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. The role of information system in multiple sclerosis management.

    Science.gov (United States)

    Ajami, Sima; Ahmadi, Golchehreh; Etemadifar, Masoud

    2014-12-01

    Multiple sclerosis (MS) is a chronic disease of central nervous system. The multiple sclerosis information system (MSIS), such as other information system (IS), depends on identification, collection and processing of data for producing useful information. Lack of the integrated IS for collecting standard data causes undesirable effects on exchanging, comparing, and managing. The aim of this study was to recognize the role of the IS in the MS management and determine the advantages and barriers in implementing of the MSIS. The present study was a nonsystematized review that was done in order to recognize the role of the IS in the MS management. In this study, electronic scientific resources such as scientific magazines and books and published topics at conferences were used. We used key words (IS, chronic disease management, and multiple sclerosis), their combination or their synonyms in title, key words, abstracts, and text of English articles and published reports from 1980 until 2013, and by using search engines such as Google, Google Scholar and scientific databases and electronic issues such as iPubMed, sufficiently important difference, Scopus, Medlib, and Magiran for gathering information. More than 200 articles and reports were collected and assessed and 139 of them. Findings showed that the MSIS can reduce of disease expenses through continuously collecting correct, accurate, sufficient, and timely patients and disease nature information; recoding; editing; processing; exchanging, and distributing among different health care centers. Although the MSIS has many advantages; but, we cannot ignore cultural, economic, technical, organizational, and managerial barriers. Therefore, it is necessary to do studies for preventing, reducing, and controlling them. One of the ways is to recognize the advantages of the MSIS and usage information technology in optimizing disease management.

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

    Science.gov (United States)

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

    2017-01-01

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

  19. Random multiple key streams for encryption with added CBC mode of operation

    Directory of Open Access Journals (Sweden)

    P. Penchalaiah

    2016-09-01

    For the first time, in this paper, we present a construction method to generate multiple random keys from a core-key with highest possible immunity to crack. We are with a particular emphasis on novel technique to secure user data, we have designed a secure and cost effective new cryptosystem called Rbits (Random bits cypher. In different directions we identify that Rbits having highest immunity to crack and presenting various analysis tests in support from this viewpoint and the analyzed results are reported.

  20. Multiple Role Conflict and Graduate Students' Academic Performance.

    Science.gov (United States)

    Feldmann, Shirley; Martinez-Pons, Manuel

    This study examined the effect of multiple social roles on the psychological functioning of 60 adult students (age 25 to 51 years) in an introductory graduate course in educational research. Using multiple role conflict (MRC), perceived ability to cope (PAC), subject anxiety (SA), academic self-efficacy (SE), self-regulation (SR), and course…

  1. Bearings with a key role in nuclear reactor safety

    International Nuclear Information System (INIS)

    Jackson, J.

    1981-01-01

    The most critical period during the operation of heavy-duty pumps occurs at run-up, when sudden high loads coincide with below normal oil pressure. When those pumps are a key component of a nuclear reactor safety-system, reliability takes on a special meaning. Electricite de France recently invited a British company, Michell Bearings, to find a solution to these 'black-start' problems, the details of which are described in the following article

  2. Optical code division multiple access secure communications systems with rapid reconfigurable polarization shift key user code

    Science.gov (United States)

    Gao, Kaiqiang; Wu, Chongqing; Sheng, Xinzhi; Shang, Chao; Liu, Lanlan; Wang, Jian

    2015-09-01

    An optical code division multiple access (OCDMA) secure communications system scheme with rapid reconfigurable polarization shift key (Pol-SK) bipolar user code is proposed and demonstrated. Compared to fix code OCDMA, by constantly changing the user code, the performance of anti-eavesdropping is greatly improved. The Pol-SK OCDMA experiment with a 10 Gchip/s user code and a 1.25 Gb/s user data of payload has been realized, which means this scheme has better tolerance and could be easily realized.

  3. ROLE AND IMPORTANCE OF KEY PERFORMANCE INDICATORS MEASUREMENT

    Directory of Open Access Journals (Sweden)

    Rade Stanković

    2011-03-01

    Full Text Available Key performance indicators are financial and non financial indicators that organizations use inorder to estimate and fortify how successful they are, aiming previously established long lastinggoals. Appropriate selection of indicators that will be used for measuring is of a greatest importance.Process organization of business is necessary to be constitute in order to realize such effective andefficient system or performance measuring via KPI. Process organization also implies customerorientation and necessary flexibility in nowadays condition of global competition.Explanation of process organization, the way of KPI selection, and practical example of KPImeasuring in Toyota dealerships are presented in this paper.

  4. The Multiple Roles of Exosomes in Metastasis

    Science.gov (United States)

    WEIDLE, H. ULRICH; BIRZELE, FABIAN; KOLLMORGEN, GWEN; RÜGER, RÜDIGER

    2016-01-01

    Exosomes are important contributors to cell−cell communication and their role as diagnostic markers for cancer and the pathogenesis for cancer is under intensive investigation. Here, we focus on their role in metastasis-related processes. We discuss their impact regarding promotion of invasion and migration of tumor cells, conditioning of lymph nodes, generation of premetastatic niches and organotropism of metastasis. Furthermore, we highlight interactions of exosomes with bone marrow and stromal components such as fibroblasts, endothelial cells, myeloid- and other immune-related cells in the context of metastases. For all processes as described above, we outline molecular and cellular components for therapeutic intervention with metastatic processes. PMID:28031234

  5. Zero-leakage multiple key-binding scenarios for SRAM-PUF systems based on the XOR-method

    NARCIS (Netherlands)

    Kusters, C.J.; Ignatenko, T.; Willems, F.M.J.

    2016-01-01

    We show that the XOR-method based on linear error-correcting codes can be applied to achieve the secret-key capacity of binary-symmetric SRAM-PUFs. Then we focus on multiple key-bindings. We prove that no information is leaked by all the helper data about a single secret key both in the case where

  6. Zero-leakage multiple key-binding scenarios for SRAM-PUF systems based on the XOR-Method

    NARCIS (Netherlands)

    Kusters, C.J.; Ignatenko, T.; Willems, F.M.J.

    2016-01-01

    We show that the XOR-method based on linear error-correcting codes can be applied to achieve the secret-key capacity of binary-symmetric SRAM-PUFs. Then we focus on multiple key-bindings. We prove that no information is leaked by all the helper data about a single secret key both in the case where

  7. The Role of Immunotherapy in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Mehmet Kocoglu

    2016-01-01

    Full Text Available Multiple myeloma is the second most common hematologic malignancy. The treatment of this disease has changed considerably over the last two decades with the introduction to the clinical practice of novel agents such as proteasome inhibitors and immunomodulatory drugs. Basic research efforts towards better understanding of normal and missing immune surveillence in myeloma have led to development of new strategies and therapies that require the engagement of the immune system. Many of these treatments are under clinical development and have already started providing encouraging results. We, for the second time in the last two decades, are about to witness another shift of the paradigm in the management of this ailment. This review will summarize the major approaches in myeloma immunotherapies.

  8. Multiple-Robot Systems for USAR: Key Design Attributes and Deployment Issues

    Directory of Open Access Journals (Sweden)

    Choon Yue Wong

    2011-03-01

    Full Text Available The interaction between humans and robots is undergoing an evolution. Progress in this evolution means that humans are close to robustly deploying multiple robots. Urban search and rescue (USAR can benefit greatly from such capability. The review shows that with state of the art artificial intelligence, robots can work autonomously but still require human supervision. It also shows that multiple robot deployment (MRD is more economical, shortens mission durations, adds reliability as well as addresses missions impossible with one robot and payload constraints. By combining robot autonomy and human supervision, the benefits of MRD can be applied to USAR while at the same time minimizing human exposure to danger. This is achieved with a single-human multiple-robot system (SHMRS. However, designers of the SHMRS must consider key attributes such as the size, composition and organizational structure of the robot collective. Variations in these attributes also induce fluctuations in issues within SHMRS deployment such as robot communication and computational load as well as human cognitive workload and situation awareness (SA. Research is essential to determine how the attributes can be manipulated to mitigate these issues while meeting the requirements of the USAR mission.

  9. Multiple-Robot Systems for USAR: Key Design Attributes and Deployment Issues

    Directory of Open Access Journals (Sweden)

    Choon Yue Wong

    2011-03-01

    Full Text Available The interaction between humans and robots is undergoing an evolution. Progress in this evolution means that humans are close to robustly deploying multiple robots. Urban search and rescue (USAR can benefit greatly from such capability. The review shows that with state of the art artificial intelligence, robots can work autonomously but still require human supervision. It also shows that multiple robot deployment (MRD is more economical, shortens mission durations, adds reliability as well as addresses missions impossible with one robot and payload constraints. By combining robot autonomy and human supervision, the benefits of MRD can be applied to USAR while at the same time minimizing human exposure to danger. This is achieved with a single-human multiple-robot system (SHMRS. However, designers of the SHMRS must consider key attributes such as the size, composition and organizational structure of the robot collective. Variations in these attributes also induce fluctuations in issues within SHMRS deployment such as robot communication and computational load as well as human cognitive workload and situation awareness (SA.Research is essential to determine how the attributes can be manipulated to mitigate these issues while meeting the requirements of the USAR mission.

  10. Gatekeepers’ Roles as a Fundamental Key in Money Laundering

    Directory of Open Access Journals (Sweden)

    Paku Utama

    2016-08-01

    Full Text Available This study examines problem of money laundering and identifies role of gatekeepers in utilising their expertise to conceal the proceeds of crime. In order to successfully prevent and investigate money laundering, we need to understand the development of anti-money laundering regime and how country like Indonesia adopts this development into its domestic regulations. Nevertheless, it is crucial to comprehend gatekeepers utilising various money laundering mechanisms and offshore financial centres. Scrutinised cases from Indonesia and corporate practices from Singapore on this study highlight how gatekeepers operate in the private sector, wittingly or unwittingly, use their expert knowledge of the international financial system to facilitate criminals and to secure the movement of the proceeds of crime globally. 

  11. Understanding earthquakes: The key role of radar images

    International Nuclear Information System (INIS)

    Atzori, Simone

    2013-01-01

    The investigation of the fault rupture underlying earthquakes greatly improved thanks to the spread of radar images. Following pioneer applications in the eighties, Interferometry from Synthetic Aperture Radar (InSAR) gained a prominent role in geodesy. Its capability to measure millimetric deformations for wide areas and the increased data availability from the early nineties, made InSAR a diffused and accepted analysis tool in tectonics, though several factors contribute to reduce the data quality. With the introduction of analytical or numerical modeling, InSAR maps are used to infer the source of an earthquake by means of data inversion. Newly developed algorithms, known as InSAR time-series, allowed to further improve the data accuracy and completeness, strengthening the InSAR contribution even in the study of the inter- and post-seismic phases. In this work we describe the rationale at the base of the whole processing, showing its application to the New Zealand 2010–2011 seismic sequence

  12. Understanding earthquakes: The key role of radar images

    Energy Technology Data Exchange (ETDEWEB)

    Atzori, Simone, E-mail: simone.atzori@ingv.it [Istituto Nazionale di Geofisica e Vulcanologia, Rome (Italy)

    2013-08-21

    The investigation of the fault rupture underlying earthquakes greatly improved thanks to the spread of radar images. Following pioneer applications in the eighties, Interferometry from Synthetic Aperture Radar (InSAR) gained a prominent role in geodesy. Its capability to measure millimetric deformations for wide areas and the increased data availability from the early nineties, made InSAR a diffused and accepted analysis tool in tectonics, though several factors contribute to reduce the data quality. With the introduction of analytical or numerical modeling, InSAR maps are used to infer the source of an earthquake by means of data inversion. Newly developed algorithms, known as InSAR time-series, allowed to further improve the data accuracy and completeness, strengthening the InSAR contribution even in the study of the inter- and post-seismic phases. In this work we describe the rationale at the base of the whole processing, showing its application to the New Zealand 2010–2011 seismic sequence.

  13. Poison gas and thefirst World War: key role ofpharmacists.

    Science.gov (United States)

    Bonnemain, Bruno

    2016-06-01

    Poison gas has been the subject of attention from the French army (Grand Quartier General). The 22sd of April 1915, General Joffre decided that the General Direction for Health Service was in charge of the protection of troops against what he called "this new mode of terror, disease, and death". Actions are been launched to found ways for the protection means and to obtain for the army at least equivalent weapons. Pharmacists will have a leading role thanks to their knowledge in chemistry. Research laboratories were working in two areas: individual protection and production of aggressive agents. Paul Lebeau, Gabriel Bertrand, Alexandre Degrez, Charles Moureu were among many others very committed to fight and remains at the top and to react quickly to ennemy's attacks. At the end of the war, Paul Lebeau received the Legion d'Honneur medal for his contribution to war. The school of pharmacy was recognized as faculty of pharmacy, by a decree of May 14th, 1920. The knowledge that were obtained during this period will be used for the second World War, but the chemical weapon was not much used, as opposed to more recent usage in Vietnam, Irak and Syria.

  14. Metabolism plays the key roles in Th cells differentiation

    Directory of Open Access Journals (Sweden)

    A. Hosseinzadeh

    2016-12-01

    Full Text Available The increasing rate of autoimmunity in recent decades cannot be related to only genetic instabilities and disorders. Diet can directly influence our health. Studies have shown that there is a relationship between nutritional elements and alteration in the immune system. Among immune cells, the function of T lymphocyte is important in directing immune response. T CD4+ cells lead other immune cells to respond to pathogens by secreting cytokines. HIV+ patients, who have largely lost their T CD4+ cells, are susceptible to opportunistic infections, which do not normally affect healthy people. It seems that the metabolism of T cells is critical for their differentiation and their consequent functions. After activation, T cells need to undergo clonal expansion, which is a high energy- consuming process. Studies have shown that specific metabolites deprivation or their excess supply affects T CD4+cells subsets differentiation. Abnormal induction of subsets of T CD4+ cells causes some autoimmunity reactions and hyper-sensitivity as well, which may result from imbalance of diet uptake. In this mini-review, we describe the findings about fatty acids, glucose, amino acids, and vitamins, which are effective in determining the fates of T CD4+ cells. These findings may help us uncover the role of diet in autoimmune diseases.

  15. Parliamentarians play key role in linking population and social development.

    Science.gov (United States)

    1995-01-01

    Mr. Hirofunti Ando, Deputy Executive Director of the UNFPA, delivered the statement of Dr. Nafis Sadik, Executive Director of the UNFPA at the International Meeting of Parliamentarians on Population and Social Development. The International Conference of Parliamentarians on Population and Development (ICPPD) in Cairo in September 1994 made a significant impact on the attitudes and support of parliamentarians regarding population issues. The Asian Forum of Parliamentarians on Population and Development (AFPPD) brought together a group of parliamentarians from all over the world to discuss population issues and social development. The World Summit included in its deliberations the accumulated experiences of earlier international conferences dealing with social economic issues. The ICPD Program of Action addressed concerns relevant to the agenda of the Social Summit: the crucial contribution that early population stabilization will make towards the attainment of sustainable development; the significant role of integrated policies on population and development in creating employment; the importance of population policies and programs in alleviating poverty; the contributions of reproductive health policies, including high-quality family planning services, to the enhancement of the status of women and to the achievement of gender equality; the synergy between education, family planning, and the general improvement of the human condition; and the relationship between population pressures, poverty, and environmental degradation. The ICPD Program of Action also identified critically important population and development objectives, such as ensuring access to education, especially of girls; reducing infant, child, and maternal mortality; and providing universal access to reproductive health and family planning services. Now the challenge is to mobilize the necessary resources for the Social Summit.

  16. The key role of eyewitnesses in rapid earthquake impact assessment

    Science.gov (United States)

    Bossu, Rémy; Steed, Robert; Mazet-Roux, Gilles; Roussel, Frédéric; Etivant, Caroline

    2014-05-01

    published after validation. Quake Catcher Networks (QCN) where a cheap USB MEMS motion sensors transform a PC in a seismic station are being deployed in Thessaloniki and Patras (Greece) in collaboration with Stanford University and the USGS. Flashsourcing is also used which is the analysis in real time of traffic surges observed on EMSC's earthquake information website; these surges are caused by the natural convergence of eyewitnesses who rush to the Internet to investigate the cause of the shaking that they have just felt. Within 5 minutes and independently of any seismic data, this detects felt earthquakes, maps the felt area and can detect the presence of damage. We will also explain the roles of social networks in optimising data collection and how citizen involvement has changed our earthquake information services.

  17. Memory-assisted quantum key distribution resilient against multiple-excitation effects

    Science.gov (United States)

    Lo Piparo, Nicolò; Sinclair, Neil; Razavi, Mohsen

    2018-01-01

    Memory-assisted measurement-device-independent quantum key distribution (MA-MDI-QKD) has recently been proposed as a technique to improve the rate-versus-distance behavior of QKD systems by using existing, or nearly-achievable, quantum technologies. The promise is that MA-MDI-QKD would require less demanding quantum memories than the ones needed for probabilistic quantum repeaters. Nevertheless, early investigations suggest that, in order to beat the conventional memory-less QKD schemes, the quantum memories used in the MA-MDI-QKD protocols must have high bandwidth-storage products and short interaction times. Among different types of quantum memories, ensemble-based memories offer some of the required specifications, but they typically suffer from multiple excitation effects. To avoid the latter issue, in this paper, we propose two new variants of MA-MDI-QKD both relying on single-photon sources for entangling purposes. One is based on known techniques for entanglement distribution in quantum repeaters. This scheme turns out to offer no advantage even if one uses ideal single-photon sources. By finding the root cause of the problem, we then propose another setup, which can outperform single memory-less setups even if we allow for some imperfections in our single-photon sources. For such a scheme, we compare the key rate for different types of ensemble-based memories and show that certain classes of atomic ensembles can improve the rate-versus-distance behavior.

  18. Logic programming reveals alteration of key transcription factors in multiple myeloma.

    Science.gov (United States)

    Miannay, Bertrand; Minvielle, Stéphane; Roux, Olivier; Drouin, Pierre; Avet-Loiseau, Hervé; Guérin-Charbonnel, Catherine; Gouraud, Wilfried; Attal, Michel; Facon, Thierry; Munshi, Nikhil C; Moreau, Philippe; Campion, Loïc; Magrangeas, Florence; Guziolowski, Carito

    2017-08-23

    Innovative approaches combining regulatory networks (RN) and genomic data are needed to extract biological information for a better understanding of diseases, such as cancer, by improving the identification of entities and thereby leading to potential new therapeutic avenues. In this study, we confronted an automatically generated RN with gene expression profiles (GEP) from a cohort of multiple myeloma (MM) patients and normal individuals using global reasoning on the RN causality to identify key-nodes. We modeled each patient by his or her GEP, the RN and the possible automatically detected repairs needed to establish a coherent flow of the information that explains the logic of the GEP. These repairs could represent cancer mutations leading to GEP variability. With this reasoning, unmeasured protein states can be inferred, and we can simulate the impact of a protein perturbation on the RN behavior to identify therapeutic targets. We showed that JUN/FOS and FOXM1 activities are altered in almost all MM patients and identified two survival markers for MM patients. Our results suggest that JUN/FOS-activation has a strong impact on the RN in view of the whole GEP, whereas FOXM1-activation could be an interesting way to perturb an MM subgroup identified by our method.

  19. The essential role of t cells in multiple sclerosis: A reappraisal

    Directory of Open Access Journals (Sweden)

    Cris S Constantinescu

    2014-04-01

    Full Text Available Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system in which destruction of myelin and nerve axons has been shown to be mediated by immune mechanisms. Although the focus of research has been traditionally on T cells as key mediators of the immunopathology, more recent efforts at understanding this complex disorder have been directed increasingly at other cellular and humoral elements of the immune response. This review is a reappraisal of the crucial role of T cells, in particular the CD4+ helper T-cell subset, in multiple sclerosis. Recent evidence is discussed underlining the predominant contribution of T-cell-associated genes to the genome-wide association study results of multiple sclerosis susceptibility, the loss of T-cell quiescence in the conversion from clinically isolated syndrome to clinically definite multiple sclerosis, and the fact that T cells represent the main target of effective immunomodulatory and immunosuppressive treatments in multiple sclerosis.

  20. Role of Proangiogenic Factors in Immunopathogenesis of Multiple Sclerosis.

    Science.gov (United States)

    Hamid, Kabir Magaji; Mirshafiey, Abbas

    2016-02-01

    Angiogenesis is a complex and balanced process in which new blood vessels form from preexisting ones by sprouting, splitting, growth and remodeling. This phenomenon plays a vital role in many physiological and pathological processes. However, the disturbance in physiological process can play a role in pathogenesis of some chronic inflammatory diseases, including multiple sclerosis (MS) in human and its animal model. Although the relation between abnormal blood vessels and MS lesions was established in previous studies, but the role of pathological angiogenesis remains unclear. In this study, the link between proangiogenic factors and multiple sclerosis pathogenesis was examined by conducting a systemic review. Thus we searched the English medical literature via PubMed, ISI web of knowledge, Medline and virtual health library (VHL) databases. In this review, we describe direct and indirect roles of some proangiogenic factors in MS pathogenesis and report the association of these factors with pathological and inflammatory angiogenesis.

  1. Key role for efflux in the preservative susceptibility and adaptive resistance of Burkholderia cepacia complex bacteria.

    Science.gov (United States)

    Rushton, Laura; Sass, Andrea; Baldwin, Adam; Dowson, Christopher G; Donoghue, Denise; Mahenthiralingam, Eshwar

    2013-07-01

    Bacteria from the Burkholderia cepacia complex (Bcc) are encountered as industrial contaminants, and little is known about the species involved or their mechanisms of preservative resistance. Multilocus sequence typing (MLST) revealed that multiple Bcc species may cause contamination, with B. lata (n = 17) and B. cenocepacia (n = 11) dominant within the collection examined. At the strain level, 11 of the 31 industrial sequence types identified had also been recovered from either natural environments or clinical infections. Minimal inhibitory (MIC) and minimum bactericidal (MBC) preservative concentrations varied across 83 selected Bcc strains, with industrial strains demonstrating increased tolerance for dimethylol dimethyl hydantoin (DMDMH). Benzisothiazolinone (BIT), DMDMH, methylisothiazolinone (MIT), a blend of 3:1 methylisothiazolinone-chloromethylisothiazolinone (M-CMIT), methyl paraben (MP), and phenoxyethanol (PH), were all effective anti-Bcc preservatives; benzethonium chloride (BC) and sodium benzoate (SB) were least effective. Since B. lata was the dominant industrial Bcc species, the type strain, 383(T) (LMG 22485(T)), was used to study preservative tolerance. Strain 383 developed stable preservative tolerance for M-CMIT, MIT, BIT, and BC, which resulted in preservative cross-resistance and altered antibiotic susceptibility, motility, and biofilm formation. Transcriptomic analysis of the B. lata 383 M-CMIT-adapted strain demonstrated that efflux played a key role in its M-CMIT tolerance and elevated fluoroquinolone resistance. The role of efflux was corroborated using the inhibitor l-Phe-Arg-β-napthylamide, which reduced the MICs of M-CMIT and ciprofloxacin. In summary, intrinsic preservative tolerance and stable adaptive changes, such as enhanced efflux, play a role in the ability of Bcc bacteria to cause industrial contamination.

  2. The Multiple Roles of Women Pursuing Doctoral Studies

    OpenAIRE

    Malone, Laurell Coleman M.S.

    1998-01-01

    Increases in the employment of women in administrative and managerial careers have drawn attention to a need for research that examines the interdependency of work and family roles, a need that is particularly crucial in the area of academic administration. This was a qualitative study of the strategies and support systems women educational administrators use to deal with the multiple roles they perform in life and work while pursuing doctoral studies. Forty-four women educational admini...

  3. Key Process Uncertainties in Soil Carbon Dynamics: Comparing Multiple Model Structures and Observational Meta-analysis

    Science.gov (United States)

    Sulman, B. N.; Moore, J.; Averill, C.; Abramoff, R. Z.; Bradford, M.; Classen, A. T.; Hartman, M. D.; Kivlin, S. N.; Luo, Y.; Mayes, M. A.; Morrison, E. W.; Riley, W. J.; Salazar, A.; Schimel, J.; Sridhar, B.; Tang, J.; Wang, G.; Wieder, W. R.

    2016-12-01

    Soil carbon (C) dynamics are crucial to understanding and predicting C cycle responses to global change and soil C modeling is a key tool for understanding these dynamics. While first order model structures have historically dominated this area, a recent proliferation of alternative model structures representing different assumptions about microbial activity and mineral protection is providing new opportunities to explore process uncertainties related to soil C dynamics. We conducted idealized simulations of soil C responses to warming and litter addition using models from five research groups that incorporated different sets of assumptions about processes governing soil C decomposition and stabilization. We conducted a meta-analysis of published warming and C addition experiments for comparison with simulations. Assumptions related to mineral protection and microbial dynamics drove strong differences among models. In response to C additions, some models predicted long-term C accumulation while others predicted transient increases that were counteracted by accelerating decomposition. In experimental manipulations, doubling litter addition did not change soil C stocks in studies spanning as long as two decades. This result agreed with simulations from models with strong microbial growth responses and limited mineral sorption capacity. In observations, warming initially drove soil C loss via increased CO2 production, but in some studies soil C rebounded and increased over decadal time scales. In contrast, all models predicted sustained C losses under warming. The disagreement with experimental results could be explained by physiological or community-level acclimation, or by warming-related changes in plant growth. In addition to the role of microbial activity, assumptions related to mineral sorption and protected C played a key role in driving long-term model responses. In general, simulations were similar in their initial responses to perturbations but diverged over

  4. On the diversity-multiplexing tradeoff of secret-key agreement over multiple-antenna channels

    KAUST Repository

    Zorgui, Marwen

    2014-09-01

    We consider secret-key agreement with public discussion over Rayleigh fading quasi-static channels. First, the secret-key diversity gain and the secret-key multiplexing gain are defined. Then, the secret-key diversity multiplexing tradeoff (DMT) is established. The eavesdropper is shown to \\'steal\\' only transmit antennas. We show that likewise the DMT without secrecy constraint, the secret-key DMT is the same either with or without full channel state information (CSI) at the transmitter (CSI-T). This insensitivity of secret-key DMT toward CSI-T highlights a fundamental difference between secret-key agreement and the wiretap channel whose secret DMT depends crucially on CSI-T. Several secret-key DMT-achieving schemes are presented in case of full CSI-T.

  5. On the diversity-multiplexing tradeoff of secret-key agreement over multiple-antenna channels

    KAUST Repository

    Zorgui, Marwen; Rezki, Zouheir; Alomair, Basel; Alouini, Mohamed-Slim

    2014-01-01

    We consider secret-key agreement with public discussion over Rayleigh fading quasi-static channels. First, the secret-key diversity gain and the secret-key multiplexing gain are defined. Then, the secret-key diversity multiplexing tradeoff (DMT) is established. The eavesdropper is shown to 'steal' only transmit antennas. We show that likewise the DMT without secrecy constraint, the secret-key DMT is the same either with or without full channel state information (CSI) at the transmitter (CSI-T). This insensitivity of secret-key DMT toward CSI-T highlights a fundamental difference between secret-key agreement and the wiretap channel whose secret DMT depends crucially on CSI-T. Several secret-key DMT-achieving schemes are presented in case of full CSI-T.

  6. Homesickness in University Students: The Role of Multiple Place Attachment

    Science.gov (United States)

    Scopelliti, Massimiliano; Tiberio, Lorenza

    2010-01-01

    The transition to college or university can lead to the challenge of adapting to a new setting. Homesickness has been frequently investigated as a potential negative consequence of relocation. This study analyzed the role of multiple place attachment in the development of homesickness among university students. The study used a multicausal…

  7. Lateral root formation and the multiple roles of auxin

    NARCIS (Netherlands)

    Du, Yujuan; Scheres, Ben

    2018-01-01

    Root systems can display variable architectures that contribute to survival strategies of plants. The model plant Arabidopsis thaliana possesses a tap root system, in which the primary root and lateral roots (LRs) are major architectural determinants. The phytohormone auxin fulfils multiple roles

  8. Novel Pectate Lyase Genes of Heterodera glycines Play Key Roles in the Early Stage of Parasitism.

    Directory of Open Access Journals (Sweden)

    Huan Peng

    Full Text Available Pectate lyases are known to play a key role in pectin degradation by catalyzing the random cleavage of internal polymer linkages (endo-pectinases. In this paper, four novel cDNAs, designated Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7, that encode pectate lyases were cloned and characterized from the soybean cyst nematode, Heterodera glycines. The predicted protein sequences of HG-PEL-3, HG-PEL-4 and HG-PEL-6 differed significantly in both their amino acid sequences and their genomic structures from other pectate lyases of H. glycines (HG-PEL-1, HG-PEL-2 and HG-PEL-7. A phylogenetic study revealed that the pectate lyase proteins of H. glycines are clustered into distinct clades and have distinct numbers and positioning of introns, which suggests that the pectate lyase genes of H. glycines may have evolved from at least two ancestral genes. A Southern blot analysis revealed that multiple Hg-pel-6-like genes were present in the H. glycines genome. In situ hybridization showed that four novel pectate lyases (Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7 were actively transcribed in the subventral esophageal gland cells. A semi-quantitative RT-PCR assay supported the finding that the expression of these genes was strong in the egg, pre-parasitic second-stage juvenile (J2 and early parasitic J2 stages and that it declined in further developmental stages of the nematode. This expression pattern suggests that these proteins play a role in the migratory phase of the nematode life cycle. Knocking down Hg-pel-6 using in vitro RNA interference resulted in a 46.9% reduction of the number of nematodes that invaded the plants and a 61.5% suppression of the development of H. glycines females within roots compared to the GFP-dsRNA control. Plant host-derived RNAi induced the silencing of the Hg-pel-6gene, which significantly reduced the nematode infection levels at 7 Days post inoculation (dpi. Similarly, this procedure reduced the number of female adults at 40 dpi

  9. The Diversity-Multiplexing Tradeoff of Secret-Key Agreement over Multiple-Antenna Channels

    KAUST Repository

    Zorgui, Marwen

    2015-10-26

    We study the problem of secret-key agreement between two legitimate parties, Alice and Bob, in presence an of eavesdropper Eve. There is a public channel with unlimited capacity that is available to the legitimate parties and is also observed by Eve. Our focus is on Rayleigh fading quasi-static channels. The legitimate receiver and the eavesdropper are assumed to have perfect channel knowledge of their channels. We study the system in the high-power regime. First, we define the secret-key diversity gain and the secret-key multiplexing gain. Second, we establish the secret-key diversity multiplexing tradeoff (DMT) under no channel state information (CSI) at the transmitter (CSI-T). The eavesdropper is shown to “steal” only transmit antennas. We show that, likewise the DMT without secrecy constraint, the secret-key DMT is the same either with or without full channel state information at the transmitter. This insensitivity of secret-key DMT toward CSI-T features a fundamental difference between secret-key agreement and the wiretap channel, in which secret DMT depends heavily on CSI-T. Finally, we present several secret-key DMT-achieving schemes in case of full CSI-T. We argue that secret DMT-achieving schemes are also key DMT-achieving. Moreover, we show formally that artificial noise (AN), likewise zero-forcing (ZF), is DMT-achieving. We also show that the public feedback channel improves the outage performance without having any effect on the DMT.

  10. The Diversity-Multiplexing Tradeoff of Secret-Key Agreement over Multiple-Antenna Channels

    KAUST Repository

    Zorgui, Marwen; Rezki, Zouheir; Alomair, Basel; Alouini, Mohamed-Slim

    2015-01-01

    We study the problem of secret-key agreement between two legitimate parties, Alice and Bob, in presence an of eavesdropper Eve. There is a public channel with unlimited capacity that is available to the legitimate parties and is also observed by Eve. Our focus is on Rayleigh fading quasi-static channels. The legitimate receiver and the eavesdropper are assumed to have perfect channel knowledge of their channels. We study the system in the high-power regime. First, we define the secret-key diversity gain and the secret-key multiplexing gain. Second, we establish the secret-key diversity multiplexing tradeoff (DMT) under no channel state information (CSI) at the transmitter (CSI-T). The eavesdropper is shown to “steal” only transmit antennas. We show that, likewise the DMT without secrecy constraint, the secret-key DMT is the same either with or without full channel state information at the transmitter. This insensitivity of secret-key DMT toward CSI-T features a fundamental difference between secret-key agreement and the wiretap channel, in which secret DMT depends heavily on CSI-T. Finally, we present several secret-key DMT-achieving schemes in case of full CSI-T. We argue that secret DMT-achieving schemes are also key DMT-achieving. Moreover, we show formally that artificial noise (AN), likewise zero-forcing (ZF), is DMT-achieving. We also show that the public feedback channel improves the outage performance without having any effect on the DMT.

  11. Multiple Roles and Women's Mental Health in Canada.

    Science.gov (United States)

    Maclean, Heather; Glynn, Keva; Ansara, Donna

    2004-08-25

    HEALTH ISSUE: Research on the relationship between women's social roles and mental health has been equivocal. Although a greater number of roles often protect mental health, certain combinations can lead to strain. Our study explored the moderating affects of different role combinations on women's mental health by examining associations with socioeconomic status and differences in women's distress (depressive symptoms, personal stress (role strain) and chronic stress (role strain plus environmental stressors). KEY FINDINGS: Women with children, whether single or partnered, had a higher risk of personal stress. Distress, stress and chronic stress levels of mothers, regardless of employment, or marital status, are staggeringly high. Single, unemployed mothers were significantly more likely than all other groups to experience financial stress and food insecurity. For partnered mothers, rates of personal stress and chronic stress were significantly lower among unemployed partnered mothers. Married and partnered mothers reported better mental health than their single counterparts. Lone, unemployed mothers were twice as likely to report a high level of distress compared with other groups. Lone mothers, regardless of employment status, were more likely to report high personal and chronic stress. DATA GAPS AND RECOMMENDATIONS: National health surveys need to collect more data on the characteristics of women's work environment and their care giving responsibilities. Questions on household composition should include inter-generational households, same sex couples and multifamily arrangements. Data disaggregation by ethno-racial background would be helpful. Data should be collected on perceived quality of domestic and partnership roles and division of labours.

  12. Conformational flexibility of BECN1: Essential to its key role in autophagy and beyond: BECN1 Structure and Mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Mei, Yang [Department of Chemistry and Biochemistry, North Dakota State University, Fargo North Dakota 58108-6050; Glover, Karen [Department of Chemistry and Biochemistry, North Dakota State University, Fargo North Dakota 58108-6050; Su, Minfei [Department of Chemistry and Biochemistry, North Dakota State University, Fargo North Dakota 58108-6050; Sinha, Sangita C. [Department of Chemistry and Biochemistry, North Dakota State University, Fargo North Dakota 58108-6050

    2016-08-13

    BECN1 (Beclin 1), a highly conserved eukaryotic protein, is a key regulator of autophagy, a cellular homeostasis pathway, and also participates in vacuolar protein sorting, endocytic trafficking, and apoptosis. BECN1 is important for embryonic development, the innate immune response, tumor suppression, and protection against neurodegenerative disorders, diabetes, and heart disease. BECN1 mediates autophagy as a core component of the class III phosphatidylinositol 3-kinase complexes. However, the exact mechanism by which it regulates the activity of these complexes, or mediates its other diverse functions is unclear. BECN1 interacts with several diverse protein partners, perhaps serving as a scaffold or interaction hub for autophagy. Based on extensive structural, biophysical and bioinformatics analyses, BECN1 consists of an intrinsically disordered region (IDR), which includes a BH3 homology domain (BH3D); a flexible helical domain (FHD); a coiled-coil domain (CCD); and a β-α-repeated autophagy-specific domain (BARAD). Each of these BECN1 domains mediates multiple diverse interactions that involve concomitant conformational changes. Thus, BECN1 conformational flexibility likely plays a key role in facilitating diverse protein interactions. Further, BECN1 conformation and interactions are also modulated by numerous post-translational modifications. A better structure-based understanding of the interplay between different BECN1 conformational and binding states, and the impact of post-translational modifications will be essential to elucidating the mechanism of its multiple biological roles.

  13. Multiple sclerosis

    International Nuclear Information System (INIS)

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

  14. Key aspects in managing safety when working with multiple contractors: A case study

    NARCIS (Netherlands)

    Drupsteen, L.; Rasmussen, H.B.; Ustailieva, E.; Kampen, J. van

    2015-01-01

    Working with multiple contractors in a shared workplace can introduce and increase safety risks due to complexity. The aim of this study was to explore how safety issues are recognized in a specific case and to identify whether clients and contractors perceive problems similarly. The safety issues

  15. Strategies for Supporting Physician-Scientists in Faculty Roles: A Narrative Review With Key Informant Consultations.

    Science.gov (United States)

    Lingard, Lorelei; Zhang, Peter; Strong, Michael; Steele, Margaret; Yoo, John; Lewis, James

    2017-10-01

    Physician-scientists are a population in decline globally. Solutions to reverse this decline often have focused on the training pipeline. Less attention has been paid to reducing attrition post training, when physician-scientists take up faculty roles. However, this period is a known time of vulnerability because of the pressures of clinical duties and the long timeline to securing independent research funding. This narrative review explored existing knowledge regarding how best to support physician-scientists for success in their faculty roles. The authors searched the Medline, Embase, ERIC, and Cochrane Library databases for articles published from 2000 to 2016 on this topic and interviewed key informants in 2015 to solicit their input on the review results. The authors reviewed 78 articles and interviewed 16 key informants. From the literature, they developed a framework of organizational (facilitate mentorship, foster community, value the physician-scientist role, minimize financial barriers) and individual (develop professional and research skills) strategies for supporting physician-scientists. They also outlined key knowledge gaps representing topics either rarely or never addressed in the reviewed articles (percent research time, structural hypocrisy, objective assessment, group metrics, professional identity). The key informants confirmed the identified strategies and discussed how the gaps were particularly important and impactful. This framework offers a basis for assessing an organization's existing support strategies, identifying outstanding needs, and developing targeted programming. The identified gaps require attention, as they threaten to undermine the benefits of existing support strategies.

  16. The role of epigenetics in the biology of multiple myeloma

    DEFF Research Database (Denmark)

    Dimopoulos, K; Gimsing, P; Grønbæk, K

    2014-01-01

    Several recent studies have highlighted the biological complexity of multiple myeloma (MM) that arises as a result of several disrupted cancer pathways. Apart from the central role of genetic abnormalities, epigenetic aberrations have also been shown to be important players in the development of MM......, and a lot of research during the past decades has focused on the ways DNA methylation, histone modifications and noncoding RNAs contribute to the pathobiology of MM. This has led to, apart from better understanding of the disease biology, the development of epigenetic drugs, such as histone deacetylase...... inhibitors that are already used in clinical trials in MM with promising results. This review will present the role of epigenetic abnormalities in MM and how these can affect specific pathways, and focus on the potential of novel 'epidrugs' as future treatment modalities for MM....

  17. Role of intestinal microbiota in the development of multiple sclerosis.

    Science.gov (United States)

    Castillo-Álvarez, F; Marzo-Sola, M E

    2017-04-01

    Multiple sclerosis (MS) is a demyelinating disease that affects young adults; in that age group, it represents the second leading cause of disability in our setting. Its precise aetiology has not been elucidated, but it is widely accepted to occur in genetically predisposed patients who are exposed to certain environmental factors. The discovery of the regulatory role played by intestinal microbiota in various autoimmune diseases has opened a new line of research in this field, which is discussed in this review. We reviewed published studies on the role of the microbiota in the development of both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). In mice, it has been shown that intestinal microorganisms regulate the polarisation of T helper cells from Th1-Th17 up to Th2, the function of regulatory T cells, and the activity of B cells; they participate in the pathogenesis of EAE and contribute to its prevention and treatment. In contrast, evidence in humans is still scarce and mainly based on case-control studies that point to the presence of differences in certain bacterial communities. Multiple evidence points to the role of microbiota in EAE. Extrapolation of these results to MS is still in the early stages of research, and studies are needed to define which bacterial populations are associated with MS, the role they play in pathogenesis, and the therapeutic possibilities this knowledge offers us. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. On the Ergodic Secret-Key Agreement over Spatially Correlated Multiple-Antenna Channels with Public Discussion

    KAUST Repository

    Zorgui, Marwen

    2015-09-28

    We consider secret-key agreement with public discussion over multiple-input multiple-output (MIMO) Rayleigh fast-fading channels under correlated environment. We assume that transmit, legitimate receiver and eavesdropper antennas are correlated. The legitimate receiver and the eavesdropper are assumed to have perfect channel knowledge while the transmitter has only knowledge of the correlation matrices. First, we derive the expression of the secret-key capacity under the considered setup. We prove that the optimal transmit strategy achieving the secret-key capacity consists in transmitting independent Gaussian signals along the eingenvectors of the transmit correlation matrix. The powers allocated to each channel mode are determined as the solution to a numerical optimization problem. A necessary and sufficient condition for beamforming (i.e., transmitting along the strongest channel mode) to be capacity-achieving is derived. Moreover, we analyze the impact of correlation matrices on the system performance. Finally, we study the system’s performance in the two extreme power regimes. In the high-power regime, we provide closed-form expressions of the gain/loss due to correlation. In the low signal-to-noise ratio (SNR) regime, we investigate the energy efficiency of the system by determining the minimum energy required for sharing a secret-key bit and the wideband slope while highlighting the impact of correlation matrices.

  19. Single blastocyst transfer: The key to reduce multiple pregnancy rates without compromising the live birth rate

    Directory of Open Access Journals (Sweden)

    Uma M Sundhararaj

    2017-01-01

    Full Text Available Background: Historically, to achieve higher pregnancy rates, multiple embryos were transferred after an in-vitro fertilisation (IVF. However, this practice is being reassessed, because it leads to multiple pregnancies that is known to cause adverse maternal and fetal outcomes. Aim: To compare the pregnancy outcomes in fresh IVF or intracytoplasmic sperm injection (ICSI cycles among women undergoing elective single blastocyst transfer (eSBT vs. those undergoing double blastocyst transfer (DBT. Settings and Design: It is a retrospective data analysis of 582 patients undergoing fresh IVF/ICSI cycles performed from January 2012 to June 2015. Materials and Methods: Patients, who underwent IVF/ICSI and developed more than one blastocyst, were included in the study. Donor cycles were excluded from the study. All the embryos were cultured to blastocyst stage in sequential media followed by transfer of two blastocysts (DBT or eSBT and cryopreservation of the remaining. Statistical Analysis: Statistical analysis was performed using chi square test. Results: Out of 582 patients, in 149 patients one blastocyst was transferred and in 433 patients two blastocysts were transferred. There was no statistical difference in the biochemical pregnancy rate, clinical pregnancy rate and live birth rate in both the groups. Statistics demonstrated a significant drop in miscarriage rate in eSBT group. There was no incidence of twins in eSBT group, whereas twin birth rate per clinical pregnancy was 29.02% in DBT group. Conclusion: Single blastocyst transfer is an effective method to reduce the risk of multiple births without compromising the pregnancy outcomes. Given the promising potential of vitrification; the remaining blastocyst can be cryopreserved.

  20. Key issues of multiple access technique for LEO satellite communication systems

    Institute of Scientific and Technical Information of China (English)

    温萍萍; 顾学迈

    2004-01-01

    The large carrier frequency shift caused by the high-speed movement of satellite (Doppler effects) and the propagation delay on the up-down link are very critical issues in an LEO satellite communication system, which affects both the selection and the implementation of a suitable access method. A Doppler based multiple access technique is used here to control the flow and an MPRMA-HS protocol is proposed for the application in LEO satellite communication systems. The extended simulation trials prove that the proposed scheme seems to be a very promising access method.

  1. Assessing the Role of Energy in Development and Climate Policies - Conceptual Approach and Key Indicators

    DEFF Research Database (Denmark)

    Halsnæs, Kirsten; Garg, Amit

    2011-01-01

    The paper discusses a number of key conceptual issues related to the role of energy in development and its potential synergies and tradeoffs with climate change. The relationship between economic development and energy over time is discussed and illustrated by data from China, India and South...... Africa, and some other countries. It concludes that energy plays an important role as a productivity enhancing factor in economic development and in human well being. Several policy goals related to sustainable development, energy, and climate can be integrated. However, meeting all these policy goals...

  2. Resilience in homeless youth: the key role of self-esteem.

    Science.gov (United States)

    Kidd, Sean; Shahar, Golan

    2008-04-01

    This study examined the protective role of self-esteem, social involvement, and secure attachment among homeless youths. These protective factors were examined as they ameliorate risks among 208 homeless youths surveyed in New York City and Toronto. Both mental and physical health indicators were employed in this study, including loneliness, feeling trapped, suicidal ideation, subjective health status, and substance use. Self-esteem emerged as a key protective factor, predicting levels of loneliness, feeling trapped, and suicide ideation, and buffering against the deleterious effect of fearful attachment on loneliness. Findings highlight the role of the self-concept in risk and resilience among homeless youth. Copyright 2008 APA, all rights reserved.

  3. Corporate strategy in turbulent environments: Key roles of the corporate level

    OpenAIRE

    Caldart, Adrian A.; Ricart, Joan E.

    2006-01-01

    This paper analyzes the evolution during the period 1986-2002 of the corporate strategy of Lujan, a highly successful car components manufacturer headquartered in Spain, as a way to explore how the corporate level influences the successful evolution of a company exposed to a "turbulent" environment over a long period. We find that the corporate level plays three key roles. First, it drives a firm's evolution by developing a cognitive representation of the firm's competitive landscape. Second,...

  4. Multiple Information Fusion Face Recognition Using Key Feature Points

    Directory of Open Access Journals (Sweden)

    LIN Kezheng

    2017-06-01

    Full Text Available After years of face recognition research,due to the effect of illumination,noise and other conditions have led to the recognition rate is relatively low,2 d face recognition technology has couldn’t keep up with the pace of The Times the forefront,Although 3 d face recognition technology is developing step by step,but it has a higher complexity. In order to solve this problem,based on the traditional depth information positioning method and local characteristic analysis methods LFA,puts forward an improved 3 d face key feature points localization algorithm, and on the basis of the trained sample which obtained by complete cluster,further put forward the global and local feature extraction algorithm of weighted fusion. Through FRGC and BU-3DFE experiment data comparison and analysis of the two face library,the method in terms of 3 d face recognition effect has a higher robustness.

  5. Insights into the key roles of proteoglycans in breast cancer biology and translational medicine

    DEFF Research Database (Denmark)

    Theocharis, Achilleas D.; Skandalis, Spyros S.; Neill, Thomas

    2015-01-01

    of proteoglycans on tumor and stromal cell membranes affects cancer cell signaling, growth and survival, cell adhesion, migration and angiogenesis. Despite the high complexity and heterogeneity of breast cancer, the rapid evolution in our knowledge that proteoglycans are among the key players in the breast tumor...... in the proteoglycans that will be presented herein provides the potential for multiple layers of regulation of breast tumor behavior. This review summarizes recent developments concerning the biology of selected proteoglycans in breast cancer, and presents potential targeted therapeutic approaches based on their novel...

  6. The role of astrocytes in multiple sclerosis pathogenesis.

    Science.gov (United States)

    Guerrero-García, J J

    2017-09-25

    Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS), in which astrocytes play an important role as CNS immune cells. However, the activity of astrocytes as antigen-presenting cells (APC) continues to be subject to debate. This review analyses the existing evidence on the participation of astrocytes in CNS inflammation in MS and on several mechanisms that modify astrocyte activity in the disease. Astrocytes play a crucial role in the pathogenesis of MS because they express toll-like receptors (TLR) and major histocompatibility complex (MHC) classI andII. In addition, astrocytes participate in regulating the blood-brain barrier (BBB) and in modulating T cell activity through the production of cytokines. Future studies should focus on the role of astrocytes in order to find new therapeutic targets for the treatment of MS. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Secret-key agreement over spatially correlated fast-fading multiple-antenna channels with public discussion

    KAUST Repository

    Zorgui, Marwen

    2015-06-14

    We consider secret-key agreement with public discussion over multiple-input multiple-output (MIMO) Rayleigh fast-fading channels under correlated environment. We assume that transmit, legitimate receiver and eavesdropper antennas are correlated. The legitimate receiver and the eavesdropper are assumed to have perfect channel knowledge while the transmitter has only knowledge of the correlation matrices. First, we derive the expression of the secret-key capacity under the considered setup. Then, we prove that the optimal transmit strategy achieving the secret-key capacity consists in transmitting independent Gaussian signals along the eingenvectors of the transmit correlation matrix. The powers allocated to each channel mode are determined as the solution to a numerical optimization problem that we derive. A necessary and sufficient condition for beamforming (i.e., transmitting along the strongest channel mode) to be capacity-achieving is derived. Finally, we analyze the impact of correlation matrices on the system performance and provide closed-form expressions of the gain/loss due to correlation in the high power regime.

  8. Multiple role occupancy and social participation among midlife wives and husbands in the United Kingdom.

    Science.gov (United States)

    Glaser, Karen; Evandrou, Maria; Tomassini, Cecilia

    2006-01-01

    We investigated the relationship between intensive multiple role occupancy and one key dimension of well-being, social participation (i.e., frequency of participation in social and leisure activities and meeting friends or relatives). Moreover, we examined gender differences in the association between individual, spousal and couple intensive multiple role commitments and individual social participation. Our research is based on a sample of mid-life wives (45-59) and their husbands from the 2000 British Household Panel Study (BHPS). Our findings show that, among wives whose husbands were providing care to a dependent for 20 or more hours a week, there was a negative association with social and leisure activity participation, whereas husbands' level of participation in social and leisure activities was higher if their wives were in full-time paid work. We also found lower odds of meeting friends or relatives among wives and husbands in full-time employment, and higher odds of meeting friends and relatives among wives providing care for 20 or more hours a week. Our results will aid policy thinking in addressing how people can be best supported to balance work and family commitments in order to optimize different dimensions of well-being in later life and help alleviate the pressures associated with multiple-role occupancy in mid-life.

  9. The clinical role of lecturers in nursing in Ireland: perceptions from key stakeholder groups in nurse education on the role.

    Science.gov (United States)

    Meskell, Pauline; Murphy, Kathleen; Shaw, David

    2009-10-01

    The clinical role of lecturers in nursing has been a focus of debate since the integration of nurse education into higher education institutions. The purpose of this paper is to report the findings from the preliminary phase of a study, undertaken to investigate the perceptions of key stakeholder groups in nurse education, regarding the current clinical role of nurse lecturers in Ireland. A descriptive exploratory design was used involving focus group and individual interviews, soliciting views of purposefully selected educationalists, clinicians, policy formulators and students. The issue was examined from a policy perspective, aiming to collectively represent views of all participant groups. This approach facilitated a more complete picture of perceptions of the role to emerge, to better inform future decision making. Twenty two focus group interviews and twenty one individual interviews were conducted. Content analysis was used to identify themes. All groups were in agreement that role definition was urgently required to dispel ambiguities surrounding what the clinical role should involve. Conflicting views were evident among groups regarding lecturers' clinical credibility, visibility and teaching effectiveness. Findings highlight the essential nature of nurse lecturers engaging with clinical areas to maintain their skills, demonstrate a value for the practice component of the role and provide a link between education and practice.

  10. Same pattern, different mechanism: Locking onto the role of key species in seafloor ecosystem process.

    Science.gov (United States)

    Woodin, Sarah Ann; Volkenborn, Nils; Pilditch, Conrad A; Lohrer, Andrew M; Wethey, David S; Hewitt, Judi E; Thrush, Simon F

    2016-05-27

    Seafloor biodiversity is a key mediator of ecosystem functioning, but its role is often excluded from global budgets or simplified to black boxes in models. New techniques allow quantification of the behavior of animals living below the sediment surface and assessment of the ecosystem consequences of complex interactions, yielding a better understanding of the role of seafloor animals in affecting key processes like primary productivity. Combining predictions based on natural history, behavior of key benthic species and environmental context allow assessment of differences in functioning and process, even when the measured ecosystem property in different systems is similar. Data from three sedimentary systems in New Zealand illustrate this. Analysis of the behaviors of the infaunal ecosystem engineers in each system revealed three very different mechanisms driving ecosystem function: density and excretion, sediment turnover and surface rugosity, and hydraulic activities and porewater bioadvection. Integrative metrics of ecosystem function in some cases differentiate among the systems (gross primary production) and in others do not (photosynthetic efficiency). Analyses based on behaviors and activities revealed important ecosystem functional differences and can dramatically improve our ability to model the impact of stressors on ecosystem and global processes.

  11. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti

    2011-01-01

    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown...... the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture...... underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working...

  12. Epilepsy in multiple sclerosis: The role of temporal lobe damage.

    Science.gov (United States)

    Calabrese, M; Castellaro, M; Bertoldo, A; De Luca, A; Pizzini, F B; Ricciardi, G K; Pitteri, M; Zimatore, S; Magliozzi, R; Benedetti, M D; Manganotti, P; Montemezzi, S; Reynolds, R; Gajofatto, A; Monaco, S

    2017-03-01

    Although temporal lobe pathology may explain some of the symptoms of multiple sclerosis (MS), its role in the pathogenesis of seizures has not been clarified yet. To investigate the role of temporal lobe damage in MS patients suffering from epilepsy, by the application of advanced multimodal 3T magnetic resonance imaging (MRI) analysis. A total of 23 relapsing remitting MS patients who had epileptic seizures (RRMS/E) and 23 disease duration matched RRMS patients without any history of seizures were enrolled. Each patient underwent advanced 3T MRI protocol specifically conceived to evaluate grey matter (GM) damage. This includes grey matter lesions (GMLs) identification, evaluation of regional cortical thickness and indices derived from the Neurite Orientation Dispersion and Density Imaging model. Regional analysis revealed that in RRMS/E, the regions most affected by GMLs were the hippocampus (14.2%), the lateral temporal lobe (13.5%), the cingulate (10.0%) and the insula (8.4%). Cortical thinning and alteration of diffusion metrics were observed in several regions of temporal lobe, in insular cortex and in cingulate gyrus of RRMS/E compared to RRMS ( ptemporal lobe, which exceeds what would be expected on the basis of the global GM damage observed.

  13. Lateral root formation and the multiple roles of auxin.

    Science.gov (United States)

    Du, Yujuan; Scheres, Ben

    2018-01-04

    Root systems can display variable architectures that contribute to survival strategies of plants. The model plant Arabidopsis thaliana possesses a tap root system, in which the primary root and lateral roots (LRs) are major architectural determinants. The phytohormone auxin fulfils multiple roles throughout LR development. In this review, we summarize recent advances in our understanding of four aspects of LR formation: (i) LR positioning, which determines the spatial distribution of lateral root primordia (LRP) and LRs along primary roots; (ii) LR initiation, encompassing the activation of nuclear migration in specified lateral root founder cells (LRFCs) up to the first asymmetric cell division; (iii) LR outgrowth, the 'primordium-intrinsic' patterning of de novo organ tissues and a meristem; and (iv) LR emergence, an interaction between LRP and overlaying tissues to allow passage through cell layers. We discuss how auxin signaling, embedded in a changing developmental context, plays important roles in all four phases. In addition, we discuss how rapid progress in gene network identification and analysis, modeling, and four-dimensional imaging techniques have led to an increasingly detailed understanding of the dynamic regulatory networks that control LR development. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Yersinia pestis Ail: multiple roles of a single protein

    Science.gov (United States)

    Kolodziejek, Anna M.; Hovde, Carolyn J.; Minnich, Scott A.

    2012-01-01

    Yersinia pestis is one of the most virulent bacteria identified. It is the causative agent of plague—a systemic disease that has claimed millions of human lives throughout history. Y. pestis survival in insect and mammalian host species requires fine-tuning to sense and respond to varying environmental cues. Multiple Y. pestis attributes participate in this process and contribute to its pathogenicity and highly efficient transmission between hosts. These include factors inherited from its enteric predecessors; Y. enterocolitica and Y. pseudotuberculosis, as well as phenotypes acquired or lost during Y. pestis speciation. Representatives of a large Enterobacteriaceae Ail/OmpX/PagC/Lom family of outer membrane proteins (OMPs) are found in the genomes of all pathogenic Yersiniae. This review describes the current knowledge regarding the role of Ail in Y. pestis pathogenesis and virulence. The pronounced role of Ail in the following areas are discussed (1) inhibition of the bactericidal properties of complement, (2) attachment and Yersinia outer proteins (Yop) delivery to host tissue, (3) prevention of PMNL recruitment to the lymph nodes, and (4) inhibition of the inflammatory response. Finally, Ail homologs in Y. enterocolitica and Y. pseudotuberculosis are compared to illustrate differences that may have contributed to the drastic bacterial lifestyle change that shifted Y. pestis from an enteric to a vector-born systemic pathogen. PMID:22919692

  15. THE ROLE OF MULTIPLICITY IN DISK EVOLUTION AND PLANET FORMATION

    Energy Technology Data Exchange (ETDEWEB)

    Kraus, Adam L. [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Dr., Honolulu, HI 96822 (United States); Ireland, Michael J. [Sydney Institute for Astronomy (SIfA), School of Physics, University of Sydney, NSW 2006 (Australia); Hillenbrand, Lynne A. [California Institute of Technology, Department of Astrophysics, MC 249-17, Pasadena, CA 91125 (United States); Martinache, Frantz [National Astronomical Observatory of Japan, Subaru Telescope, Hilo, HI 96720 (United States)

    2012-01-20

    The past decade has seen a revolution in our understanding of protoplanetary disk evolution and planet formation in single-star systems. However, the majority of solar-type stars form in binary systems, so the impact of binary companions on protoplanetary disks is an important element in our understanding of planet formation. We have compiled a combined multiplicity/disk census of Taurus-Auriga, plus a restricted sample of close binaries in other regions, in order to explore the role of multiplicity in disk evolution. Our results imply that the tidal influence of a close ({approx}<40 AU) binary companion significantly hastens the process of protoplanetary disk dispersal, as {approx}2/3 of all close binaries promptly disperse their disks within {approx}<1 Myr after formation. However, prompt disk dispersal only occurs for a small fraction of wide binaries and single stars, with {approx}80%-90% retaining their disks for at least {approx}2-3 Myr (but rarely for more than {approx}5 Myr). Our new constraints on the disk clearing timescale have significant implications for giant planet formation; most single stars have 3-5 Myr within which to form giant planets, whereas most close binary systems would have to form giant planets within {approx}<1 Myr. If core accretion is the primary mode for giant planet formation, then gas giants in close binaries should be rare. Conversely, since almost all single stars have a similar period of time within which to form gas giants, their relative rarity in radial velocity (RV) surveys indicates either that the giant planet formation timescale is very well matched to the disk dispersal timescale or that features beyond the disk lifetime set the likelihood of giant planet formation.

  16. AMP-Activated Protein Kinase: An Ubiquitous Signaling Pathway With Key Roles in the Cardiovascular System.

    Science.gov (United States)

    Salt, Ian P; Hardie, D Grahame

    2017-05-26

    The AMP-activated protein kinase (AMPK) is a key regulator of cellular and whole-body energy homeostasis, which acts to restore energy homoeostasis whenever cellular energy charge is depleted. Over the last 2 decades, it has become apparent that AMPK regulates several other cellular functions and has specific roles in cardiovascular tissues, acting to regulate cardiac metabolism and contractile function, as well as promoting anticontractile, anti-inflammatory, and antiatherogenic actions in blood vessels. In this review, we discuss the role of AMPK in the cardiovascular system, including the molecular basis of mutations in AMPK that alter cardiac physiology and the proposed mechanisms by which AMPK regulates vascular function under physiological and pathophysiological conditions. © 2017 American Heart Association, Inc.

  17. Connecting metabolism and reproduction: roles of central energy sensors and key molecular mediators.

    Science.gov (United States)

    Roa, Juan; Tena-Sempere, Manuel

    2014-11-01

    It is well established that pubertal activation of the reproductive axis and maintenance of fertility are critically dependent on the magnitude of body energy reserves and the metabolic state of the organism. Hence, conditions of impaired energy homeostasis often result in deregulation of puberty and reproduction, whereas gonadal dysfunction can be associated with the worsening of the metabolic profile and, eventually, changes in body weight. While much progress has taken place in our knowledge about the neuroendocrine mechanisms linking metabolism and reproduction, our understanding of how such dynamic interplay happens is still incomplete. As paradigmatic example, much has been learned in the last two decades on the reproductive roles of key metabolic hormones (such as leptin, insulin and ghrelin), their brain targets and the major transmitters and neuropeptides involved. Yet, the molecular mechanisms whereby metabolic information is translated and engages into the reproductive circuits remain largely unsolved. In this work, we will summarize recent developments in the characterization of the putative central roles of key cellular energy sensors, such as mTOR, in this phenomenon, and will relate these with other molecular mechanisms likely contributing to the brain coupling of energy balance and fertility. In doing so, we aim to provide an updated view of an area that, despite still underdeveloped, may be critically important to fully understand how reproduction and metabolism are tightly connected in health and disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. The role of multiple barriers in assuring waste package reliability

    International Nuclear Information System (INIS)

    Bradford, R.M.

    1993-08-01

    Yucca Mountain in southwestern Nevada is being studied as a potential repository site for the permanent storage of high-level nuclear waste. Regulators have set performance standards that the potential repository must meet in order to obtain regulatory approval. Nuclear Regulatory Commission (NRC) regulations state that containment of radioactivity must be ''substantially complete'' for the first 1000 years after closure of the facility. Thereafter, the acceptable annual limit on releases is 1/100,000 of each radionuclide remaining in the inventory after 1000 years. To demonstrate that the potential facility is in compliance with the regulations, it is necessary to obtain some understanding of the probability distribution of the cumulative quantity of releases by certain time points. This paper will discuss the probability distribution of waste container lifetimes and how the understanding of this distribution will play a role in finding the distribution of the release quantities over time. It will be shown that, for reasonable assumptions about the process of barrier failure, the reliability of a multiple-barrier container can be achieved and demonstrated much more readily than a container consisting of a single barrier. The discussion will focus primarily on the requirement of substantially complete containment for the first 1000 years

  19. The Role of Fungi in the Etiology of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Julián Benito-León

    2017-10-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system. Infectious triggers of MS are being actively investigated. Substantial evidence supports the involvement of the Epstein-Barr virus (EBV, though other viruses, bacteria, protists, and fungi are also being considered. Many links between fungi and diseases involving chronic inflammation have been found recently. Evidence linking MS and fungi is reviewed here. The HLA-DRB1*15 allele group is the most important genetic risk factor of MS, and is a risk factor in several other conditions linked to fungal infections. Many biomarkers of MS are consistent with fungal infections, such as IL-17, chitotriosidase, and antibodies against fungi. Dimethyl fumarate (DMF, first used as an industrial fungicide, was recently repurposed to reduce MS symptoms. Its mechanisms of action in MS have not been firmly established. The low risk of MS during childhood and its moderate association with herpes simplex virus type 2 suggest genital exposure to microbes (including fungi should be investigated as a possible trigger. Molecular and epidemiological evidence support a role for infections such as EBV in MS. Though fungal infections have not been widely studied in MS, many lines of evidence are consistent with a fungal etiology. Future microbiome and serological studies should consider fungi as a possible risk factor for MS, and future clinical studies should consider the effect of fungicides other than DMF on MS symptoms.

  20. Multiple roles of the coagulation protease cascade during virus infection.

    Science.gov (United States)

    Antoniak, Silvio; Mackman, Nigel

    2014-04-24

    The coagulation cascade is activated during viral infections. This response may be part of the host defense system to limit spread of the pathogen. However, excessive activation of the coagulation cascade can be deleterious. In fact, inhibition of the tissue factor/factor VIIa complex reduced mortality in a monkey model of Ebola hemorrhagic fever. Other studies showed that incorporation of tissue factor into the envelope of herpes simplex virus increases infection of endothelial cells and mice. Furthermore, binding of factor X to adenovirus serotype 5 enhances infection of hepatocytes but also increases the activation of the innate immune response to the virus. Coagulation proteases activate protease-activated receptors (PARs). Interestingly, we and others found that PAR1 and PAR2 modulate the immune response to viral infection. For instance, PAR1 positively regulates TLR3-dependent expression of the antiviral protein interferon β, whereas PAR2 negatively regulates expression during coxsackievirus group B infection. These studies indicate that the coagulation cascade plays multiple roles during viral infections.

  1. The multiple roles and functions of English in South Korea

    Directory of Open Access Journals (Sweden)

    Gene Vasilopoulos

    2013-10-01

    Full Text Available In the field of language and identity, the subcategory of gender has been an area of growing interest (Pavlenko, 2001; Norton & Pavlenko, 2004; Menard-Warwick, 2008; and Higgins, 2010. Adopting the view of gender as “a system of social relationships and discursive practices” (Norton & Pavlenko, 2004, p. 504, social context is fundamental in understanding how gender relates to foreign language learning. This qualitative study focused on the extent to which gender impacts English language learning and English language use in the context of teaching English as a foreign language in South Korea. More specifically, it investigates how gender shapes self and social identity, and how these identities relate to English language learning and English language use, at present and/or in the future, in both real and/or imagined communities. Four male and four female participants were selected using purposive homogenous sampling techniques based on the criteria of having lived abroad in an English speaking community for over 5 years—a criterion which assumes the formation of self and social identity in addition to their native Korean L1. Data was collected through multiple methods including open-ended questionnaires, in-depth interviews, and focus group discussions. Interview and questionnaire data reveals gender differences in the symbolic meaning of English language, the relevance of English in self and social positioning, and the role of English in shaping future professional trajectories with males situating themselves in international contexts and females in the local.

  2. Immune resistance of Multiple Myeloma : the role of the microenvironment

    NARCIS (Netherlands)

    de Haart, SJ

    2017-01-01

    Immunotherapeutic strategies in Multiple Myeloma are under development. In this thesis we present a new perspective in optimizing immunotherapy in Multiple Myeloma patient. We propose that currently, immunotherapy is limited in efficacy through interactions of Multiple Myeloma cells with the bone

  3. Phytochelatins play a key role in arsenic accumulation and tolerance in the aquatic macrophyte Wolffia globosa

    International Nuclear Information System (INIS)

    Zhang Xin; Uroic, M. Kalle; Xie Wanying; Zhu Yongguan; Chen Baodong; McGrath, Steve P.; Feldmann, Jörg; Zhao Fangjie

    2012-01-01

    The rootless duckweed Wolffia globosa can accumulate and tolerate relatively large amounts of arsenic (As); however, the underlying mechanisms were unknown. W. globosa was exposed to different concentrations of arsenate with or without L-buthionine sulphoximine (BSO), a specific inhibitor of γ-glutamylcysteine synthetase. Free thiol compounds and As(III)–thiol complexes were identified and quantified using HPLC – high resolution ICP-MS – accurate mass ESI-MS. Without BSO, 74% of the As accumulated in the duckweed was complexed with phytochelatins (PCs), with As(III)–PC 4 and As(III)–PC 3 being the main species. BSO was taken up by the duckweed and partly deaminated. The BSO treatment completely suppressed the synthesis of PCs and the formation of As(III)–PC complexes, and also inhibited the reduction of arsenate to arsenite. BSO markedly decreased both As accumulation and As tolerance in W. globosa. The results demonstrate an important role of PCs in detoxifying As and enabling As accumulation in W. globosa. - Highlights: ► W. globosa can accumulate and tolerate relatively large amounts of arsenic. ► Majority of the As accumulated in W. globosa was complexed with phytochelatins (PCs). ► As(III)–PC 4 and As(III)–PC 3 are the main complex species. ► Complexation of arsenite with phytochelatins plays a key role in As tolerance and accumulation. - Complexation of arsenite with phytochelatins plays a key role in both arsenic tolerance and accumulation in the aquatic macrophyte Wolffia globosa.

  4. Roles and responsibilities of pharmacists with respect to natural health products: key informant interviews.

    Science.gov (United States)

    Olatunde, Shade; Boon, Heather; Hirschkorn, Kristine; Welsh, Sandy; Bajcar, Jana

    2010-03-01

    Although many pharmacies sell natural health products (NHPs), there is no clear definition as to the roles and responsibilities (if any) of pharmacists with respect to these products. The purpose of this study was to explore pharmacy and stakeholder leaders' perceptions of pharmacists' professional NHP roles and responsibilities. Semi-structured key informant interviews were conducted with pharmacy leaders (n=17) and stakeholder (n=18) leaders representing consumers, complementary and alternative medicine practitioners, conventional health care practitioners, and industry across Canada. All participants believed a main NHP responsibility for pharmacists was in safety monitoring, although a one challenge identified in the interviews was pharmacists' general lack of NHP knowledge; however, stakeholder leaders did not expect pharmacists to be experts, but should have a basic level of knowledge about NHPs. Participants described pharmacists' professional roles and responsibilities for NHPs as similar to those for over-the-counter drugs; more awareness of existing NHP-related pharmacy policies is needed, and pharmacy owners/managers should provide additional training to ensure front-line pharmacists have appropriate knowledge of NHPs sold in the pharmacy. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Insights into the key roles of epigenetics in matrix macromolecules-associated wound healing.

    Science.gov (United States)

    Piperigkou, Zoi; Götte, Martin; Theocharis, Achilleas D; Karamanos, Nikos K

    2017-10-24

    Extracellular matrix (ECM) is a dynamic network of macromolecules, playing a regulatory role in cell functions, tissue regeneration and remodeling. Wound healing is a tissue repair process necessary for the maintenance of the functionality of tissues and organs. This highly orchestrated process is divided into four temporally overlapping phases, including hemostasis, inflammation, proliferation and tissue remodeling. The dynamic interplay between ECM and resident cells exerts its critical role in many aspects of wound healing, including cell proliferation, migration, differentiation, survival, matrix degradation and biosynthesis. Several epigenetic regulatory factors, such as the endogenous non-coding microRNAs (miRNAs), are the drivers of the wound healing response. microRNAs have pivotal roles in regulating ECM composition during wound healing and dermal regeneration. Their expression is associated with the distinct phases of wound healing and they serve as target biomarkers and targets for systematic regulation of wound repair. In this article we critically present the importance of epigenetics with particular emphasis on miRNAs regulating ECM components (i.e. glycoproteins, proteoglycans and matrix proteases) that are key players in wound healing. The clinical relevance of miRNA targeting as well as the delivery strategies designed for clinical applications are also presented and discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Current role of radiation therapy for multiple myeloma.

    Science.gov (United States)

    Talamo, Giampaolo; Dimaio, Christopher; Abbi, Kamal K S; Pandey, Manoj K; Malysz, Jozef; Creer, Michael H; Zhu, Junjia; Mir, Muhammad A; Varlotto, John M

    2015-01-01

    Radiation therapy (RT) is a treatment modality traditionally used in patients with multiple myeloma (MM), but little is known regarding the role and effectiveness of RT in the era of novel agents, i.e., immunomodulatory drugs and proteasome inhibitors. We retrospectively reviewed data from 449 consecutive MM patients seen at our institute in 2010-2012 to assess indications for RT as well as its effectiveness. Pain response was scored similarly to RTOG 0631 and used the Numerical Rating Pain Scale. Among 442 evaluable patients, 149 (34%) patients and 262 sites received RT. The most common indication for RT was palliation of bone pain (n = 109, 42%), followed by prevention/treatment of pathological fractures (n = 73, 28%), spinal cord compression (n = 26, 10%), and involvement of vital organs/extramedullary disease (n = 25, 10%). Of the 55 patients evaluable for pain relief, complete and partial responses were obtained in 76.4 and 7.2%, respectively. Prior RT did not significantly decrease the median number of peripheral blood stem cells collected for autologous transplant, even when prior RT was given to both the spine and pelvis. Inadequacy of stem cell collection for autologous stem cell transplant (ASCT) was not significantly different and it occurred in 9 and 15% of patients receiving no RT and spine/pelvic RT, respectively. None of the three cases of therapy-induced acute myelogenous leukemia/MDS occurred in the RT group. Despite the introduction of novel effective agents in the treatment of MM, RT remains a major therapeutic component for the management in 34% of patients, and it effectively provides pain relief while not interfering with successful peripheral blood stem cell collection for ASCT.

  7. [Key role played by the gut associated lymphoid tissue during human immunodeficiency virus infection].

    Science.gov (United States)

    Vergnon-Miszczycha, Delphine; Lucht, Frédéric; Roblin, Xavier; Pozzetto, Bruno; Paul, Stéphane; Bourlet, Thomas

    2015-12-01

    The gut associated lymphoid tissue (GALT) is the site of numerous immunological disturbances during HIV-1 infection. It constitutes the largest reservoir for HIV, not or very poorly susceptible to antiretroviral therapy (ART), making it a major obstacle to HIV cure. Moreover, the GALT is involved in systemic immune activation in HIV-infected individuals: intestinal damage due to viral replication and severe CD4(+) T cell depletion in the GALT leads to microbial translocation, a key driver of immune activation, and in turn, disease progression. In this review, we describe the role of the GALT in HIV infection and we discuss therapeutic options to decrease the intestinal viral reservoir and to preserve immune function in the gut of HIV-infected people. Achieving these goals is necessary for a long-term infection control after the interruption of ART. © 2015 médecine/sciences – Inserm.

  8. Quantitative proteomics reveals that peroxidases play key roles in post-flooding recovery in soybean roots.

    Science.gov (United States)

    Khan, Mudassar Nawaz; Sakata, Katsumi; Hiraga, Susumu; Komatsu, Setsuko

    2014-12-05

    Soybean is an important legume crop that exhibits markedly reduced growth and yields under flooding conditions. To unravel the mechanisms involved in recovery after flooding in soybean root, gel-free proteomic analysis was performed. Morphological analysis revealed that growth suppression was more severe with increased flooding duration. Out of a total of 1645 and 1707 identified proteins, 73 and 21 proteins were changed significantly during the recovery stage following 2 and 4 days flooding, respectively. Based on the proteomic, clustering, and in silico protein-protein interaction analyses, six key enzymes were analyzed at the mRNA level. Lipoxygenase 1, which was increased at the protein level during the recovery period, was steadily down-regulated at the mRNA level. The peroxidase superfamily protein continuously increased in abundance during the course of recovery and was up-regulated at the mRNA level. HAD acid phosphatase was decreased at the protein level and down-regulated at the transcript level, while isoflavone reductase and an unknown protein were increased at both the protein and mRNA levels. Consistent with these findings, the enzymatic activity of peroxidase was decreased under flooding stress but increased significantly during the recovery sage. These results suggest that peroxidases might play key roles in post-flooding recovery in soybean roots through the scavenging of toxic radicals.

  9. Multiple Roles and Women's Mental Health in Canada

    OpenAIRE

    Ansara Donna; Glynn Keva; Maclean Heather

    2004-01-01

    Abstract Health Issue Research on the relationship between women's social roles and mental health has been equivocal. Although a greater number of roles often protect mental health, certain combinations can lead to strain. Our study explored the moderating affects of different role combinations on women's mental health by examining associations with socioeconomic status and differences in women's distress (depressive symptoms, personal stress (role strain) and chronic stress (role strain plus...

  10. Health and well-being at work: The key role of supervisor support

    Directory of Open Access Journals (Sweden)

    Oliver Hämmig

    2017-12-01

    Full Text Available This study aims to explore whether and in what way social support from different sources and domains makes an additional or different and independent contribution to various health and work-related outcomes. Cross-sectional data were used from an employee survey among the workforces of four service companies from different industries in Switzerland. The study sample covered 5,877 employees of working age. The lack of social support from a spouse, relatives, friends, direct supervisors, closest colleagues at work and other co-workers in case of problems at work and at home were assessed and studied individually and jointly as risk factors with respect to a total number of eight outcomes. Health-related outcomes covered poor self-rated health, musculoskeletal disorders, stress feelings and burnout symptoms. Work-related outcomes included feeling overwhelmed at work, difficulty with switching off after work, job dissatisfaction and intention to turnover. Social support from multiple sources in contrast to only individual sources in both life domains was found to be more frequent in women than in men and proved to be most protective and beneficial with regard to health and well-being at work. However, after mutual adjustment of all single sources of social support from both domains, a lack of supervisor support turned out to be the only or the strongest of the few remaining support measures and statistically significant risk factors for the studied outcomes throughout and by far. Being unable to count on the support of a direct supervisor in case of problems at work and even at home was shown to involve a substantially increased risk of poor health and work-related outcomes (aOR = up to 3.8. Multiple sources of social support, and particularly supervisor support, seem to be important resources of health and well-being at work and need to be considered as key factors in workplace health promotion.

  11. Health and well-being at work: The key role of supervisor support.

    Science.gov (United States)

    Hämmig, Oliver

    2017-12-01

    This study aims to explore whether and in what way social support from different sources and domains makes an additional or different and independent contribution to various health and work-related outcomes. Cross-sectional data were used from an employee survey among the workforces of four service companies from different industries in Switzerland. The study sample covered 5,877 employees of working age. The lack of social support from a spouse, relatives, friends, direct supervisors, closest colleagues at work and other co-workers in case of problems at work and at home were assessed and studied individually and jointly as risk factors with respect to a total number of eight outcomes. Health-related outcomes covered poor self-rated health, musculoskeletal disorders, stress feelings and burnout symptoms. Work-related outcomes included feeling overwhelmed at work, difficulty with switching off after work, job dissatisfaction and intention to turnover. Social support from multiple sources in contrast to only individual sources in both life domains was found to be more frequent in women than in men and proved to be most protective and beneficial with regard to health and well-being at work. However, after mutual adjustment of all single sources of social support from both domains, a lack of supervisor support turned out to be the only or the strongest of the few remaining support measures and statistically significant risk factors for the studied outcomes throughout and by far. Being unable to count on the support of a direct supervisor in case of problems at work and even at home was shown to involve a substantially increased risk of poor health and work-related outcomes (aOR = up to 3.8). Multiple sources of social support, and particularly supervisor support, seem to be important resources of health and well-being at work and need to be considered as key factors in workplace health promotion.

  12. The Key Success and Strategic Role of Accrual Based Accounting Implementation

    Directory of Open Access Journals (Sweden)

    Surepno Surepno

    2015-09-01

    Full Text Available Central Government policy to adopt accrual-based accounting system providing consequences for local governments to apply accrual accounting in the financial statements. Empirical evidence shows that the readiness of the local government in Indonesia in the process of implementation of accrual accounting is still relatively low. This study aimed to analyze the success of Semarang Government in implementing accrual accounting. This study also analyzes the offender's response to the implementation of the strategic role of accrual accounting in transparency and accountability. Furthermore, the method used in this study is a qualitative approach to perform a case study at the Department of Finance and Asset Management Area (DPKAD Semarang by means of interviewing the key actors of implementation. The results showed that the successful implementation of accrual accounting Semarang government is supported by four main strategies, namely management commitment, regulatory development, information systems development and human resource development. Furthermore, based on the conclusions of the implementers shows that accrual accounting has a strategic role in increasing transparency and accountability through financial reporting.

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

    Directory of Open Access Journals (Sweden)

    Laura E Via

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

  14. The role of primary care in adult weight management: qualitative interviews with key stakeholders in weight management services

    OpenAIRE

    Blane, David N.; Macdonald, Sara; Morrison, David; O’Donnell, Catherine A.

    2017-01-01

    Background Primary care has a key role to play in the prevention and management of obesity, but there remain barriers to engagement in weight management by primary care practitioners. The aim of this study was to explore the views of key stakeholders in adult weight management services on the role of primary care in adult weight management. Methods Qualitative study involving semi-structured interviews with nine senior dietitians involved in NHS weight management from seven Scottish health bo...

  15. CD155/PVR plays a key role in cell motility during tumor cell invasion and migration

    International Nuclear Information System (INIS)

    Sloan, Kevin E; Ilag, Leodevico L; Jay, Daniel G; Eustace, Brenda K; Stewart, Jean K; Zehetmeier, Carol; Torella, Claudia; Simeone, Marina; Roy, Jennifer E; Unger, Christine; Louis, David N

    2004-01-01

    Invasion is an important early step of cancer metastasis that is not well understood. Developing therapeutics to limit metastasis requires the identification and validation of candidate proteins necessary for invasion and migration. We developed a functional proteomic screen to identify mediators of tumor cell invasion. This screen couples Fluorophore Assisted Light Inactivation (FALI) to a scFv antibody library to systematically inactivate surface proteins expressed by human fibrosarcoma cells followed by a high-throughput assessment of transwell invasion. Using this screen, we have identified CD155 (the poliovirus receptor) as a mediator of tumor cell invasion through its role in migration. Knockdown of CD155 by FALI or by RNAi resulted in a significant decrease in transwell migration of HT1080 fibrosarcoma cells towards a serum chemoattractant. CD155 was found to be highly expressed in multiple cancer cell lines and primary tumors including glioblastoma (GBM). Knockdown of CD155 also decreased migration of U87MG GBM cells. CD155 is recruited to the leading edge of migrating cells where it colocalizes with actin and αv-integrin, known mediators of motility and adhesion. Knockdown of CD155 also altered cellular morphology, resulting in cells that were larger and more elongated than controls when plated on a Matrigel substrate. These results implicate a role for CD155 in mediating tumor cell invasion and migration and suggest that CD155 may contribute to tumorigenesis

  16. The nonstructural proteins of Nipah virus play a key role in pathogenicity in experimentally infected animals.

    Directory of Open Access Journals (Sweden)

    Misako Yoneda

    Full Text Available Nipah virus (NiV P gene encodes P protein and three accessory proteins (V, C and W. It has been reported that all four P gene products have IFN antagonist activity when the proteins were transiently expressed. However, the role of those accessory proteins in natural infection with NiV remains unknown. We generated recombinant NiVs lacking V, C or W protein, rNiV(V-, rNiV(C-, and rNiV(W-, respectively, to analyze the functions of these proteins in infected cells and the implications in in vivo pathogenicity. All the recombinants grew well in cell culture, although the maximum titers of rNiV(V- and rNiV(C- were lower than the other recombinants. The rNiV(V-, rNiV(C- and rNiV(W- suppressed the IFN response as well as the parental rNiV, thereby indicating that the lack of each accessory protein does not significantly affect the inhibition of IFN signaling in infected cells. In experimentally infected golden hamsters, rNiV(V- and rNiV(C- but not the rNiV(W- virus showed a significant reduction in virulence. These results suggest that V and C proteins play key roles in NiV pathogenicity, and the roles are independent of their IFN-antagonist activity. This is the first report that identifies the molecular determinants of NiV in pathogenicity in vivo.

  17. NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis.

    Science.gov (United States)

    Hirota, Simon A; Ng, Jeffrey; Lueng, Alan; Khajah, Maitham; Parhar, Ken; Li, Yan; Lam, Victor; Potentier, Mireille S; Ng, Kelvin; Bawa, Misha; McCafferty, Donna-Marie; Rioux, Kevin P; Ghosh, Subrata; Xavier, Ramnik J; Colgan, Sean P; Tschopp, Jurg; Muruve, Daniel; MacDonald, Justin A; Beck, Paul L

    2011-06-01

    Attenuated innate immune responses to the intestinal microbiota have been linked to the pathogenesis of Crohn's disease (CD). Recent genetic studies have revealed that hypofunctional mutations of NLRP3, a member of the NOD-like receptor (NLR) superfamily, are associated with an increased risk of developing CD. NLRP3 is a key component of the inflammasome, an intracellular danger sensor of the innate immune system. When activated, the inflammasome triggers caspase-1-dependent processing of inflammatory mediators, such as IL-1β and IL-18. In the current study we sought to assess the role of the NLRP3 inflammasome in the maintenance of intestinal homeostasis through its regulation of innate protective processes. To investigate this role, Nlrp3(-/-) and wildtype mice were assessed in the dextran sulfate sodium and 2,4,6-trinitrobenzenesulfonic acid models of experimental colitis. Nlrp3(-/-) mice were found to be more susceptible to experimental colitis, an observation that was associated with reduced IL-1β, reduced antiinflammatory cytokine IL-10, and reduced protective growth factor TGF-β. Macrophages isolated from Nlrp3(-/-) mice failed to respond to bacterial muramyl dipeptide. Furthermore, Nlrp3-deficient neutrophils exhibited reduced chemotaxis and enhanced spontaneous apoptosis, but no change in oxidative burst. Lastly, Nlrp3(-/-) mice displayed altered colonic β-defensin expression, reduced colonic antimicrobial secretions, and a unique intestinal microbiota. Our data confirm an essential role for the NLRP3 inflammasome in the regulation of intestinal homeostasis and provide biological insight into disease mechanisms associated with increased risk of CD in individuals with NLRP3 mutations. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

  18. Closing the water cycle - the key role of water and wastewater management in a circular economy

    Science.gov (United States)

    Uhlenbrook, Stefan; Connor, Rick; Koncagul, Engin; Ortigara, Angela

    2017-04-01

    Planetary water boundaries are exceeded locally and regionally as water demand and use are escalating and per capita water availability is decreasing. However, wastewater represents an alternative yet reliable source containing for instance, nutrients (for use as fertilizer) and metals that can be extracted, and can be a source of energy. These characteristics mean that water and wastewater are set to play a key role in the circular economy. Furthermore, wastewater use can generate business opportunities and enhance water, food and energy security, therefore helping to alleviate poverty. However, to increase the collection, treatment and use of wastewater, investments in infrastructure and appropriate (low cost) technologies are needed. Ensuring the development of human and institutional capacity is also essential for proper wastewater management. The UN World Water Assessment Programme (WWAP) produces together with several UN-Water Members and Partners the annual World Water Development Report (WWDR). Its 2017 edition "Wastewater: The Untapped Resource" focuses on the critical role of wastewater management for vibrant economies, resilient societies and the maintenance of a healthy environment. Wastewater issues play also a central role in the 2030 Agenda for Sustainable Development, most notably through Sustainable Development Goal (SDG) target 6.3 that aims to improve water quality by reducing the proportion of untreated wastewater released to the environment and increasing its recycling and safe reuse globally. This target is interlinked with several other targets of SDG 6 ('the water goal') as well as to several other SDGs that relate to, poverty reduction, health, energy and food security, among others. The main policy-relevant messages of the WWDR 2017 will be introduced and linked to socio-hydrological approaches. These messages are an important input to the implementation of the water research agenda of the Panta Rhei initiative of IAHS.

  19. Developmental programming: the concept, large animal models, and the key role of uteroplacental vascular development.

    Science.gov (United States)

    Reynolds, L P; Borowicz, P P; Caton, J S; Vonnahme, K A; Luther, J S; Hammer, C J; Maddock Carlin, K R; Grazul-Bilska, A T; Redmer, D A

    2010-04-01

    Developmental programming refers to the programming of various bodily systems and processes by a stressor of the maternal system during pregnancy or during the neonatal period. Such stressors include nutritional stress, multiple pregnancy (i.e., increased numbers of fetuses in the gravid uterus), environmental stress (e.g., high environmental temperature, high altitude, prenatal steroid exposure), gynecological immaturity, and maternal or fetal genotype. Programming refers to impaired function of numerous bodily systems or processes, leading to poor growth, altered body composition, metabolic dysfunction, and poor productivity (e.g., poor growth, reproductive dysfunction) of the offspring throughout their lifespan and even across generations. A key component of developmental programming seems to be placental dysfunction, leading to altered fetal growth and development. We discuss various large animal models of developmental programming and how they have and will continue to contribute to our understanding of the mechanisms underlying altered placental function and developmental programming, and, further, how large animal models also will be critical to the identification and application of therapeutic strategies that will alleviate the negative consequences of developmental programming to improve offspring performance in livestock production and human medicine.

  20. 231 Using Multiple Regression Analysis in Modelling the Role of ...

    African Journals Online (AJOL)

    User

    of Internal Revenue, Tourism Bureau and hotel records. The multiple regression .... additional guest facilities such as restaurant, a swimming pool or child care and social function ... and provide good quality service to the public. Conclusion.

  1. Resolving Key Uncertainties in Subsurface Energy Recovery: One Role of In Situ Experimentation and URLs (Invited)

    Science.gov (United States)

    Elsworth, D.

    2013-12-01

    Significant uncertainties remain and influence the recovery of energy from the subsurface. These uncertainties include the fate and transport of long-lived radioactive wastes that result from the generation of nuclear power and have been the focus of an active network of international underground research laboratories dating back at least 35 years. However, other nascent carbon-free energy technologies including conventional and EGS geothermal methods, carbon-neutral methods such as carbon capture and sequestration and the utilization of reduced-carbon resources such as unconventional gas reservoirs offer significant challenges in their effective deployment. We illustrate the important role that in situ experiments may play in resolving behaviors at extended length- and time-scales for issues related to chemical-mechanical interactions. Significantly, these include the evolution of transport and mechanical characteristics of stress-sensitive fractured media and their influence of the long-term behavior of the system. Importantly, these interests typically relate to either creating reservoirs (hydroshearing in EGS reservoirs, artificial fractures in shales and coals) or maintaining seals at depth where the permeating fluids may include mixed brines, CO2, methane and other hydrocarbons. Critical questions relate to the interaction of these various fluid mixtures and compositions with the fractured substrate. Important needs are in understanding the roles of key processes (transmission, dissolution, precipitation, sorption and dynamic stressing) on the modification of effective stresses and their influence on the evolution of permeability, strength and induced seismicity on the resulting development of either wanted or unwanted fluid pathways. In situ experimentation has already contributed to addressing some crucial issues of these complex interactions at field scale. Important contributions are noted in understanding the fate and transport of long-lived wastes

  2. Oxidative responsiveness to multiple stressors in the key Antarctic species, Adamussium colbecki: Interactions between temperature, acidification and cadmium exposure.

    Science.gov (United States)

    Benedetti, Maura; Lanzoni, Ilaria; Nardi, Alessandro; d'Errico, Giuseppe; Di Carlo, Marta; Fattorini, Daniele; Nigro, Marco; Regoli, Francesco

    2016-10-01

    High-latitude marine ecosystems are ranked to be among the most sensitive regions to climate change since highly stenothermal and specially adapted organisms might be seriously affected by global warming and ocean acidification. The present investigation was aimed to provide new insights on the sensitivity to such environmental stressors in the key Antarctic species, Adamussium colbecki, focussing also on their synergistic effects with cadmium exposure, naturally abundant in this area for upwelling phenomena. Scallops were exposed for 2 weeks to various combinations of Cd (0 and 40 μgL-1), pH (8.05 and 7.60) and temperature (-1 and +1 °C). Beside Cd bioaccumulation, a wide panel of early warning biomarkers were analysed in digestive glands and gills including levels of metallothioneins, individual antioxidants and total oxyradical scavenging capacity, onset of oxidative cell damage like lipid peroxidation, lysosomal stability, DNA integrity and peroxisomal proliferation. Results indicated reciprocal interactions between multiple stressors and their elaboration by a quantitative hazard model based on the relevance and magnitude of effects, highlighted a different sensitivity of analysed tissues. Due to cellular adaptations to high basal Cd content, digestive gland appeared more tolerant toward other prooxidant stressors, but sensitive to variations of the metal. On the other hand, gills were more affected by various combinations of stressors occurring at higher temperature. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Kalrn plays key roles within and outside of the nervous system

    Directory of Open Access Journals (Sweden)

    Mandela Prashant

    2012-11-01

    Full Text Available Abstract Background The human KALRN gene, which encodes a complex, multifunctional Rho GDP/GTP exchange factor, has been linked to cardiovascular disease, psychiatric disorders and neurodegeneration. Examination of existing Kalrn knockout mouse models has focused only on neuronal phenotypes. However, Kalirin was first identified through its interaction with an enzyme involved in the synthesis and secretion of multiple bioactive peptides, and studies in C.elegans revealed roles for its orthologue in neurosecretion. Results We used a broad array of tests to evaluate the effects of ablating a single exon in the spectrin repeat region of Kalrn (KalSRKO/KO; transcripts encoding Kalrn isoforms containing only the second GEF domain can still be produced from the single remaining functional Kalrn promoter. As expected, KalSRKO/KO mice showed a decrease in anxiety-like behavior and a passive avoidance deficit. No changes were observed in prepulse inhibition of acoustic startle or tests of depression-like behavior. Growth rate, parturition and pituitary secretion of growth hormone and prolactin were deficient in the KalSRKO/KO mice. Based on the fact that a subset of Kalrn isoforms is expressed in mouse skeletal muscle and the observation that muscle function in C.elegans requires its Kalrn orthologue, KalSRKO/KO mice were evaluated in the rotarod and wire hang tests. KalSRKO/KO mice showed a profound decrease in neuromuscular function, with deficits apparent in KalSR+/KO mice; these deficits were not as marked when loss of Kalrn expression was restricted to the nervous system. Pre- and postsynaptic deficits in the neuromuscular junction were observed, along with alterations in sarcomere length. Conclusions Many of the widespread and diverse deficits observed both within and outside of the nervous system when expression of Kalrn is eliminated may reflect its role in secretory granule function and its expression outside of the nervous system.

  4. Mental Health and American Indian Women's Multiple Roles.

    Science.gov (United States)

    Napholz, Linda

    1995-01-01

    Survey of 148 college educated, employed American Indian women in urban Wisconsin examined sex role orientation and indicators of mental well-being. Sex-typed respondents had significantly higher depression, higher role conflict, lower self-esteem, and lower life satisfaction than cross-typed or androgynous respondents. Undifferentiated…

  5. Key role of symbiotic dinitrogen fixation in tropical forest secondary succession

    Science.gov (United States)

    Batterman, Sarah A.; Hedin, Lars O.; van Breugel, Michiel; Ransijn, Johannes; Craven, Dylan J.; Hall, Jefferson S.

    2013-10-01

    Forests contribute a significant portion of the land carbon sink, but their ability to sequester CO2 may be constrained by nitrogen, a major plant-limiting nutrient. Many tropical forests possess tree species capable of fixing atmospheric dinitrogen (N2), but it is unclear whether this functional group can supply the nitrogen needed as forests recover from disturbance or previous land use, or expand in response to rising CO2 (refs 6, 8). Here we identify a powerful feedback mechanism in which N2 fixation can overcome ecosystem-scale deficiencies in nitrogen that emerge during periods of rapid biomass accumulation in tropical forests. Over a 300-year chronosequence in Panama, N2-fixing tree species accumulated carbon up to nine times faster per individual than their non-fixing neighbours (greatest difference in youngest forests), and showed species-specific differences in the amount and timing of fixation. As a result of fast growth and high fixation, fixers provided a large fraction of the nitrogen needed to support net forest growth (50,000kg carbon per hectare) in the first 12years. A key element of ecosystem functional diversity was ensured by the presence of different N2-fixing tree species across the entire forest age sequence. These findings show that symbiotic N2 fixation can have a central role in nitrogen cycling during tropical forest stand development, with potentially important implications for the ability of tropical forests to sequester CO2.

  6. AF10 plays a key role in the survival of uncommitted hematopoietic cells.

    Directory of Open Access Journals (Sweden)

    Raquel Chamorro-Garcia

    Full Text Available Hematopoiesis is a complex process regulated by both cell intrinsic and cell extrinsic factors. Alterations in the expression of critical genes during hematopoiesis can modify the balance between stem cell differentiation and proliferation, and may ultimately give rise to leukemia and other diseases. AF10 is a transcription factor that has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. The link between AF10 and leukemia, together with the known interactions between AF10 and hematopoietic regulators, suggests that AF10 may be important in hematopoiesis and in leukemic transformation. Here we show that AF10 is important for proper hematopoietic differentiation. The induction of hematopoietic differentiation in both human hematopoietic cell lines and murine total bone marrow cells triggers a decrease of AF10 mRNA and protein levels, particularly in stem cells and multipotent progenitors. Gain- and loss-of-function studies demonstrate that over- or under-expression of AF10 leads to apoptotic cell death in stem cells and multipotent progenitors. We conclude that AF10 plays a key role in the maintenance of multipotent hematopoietic cells.

  7. Antimicrobial Nanoplexes meet Model Bacterial Membranes: the key role of Cardiolipin

    Science.gov (United States)

    Marín-Menéndez, Alejandro; Montis, Costanza; Díaz-Calvo, Teresa; Carta, Davide; Hatzixanthis, Kostas; Morris, Christopher J.; McArthur, Michael; Berti, Debora

    2017-01-01

    Antimicrobial resistance to traditional antibiotics is a crucial challenge of medical research. Oligonucleotide therapeutics, such as antisense or Transcription Factor Decoys (TFDs), have the potential to circumvent current resistance mechanisms by acting on novel targets. However, their full translation into clinical application requires efficient delivery strategies and fundamental comprehension of their interaction with target bacterial cells. To address these points, we employed a novel cationic bolaamphiphile that binds TFDs with high affinity to form self-assembled complexes (nanoplexes). Confocal microscopy revealed that nanoplexes efficiently transfect bacterial cells, consistently with biological efficacy on animal models. To understand the factors affecting the delivery process, liposomes with varying compositions, taken as model synthetic bilayers, were challenged with nanoplexes and investigated with Scattering and Fluorescence techniques. Thanks to the combination of results on bacteria and synthetic membrane models we demonstrate for the first time that the prokaryotic-enriched anionic lipid Cardiolipin (CL) plays a key-role in the TFDs delivery to bacteria. Moreover, we can hypothesize an overall TFD delivery mechanism, where bacterial membrane reorganization with permeability increase and release of the TFD from the nanoplexes are the main factors. These results will be of great benefit to boost the development of oligonucleotides-based antimicrobials of superior efficacy.

  8. Hidden keys to survival: the type, density, pattern and functional role of emperor penguin body feathers.

    Science.gov (United States)

    Williams, Cassondra L; Hagelin, Julie C; Kooyman, Gerald L

    2015-10-22

    Antarctic penguins survive some of the harshest conditions on the planet. Emperor penguins breed on the sea ice where temperatures drop below -40°C and forage in -1.8°C waters. Their ability to maintain 38°C body temperature in these conditions is due in large part to their feathered coat. Penguins have been reported to have the highest contour feather density of any bird, and both filoplumes and plumules (downy feathers) are reported absent in penguins. In studies modelling the heat transfer properties and the potential biomimetic applications of penguin plumage design, the insulative properties of penguin plumage have been attributed to the single afterfeather attached to contour feathers. This attribution of the afterfeather as the sole insulation component has been repeated in subsequent studies. Our results demonstrate the presence of both plumules and filoplumes in the penguin body plumage. The downy plumules are four times denser than afterfeathers and play a key, previously overlooked role in penguin survival. Our study also does not support the report that emperor penguins have the highest contour feather density. © 2015 The Author(s).

  9. Key role of symbiotic dinitrogen fixation in tropical forest secondary succession.

    Science.gov (United States)

    Batterman, Sarah A; Hedin, Lars O; van Breugel, Michiel; Ransijn, Johannes; Craven, Dylan J; Hall, Jefferson S

    2013-10-10

    Forests contribute a significant portion of the land carbon sink, but their ability to sequester CO2 may be constrained by nitrogen, a major plant-limiting nutrient. Many tropical forests possess tree species capable of fixing atmospheric dinitrogen (N2), but it is unclear whether this functional group can supply the nitrogen needed as forests recover from disturbance or previous land use, or expand in response to rising CO2 (refs 6, 8). Here we identify a powerful feedback mechanism in which N2 fixation can overcome ecosystem-scale deficiencies in nitrogen that emerge during periods of rapid biomass accumulation in tropical forests. Over a 300-year chronosequence in Panama, N2-fixing tree species accumulated carbon up to nine times faster per individual than their non-fixing neighbours (greatest difference in youngest forests), and showed species-specific differences in the amount and timing of fixation. As a result of fast growth and high fixation, fixers provided a large fraction of the nitrogen needed to support net forest growth (50,000 kg carbon per hectare) in the first 12 years. A key element of ecosystem functional diversity was ensured by the presence of different N2-fixing tree species across the entire forest age sequence. These findings show that symbiotic N2 fixation can have a central role in nitrogen cycling during tropical forest stand development, with potentially important implications for the ability of tropical forests to sequester CO2.

  10. Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera.

    Science.gov (United States)

    Gallardo, Miguel; Barrio, Santiago; Fernandez, Marisol; Paradela, Alberto; Arenas, Alicia; Toldos, Oscar; Ayala, Rosa; Albizua, Enriqueta; Jimenez, Ana; Redondo, Santiago; Garcia-Martin, Rosa Maria; Gilsanz, Florinda; Albar, Juan Pablo; Martinez-Lopez, Joaquin

    2013-11-19

    JAK-STAT signaling through the JAK2V617F mutation is central to the pathogenesis of myeloproliferative neoplasms (MPN). However, other events could precede the JAK2 mutation. The aim of this study is to analyze the phenotypic divergence between polycytemia vera (PV) and essential thrombocytemia (ET) to find novel therapeutics targets by a proteomic and functional approach to identify alternative routes to JAK2 activation. Through 2D-DIGE and mass spectrometry of granulocyte protein from 20 MPN samples, showed differential expression of HSP70 in PV and ET besides other 60 proteins. Immunohistochemistry of 46 MPN bone marrow samples confirmed HSP70 expression. The median of positive granulocytes was 80% in PV (SD 35%) vs. 23% in ET (SD 34.25%). In an ex vivo model KNK437 was used as an inhibition model assay of HSP70, showed dose-dependent inhibition of cell growth and burst formation unit erythroid (BFU-E) in PV and ET, increased apoptosis in the erythroid lineage, and decreased pJAK2 signaling, as well as a specific siRNA for HSP70. These data suggest a key role for HSP70 in proliferation and survival of the erythroid lineage in PV, and may represent a potential therapeutic target in MPN, especially in PV.

  11. On the key role of droughts in the dynamics of summer fires in Mediterranean Europe.

    Science.gov (United States)

    Turco, Marco; von Hardenberg, Jost; AghaKouchak, Amir; Llasat, Maria Carmen; Provenzale, Antonello; Trigo, Ricardo M

    2017-03-06

    Summer fires frequently rage across Mediterranean Europe, often intensified by high temperatures and droughts. According to the state-of-the-art regional fire risk projections, in forthcoming decades climate effects are expected to become stronger and possibly overcome fire prevention efforts. However, significant uncertainties exist and the direct effect of climate change in regulating fuel moisture (e.g. warmer conditions increasing fuel dryness) could be counterbalanced by the indirect effects on fuel structure (e.g. warmer conditions limiting fuel amount), affecting the transition between climate-driven and fuel-limited fire regimes as temperatures increase. Here we analyse and model the impact of coincident drought and antecedent wet conditions (proxy for the climatic factor influencing total fuel and fine fuel structure) on the summer Burned Area (BA) across all eco-regions in Mediterranean Europe. This approach allows BA to be linked to the key drivers of fire in the region. We show a statistically significant relationship between fire and same-summer droughts in most regions, while antecedent climate conditions play a relatively minor role, except in few specific eco-regions. The presented models for individual eco-regions provide insights on the impacts of climate variability on BA, and appear to be promising for developing a seasonal forecast system supporting fire management strategies.

  12. Induction of AGAMOUS gene expression plays a key role in ripening of tomato sepals in vitro.

    Science.gov (United States)

    Ishida, B K; Jenkins, S M; Say, B

    1998-03-01

    In vitro culture of VFNT Cherry tomato sepals (calyx) at 16-21 degrees C results in developmental changes that are similar to those that occur in fruit tissue [10]. Sepals become swollen, red, and succulent, produce ethylene, and have increased levels of polygalacturonase RNA. They also produce many flavor volatiles characteristic of ripe tomato fruit and undergo similar changes in sugar content [11]. We examined the expression of the tomato AGAMOUS gene, TAG1, in ripening, in vitro sepal cultures and other tissues from the plant and found that TAG1 RNA accumulates to higher levels than expected from data from other plants. Contrary to reports on the absence of AGAMOUS in sepals, TAG1 RNA levels in green sepals from greenhouse-grown plants is detectable, its concentration increasing with in vitro ripening to levels that were even higher than in red, ripe fruit. Sepals of fruit on transgenic tomato plants that expressed TAG1 ectopically were induced by low temperature to ripen in vivo, producing lycopene and undergoing cell wall softening as is characteristic of pericarpic tissue. We therefore propose that the induction of elevated TAG1 gene expression plays a key role in developmental changes that result in sepal ripening.

  13. Role of key-regulator genes in melanoma susceptibility and pathogenesis among patients from South Italy

    International Nuclear Information System (INIS)

    Casula, Milena; Sini, MariaCristina; Palomba, Grazia; The Italian Melanoma Intergroup; Palmieri, Giuseppe; Muggiano, Antonio; Cossu, Antonio; Budroni, Mario; Caracò, Corrado; Ascierto, Paolo A; Pagani, Elena; Stanganelli, Ignazio; Canzanella, Sergio

    2009-01-01

    Several genetic alterations have been demonstrated to contribute to the development and progression of melanoma. In this study, we further investigated the impact of key-regulator genes in susceptibility and pathogenesis of such a disease. A large series (N = 846) of sporadic and familial cases originating from South Italy was screened for germline mutations in p16 CDKN2A , BRCA2, and MC1R genes by DHPLC analysis and automated DNA sequencing. Paired primary melanomas and lymph node metastases from same patients (N = 35) as well as melanoma cell lines (N = 18) were analyzed for somatic mutations in NRAS, BRAF, and p16 CDKN2A genes. For melanoma susceptibility, investigations at germline level indicated that p16 CDKN2A was exclusively mutated in 16/545 (2.9%) non-Sardinian patients, whereas BRCA2 germline mutations were observed in 4/91 (4.4%) patients from North Sardinia only. Two MC1R germline variants, Arg151Cys and Asp294His, were significantly associated with melanoma in Sardinia. Regarding genetic events involved in melanoma pathogenesis at somatic level, mutually-exclusive mutations of NRAS and BRAF genes were observed at quite same rate (about two thirds) in cultured and in vivo melanomas (either primary or metastatic lesions). Conversely, p16 CDKN2A gene alterations were observed at increased rates moving from primary to metastatic melanomas and melanoma cell lines. Activation of the ERK gene product was demonstrated to be consistently induced by a combination of molecular alterations (NRAS/BRAF mutations and p16 CDKN2A silencing). Our findings further clarified that: a) mutation prevalence in melanoma susceptibility genes may vary within each specific geographical area; b) multiple molecular events are accumulating during melanomagenesis

  14. Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival

    International Nuclear Information System (INIS)

    Rubert, Joëlle; Qian, Zhiyan; Andraos, Rita; Guthy, Daniel A; Radimerski, Thomas

    2011-01-01

    The JAK2 V617F mutation plays a major role in the pathogenesis of myeloproliferative neoplasms and is found in the vast majority of patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia or from primary myelofibrosis. The V617F mutation is thought to provide hematopoietic stem cells and myeloid progenitors with a survival and proliferation advantage. It has previously been shown that activated JAK2 promotes cell survival by upregulating the anti-apoptotic STAT5 target gene Bcl-xL. In this study, we have investigated the role of additional apoptotic players, the pro-apoptotic protein Bim as well as the anti-apoptotic protein Mcl-1. Pharmacological inhibition of JAK2/STAT5 signaling in JAK2 V617F mutant SET-2 and MB-02 cells was used to study effects on signaling, cell proliferation and apoptosis by Western blot analysis, WST-1 proliferation assays and flow cytometry. Cells were transfected with siRNA oligos to deplete candidate pro- and anti-apoptotic proteins. Co-immunoprecipitation assays were performed to assess the impact of JAK2 inhibition on complexes of pro- and anti-apoptotic proteins. Treatment of JAK2 V617F mutant cell lines with a JAK2 inhibitor was found to trigger Bim activation. Furthermore, Bim depletion by RNAi suppressed JAK2 inhibitor-induced cell death. Bim activation following JAK2 inhibition led to enhanced sequestration of Mcl-1, besides Bcl-xL. Importantly, Mcl-1 depletion by RNAi was sufficient to compromise JAK2 V617F mutant cell viability and sensitized the cells to JAK2 inhibition. We conclude that Bim and Mcl-1 have key opposing roles in regulating JAK2 V617F cell survival and propose that inactivation of aberrant JAK2 signaling leads to changes in Bim complexes that trigger cell death. Thus, further preclinical evaluation of combinations of JAK2 inhibitors with Bcl-2 family antagonists that also tackle Mcl-1, besides Bcl-xL, is warranted to assess the therapeutic potential

  15. Role of phytohormones in organogenic ability of elm multiplicated shoots

    Czech Academy of Sciences Publication Activity Database

    Malá, J.; Gaudinová, Alena; Dobrev, Petre; Eder, Josef; Cvikrová, Milena

    2006-01-01

    Roč. 50, č. 1 (2006), s. 8-14 ISSN 0006-3134 Institutional research plan: CEZ:AV0Z5038910; CEZ:AV0Z50380511 Keywords : auxin * cytokinins * multiplication of elm Subject RIV: GK - Forestry Impact factor: 1.198, year: 2006

  16. The role of the cerebellum in multiple sclerosis

    DEFF Research Database (Denmark)

    Weier, Katrin; Banwell, Brenda; Cerasa, Antonio

    2015-01-01

    In multiple sclerosis (MS), cerebellar signs and symptoms as well as cognitive dysfunction are frequent and contribute to clinical disability with only poor response to symptomatic treatment. The current consensus paper highlights the broad range of clinical signs and symptoms of MS patients, which...

  17. A Role for Attentional Reorienting During Approximate Multiplication and Division

    Directory of Open Access Journals (Sweden)

    Curren Katz

    2017-12-01

    Full Text Available When asked to estimate the outcome of arithmetic problems, participants overestimate for addition problems and underestimate for subtraction problems, both in symbolic and non-symbolic format. This bias is referred to as operational momentum effect (OM. The attentional shifts account holds that during computation of the outcome participants are propelled too far along a spatial number representation. OM was observed in non-symbolic multiplication and division while being absent in symbolic multiplication and division. Here, we investigate whether (a the absence of the OM in symbolic multiplication and division was due to the presentation of the correct outcome amongst the response alternatives, putatively triggering verbally mediated fact retrieval, and whether (b OM is correlated with attentional parameters, as stipulated by the attentional account. Participants were presented with symbolic and non-symbolic multiplication and division problems. Among seven incorrect response alternatives participants selected the most plausible result. Participants were also presented with a Posner task, with valid (70%, invalid (15% and neutral (15% cues pointing to the position at which a subsequent target would appear. While no OM was observed in symbolic format, non-symbolic problems were subject to OM. The non-symbolic OM was positively correlated with reorienting after invalid cues. These results provide further evidence for a functional association between spatial attention and approximate arithmetic, as stipulated by the attentional shifts account of OM. They also suggest that the cognitive processes underlying multiplication and division are less prone to spatial biases compared to addition and subtraction, further underlining the involvement of differential cognitive processes.

  18. Key role of phosphodiesterase 4A (PDE4A) in autophagy triggered by yessotoxin

    International Nuclear Information System (INIS)

    Fernández-Araujo, A.; Alfonso, A.; Vieytes, M.R.; Botana, L.M.

    2015-01-01

    Highlights: • YTX activates autophagic cell death after 48 h of treatment. • After 24 h of YTX incubation, the autophagic LC3B expression is increased. • High LC3B levels after 24 h can be related with extrinsic apoptosis activated by YTX. • PDEA4 plays a key role in the autophagy activation. - Abstract: Understanding the mechanism of action of the yessotoxin (YTX) is crucial since this drug has potential pharmacological effects in allergic processes, tumor proliferation and neurodegenerative diseases. It has been described that YTX activates apoptosis after 24 h of treatment, while after 48 h of incubation with the toxin a decrease in cell viability corresponding to cellular differentiation or non-apoptotic cell death was observed. In this paper, these processes were extensively studied by using the erythroleukemia K-562 cell line. On one hand, events of K-562 cell differentiation into erythrocytes after YTX treatment were studied using hemin as positive control of cell differentiation. Cell differentiation was studied through the cyclic nucleotide response element binding (phospho-CREB) and the transferrin receptor (TfR) expression. On the other hand, using rapamycin as positive control, autophagic hallmarks, as non-apoptotic cell death, were studied after toxin exposure. In this case, the mechanistic target of rapamycin (mTOR) and light chain 3B (LC3B) levels were measured to check autophagy activation. The results showed that cell differentiation was not occurring after 48 h of toxin incubation while at this time the autophagy was triggered. Furthermore after 24 h of toxin treatment none of these processes were activated. In addition, the role of the type 4A phosphodiesterase (PDE4A), the intracellular target of YTX, was checked. PDE4A-silencing experiments showed different regulation steps of PDE4A in the autophagic processes triggered either by traditional compounds or YTX. In summary, after 48 h YTX treatment PDE4A-dependent autophagy, as non

  19. Key role of lipid management in nitrogen and aroma metabolism in an evolved wine yeast strain.

    Science.gov (United States)

    Rollero, Stéphanie; Mouret, Jean-Roch; Sanchez, Isabelle; Camarasa, Carole; Ortiz-Julien, Anne; Sablayrolles, Jean-Marie; Dequin, Sylvie

    2016-02-09

    Fermentative aromas play a key role in the organoleptic profile of young wines. Their production depends both on yeast strain and fermentation conditions. A present-day trend in the wine industry consists in developing new strains with aromatic properties using adaptive evolution approaches. An evolved strain, Affinity™ ECA5, overproducing esters, was recently obtained. In this study, dynamics of nitrogen consumption and of the fermentative aroma synthesis of the evolved and its ancestral strains were compared and coupled with a transcriptomic analysis approach to better understand the metabolic reshaping of Affinity™ ECA5. Nitrogen assimilation was different between the two strains, particularly amino acids transported by carriers regulated by nitrogen catabolite repression. We also observed differences in the kinetics of fermentative aroma production, especially in the bioconversion of higher alcohols into acetate esters. Finally, transcriptomic data showed that the enhanced bioconversion into acetate esters by the evolved strain was associated with the repression of genes involved in sterol biosynthesis rather than an enhanced expression of ATF1 and ATF2 (genes coding for the enzymes responsible for the synthesis of acetate esters from higher alcohols). An integrated approach to yeast metabolism-combining transcriptomic analyses and online monitoring data-showed differences between the two strains at different levels. Differences in nitrogen source consumption were observed suggesting modifications of NCR in the evolved strain. Moreover, the evolved strain showed a different way of managing the lipid source, which notably affected the production of acetate esters, likely because of a greater availability of acetyl-CoA for the evolved strain.

  20. Performance Analysis of Direct-Sequence Code-Division Multiple-Access Communications with Asymmetric Quadrature Phase-Shift-Keying Modulation

    Science.gov (United States)

    Wang, C.-W.; Stark, W.

    2005-01-01

    This article considers a quaternary direct-sequence code-division multiple-access (DS-CDMA) communication system with asymmetric quadrature phase-shift-keying (AQPSK) modulation for unequal error protection (UEP) capability. Both time synchronous and asynchronous cases are investigated. An expression for the probability distribution of the multiple-access interference is derived. The exact bit-error performance and the approximate performance using a Gaussian approximation and random signature sequences are evaluated by extending the techniques used for uniform quadrature phase-shift-keying (QPSK) and binary phase-shift-keying (BPSK) DS-CDMA systems. Finally, a general system model with unequal user power and the near-far problem is considered and analyzed. The results show that, for a system with UEP capability, the less protected data bits are more sensitive to the near-far effect that occurs in a multiple-access environment than are the more protected bits.

  1. Multiple roles for orexin/hypocretin in addiction

    Science.gov (United States)

    Mahler, Stephen V.; Smith, Rachel J.; Moorman, David E.; Sartor, Gregory C.; Aston-Jones, Gary

    2013-01-01

    Orexins/hypocretins are hypothalamic peptides involved in arousal and wakefulness, but also play a critical role in drug addiction and reward-related behaviors. Here, we review the roles played by orexins in a variety of animal models of drug addiction, emphasizing both commonalities and differences for orexin’s involvement in seeking of the major classes of abused drugs, as well as food. One common theme that emerges is an involvement of orexins in drug seeking triggered by external stimuli (e.g., cues, contexts or stressors). We also discuss the functional neuronal circuits in which orexins are embedded, and how these circuits mediate addiction-related behaviors, with particular focus on the role of orexin and glutamate interactions within the ventral tegmental area. Finally, we attempt to contextualize the role of orexins in reward by discussing ways in which these peptides, expressed in only a few thousand neurons in the brain, can have such wide-ranging effects on behavior. PMID:22813971

  2. The Multiple Roles that Youth Development Program Leaders Adopt with Youth

    Science.gov (United States)

    Walker, Kathrin C.

    2011-01-01

    The roles that program leaders establish in their relationships with youth structure how leaders are able to foster youth development. This article examines the complex roles program leaders create in youth programs and investigates how they balanced multiple roles to most effectively respond to the youth they serve. Analyses of qualitative data…

  3. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

    Science.gov (United States)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C.A.; Patsopoulos, Nikolaos A.; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Booth, David R.; Potter, Simon C.; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D’alfonso, Sandra; Blackburn, Hannah; Boneschi, Filippo Martinelli; Liddle, Jennifer; Harbo, Hanne F.; Perez, Marc L.; Spurkland, Anne; Waller, Matthew J; Mycko, Marcin P.; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T.; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J.; Barcellos, Lisa F.; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E.; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P.; Brassat, David; Broadley, Simon A.; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M.; Cavalla, Paola; Celius, Elisabeth G.; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B.; Cozen, Wendy; Cree, Bruce A.C.; Cross, Anne H.; Cusi, Daniele; Daly, Mark J.; Davis, Emma; de Bakker, Paul I.W.; Debouverie, Marc; D’hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F.A.; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans-Peter; Heard, Rob N.; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G.; Kilpatrick, Trevor J.; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S.; Leone, Maurizio A.; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R.; Link, Jenny; Liu, Jianjun; Lorentzen, Åslaug R.; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L.; Mentch, Frank; Mero, Inger-Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell-Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L.; Ramsay, Patricia P.; Reunanen, Mauri; Reynolds, Richard; Rioux, John D.; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P.; Rückert, Ina-Maria; Salvetti, Marco; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A.; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J.; Sellebjerg, Finn; Selmaj, Krzysztof W.; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M.A.; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C.; Sulonen, Anna-Maija; Sundqvist, Emilie; Syvänen, Ann-Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M.; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A.; Tronczynska, Ewa; Casas, Juan P.; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S.; Wang, Kai; Mathew, Christopher G.; Wason, James; Palmer, Colin N.A.; Wichmann, H-Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C.; Yaouanq, Jacqueline; Viswanathan, Ananth C.; Zhang, Haitao; Wood, Nicholas W.; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J.; De Jager, Philip L.; Peltonen, Leena; Stewart, Graeme J.; Hafler, David A.; Hauser, Stephen L.; McVean, Gil; Donnelly, Peter; Compston, Alastair

    2011-01-01

    Multiple sclerosis (OMIM 126200) is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability.1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals;2,3 and systematic attempts to identify linkage in multiplex families have confirmed that variation within the Major Histocompatibility Complex (MHC) exerts the greatest individual effect on risk.4 Modestly powered Genome-Wide Association Studies (GWAS)5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects play a key role in disease susceptibility.11 Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the Class I region. Immunologically relevant genes are significantly over-represented amongst those mapping close to the identified loci and particularly implicate T helper cell differentiation in the pathogenesis of multiple sclerosis. PMID:21833088

  4. Strangulation and Its Role in Multiple Causes of Death.

    Science.gov (United States)

    Hlavaty, Leigh; Sung, LokMan

    2017-12-01

    Forensic pathologists have a duty to determine the cause and manner of death and are bound by international guidelines in the completion of the death certificate. Sometimes, there are complex circumstances surrounding a death that cannot be captured in the structure of the death certificate and its requirement of listing only 1 cause of death per line. Cases may have multiple causes of death with comorbid medical conditions or inflicted injuries that equally contribute to the ultimate demise. Compared with other forms of homicide, autopsy evidence of strangulation will often be found with other life-threatening traumatic injuries. The Wayne County Medical Examiner's Office conducted a retrospective study of strangulation cases that came into the office from mid-2007 to the end of 2016. The purpose of the study was to examine patterns of injuries in strangulation cases and identify those with additional traumatic injuries of commensurate extent that required incorporation into the cause of death. A total of 43 strangulation cases were found, of which there were equal numbers of ligature and manual strangulations (19 each) and 5 cases in which the method was not specified, and decedents were divided: 63% female and 37% male. Fourteen of these cases were recognized to have multiple causes of death, where blunt force trauma was the most common additional cause, and the sex distribution weighed heavily toward the female (approximately 79%).

  5. An Analysis of Student Affairs Professionals' Management of Role Conflict and Multiple Roles in Relation to Work/Life Balance

    Science.gov (United States)

    Mayo, Nicole Lepone

    2013-01-01

    The purpose of this inquiry is to study how student affairs professionals manage role conflict in relation to work/life balance based on the challenging culture of the field. The underlying goals are to identify the barriers or challenges of managing multiple roles as a student affairs administrator and identify strategies to assist employees in…

  6. The multiple roles of Fatty Acid Handling Proteins in brain

    Directory of Open Access Journals (Sweden)

    Valentine SF Moullé

    2012-09-01

    Full Text Available Lipids are essential components of a living organism as energy source but also as constituent of the membrane lipid bilayer. In addition fatty acid (FA derivatives interact with many signaling pathways. FAs have amphipathic properties and therefore require being associated to protein for both transport and intracellular trafficking. Here we will focus on several fatty acid handling proteins, among which the fatty acid translocase/CD36 (FAT/CD36, members of fatty acid transport proteins (FATPs, and lipid chaperones fatty acid-binding proteins (FABPs. A decade of extensive studies has helped decipher the mechanism of action of these proteins in peripheral tissue with high lipid metabolism. However, considerably less information is available regarding their role in the brain, despite the high lipid content of this tissue. This review will primarily focus on the recent studies that have highlighted the crucial role of lipid handling proteins in brain FA transport, neuronal differentiation and development, cognitive processes and brain diseases. Finally a special focus will be made on the recent studies that have revealed the role of FAT/CD36 in brain lipid sensing and nervous control of energy balance.

  7. Multiple roles for the actin cytoskeleton during regulated exocytosis

    Science.gov (United States)

    Porat-Shliom, Natalie; Milberg, Oleg; Masedunskas, Andrius; Weigert, Roberto

    2014-01-01

    Regulated exocytosis is the main mechanism utilized by specialized secretory cells to deliver molecules to the cell surface by virtue of membranous containers (i.e. secretory vesicles). The process involves a series of highly coordinated and sequential steps, which include the biogenesis of the vesicles, their delivery to the cell periphery, their fusion with the plasma membrane and the release of their content into the extracellular space. Each of these steps is regulated by the actin cytoskeleton. In this review, we summarize the current knowledge regarding the involvement of actin and its associated molecules during each of the exocytic steps in vertebrates, and suggest that the overall role of the actin cytoskeleton during regulated exocytosis is linked to the architecture and the physiology of the secretory cells under examination. Specifically, in neurons, neuroendocrine, endocrine, and hematopoietic cells, which contain small secretory vesicles that undergo rapid exocytosis (on the order of milliseconds), the actin cytoskeleton plays a role in pre-fusion events, where it acts primarily as a functional barrier and facilitates docking. In exocrine and other secretory cells, which contain large secretory vesicles that undergo slow exocytosis (seconds to minutes), the actin cytoskeleton plays a role in post-fusion events, where it regulates the dynamics of the fusion pore, facilitates the integration of the vesicles into the plasma membrane, provides structural support, and promotes the expulsion of large cargo molecules. PMID:22986507

  8. Role Clarification Processes for Better Integration of Nurse Practitioners into Primary Healthcare Teams: A Multiple-Case Study

    Directory of Open Access Journals (Sweden)

    Isabelle Brault

    2014-01-01

    Full Text Available Role clarity is a crucial issue for effective interprofessional collaboration. Poorly defined roles can become a source of conflict in clinical teams and reduce the effectiveness of care and services delivered to the population. Our objective in this paper is to outline processes for clarifying professional roles when a new role is introduced into clinical teams, that of the primary healthcare nurse practitioner (PHCNP. To support our empirical analysis we used the Canadian National Interprofessional Competency Framework, which defines the essential components for role clarification among professionals. A qualitative multiple-case study was conducted on six cases in which the PHCNP role was introduced into primary care teams. Data collection included 34 semistructured interviews with key informants involved in the implementation of the PHCNP role. Our results revealed that the best performing primary care teams were those that used a variety of organizational and individual strategies to carry out role clarification processes. From this study, we conclude that role clarification is both an organizational process to be developed and a competency that each member of the primary care team must mobilize to ensure effective interprofessional collaboration.

  9. Role clarification processes for better integration of nurse practitioners into primary healthcare teams: a multiple-case study.

    Science.gov (United States)

    Brault, Isabelle; Kilpatrick, Kelley; D'Amour, Danielle; Contandriopoulos, Damien; Chouinard, Véronique; Dubois, Carl-Ardy; Perroux, Mélanie; Beaulieu, Marie-Dominique

    2014-01-01

    Role clarity is a crucial issue for effective interprofessional collaboration. Poorly defined roles can become a source of conflict in clinical teams and reduce the effectiveness of care and services delivered to the population. Our objective in this paper is to outline processes for clarifying professional roles when a new role is introduced into clinical teams, that of the primary healthcare nurse practitioner (PHCNP). To support our empirical analysis we used the Canadian National Interprofessional Competency Framework, which defines the essential components for role clarification among professionals. A qualitative multiple-case study was conducted on six cases in which the PHCNP role was introduced into primary care teams. Data collection included 34 semistructured interviews with key informants involved in the implementation of the PHCNP role. Our results revealed that the best performing primary care teams were those that used a variety of organizational and individual strategies to carry out role clarification processes. From this study, we conclude that role clarification is both an organizational process to be developed and a competency that each member of the primary care team must mobilize to ensure effective interprofessional collaboration.

  10. A no-key-exchange secure image sharing scheme based on Shamir's three-pass cryptography protocol and the multiple-parameter fractional Fourier transform.

    Science.gov (United States)

    Lang, Jun

    2012-01-30

    In this paper, we propose a novel secure image sharing scheme based on Shamir's three-pass protocol and the multiple-parameter fractional Fourier transform (MPFRFT), which can safely exchange information with no advance distribution of either secret keys or public keys between users. The image is encrypted directly by the MPFRFT spectrum without the use of phase keys, and information can be shared by transmitting the encrypted image (or message) three times between users. Numerical simulation results are given to verify the performance of the proposed algorithm.

  11. Multiple Continental Radiations and Correlates of Diversification in Lupinus (Leguminosae): Testing for Key Innovation with Incomplete Taxon Sampling

    Science.gov (United States)

    Drummond, Christopher S.; Eastwood, Ruth J.; Miotto, Silvia T. S.; Hughes, Colin E.

    2012-01-01

    Replicate radiations provide powerful comparative systems to address questions about the interplay between opportunity and innovation in driving episodes of diversification and the factors limiting their subsequent progression. However, such systems have been rarely documented at intercontinental scales. Here, we evaluate the hypothesis of multiple radiations in the genus Lupinus (Leguminosae), which exhibits some of the highest known rates of net diversification in plants. Given that incomplete taxon sampling, background extinction, and lineage-specific variation in diversification rates can confound macroevolutionary inferences regarding the timing and mechanisms of cladogenesis, we used Bayesian relaxed clock phylogenetic analyses as well as MEDUSA and BiSSE birth–death likelihood models of diversification, to evaluate the evolutionary patterns of lineage accumulation in Lupinus. We identified 3 significant shifts to increased rates of net diversification (r) relative to background levels in the genus (r = 0.18–0.48 lineages/myr). The primary shift occurred approximately 4.6 Ma (r = 0.48–1.76) in the montane regions of western North America, followed by a secondary shift approximately 2.7 Ma (r = 0.89–3.33) associated with range expansion and diversification of allopatrically distributed sister clades in the Mexican highlands and Andes. We also recovered evidence for a third independent shift approximately 6.5 Ma at the base of a lower elevation eastern South American grassland and campo rupestre clade (r = 0.36–1.33). Bayesian ancestral state reconstructions and BiSSE likelihood analyses of correlated diversification indicated that increased rates of speciation are strongly associated with the derived evolution of perennial life history and invasion of montane ecosystems. Although we currently lack hard evidence for “replicate adaptive radiations” in the sense of convergent morphological and ecological trajectories among species in different

  12. Characterization of osteopontin-uranyl interaction: role of multiple phosphorylations

    International Nuclear Information System (INIS)

    Qi, Lei

    2014-01-01

    While some metals are essential for Life, other ones are only toxicants for living organisms, tolerated below well-definite concentrations. This is the case for uranium, a natural element which has no known biological function. It is a low α emitter and its chemical toxicity rather than its radiological toxicity is a subject of concern. Once in the body, this metal reaches the blood and accumulates in the bones under the action of unknown mechanisms. Uranium mainly exists in form of uranyl ion (UO 2 2+ ) in aqueous media and particularly reacts with carboxylates, phenolates and phosphates of the proteins. Previous studies have highlighted that UO 2 2+ modulates the SPP1 expression, a gene which codes for osteopontin (OPN). This highly phosphorylated glycoprotein plays an important role in bone homeostasis. This role and its biochemical properties led us to hypothesize that OPN might be a potential target of UO 2 2+ and involved in its accumulation in bones. A simple and original purification process was optimized to produce very highly purified OPN starting from human and bovine milk. Various biophysical approaches were set up and confirmed that both bovine and human OPN display very high affinity for UO 2 2+ . Moreover, the formation of stable UO 2 -protein complexes originating from structural changes was evidenced. The major role of phosphorylations, both on the OPN's affinity for UO 2 2+ and the stability of the UO 2 -protein complexes, was confirmed. These results demonstrate that OPN presents all the characteristics to be a major UO 2 2+ binding-protein in vitro, and they open new insights in the understanding of the UO 2 2+ mineralization process mechanisms. (author) [fr

  13. Multiple role occupancy in midlife: balancing work and family life in Britain.

    Science.gov (United States)

    Evandrou, Maria; Glaser, Karen; Henz, Ursula

    2002-12-01

    This article investigates the extent of multiple-role occupancy among midlife individuals in Britain in cross-section and over the life course, focusing on work and family commitments. The association between demographic and social factors and multiple-role obligations is also investigated. The research is based on secondary analysis of the British Family and Working Lives Survey, which contains retrospective paid work, caregiving, and child coresidence histories. The proportion of individuals in midlife (women aged 45-59 and men aged 45-64) who have multiple roles, in terms of paid work and consistent family care, at any one point in time is low (2%). This is primarily due to the relatively small proportion (7%) of people in this age group who are caring for a dependent. Being older, unmarried, and in poor health significantly reduces the number of roles held among men and women. Although the frequency of multiple role occupancy, and intensive multiple role occupancy, is low on a cross-sectional basis, a much higher proportion of individuals have ever occupied multiple roles over their life course (14%). The findings will inform debate on how policy can best aid those endeavouring to balance paid work, family life, and caring responsibilities.

  14. Multiple roles of genome-attached bacteriophage terminal proteins

    International Nuclear Information System (INIS)

    Redrejo-Rodríguez, Modesto; Salas, Margarita

    2014-01-01

    Protein-primed replication constitutes a generalized mechanism to initiate DNA or RNA synthesis in linear genomes, including viruses, gram-positive bacteria, linear plasmids and mobile elements. By this mechanism a specific amino acid primes replication and becomes covalently linked to the genome ends. Despite the fact that TPs lack sequence homology, they share a similar structural arrangement, with the priming residue in the C-terminal half of the protein and an accumulation of positively charged residues at the N-terminal end. In addition, various bacteriophage TPs have been shown to have DNA-binding capacity that targets TPs and their attached genomes to the host nucleoid. Furthermore, a number of bacteriophage TPs from different viral families and with diverse hosts also contain putative nuclear localization signals and localize in the eukaryotic nucleus, which could lead to the transport of the attached DNA. This suggests a possible role of bacteriophage TPs in prokaryote-to-eukaryote horizontal gene transfer. - Highlights: • Protein-primed genome replication constitutes a strategy to initiate DNA or RNA synthesis in linear genomes. • Bacteriophage terminal proteins (TPs) are covalently attached to viral genomes by their primary function priming DNA replication. • TPs are also DNA-binding proteins and target phage genomes to the host nucleoid. • TPs can also localize in the eukaryotic nucleus and may have a role in phage-mediated interkingdom gene transfer

  15. Multiple roles of genome-attached bacteriophage terminal proteins

    Energy Technology Data Exchange (ETDEWEB)

    Redrejo-Rodríguez, Modesto; Salas, Margarita, E-mail: msalas@cbm.csic.es

    2014-11-15

    Protein-primed replication constitutes a generalized mechanism to initiate DNA or RNA synthesis in linear genomes, including viruses, gram-positive bacteria, linear plasmids and mobile elements. By this mechanism a specific amino acid primes replication and becomes covalently linked to the genome ends. Despite the fact that TPs lack sequence homology, they share a similar structural arrangement, with the priming residue in the C-terminal half of the protein and an accumulation of positively charged residues at the N-terminal end. In addition, various bacteriophage TPs have been shown to have DNA-binding capacity that targets TPs and their attached genomes to the host nucleoid. Furthermore, a number of bacteriophage TPs from different viral families and with diverse hosts also contain putative nuclear localization signals and localize in the eukaryotic nucleus, which could lead to the transport of the attached DNA. This suggests a possible role of bacteriophage TPs in prokaryote-to-eukaryote horizontal gene transfer. - Highlights: • Protein-primed genome replication constitutes a strategy to initiate DNA or RNA synthesis in linear genomes. • Bacteriophage terminal proteins (TPs) are covalently attached to viral genomes by their primary function priming DNA replication. • TPs are also DNA-binding proteins and target phage genomes to the host nucleoid. • TPs can also localize in the eukaryotic nucleus and may have a role in phage-mediated interkingdom gene transfer.

  16. [Role of radiotherapy in the treatment of multiple myeloma].

    Science.gov (United States)

    Mose, S; Pfitzner, D; Rahn, A; Nierhoff, C; Schiemann, M; Böttcher, H D

    2000-11-01

    Chemotherapy is the treatment of choice in multiple myeloma; but there are no curative options. Therefore, the treatment rationale is characterized by reduction of symptoms and inhibition of complications. Regarding reduction of pain, treatment of (impending) fractures, and spinal cord compression radiation is an important part of palliative treatment. In our retrospective study we report the effect of radiotherapy on reduction of pain, recalcification and the reduction of neurological symptoms and evaluate factors which have an impact on therapeutic outcome. From 1, Jan 1988 to 31, Dec 1998, 42 patients (19 women, 23 men; range of ages 46 to 85 years, median age 64.9 years) with 71 target volumes were irradiated (median dose 36 Gy, 2 to 3 Gy 5 times/week) because of symptomatic disease (67/71: osseous pain, 45/71: fractures/impending fractures, 13/71: spinal cord compression) (Tables 1 and 2). The median time from diagnosis to the first course of radiotherapy was 11.9 months (0.3 to 90 months). At the time of first irradiation, 5 and 37 patients were in tumor Stage II and III (Salmon/Durie), respectively. The median value of the Karnofsky performance was 70% (40 to 90%). During follow-up (at least 6 months) in 85% of target volumes complete and partial pain relief (measured by patients' perception and the use of analgetic medication) was achieved; recurrences were seen in 8.8%. In 26/56 (46.4%) lesions evaluable a recalcification was seen whereas 17.9% showed progressive disease (comparison of radiographs before and after radiation). In 22.3% of all lesions initially with impending fracture (4/18) radiotherapy failed because of fracture after treatment (Tables 3 and 4). Simultaneous chemotherapy and a Karnofsky performance > or = 70 had a significant impact on a positive response to treatment, respectively. Spinal cord compression symptoms were reduced in 7/13 (53.8%) of patients (scaled due to the classification by Findlay 1987). The median survival from

  17. Sortilin and Its Multiple Roles in Cardiovascular and Metabolic Diseases

    DEFF Research Database (Denmark)

    Goettsch, Claudia; Kjølby, Mads Fuglsang; Aikawa, Elena

    2018-01-01

    Cardiovascular disease is a leading cause of morbidity and mortality in the Western world. Studies of sortilin's influence on cardiovascular and metabolic diseases goes far beyond the genome-wide association studies that have revealed an association between cardiovascular diseases and the 1p13...... locus that encodes sortilin. Emerging evidence suggests a significant role of sortilin in the pathogenesis of vascular and metabolic diseases; this includes type II diabetes mellitus via regulation of insulin resistance, atherosclerosis through arterial wall inflammation and calcification...... of sortilin's contributions to cardiovascular and metabolic diseases but focuses particularly on atherosclerosis. We summarize recent clinical findings that suggest that sortilin may be a cardiovascular risk biomarker and also discuss sortilin as a potential drug target....

  18. Basic roles of key molecules connected with NMDAR signaling pathway on regulating learning and memory and synaptic plasticity

    Institute of Scientific and Technical Information of China (English)

    Hui Wang; Rui-Yun Peng

    2016-01-01

    With key roles in essential brain functions ranging from the long-term potentiation (LTP) to synaptic plasticity,the N-methyl-D-aspartic acid receptor (NMDAR) can be considered as one of the fundamental glutamate receptors in the central nervous system.The role of NMDA R was first identified in synaptic plasticity and has been extensively studied.Some molecules,such as Ca2+,postsynaptic density 95 (PSD-95),calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ),protein kinase A (PKA),mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate (cAMP) responsive element binding protein (CREB),are of special importance in learning and memory.This review mainly focused on the new research of key molecules connected with learning and memory,which played important roles in the NMDAR signaling pathway.

  19. Role of radiotherapy in the treatment of multiple myeloma

    International Nuclear Information System (INIS)

    Mose, S.; Pfitzner, D.; Rahn, A.; Nierhoff, C.; Schiemann, M.; Boettcher, H.D.

    2000-01-01

    suppose that in multiple myeloma the local response to radiation is supported by a favorable performance status and simultaneous chemotherapy. Irradiation treatment does not change prognosis regarding overall survival. (orig.) [de

  20. Measuring Public Leadership: Developing Scales for Four Key Public Leadership Roles

    NARCIS (Netherlands)

    Tummers, Lars; Knies, Eva|info:eu-repo/dai/nl/313875421

    2016-01-01

    This article on public leadership contributes to the literature by (1) focusing on the ‘public’ aspect of leadership and (2) developing quantitative scales for measuring four public leadership roles. These roles all refer to the extent to which public leaders actively support their employees in

  1. The emerging role of Big Data in key development issues: Opportunities, challenges, and concerns

    Directory of Open Access Journals (Sweden)

    Nir Kshetri

    2014-12-01

    Full Text Available This paper presents a review of academic literature, policy documents from government organizations and international agencies, and reports from industries and popular media on the trends in Big Data utilization in key development issues and its worthwhileness, usefulness, and relevance. By looking at Big Data deployment in a number of key economic sectors, it seeks to provide a better understanding of the opportunities and challenges of using it for addressing key issues facing the developing world. It reviews the uses of Big Data in agriculture and farming activities in developing countries to assess the capabilities required at various levels to benefit from Big Data. It also provides insights into how the current digital divide is associated with and facilitated by the pattern of Big Data diffusion and its effective use in key development areas. It also discusses the lessons that developing countries can learn from the utilization of Big Data in big corporations as well as in other activities in industrialized countries.

  2. Increasing Physical Activity among Adults with Disabilities: Doctors Can Play a Key Role

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. Dianna Carroll, a senior health scientist with CDC’s Division of Human Development and Disability, talks about the role of doctors and other health professionals in increasing physical activity among adults with disabilities.

  3. KEYING AND ROLE PLAY IN BUSINESS COMMUNICATION: GENDER, AGE AND RACE CUES

    Directory of Open Access Journals (Sweden)

    GABRIELA DUMBRAVĂ

    2013-10-01

    Full Text Available This study comes as a sequel to other two papers published in this journal in 2010 and 2012 being part of a larger research that approaches business communication from the perspective of Goffman’s theory of the relational dimension of meaning. The paper starts from the premise that meaning is generated within the context of each specific interaction, as a result of a culturally determined process of framing, during which inherited patterns of thought and behavior establish well defined positions from which the interlocutors perceive and respond to one another. It also aims at further analyzing the process of keying by identifying the paradigm shifts that individualize business encounters according to gender, age, and race cues, as well as the communication malfunctions induced by keying errors (misunderstandings, conflict and discrimination.

  4. Thioredoxin plays a key role in retinal neuropathy prior to endothelial damage in diabetic mice

    OpenAIRE

    Ren, Xiang; Li, Chen; Liu, Junli; Zhang, Chenghong; Fu, Yuzhen; Wang, Nina; Ma, Haiying; Lu, Heyuan; Kong, Hui; Kong, Li

    2017-01-01

    Diabetes is a chronic metabolic syndrome that results in changes in carbohydrate, lipid and protein metabolism. With diabetes for a long time, it increases the risk of diabetic retinopathy (DR) and long-term morbidity and mortality. Moreover, emerging evidence suggests that neuron damage occurs earlier than microvascular complications in DR patients, but the underlying mechanism is unclear. We investigated diabetes-induced retinal neuropathy and elucidated key molecular events to identify new...

  5. KeyPathwayMiner - De-novo network enrichment by combining multiple OMICS data and biological networks

    DEFF Research Database (Denmark)

    Baumbach, Jan; Alcaraz, Nicolas; Pauling, Josch K.

    We tackle the problem of de-novo pathway extraction. Given a biological network and a set of case-control studies, KeyPathwayMiner efficiently extracts and visualizes all maximal connected sub-networks that contain mainly genes that are dysregulated, e.g., differentially expressed, in most cases ...

  6. Secret-key agreement over spatially correlated multiple-antenna channels in the low-SNR regime

    KAUST Repository

    Zorgui, Marwen; Rezki, Zouheir; Alomair, Basel; Jorswieck, Eduard A.; Alouini, Mohamed-Slim

    2015-01-01

    We consider secret-key agreement with public discussion over Rayleigh fast-fading channels with transmit, receive and eavesdropper correlation. The legitimate receiver along with the eavesdropper are assumed to have perfect channel knowledge while the transmitter has only knowledge of the correlation matrices. We analyze the secret-key capacity in the low signal-to-noise ratio (SNR) regime. We derive closed-form expressions for the first and the second derivatives of the secret-key capacity with respect to SNR at SNR= 0, for arbitrary correlation matrices and number of transmit, receive and eavesdropper antennas. Moreover, we identify optimal transmission strategies achieving these derivatives. For instance, we prove that achieving the first and the second derivatives requires a uniform power distribution between the eigenvectors spanning the maximal-eigenvalue eigenspace of the transmit correlation matrix. We also compare the optimal transmission scheme to a simple uniform power allocation. Finally, we express the minimum energy required for sharing a secret-key bit as well as the wideband slope in terms of the system parameters.

  7. Secret-key agreement over spatially correlated multiple-antenna channels in the low-SNR regime

    KAUST Repository

    Zorgui, Marwen

    2015-09-28

    We consider secret-key agreement with public discussion over Rayleigh fast-fading channels with transmit, receive and eavesdropper correlation. The legitimate receiver along with the eavesdropper are assumed to have perfect channel knowledge while the transmitter has only knowledge of the correlation matrices. We analyze the secret-key capacity in the low signal-to-noise ratio (SNR) regime. We derive closed-form expressions for the first and the second derivatives of the secret-key capacity with respect to SNR at SNR= 0, for arbitrary correlation matrices and number of transmit, receive and eavesdropper antennas. Moreover, we identify optimal transmission strategies achieving these derivatives. For instance, we prove that achieving the first and the second derivatives requires a uniform power distribution between the eigenvectors spanning the maximal-eigenvalue eigenspace of the transmit correlation matrix. We also compare the optimal transmission scheme to a simple uniform power allocation. Finally, we express the minimum energy required for sharing a secret-key bit as well as the wideband slope in terms of the system parameters.

  8. The key role of causal explanation in the climate change issue

    Directory of Open Access Journals (Sweden)

    Francesca Pongiglione

    2012-06-01

    Full Text Available The basis for adoption of pro-environment behaviour is the understanding of causal passages within climate dynamics. The understanding of the causes of climate change is necessary in order to be able to take mitigation actions  (the subject needs to be aware of his role as a causal agent. Conversely, the understanding of the consequences of climate change is essential in motivating action (the subject must be aware of the risks caused by it in order to prevent them. The case of ozone depletion confirms this view: the understanding of its causal dynamics played a determining role in people’s behavioural response.

  9. Host association of Borrelia burgdorferi sensu lato--the key role of host complement.

    Science.gov (United States)

    Kurtenbach, Klaus; De Michelis, Simona; Etti, Susanne; Schäfer, Stefanie M; Sewell, Henna-Sisko; Brade, Volker; Kraiczy, Peter

    2002-02-01

    Borrelia burgdorferi sensu lato (s.l.), the tick-borne agent of Lyme borreliosis, is a bacterial species complex comprising 11 genospecies. Here, we discuss whether the delineation of genospecies is ecologically relevant. We provide evidence that B. burgdorferi s.l. is structured ecologically into distinct clusters that are host specific. An immunological model for niche adaptation is proposed that suggests the operation of complement-mediated selection in the midgut of the feeding tick. We conclude that vertebrate hosts rather than tick species are the key to Lyme borreliosis spirochaete diversity.

  10. Change Management and the SENCo Role: Developing Key Performance Indicators of Inclusivity

    Science.gov (United States)

    Done, Elizabeth; Murphy, Mike; Bedford, Clare

    2016-01-01

    This article highlights the changing role of special educational needs co-ordinators (SENCos) in England. SENCos are now required to manage change strategically and deliver inclusive school cultures. A school-based evaluative study undertaken by a teacher who is studying for the postgraduate National Award for SEN Co-ordination (NASENCO) for…

  11. Change Management and the SENCo Role: Developing Key Performance Indicators in the Strategic Development of Inclusivity

    Science.gov (United States)

    Done, Liz; Murphy, Mike; Watt, Mia

    2016-01-01

    This article follows an earlier publication highlighting the changing role of special educational needs co-ordinators (SENCos) in England. SENCos are now required to manage change strategically and deliver inclusive school cultures. School-based action research undertaken by a teacher studying for the postgraduate National Award for SEN…

  12. Make Time to Recharge: Growth and Renewal Play Key Roles in Sustaining School Leaders

    Science.gov (United States)

    Drago-Severson, Ellie; Blum-DeStefano, Jessica

    2015-01-01

    Being a school leader in any role is hard, gratifying, and a gift of love. While it can be enormously satisfying to serve students, teachers, families, and school communities, leaders need to refill themselves in order to continue giving to others. This article highlights a learning-oriented model of leadership development and capacity building…

  13. [The multiple social roles of female lay caretakers of hospitalized children].

    Science.gov (United States)

    Wegner, Wiliam; Pedro, Eva Neri Rubim

    2010-06-01

    This is a qualitative, descriptive, exploratory, and interventionist research carried out with nine female lay caretakers of children undergoing oncologic treatment. The objectives were to present the multiple social roles performed by female lay caretakers of children with cancer and to discuss the caretaker's role in society. The study was carried out between March and April, 2007, at Hospital de Clinicas de Porto Alegre, Rio Grande do Sul, Brazil. The data collection was performed with the focal group technique. The results were examined through the analysis of thematic content, which evidenced the multiple social roles performed by women, the main group of caretakers in society, regardless of the context. Final considerations enhance a discussion in the educational, political and social levels about the redistribution of social roles, particularly family responsibility between men and women. The participation of the nursing staff can take place through the comprehension of those roles imposed by the context and facilitate family inclusion in the care relationship.

  14. Increasing Physical Activity among Adults with Disabilities: Doctors Can Play a Key Role

    Centers for Disease Control (CDC) Podcasts

    2014-04-22

    In this podcast, Dr. Dianna Carroll, a senior health scientist with CDC’s Division of Human Development and Disability, talks about the role of doctors and other health professionals in increasing physical activity among adults with disabilities.  Created: 4/22/2014 by National Center on Birth Defects and Developmental Disabilities (NCBDDD).   Date Released: 5/7/2014.

  15. Histidine Metabolism and IGPD Play a Key Role in Cefquinome Inhibiting Biofilm Formation of Staphylococcus xylosus

    Directory of Open Access Journals (Sweden)

    Yong-hui Zhou

    2018-04-01

    Full Text Available Staphylococcus xylosus (S. xylosus is an AT-rich and coagulase-negative Staphylococcus (CNS. It is normally regarded as non-pathogenic, however, recent studies have demonstrated that it is related to human opportunistic infections and bovine mastitis. In addition, S. xylosus strains have the ability to form biofilm. Biofilms are also involved in chronic infections and antibiotic resistance, there are only a few reports about cefquinome inhibiting S. xylosus biofilm formation and the protein targets of cefquinome. In our study, we found that sub-MICs of cefquinome were sufficient to inhibit biofilm formation. To investigate the potential protein targets of cefquinome, we used iTRAQ for the analyses of cells at two different conditions: 1/2-MIC (0.125 μg/mL cefquinome treatment and no treatment. Using iTRAQ technique and KEGG database analysis, we found that proteins differently expression in histidine metabolism pathway may play a role in the process by which 1/2-MIC (0.125 μg/mL cefquinome inhibits S. xylosus biofilm formation. Interestingly, we found a sharply down-regulated enzyme [A0A068E9J3 imidazoleglycerol-phosphate dehydratase (IGPD] involved in histidine metabolism pathway in cefquinome-treated cells. We demonstrated the important role of IGPD in sub-MICs cefquinome inhibiting biofilm formation of S. xylosus by gene (hisB knockout, IGPD enzyme activity and histidine content assays. Thus, our data sheds light on important role of histidine metabolism in S. xylosus biofilm formation; especially, IGPD involved in histidine metabolism might play a crucial role in sub-MICs cefquinome inhibition of biofilm formation of S. xylosus, and we propose IGPD as an attractive protein target of cefquinome.

  16. Stress and the multiple-role woman: taking a closer look at the "superwoman".

    Science.gov (United States)

    Sumra, Monika K; Schillaci, Michael A

    2015-01-01

    In the academic literature there is debate as to whether women who engage in multiple social roles experience more or less stress than women in fewer roles. For the present research we examined the relationship between levels of engagement in seven distinct roles and perceived stress and life satisfaction in a small non-random sample of women in North America (N = 308). We did not find a significant correlation between role engagement and perceived stress, though we did find a small but significant positive correlation between role engagement and life satisfaction. Similarly, in a subset of the participants (N = 31), there was not a significant relationship between the level of role engagement and physiological stress as measured by hair or urinary cortisol levels. We found a significant negative correlation between perceived stress and life satisfaction, and role satisfaction. The results from multiple regression models did not identify the level of role engagement as a significant predictor of either perceived stress or life satisfaction. Role satisfaction in addition to several life style variables such as the frequency of sex and exercise were identified as significant predictors of both outcome variables. We also examined the popularized notion of the "superwoman", which we defined as women who fell within the 4th quartile of role engagement, or those engaged in the wife/mother/worker/homemaker role combination. Based on popular discourses surrounding the superwoman we expected that superwomen would exhibit higher levels of perceived stress. Our results revealed that superwomen do not experience a significantly higher level of perceived stress than non-superwomen. The results of our study therefore suggest that multiple role engagement in women, even at a relatively high level as experienced by "superwomen", is not associated with significantly higher stress, or reduced life satisfaction.

  17. Stress and the multiple-role woman: taking a closer look at the "superwoman".

    Directory of Open Access Journals (Sweden)

    Monika K Sumra

    Full Text Available In the academic literature there is debate as to whether women who engage in multiple social roles experience more or less stress than women in fewer roles. For the present research we examined the relationship between levels of engagement in seven distinct roles and perceived stress and life satisfaction in a small non-random sample of women in North America (N = 308. We did not find a significant correlation between role engagement and perceived stress, though we did find a small but significant positive correlation between role engagement and life satisfaction. Similarly, in a subset of the participants (N = 31, there was not a significant relationship between the level of role engagement and physiological stress as measured by hair or urinary cortisol levels. We found a significant negative correlation between perceived stress and life satisfaction, and role satisfaction. The results from multiple regression models did not identify the level of role engagement as a significant predictor of either perceived stress or life satisfaction. Role satisfaction in addition to several life style variables such as the frequency of sex and exercise were identified as significant predictors of both outcome variables. We also examined the popularized notion of the "superwoman", which we defined as women who fell within the 4th quartile of role engagement, or those engaged in the wife/mother/worker/homemaker role combination. Based on popular discourses surrounding the superwoman we expected that superwomen would exhibit higher levels of perceived stress. Our results revealed that superwomen do not experience a significantly higher level of perceived stress than non-superwomen. The results of our study therefore suggest that multiple role engagement in women, even at a relatively high level as experienced by "superwomen", is not associated with significantly higher stress, or reduced life satisfaction.

  18. Stress and the Multiple-Role Woman: Taking a Closer Look at the “Superwoman”

    Science.gov (United States)

    Sumra, Monika K.; Schillaci, Michael A.

    2015-01-01

    In the academic literature there is debate as to whether women who engage in multiple social roles experience more or less stress than women in fewer roles. For the present research we examined the relationship between levels of engagement in seven distinct roles and perceived stress and life satisfaction in a small non-random sample of women in North America (N = 308). We did not find a significant correlation between role engagement and perceived stress, though we did find a small but significant positive correlation between role engagement and life satisfaction. Similarly, in a subset of the participants (N = 31), there was not a significant relationship between the level of role engagement and physiological stress as measured by hair or urinary cortisol levels. We found a significant negative correlation between perceived stress and life satisfaction, and role satisfaction. The results from multiple regression models did not identify the level of role engagement as a significant predictor of either perceived stress or life satisfaction. Role satisfaction in addition to several life style variables such as the frequency of sex and exercise were identified as significant predictors of both outcome variables. We also examined the popularized notion of the “superwoman”, which we defined as women who fell within the 4th quartile of role engagement, or those engaged in the wife/mother/worker/homemaker role combination. Based on popular discourses surrounding the superwoman we expected that superwomen would exhibit higher levels of perceived stress. Our results revealed that superwomen do not experience a significantly higher level of perceived stress than non-superwomen. The results of our study therefore suggest that multiple role engagement in women, even at a relatively high level as experienced by “superwomen”, is not associated with significantly higher stress, or reduced life satisfaction. PMID:25816317

  19. The key role of supply chain actors in groundwater irrigation development in North Africa

    Science.gov (United States)

    Lejars, Caroline; Daoudi, Ali; Amichi, Hichem

    2017-09-01

    The role played by supply chain actors in the rapid development of groundwater-based irrigated agriculture is analyzed. Agricultural groundwater use has increased tremendously in the past 50 years, leading to the decline of water tables. Groundwater use has enabled intensification of existing farming systems and ensured economic growth. This "groundwater economy" has been growing rapidly due to the initiative of farmers and the involvement of a wide range of supply chain actors, including suppliers of equipment, inputs retailers, and distributors of irrigated agricultural products. In North Africa, the actors in irrigated production chains often operate at the margin of public policies and are usually described as "informal", "unstructured", and as participating in "groundwater anarchy". This paper underlines the crucial role of supply chain actors in the development of groundwater irrigation, a role largely ignored by public policies and rarely studied. The analysis is based on three case studies in Morocco, Tunisia and Algeria, and focuses on the horticultural sub-sector, in particular on onions and tomatoes, which are irrigated high value crops. The study demonstrates that although supply chain actors are catalyzers of the expansion of groundwater irrigation, they could also become actors in adaptation to the declining water tables. Through their informal activities, they help reduce market risks, facilitate credit and access to subsidies, and disseminate innovation. The interest associated with making these actors visible to agricultural institutions is discussed, along with methods of getting them involved in the management of the resource on which they depend.

  20. The PICALM protein plays a key role in iron homeostasis and cell proliferation.

    Directory of Open Access Journals (Sweden)

    Paula B Scotland

    Full Text Available The ubiquitously expressed phosphatidylinositol binding clathrin assembly (PICALM protein associates with the plasma membrane, binds clathrin, and plays a role in clathrin-mediated endocytosis. Alterations of the human PICALM gene are present in aggressive hematopoietic malignancies, and genome-wide association studies have recently linked the PICALM locus to late-onset Alzheimer's disease. Inactivating and hypomorphic Picalm mutations in mice cause different degrees of severity of anemia, abnormal iron metabolism, growth retardation and shortened lifespan. To understand PICALM's function, we studied the consequences of PICALM overexpression and characterized PICALM-deficient cells derived from mutant fit1 mice. Our results identify a role for PICALM in transferrin receptor (TfR internalization and demonstrate that the C-terminal PICALM residues are critical for its association with clathrin and for the inhibitory effect of PICALM overexpression on TfR internalization. Murine embryonic fibroblasts (MEFs that are deficient in PICALM display several characteristics of iron deficiency (increased surface TfR expression, decreased intracellular iron levels, and reduced cellular proliferation, all of which are rescued by retroviral PICALM expression. The proliferation defect of cells that lack PICALM results, at least in part, from insufficient iron uptake, since it can be corrected by iron supplementation. Moreover, PICALM-deficient cells are particularly sensitive to iron chelation. Taken together, these data reveal that PICALM plays a critical role in iron homeostasis, and offer new perspectives into the pathogenesis of PICALM-associated diseases.

  1. RE: Forests and forest management plays a key role in mitigating climate change

    DEFF Research Database (Denmark)

    Bentsen, Niclas Scott; Nord-Larsen, Thomas; Larsen, Søren

    2016-01-01

    as also reported by Naudts et al. By ignoring the link between forestry and fossil carbon pools and not considering development in the absence of forest management, there is no accounting for the effect on GHG emissions, and no basis for estimating the contribution of forest management to cl......The report by Naudts et al. concludes that forest management in Europe during the last 260 years has failed to result in net CO2 removal from the atmosphere. The authors have reached this conclusion through their failure to consider a key factor in their otherwise comprehensive analysis....... The authors present an analysis of net carbon emissions from forest, but omit substitution effects related to the link between forest management and the fossil carbon pool. The link between fossil and terrestrial carbon pools is however critical for modelling climate impacts. To conclude as they do...

  2. Hypoxia-inducible factor-1 alpha has a key role in hypoxic preconditioning.

    Science.gov (United States)

    Taie, Satoshi; Ono, Junichiro; Iwanaga, Yasuyuki; Tomita, Shuhei; Asaga, Takehiko; Chujo, Kosuke; Ueki, Masaaki

    2009-08-01

    Sublethal hypoxia induces tolerance to subsequent hypoxic insults in a process known as hypoxic preconditioning (HP). Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a key transcription protein involved in the mechanism of HP. In this study, we investigated the effects of HP on tissue oxygenation and expression of HIF-1 alpha gene targets in the brain using neural cell-specific HIF-1 alpha-deficient mice. The animals were exposed to 8% oxygen for 3 hours. Twenty-four hours later, the oxygen partial pressure (pO(2)) of brain tissue and gene expression were measured during hypoxia. HP improved the pO(2) of brain tissue during subsequent hypoxia with upregulated inducible nitric oxide synthase in wild-type mice, whereas HP had no detectable effect in the mutant mice. Our results indicate that the protective effects of HP may be partially mediated by improving tissue oxygenation via HIF-1 alpha and inducible nitric oxide synthase.

  3. A role for VAV1 in experimental autoimmune encephalomyelitis and multiple sclerosis

    DEFF Research Database (Denmark)

    Jagodic, Maja; Colacios, Celine; Nohra, Rita

    2009-01-01

    Multiple sclerosis, the most common cause of progressive neurological disability in young adults, is a chronic inflammatory disease. There is solid evidence for a genetic influence in multiple sclerosis, and deciphering the causative genes could reveal key pathways influencing the disease. A genome...... region on rat chromosome 9 regulates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Using interval-specific congenic rat lines and association of single-nucleotide polymorphisms with inflammatory phenotypes, we localized the gene of influence to Vav1, which codes for a signal......-transducing protein in leukocytes. Analysis of seven human cohorts (12,735 individuals) demonstrated an association of rs2546133-rs2617822 haplotypes in the first VAV1 intron with multiple sclerosis (CA: odds ratio, 1.18; CG: odds ratio, 0.86; TG: odds ratio, 0.90). The risk CA haplotype also predisposed for higher...

  4. The key incident monitoring and management system - history and role in quality improvement.

    Science.gov (United States)

    Badrick, Tony; Gay, Stephanie; Mackay, Mark; Sikaris, Ken

    2018-01-26

    The determination of reliable, practical Quality Indicators (QIs) from presentation of the patient with a pathology request form through to the clinician receiving the report (the Total Testing Process or TTP) is a key step in identifying areas where improvement is necessary in laboratories. The Australasian QIs programme Key Incident Monitoring and Management System (KIMMS) began in 2008. It records incidents (process defects) and episodes (occasions at which incidents may occur) to calculate incident rates. KIMMS also uses the Failure Mode Effects Analysis (FMEA) to assign quantified risk to each incident type. The system defines risk as incident frequency multiplied by both a harm rating (on a 1-10 scale) and detection difficulty score (also a 1-10 scale). Between 2008 and 2016, laboratories participating rose from 22 to 69. Episodes rose from 13.2 to 43.4 million; incidents rose from 114,082 to 756,432. We attribute the rise in incident rate from 0.86% to 1.75% to increased monitoring. Haemolysis shows the highest incidence (22.6% of total incidents) and the highest risk (26.68% of total risk). "Sample is suspected to be from the wrong patient" has the second lowest frequency, but receives the highest harm rating (10/10) and detection difficulty score (10/10), so it is calculated to be the 8th highest risk (2.92%). Similarly, retracted (incorrect) reports QI has the 10th highest frequency (3.9%) but the harm/difficulty calculation confers the second highest risk (11.17%). TTP incident rates are generally low (less than 2% of observed episodes), however, incident risks, their frequencies multiplied by both ratings of harm and discovery difficulty scores, concentrate improvement attention and resources on the monitored incident types most important to manage.

  5. THE KEY ROLE OF SOLAR DYNAMICS IN THE CHROMOSPHERIC HANLE POLARIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Carlin, E. S.; Bianda, M., E-mail: escarlin@irsol.ch [Istituto Ricerche Solari Locarno, 6600 Locarno (Switzerland)

    2016-11-01

    The quantum theory of polarized light allows one to model scattering in the solar atmosphere for inferring its properties. This powerful approach has revealed two key long-standing problems in solar physics: the puzzling dilemmas between theory and observations in several anomalously polarized spectral lines and the need for inferring the ubiquitous weak chromospheric magnetic fields, which requires discriminating the Hanle effect in dynamic optically thick plasmas. However, the ever-present dynamics, i.e., the temporal evolution of heatings and macroscopic motions, has been widely disregarded when modeling and interpreting the scattering polarization. This has hindered a consistent theoretical solution to the puzzle while falsifying the Hanle diagnosis. Here, we show that the dynamical evolution is a keystone for solving both problems because its systematic impact allows an explanation of the observations from “anomalous” instantaneous polarization signals. Evolution accounted for, we reproduce amplitudes and (spectral and spatial) shapes of the Ca i 4227 Å polarization at solar disk center, identifying a restrictive arrangement of magnetic fields, kinematics, heatings, and spatio-temporal resolution. We find that the joint action of dynamics, Hanle effect, and low temporal resolutions mimics Zeeman linear polarization profiles, the true weak-field Zeeman signals being negligible. Our results allow reinterpretation of many polarization signals of the solar spectra and support time-dependent scattering polarization as a powerful tool for deciphering the spatio-temporal distribution of chromospheric heatings and fields. This approach may be a key aid in developing the Hanle diagnosis for the solar atmosphere.

  6. Key Roles for MYC, KIT and RET signaling in secondary angiosarcomas

    DEFF Research Database (Denmark)

    Styring, E; Seinen, J; Dominguez-Valentin, M

    2014-01-01

    of the gene signature to an external data set. RESULTS: In total, 103 genes were significantly deregulated between primary and secondary angiosarcomas. Secondary angiosarcomas showed upregulation of MYC, KIT and RET and downregulation of CDKN2C. Functional annotation analysis identified multiple target genes...... in the receptor protein tyrosine kinase pathway. The results were validated using RT-qPCR and immunohistochemistry. Further, the gene signature was applied to an external data set and, herein, distinguished primary from secondary angiosarcomas. CONCLUSIONS: Upregulation of MYC, KIT and RET and downregulation......BACKGROUND: Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically...

  7. Balancing multiple roles among a group of urban midlife American Indian working women.

    Science.gov (United States)

    Napholz, L

    2000-06-01

    Presented are the results of a secondary analysis of group data from a study of a six-week role conflict reduction intervention among a group of urban American Indian women (n = 8). The specific aim of this researcher was to understand the process of balancing multiple roles as expressed in the participants' daily lived experiences as mothers, wives, and workers. A construction of the process of balancing multiple roles was accomplished through the use of narratives. Balancing multiple roles represented a major current attempt on the part of the participants to integrate and balance traditional and contemporary feminine strengths in a positive, culturally consistent manner. The study themes included: traditional sex role expectation conflicts, family guilt, guilt management, transitioning inner conflict and stress, breaking the silence-learning to say no, and healing the spirit to reclaim the self. Further support for retraditionalization of roles for this group of Indian women was maintained as an effective means of balancing roles and achieving Indian self-determination.

  8. Cytosolic NADP+-dependent isocitrate dehydrogenase plays a key role in lipid metabolism.

    Science.gov (United States)

    Koh, Ho-Jin; Lee, Su-Min; Son, Byung-Gap; Lee, Soh-Hyun; Ryoo, Zae Young; Chang, Kyu-Tae; Park, Jeen-Woo; Park, Dong-Chan; Song, Byoung J; Veech, Richard L; Song, Hebok; Huh, Tae-Lin

    2004-09-17

    NADPH is an essential cofactor for many enzymatic reactions including glutathione metabolism and fat and cholesterol biosynthesis. We have reported recently an important role for mitochondrial NADP(+)-dependent isocitrate dehydrogenase in cellular defense against oxidative damage by providing NADPH needed for the regeneration of reduced glutathione. However, the role of cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) is still unclear. We report here for the first time that IDPc plays a critical role in fat and cholesterol biosynthesis. During differentiation of 3T3-L1 adipocytes, both IDPc enzyme activity and its protein content were increased in parallel in a time-dependent manner. Increased expression of IDPc by stable transfection of IDPc cDNA positively correlated with adipogenesis of 3T3-L1 cells, whereas decreased IDPc expression by an antisense IDPc vector retarded adipogenesis. Furthermore, transgenic mice with overexpressed IDPc exhibited fatty liver, hyperlipidemia, and obesity. In the epididymal fat pads of the transgenic mice, the expressions of adipocyte-specific genes including peroxisome proliferator-activated receptor gamma were markedly elevated. The hepatic and epididymal fat pad contents of acetyl-CoA and malonyl-CoA in the transgenic mice were significantly lower, whereas the total triglyceride and cholesterol contents were markedly higher in the liver and serum of transgenic mice compared with those measured in wild type mice, suggesting that the consumption rate of those lipogenic precursors needed for fat biosynthesis must be increased by elevated IDPc activity. Taken together, our findings strongly indicate that IDPc would be a major NADPH producer required for fat and cholesterol synthesis.

  9. Amygdalar glutamatergic neuronal systems play a key role on the hibernating state of hamsters

    Directory of Open Access Journals (Sweden)

    Facciolo Rosa

    2011-01-01

    Full Text Available Abstract Background Excitatory transmitting mechanisms are proving to play a critical role on neuronal homeostasis conditions of facultative hibernators such as the Syrian golden hamster. Indeed works have shown that the glutamatergic system of the main olfactory brain station (amygdala is capable of controlling thermoregulatory responses, which are considered vital for the different hibernating states. In the present study the role of amygdalar glutamatergic circuits on non-hibernating (NHIB and hibernating (HIB hamsters were assessed on drinking stimuli and subsequently compared to expression variations of some glutamatergic subtype mRNA levels in limbic areas. For this study the two major glutamatergic antagonists and namely that of N-methyl-D-aspartate receptor (NMDAR, 3-(+-2-carboxypiperazin-4-yl-propyl-1-phosphonate (CPP plus that of the acid α-amine-3-hydroxy-5-metil-4-isoxazol-propionic receptor (AMPAR site, cyano-7-nitro-quinoxaline-2,3-dione (CNQX were infused into the basolateral amygdala nucleus. Attempts were made to establish the type of effects evoked by amygdalar glutamatergic cross-talking processes during drinking stimuli, a response that may corroborate their major role at least during some stages of this physiological activity in hibernators. Results From the behavioral results it appears that the two glutamatergic compounds exerted distinct effects. In the first case local infusion of basolateral complexes (BLA with NMDAR antagonist caused very great (p Conclusion We conclude that predominant drinking events evoked by glutamatergic mechanisms, in the presence of prevalently down regulated levels of NR1/2A of some telencephalic and hypothalamic areas appear to constitute an important neuronal switch at least during arousal stage of hibernation. The establishment of the type of glutamatergic subtypes that are linked to successful hibernating states, via drinking stimuli, may have useful bearings toward sleeping disorders.

  10. How coaching can play a key role in the development of nurse managers.

    Science.gov (United States)

    Westcott, Liz

    2016-09-01

    The aim of this study was to explore empirically the role that coaching plays in the development of nurse managers in order to inform further research and policy makers about the potential utility and value of this means of development. There is evidence of the importance of the role of nurse managers who are first line managers of a team of nurses within any health sector. However, there appears to be little understanding of the United Kingdom wide scope of nurse manager development across the United Kingdom and the means to increase its effectiveness. At the same time, it appears that some nurse managers receive coaching to help in their development. This is a mixed methods study, using a pragmatist paradigm. Data was gathered from a quantitative survey and qualitative interviews. This paper is reporting the results of the qualitative interviews only. Twenty-one qualitative interviews were undertaken with nurse managers, coaches and directors of nursing to draw out their own experiences of coaching for nurse managers. Thematic analysis framework was used for data interrogation, identifying new patterns and emerging themes. Themes that emerged from interviews include how nurse managers were introduced to coaching, how they balanced transitions, the role of reflection, the value of relationships and overlaps between clinical supervision, mentoring and coaching. Findings show that following coaching, nurse managers gained increased resilience, confidence and better coping mechanisms. This resulted in perceived improved team management and cohesion and appeared to lead to better quality of care for patients. This study suggests the importance of nurse managers accessing coaching, to enable transformational leadership of their teams of nurses. It suggests also the importance of organisations supporting a coaching culture, to ensure staff satisfaction, motivation and improved quality of patient care. © 2016 John Wiley & Sons Ltd.

  11. Key role of symbiotic dinitrogen fixation in tropical forest secondary succession

    DEFF Research Database (Denmark)

    Batterman, Sarah A.; Hedin, Lars O.; Van Breugel, Michiel

    2013-01-01

    Forests contribute a significant portion of the land carbon sink, but their ability to sequester CO 2 may be constrained by nitrogen, a major plant-limiting nutrient. Many tropical forests possess tree species capable of fixing atmospheric dinitrogen (N 2), but it is unclear whether this function...... tree species across the entire forest age sequence. These findings show that symbiotic N 2 fixation can have a central role in nitrogen cycling during tropical forest stand development, with potentially important implications for the ability of tropical forests to sequester CO 2....

  12. A novel microglial subset plays a key role in myelinogenesis in developing brain

    DEFF Research Database (Denmark)

    Wlodarczyk, Agnieszka; Holtman, Inge; Krueger, Martin

    2017-01-01

    Microglia are resident macrophages of the central nervous system that contribute to homeostasis and neuroinflammation. Although known to play an important role in brain development, their exact function has not been fully described. Here we show that in contrast to healthy adult and inflammation......-activated cells, neonatal microglia show a unique myelinogenic and neurogenic phenotype. A CD11c+ microglial subset that predominates in primary myelinating areas of the developing brain expresses genes for neuronal and glial survival, migration and differentiation. These cells are the major source of insulin...

  13. The views of key leaders in South Africa on implementation of family medicine: critical role in the district health system.

    Science.gov (United States)

    Moosa, Shabir; Mash, Bob; Derese, Anselme; Peersman, Wim

    2014-06-25

    Integrated team-based primary care is an international imperative. This is required more so in Africa, where fragmented verticalised care dominates. South Africa is trying to address this with health reforms, including Primary Health Care Re-engineering. Family physicians are already contributing to primary care despite family medicine being only fully registered as a full specialty in South Africa in 2008. However the views of leaders on family medicine and the role of family physicians is not clear, especially with recent health reforms. The aim of this study was to understand the views of key government and academic leaders in South Africa on family medicine, roles of family physicians and human resource issues. This was a qualitative study with academic and government leaders across South Africa. In-depth interviews were conducted with sixteen purposively selected leaders using an interview guide. Thematic content analysis was based on the framework method. Whilst family physicians were seen as critical to the district health system there was ambivalence on their leadership role and 'specialist' status. National health reforms were creating both threats and opportunities for family medicine. Three key roles for family physicians emerged: supporting referrals; clinical governance/quality improvement; and providing support to community-oriented care. Respondents' urged family physicians to consolidate the development and training of family physicians, and shape human resource policy to include family physicians. Family physicians were seen as critical to the district health system in South Africa despite difficulties around their precise role. Whilst their role was dominated by filling gaps at district hospitals to reduce referrals it extended to clinical governance and developing community-oriented primary care - a tall order, requiring strong teamwork. Innovative team-based service delivery is possible despite human resource challenges, but requires family

  14. Key role of European rabbits in the conservation of the Western Mediterranean basin hotspot.

    Science.gov (United States)

    Delibes-Mateos, Miguel; Delibes, Miguel; Ferreras, Pablo; Villafuerte, Rafael

    2008-10-01

    The Mediterranean Basin is a global hotspot of biodiversity. Hotspots are said to be experiencing a major loss of habitat, but an added risk could be the decline of some species having a special role in ecological relationships of the system. We reviewed the role of European rabbits (Oryctolagus cuniculus) as a keystone species in the Iberian Peninsula portion of the Mediterranean hotspot. Rabbits conspicuously alter plant species composition and vegetation structure through grazing and seed dispersal, which creates open areas and preserves plant species diversity. Moreover, rabbit latrines have a demonstrable effect on soil fertility and plant growth and provide new feeding resources for many invertebrate species. Rabbit burrows provide nest sites and shelter for vertebrates and invertebrates. In addition, rabbits serve as prey for a number of predators, including the critically endangered Iberian lynx (Lynx pardinus) and Spanish Imperial Eagle (Aquila adalberti). Thus, the Mediterranean ecosystem of the Iberian Peninsula should be termed "the rabbit's ecosystem." To our knowledge, this is the first empirical support for existence of a multifunctional keystone species in a global hotspot of biodiversity. Rabbit populations have declined drastically on the Iberian Peninsula, with potential cascading effects and serious ecological and economic consequences. From this perspective, rabbit recovery is one of the biggest challenges for conservation of the Mediterranean Basin hotspot.

  15. A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ian Smyth

    2008-09-01

    Full Text Available Harlequin Ichthyosis (HI is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis.

  16. The key role of CYC2 during meiosis in Tetrahymena thermophila.

    Science.gov (United States)

    Xu, Qianlan; Wang, Ruoyu; Ghanam, A R; Yan, Guanxiong; Miao, Wei; Song, Xiaoyuan

    2016-04-01

    Meiotic recombination is carried out through a specialized pathway for the formation and repair of DNA double-strand breaks (DSBs) made by the Spo11 protein. The present study shed light on the functional role of cyclin, CYC2, in Tetrahymena thermophila which has transcriptionally high expression level during meiosis process. Knocking out the CYC2 gene results in arrest of meiotic conjugation process at 2.5-3.5 h after conjugation initiation, before the meiosis division starts, and in company with the absence of DSBs. To investigate the underlying mechanism of this phenomenon, a complete transcriptome profile was performed between wild-type strain and CYC2 knock-out strain. Functional analysis of RNA-Seq results identifies related differentially expressed genes (DEGs) including SPO11 and these DEGs are enriched in DNA repair/mismatch repair (MMR) terms in homologous recombination (HR), which indicates that CYC2 could play a crucial role in meiosis by regulating SPO11 and participating in HR.

  17. Genetic Disruption of 2-Arachidonoylglycerol Synthesis Reveals a Key Role for Endocannabinoid Signaling in Anxiety Modulation

    Directory of Open Access Journals (Sweden)

    Brian C. Shonesy

    2014-12-01

    Full Text Available Summary: Endocannabinoid (eCB signaling has been heavily implicated in the modulation of anxiety and depressive behaviors and emotional learning. However, the role of the most-abundant endocannabinoid 2-arachidonoylglycerol (2-AG in the physiological regulation of affective behaviors is not well understood. Here, we show that genetic deletion of the 2-AG synthetic enzyme diacylglycerol lipase α (DAGLα in mice reduces brain, but not circulating, 2-AG levels. DAGLα deletion also results in anxiety-like and sex-specific anhedonic phenotypes associated with impaired activity-dependent eCB retrograde signaling at amygdala glutamatergic synapses. Importantly, acute pharmacological normalization of 2-AG levels reverses both phenotypes of DAGLα-deficient mice. These data suggest 2-AG deficiency could contribute to the pathogenesis of affective disorders and that pharmacological normalization of 2-AG signaling could represent an approach for the treatment of mood and anxiety disorders. : The role of the primary endogenous cannabinoid 2-AG in mood and anxiety regulation is not well understood. Shonesy et al. show that deletion of a primary 2-AG synthetic enzyme, DAGLα, results in anxiety and sex-specific depressive phenotypes, which can be rapidly reversed by pharmacological normalization of endocannabinoid levels.

  18. Closing the Loop: Key Role of Iron in Metal-Bearing Waste Recycling

    Directory of Open Access Journals (Sweden)

    Sedlakova-Kadukova J.

    2017-09-01

    Full Text Available The role of iron in metal-bearing waste bioleaching was studied. Four various types of waste (printed circuit boards (PCBs, Ni-Cd batteries, alkaline batteries and Li-ion batteries were treated by bioleaching using the acidophilic bacteria A. ferrooxidans and A. thiooxidans (separately or in mixture. Role of main leaching agents (Fe3+ ions or sulphuric acid was simulated in abiotic experiments. Results showed that oxidation abilities of Fe3+ ions were crucial for recovery of Cu and Zn from PCBs, with the efficiencies of 88% and 100%, respectively. To recover 68% of Ni from PCBs, and 55% and 100% of Ni and Cd, respectively, from Ni-Cd batteries both oxidation action and hydrolysis of Fe3+ were required. The importance of Fe2+ ions as a reducing agent was showed in bioleaching of Co from Li-ion batteries and Mn from alkaline batteries. The efficiency of the processes has increased by 70% and 40% in Co and Mn bioleaching, respectively, in the presence of Fe2+ ions. Based on the results we suggest the integrated biometallurgical model of metal-bearing waste recycling in the effort to develop zero-waste and less energy-dependent technologies.

  19. Strengthening a consolidated memory: the key role of the reconsolidation process.

    Science.gov (United States)

    Forcato, Cecilia; Fernandez, Rodrigo S; Pedreira, María E

    2014-01-01

    The reconsolidation hypothesis posits that the presentation of a specific cue, previously associated with a life event, makes the stored memory pass from a stable to a reactivated state. In this state, memory is again labile and susceptible to different agents, which may either damage or improve the original memory. Such susceptibility decreases over time and leads to a re-stabilization phase known as reconsolidation process. This process has been assigned two biological roles: memory updating, which suggests that destabilization of the original memory allows the integration of new information into the background of the original memory; and memory strengthening, which postulates that the labilization-reconsolidation process strengthens the original memory. The aim of this review is to analyze the strengthening as an improvement obtained only by triggering such process without any other treatment. In our lab, we have demonstrated that when triggering the labilization-reconsolidation process at least once the original memory becomes strengthened and increases its persistence. We have also shown that repeated labilization-reconsolidation processes strengthened the original memory by enlarging its precision, and said reinforced memories were more resistant to interference. Finally, we have shown that the strengthening function is not operative in older memories. We present and discuss both our findings and those of others, trying to reveal the central role of reconsolidation in the modification of stored information. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Spread of Zika virus:The key role of mosquito vector control

    Institute of Scientific and Technical Information of China (English)

    Giovanni Benelli

    2016-01-01

    Mosquitoes (Diptera: Culicidae) represent a key threat for millions of humans and ani-mals worldwide, since they act as vectors for important parasites and pathogens, including malaria, filariasis and a wide number of arboviruses. The recent outbreaks of Zika virus infections occurring in South America, Central America, and the Caribbean, represent the most recent four arrivals of important arboviruses in the western hemi-sphere, over the last 20 years, namely dengue, West Nile virus, and chikungunya. Since there are no specific treatments for Zika virus and the other arboviruses mentioned above, it should be highlighted that the eco-friendly and effective control of mosquito vectors is of pivotal importance. Besides radiation, transgenic and symbiont-based mosquito control approaches, an effective option may be the employ of biological control agents of mosquito young instars, in presence of ultra-low quantities of green-synthesized nano-particles, which magnify their predation efficiency. Furthermore, behaviour-based control tools relying on the employ of swarming behaviour manipulation (i.e. the“lure and kill”approach), pheromone traps, sound traps need further research attention. In particular, detailed basic information on the physical and chemical cues routing mosquito swarming and mating dynamics is urgently required.

  1. Spread of Zika virus:The key role of mosquito vector control

    Institute of Scientific and Technical Information of China (English)

    Giovanni Benelli

    2016-01-01

    Mosquitoes(Diptera: Culicidae) represent a key threat for millions of humans and animals worldwide, since they act as vectors for important parasites and pathogens,including malaria, filariasis and a wide number of arboviruses. The recent outbreaks of Zika virus infections occurring in South America, Central America, and the Caribbean,represent the most recent four arrivals of important arboviruses in the western hemisphere, over the last 20 years, namely dengue, West Nile virus, and chikungunya. Since there are no specific treatments for Zika virus and the other arboviruses mentioned above,it should be highlighted that the eco-friendly and effective control of mosquito vectors is of pivotal importance. Besides radiation, transgenic and symbiont-based mosquito control approaches, an effective option may be the employ of biological control agents of mosquito young instars, in presence of ultra-low quantities of green-synthesized nanoparticles, which magnify their predation efficiency. Furthermore, behaviour-based control tools relying on the employ of swarming behaviour manipulation(i.e. the "lure and kill"approach), pheromone traps, sound traps need further research attention. In particular,detailed basic information on the physical and chemical cues routing mosquito swarming and mating dynamics is urgently required.

  2. From rapid place learning to behavioral performance: a key role for the intermediate hippocampus.

    Directory of Open Access Journals (Sweden)

    Tobias Bast

    2009-04-01

    Full Text Available Rapid place encoding by hippocampal neurons, as reflected by place-related firing, has been intensely studied, whereas the substrates that translate hippocampal place codes into behavior have received little attention. A key point relevant to this translation is that hippocampal organization is characterized by functional-anatomical gradients along the septotemporal axis: Whereas the ability of hippocampal neurons to encode accurate place information declines from the septal to temporal end, hippocampal connectivity to prefrontal and subcortical sites that might relate such place information to behavioral-control processes shows an opposite gradient. We examined in rats the impact of selective lesions to relevant parts of the hippocampus on behavioral tests requiring place learning (watermaze procedures and on in vivo electrophysiological models of hippocampal encoding (long-term potentiation [LTP], place cells. We found that the intermediate hippocampus is necessary and largely sufficient for behavioral performance based on rapid place learning. In contrast, a residual septal pole of the hippocampus, although displaying intact electrophysiological indices of rapid information encoding (LTP, precise place-related firing, and rapid remapping, failed to sustain watermaze performance based on rapid place learning. These data highlight the important distinction between hippocampal encoding and the behavioral performance based on such encoding, and suggest that the intermediate hippocampus, where substrates of rapid accurate place encoding converge with links to behavioral control, is critical to translate rapid (one-trial place learning into navigational performance.

  3. Aroma extraction dilution analysis of Sauternes wines. Key role of polyfunctional thiols.

    Science.gov (United States)

    Bailly, Sabine; Jerkovic, Vesna; Marchand-Brynaert, Jacqueline; Collin, Sonia

    2006-09-20

    The aim of the present work was to investigate Sauternes wine aromas. In all wine extracts, polyfunctional thiols were revealed to have a huge impact. A very strong bacon-petroleum odor emerged at RI = 845 from a CP-Sil5-CB column. Two thiols proved to participate in this perception: 3-methyl-3-sulfanylbutanal and 2-methylfuran-3-thiol. A strong synergetic effect was evidenced between the two compounds. The former, never mentioned before in wines, and not found in the musts of this study, is most probably synthesized during fermentation. 3-Methylbut-2-ene-1-thiol, 3-sulfanylpropyl acetate, 3-sulfanylhexan-1-ol, and 3-sulfanylheptanal also contribute to the global aromas of Sauternes wines. Among other key odorants, the presence of a varietal aroma (alpha-terpineol), sotolon, fermentation alcohols (3-methylbutan-1-ol and 2-phenylethanol) and esters (ethyl butyrate, ethyl hexanoate, and ethyl isovalerate), carbonyls (trans-non-2-enal and beta-damascenone), and wood flavors (guaiacol, vanillin, eugenol, beta-methyl-gamma-octalactone, and Furaneol) is worth stressing.

  4. The key role of patrilineal inheritance in shaping the genetic variation of Dagestan highlanders.

    Science.gov (United States)

    Caciagli, Laura; Bulayeva, Kazima; Bulayev, Oleg; Bertoncini, Stefania; Taglioli, Luca; Pagani, Luca; Paoli, Giorgio; Tofanelli, Sergio

    2009-12-01

    The Caucasus region is a complex cultural and ethnic mosaic, comprising populations that speak Caucasian, Indo-European and Altaic languages. Isolated mountain villages (auls) in Dagestan still preserve high level of genetic and cultural diversity and have patriarchal societies with a long history of isolation. The aim of this study was to understand the genetic history of five Dagestan highland auls with distinct ethnic affiliation (Avars, Chechens-Akkins, Kubachians, Laks, Tabasarans) using markers on the male-specific region of the Y chromosome. The groups analyzed here are all Muslims but speak different languages all belonging to the Nakh-Dagestanian linguistic family. The results show that the Dagestan ethnic groups share a common Y-genetic background, with deep-rooted genealogies and rare alleles, dating back to an early phase in the post-glacial recolonization of Europe. Geography and stochastic factors, such as founder effect and long-term genetic drift, driven by the rigid structuring of societies in groups of patrilineal descent, most likely acted as mutually reinforcing key factors in determining the high degree of Y-genetic divergence among these ethnic groups.

  5. When cooperation begets cooperation: the role of key individuals in galvanizing support.

    Science.gov (United States)

    McAuliffe, Katherine; Wrangham, Richard; Glowacki, Luke; Russell, Andrew F

    2015-12-05

    Life abounds with examples of conspecifics actively cooperating to a common end, despite conflicts of interest being expected concerning how much each individual should contribute. Mathematical models typically find that such conflict can be resolved by partial-response strategies, leading investors to contribute relatively equitably. Using a case study approach, we show that such model expectations can be contradicted in at least four disparate contexts: (i) bi-parental care; (ii) cooperative breeding; (iii) cooperative hunting; and (iv) human cooperation. We highlight that: (a) marked variation in contributions is commonplace; and (b) individuals can often respond positively rather than negatively to the contributions of others. Existing models have surprisingly limited power in explaining these phenomena. Here, we propose that, although among-individual variation in cooperative contributions will be influenced by differential costs and benefits, there is likely to be a strong genetic or epigenetic component. We then suggest that selection can maintain high investors (key individuals) when their contributions promote support by increasing the benefits and/or reducing the costs for others. Our intentions are to raise awareness in--and provide testable hypotheses of--two of the most poorly understood, yet integral, questions regarding cooperative ventures: why do individuals vary in their contributions and when does cooperation beget cooperation? © 2015 The Author(s).

  6. Key processes shaping the current role and operation of higher education institutions in society

    Directory of Open Access Journals (Sweden)

    Piróg Danuta

    2016-03-01

    Full Text Available The concurrent processes of globalisation, computerisation, and integration shape and constantly modify developmental factors and generate multidirectional social changes. Among social life fields, one of them has been particularly sensitive to the impact of those processes and has remained in clear feedback relationship with them is education, including university-level education. This article aims to present some reflections on the key processes which influence the environment of higher education institutions’ activity and on what their impact specifically is. The factors taken into account include: the transformation of the political and economic system, integration with the European higher education area, the market shift of education, evolving social demands towards higher education institutions and society’s attitude towards work. As knowledge has become an asset largely affecting the quality of life of people and society, universities have changed their focus from searching for and exploring truth, good and beauty in the world towards becoming innovation centres, transferring knowledge as offering their educational services. In this article, those trends have been exemplified in relation to geography degree programmes, and shown through an evolution of the model of the university. Based on a review of the literature, it seems that the processes discussed also concern geography degree programmes, and the future operation of these programmes closely depends on whether they can maintain their care for high quality education coupled with genuine efforts to ensure the smooth transition of graduates into the labour market.

  7. Spread of Zika virus: The key role of mosquito vector control

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    Giovanni Benelli

    2016-06-01

    Full Text Available Mosquitoes (Diptera: Culicidae represent a key threat for millions of humans and animals worldwide, since they act as vectors for important parasites and pathogens, including malaria, filariasis and a wide number of arboviruses. The recent outbreaks of Zika virus infections occurring in South America, Central America, and the Caribbean, represent the most recent four arrivals of important arboviruses in the western hemisphere, over the last 20 years, namely dengue, West Nile virus, and chikungunya. Since there are no specific treatments for Zika virus and the other arboviruses mentioned above, it should be highlighted that the eco-friendly and effective control of mosquito vectors is of pivotal importance. Besides radiation, transgenic and symbiont-based mosquito control approaches, an effective option may be the employ of biological control agents of mosquito young instars, in presence of ultra-low quantities of green-synthesized nanoparticles, which magnify their predation efficiency. Furthermore, behaviour-based control tools relying on the employ of swarming behaviour manipulation (i.e. the “lure and kill” approach, pheromone traps, sound traps need further research attention. In particular, detailed basic information on the physical and chemical cues routing mosquito swarming and mating dynamics is urgently required.

  8. The Expanding Role of Traceability in Seafood: Tools and Key Initiatives.

    Science.gov (United States)

    Lewis, Sara G; Boyle, Mariah

    2017-08-01

    In the last decade, a range of drivers within the seafood sector have incentivized the application of traceability to issues beyond food safety and inventory management. Some of the issues motivating the expanded use of traceability within the global seafood sector include: increased media attention on the legal and social risks within some seafood supply chains, governmental traceability requirements, private-sector sustainability commitments, and others. This article begins with an overview of these topics in the seafood industry, and why many nongovernment organizations (NGOs), companies, and government actors have turned to traceability as a tool to address them. We discuss how traceability connects to key requirements of environmental sustainability and social responsibility. Later, we review the range of traceability services, tools, software solutions, and the due diligence measures that are currently being leveraged within the seafood sector. The paper concludes with a discussion of several NGO- and industry-led traceability initiatives that are examples of seafood traceability improvements. © 2017 Institute of Food Technologists®.

  9. Gender and gender role differences in self- and other-estimates of multiple intelligences.

    Science.gov (United States)

    Szymanowicz, Agata; Furnham, Adrian

    2013-01-01

    This study examined participant gender and gender role differences in estimates of multiple intelligences for self, partner, and various hypothetical, stereotypical, and counter-stereotypical target persons. A general population sample of 261 British participants completed one of four questionnaires that required them to estimate their own and others' multiple intelligences and personality traits. Males estimated their general IQ slightly, but mathematic IQ significantly higher than females, who rated their social and emotional intelligence higher than males. Masculine individuals awarded themselves somewhat higher verbal and practical IQ scores than did female participants. Both participant gender and gender role differences in IQ estimates were found, with gender effects stronger in cognitive and gender role than in "personal" ability estimates. There was a significant effect of gender role on hypothetical persons' intelligence evaluations, with masculine targets receiving significantly higher intelligence estimates compared to feminine targets. More intelligent hypothetical figures were judged as more masculine and less feminine than less intelligent ones.

  10. Mitochondria as key targets of cardioprotection in cardiac ischemic disease: role of thyroid hormone triiodothyronine.

    Science.gov (United States)

    Forini, Francesca; Nicolini, Giuseppina; Iervasi, Giorgio

    2015-03-19

    Ischemic heart disease is the major cause of mortality and morbidity worldwide. Early reperfusion after acute myocardial ischemia has reduced short-term mortality, but it is also responsible for additional myocardial damage, which in the long run favors adverse cardiac remodeling and heart failure evolution. A growing body of experimental and clinical evidence show that the mitochondrion is an essential end effector of ischemia/ reperfusion injury and a major trigger of cell death in the acute ischemic phase (up to 48-72 h after the insult), the subacute phase (from 72 h to 7-10 days) and chronic stage (from 10-14 days to one month after the insult). As such, in recent years scientific efforts have focused on mitochondria as a target for cardioprotective strategies in ischemic heart disease and cardiomyopathy. The present review discusses recent advances in this field, with special emphasis on the emerging role of the biologically active thyroid hormone triiodothyronine (T3).

  11. The Key Role of Epigenetics in the Persistence of Asexual Lineages

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    Emilie Castonguay

    2012-01-01

    Full Text Available Asexual organisms, often perceived as evolutionary dead ends, can be long-lived and geographically widespread. We propose that epigenetic mechanisms could play a crucial role in the evolutionary persistence of these lineages. Genetically identical organisms could rely on phenotypic plasticity to face environmental variation. Epigenetic modifications could be the molecular mechanism enabling such phenotypic plasticity; they can be influenced by the environment and act at shorter timescales than mutation. Recent work on the asexual vertebrate Chrosomus eos-neogaeus (Pisces: Cyprinidae provides broad insights into the contribution of epigenetics in genetically identical individuals. We discuss the extension of these results to other asexual organisms, in particular those resulting from interspecific hybridizations. We finally develop on the evolutionary relevance of epigenetic variation in the context of heritability.

  12. The key role of the scaffold on the efficiency of dendrimer nanodrugs

    Science.gov (United States)

    Caminade, Anne-Marie; Fruchon, Séverine; Turrin, Cédric-Olivier; Poupot, Mary; Ouali, Armelle; Maraval, Alexandrine; Garzoni, Matteo; Maly, Marek; Furer, Victor; Kovalenko, Valeri; Majoral, Jean-Pierre; Pavan, Giovanni M.; Poupot, Rémy

    2015-01-01

    Dendrimers are well-defined macromolecules whose highly branched structure is reminiscent of many natural structures, such as trees, dendritic cells, neurons or the networks of kidneys and lungs. Nature has privileged such branched structures for increasing the efficiency of exchanges with the external medium; thus, the whole structure is of pivotal importance for these natural networks. On the contrary, it is generally believed that the properties of dendrimers are essentially related to their terminal groups, and that the internal structure plays the minor role of an ‘innocent' scaffold. Here we show that such an assertion is misleading, using convergent information from biological data (human monocytes activation) and all-atom molecular dynamics simulations on seven families of dendrimers (13 compounds) that we have synthesized, possessing identical terminal groups, but different internal structures. This work demonstrates that the scaffold of nanodrugs strongly influences their properties, somewhat reminiscent of the backbone of proteins. PMID:26169490

  13. MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Menachery, Vineet D.; Mitchell, Hugh D.; Cockrell, Adam S.; Gralinski, Lisa E.; Yount, Boyd L.; Graham, Rachel L.; McAnarney, Eileen T.; Douglas, Madeline G.; Scobey, Trevor; Beall, Anne; Dinnon, Kenneth; Kocher, Jacob F.; Hale, Andrew E.; Stratton, Kelly G.; Waters, Katrina M.; Baric, Ralph S.; Racaniello, Vincent R.

    2017-08-22

    ABSTRACT

    While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation.In vitroreplication attenuation also extends toin vivomodels, allowing use of dORF3-5 as a live attenuated vaccine platform. Finally, examination of ORF5 implicates a partial role in modulation of NF-κB-mediated inflammation. Together, the results demonstrate the importance of MERS-CoV accessory ORFs for pathogenesis and highlight them as potential targets for surveillance and therapeutic treatments moving forward.

    IMPORTANCEThe initial emergence and periodic outbreaks of MERS-CoV highlight a continuing threat posed by zoonotic pathogens to global public health. In these studies, mutant virus generation demonstrates the necessity of accessory ORFs in regard to MERS-CoV infection and pathogenesis. With this in mind, accessory ORF functions can be targeted for both therapeutic and vaccine treatments in response to MERS-CoV and related group 2C coronaviruses. In addition, disruption of accessory ORFs in parallel may offer a rapid response platform to attenuation of future emergent strains based on both SARS- and MERS-CoV accessory ORF mutants.

  14. The role of key image notes in CT imaging study interpretation.

    Science.gov (United States)

    Fan, Shu-Feng; Xu, Zhe; He, Hai-Qing; Ding, Jian-Rong; Teng, Gao-Jun

    2011-04-01

    The objective of the study was to investigate the clinical effects of CT key image notes (KIN) in the interpretation of a CT image study. All experiments were approved by the ethics committee of the local district. Six experienced radiologists were equally divided into routine reporting (RR) group and KIN reporting (KIN) group. CT scans of each 100 consecutive cases before and after using KIN technique were randomly selected, and the reports were made by group RR and KIN, respectively. All the reports were again reviewed 3 months later by both groups. All the results with using or not using KIN were interpreted and reinterpreted after 3 months by six clinicians, who were experienced in picture archiving and communication system (PACS) applications and were equally divided into the clinical routine report group and the clinical KIN report group, respectively. The results were statistically analyzed; the time used in making a report, the re-reading time 3 months later, and the consistency of imaging interpretation were determined and compared between groups. After using KIN technique, the time used in making a report was significantly increased (8.77 ± 5.27 vs. 10.53 ± 5.71 min, P < 0.05), the re-reading time was decreased (5.23 ± 2.54 vs. 4.99 ± 1.70 min, P < 0.05), the clinical interpretation and reinterpretation time after 3 months were decreased, and the consistency of the interpretation, reinterpretation between different doctors in different time was markedly improved (P < 0.01). CT report with KIN technique in PACS can significantly improve the consistency of the interpretation and efficiency in routine clinical work.

  15. The Role of Biotechnology in Sustainable Agriculture: Views and Perceptions among Key Actors in the Swedish Food Supply Chain

    Directory of Open Access Journals (Sweden)

    Karin Edvardsson Björnberg

    2015-06-01

    Full Text Available Researchers have put forward agricultural biotechnology as one possible tool for increasing food production and making agriculture more sustainable. In this paper, it is investigated how key actors in the Swedish food supply chain perceive the concept of agricultural sustainability and the role of biotechnology in creating more sustainable agricultural production systems. Based on policy documents and semi-structured interviews with representatives of five organizations active in producing, processing and retailing food in Sweden, an attempt is made to answer the following three questions: How do key actors in the Swedish food supply chain define and operationalize the concept of agricultural sustainability? Who/what influences these organizations’ sustainability policies and their respective positions on agricultural biotechnology? What are the organizations’ views and perceptions of biotechnology and its possible role in creating agricultural sustainability? Based on collected data, it is concluded that, although there is a shared view of the core constituents of agricultural sustainability among the organizations, there is less explicit consensus on how the concept should be put into practice or what role biotechnology can play in furthering agricultural sustainability.

  16. GTPase activity plays a key role in the pathobiology of LRRK2.

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    Yulan Xiong

    2010-04-01

    Full Text Available Mutations in the leucine-rich repeat kinase 2 (LRRK2 gene are associated with late-onset, autosomal-dominant, familial Parkinson's disease (PD and also contribute to sporadic disease. The LRRK2 gene encodes a large protein with multiple domains, including functional Roc GTPase and protein kinase domains. Mutations in LRRK2 most likely cause disease through a toxic gain-of-function mechanism. The expression of human LRRK2 variants in cultured primary neurons induces toxicity that is dependent on intact GTP binding or kinase activities. However, the mechanism(s underlying LRRK2-induced neuronal toxicity is poorly understood, and the contribution of GTPase and/or kinase activity to LRRK2 pathobiology is not well defined. To explore the pathobiology of LRRK2, we have developed a model of LRRK2 cytotoxicity in the baker's yeast Saccharomyces cerevisiae. Protein domain analysis in this model reveals that expression of GTPase domain-containing fragments of human LRRK2 are toxic. LRRK2 toxicity in yeast can be modulated by altering GTPase activity and is closely associated with defects in endocytic vesicular trafficking and autophagy. These truncated LRRK2 variants induce similar toxicity in both yeast and primary neuronal models and cause similar vesicular defects in yeast as full-length LRRK2 causes in primary neurons. The toxicity induced by truncated LRRK2 variants in yeast acts through a mechanism distinct from toxicity induced by human alpha-synuclein. A genome-wide genetic screen identified modifiers of LRRK2-induced toxicity in yeast including components of vesicular trafficking pathways, which can also modulate the trafficking defects caused by expression of truncated LRRK2 variants. Our results provide insight into the basic pathobiology of LRRK2 and suggest that the GTPase domain may contribute to the toxicity of LRRK2. These findings may guide future therapeutic strategies aimed at attenuating LRRK2-mediated neurodegeneration.

  17. Molecular locks and keys: the role of small molecules in phytohormone research

    Directory of Open Access Journals (Sweden)

    Sandra eFonseca

    2014-12-01

    Full Text Available Plant adaptation, growth and development rely on the integration of many environmental and endogenous signals that collectively determine the overall plant phenotypic plasticity. Plant signalling molecules, also known as phytohormones, are fundamental to this process. These molecules act at low concentrations and regulate multiple aspects of plant fitness and development via complex signalling networks. By its nature, phytohormone research lies at the interface between chemistry and biology. Classically, the scientific community has always used synthetic phytohormones and analogs to study hormone functions and responses. However, recent advances in synthetic and combinational chemistry, have allowed a new field, plant chemical biology, to emerge and this has provided a powerful tool with which to study phytohormone function.Plant chemical biology is helping to address some of the most enduring questions in phytohormone research such as: Are there still undiscovered plant hormones? How can we identify novel signalling molecules? How can plants activate specific hormone responses in a tissue-specific manner? How can we modulate hormone responses in one developmental context without inducing detrimental effects on other processes? The chemical genomics approaches rely on the identification of small molecules modulating different biological processes and have recently identified active forms of plant hormones and molecules regulating many aspects of hormone synthesis, transport and response. We envision that the field of chemical genomics will continue to provide novel molecules able to elucidate specific aspects of hormone-mediated responses. In addition, compounds blocking specific responses could uncover how complex biological responses are regulated. As we gain information about such compounds we can design small alterations to the chemical structure to further alter specificity, enhance affinity or modulate the activity of these compounds.

  18. Key Role of Drug Shops and Pharmacies for Family Planning in Urban Nigeria and Kenya.

    Science.gov (United States)

    Corroon, Meghan; Kebede, Essete; Spektor, Gean; Speizer, Ilene

    2016-12-23

    The Family Planning 2020 initiative aims to reach 120 million new family planning users by 2020. Drug shops and pharmacies are important private-sector sources of contraception in many contexts but are less well understood than public-sector sources, especially in urban environments. This article explores the role that drug shops and pharmacies play in the provision of contraceptive methods in selected urban areas of Nigeria and Kenya as well as factors associated with women's choice of where to obtain these methods. Using data collected in 2010/2011 from representative samples of women in selected urban areas of Nigeria and Kenya as well as a census of pharmacies and drug shops audited in 2011, we examine the role of drug shops and pharmacies in the provision of short-acting contraceptive methods and factors associated with a women's choice of family planning source. In urban Nigeria and Kenya, drug shops and pharmacies were the major source for the family planning methods of oral contraceptive pills, emergency contraceptives, and condoms. The majority of injectable users obtained their method from public facilities in both countries, but 14% of women in Nigeria and 6% in Kenya obtained injectables from drug shops or pharmacies. Harder-to-reach populations were the most likely to choose these outlets to obtain their short-acting methods. For example, among users of these methods in Nigeria, younger women (family planning users who had never been married were significantly more likely than married users to obtain these methods from a drug shop or a pharmacy than from a public-sector health facility. Low levels of family planning-related training (57% of providers in Kenya and 41% in Nigeria had received training) and lack of family planning promotional activities in pharmacies and drug shops in both countries indicate the need for additional support from family planning programs to leverage this important access point. Drug shops and pharmacies offer an important

  19. A Multi-Compartment Hybrid Computational Model Predicts Key Roles for Dendritic Cells in Tuberculosis Infection

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    Simeone Marino

    2016-10-01

    Full Text Available Tuberculosis (TB is a world-wide health problem with approximately 2 billion people infected with Mycobacterium tuberculosis (Mtb, the causative bacterium of TB. The pathologic hallmark of Mtb infection in humans and Non-Human Primates (NHPs is the formation of spherical structures, primarily in lungs, called granulomas. Infection occurs after inhalation of bacteria into lungs, where resident antigen-presenting cells (APCs, take up bacteria and initiate the immune response to Mtb infection. APCs traffic from the site of infection (lung to lung-draining lymph nodes (LNs where they prime T cells to recognize Mtb. These T cells, circulating back through blood, migrate back to lungs to perform their immune effector functions. We have previously developed a hybrid agent-based model (ABM, labeled GranSim describing in silico immune cell, bacterial (Mtb and molecular behaviors during tuberculosis infection and recently linked that model to operate across three physiological compartments: lung (infection site where granulomas form, lung draining lymph node (LN, site of generation of adaptive immunity and blood (a measurable compartment. Granuloma formation and function is captured by a spatio-temporal model (i.e., ABM, while LN and blood compartments represent temporal dynamics of the whole body in response to infection and are captured with ordinary differential equations (ODEs. In order to have a more mechanistic representation of APC trafficking from the lung to the lymph node, and to better capture antigen presentation in a draining LN, this current study incorporates the role of dendritic cells (DCs in a computational fashion into GranSim. Results: The model was calibrated using experimental data from the lungs and blood of NHPs. The addition of DCs allowed us to investigate in greater detail mechanisms of recruitment, trafficking and antigen presentation and their role in tuberculosis infection. Conclusion: The main conclusion of this study is

  20. MAGNETIC GAMES BETWEEN A PLANET AND ITS HOST STAR: THE KEY ROLE OF TOPOLOGY

    International Nuclear Information System (INIS)

    Strugarek, A.; Brun, A. S.; Réville, V.; Matt, S. P.

    2015-01-01

    Magnetic interactions between a star and a close-in planet are postulated to be a source of enhanced emissions and to play a role in the secular evolution of the orbital system. Close-in planets generally orbit in the sub-alfvénic region of the stellar wind, which leads to efficient transfers of energy and angular momentum between the star and the planet. We model the magnetic interactions occurring in close-in star–planet systems with three-dimensional, global, compressible magnetohydrodynamic numerical simulations of a planet orbiting in a self-consistent stellar wind. We focus on the cases of magnetized planets and explore three representative magnetic configurations. The Poynting flux originating from the magnetic interactions is an energy source for enhanced emissions in star–planet systems. Our results suggest a simple geometrical explanation for ubiquitous on/off enhanced emissions associated with close-in planets, and confirm that the Poynting fluxes can reach powers of the order of 10 19 W. Close-in planets are also shown to migrate due to magnetic torques for sufficiently strong stellar wind magnetic fields. The topology of the interaction significantly modifies the shape of the magnetic obstacle that leads to magnetic torques. As a consequence, the torques can vary by at least an order of magnitude as the magnetic topology of the interaction varies

  1. Scaffolding as a key role for teaching assistants: Perceptions of their pedagogical strategies.

    Science.gov (United States)

    Bowles, David; Radford, Julie; Bakopoulou, Ioanna

    2017-11-19

    Inclusive education policies have led to a worldwide increase in the number of teaching assistants (TAs) working in mainstream schools. TAs have a large amount of responsibility for supporting children with special educational needs and disabilities (SEND), a role which by default has become instructional in practice, and for which training and preparation are rarely adequate. While there is some research into the nature of TAs' interactions with pupils and the strategies they use which are helpful for children's learning, TAs' perspectives on their own classroom practice have yet to be explored. To explore TAs' perceptions about their use of inclusive pedagogical strategies. The study involved eleven TAs in two mainstream primary schools. The TAs were interviewed face to face to explore their views about inclusive pedagogical strategies. The data were analysed using thematic analysis. TAs were clear about the strategies they use to offer emotional and relational support to children. There were some gaps, however, in their knowledge about how children learn, specifically in terms of transferring responsibility for learning onto children. The study advances understanding of scaffolding from a TA perspective and highlights the importance of training TAs in scaffolding theory. © 2017 The British Psychological Society.

  2. Swimming motility plays a key role in the stochastic dynamics of cell clumping

    International Nuclear Information System (INIS)

    Qi, Xianghong; Nellas, Ricky B; Byrn, Matthew W; Russell, Matthew H; Bible, Amber N; Alexandre, Gladys; Shen, Tongye

    2013-01-01

    Dynamic cell-to-cell interactions are a prerequisite to many biological processes, including development and biofilm formation. Flagellum induced motility has been shown to modulate the initial cell–cell or cell–surface interaction and to contribute to the emergence of macroscopic patterns. While the role of swimming motility in surface colonization has been analyzed in some detail, a quantitative physical analysis of transient interactions between motile cells is lacking. We examined the Brownian dynamics of swimming cells in a crowded environment using a model of motorized adhesive tandem particles. Focusing on the motility and geometry of an exemplary motile bacterium Azospirillum brasilense, which is capable of transient cell–cell association (clumping), we constructed a physical model with proper parameters for the computer simulation of the clumping dynamics. By modulating mechanical interaction (‘stickiness’) between cells and swimming speed, we investigated how equilibrium and active features affect the clumping dynamics. We found that the modulation of active motion is required for the initial aggregation of cells to occur at a realistic time scale. Slowing down the rotation of flagellar motors (and thus swimming speeds) is correlated to the degree of clumping, which is consistent with the experimental results obtained for A. brasilense. (paper)

  3. Nanomaterials towards fabrication of cholesterol biosensors: Key roles and design approaches.

    Science.gov (United States)

    Saxena, Urmila; Das, Asim Bikas

    2016-01-15

    Importance of cholesterol biosensors is already recognized in the clinical diagnosis of cardiac and brain vascular diseases as discernible from the enormous amount of research in this field. Nevertheless, the practical application of a majority of the fabricated cholesterol biosensors is ordinarily limited by their inadequate performance in terms of one or more analytical parameters including stability, sensitivity and detection limit. Nanoscale materials offer distinctive size tunable electronic, catalytic and optical properties which opened new opportunities for designing highly efficient biosensor devices. Incorporation of nanomaterials in biosensing devices has found to improve the electroactive surface, electronic conductivity and biocompatibility of the electrode surfaces which then improves the analytical performance of the biosensors. Here we have reviewed recent advances in nanomaterial-based cholesterol biosensors. Foremost, the diverse roles of nanomaterials in these sensor systems have been discussed. Later, we have exhaustively explored the strategies used for engineering cholesterol biosensors with nanotubes, nanoparticles and nanocomposites. Finally, this review concludes with future outlook signifying some challenges of these nanoengineered cholesterol sensors. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. MAGNETIC GAMES BETWEEN A PLANET AND ITS HOST STAR: THE KEY ROLE OF TOPOLOGY

    Energy Technology Data Exchange (ETDEWEB)

    Strugarek, A. [Département de physique, Université de Montréal, C.P. 6128 Succ. Centre-Ville, Montréal, QC H3C 3J7 (Canada); Brun, A. S.; Réville, V. [Laboratoire AIM Paris-Saclay, CEA/Irfu Université Paris-Diderot CNRS/INSU, F-91191 Gif-sur-Yvette (France); Matt, S. P., E-mail: strugarek@astro.umontreal.ca [Astrophysics group, School of Physics, University of Exeter, Stocker Road, Exeter EX4 4QL (United Kingdom)

    2015-12-20

    Magnetic interactions between a star and a close-in planet are postulated to be a source of enhanced emissions and to play a role in the secular evolution of the orbital system. Close-in planets generally orbit in the sub-alfvénic region of the stellar wind, which leads to efficient transfers of energy and angular momentum between the star and the planet. We model the magnetic interactions occurring in close-in star–planet systems with three-dimensional, global, compressible magnetohydrodynamic numerical simulations of a planet orbiting in a self-consistent stellar wind. We focus on the cases of magnetized planets and explore three representative magnetic configurations. The Poynting flux originating from the magnetic interactions is an energy source for enhanced emissions in star–planet systems. Our results suggest a simple geometrical explanation for ubiquitous on/off enhanced emissions associated with close-in planets, and confirm that the Poynting fluxes can reach powers of the order of 10{sup 19} W. Close-in planets are also shown to migrate due to magnetic torques for sufficiently strong stellar wind magnetic fields. The topology of the interaction significantly modifies the shape of the magnetic obstacle that leads to magnetic torques. As a consequence, the torques can vary by at least an order of magnitude as the magnetic topology of the interaction varies.

  5. Global citizenship is key to securing global health: the role of higher education.

    Science.gov (United States)

    Stoner, Lee; Perry, Lane; Wadsworth, Daniel; Stoner, Krystina R; Tarrant, Michael A

    2014-07-01

    Despite growing public awareness, health systems are struggling under the escalating burden of non-communicable diseases. While personal responsibility is crucial, alone it is insufficient. We argue that one must place themselves within the broader/global context to begin to truly understand the health implications of personal choices. Global citizenship competency has become an integral part of the higher education discourse; this discourse can and should be extended to include global health. A global citizen is someone who is (1) aware of global issues, (2) socially responsible, and (3) civically engaged. From this perspective, personal health is not solely an individual, self-serving act; rather, the consequences of our lifestyle choices and behaviors have far-reaching implications. This paper will argue that, through consciously identifying global health within the constructs of global citizenship, institutions of higher education can play an instrumental role in fostering civically engaged students capable of driving social change. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Mitochondria as Key Targets of Cardioprotection in Cardiac Ischemic Disease: Role of Thyroid Hormone Triiodothyronine

    Directory of Open Access Journals (Sweden)

    Francesca Forini

    2015-03-01

    Full Text Available Ischemic heart disease is the major cause of mortality and morbidity worldwide. Early reperfusion after acute myocardial ischemia has reduced short-term mortality, but it is also responsible for additional myocardial damage, which in the long run favors adverse cardiac remodeling and heart failure evolution. A growing body of experimental and clinical evidence show that the mitochondrion is an essential end effector of ischemia/ reperfusion injury and a major trigger of cell death in the acute ischemic phase (up to 48–72 h after the insult, the subacute phase (from 72 h to 7–10 days and chronic stage (from 10–14 days to one month after the insult. As such, in recent years scientific efforts have focused on mitochondria as a target for cardioprotective strategies in ischemic heart disease and cardiomyopathy. The present review discusses recent advances in this field, with special emphasis on the emerging role of the biologically active thyroid hormone triiodothyronine (T3.

  7. How self-determined choice facilitates performance: a key role of the ventromedial prefrontal cortex.

    Science.gov (United States)

    Murayama, Kou; Matsumoto, Madoka; Izuma, Keise; Sugiura, Ayaka; Ryan, Richard M; Deci, Edward L; Matsumoto, Kenji

    2015-05-01

    Recent studies have documented that self-determined choice does indeed enhance performance. However, the precise neural mechanisms underlying this effect are not well understood. We examined the neural correlates of the facilitative effects of self-determined choice using functional magnetic resonance imaging (fMRI). Participants played a game-like task involving a stopwatch with either a stopwatch they selected (self-determined-choice condition) or one they were assigned without choice (forced-choice condition). Our results showed that self-determined choice enhanced performance on the stopwatch task, despite the fact that the choices were clearly irrelevant to task difficulty. Neuroimaging results showed that failure feedback, compared with success feedback, elicited a drop in the vmPFC activation in the forced-choice condition, but not in the self-determined-choice condition, indicating that negative reward value associated with the failure feedback vanished in the self-determined-choice condition. Moreover, the vmPFC resilience to failure in the self-determined-choice condition was significantly correlated with the increased performance. Striatal responses to failure and success feedback were not modulated by the choice condition, indicating the dissociation between the vmPFC and striatal activation pattern. These findings suggest that the vmPFC plays a unique and critical role in the facilitative effects of self-determined choice on performance. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Contextualising change through a common strategy: Lecturers' perceptions and key role in supporting academic reform

    Science.gov (United States)

    Kindelan, Paz; Martin, Ana

    2014-05-01

    European universities are currently going through a process of change in order to meet the common goals set for higher education by the European Commission. They are revising their educational models to adjust them to the guidelines of the "Bologna Process" and are devising an institutional strategy for its implementation. In practical terms, this means aligning former national degrees and diplomas to standard European Bachelor and Masters degrees and PhD doctorates, by creating acknowledged professional qualification benchmarks that also include adjusted course lengths and contents. This process, in the end, mostly affects academic staff members who have a fundamental role to play in carrying out the pedagogical reforms on the teaching front. Besides presenting a commentary on the institutional approach of one particular technical university in Spain, the purpose of this paper is to propose, from the authors' point of view as lecturers, a strategy which has the potential to create a favourable atmosphere for carrying out such a reform. The article's main objective is to highlight a series of action points which may serve to reinforce and advance the main institutional strategy by relying on the powerful influence of its academic staff members.

  9. The Key Role of Government in Addressing the Pandemic of Micronutrient Deficiency Conditions in Southeast Asia

    Directory of Open Access Journals (Sweden)

    Theodore H. Tulchinsky

    2015-04-01

    Full Text Available Micronutrient deficiency conditions are a major global public health problem. While the private sector has an important role in addressing this problem, the main responsibility lies with national governments, in cooperation with international agencies and donors. Mandatory fortification of basic foods provides a basic necessary intake for the majority and needs to be supported by provision of essential vitamin and mineral supplements for mothers and children and other high risk groups. Fortification by government mandate and regulation is essential with cooperation by private sector food manufacturers, and in the context of broader policies for poverty reduction, education and agricultural reform. Iron, iodine, vitamin A, vitamin B complex, folic acid, zinc, vitamin D and vitamin B12 are prime examples of international fortification experience achieved by proactive governmental nutrition policies. These are essential to achieve the Millennium Development Goals and their follow-up sustainable global health targets. National governmental policies for nutritional security and initiatives are essential to implement both food fortification and targeted supplementation policies to reduce the huge burden of micronutrient deficiency conditions in Southeast Asia and other parts of the world.

  10. How to Achieve High-Quality Oocytes? The Key Role of Myo-Inositol and Melatonin

    Directory of Open Access Journals (Sweden)

    Salvatore Giovanni Vitale

    2016-01-01

    Full Text Available Assisted reproductive technologies (ART have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes. Although many authors have studied how supplementation therapy may affect this important parameter for both in vivo and in vitro models, data are not yet robust enough to support firm conclusions. Regarding this last point, in this review our objective has been to evaluate the state of the art regarding supplementation with melatonin and myo-inositol in order to improve oocyte quality during ART. On the one hand, the antioxidant effect of melatonin is well known as being useful during ovulation and oocyte incubation, two occasions with a high level of oxidative stress. On the other hand, myo-inositol is important in cellular structure and in cellular signaling pathways. Our analysis suggests that the use of these two molecules may significantly improve the quality of oocytes and the quality of embryos: melatonin seems to raise the fertilization rate, and myo-inositol improves the pregnancy rate, although all published studies do not fully agree with these conclusions. However, previous studies have demonstrated that cotreatment improves these results compared with melatonin alone or myo-inositol alone. We recommend that further studies be performed in order to confirm these positive outcomes in routine ART treatment.

  11. Swimming motility plays a key role in the stochastic dynamics of cell clumping

    Science.gov (United States)

    Qi, Xianghong; Nellas, Ricky B.; Byrn, Matthew W.; Russell, Matthew H.; Bible, Amber N.; Alexandre, Gladys; Shen, Tongye

    2013-04-01

    Dynamic cell-to-cell interactions are a prerequisite to many biological processes, including development and biofilm formation. Flagellum induced motility has been shown to modulate the initial cell-cell or cell-surface interaction and to contribute to the emergence of macroscopic patterns. While the role of swimming motility in surface colonization has been analyzed in some detail, a quantitative physical analysis of transient interactions between motile cells is lacking. We examined the Brownian dynamics of swimming cells in a crowded environment using a model of motorized adhesive tandem particles. Focusing on the motility and geometry of an exemplary motile bacterium Azospirillum brasilense, which is capable of transient cell-cell association (clumping), we constructed a physical model with proper parameters for the computer simulation of the clumping dynamics. By modulating mechanical interaction (‘stickiness’) between cells and swimming speed, we investigated how equilibrium and active features affect the clumping dynamics. We found that the modulation of active motion is required for the initial aggregation of cells to occur at a realistic time scale. Slowing down the rotation of flagellar motors (and thus swimming speeds) is correlated to the degree of clumping, which is consistent with the experimental results obtained for A. brasilense.

  12. Breast cancers radiation-resistance: key role of the cancer stem cells marker CD24

    International Nuclear Information System (INIS)

    Bensimon, Julie

    2013-01-01

    This work focuses on the characterization of radiation-resistant breast cancer cells, responsible for relapse after radiotherapy. The 'Cancer Stem Cells' (CSC) theory describes a radiation-resistant cellular sub-population, with enhanced capacity to induce tumors and proliferate. In this work, we show that only the CSC marker CD24-/low defines a radiation resistant cell population, able to transmit the 'memory' of irradiation, expressed as long term genomic instability in the progeny of irradiated cells. We show that CD24 is not only a marker, but is an actor of radiation-response. So, CD24 expression controls cell proliferation in vitro and in vivo, and ROS level before and after irradiation. As a result, CD24-/low cells display enhanced radiation-resistance and genomic stability. For the first time, our results attribute a role to CD24-/low CSCs in the transmission of genomic instability. Moreover, by providing informations on tumor intrinsic radiation-sensitivity, CD24- marker could help to design new radiotherapy protocols. (author)

  13. β-Adrenergic modulation of skeletal muscle contraction: key role of excitation-contraction coupling.

    Science.gov (United States)

    Cairns, Simeon P; Borrani, Fabio

    2015-11-01

    Our aim is to describe the acute effects of catecholamines/β-adrenergic agonists on contraction of non-fatigued skeletal muscle in animals and humans, and explain the mechanisms involved. Adrenaline/β-agonists (0.1-30 μm) generally augment peak force across animal species (positive inotropic effect) and abbreviate relaxation of slow-twitch muscles (positive lusitropic effect). A peak force reduction also occurs in slow-twitch muscles in some conditions. β2 -Adrenoceptor stimulation activates distinct cyclic AMP-dependent protein kinases to phosphorylate multiple target proteins. β-Agonists modulate sarcolemmal processes (increased resting membrane potential and action potential amplitude) via enhanced Na(+) -K(+) pump and Na(+) -K(+) -2Cl(-) cotransporter function, but this does not increase force. Myofibrillar Ca(2+) sensitivity and maximum Ca(2+) -activated force are unchanged. All force potentiation involves amplified myoplasmic Ca(2+) transients consequent to increased Ca(2+) release from sarcoplasmic reticulum (SR). This unequivocally requires phosphorylation of SR Ca(2+) release channels/ryanodine receptors (RyR1) which sensitize the Ca(2+) -induced Ca(2+) release mechanism. Enhanced trans-sarcolemmal Ca(2+) influx through phosphorylated voltage-activated Ca(2+) channels contributes to force potentiation in diaphragm and amphibian muscle, but not mammalian limb muscle. Phosphorylation of phospholamban increases SR Ca(2+) pump activity in slow-twitch fibres but does not augment force; this process accelerates relaxation and may depress force. Greater Ca(2+) loading of SR may assist force potentiation in fast-twitch muscle. Some human studies show no significant force potentiation which appears to be related to the β-agonist concentration used. Indeed high-dose β-agonists (∼0.1 μm) enhance SR Ca(2+) -release rates, maximum voluntary contraction strength and peak Wingate power in trained humans. The combined findings can explain how adrenaline

  14. Managing multiple roles - Personality, stress, and work-family interference in dual-earner couples

    NARCIS (Netherlands)

    Wierda-Boer, H.H.; Gerris, J.R.M.; Vermulst, A.A.

    2009-01-01

    Today many parents have multiple roles. This study examined how personality, domain-specific stress, and work-family interference are interrelated. Questionnaire data of 276 Dutch dual-earner couples with young children were analyzed using structural equation modeling. Findings demonstrated that job

  15. Epistemological and Reading Beliefs Profiles and Their Role in Multiple Text Comprehension

    Science.gov (United States)

    Mateos, Mar; Solé, Isabel; Martín, Elena; Castells, Nuria; Cuevas, Isabel; González-Lamas, Jara

    2016-01-01

    Introduction: The aim of this study was to analyse the role of epistemological beliefs and reading beliefs in the comprehension of multiple texts which presented conflicting positions about a controversial topic (nuclear energy). More specifically, we investigated the influence of the multidimensional configuration of epistemological and reading…

  16. Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy

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    Couture Réjean

    2010-06-01

    Full Text Available Abstract Background The pro-nociceptive kinin B1 receptor (B1R is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ-diabetic rat. This study aims at defining the role of microglial kinin B1R in diabetic pain neuropathy. Methods Sprague-Dawley rats were made diabetic with STZ (65 mg/kg, i.p., and 4 days later, two specific inhibitors of microglial cells (fluorocitrate, 1 nmol, i.t.; minocycline, 10 mg/kg, i.p. were administered to assess the impact on thermal hyperalgesia, allodynia and mRNA expression (qRT-PCR of B1R and pro-inflammatory markers. Spinal B1R binding sites ((125I-HPP-desArg10-Hoe 140 were also measured by quantitative autoradiography. Inhibition of microglia was confirmed by confocal microscopy with the specific marker Iba-1. Effects of intrathecal and/or systemic administration of B1R agonist (des-Arg9-BK and antagonists (SSR240612 and R-715 were measured on neuropathic pain manifestations. Results STZ-diabetic rats displayed significant tactile and cold allodynia compared with control rats. Intrathecal or peripheral blockade of B1R or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. Microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-Arg9-BK without affecting hyperglycemia in STZ rats. The enhanced mRNA expression (B1R, IL-1β, TNF-α, TRPV1 and Iba-1 immunoreactivity in the STZ spinal cord were normalized by fluorocitrate or minocycline, yet B1R binding sites were reduced by 38%. Conclusion The upregulation of kinin B1R in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in STZ-diabetic rats.

  17. Design of a hybrid reconfigurable Software Defined Radio transceiver based on frequency shift keying using multiple encoding schemes

    Directory of Open Access Journals (Sweden)

    Nikhil Marriwala

    2016-03-01

    The aim of this paper was to analyze Frequency Shift Keying (FSK Transceiver built using Laboratory Virtual Instrumentation Engineering Workbench (LabVIEW and to measure the reduction in data errors in the presence of Forward Error Correction (FEC channel coding algorithms namely the Convolution and the Turbo Codes. Through this design a graphical representation of Bit Error Rate (BER vs Eb/N0 where (Eb is Energy per bit and (N0 is Spectral noise density has been given in the presence of Additive White Gaussian Noise (AWGN introduced in the channel. FSK is widely used for data transmission over band pass channels; hence, we have chosen FSK for the implementation of SDR. The SDR transceiver module designed has been fully implemented and has the ability to navigate over a wide range of frequencies with programmable channel bandwidth and modulation characteristics. We are able to build an interactive FSK based SDR transceiver in a shorter time with the use of LabVIEW. The outputs achieved show a low BER for very high data rates in the presence of AWGN noise.

  18. Defining key features of the broad autism phenotype: a comparison across parents of multiple- and single-incidence autism families.

    Science.gov (United States)

    Losh, Molly; Childress, Debra; Lam, Kristen; Piven, Joseph

    2008-06-05

    This study examined the frequency of personality, language, and social-behavioral characteristics believed to comprise the broad autism phenotype (BAP), across families differing in genetic liability to autism. We hypothesized that within this unique sample comprised of multiple-incidence autism families (MIAF), single-incidence autism families (SIAF), and control Down syndrome families (DWNS), a graded expression would be observed for the principal characteristics conferring genetic susceptibility to autism, in which such features would express most profoundly among parents from MIAFs, less strongly among SIAFs, and least of all among comparison parents from DWNS families, who should display population base rates. Analyses detected linear expression of traits in line with hypotheses, and further suggested differential intrafamilial expression across family types. In the vast majority of MIAFs both parents displayed BAP characteristics, whereas within SIAFs, it was equally likely that one, both, or neither parent show BAP features. The significance of these findings is discussed in relation to etiologic mechanisms in autism and relevance to molecular genetic studies. (c) 2007 Wiley-Liss, Inc.

  19. p38 mitogen-activated protein kinase plays a key role in regulating MAPKAPK2 expression

    International Nuclear Information System (INIS)

    Sudo, Tatsuhiko; Kawai, Kayoko; Matsuzaki, Hiroshi; Osada, Hiroyuki

    2005-01-01

    One of three major families of the mitogen-activated kinases (MAPK), p38 as well as JNK, has been shown to transduce extracellular stress stimuli into cellular responses by phospho-relay cascades. Among p38 families, p38α is a widely characterized isoform and the biological phenomena are explained by its kinase activity regulating functions of its downstream substrates. However, its specific contributions to each phenomenon are yet not fully elucidated. For better understanding of the role of MAPKs, especially p38α, we utilized newly established mouse fibroblast cell lines originated from a p38α null mouse, namely, a parental cell line without p38α gene locus, knockout of p38α (KOP), Zeosin-resistant (ZKOP), revertant of p38α (RKOP), and Exip revertant (EKOP). EKOP is smaller in size but grows faster than the others. Although comparable amounts of ERK and JNK are expressed in each cell line, ERK is highly phosphorylated in EKOP even in normal culture conditions. Serum stimulation after serum starvation led to ERK phosphorylation in RKOP and ZKOP, but not in EKOP as much. On the contrary, relative phosphorylation level of JNK to total JNK in response to UV was low in RKOP. And its phosphorylation as well as total JNK is slightly lower in EKOP. RKOP is less sensitive to UV irradiation as judged by the survival rate. Stress response upon UV or sorbitol stimuli, leading to mitogen activate protein kinase activated kinase 2 (MAPKAPK2) phosphorylation, was only observed in RKOP. Further experiments reveal that MAPKAPK2 expression is largely suppressed in ZKOP and EKOP. Its expression was recovered by re-introduction of p38α. The loss of MAPKAPK2 expression accompanied by the defect of p38α is confirmed in an embryonic extract prepared from p38α null mice. These data demonstrate that p38 signal pathway is regulated not only by phosphorylation but also by modulation of the expression of its component. Together, we have established cell lines that can be used in

  20. A review on potential roles of vitamins in incidence, progression, and improvement of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Matin Khosravi-Largani

    2018-03-01

    Full Text Available Multiple Sclerosis (MS is an inflammatory and neurodegenerative disease, with unknown etiology. Vitamins, as important micronutrients playing different roles in body, seem to be important in MS pathogenesis. In vitro, in vivo and human studies, supports the protective role of some vitamins in MS occurrence or progression. Current study reviews recent insights and reports about the importance of vitamins in MS incidence or progression. In accordance, the importance of all water and fat-soluble vitamins in MS pathogenesis based on observational studies in human population and their role in the function of immune system as well as possible therapeutic opportunities are discussed in depth throughout this review. Keywords: Multiple sclerosis, Experimental autoimmune encephalomyelitis, Vitamin A, Vitamin E, Vitamin D, Folic acid, Vitamin B 12, Vitamins

  1. Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

    Directory of Open Access Journals (Sweden)

    Logan Richard M

    2010-03-01

    Full Text Available Abstract Background Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.

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

    Science.gov (United States)

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

    2017-09-27

    High-quality perovskite films can be fabricated from Lewis acid-base adducts through molecule exchange. Substantial work is needed to fully understand the formation mechanism of the perovskite films, which helps to further improve their quality. Here, we study the formation of CH 3 NH 3 PbI 3 perovskite films by introducing some dimethylacetamide into the PbI 2 /N,N-dimethylformamide solution. We reveal that there are three key processes during the formation of perovskite films through the Lewis acid-base adduct approach: molecule intercalation of solvent into the PbI 2 lattice, molecule exchange between the solvent and CH 3 NH 3 I, and dissolution-recrystallization of the perovskite grains during annealing. The Lewis base solvents play multiple functions in the above processes. The properties of the solvent, including Lewis basicity and boiling point, play key roles in forming smooth perovskite films with large grains. We also provide some rules for choosing Lewis base additives to prepare high-quality perovskite films through the Lewis adduct approach.

  3. Development and validation of the work-family-school role conflicts and role-related social support scales among registered nurses with multiple roles.

    Science.gov (United States)

    Xu, Lijuan; Song, Rhayun

    2013-10-01

    The purpose of this study was to develop work-family-school role conflicts and role-related social support scales, and to validate the psychometrics of those scales among registered nurses with multiple roles. The concepts, generation of items, and the scale domains of work-family-school role conflicts and role-related social support scales were constructed based on a review of the literature. The validity and reliability of the scales were examined by administering them to 201 registered nurses who were recruited from 8 university hospitals in South Korea. The content validity was examined by nursing experts using a content validity index. Exploratory factor analysis and confirmatory factor analysis were used to establish the construct validity. The correlation with depression was examined to assess concurrent validity. Finally, internal consistency was assessed using Cronbach's alpha coefficients. The work-family-school role conflicts scale comprised ten items with three factors: work-school-to-family conflict (three items), family-school-to-work conflict (three items), and work-family-to-school conflict (four items). The role-related social support scale comprised nine items with three factors: support from family (three items), support from work (three items), and support from school (three items). Cronbach's alphas were 0.83 and 0.76 for the work-family-school role conflicts and role-related social support scales, respectively. Both instruments exhibited acceptable construct and concurrent validity. The validity and reliability of the developed scales indicate their potential usefulness for the assessment of work-family-school role conflict and role-related social support among registered nurses with multiple roles in Korea. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Mothers of young adults with intellectual disability: multiple roles, ethnicity and well-being.

    Science.gov (United States)

    Eisenhower, A; Blacher, J

    2006-12-01

    Two opposing perspectives--role strain and role enhancement--were considered as predictive of women's psychological and physical health. The authors examined the relation between multiple role occupancy (parenting, employment, marriage) and well-being (depression and health) among mothers of young adults with intellectual disability (ID). Participants were 226 mothers aged 35-70 years old caring for a young adult aged 16-26 years old with moderate to severe/profound ID. Mothers were of either Latino ethnicity (n=117) or Anglo (n=109). Mothers' ethnicity and degree of acculturation and young adults' adaptive behaviour and behaviour problems were examined as potential moderators. Mothers who were employed, married, or both reported better well-being than mothers who were both unemployed and unmarried, especially when their offspring had relatively higher adaptive functioning. This relationship between role occupancy and well-being was fully mediated by socio-economic status (SES) factors. Results did not suggest a role enhancement effect, but instead indicated a role shortage effect; unemployed, unmarried mothers experienced markedly poor well-being, while all other mothers experienced comparable well-being. Well-being scores were higher for Anglo than for Latino mothers; this relationship was entirely accounted for by SES. In Latina mothers, the relation between role occupancy and well-being was moderated by degree of acculturation. Findings suggest that multiple roles benefit mothers of young adults with ID primarily through their impact on socio-economic resources. For more acculturated Latina mothers, occupying more roles predicted better well-being even after controlling for SES. Latina mothers who were unemployed and unmarried had lower SES, and this group emerged as at particular risk. The latter group may benefit most from respite assistance and other interventions aimed at addressing their physical and mental health.

  5. Bridges or Barriers? Conceptualization of the Role of Multiple Identity Gateway Groups in Intergroup Relations

    Directory of Open Access Journals (Sweden)

    Aharon Levy

    2017-06-01

    Full Text Available The modern era of globalization has been accompanied by a massive growth in interconnections between groups, and has led to the sharing of multiple identities by individuals and groups. Following these developments, research has focused on the issue of multiple identities, and has shed important light on how individuals who hold these complex forms of identity feel and behave, and on the reactions they elicit from members of other groups. However, the potential of groups with such multiple identities (e.g., biracials, immigrants, etc. to affect the intergroup relations between the groups that represent the respective sources of the different identities (e.g., Blacks and Whites, country of origin and country of residence, etc. has not been examined to date. Accordingly, in this paper, we first systematically explore the potential of groups in which people identify with multiple social categories, or groups that are perceived as such by others, to play a role in intergroup dynamics. Next, we offer a theoretical framework outlining what functions groups of people with shared multiple identities may serve (as bridges or barriers by proposing how their presence may facilitate or deteriorate intergroup relations. Finally, we present recent empirical research examining how groups of people with shared multiple identities can act as gateways and bridge the cleft between two separate groups that represent the respective sources of their different identities, and discuss the theoretical and practical implications for the field of intergroup relations.

  6. Cost-effectiveness analysis and efficient use of the pharmaceutical budget: the key role of clinical pharmacologists.

    Science.gov (United States)

    Edlin, Richard; Round, Jeff; Hulme, Claire; McCabe, Christopher

    2010-09-01

    The purpose of this paper is to provide information about cost-effectiveness analysis and the roles of clinical pharmacologists generally in providing efficient health care. The paper highlights the potential consequences of 'off-label prescribing' and 'indication creep' behaviour given slower growth (or potential cuts) in the NHS budget. This paper highlights the key roles of clinical pharmacologists in delivering an efficient health care system when resources are allocated using cost-effectiveness analyses. It describes what cost-effectiveness analysis (CEA) is and how incremental cost-effectiveness ratios (ICERs) are used to identify efficient options. After outlining the theoretical framework within which using CEA can promote the efficient allocation of the health care budget, it considers the place of disinvestment within achieving efficient resource allocation. Clinical pharmacologists are argued to be critical to providing improved population health under CEA-based resource allocation processes because of their roles in implementation and disinvestment. Given that the challenges facing the United Kingdom National Health Service (NHS) are likely to increase, this paper sets out the stark choices facing clinical pharmacologists.

  7. Key role of integrin α(IIb)β (3) signaling to Syk kinase in tissue factor-induced thrombin generation.

    Science.gov (United States)

    van der Meijden, Paola E J; Feijge, Marion A H; Swieringa, Frauke; Gilio, Karen; Nergiz-Unal, Reyhan; Hamulyák, Karly; Heemskerk, Johan W M

    2012-10-01

    The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.

  8. The regulation of the chloroplast proton motive force plays a key role for photosynthesis in fluctuating light.

    Science.gov (United States)

    Armbruster, Ute; Correa Galvis, Viviana; Kunz, Hans-Henning; Strand, Deserah D

    2017-06-01

    Plants use sunlight as their primary energy source. During photosynthesis, absorbed light energy generates reducing power by driving electron transfer reactions. These are coupled to the transfer of protons into the thylakoid lumen, generating a proton motive force (pmf) required for ATP synthesis. Sudden alterations in light availability have to be met by regulatory mechanisms to avoid the over-accumulation of reactive intermediates and maximize energy efficiency. Here, the acidification of the lumen, as an intermediate product of photosynthesis, plays an important role by regulating photosynthesis in response to excitation energy levels. Recent findings reveal pmf regulation and the modulation of its composition as key determinants for efficient photosynthesis, plant growth, and survival in fluctuating light environments. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Decisional role preferences, risk knowledge and information interests in patients with multiple sclerosis.

    Science.gov (United States)

    Heesen, Christoph; Kasper, Jürgen; Segal, Julia; Köpke, Sascha; Mühlhauser, Ingrid

    2004-12-01

    Shared decision making is increasingly recognized as the ideal model of patient-physician communication especially in chronic diseases with partially effective treatments as multiple sclerosis (MS). To evaluate prerequisite factors for this kind of decision making we studied patients' decisional role preferences in medical decision making, knowledge on risks, information interests and the relations between these factors in MS. After conducting focus groups to generate hypotheses, 219 randomly selected patients from the MS Outpatient Clinic register (n = 1374) of the University Hospital Hamburg received mailed questionnaires on their knowledge of risks in MS, their perception of their own level of knowledge, information interests and role preferences. Most patients (79%) indicated that they preferred an active role in treatment decisions giving the shared decision and the informed choice model the highest priority. MS risk knowledge was low but questionnaire results depended on disease course, disease duration and ongoing immune therapy. Measured knowledge as well as perceived knowledge was only weakly correlated with preferences of active roles. Major information interests were related to symptom alleviation, diagnostic procedures and prognosis. Patients with MS claimed autonomous roles in their health care decisions. The weak correlation between knowledge and preferences for active roles implicates that other factors largely influence role preferences.

  10. Presentation of MSc in Higher Education Dissertation School Meeting : What are the key dimensions of the personal tutor role for nurse education today?,

    OpenAIRE

    Leddington, Susan

    2012-01-01

    Presentation of MSc in Higher Education Dissertation School Meeting : What are the key dimensions of the personal tutor role for nurse education today?, A literature review, Missenden Abbey, June 2009, presentation

  11. Managing multiple roles: development of the Work-Family Conciliation Strategies Scale.

    Science.gov (United States)

    Matias, Marisa; Fontaine, Anne Marie

    2014-07-17

    Juggling the demands of work and family is becoming increasingly difficult in today's world. As dual-earners are now a majority and men and women's roles in both the workplace and at home have changed, questions have been raised regarding how individuals and couples can balance family and work. Nevertheless, research addressing work-family conciliation strategies is limited to a conflict-driven approach and context-specific instruments are scarce. This study develops an instrument for assessing how dual-earners manage their multiple roles detaching from a conflict point of view highlighting the work-family conciliation strategies put forward by these couples. Through qualitative and quantitative procedures the Work-Family Conciliation Strategies Scales was developed and is composed by 5 factors: Couple Coping; Positive Attitude Towards Multiple Roles, Planning and Management Skills, Professional Adjustments and Institutional Support; with good adjustment [χ2/df = 1.22; CFI = .90, RMSEA = .04, SRMR = .08.] and good reliability coefficients [from .67 to .87]. The developed scale contributes to research because of its specificity to the work-family framework and its focus on the proactive nature of balancing work and family roles. The results support further use of this instrument.

  12. The key role of exudative lesions and their encapsulation: lessons learned from the pathology of human pulmonary tuberculosis.

    Science.gov (United States)

    Cardona, Pere-Joan

    2015-01-01

    A review of the pathology of human pulmonary TB cases at different stages of evolution in the pre-antibiotic era suggests that neutrophils play an instrumental role in the progression toward active TB. This progression is determined by the type of lesion generated. Thus, exudative lesions, in which neutrophils are the major cell type, are both triggered by and induce local high bacillary load, and tend to enlarge and progress toward liquefaction and cavitation. In contrast, proliferative lesions are triggered by low bacillary loads, mainly comprise epithelioid cells and fibroblasts and tend to fibrose, encapsulate and calcify, thus controlling the infection. Infection of the upper lobes is key to the progression toward active TB for two main reasons, namely poor breathing amplitude, which allows local bacillary accumulation, and the high mechanical stress to which the interlobular septae (which enclose secondary lobes) are submitted, which hampers their ability to encapsulate lesions. Overall, progressing factors can be defined as internal (exudative lesion, local bronchogenous dissemination, coalescence of lesions), with lympho-hematological dissemination playing a very limited role, or external (exogenous reinfection). Abrogating factors include control of the bacillary load and the local encapsulation process, as directed by interlobular septae. The age and extent of disease depend on the quality and speed with which lesions liquefy and disseminate bronchially, the volume of the slough, and the amount and distribution of the sloughing debris dispersed.

  13. The Impact of Multiple Roles on Psychological Distress among Japanese Workers.

    Science.gov (United States)

    Honda, Ayumi; Abe, Yasuyo; Date, Yutaka; Honda, Sumihisa

    2015-06-01

    There has been considerable interest in Japanese society in the problem of work-related stress leading to depressive symptoms, and an increasing number of primary houseworkers maintain paid employment. The purpose of this study was to examine the differential impact of multiple roles associated with psychological distress among Japanese workers. We studied 722 men and women aged 18-83 years in a cross-sectional study. The K10 questionnaire was used to examine psychological distress. The proportion of participants with psychological distress was higher in women (17.8%) compared with men (11.5%). Having three roles significantly decreased the risk of psychological distress [women: odds ratio (OR), 0.37-fold; men: OR, 0.41] compared with only one role. In working married women, there was significantly less psychological distress (OR, 0.27), and those with childrearing or caregiving responsibilities for elderly parents had significantly less psychological distress (OR, 0.38) than those with only an employment role. Similarly, working married men who had childrearing or caregiving responsibilities for elderly parents had significantly less psychological distress (OR, 0.41) than those who had only an employment role. The present study demonstrated that participants who had only an employment role had an increased risk of psychological distress. The degree of psychological distress was not determined solely by the number of roles. It is important to have balance between work and family life to reduce role conflict and/or role submersion, which in turn may reduce the risk of psychological distress.

  14. Playing [with] multiple roles: Readers, authors, and characters in "Who Is Blaise Zabini?" [symposium

    Directory of Open Access Journals (Sweden)

    Anne Collins Smith

    2009-11-01

    Full Text Available Fans who produce fan works in genres such as fiction, music, and music video take on dual roles in the process, as readers of the original canon and as creators of their own products. These roles—and more—are creatively explored in the Parselmouths' wizard rock composition "Who Is Blaise Zabini?". Like many works of fan fiction, the Parselmouths' songs move beyond a reader's ordinary role, taking on an authorial role to generate new characters and events in the Harry Potter universe. What makes this particular work unusual is that at the same time that they are adopting the roles of authors, and even of participants, the Parselmouths also restrict their own authorial and participatory power, claiming that the Slytherin characters they portray could not perceive their classmate Blaise Zabini until J. K. Rowling provided a complete description of him. To untangle their multiple roles and to recognize the creativity exercised by the Parselmouths in collapsing the boundaries among them, it will be helpful to turn to a theory of audience response that delineates specific roles and that specifies the limitations and the powers inherent in them.

  15. The Part-Time Student Role: Implications for the Emotional Experience of Managing Multiple Roles amongst Hong Kong Public Health Nurses.

    Science.gov (United States)

    Shiu, Ann Tak-Ying

    1999-01-01

    Nine public-health nurses studying part time and 11 other nurses sampled their mood states randomly over seven days. The part-time student role created additional strain for nurses with children. The stress of managing multiple roles was greatest when both work and nonwork role responsibilities were heavy. (SK)

  16. Striking Plasticity of CRISPR-Cas9 and Key Role of Non-target DNA, as Revealed by Molecular Simulations.

    Science.gov (United States)

    Palermo, Giulia; Miao, Yinglong; Walker, Ross C; Jinek, Martin; McCammon, J Andrew

    2016-10-26

    The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system recently emerged as a transformative genome-editing technology that is innovating basic bioscience and applied medicine and biotechnology. The endonuclease Cas9 associates with a guide RNA to match and cleave complementary sequences in double stranded DNA, forming an RNA:DNA hybrid and a displaced non-target DNA strand. Although extensive structural studies are ongoing, the conformational dynamics of Cas9 and its interplay with the nucleic acids during association and DNA cleavage are largely unclear. Here, by employing multi-microsecond time scale molecular dynamics, we reveal the conformational plasticity of Cas9 and identify key determinants that allow its large-scale conformational changes during nucleic acid binding and processing. We show how the "closure" of the protein, which accompanies nucleic acid binding, fundamentally relies on highly coupled and specific motions of the protein domains, collectively initiating the prominent conformational changes needed for nucleic acid association. We further reveal a key role of the non-target DNA during the process of activation of the nuclease HNH domain, showing how the nontarget DNA positioning triggers local conformational changes that favor the formation of a catalytically competent Cas9. Finally, a remarkable conformational plasticity is identified as an intrinsic property of the HNH domain, constituting a necessary element that allows for the HNH repositioning. These novel findings constitute a reference for future experimental studies aimed at a full characterization of the dynamic features of the CRISPR-Cas9 system, and-more importantly-call for novel structure engineering efforts that are of fundamental importance for the rational design of new genome-engineering applications.

  17. The role of glatiramer acetate in the early treatment of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    David W Brandes

    2010-06-01

    Full Text Available David W BrandesHope MS Center, Knoxville, TN, USA; ULCA, Los Angeles, CA, USAAbstract: The treatment of the underlying disease process causing multiple sclerosis has continued to evolve since the initial approval of interferon-beta-1b in 1993. Current emphasis is on early treatment, including treatment after a single clinical attack (clinically isolated syndrome. The assessment of which disease modifying medication to use as initial therapy has continued to remain a combination of science and the art of medicine. Equally important are the assessment of treatment failure and the subsequent choice of medication change. This article will present scientific information, as well as information about clinical decision making, about these choices, with emphasis on the changing role of glatiramer acetate in this process.Keywords: glatiramer acetate, early treatment, multiple sclerosis

  18. The Role of CLEAR Thinking in Learning Science from Multiple-Document Inquiry Tasks

    Directory of Open Access Journals (Sweden)

    Thomas D. GRIFFIN

    2012-10-01

    Full Text Available The main goal for the current study was to investigate whether individual differences in domaingeneral thinking dispositions might affect learning from multiple-document inquiry tasks in science.Middle school students were given a set of documents and were tasked with understanding how and why recent patterns in global temperature might be different from what has been observed in the past from those documents. Understanding was assessed with two measures: an essay task and an inference verification task. Domain-general thinking dispositions were assessed with a Commitment to Logic, Evidence, and Reasoning (CLEAR thinking scale. The measures of understanding wereuniquely predicted by both reading skills and CLEAR thinking scores, and these effects were not attributable to prior knowledge or interest. The results suggest independent roles for thinkingdispositions and reading ability when students read to learn from multiple-document inquiry tasks in science.

  19. Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice.

    Science.gov (United States)

    Xu, Bing; Jiang, Mingzuo; Chu, Yi; Wang, Weijie; Chen, Di; Li, Xiaowei; Zhang, Zhao; Zhang, Di; Fan, Daiming; Nie, Yongzhan; Shao, Feng; Wu, Kaichun; Liang, Jie

    2017-12-20

    Gasdermin D (GSDMD)-executed programmed necrosis is involved in inflammation and controls interleukin (IL)-1β release. However, the role of GSDMD in non-alcoholic steatohepatitis (NASH) remains unclear. We investigated the role of GSDMD in the pathogenesis of steatohepatitis. Human liver tissues from patients with non-alcoholic fatty liver disease (NAFLD) and control individuals were obtained to evaluate GSDMD expression. Gsdmd knockout (Gsdmd -/- ) mice, obese db/db mice and their wild-type (WT) littermates were fed with methionine-choline deficient (MCD) or control diet to induce steatohepatitis. The Gsdmd -/- and WT mice were also used in a high-fat diet (HFD)-induced NAFLD model. In addition, Alb-Cre mice were administered an adeno-associated virus (AAV) vector that expressed the gasdermin-N domain (AAV9-FLEX-GSDMD-N) and were fed with either MCD or control diet for 10 days. GSDMD and its pyroptosis-inducing fragment GSDMD-N were upregulated in liver tissues of human NAFLD/NASH. Importantly, hepatic GSDMD-N protein levels were significantly higher in human NASH and correlated with the NAFLD activity score and fibrosis. GSDMD-N remained a potential biomarker for the diagnosis of NASH. MCD-fed Gsdmd -/- mice exhibit decreased severity of steatosis and inflammation compared with WT littermates. GSDMD was associated with the secretion of pro-inflammatory cytokines (IL-1β, TNF-α, and MCP-1 [CCL2]) and persistent activation of the NF-ĸB signaling pathway. Gsdmd -/- mice showed lower steatosis, mainly because of reduced expression of the lipogenic gene Srebp1c (Srebf1) and upregulated expression of lipolytic genes, including Pparα, Aco [Klk15], Lcad [Acadl], Cyp4a10 and Cyp4a14. Alb-Cre mice administered with AAV9-FLEX-GSDMD-N showed significantly aggravated steatohepatitis when fed with MCD diet. As an executor of pyroptosis, GSDMD plays a key role in the pathogenesis of steatohepatitis, by controlling cytokine secretion, NF-ĸB activation, and lipogenesis

  20. How educational innovations and attention to competencies in postgraduate medical education relate to preparedness for practice: the key role of the learning environment.

    Science.gov (United States)

    Dijkstra, Ids S; Pols, Jan; Remmelts, Pine; Rietzschel, Eric F; Cohen-Schotanus, Janke; Brand, Paul L P

    2015-12-01

    Many training programmes in postgraduate medical education (PGME) have introduced competency frameworks, but the effects of this change on preparedness for practice are unknown. Therefore, we explored how elements of competency-based programmes in PGME (educational innovations, attention to competencies and learning environment) were related to perceived preparedness for practice among new consultants. A questionnaire was distributed among 330 new consultants. Respondents rated how well their PGME training programme prepared them for practice, the extent to which educational innovations (portfolio, Mini-CEX) were implemented, and how much attention was paid to CanMEDS competencies during feedback and coaching, and they answered questions on the learning environment and general self-efficacy. Multiple regression and mediation analyses were used to analyze data. The response rate was 43 % (143/330). Controlling for self-efficacy and gender, the learning environment was the strongest predictor of preparedness for practice (B = 0.42, p competencies (B = 0.29, p competencies mediated the relationship between educational innovations and preparedness for practice. This mediation became stronger at higher learning environment values. The learning environment plays a key role in determining the degree to which competency-based PGME prepares trainees for independent practice.

  1. Development of a questionnaire to measure the key attributes of the community palliative care specialist nurse role.

    Science.gov (United States)

    Cameron, Dee; Johnston, Bridget

    2015-02-01

    Recent worldwide economic events have forced an examination of the nurse's contribution to high-quality, effective, person-centred care. Since the role of specialist nurses is considered one of the least understood or valued developments in nursing, specialist nurses must demonstrate their contribution to quality, person-centred health care. To develop a questionnaire which aims to measure the quality of care provided by palliative care specialist nurses from the patients' perspective and to undertake initial validation. The process of questionnaire development involved six phases including systematic literature reviews, patient advisory groups and expert panel reviews, each of which contributed to the questionnaire face and content validity. Johnston's Expert Palliative Care Nurse Model (2002; 2005) provided an evidence-based framework for the development of the questionnaire, and enabled the identification of the key attributes of the palliative care specialist nurse role, thereby providing the themes on which to base the questionnaire. The Quality Measure for Palliative Nursing, a questionnaire, was developed. The themes identified in the questionnaire--personal characteristics, communication skills, knowledge, relationship with patient and providing comfort--aim to facilitate measurement of the quality of care provided by palliative care specialist nurses. Designed for use by palliative patients the Quality Measure for Palliative Nursing is a one-page questionnaire comprising of 15 questions. The Quality Measure for Palliative Nursing is unique since it aims to measure the quality of care provided by community palliative care specialist nurses, and could also be used to measure patient satisfaction with the quality of care provided. Further testing is recommended to ensure that this questionnaire can provide reliable and valid results.

  2. The potential role for ocrelizumab in the treatment of multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg; Blinkenberg, Morten

    2016-01-01

    B cells play a central role in the pathogenesis in multiple sclerosis (MS), being involved in the activation of proinflammatory T cells, secretion of proinflammatory cytokines, and production of autoantibodies directed against myelin. Hence, the usage of B-cell-depleting monoclonal antibodies....... Other anti-CD20 monoclonal antibodies have been tested as treatments for MS, including ofatumumab that has shown beneficial results in placebo-controlled phase II trials in patients with relapsing-remitting MS. Ocrelizumab is now in phase III development for the treatment of relapsing-remitting MS...

  3. Integrating the ICF with positive psychology: Factors predicting role participation for mothers with multiple sclerosis.

    Science.gov (United States)

    Farber, Ruth S; Kern, Margaret L; Brusilovsky, Eugene

    2015-05-01

    Being a mother has become a realizable life role for women with disabilities and chronic illnesses, including multiple sclerosis (MS). Identifying psychosocial factors that facilitate participation in important life roles-including motherhood-is essential to help women have fuller lives despite the challenge of their illness. By integrating the International Classification of Functioning, Disability, and Health (ICF) and a positive psychology perspective, this study examined how environmental social factors and positive personal factors contribute to daily role participation and satisfaction with parental participation. One hundred and 11 community-dwelling mothers with MS completed Ryff's Psychological Well-Being Scales, the Medical Outcome Study Social Support Survey, the Short Form-36, and the Parental Participation Scale. Hierarchical regression analyses examined associations between social support and positive personal factors (environmental mastery, self-acceptance, purpose in life) with daily role participation (physical and emotional) and satisfaction with parental participation. One-way ANOVAs tested synergistic combinations of social support and positive personal factors. Social support predicted daily role participation (fewer limitations) and greater satisfaction with parental participation. Positive personal factors contributed additional unique variance. Positive personal factors and social support synergistically predicted better function and greater satisfaction than either alone. Integrating components of the ICF and positive psychology provides a useful model for understanding how mothers with MS can thrive despite challenge or impairment. Both positive personal factors and environmental social factors were important contributors to positive role functioning. Incorporating these paradigms into treatment may help mothers with MS participate more fully in meaningful life roles. (c) 2015 APA, all rights reserved).

  4. New developments in the management of relapsed/refractory multiple myeloma – the role of ixazomib

    Directory of Open Access Journals (Sweden)

    Richardson PG

    2017-08-01

    Full Text Available Paul G Richardson,1 Shaji Kumar,2 Jacob P Laubach,1 Claudia Paba-Prada,1 Neeraj Gupta,3 Deborah Berg,3 Helgi van de Velde,3 Philippe Moreau4 1Division of Hematologic Malignancy, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA; 2Division of Hematology, Mayo Clinic, Rochester, MN, USA; 3Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA; 4Hematology Department, University Hospital Hotel-Dieu, Nantes, France Abstract: Ixazomib is the first oral proteasome inhibitor to be approved, in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was on the basis of results from the phase 3, double-blind, placebo-controlled TOURMALINE-MM1 study, which demonstrated a 35% improvement in progression-free survival with the all-oral combination of ixazomib plus lenalidomide–dexamethasone versus lenalidomide–dexamethasone alone (median: 20.6 vs 14.7 months; hazard ratio: 0.74, p=0.012; median follow-up 14.7 months. The addition of ixazomib to the lenalidomide–dexamethasone regimen was associated with limited additional toxicity and had no adverse impact on patient-reported quality of life. Common grade ≥3 adverse events with ixazomib include gastrointestinal adverse events, rash, and thrombocytopenia. Here, we review the efficacy, safety, pharmacokinetics, and patient-reported quality of life data seen with ixazomib, and discuss the role of this oral agent in the treatment of patients with relapsed/refractory multiple myeloma, including in patients with high-risk cytogenetic abnormalities and those with multiple prior therapies. Keywords: ixazomib, multiple myeloma, proteasome inhibitor, clinical, efficacy, tolerability, pharmacokinetics 

  5. ADP-glucose pyrophosphorylase gene plays a key role in the quality of corm and yield of cormels in gladiolus

    International Nuclear Information System (INIS)

    Seng, Shanshan; Wu, Jian; Sui, Juanjuan; Wu, Chenyu; Zhong, Xionghui; Liu, Chen; Liu, Chao; Gong, Benhe; Zhang, Fengqin; He, Junna; Yi, Mingfang

    2016-01-01

    Starch is the main storage compound in underground organs like corms. ADP-glucose pyrophosphorylase (AGPase) plays a key role in regulating starch biosynthesis in storage organs and is likely one of the most important determinant of sink strength. Here, we identify an AGPase gene (GhAGPS1) from gladiolus. The highest transcriptional levels of GhAGPS1 were observed in cormels and corms. Transformation of GhAGPS1 into Arabidopsis rescued the phenotype of aps1 mutant. Silencing GhAGPS1 in gladiolus corms by virus-induced gene silencing (VIGS) decreased the transcriptional levels of two genes and starch content. Transmission electron microscopy analyses of leaf and corm sections confirmed that starch biosynthesis was inhibited. Corm weight and cormel number reduced significantly in the silenced plants. Taken together, these results indicate that inhibiting the expression of AGPase gene could impair starch synthesis, which results in the lowered corm quality and cormel yield in gladiolus. -- Highlights: •Cormel quantity was reduced significantly in silenced Gladiolus plants. •Corm quality was declined significantly in silenced Gladiolus plants. •Starch synthesis was inhibited in silenced Gladiolus plants.

  6. Mechanism of conformational coupling in SecA: Key role of hydrogen-bonding networks and water interactions.

    Science.gov (United States)

    Milenkovic, Stefan; Bondar, Ana-Nicoleta

    2016-02-01

    SecA uses the energy yielded by the binding and hydrolysis of adenosine triphosphate (ATP) to push secretory pre-proteins across the plasma membrane in bacteria. Hydrolysis of ATP occurs at the nucleotide-binding site, which contains the conserved carboxylate groups of the DEAD-box helicases. Although crystal structures provide valuable snapshots of SecA along its reaction cycle, the mechanism that ensures conformational coupling between the nucleotide-binding site and the other domains of SecA remains unclear. The observation that SecA contains numerous hydrogen-bonding groups raises important questions about the role of hydrogen-bonding networks and hydrogen-bond dynamics in long-distance conformational couplings. To address these questions, we explored the molecular dynamics of SecA from three different organisms, with and without bound nucleotide, in water. By computing two-dimensional hydrogen-bonding maps we identify networks of hydrogen bonds that connect the nucleotide-binding site to remote regions of the protein, and sites in the protein that respond to specific perturbations. We find that the nucleotide-binding site of ADP-bound SecA has a preferred geometry whereby the first two carboxylates of the DEAD motif bridge via hydrogen-bonding water. Simulations of a mutant with perturbed ATP hydrolysis highlight the water-bridged geometry as a key structural element of the reaction path. Copyright © 2015. Published by Elsevier B.V.

  7. Confirming the key role of Ar+ ion bombardment in the growth feature of nanostructured carbon materials by PECVD.

    Science.gov (United States)

    Liu, Yulin; Lin, Jinghuang; Jia, Henan; Chen, Shulin; Qi, Junlei; Qu, Chaoqun; Cao, Jian; Feng, Jicai; Fei, Weidong

    2017-11-24

    In order to confirm the key role of Ar + ion bombardment in the growth feature of nanostructured carbon materials (NCMs), here we report a novel strategy to create different Ar + ion states in situ in plasma enhanced chemical vapor deposition (PECVD) by separating catalyst film from the substrate. Different bombardment environments on either side of the catalyst film were created simultaneously to achieve multi-layered structural NCMs. Results showed that Ar + ion bombardment is crucial and complex for the growth of NCMs. Firstly, Ar + ion bombardment has both positive and negative effects on carbon nanotubes (CNTs). On one hand, Ar + ions can break up the graphic structure of CNTs and suppress thin CNT nucleation and growth. On the other hand, Ar + ion bombardment can remove redundant carbon layers on the surface of large catalyst particles which is essential for thick CNTs. As a result, the diameter of the CNTs depends on the Ar + ion state. As for vertically oriented few-layer graphene (VFG), Ar + ions are essential and can even convert the CNTs into VFG. Therefore, by combining with the catalyst separation method, specific or multi-layered structural NCMs can be obtained by PECVD only by changing the intensity of Ar + ion bombardment, and these special NCMs are promising in many fields.

  8. The key role of the meat industry in transformation to a low-carbon, climate resilient, sustainable economy.

    Science.gov (United States)

    Rijsberman, Frank

    2017-10-01

    Climate change, air pollution and refugees have become key global challenges threatening sustainability of lifestyles, economies and ecosystems. Agri-food systems are the number one driver of environmental change. Livestock production is the world's largest land user, responsible for half of greenhouse gas emissions from agri-food systems, and the source of repeated health crises. Poor diets have become the number one cause of ill health. Recommendations for a healthy diet emphasize plant-based food. Rapidly falling costs in information technology, biotechnology, renewable energy and battery technology will disrupt current energy and transportation systems and offer opportunities for responsible meat production. Growing consumer interest in healthy food, combined with innovative information systems, offer opportunities to create value through quality control and consumer information in integrated value chains. Meat scientists have a major role to play in the necessary transformation of global agri-food systems towards a new model of green economic growth that is climate resilient, sustainable and provides green jobs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Confirming the key role of Ar+ ion bombardment in the growth feature of nanostructured carbon materials by PECVD

    Science.gov (United States)

    Liu, Yulin; Lin, Jinghuang; Jia, Henan; Chen, Shulin; Qi, Junlei; Qu, Chaoqun; Cao, Jian; Feng, Jicai; Fei, Weidong

    2017-11-01

    In order to confirm the key role of Ar+ ion bombardment in the growth feature of nanostructured carbon materials (NCMs), here we report a novel strategy to create different Ar+ ion states in situ in plasma enhanced chemical vapor deposition (PECVD) by separating catalyst film from the substrate. Different bombardment environments on either side of the catalyst film were created simultaneously to achieve multi-layered structural NCMs. Results showed that Ar+ ion bombardment is crucial and complex for the growth of NCMs. Firstly, Ar+ ion bombardment has both positive and negative effects on carbon nanotubes (CNTs). On one hand, Ar+ ions can break up the graphic structure of CNTs and suppress thin CNT nucleation and growth. On the other hand, Ar+ ion bombardment can remove redundant carbon layers on the surface of large catalyst particles which is essential for thick CNTs. As a result, the diameter of the CNTs depends on the Ar+ ion state. As for vertically oriented few-layer graphene (VFG), Ar+ ions are essential and can even convert the CNTs into VFG. Therefore, by combining with the catalyst separation method, specific or multi-layered structural NCMs can be obtained by PECVD only by changing the intensity of Ar+ ion bombardment, and these special NCMs are promising in many fields.

  10. ADP-glucose pyrophosphorylase gene plays a key role in the quality of corm and yield of cormels in gladiolus

    Energy Technology Data Exchange (ETDEWEB)

    Seng, Shanshan, E-mail: seshsh108@126.com [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Yuan Mingyuan Western Road 2#, Beijing 100193 (China); Wu, Jian [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Yuan Mingyuan Western Road 2#, Beijing 100193 (China); Sui, Juanjuan [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Yuan Mingyuan Western Road 2#, Beijing 100193 (China); College of Biology, Fuyang Normal College, Qinghe Western Road 100#, Fuyang 236037, Anhui (China); Wu, Chenyu; Zhong, Xionghui; Liu, Chen; Liu, Chao; Gong, Benhe; Zhang, Fengqin; He, Junna [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Yuan Mingyuan Western Road 2#, Beijing 100193 (China); Yi, Mingfang, E-mail: ymfang@cau.edu.cn [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Yuan Mingyuan Western Road 2#, Beijing 100193 (China)

    2016-05-20

    Starch is the main storage compound in underground organs like corms. ADP-glucose pyrophosphorylase (AGPase) plays a key role in regulating starch biosynthesis in storage organs and is likely one of the most important determinant of sink strength. Here, we identify an AGPase gene (GhAGPS1) from gladiolus. The highest transcriptional levels of GhAGPS1 were observed in cormels and corms. Transformation of GhAGPS1 into Arabidopsis rescued the phenotype of aps1 mutant. Silencing GhAGPS1 in gladiolus corms by virus-induced gene silencing (VIGS) decreased the transcriptional levels of two genes and starch content. Transmission electron microscopy analyses of leaf and corm sections confirmed that starch biosynthesis was inhibited. Corm weight and cormel number reduced significantly in the silenced plants. Taken together, these results indicate that inhibiting the expression of AGPase gene could impair starch synthesis, which results in the lowered corm quality and cormel yield in gladiolus. -- Highlights: •Cormel quantity was reduced significantly in silenced Gladiolus plants. •Corm quality was declined significantly in silenced Gladiolus plants. •Starch synthesis was inhibited in silenced Gladiolus plants.

  11. Nitric oxide synthase and oxidative-nitrosative stress play a key role in placental infection by Trypanosoma cruzi.

    Science.gov (United States)

    Triquell, María Fernanda; Díaz-Luján, Cintia; Romanini, María Cristina; Ramirez, Juan Carlos; Paglini-Oliva, Patricia; Schijman, Alejandro Gabriel; Fretes, Ricardo Emilio

    2018-03-25

    The innate immune response of the placenta may participate in the congenital transmission of Chagas disease through releasing reactive oxygen and nitrogen intermediates. Placental explants were cultured with 1 × 10 6 and 1 × 10 5 trypomastigotes of Tulahuen and Lucky strains and controls without parasites, and with the addition of nitric oxide synthase inhibitor Nω-Nitro-l-arginine methyl ester (l-NAME) and N-acetyl cysteine (NAC) as the reactive oxygen species (ROS) scavenger. Detachment of the syncytiotrophoblast (STB) was examined by histological analysis, and the nitric oxide synthase, endothelial (eNOS), and nitrotyrosine expressions were analyzed by immunohistochemistry, as well as the human chorionic gonadotrophin (hCG) levels in the culture supernatant through ELISA assays. Parasite load with qPCR using Taqman primers was quantified. The higher number of T. cruzi (10 6 ) increased placental infection, eNOS expression, nitrosative stress, and STB detachment, with the placental barrier being injured by oxidative stress. The higher number of parasites caused deleterious consequences to the placental barrier, and the inhibitors (l-NAME and NAC) prevented the damage caused by trypomastigotes in placental villi but not that of the infection. Moreover, trophoblast eNOS played a key role in placental infection with the highest inoculum of Lucky, demonstrating the importance of the enzyme and nitrosative-oxidative stress in Chagas congenital transmission. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. The role of infections in the pathogenesis and course of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Pawate Siddharama

    2010-01-01

    Full Text Available Interplay between susceptibility genes and environmental factors is considered important player in the genesis of multiple sclerosis (MS. Among environmental factors, a role for an infectious pathogen has long been considered central to the disease process. This opinion has support both from epidemiological data and the findings of immunological abnormalities in spinal fluid that reflect an immune response to an as yet undetermined antigen, possibly a pathogen, in the cerebrospinal fluid. Our review will outline the current understanding of the role of infection in the causation and progression of MS. We will review the data that point to an infectious cause of MS and consider the specific agents Chlamydophila (Chlamydia pneumoniae, Human Herpes Virus 6, and Epstein-Barr Virus, that are implicated in either the development or progression of MS.

  13. The Drosophila BTB domain protein Jim Lovell has roles in multiple larval and adult behaviors.

    Directory of Open Access Journals (Sweden)

    Sonia M Bjorum

    Full Text Available Innate behaviors have their origins in the specification of neural fates during development. Within Drosophila, BTB (Bric-a-brac,Tramtrack, Broad domain proteins such as Fruitless are known to play key roles in the neural differentiation underlying such responses. We previously identified a gene, which we have termed jim lovell (lov, encoding a BTB protein with a role in gravity responses. To understand more fully the behavioral roles of this gene we have investigated its function through several approaches. Transcript and protein expression patterns have been examined and behavioral phenotypes of new lov mutations have been characterized. Lov is a nuclear protein, suggesting a role as a transcriptional regulator, as for other BTB proteins. In late embryogenesis, Lov is expressed in many CNS and PNS neurons. An examination of the PNS expression indicates that lov functions in the late specification of several classes of sensory neurons. In particular, only two of the five abdominal lateral chordotonal neurons express Lov, predicting functional variation within this highly similar group. Surprisingly, Lov is also expressed very early in embryogenesis in ways that suggests roles in morphogenetic movements, amnioserosa function and head neurogenesis. The phenotypes of two new lov mutations that delete adjacent non-coding DNA regions are strikingly different suggesting removal of different regulatory elements. In lov(47 , Lov expression is lost in many embryonic neurons including the two lateral chordotonal neurons. lov(47 mutant larvae show feeding and locomotor defects including spontaneous backward movement. Adult lov(47 males perform aberrant courtship behavior distinguished by courtship displays that are not directed at the female. lov(47 adults also show more defective negative gravitaxis than the previously isolated lov(91Y mutant. In contrast, lov(66 produces largely normal behavior but severe female sterility associated with ectopic lov

  14. Cerebellar metastases – may surgery play a role in the presence of multiple lesions?

    Directory of Open Access Journals (Sweden)

    Dabija M.

    2017-06-01

    Full Text Available Brain metastases are the most common form of malignancy presence in the CNS having a more frequent appearance than primary brain tumors. Although secondary cerebellar tumors represent only 15% of all intracranial metastases, they are quite frequent among primary oncological patients and pose a challenge for all of the medical caretakers starting with the neurosurgeon. Among those, a small percent of patients have multiple cerebellar lesions and the therapeutic challenge turns into a medical controversy, especially when it comes to surgical treatment taking into consideration that the life expectancy is lower than one year. A key asset which we have on our side is the anatomical vicinity these lesions occur, this leading us to take into consideration eliminating as many lesions in one single operative time as possible without changing the position of the head during surgery. Based on a retrospective study which concluded that patients with resection of all lesions tend to have a longer life expectancy, and on modern concepts of risks and benefits of oncological surgery and surgery in general, we followed up on three patients presenting posterior and even multiple posterior fossa metastases, taking into consideration individual comorbidities, tumor aspects and the possibility/opportunity of surgical treatment. It turned out that surgery is a safe and effective treatment option and should not be considered harmful or aggressive especially because all of the patients which were under study had a favorable post-operative prognostic and an improved quality of life. We emphasize furthermore the importance of complete lesion resection in as few interventions as possible followed up by radiotherapy/chemotherapy as a key in prolonging these patients life expectancy taking into consideration that the outcome is directly related to the number of lesions rather to the location or volume of them.

  15. The Arabidopsis thaliana homolog of the helicase RTEL1 plays multiple roles in preserving genome stability.

    Science.gov (United States)

    Recker, Julia; Knoll, Alexander; Puchta, Holger

    2014-12-01

    In humans, mutations in the DNA helicase Regulator of Telomere Elongation Helicase1 (RTEL1) lead to Hoyeraal-Hreidarsson syndrome, a severe, multisystem disorder. Here, we demonstrate that the RTEL1 homolog in Arabidopsis thaliana plays multiple roles in preserving genome stability. RTEL1 suppresses homologous recombination in a pathway parallel to that of the DNA translocase FANCM. Cytological analyses of root meristems indicate that RTEL1 is involved in processing DNA replication intermediates independently from FANCM and the nuclease MUS81. Moreover, RTEL1 is involved in interstrand and intrastrand DNA cross-link repair independently from FANCM and (in intrastrand cross-link repair) parallel to MUS81. RTEL1 contributes to telomere homeostasis; the concurrent loss of RTEL1 and the telomerase TERT leads to rapid, severe telomere shortening, which occurs much more rapidly than it does in the single-mutant line tert, resulting in developmental arrest after four generations. The double mutant rtel1-1 recq4A-4 exhibits massive growth defects, indicating that this RecQ family helicase, which is also involved in the suppression of homologous recombination and the repair of DNA lesions, can partially replace RTEL1 in the processing of DNA intermediates. The requirement for RTEL1 in multiple pathways to preserve genome stability in plants can be explained by its putative role in the destabilization of DNA loop structures, such as D-loops and T-loops. © 2014 American Society of Plant Biologists. All rights reserved.

  16. Role of whole-body 64-slice multidetector computed tomography in treatment planning for multiple myeloma.

    Science.gov (United States)

    Razek, Ahmed Abdel Khalek Abdel; Ezzat, Amany; Azmy, Emad; Tharwat, Nehal

    2013-08-01

    The authors evaluated the role of whole-body 64-slice multidetector computed tomography (WB-MDCT) in treatment planning for multiple myeloma. This was a prospective study of 28 consecutive patients with multiple myeloma (19 men, nine women; age range, 51-73 years; mean age, 60 years) who underwent WB-MDCT and conventional radiography (CR) of the skeleton. The images were interpreted for the presence of bony lesions, medullary lesions, fractures and extraosseous lesions. We evaluated any changes in treatment planning as a result of WB-MDCT findings. WB-MDCT was superior to CR for detecting bony lesions (p=0.001), especially of the spine (p=0.001) and thoracic cage (p=0.006). WB-MDCT upstaged 14 patients, with a significant difference in staging (p=0.002) between WB-MDCT and CR. Medullary involvement either focal (n=6) or diffuse (n=3) had a positive correlation with the overall score (r=0.790) and stage (r=0.618) of disease. Spine fractures were better detected at WB-MDCT (n=4) than at CR (n=2). Extraosseous soft tissue lesions (n=7) were detected only at WB-MDCT. Findings detected at the WB-MDCT led to changes in the patient's treatment plan in 39% of cases. Upstaging of seven patients (25%) altered the medical treatment plan, and four of 28 (14%) patients required additional radiotherapy (7%) and vertebroplasty (7%). We conclude that WB-MDCT has an impact on treatment planning and prognosis in patients with multiple myeloma, as it has high rate of detecting cortical and medullary bone lesions, spinal fracture and extraosseous lesions. This information may alter treatment planning in multiple myeloma due to disease upstaging and detection of spine fracture and extraosseous spinal lesions.

  17. Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling.

    Science.gov (United States)

    Singhal, Sharad S; Singh, Sharda P; Singhal, Preeti; Horne, David; Singhal, Jyotsana; Awasthi, Sanjay

    2015-12-15

    4-Hydroxy-2-trans-nonenal (4HNE), one of the major end products of lipid peroxidation (LPO), has been shown to induce apoptosis in a variety of cell lines. It appears to modulate signaling processes in more than one way because it has been suggested to have a role in signaling for differentiation and proliferation. It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione-peroxidase activity and that these enzymes can also detoxify LPO end-products such as 4HNE. Available evidence from earlier studies together with results of recent studies in our laboratories strongly suggests that LPO products, particularly hydroperoxides and 4HNE, are involved in the mechanisms of stress-mediated signaling and that it can be modulated by the alpha-class GSTs through the regulation of the intracellular concentrations of 4HNE. We demonstrate that 4HNE induced apoptosis in various cell lines is accompanied with c-Jun-N-terminal kinase (JNK) and caspase-3 activation. Cells exposed to mild, transient heat or oxidative stress acquire the capacity to exclude intracellular 4HNE at a faster rate by inducing GSTA4-4 which conjugates 4HNE to glutathione (GSH), and RLIP76 which mediates the ATP-dependent transport of the GSH-conjugate of 4HNE (GS-HNE). The balance between formation and exclusion promotes different cellular processes - higher concentrations of 4HNE promote apoptosis; whereas, lower concentrations promote proliferation. In this article, we provide a brief summary of the cellular effects of 4HNE, followed by a review of its GST-catalyzed detoxification, with an emphasis on the structural attributes that play an important role in the interactions with alpha-class GSTA4-4. Taken together, 4HNE is a key signaling molecule and that GSTs being determinants of its intracellular concentrations, can regulate stress-mediated signaling, are reviewed in this article. Copyright © 2015 Elsevier Inc. All rights

  18. Double positive CD4+CD8+ T cells: key suppressive role in the production of autoantibodies in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Yongkang Wu

    2014-01-01

    Full Text Available Background & objectives: The presence of CD4+CD8+ (double positive T cells (DPT in the target organs of several autoimmune diseases has been reported. The aim of this study was to investigate the pathogenic role of DPT in systemic lupus erythematosus (SLE. Methods: A total of 175 SLE cases and 125 matched healthy controls were investigated for CD3+, CD4+, CD8+ lymphocytes and DPT by flow cytometry. Serum samples from SLE patients and controls were tested for antinuclear antibody (ANA, anti-double strain deoxyribonucleic acid (anti-dsDNA, anti-U1 ribonucleoprotein (anti-U1 RNP, anti-sjogren syndrome A (anti-SSA, anti-ribosomal P protein (anti-rib-P, anti-Smith (anti-Sm, anti-Sjogren syndrome B (anti-SSB, complement 3 (C3 and complement 4 (C4. Results: The DPT median and 5-95 per cent range of SLE cases and healthy controls were 0.50 [0.10-2.60] and 0.80 [0.20-2.74] respectively (P<0.001. SLE patients were divided into a ≥1:1000 subgroup and a <1:1000 subgroup according to the ANA titre. The DPT of the former subgroup was significantly lower than that of the latter (P=0.032. The DPT medians of positive subgroups with anti-dsDNA (P<0.001, anti-U1RNP (P=0.018, anti-SSA (P=0.021 or anti-rib-P (P=0.039 were also significantly lower than the negative subgroups. Likewise, DPT was significantly lower in SLE subgroups with low concentration of C3 or C4 than those with high concentration (P<0.006. Interpretation & conclusions: Our findings show that the DPT cells may play a key suppressive role in the production of autoantibodies in SLE. Direct evidence that DPT regulates the pathogenesis of SLE needs to be investigated in future work.

  19. Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling

    International Nuclear Information System (INIS)

    Singhal, Sharad S.; Singh, Sharda P.; Singhal, Preeti; Horne, David; Singhal, Jyotsana; Awasthi, Sanjay

    2015-01-01

    4-Hydroxy-2-trans-nonenal (4HNE), one of the major end products of lipid peroxidation (LPO), has been shown to induce apoptosis in a variety of cell lines. It appears to modulate signaling processes in more than one way because it has been suggested to have a role in signaling for differentiation and proliferation. It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione-peroxidase activity and that these enzymes can also detoxify LPO end-products such as 4HNE. Available evidence from earlier studies together with results of recent studies in our laboratories strongly suggests that LPO products, particularly hydroperoxides and 4HNE, are involved in the mechanisms of stress-mediated signaling and that it can be modulated by the alpha-class GSTs through the regulation of the intracellular concentrations of 4HNE. We demonstrate that 4HNE induced apoptosis in various cell lines is accompanied with c-Jun-N-terminal kinase (JNK) and caspase-3 activation. Cells exposed to mild, transient heat or oxidative stress acquire the capacity to exclude intracellular 4HNE at a faster rate by inducing GSTA4-4 which conjugates 4HNE to glutathione (GSH), and RLIP76 which mediates the ATP-dependent transport of the GSH-conjugate of 4HNE (GS-HNE). The balance between formation and exclusion promotes different cellular processes — higher concentrations of 4HNE promote apoptosis; whereas, lower concentrations promote proliferation. In this article, we provide a brief summary of the cellular effects of 4HNE, followed by a review of its GST-catalyzed detoxification, with an emphasis on the structural attributes that play an important role in the interactions with alpha-class GSTA4-4. Taken together, 4HNE is a key signaling molecule and that GSTs being determinants of its intracellular concentrations, can regulate stress-mediated signaling, are reviewed in this article. - Highlights: • GSTs are the major

  20. The agricultural heritage of Lampedusa (Pelagie Archipelago, South Italy and its key role for cultivar and wildlife conservation

    Directory of Open Access Journals (Sweden)

    Tommaso La Mantia

    2011-04-01

    Full Text Available As occurred on many other small Mediterranean islands, agricultural activity at Lampedusa (Strait of Sicily underwent a very strong decline in terms of surface area during the second half of the last century. In particular, cereal crops have ceased and horticulture is disappearing, while vineyards still occupy a reduced area but are quickly vanishing and currently survive thanks to a small number of old farmers. Here are presented the results of a research carried out by interviewing seven farmers in order to study not only the techniques and the germplasm used in local viticulture, but also the final use of grapes and an evaluation on the connection between traditional farming and agro-ecosystems plant species-richness. Vines were grown for wine, to produce fresh and sun-dried grapes, or to preserve them in alcohol. Several names of the local varieties suggest that they might have been introduced in Lampedusa from the neighbouring territories: being fishermen and farmers at the same time, local people had trade relationships with other Mediterranean areas such as Tunisia, Malta and Southern Italy. Furthermore, local farming plays a key role in plant conservation. In fact, the disappearance of agricultural systems is leading to the extinction of 43 plant species, some of them considered rare not only on the local level, but also on the regional and national one. Because of the small size of farmland and its fragmentation, local agriculture cannot be supported by the European Community. Therefore, in order to safeguard local viticulture, special systems of assistance and new managing policies - focused on rural development plans and showing which concrete actions are necessary and feasible to protect the agroecosystems - are needed.

  1. Role of dimethyl fumarate in oxidative stress of multiple sclerosis: A review.

    Science.gov (United States)

    Suneetha, A; Raja Rajeswari, K

    2016-04-15

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS affecting both white and grey matter. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis. Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for MS treatment. Oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapy with dimethyl fumarate. The clinical utility of DMF in multiple sclerosis is being explored through phase III trials with BG-12, which is an oral therapeutic agent. Currently a wide research is going on to find out the exact mechanism of DMF, till date it is not clear. Based on strong signals of nephrotoxicity in non-humans and the theoretical risk of renal cell cancer from intracellular accumulation of fumarate, post-marketing study of a large population of patients will be necessary to fully assess the long-term safety of dimethyl fumarate. The current treatment goals are to shorten the duration and severity of relapses, prolong the time between relapses, and delay progression of disability. In this regard, dimethyl fumarate offers a promising alternative to orally administered fingolimod (GILENYA) or teriflunomide (AUBAGIO), which are currently marketed in the United States under FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) programs because of serious safety concerns. More clinical experience with all three agents will be necessary to differentiate the tolerability of long-term therapy for patients diagnosed with multiple sclerosis. This write-up provides the detailed information of dimethyl fumarate in treating the neuro disease, multiple sclerosis and its mechanism involved via

  2. The Role of the Gut Microbiome in Multiple Sclerosis Risk and Progression: Towards Characterization of the "MS Microbiome".

    Science.gov (United States)

    Pröbstel, Anne-Katrin; Baranzini, Sergio E

    2018-01-01

    Multiple sclerosis (MS) is the prototypic complex disease, in which both genes and the environment contribute to its pathogenesis. To date, > 200 independent loci across the genome have been associated with MS risk. However, these only explain a fraction of the total phenotypic variance, suggesting the possible presence of additional genetic factors, and, most likely, also environmental factors. New DNA sequencing technologies have enabled the sequencing of all kinds of microorganisms, including those living in and around humans (i.e., microbiomes). The study of bacterial populations inhabiting the gut is of particular interest in autoimmune diseases owing to their key role in shaping immune responses. In this review, we address the potential crosstalk between B cells and the gut microbiota, a relevant scenario in light of recently approved anti-B-cell therapies for MS. In addition, we review recent efforts to characterize the gut microbiome in patients with MS and discuss potential challenges and future opportunities. Finally, we describe the international MS microbiome study, a multicenter effort to study a large population of patients with MS and their healthy household partners to define the core MS microbiome, how it is shaped by disease-modifying therapies, and to explore potential therapeutic interventions.

  3. Managing treatment fatigue in patients with multiple sclerosis on long-term therapy: the role of multiple sclerosis nurses

    Directory of Open Access Journals (Sweden)

    Crawford A

    2014-08-01

    Full Text Available Ann Crawford, Sally Jewell,* Holly Mara, Laura McCatty, Regina Pelfrey The Lash Group; Frisco, TX, USA *Sally Jewell is now retired Abstract: This article discusses the many ways that nurses can address the factors that lead to treatment fatigue in patients with multiple sclerosis (MS on long-term disease-modifying therapy, ultimately helping to preserve the patient’s health and quality of life. Patients with MS on long-term therapy may suffer from treatment fatigue and poor adherence due to a variety of different factors, including difficulties with injections, anxiety/depression, financial problems, and inaccurate beliefs about the MS disease process. Because MS nurses have regular interactions with patients, they are ideally situated to help patients cope with these and other factors that may limit adherence. Keywords: multiple sclerosis, disease-modifying therapy, injection, nurse

  4. The role of KIR2DS1 in multiple sclerosis--KIR in Portuguese MS patients.

    Science.gov (United States)

    Bettencourt, Andreia; Silva, Ana Martins; Carvalho, Cláudia; Leal, Bárbara; Santos, Ernestina; Costa, Paulo P; Silva, Berta M

    2014-04-15

    Killer Immunoglobulin-like Receptor (KIR) genes may influence both resistance and susceptibility to different autoimmune diseases, but their role in the pathogenesis of Multiple Sclerosis (MS) is still unclear. We investigated the influence of KIR genes on MS susceptibility in 447 MS Portuguese patients, and also whether genetic interactions between specific KIR genes and their HLA class I ligands could contribute to the pathogenesis of MS. We observed a negative association between the activating KIR2DS1 gene and MS (adjusted OR=0.450, p=0.030) independently from the presence of HLA-DRB1*15 allele. The activating KIR2DS1 receptor seems to confer protection against MS most probably through modulation of autoreactive T cells by Natural Killer cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. The key role of U{sub 28} in the aqueous self-assembly of uranyl peroxide nanocages

    Energy Technology Data Exchange (ETDEWEB)

    Falaise, Clement; Nyman, May [Energy Frontier Research Center, Materials Science of Actinides, Department of Chemistry, Oregon State University, Corvallis, OR (United States)

    2016-10-04

    For 11 years now, the structural diversity and aesthetic beauty of uranyl-peroxide capsules have fascinated researchers from the diverse fields of mineralogy, polyoxometalate chemistry, and nuclear fuel technologies. There is still much to be learned about the mechanisms of the self-assembly process, and the role of solution parameters including pH, alkali template, temperature, time, and others. Here we have exploited the high solubility of the UO{sub 2}{sup 2+}/H{sub 2}O{sub 2}/LiOH aqueous system to address the effect of the hydroxide concentration. Important techniques of this study are single-crystal X-ray diffraction, small-angle X-ray scattering, and Raman spectroscopy. Three key phases dominate the solution speciation as a function of time and the LiOH/UO{sub 2}{sup 2+} ratio: the uranyl-triperoxide monomer [UO{sub 2}(O{sub 2}){sub 3}]{sup 4-}and the two capsules [(UO{sub 2})(O{sub 2})(OH)]{sub 24}{sup 24-}(U{sub 24}) and [(UO{sub 2})(O{sub 2}){sub 1.5}]{sub 28}{sup 28-}(U{sub 28}). When the LiOH/U ratio is around three, U{sub 28} forms rapidly and this cluster can be isolated in high yield and purity. This result was most surprising and challenges the hypothesis that alkali templating is the most important determinant in the cluster geometry. Moreover, analogous experiments with KOH, NH{sub 4}OH, and TEAOH (TEA=tetraethylammonium) also rapidly yield U{sub 28}, which suggests that U{sub 28} is the kinetically favored species. Complete mapping of the pH-time phase space reveals only a narrow window of the U{sub 28} dominance, which is why it was previously overlooked as an important kinetic species in this chemical system, as well as others with different counterions. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  6. Key role of the endothelial TGF-β/ALK1/endoglin signaling pathway in humans and rodents pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Benoît Gore

    Full Text Available Mutations affecting transforming growth factor-beta (TGF-β superfamily receptors, activin receptor-like kinase (ALK-1, and endoglin (ENG occur in patients with pulmonary arterial hypertension (PAH. To determine whether the TGF-β/ALK1/ENG pathway was involved in PAH, we investigated pulmonary TGF-β, ALK1, ALK5, and ENG expressions in human lung tissue and cultured pulmonary-artery smooth-muscle-cells (PA-SMCs and pulmonary endothelial cells (PECs from 14 patients with idiopathic PAH (iPAH and 15 controls. Seeing that ENG was highly expressed in PEC, we assessed the effects of TGF-β on Smad1/5/8 and Smad2/3 activation and on growth factor production by the cells. Finally, we studied the consequence of ENG deficiency on the chronic hypoxic-PH development by measuring right ventricular (RV systolic pressure (RVSP, RV hypertrophy, and pulmonary arteriolar remodeling in ENG-deficient (Eng+/- and wild-type (Eng+/+ mice. We also evaluated the pulmonary blood vessel density, macrophage infiltration, and cytokine expression in the lungs of the animals. Compared to controls, iPAH patients had higher serum and pulmonary TGF-β levels and increased ALK1 and ENG expressions in lung tissue, predominantly in PECs. Incubation of the cells with TGF-β led to Smad1/5/8 phosphorylation and to a production of FGF2, PDGFb and endothelin-inducing PA-SMC growth. Endoglin deficiency protected mice from hypoxic PH. As compared to wild-type, Eng+/- mice had a lower pulmonary vessel density, and no change in macrophage infiltration after exposure to chronic hypoxia despite the higher pulmonary expressions of interleukin-6 and monocyte chemoattractant protein-1. The TGF-β/ALK1/ENG signaling pathway plays a key role in iPAH and experimental hypoxic PH via a direct effect on PECs leading to production of growth factors and inflammatory cytokines involved in the pathogenesis of PAH.

  7. Calcineurin plays key roles in the dimorphic transition and virulence of the human pathogenic zygomycete Mucor circinelloides.

    Science.gov (United States)

    Lee, Soo Chan; Li, Alicia; Calo, Silvia; Heitman, Joseph

    2013-01-01

    Many pathogenic fungi are dimorphic and switch between yeast and filamentous states. This switch alters host-microbe interactions and is critical for pathogenicity. However, in zygomycetes, whether dimorphism contributes to virulence is a central unanswered question. The pathogenic zygomycete Mucor circinelloides exhibits hyphal growth in aerobic conditions but switches to multi-budded yeast growth under anaerobic/high CO₂ conditions. We found that in the presence of the calcineurin inhibitor FK506, Mucor exhibits exclusively multi-budded yeast growth. We also found that M. circinelloides encodes three calcineurin catalytic A subunits (CnaA, CnaB, and CnaC) and one calcineurin regulatory B subunit (CnbR). Mutations in the latch region of CnbR and in the FKBP12-FK506 binding domain of CnaA result in hyphal growth of Mucor in the presence of FK506. Disruption of the cnbR gene encoding the sole calcineurin B subunit necessary for calcineurin activity yielded mutants locked in permanent yeast phase growth. These findings reveal that the calcineurin pathway plays key roles in the dimorphic transition from yeast to hyphae. The cnbR yeast-locked mutants are less virulent than the wild-type strain in a heterologous host system, providing evidence that hyphae or the yeast-hyphal transition are linked to virulence. Protein kinase A activity (PKA) is elevated during yeast growth under anaerobic conditions, in the presence of FK506, or in the yeast-locked cnbR mutants, suggesting a novel connection between PKA and calcineurin. cnaA mutants lacking the CnaA catalytic subunit are hypersensitive to calcineurin inhibitors, display a hyphal polarity defect, and produce a mixture of yeast and hyphae in aerobic culture. The cnaA mutants also produce spores that are larger than wild-type, and spore size is correlated with virulence potential. Our results demonstrate that the calcineurin pathway orchestrates the yeast-hyphal and spore size dimorphic transitions that contribute to

  8. Upregulation of NOXA by 10-Hydroxycamptothecin plays a key role in inducing fibroblasts apoptosis and reducing epidural fibrosis

    Directory of Open Access Journals (Sweden)

    Jihang Dai

    2017-01-01

    the first to demonstrate that upregulation of NOXA by HCPT plays a key role in inducing fibroblast apoptosis and in reducing epidural fibrosis. These findings might provide a potential therapeutic target for preventing epidural fibrosis following laminectomy.

  9. Regulation of Neph3 gene in podocytes - key roles of transcription factors NF-kappaB and Sp1

    LENUS (Irish Health Repository)

    Ristola, Mervi

    2009-08-24

    Abstract Background Neph3 (filtrin) is expressed in the glomerular podocytes where it localizes at the specialized cell adhesion structures of the foot processes called slit diaphragms which form the outermost layer of the glomerular filtration barrier. Neph3 protein shows homology and structural similarity to Neph1, Neph2 and nephrin, which all are crucial for maintaining the normal glomerular ultrafiltration function. The exact function of Neph3 in the kidney is not known but we have previously shown that the level of Neph3 mRNA is decreased in proteinuric diseases. This suggests that Neph3 may play a role in the pathogenesis of kidney damage, and emphasizes the need to analyze the regulatory mechanisms of Neph3 gene. In this study we investigated the transcriptional regulation of Neph3 gene by identifying transcription factors that control Neph3 expression. Results We cloned and characterized approximately 5 kb fragment upstream of the Neph3 gene. Neph3 proximal promoter near the transcription start site was found to be devoid of TATA and CAAT boxes, but to contain a highly GC-rich area. Using promoter reporter gene constructs, we localized the main activating regulatory region of Neph3 gene in its proximal promoter region from -105 to -57. Within this region, putative transcription factor binding sites for NF-κB and Sp1 were found by computational analysis. Mutational screening indicated that NF-κB and Sp1 response elements are essential for the basal transcriptional activity of the Neph3 promoter. Co-transfection studies further showed that NF-κB and Sp1 regulate Neph3 promoter activity. In addition, overexpression of NF-κB increased endogenous Neph3 gene expression. Chromatin immunoprecipitation assay using cultured human podocytes demonstrated that both NF-κB and Sp1 interact with the Neph3 promoter. Conclusion Our results show that NF-κB and Sp1 are key regulators of Neph3 expression at the basal level in podocytes, therefore providing new insight

  10. Concomitant targeting of multiple key transcription factors effectively disrupts cancer stem cells enriched in side population of human pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Xiyan Wang

    Full Text Available A major challenge in the treatment of pancreatic ductal adenocarcinoma is the failure of chemotherapy, which is likely due to the presence of the cancer stem cells (CSCs.To identify side population (SP cells and characterize s-like properties in human pancreatic cancer cell lines (h-PCCLs and to exploit the efficacy of concomitant targeting of multiple key transcription factors governing the stemness of pancreatic CSCs in suppressing CSC-like phenotypes.Flow cytometry and Hoechst 33342 DNA-binding dye efflux assay were used to sort SP and non-SP (NSP cells from three h-PCCLs: PANC-1, SW1990, and BxPc-3. The self-renewal ability, invasiveness, migration and drug resistance of SP cells were evaluated. Expression of CSC marker genes was analyzed. Tumorigenicity was assessed using a xenograft model in nude mice. Effects of a complex decoy oligonucleotide (cdODN-SCO designed to simultaneously targeting Sox2, Oct4 and c-Myc were assessed.CSCs were enriched in the side proportion (SP cells contained in the h-PCCLs and they possessed aggressive growth, invasion, migration and drug-resistance properties, compared with NSP cells. SP cells overexpressed stem cell markers CD133 and ALDH1, pluripotency maintaining factors Nanog, Sox2 and Oct4, oncogenic transcription factor c-Myc, signaling molecule Notch1, and drug resistant gene ABCG2. Moreover, SP cells consistently demonstrated significantly greater tumorigenicity than NSP cells in xenograft model of nude mice. CdODN-SOC efficiently suppressed all CSC properties and phenotypes, and minimized the tumorigenic capability of the SP cells and the resistance to chemotherapy. By comparison, the negative control failed to do so.The findings indicate that targeting the key genes conferring the stemness of CSCs can efficiently eliminate CSC-like phenotypes, and thus may be considered a new approach for cancer therapy. Specifically, the present study establishes the combination of Sox2/Oct4/c-Myc targeting as a

  11. Association studies suggest a key role for endothelin-1 in the pathogenesis of preeclampsia and the accompanying renin-angiotensin-aldosterone system suppression.

    Science.gov (United States)

    Verdonk, Koen; Saleh, Langeza; Lankhorst, Stephanie; Smilde, J E Ilse; van Ingen, Manon M; Garrelds, Ingrid M; Friesema, Edith C H; Russcher, Henk; van den Meiracker, Anton H; Visser, Willy; Danser, A H Jan

    2015-06-01

    Women with preeclampsia display low renin-angiotensin-aldosterone system activity and a high antiangiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase (sFlt)-1 and reduced placental growth factor levels. To investigate whether renin-angiotensin-aldosterone system suppression in preeclampsia is because of this disturbed angiogenic balance, we measured mean arterial pressure, creatinine, endothelin-1 (ET-1), and renin-angiotensin-aldosterone system components in pregnant women with a high (≥85; n=38) or low (<85; n=65) soluble Fms-like tyrosine kinase-1/placental growth factor ratio. Plasma ET-1 levels were increased in women with a high ratio, whereas their plasma renin activity and plasma concentrations of renin, angiotensinogen, and aldosterone were decreased. Plasma renin activity-aldosterone relationships were identical in both the groups. Multiple regression analysis revealed that plasma renin concentration correlated independently with mean arterial pressure and plasma ET-1. Plasma ET-1 correlated positively with soluble Fms-like tyrosine kinase-1 and negatively with plasma renin concentration, and urinary protein correlated with plasma ET-1 and mean arterial pressure. Despite the lower plasma levels of renin and angiotensinogen in the high-ratio group, their urinary levels of these components were elevated. Correction for albumin revealed that this was because of increased glomerular filtration. Subcutaneous arteries obtained from patients with preeclampsia displayed an enhanced, AT2 receptor-mediated response to angiotensin II. In conclusion, a high antiangiogenic state associates with ET-1 activation, which together with the increased mean arterial pressure may underlie the parallel reductions in renin and aldosterone in preeclampsia. Because ET-1 also was a major determinant of urinary protein, our data reveal a key role for ET-1 in the pathogenesis of preeclampsia. Finally, the enhanced angiotensin responsiveness

  12. Multiple functions and essential roles of nuclear receptor coactivators of bHLH-PAS family.

    Science.gov (United States)

    Pecenova, L; Farkas, Robert

    2016-07-01

    Classical non-peptide hormones, such as steroids, retinoids, thyroid hormones, vitamin D3 and their derivatives including prostaglandins, benzoates, oxysterols, and bile acids, are collectively designated as small lipophilic ligands, acting via binding to the nuclear receptors (NRs). The NRs form a large superfamily of transcription factors that participate virtually in every key biological process. They control various aspects of animal development, fertility, gametogenesis, and numerous metabolic pathways, and can be misregulated in many types of cancers. Their enormous functional plasticity, as transcription factors, relates in part to NR-mediated interactions with plethora of coregulatory proteins upon ligand binding to their ligand binding domains (LBD), or following covalent modification. Here, we review some general views of a specific group of NR coregulators, so-called nuclear receptor coactivators (NRCs) or steroid receptor coactivators (SRCs) and highlight some of their unique functions/roles, which are less extensively mentioned and discussed in other reviews. We also try to pinpoint few neglected moments in the cooperative action of SRCs, which may also indicate their variable roles in the hormone-independent signaling pathways.

  13. 8C.03: A KEY ROLE FOR ENDOTHELIN-1 IN THE PATHOGENESIS OF PREECLAMPSIA AND THE ASSOCIATED SUPPRESSION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM.

    Science.gov (United States)

    Verdonk, K; Saleh, L; Smilde, J E; van Ingen, M M; Garrelds, I M; Friesema, E C; Russcher, H; Steegers, E A P; van den Meiracker, A H; Visser, W; Danser, A H J

    2015-06-01

    aldosterone argues against studies reporting that a high anti-angiogenic state, via a reduction of adrenal capillary density, selectively suppresses aldosterone. Since ET-1 also was a major determinant of PCR, our data reveal a key role for ET-1 in the pathogenesis of PE.

  14. Exploring the role of microglia in mood disorders associated with experimental multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Antonietta eGentile

    2015-06-01

    Full Text Available Microglia is increasingly recognized to play a crucial role in the pathogenesis of psychiatric diseases. In particular, microglia may be the cellular link between inflammation and behavioural alterations: by releasing a number of soluble factors, among which pro-inflammatory cytokines, they can regulate synaptic activity, thereby leading to perturbation of behaviour.In multiple sclerosis (MS, the most common neuroinflammatory disorder affecting young adults, microglia activation and dysfunction may account for mood symptoms, like depression and anxiety, that are often diagnosed in patients even in the absence of motor disability. Behavioural studies in experimental autoimmune encephalomyelitis (EAE, the animal model of MS, have shown that emotional changes occur early in the disease and in correlation to inflammatory mediator and neurotransmitter level alterations. However, such studies lack a full and comprehensive analysis of the role played by microglia in EAE-behavioural syndrome. We review the experimental studies addressing behavioural symptoms in EAE, and propose the study of neuron-glia interaction as a powerful but still poorly explored tool to investigate the burden of microglia in mood alterations associated to MS.

  15. Physics and Its Multiple Roles in the International Atomic Energy Agency

    Science.gov (United States)

    Massey, Charles D.

    2017-01-01

    The IAEA is the world's centre for cooperation in the nuclear field. It was set up as the world's ``Atoms for Peace'' organization in 1957 within the United Nations family. The Agency works with its Member States and multiple partners worldwide to promote the safe, secure and peaceful use of nuclear technologies. Three main areas of work underpin the IAEA's mission: Safety and Security, Science and Technology, and Safeguards and Verification. To carry out its mission, the Agency is authorized to encourage and assist research on, and development and practical application of, atomic energy for peaceful uses throughout the world; foster the exchange of scientific and technical information on peaceful uses of atomic energy; and encourage the exchange of training of scientists and experts in the field of peaceful uses of atomic energy. Nowadays, nuclear physics and nuclear technology are applied in a great variety of social areas, such as power production, medical diagnosis and therapies, environmental protection, security control, material tests, food processing, waste treatments, agriculture and artifacts analysis. This presentation will cover the role and practical application of physics at the IAEA, and, in particular, focus on the role physics has, and will play, in nuclear security.

  16. "ROLE OF ALLOGENEIC TRANSPLANTATION IN MULTIPLE MYELOMA IN THE ERA OF NEW DRUGS"

    Directory of Open Access Journals (Sweden)

    Benedetto Bruno

    2010-06-01

                Allografting is a potentially curative treatment for a subset of multiple myeloma patients for its well documented graft-vs-myeloma effects. However, its role has been hotly debated. Even though molecular remissions have been reported up to 50% after high-dose myeloablative conditionings, their applications, given the high toxicity, have been for long limited to younger relapsed/refractory patients. These limitations have greatly been reduced through the introduction of non-myeloablative/reduced-intensity conditionings.             The introduction of new drugs, characterised by low risks of early mortality, indeed requires to define role and timing of an allograft to capture the subset of patients who may most benefit from graft-vs-myeloma effects.   Ultimately, new drugs should not be viewed as mutually exclusive with an allograft. They may be employed to achieve profound cytoreduction before and enhance graft-versus-myeloma effects as consolidation/maintenance therapy after an allograft. However, this combination should be explored only in well-designed clinical trials.

  17. RegA Plays a Key Role in Oxygen-Dependent Establishment of Persistence and in Isocitrate Lyase Activity, a Critical Determinant of In vivo Brucella suis Pathogenicity

    Directory of Open Access Journals (Sweden)

    Elias Abdou

    2017-05-01

    Full Text Available For aerobic human pathogens, adaptation to hypoxia is a critical factor for the establishment of persistent infections, as oxygen availability is low inside the host. The two-component system RegB/A of Brucella suis plays a central role in the control of respiratory systems adapted to oxygen deficiency, and in persistence in vivo. Using an original “in vitro model of persistence” consisting in gradual oxygen depletion, we compared transcriptomes and proteomes of wild-type and ΔregA strains to identify the RegA-regulon potentially involved in the set-up of persistence. Consecutive to oxygen consumption resulting in growth arrest, 12% of the genes in B. suis were potentially controlled directly or indirectly by RegA, among which numerous transcriptional regulators were up-regulated. In contrast, genes or proteins involved in envelope biogenesis and in cellular division were repressed, suggesting a possible role for RegA in the set-up of a non-proliferative persistence state. Importantly, the greatest number of the RegA-repressed genes and proteins, including aceA encoding the functional IsoCitrate Lyase (ICL, were involved in energy production. A potential consequence of this RegA impact may be the slowing-down of the central metabolism as B. suis progressively enters into persistence. Moreover, ICL is an essential determinant of pathogenesis and long-term interactions with the host, as demonstrated by the strict dependence of B. suis on ICL activity for multiplication and persistence during in vivo infection. RegA regulates gene or protein expression of all functional groups, which is why RegA is a key regulator of B. suis in adaptation to oxygen depletion. This function may contribute to the constraint of bacterial growth, typical of chronic infection. Oxygen-dependent activation of two-component systems that control persistence regulons, shared by several aerobic human pathogens, has not been studied in Brucella sp. before. This work

  18. The multiple roles of Bub1 in chromosome segregation during mitosis and meiosis

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Venkatachalam, Sundaresan

    2009-06-19

    Aneuploidy, any deviation from an exact multiple of the haploid number of chromosomes, is a common occurrence in cancer and represents the most frequent chromosomal disorder in newborns. Eukaryotes have evolved mechanisms to assure the fidelity of chromosome segregation during cell division that include a multiplicity of checks and controls. One of the main cell division control mechanisms is the spindle assembly checkpoint (SAC) that monitors the proper attachment of chromosomes to spindle fibers and prevents anaphase until all kinetochores are properly attached. The mammalian SAC is composed by at least 14 evolutionary-conserved proteins that work in a coordinated fashion to monitor the establishment of amphitelic attachment of all chromosomes before allowing cell division to occur. Among the SAC proteins, the budding uninhibited by benzimidazole protein 1 (Bub1), is a highly conserved protein of prominent importance for the proper functioning of the SAC. Studies have revealed many roles for Bub1 in both mitosis and meiosis, including the localization of other SAC proteins to the kinetochore, SAC signaling, metaphase congression and the protection of the sister chromatid cohesion. Recent data show striking sex specific differences in the response to alterations in Bub1 activity. Proper Bub1 functioning is particularly important during oogenesis in preventing the generation of aneuploid gametes that can have detrimental effects on the health status of the fetus and the newborn. These data suggest that Bub1 is a master regulator of SAC and chromosomal segregation in both mitosis and meiosis. Elucidating its many essential functions in regulating proper chromosome segregation can have important consequences for preventing tumorigenesis and developmental abnormalities.

  19. Loss of positional information when tracking multiple moving dots: the role of visual memory.

    Science.gov (United States)

    Narasimhan, Sathyasri; Tripathy, Srimant P; Barrett, Brendan T

    2009-01-01

    Pylyshyn, Z.W. and Storm, R.W. (1988) (Tracking multiple independent targets: Evidence for a parallel tracking mechanism. Spatial Vision, 3(3), 179-197) proposed that human observers could simultaneously track up to five dots when presented with an array of dots moving in a random manner. In contrast, Tripathy, S.P., and Barrett, B.T. (2004) (Severe loss of positional information when detecting deviations in multiple trajectories. Journal of Vision, 4(12):4, 1020-1043, http://journalofvision.org/4/14/4/, doi: 10.1167/4.12.4) showed that when a threshold paradigm was employed, observers' ability to track deviations in straight-line trajectories is severely compromised when attending to two or more dots. In this study we present a series of four experiments that investigates the role of attention and visual memory while tracking deviations in multiple trajectories using a threshold paradigm. Our stimuli consisted of several linear, non-parallel, left-to-right trajectories, each moving at the same speed. At the trajectory mid-point (reached simultaneously by all dots), one of the dots (target) deviated clockwise or counter-clockwise. The observers' task was to identify the direction of deviation. The target trajectory was cued in the second half of the trial either by disappearance of distractors at the monitor's mid-line (Experiment 1) or by means of a change in colour of the target (Experiment 2); in both cases deviation thresholds rose steeply when the number of distractor trajectories was increased from 0 (typical threshold approximately 2 degrees) to 3 (typical threshold>20 degrees). When all the trajectories were presented statically in a single frame (Experiment 3), thresholds for identifying the orientation change of the target trajectory remained relatively unchanged as the number of distractor trajectories was increased. When a temporal delay of a few hundred milliseconds was introduced between the first and second halves of trajectories (Experiment 4

  20. A genetic approach to elucidate the genotoxic pathway of monomethylarsonous acid suggests a key role for catalase

    Science.gov (United States)

    Although it is widely known that arsenic-contaminated drinking water causes many diseases, arsenic's exact mode of action (MOA) is not fully understood. Induction of oxidative stress has been proposed as an important key event in the toxic MOA of arsenic. Our studies are centered...

  1. A genetic approach to elucidate the genotoxic pathway of monomethylarsonousacid (MMAIII) suggests a key role for catalase

    Science.gov (United States)

    Arsenic-contaminated drinking water causes cancer, neuropathy, respiratory effects, diabetes, and cardiovascular disease. Its exact mode of action (MOA) is not fully understood. Oxidative stress has been proposed as a key event in the toxic MOA of arsenic. Our studies are centere...

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

    Science.gov (United States)

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

    2017-06-01

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

  3. Genetic factors and multiple sclerosis in the Moroccan population: a role for HLA class II.

    Science.gov (United States)

    Ouadghiri, S; El Alaoui Toussi, K; Brick, C; Ait Benhaddou, E H; Benseffaj, N; Benomar, A; El Yahyaoui, M; Essakalli, M

    2013-12-01

    Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system that mainly affects young adults. The association between susceptibility to MS and HLA class II genes, in particular the DRB1*15 allele, has been reported in diverse ethnic groups. The aim of our study was to investigate the distribution of HLA-DRB1* and -DQB1* alleles in Moroccan population and their implication in the susceptibility to the disease. Fifty-seven MS patients were compared to 172 healthy controls unrelated to one another and matched by age, sex and ethnic origin. HLA class II (DRB1* and DQB1*) typing was performed by PCR-SSP and/or Luminex (PCR-SSO). Allelic and haplotypic frequencies, P-values, odds ratio (OR) and 95% confidence interval (CI) were calculated using the software SPSS. A significant increase of DRB1*15 allele frequency (17.6% vs 8.4%, OR=2.67, 95% CI=1.36-5.23, P=0.004) and HLA-DRB1*15-DQB1*06 haplotype (8.8% vs 4.08%, OR=2.78, 95% CI=1.41-5.48, P=0.002) were observed in Moroccan MS patients. No association of the DR15 allele with sex or age at onset was appreciated. Concerning HLA-DQB1* alleles, no significant difference between patients and controls was found. Our results reveal a role for HLA-DRB1*15 allele molecules in the predisposition of Moroccan patients to MS. Although this study should be confirmed on a larger sample size, it analyzes for the first time the possible role of a genetic marker for susceptibility to MS in Moroccan population. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. Stress and serial adult metamorphosis: Multiple roles for the stress axis in socially regulated sex change

    Directory of Open Access Journals (Sweden)

    Tessa K Solomon-Lane

    2013-11-01

    Full Text Available Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis. Through actions of both corticotropin-releasing factor and glucocorticoids (GCs, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli, a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes.

  5. Stress and serial adult metamorphosis: multiple roles for the stress axis in socially regulated sex change.

    Science.gov (United States)

    Solomon-Lane, Tessa K; Crespi, Erica J; Grober, Matthew S

    2013-01-01

    Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis). Through actions of both corticotropin-releasing factor and glucocorticoids, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli), a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes.

  6. Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors

    Directory of Open Access Journals (Sweden)

    Eduardo Pimenta

    2009-06-01

    Full Text Available Eduardo Pimenta1, Suzanne Oparil21Endocrine Hypertension Research Centre and Clinical Centre of Research Excellence in Cardiovascular Disease and Metabolic Disorders, University of Queensland School of Medicine, Greenslopes Princess Alexandra Hospitals, Brisbane, QLD, Australia; 2Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham, AL, USAAbstract: The renin–angiotensin–aldosterone system (RAAS is a key mediator of blood pressure (BP and volume regulation in both normotensive and hypertensive persons. Stimulation of RAAS also contributes to hypertension-related target organ damage. The renin–angiotensinogen reaction is the first and rate-limiting step in the generation of angiotensin II (Ang II and has been a target of antihypertensive drug development for decades. Aliskiren is the first in a new class of orally effective direct renin inhibitors (DRIs and is approved for the treatment of hypertension in humans. It effectively reduces BP in the general population of hypertensive patients and has a tolerability and safety profile similar to placebo. Aliskiren has favorable effects on vascular inflammation and remodeling, on neurohumoral mediators of various forms of cardiovascular disease, including heart failure, and on proteinuria in diabetic patients. Additional outcome trials are needed to establish the role of this novel class of antihypertensive medication in preventing cardiovascular disease morbidity and mortality.Keywords: hypertension, renin inhibitors, renin-angiotensin-aldosterone system

  7. The Essential Role of Epstein-Barr Virus in the Pathogenesis of Multiple Sclerosis

    Science.gov (United States)

    Pender, Michael P.

    2011-01-01

    There is increasing evidence that infection with the Epstein-Barr virus (EBV) plays a role in the development of multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the CNS. This article provides a four-tier hypothesis proposing (1) EBV infection is essential for the development of MS; (2) EBV causes MS in genetically susceptible individuals by infecting autoreactive B cells, which seed the CNS where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells that would otherwise die in the CNS by apoptosis; (3) the susceptibility to develop MS after EBV infection is dependent on a genetically determined quantitative deficiency of the cytotoxic CD8+ T cells that normally keep EBV infection under tight control; and (4) sunlight and vitamin D protect against MS by increasing the number of CD8+ T cells available to control EBV infection. The hypothesis makes predictions that can be tested, including the prevention and successful treatment of MS by controlling EBV infection. PMID:21075971

  8. Ecstatic epileptic seizures: a glimpse into the multiple roles of the insula

    Directory of Open Access Journals (Sweden)

    Markus eGschwind

    2016-02-01

    Full Text Available Ecstatic epileptic seizures are a rare but compelling epileptic entity. During the first seconds of these seizures, ecstatic auras provoke feelings of well-being, intense serenity, bliss, and enhanced self-awareness. They are associated with the impression of time dilation, and can be described as a mystic experience by some patients. The functional neuroanatomy of ecstatic seizures is still debated. During recent years several patients presenting with ecstatic auras have been reported by others and us (in total n=49; a few of them in the setting of presurgical evaluation including electrical brain stimulation. According to the recently recognized functions of the insula, and the results of nuclear brain imaging and electrical stimulation, the ecstatic symptoms in these patients seem to localize to a functional network centered around the anterior insular cortex, where we thus propose to locate this rare ictal phenomenon. Here we summarize the role of the multiple sensory, autonomic, affective and cognitive functions of the insular cortex, which are integrated into the creation of self-awareness, and we suggest how this system may become dysfunctional on several levels during ecstatic aura.

  9. The role of Acinetobacter in the pathogenesis of multiple sclerosis examined by using Popper sequences.

    Science.gov (United States)

    Ebringer, Alan; Rashid, Taha; Wilson, Clyde

    2012-06-01

    Multiple sclerosis (MS) is an autoimmune neurological disorder. The role of 'Acinetobacter' has been examined using the method of Karl Popper and involves nine "Popper sequences". (1) The frequency of MS increases with latitudes in the Northern Hemisphere, and the reverse is found in the Southern Hemisphere. (2) Sinusitis is found frequently at colder latitudes. (3) Sinusitis occurs frequently in patients with MS. (4) Specific sequences of bovine myelin when injected into experimental animals will produce a neurological disorder resembling MS which is called "experimental allergic encephalomyelitis". (5) Computer analysis of myelin shows molecular mimicry with sequences found in Acinetobacter. (6) Antibodies to Acinetobacter bacteria are found in MS patients. (7) Acinetobacter bacteria are located on human skin and in the nasal sinuses. (8) IgA antibodies are preferentially elevated in the sera of MS patients, thereby suggesting the trigger microbe is acting across a mucosal surface probably located in the nasal sinuses. (9) Only Acinetobacter bacteria and no other microbes evoke statistically significant titres of antibodies in MS patients. These nine Popper sequences suggest that MS is most probably caused by infections with Acinetobacter bacteria in the nasal sinuses, and this could have therapeutic implications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Autographa californica multiple nucleopolyhedrovirus ac53 plays a role in nucleocapsid assembly

    International Nuclear Information System (INIS)

    Liu Chao; Li Zhaofei; Wu Wenbi; Li Lingling; Yuan Meijin; Pan Lijing; Yang Kai; Pang Yi

    2008-01-01

    Autographa californica multiple nucleopolyhedrovirus (AcMNPV) orf53 (ac53) is a highly conserved gene existing in all sequenced Lepidoptera and Hymenoptera baculoviruses, but its function remains unknown. To investigate its role in the baculovirus life cycle, an ac53 deletion virus (vAc ac53KO-PH-GFP ) was generated through homologous recombination in Escherichia coli. Fluorescence and light microscopy and titration analysis revealed that vAc ac53KO-PH-GFP could not produce infectious budded virus in infected Sf9 cells. Real-time PCR demonstrated that the ac53 deletion did not affect the levels of viral DNA replication. Electron microscopy showed that many lucent tubular shells devoid of the nucleoprotein core are present in the virogenic stroma and ring zone, indicating that the ac53 knockout affected nucleocapsid assembly. With a recombinant virus expressing an Ac53-GFP fusion protein, we observed that Ac53 was distributed within the cytoplasm and nucleus at 24 h post-infection, but afterwards accumulated predominantly near the nucleus-cytoplasm boundary. These data demonstrate that ac53 is involved in nucleocapsid assembly and is an essential gene for virus production

  11. What are the key dimensions of the personal tutor role for nurse education today? A literature review.

    OpenAIRE

    Leddington, Susan

    2012-01-01

    Background. The accepted position of the personal tutor role from the background literature includes both pastoral care and academic support. Recent government led initiatives of widening access to higher education, the Dearing report (NCIHE, 1997) and the National Student Survey (HEFCE, 2006) have changed higher education and affected the personal tutor role. The implication of these initiatives for nurse education is unclear. Aim. The aim of this literature review is to explore the dimensio...

  12. The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis

    Science.gov (United States)

    Bernstock, Joshua D.; Pluchino, Stefano

    2015-01-01

    Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in nature, yet increasing correlative evidence supports a strong association between one’s genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis. PMID:25802011

  13. Hippocampal structure and human cognition: key role of spatial processing and evidence supporting the efficiency hypothesis in females

    Science.gov (United States)

    Colom, Roberto; Stein, Jason L.; Rajagopalan, Priya; Martínez, Kenia; Hermel, David; Wang, Yalin; Álvarez-Linera, Juan; Burgaleta, Miguel; Quiroga, MªÁngeles; Shih, Pei Chun; Thompson, Paul M.

    2014-01-01

    Here we apply a method for automated segmentation of the hippocampus in 3D high-resolution structural brain MRI scans. One hundred and four healthy young adults completed twenty one tasks measuring abstract, verbal, and spatial intelligence, along with working memory, executive control, attention, and processing speed. After permutation tests corrected for multiple comparisons across vertices (p related to hippocampal structural differences. PMID:25632167

  14. Investigating the role of Clinical Nurse Consultants in one health district from multiple stakeholder perspectives: a cooperative inquiry.

    Science.gov (United States)

    Walsh, Kenneth; Bothe, Janine; Edgar, Denise; Beaven, Geraldine; Burgess, Bernadette; Dickson, Vhari; Dunn, Stephen; Horning, Lynda; Jensen, Janice; Kandl, Bronia; Nonu, Miriam; Owen, Fran; Moss, Cheryle

    2015-01-01

    The impetus for this research came from a group of 11 Clinical Nurse Consultants (CNCs) within a health service in NSW, Australia, who wanted to investigate the CNC role from multiple stakeholder perspectives. With support from academic researchers, the CNCs designed and implemented the study. The aim of this research project was to investigate the role of the CNC from the multiple perspectives of CNCs and other stakeholders who work with CNCs in the Health District. This was a co-operative inquiry that utilised qualitative descriptive research approach. Co-operative inquiry methods enabled 11 CNCs to work as co-researchers and to conduct the investigation. The co-researchers implemented a qualitative descriptive design for the research and used interviews (7) and focus groups (16) with CNC stakeholders (n = 103) to gather sufficient data to investigate the role of the CNC in the organisation. Thematic analysis was undertaken to obtain the results. The CNC role is invaluable to all stakeholders and it was seen as the "glue" which holds teams together. Stakeholder expectations of the CNC role were multiple and generally agreed. Five themes derived from the data are reported as "clinical leadership as core", "making a direct difference to patient care", "service development as an outcome", "role breadth or narrowness and boundaries", and "career development". There was clear appreciation of the work that CNCs do in their roles, and the part that the CNC role plays in achieving quality health outcomes. The role of the CNC is complex and the CNCs themselves often negotiate these complexities to ensure beneficial outcomes for the patient and organisation. For the wider audience this study has given further insights into the role of these nurses and the perspectives of those with whom they work.

  15. The key role of peltate glandular trichomes in symbiota comprising clavicipitaceous fungi of the genus periglandula and their host plants.

    Science.gov (United States)

    Steiner, Ulrike; Kucht, Sabine Hellwig neé; Ahimsa-Müller, Mahalia A; Grundmann, Nicola; Li, Shu-Ming; Drewke, Christel; Leistner, Eckhard

    2015-04-16

    Clavicipitaceous fungi producing ergot alkaloids were recently discovered to be epibiotically associated with peltate glandular trichomes of Ipomoea asarifolia and Turbina corymbosa, dicotyledonous plants of the family Convolvulaceae. Mediators of the close association between fungi and trichomes may be sesquiterpenes, main components in the volatile oil of different convolvulaceous plants. Molecular biological studies and microscopic investigations led to the observation that the trichomes do not only secrete sesquiterpenes and palmitic acid but also seem to absorb ergot alkaloids from the epibiotic fungal species of the genus Periglandula. Thus, the trichomes are likely to have a dual and key function in a metabolic dialogue between fungus and host plant.

  16. A Qualitative Exploration of Multiple Case Studies of the Perception of School Social Workers Concerning Their Roles in Public Schools

    Science.gov (United States)

    Morrison, Alesha Nicole

    2016-01-01

    This qualitative exploration in the form of multiple case studies interviewed a group of seven social workers from the St. Louis Metropolitan area to gain their perception as school social workers concerning their roles in public schools. The literature on school social workers indicated that school social workers brought unique knowledge and…

  17. Exploring the Behavioral Patterns of Learners in an Educational Massively Multiple Online Role-Playing Game (MMORPG)

    Science.gov (United States)

    Hou, Huei-Tse

    2012-01-01

    Massively multiple online role-playing games (MMORPGs) are very popular among students. Educational MMORPGs, however, are very rare, as are studies on gamers' behavioral patterns during such games. The current study is an empirical observation and analysis of the behavioral patterns of 100 gamers participating in an educational MMORPG called…

  18. The Role of the External Personal Assistants for Children with Profound Intellectual and Multiple Disabilities Working in the Children's Home

    Science.gov (United States)

    Axelsson, Anna Karin

    2015-01-01

    Background: Children with profound intellectual and multiple disabilities need support to function in an optimal way. However, there is a limited knowledge about the role of external personal assistants working in the children's home. Materials and Methods: A mixed method study was performed including qualitative data from interviews with 11…

  19. Ethnic and Racial Socialization and Self-Esteem of Asian Adoptees: The Mediating Role of Multiple Identities

    Science.gov (United States)

    Mohanty, Jayashree

    2013-01-01

    Positive identity development during adolescence in general is a complex process and may pose additional challenges for adolescents adopted from a different culture. Using a web-based survey design with a sample of 100 internationally adopted Asian adolescent and young adults, the present study examined the mediating role of multiple identities…

  20. The role of multiple neuromodulators in reinforcement learning that is based on competition between eligibility traces

    Directory of Open Access Journals (Sweden)

    Marco A Huertas

    2016-12-01

    neuromodulators for expressing the LTP and LTD traces? Here we expand on our previous model to include several neuromodulators, and illustrate through various examples how different neuromodulators contribute to learning reward-timing within a wide set of training paradigms and propose further roles that multiple neuromodulators can play in encoding additional information of the rewarding signal.

  1. The Role of Multiple Neuromodulators in Reinforcement Learning That Is Based on Competition between Eligibility Traces.

    Science.gov (United States)

    Huertas, Marco A; Schwettmann, Sarah E; Shouval, Harel Z

    2016-01-01

    expressing the LTP and LTD traces? Here we expand on our previous model to include several neuromodulators, and illustrate through various examples how different these contribute to learning reward-timing within a wide set of training paradigms and propose further roles that multiple neuromodulators can play in encoding additional information of the rewarding signal.

  2. The role of health informatics in clinical audit: part of the problem or key to the solution?

    Science.gov (United States)

    Georgiou, Andrew; Pearson, Michael

    2002-05-01

    The concepts of quality assurance (for which clinical audit is an essential part), evaluation and clinical governance each depend on the ability to derive and record measurements that describe clinical performance. Rapid IT developments have raised many new possibilities for managing health care. They have allowed for easier collection and processing of data in greater quantities. These developments have encouraged the growth of quality assurance as a key feature of health care delivery. In the past most of the emphasis has been on hospital information systems designed predominantly for the administration of patients and the management of financial performance. Large, hi-tech information system capacity does not guarantee quality information. The task of producing information that can be confidently used to monitor the quality of clinical care requires attention to key aspects of the design and operation of the audit. The Myocardial Infarction National Audit Project (MINAP) utilizes an IT-based system to collect and process data on large numbers of patients and make them readily available to contributing hospitals. The project shows that IT systems that employ rigorous health informatics methodologies can do much to improve the monitoring and provision of health care.

  3. The multiple roles of hypothetical gene BPSS1356 in Burkholderia pseudomallei.

    Directory of Open Access Journals (Sweden)

    Hokchai Yam

    Full Text Available Burkholderia pseudomallei is an opportunistic pathogen and the causative agent of melioidosis. It is able to adapt to harsh environments and can live intracellularly in its infected hosts. In this study, identification of transcriptional factors that associate with the β' subunit (RpoC of RNA polymerase was performed. The N-terminal region of this subunit is known to trigger promoter melting when associated with a sigma factor. A pull-down assay using histidine-tagged B. pseudomallei RpoC N-terminal region as bait showed that a hypothetical protein BPSS1356 was one of the proteins bound. This hypothetical protein is conserved in all B. pseudomallei strains and present only in the Burkholderia genus. A BPSS1356 deletion mutant was generated to investigate its biological function. The mutant strain exhibited reduced biofilm formation and a lower cell density during the stationary phase of growth in LB medium. Electron microscopic analysis revealed that the ΔBPSS1356 mutant cells had a shrunken cytoplasm indicative of cell plasmolysis and a rougher surface when compared to the wild type. An RNA microarray result showed that a total of 63 genes were transcriptionally affected by the BPSS1356 deletion with fold change values of higher than 4. The expression of a group of genes encoding membrane located transporters was concurrently down-regulated in ΔBPSS1356 mutant. Amongst the affected genes, the putative ion transportation genes were the most severely suppressed. Deprivation of BPSS1356 also down-regulated the transcriptions of genes for the arginine deiminase system, glycerol metabolism, type III secretion system cluster 2, cytochrome bd oxidase and arsenic resistance. It is therefore obvious that BPSS1356 plays a multiple regulatory roles on many genes.

  4. The Impact of Multiple Roles on Psychological Distress among Japanese Workers

    Directory of Open Access Journals (Sweden)

    Ayumi Honda

    2015-06-01

    Conclusion: The present study demonstrated that participants who had only an employment role had an increased risk of psychological distress. The degree of psychological distress was not determined solely by the number of roles. It is important to have balance between work and family life to reduce role conflict and/or role submersion, which in turn may reduce the risk of psychological distress.

  5. Clinical diagnostic criteria of multiple sclerosis: the role of magnetic resonance imaging

    International Nuclear Information System (INIS)

    Belair, M.; Girard, M.

    2004-01-01

    The objective of this article is to summarize the diagnostic criteria recommended by the International Panel on the Diagnosis of Multiple Sclerosis in 2001. The recommendations of another working group, the Consortium of Multiple Sclerosis Centers Consensus Meeting, which met in Vancouver in 2001, concerning the diagnosis and follow-up of patients with multiple sclerosis are also presented in an effort to standardize the protocols for magnetic resonance imaging of these patients. (author)

  6. A key role for arbuscular mycorrhiza in plant acquisition of P from sewage sludge recycled to soil

    DEFF Research Database (Denmark)

    Mackay, Jessica E.; Cavagnaro, Timothy R.; Müller-Stöver, Dorette Sophie

    2017-01-01

    Dried and incinerated sewage sludge (SS) have the potential to be used as phosphorus (P) fertilisers. Arbuscular mycorrhizal fungi (AMF) contribute to plant P uptake; however, their role in P uptake from SS has yet to be fully explored. A compartmented pot system with an isotope pool dilution...... approach was used to investigate wheat (Triticum aestivum L.) P uptake from soluble P, dried SS and incinerated SS, via roots and/or AMF hyphae. Wheat was sown into an inner compartment containing a 33P label with/without AMF (Rhizophagus irregularis) inoculum. An outer soil compartment contained the P...... access dried SS than when only roots could access dried SS. We discuss the results in terms of availability of P to roots and hyphae. We conclude that AMF play an important role in wheat P acquisition from dried SS and therefore can assist in the recycling of P in waste....

  7. Similarly Torn, Differentially Shorn? The Experience and Management of Conflict between Multiple Roles, Relationships, and Social Categories

    Directory of Open Access Journals (Sweden)

    Janelle M. Jones

    2017-10-01

    Full Text Available In three studies we examined the experience and management of conflict between different types of multiple identities. Participants described a conflict between pairs of role, relational, or social identities before rating the experience (i.e., magnitude, stress, and growth and management of conflict on a newly developed scale assessing four strategies: reconciliation, where identities are integrated, realignment, where one identity is chosen over another, retreat, where both identities are avoided, and reflection, where fit (with others, situation determines identity selection. In general, the types of identities mattered for conflict management but not its experience: Magnitude and growth did not differ, however, stress was greater for role identity conflicts (Study 3 only and participants endorsed the use of more realignment for role conflicts (Study 2 and more retreat for relational conflicts (Study 3 relative to other types of identity conflicts. Furthermore, findings suggested that the perceived flexibility of identities, not their importance or valence, were associated with realignment and retreat for roles and with retreat for relationships. Experiencing conflicts between multiple identities leaves people similarly torn, but multiple roles and relationships may be differentially shorn to manage conflict.

  8. Similarly Torn, Differentially Shorn? The Experience and Management of Conflict between Multiple Roles, Relationships, and Social Categories

    Science.gov (United States)

    Jones, Janelle M.; Hynie, Michaela

    2017-01-01

    In three studies we examined the experience and management of conflict between different types of multiple identities. Participants described a conflict between pairs of role, relational, or social identities before rating the experience (i.e., magnitude, stress, and growth) and management of conflict on a newly developed scale assessing four strategies: reconciliation, where identities are integrated, realignment, where one identity is chosen over another, retreat, where both identities are avoided, and reflection, where fit (with others, situation) determines identity selection. In general, the types of identities mattered for conflict management but not its experience: Magnitude and growth did not differ, however, stress was greater for role identity conflicts (Study 3 only) and participants endorsed the use of more realignment for role conflicts (Study 2) and more retreat for relational conflicts (Study 3) relative to other types of identity conflicts. Furthermore, findings suggested that the perceived flexibility of identities, not their importance or valence, were associated with realignment and retreat for roles and with retreat for relationships. Experiencing conflicts between multiple identities leaves people similarly torn, but multiple roles and relationships may be differentially shorn to manage conflict. PMID:29051744

  9. Similarly Torn, Differentially Shorn? The Experience and Management of Conflict between Multiple Roles, Relationships, and Social Categories.

    Science.gov (United States)

    Jones, Janelle M; Hynie, Michaela

    2017-01-01

    In three studies we examined the experience and management of conflict between different types of multiple identities. Participants described a conflict between pairs of role, relational, or social identities before rating the experience (i.e., magnitude, stress, and growth) and management of conflict on a newly developed scale assessing four strategies: reconciliation , where identities are integrated, realignment , where one identity is chosen over another, retreat , where both identities are avoided, and reflection , where fit (with others, situation) determines identity selection. In general, the types of identities mattered for conflict management but not its experience: Magnitude and growth did not differ, however, stress was greater for role identity conflicts ( Study 3 only ) and participants endorsed the use of more realignment for role conflicts ( Study 2 ) and more retreat for relational conflicts ( Study 3 ) relative to other types of identity conflicts. Furthermore, findings suggested that the perceived flexibility of identities, not their importance or valence, were associated with realignment and retreat for roles and with retreat for relationships. Experiencing conflicts between multiple identities leaves people similarly torn, but multiple roles and relationships may be differentially shorn to manage conflict.

  10. What Role Does The Executive Officer Play In Ensuring Senior Officer Success Building An Organization Of Trust Is Key

    Science.gov (United States)

    2016-02-16

    AIR WAR COLLEGE AIR UNIVERSITY WHAT ROLE DOES THE EXECUTIVE OFFICER PLAY IN ENSURING SENIOR OFFICER SUCCESS? BUILDING AN ORGANIZATION OF...talk, demonstrate respect, create transparency, right wrongs, show loyalty , deliver results, get better, confront reality, clarify expectations...When speaking for the senior leader, the exec must ensure commander’s intent is conveyed clearly and accurately. It is for this reason that execs

  11. Rich biotin content in lignocellulose biomass plays the key role in determining cellulosic glutamic acid accumulation by Corynebacterium glutamicum.

    Science.gov (United States)

    Wen, Jingbai; Xiao, Yanqiu; Liu, Ting; Gao, Qiuqiang; Bao, Jie

    2018-01-01

    Lignocellulose is one of the most promising alternative feedstocks for glutamic acid production as commodity building block chemical, but the efforts by the dominant industrial fermentation strain Corynebacterium glutamicum failed for accumulating glutamic acid using lignocellulose feedstock. We identified the existence of surprisingly high biotin concentration in corn stover hydrolysate as the determining factor for the failure of glutamic acid accumulation by Corynebacterium glutamicum . Under excessive biotin content, induction by penicillin resulted in 41.7 ± 0.1 g/L of glutamic acid with the yield of 0.50 g glutamic acid/g glucose. Our further investigation revealed that corn stover contained 353 ± 16 μg of biotin per kg dry solids, approximately one order of magnitude greater than the biotin in corn grain. Most of the biotin remained stable during the biorefining chain and the rich biotin content in corn stover hydrolysate almost completely blocked the glutamic acid accumulation. This rich biotin existence was found to be a common phenomenon in the wide range of lignocellulose biomass and this may be the key reason why the previous studies failed in cellulosic glutamic acid fermentation from lignocellulose biomass. The extended recording of the complete members of all eight vitamin B compounds in lignocellulose biomass further reveals that the major vitamin B members were also under the high concentration levels even after harsh pretreatment. The high content of biotin in wide range of lignocellulose biomass feedstocks and the corresponding hydrolysates was discovered and it was found to be the key factor in determining the cellulosic glutamic acid accumulation. The highly reserved biotin and the high content of their other vitamin B compounds in biorefining process might act as the potential nutrients to biorefining fermentations. This study creates a new insight that lignocellulose biorefining not only generates inhibitors, but also keeps nutrients

  12. Multiple magnet ingestion: is there a role for early surgical intervention?

    Science.gov (United States)

    Salimi, Amrollah; Kooraki, Soheil; Esfahani, Shadi Abdar; Mehdizadeh, Mehrzad

    2012-01-01

    Children often swallow foreign bodies. Multiple magnet ingestion is rare, but can result in serious complications. This study presents three unique cases of multiple magnet ingestion: one case an 8-year-old boy with multiple magnet ingestion resulting in gastric obstruction and the other two cases with intestinal perforations due to multiple magnet intake. History and physical examination are unreliable in children who swallow multiple magnets. Sometimes radiological findings are not conclusive, whether one magnet is swallowed or more. If magnets are not moved in sequential radiology images, we recommend early surgical intervention before gastrointestinal complications develop. Toy companies, parents, physicians, and radiologists should be warned about the potential complications of such toys.

  13. Emotion and Exclusion: Key Ideas from Vygotsky to Review our Role in a School with a Cultural Diversity Setting

    Directory of Open Access Journals (Sweden)

    Enrique Riquelme MELLA

    Full Text Available ABSTRACT: Research demonstrates that minorities' children diagnosed with Emotional and Behavioural Disorders is overrepresented, being the ethnic minorities the most affected. The diagnostics have resulted in racism and discrimination. This article reflects upon the necessity to develop more integrated and dynamic models of inclusion for the schools. Based on Vygotsky´s ideas, a reflexion is done regarding the emotional education in schools, specifically about the need to include -in the teacher formation- the main role of the culture emotional rules in the dynamic of exclusion/inclusion of minorities. The article concludes with proposals to be considered for a culturally sensible vision on inclusion.

  14. How can core self-evaluations influence job burnout? The key roles of organizational commitment and job satisfaction.

    Science.gov (United States)

    Peng, Jiaxi; Li, Dongdong; Zhang, Zhenjiang; Tian, Yu; Miao, Danmin; Xiao, Wei; Zhang, Jiaxi

    2016-01-01

    This study aimed to explore how core self-evaluations influenced job burnout and mainly focused on the confirmation of the mediator roles of organizational commitment and job satisfaction. A total of 583 female nurses accomplished the Core Self-Evaluation Scale, Organizational Commitment Scale, Minnesota Satisfaction Questionnaire, and Maslach Burnout Inventory-General Survey. The results revealed that core self-evaluations, organizational commitment, job satisfaction, and job burnout were significantly correlated with each other. Structural equation modeling indicated that core self-evaluations can significantly influence job burnout and are completely mediated by organizational commitment and job satisfaction. © The Author(s) 2014.

  15. The expression and evolution of virulence in multiple infections: the role of specificity, relative virulence and relative dose.

    Science.gov (United States)

    Ben-Ami, Frida; Routtu, Jarkko

    2013-05-03

    Multiple infections of the same host by different strains of the same microparasite species are believed to play a crucial role during the evolution of parasite virulence. We investigated the role of specificity, relative virulence and relative dose in determining the competitive outcome of multiple infections in the Daphnia magna-Pasteuria ramosa host-parasite system. We found that infections by P. ramosa clones (single genotype) were less virulent and produced more spores than infections by P. ramosa isolates (possibly containing multiple genotypes). We also found that two similarly virulent isolates of P. ramosa differed considerably in their within-host competitiveness and their effects on host offspring production when faced with coinfecting P. ramosa isolates and clones. Although the relative virulence of a P. ramosa isolate/clone appears to be a good indicator of its competitiveness during multiple infections, the relative dose may alter the competitive outcome. Moreover, spore counts on day 20 post-infection indicate that the competitive outcome is largely decided early in the parasite's growth phase, possibly mediated by direct interference or apparent competition. Our results emphasize the importance of epidemiology as well as of various parasite traits in determining the outcome of within-host competition. Incorporating realistic epidemiological and ecological conditions when testing theoretical models of multiple infections, as well as using a wider range of host and parasite genotypes, will enable us to better understand the course of virulence evolution.

  16. Searching for a Role of Nursing Personnel in Developing Landscape of Ehealth: Factors Determining Attitudes toward Key Patient Empowering Applications.

    Science.gov (United States)

    Duplaga, Mariusz

    2016-01-01

    Nurses may play an important role in the delivery of medical services based on the use of ehealth tools. Nevertheless, their taking an active role in an ehealth environment depends on their possessing the appropriate skills and mindset. The main objective of this paper was to assess nurses' opinions and to analyze the predictors of their acceptance of ehealth features relevant to patient empowerment with a strong focus on chronic care. A survey was conducted among nurses from hospital centers of south-eastern Poland based on a questionnaire designed to assess their attitudes toward the ehealth domain. The predictors of the nurses' acceptance of ehealth usage within specific contexts were assessed with uni- and multivariate logistic regression. An analysis was performed on data from 648 questionnaires retained after a quality check. The duration of Internet use was consistently related to higher acceptance of ehealth applications and more certainty regarding the reliability of health-related information available on the Internet. Nurses from urban medical centers were more skeptical about the use of specific ehealth solutions. Previous experience in using information technologies is the main factor influencing the acceptance of specific ehealth solutions relevant for care provided to patients suffering from chronic conditions.

  17. The Relation Between Emotion Understanding and Theory of Mind in Children Aged 3 to 8: The Key Role of Language

    Directory of Open Access Journals (Sweden)

    Ilaria Grazzani

    2018-05-01

    Full Text Available Although a significant body of research has investigated the relationships among children’s emotion understanding (EU, theory of mind (ToM, and language abilities. As far as we know, no study to date has been conducted with a sizeable sample of both preschool and school-age children exploring the direct effect of EU on ToM when the role of language was evaluated as a potential exogenous factor in a single comprehensive model. Participants in the current study were 389 children (age range: 37–97 months, M = 60.79 months; SD = 12.66, to whom a False-Belief understanding battery, the Test of Emotion Comprehension, and the Peabody Test were administered. Children’s EU, ToM, and language ability (receptive vocabulary were positively correlated. Furthermore, EU scores explained variability in ToM scores independently of participants’ age and gender. Finally, language was found to play a crucial role in both explaining variance in ToM scores and in mediating the relationship between EU and ToM. We discuss the theoretical and educational implications of these outcomes, particularly in relation to offering social and emotional learning programs through schools.

  18. The Relation Between Emotion Understanding and Theory of Mind in Children Aged 3 to 8: The Key Role of Language.

    Science.gov (United States)

    Grazzani, Ilaria; Ornaghi, Veronica; Conte, Elisabetta; Pepe, Alessandro; Caprin, Claudia

    2018-01-01

    Although a significant body of research has investigated the relationships among children's emotion understanding (EU), theory of mind (ToM), and language abilities. As far as we know, no study to date has been conducted with a sizeable sample of both preschool and school-age children exploring the direct effect of EU on ToM when the role of language was evaluated as a potential exogenous factor in a single comprehensive model. Participants in the current study were 389 children (age range: 37-97 months, M = 60.79 months; SD = 12.66), to whom a False-Belief understanding battery, the Test of Emotion Comprehension, and the Peabody Test were administered. Children's EU, ToM, and language ability (receptive vocabulary) were positively correlated. Furthermore, EU scores explained variability in ToM scores independently of participants' age and gender. Finally, language was found to play a crucial role in both explaining variance in ToM scores and in mediating the relationship between EU and ToM. We discuss the theoretical and educational implications of these outcomes, particularly in relation to offering social and emotional learning programs through schools.

  19. Disturbance of Oligodendrocyte Function Plays a Key Role in the Pathogenesis of Schizophrenia and Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Shingo Miyata

    2015-01-01

    Full Text Available The major psychiatric disorders such as schizophrenia (SZ and major depressive disorder (MDD are thought to be multifactorial diseases related to both genetic and environmental factors. However, the genes responsible and the molecular mechanisms underlying the pathogenesis of SZ and MDD remain unclear. We previously reported that abnormalities of disrupted-in-Schizophrenia-1 (DISC1 and DISC1 binding zinc finger (DBZ might cause major psychiatric disorders such as SZ. Interestingly, both DISC and DBZ have been further detected in oligodendrocytes and implicated in regulating oligodendrocyte differentiation. DISC1 negatively regulates the differentiation of oligodendrocytes, whereas DBZ plays a positive regulatory role in oligodendrocyte differentiation. We have reported that repeated stressful events, one of the major risk factors of MDD, can induce sustained upregulation of plasma corticosterone levels and serum/glucocorticoid regulated kinase 1 (Sgk1 mRNA expression in oligodendrocytes. Repeated stressful events can also activate the SGK1 cascade and cause excess arborization of oligodendrocyte processes, which is thought to be related to depressive-like symptoms. In this review, we discuss the expression of DISC1, DBZ, and SGK1 in oligodendrocytes, their roles in the regulation of oligodendrocyte function, possible interactions of DISC1 and DBZ in relation to SZ, and the activation of the SGK1 signaling cascade in relation to MDD.

  20. Vitamin D receptor: key roles in bone mineral pathophysiology, molecular mechanism of action, and novel nutritional ligands.

    Science.gov (United States)

    Jurutka, Peter W; Bartik, Leonid; Whitfield, G Kerr; Mathern, Douglas R; Barthel, Thomas K; Gurevich, Miriam; Hsieh, Jui-Cheng; Kaczmarska, Magdalena; Haussler, Carol A; Haussler, Mark R

    2007-12-01

    The vitamin D hormone, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], binds with high affinity to the nuclear vitamin D receptor (VDR), which recruits its retinoid X receptor (RXR) heterodimeric partner to recognize vitamin D responsive elements (VDREs) in target genes. 1,25(OH)(2)D(3) is known primarily as a regulator of calcium, but it also controls phosphate (re)absorption at the intestine and kidney. Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced in osteoblasts that, like PTH, lowers serum phosphate by inhibiting renal reabsorption through Npt2a/Npt2c. Real-time PCR and reporter gene transfection assays were used to probe VDR-mediated transcriptional control by 1,25(OH)(2)D(3). Reporter gene and mammalian two-hybrid transfections, plus competitive receptor binding assays, were used to discover novel VDR ligands. 1,25(OH)(2)D(3) induces FGF23 78-fold in osteoblasts, and because FGF23 in turn represses 1,25(OH)(2)D(3) synthesis, a reciprocal relationship is established, with FGF23 indirectly curtailing 1,25(OH)(2)D(3)-mediated intestinal absorption and counterbalancing renal reabsorption of phosphate, thereby reversing hyperphosphatemia and preventing ectopic calcification. Therefore, a 1,25(OH)(2)D(3)-FGF23 axis regulating phosphate is comparable in importance to the 1,25(OH)(2)D(3)-PTH axis that regulates calcium. 1,25(OH)(2)D(3) also elicits regulation of LRP5, Runx2, PHEX, TRPV6, and Npt2c, all anabolic toward bone, and RANKL, which is catabolic. Regulation of mouse RANKL by 1,25(OH)(2)D(3) supports a cloverleaf model, whereby VDR-RXR heterodimers bound to multiple VDREs are juxtapositioned through chromatin looping to form a supercomplex, potentially allowing simultaneous interactions with multiple co-modulators and chromatin remodeling enzymes. VDR also selectively binds certain omega3/omega6 polyunsaturated fatty acids (PUFAs) with low affinity, leading to transcriptionally active VDR-RXR complexes. Moreover, the turmeric

  1. Centrality of women's multiple roles: beneficial and detrimental consequences for psychological well-being.

    Science.gov (United States)

    Martire, L M; Stephens, M A; Townsend, A L

    2000-03-01

    Theorists have proposed that greater centrality (personal importance) of a social role is associated with better psychological well-being but that role centrality exacerbates the negative effects of stress in that same social role on well-being. The present study found evidence to support both hypotheses in a sample of 296 women who simultaneously occupied the roles of parent care provider, mother, wife, and employee. Greater centrality of all four roles was related to better psychological well-being. As predicted, wife centrality exacerbated the effects of wife stress on life satisfaction, and employee centrality exacerbated the effects of employee stress on depressive symptoms. Contrary to prediction, centrality of the mother role buffered women from the negative effects of mother stress on depressive symptoms. These findings point to an aspect of role identity that can benefit well-being but that has complex effects in the context of role stress.

  2. First clinical use of stereotaxy in humans: the key role of x-ray localization discovered by Gaston Contremoulins.

    Science.gov (United States)

    Bourdillon, Pierre; Apra, Caroline; Lévêque, Marc

    2018-03-01

    Although attempts to develop stereotactic approaches to intracranial surgery started in the late 19th century with Dittmar, Zernov, and more famously, Horsley and Clarke, widespread use of the technique for human brain surgery started in the second part of the 20th century. Remarkably, a significant similar surgical procedure had already been performed in the late 19th century by Gaston Contremoulins in France and has remained unknown. Contremoulins used the principles of modern stereotaxy in association with radiography for the first time, allowing the successful removal of intracranial bullets in 2 patients. This surgical premiere, greatly acknowledged in the popular French newspaper L'Illustration in 1897, received little scientific or governmental interest at the time, as it emanated from a young self-taught scientist without official medical education. This surgical innovation was only made possible financially by popular crowdfunding and, despite widespread military use during World War I, with 37,780 patients having benefited from this technique for intra- or extracranial foreign bodies, it never attracted academic or neurosurgical consideration. The authors of this paper describe the historical context of stereotactic developments and the personal history of Contremoulins, who worked in the department of experimental physiology of the French Academy of Sciences led by Étienne-Jules Marey in Paris, and later devoted himself to radiography and radioprotection. The authors also give precise information about his original stereotactic tool "the bullet finder" ("le chercheur de projectiles") and its key concepts.

  3. The Fatty Acid Biosynthesis Enzyme FabI Plays a Key Role In the Development of Liver Stage Malarial Parasites

    Science.gov (United States)

    Yu, Min; Santha Kumar, T. R.; Nkrumah, Louis J.; Coppi, Alida; Retzlaff, Silke; Li, Celeste D.; Kelly, Brendan J.; Moura, Pedro A.; Lakshmanan, Viswanathan; Freundlich, Joel S.; Valderramos, Juan-Carlos; Vilcheze, Catherine; Siedner, Mark; Tsai, Jennifer H.-C.; Falkard, Brie; Sidhu, Amar bir Singh; Purcell, Lisa A.; Gratraud, Paul; Kremer, Laurent; Waters, Andy P.; Schiehser, Guy; Jacobus, David P.; Janse, Chris J.; Ager, Arba; Jacobs, William R.; Sacchettini, James C.; Heussler, Volker; Sinnis, Photini; Fidock, David A.

    2008-01-01

    SUMMARY Fatty acid biosynthesis has been viewed as an important biological function of and therapeutic target for Plasmodium falciparum asexual blood stage infection. This apicoplast-resident type II pathway, distinct from the mammalian type I process, includes FabI. Here, we report synthetic chemistry and transfection studies concluding that Plasmodium FabI is not the target of the antimalarial activity of the bacterial FabI inhibitor triclosan. Disruption of fabI in P. falciparum or the rodent parasite P. berghei does not impede blood stage growth. In contrast, mosquito-derived fabI-deficient P. berghei sporozoites are markedly less infective for mice and typically fail to complete liver stage development in vitro. This is characterized by an inability to form intra-hepatic merosomes that normally initiate blood stage infections. These data illuminate key differences between liver and blood stage parasites in their requirements for host versus de novo synthesized fatty acids, and create new prospects for stage-specific antimalarial interventions. PMID:19064257

  4. Key Role of Nitrate in Phase Transitions of Urban Particles: Implications of Important Reactive Surfaces for Secondary Aerosol Formation

    Science.gov (United States)

    Sun, Jiaxing; Liu, Lei; Xu, Liang; Wang, Yuanyuan; Wu, Zhijun; Hu, Min; Shi, Zongbo; Li, Yongjie; Zhang, Xiaoye; Chen, Jianmin; Li, Weijun

    2018-01-01

    Ammonium sulfate (AS) and ammonium nitrate (AN) are key components of urban fine particles. Both field and model studies showed that heterogeneous reactions of SO2, NO2, and NH3 on wet aerosols accelerated the haze formation in northern China. However, little is known on phase transitions of AS-AN containing haze particles. Here hygroscopic properties of laboratory-generated AS-AN particles and individual particles collected during haze events in an urban site were investigated using an individual particle hygroscopicity system. AS-AN particles showed a two-stage deliquescence at mutual deliquescence relative humidity (MDRH) and full deliquescence relative humidity (DRH) and three physical states: solid before MDRH, solid-aqueous between MDRH and DRH, and aqueous after DRH. During hydration, urban haze particles displayed a solid core and aqueous shell at RH = 60-80% and aqueous phase at RH > 80%. Most particles were in aqueous phase at RH > 50% during dehydration. Our results show that AS content in individual particles determines their DRH and AN content determines their MDRH. AN content increase can reduce MDRH, which indicates occurrence of aqueous shell at lower RH. The humidity-dependent phase transitions of nitrate-abundant urban particles are important to provide reactive surfaces of secondary aerosol formation in the polluted air.

  5. Potential role of multiple carbon fixation pathways during lipid accumulation in Phaeodactylum tricornutum

    Directory of Open Access Journals (Sweden)

    Valenzuela Jacob

    2012-06-01

    Full Text Available Abstract Background Phaeodactylum tricornutum is a unicellular diatom in the class Bacillariophyceae. The full genome has been sequenced (P. tricornutum gene expression profiles during nutrient-deprivation and lipid-accumulation, cell cultures were grown with a nitrate to phosphate ratio of 20:1 (N:P and whole-genome transcripts were monitored over time via RNA-sequence determination. Results The specific Nile Red (NR fluorescence (NR fluorescence per cell increased over time; however, the increase in NR fluorescence was initiated before external nitrate was completely exhausted. Exogenous phosphate was depleted before nitrate, and these results indicated that the depletion of exogenous phosphate might be an early trigger for lipid accumulation that is magnified upon nitrate depletion. As expected, many of the genes associated with nitrate and phosphate utilization were up-expressed. The diatom-specific cyclins cyc7 and cyc10 were down-expressed during the nutrient-deplete state, and cyclin B1 was up-expressed during lipid-accumulation after growth cessation. While many of the genes associated with the C3 pathway for photosynthetic carbon reduction were not significantly altered, genes involved in a putative C4 pathway for photosynthetic carbon assimilation were up-expressed as the cells depleted nitrate, phosphate, and exogenous dissolved inorganic carbon (DIC levels. P. tricornutum has multiple, putative carbonic anhydrases, but only two were significantly up-expressed (2-fold and 4-fold at the last time point when exogenous DIC levels had increased after the cessation of growth. Alternative pathways that could utilize HCO3- were also suggested by the gene expression profiles (e.g., putative propionyl-CoA and methylmalonyl-CoA decarboxylases. Conclusions The results indicate that P. tricornutum continued carbon dioxide reduction when population growth was arrested and different carbon-concentrating mechanisms were used dependent upon exogenous

  6. Glutathione oxidation in response to intracellular H2O2: Key but overlapping roles for dehydroascorbate reductases.

    Science.gov (United States)

    Rahantaniaina, Marie-Sylviane; Li, Shengchun; Chatel-Innocenti, Gilles; Tuzet, Andrée; Mhamdi, Amna; Vanacker, Hélène; Noctor, Graham

    2017-08-03

    Glutathione is a pivotal molecule in oxidative stress, during which it is potentially oxidized by several pathways linked to H 2 O 2 detoxification. We have investigated the response and functional importance of 3 potential routes for glutathione oxidation pathways mediated by glutathione S-transferases (GST), glutaredoxin-dependent peroxiredoxins (PRXII), and dehydroascorbate reductases (DHAR) in Arabidopsis during oxidative stress. Loss-of-function gstU8, gstU24, gstF8, prxIIE and prxIIF mutants as well as double gstU8 gstU24, gstU8 gstF8, gstU24 gstF8, prxIIE prxIIF mutants were obtained. No mutant lines showed marked changes in their phenotype and glutathione profiles in comparison to the wild-type plants in either optimal conditions or oxidative stress triggered by catalase inhibition. By contrast, multiple loss of DHAR functions markedly decreased glutathione oxidation triggered by catalase deficiency. To assess whether this effect was mediated directly by loss of DHAR enzyme activity, or more indirectly by upregulation of other enzymes involved in glutathione and ascorbate recycling, we measured expression of glutathione reductase (GR) and expression and activity of monodehydroascorbate reductases (MDHAR). No evidence was obtained that either GRs or MDHARs were upregulated in plants lacking DHAR function. Hence, interplay between different DHARs appears to be necessary to couple ascorbate and glutathione pools and to allow glutathione-related signaling during enhanced H 2 O 2 metabolism.

  7. Long-range correlations of different EEG derivations in rats: sleep stage-dependent generators may play a key role

    International Nuclear Information System (INIS)

    Fang, Guangzhan; Xia, Yang; Lai, Yongxiu; You, Zili; Yao, Dezhong

    2010-01-01

    For the electroencephalogram (EEG), topographic differences in the long-range temporal correlations would imply that these signals might be affected by specific mechanisms related to the generation of a given neuronal process. So the properties of the generators of various EEG oscillations might be investigated by their spatial differences of the long-range temporal correlations. In the present study, these correlations were characterized with respect to their topography during different vigilance states by detrended fluctuation analysis (DFA). The results indicated that (1) most of the scaling exponents acquired from different EEG derivations for various oscillations were significantly different in each vigilance state; these differences might be resulted from the different quantities and different locations of sleep stage-dependent generators of various neuronal processes; (2) there might be multiple generators of delta and theta over the brain and many of them were sleep stage-dependent; (3) the best site of the frontal electrode in a fronto-parietal bipolar electrode for sleep staging might be above the anterior midline cortex. We suggest that DFA analysis can be used to explore the properties of the generators of a given neuronal oscillation, and the localizations of these generators if more electrodes are involved

  8. Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages.

    Science.gov (United States)

    Maler, Mareike D; Nielsen, Peter J; Stichling, Nicole; Cohen, Idan; Ruzsics, Zsolt; Wood, Connor; Engelhard, Peggy; Suomalainen, Maarit; Gyory, Ildiko; Huber, Michael; Müller-Quernheim, Joachim; Schamel, Wolfgang W A; Gordon, Siamon; Jakob, Thilo; Martin, Stefan F; Jahnen-Dechent, Willi; Greber, Urs F; Freudenberg, Marina A; Fejer, György

    2017-08-01

    The scavenger receptor MARCO is expressed in several subsets of naive tissue-resident macrophages and has been shown to participate in the recognition of various bacterial pathogens. However, the role of MARCO in antiviral defense is largely unexplored. Here, we investigated whether MARCO might be involved in the innate sensing of infection with adenovirus and recombinant adenoviral vectors by macrophages, which elicit vigorous immune responses in vivo Using cells derived from mice, we show that adenovirus infection is significantly more efficient in MARCO-positive alveolar macrophages (AMs) and in AM-like primary macrophage lines (Max Planck Institute cells) than in MARCO-negative bone marrow-derived macrophages. Using antibodies blocking ligand binding to MARCO, as well as gene-deficient and MARCO-transfected cells, we show that MARCO mediates the rapid adenovirus transduction of macrophages. By enhancing adenovirus infection, MARCO contributes to efficient innate virus recognition through the cytoplasmic DNA sensor cGAS. This leads to strong proinflammatory responses, including the production of interleukin-6 (IL-6), alpha/beta interferon, and mature IL-1α. These findings contribute to the understanding of viral pathogenesis in macrophages and may open new possibilities for the development of tools to influence the outcome of infection with adenovirus or adenovirus vectors. IMPORTANCE Macrophages play crucial roles in inflammation and defense against infection. Several macrophage subtypes have been identified with differing abilities to respond to infection with both natural adenoviruses and recombinant adenoviral vectors. Adenoviruses are important respiratory pathogens that elicit vigorous innate responses in vitro and in vivo The cell surface receptors mediating macrophage type-specific adenovirus sensing are largely unknown. The scavenger receptor MARCO is expressed on some subsets of naive tissue-resident macrophages, including lung alveolar macrophages

  9. Metabolomic analysis reveals key metabolites related to the rapid adaptation of Saccharomyce cerevisiae to multiple inhibitors of furfural, acetic acid, and phenol.

    Science.gov (United States)

    Wang, Xin; Li, Bing-Zhi; Ding, Ming-Zhu; Zhang, Wei-Wen; Yuan, Ying-Jin

    2013-03-01

    During hydrolysis of lignocellulosic biomass, a broad range of inhibitors are generated, which interfere with yeast growth and bioethanol production. In order to improve the strain tolerance to multiple inhibitors--acetic acid, furfural, and phenol (three representative lignocellulose-derived inhibitors) and uncover the underlying tolerant mechanism, an adaptation experiment was performed in which the industrial Saccharomyces cerevisiae was cultivated repeatedly in a medium containing multiple inhibitors. The adaptation occurred quickly, accompanied with distinct increase in growth rate, glucose utilization rate, furfural metabolism rate, and ethanol yield, only after the first transfer. A similar rapid adaptation was also observed for the lab strains of BY4742 and BY4743. The metabolomic analysis was employed to investigate the responses of the industrial S. cereviaise to three inhibitors during the adaptation. The results showed that higher levels of 2-furoic acid, 2, 3-butanediol, intermediates in glycolytic pathway, and amino acids derived from glycolysis, were discovered in the adapted strains, suggesting that enhanced metabolic activity in these pathways may relate to resistance against inhibitors. Additionally, through single-gene knockouts, several genes related to alanine metabolism, GABA shunt, and glycerol metabolism were verified to be crucial for the resistance to multiple inhibitors. This study provides new insights into the tolerance mechanism against multiple inhibitors, and guides for the improvement of tolerant ethanologenic yeast strains for lignocellulose-bioethanol fermentation.

  10. A key role of microRNA-29b for the suppression of colon cancer cell migration by American ginseng.

    Directory of Open Access Journals (Sweden)

    Deepak Poudyal

    Full Text Available Metastasis of colon cancer cells increases the risk of colon cancer mortality. We have recently shown that American ginseng prevents colon cancer, and a Hexane extract of American Ginseng (HAG has particularly potent anti-inflammatory and anti-cancer properties. Dysregulated microRNA (miR expression has been observed in several disease conditions including colon cancer. Using global miR expression profiling, we observed increased miR-29b in colon cancer cells following exposure to HAG. Since miR-29b plays a role in regulating the migration of cancer cells, we hypothesized that HAG induces miR-29b expression to target matrix metalloproteinase-2 (MMP-2 thereby suppressing the migration of colon cancer cells. Results are consistent with this hypothesis. Our study supports the understanding that targeting MMP-2 by miR-29b is a mechanism by which HAG suppresses the migration of colon cancer cells.

  11. Sucrose in Cyanobacteria: From a Salt-Response Molecule to Play a Key Role in Nitrogen Fixation

    Directory of Open Access Journals (Sweden)

    María A. Kolman

    2015-01-01

    Full Text Available In the biosphere, sucrose is mainly synthesized in oxygenic photosynthetic organisms, such as cyanobacteria, green algae and land plants, as part of the carbon dioxide assimilation pathway. Even though its central position in the functional biology of plants is well documented, much less is known about the role of sucrose in cyanobacteria. In those prokaryotes, sucrose accumulation has been associated with salt acclimation, and considered as a compatible solute in low-salt tolerant strains. In the last years, functional characterizations of sucrose metabolizing enzymes, metabolic control analysis, cellular localization of gene expressions, and reverse genetic experiments have revealed that sucrose metabolism is crucial in the diazotrophic growth of heterocystic strains, and besides, that it can be connected to glycogen synthesis. This article briefly summarizes the current state of knowledge of sucrose physiological functions in modern cyanobacteria and how they might have evolved taking into account the phylogenetic analyses of sucrose enzymes.

  12. Glycogen metabolism has a key role in the cancer microenvironment and provides new targets for cancer therapy.

    Science.gov (United States)

    Zois, Christos E; Harris, Adrian L

    2016-02-01

    Metabolic reprogramming is a hallmark of cancer cells and contributes to their adaption within the tumour microenvironment and resistance to anticancer therapies. Recently, glycogen metabolism has become a recognised feature of cancer cells since it is upregulated in many tumour types, suggesting that it is an important aspect of cancer cell pathophysiology. Here, we provide an overview of glycogen metabolism and its regulation, with a focus on its role in metabolic reprogramming of cancer cells under stress conditions such as hypoxia, glucose deprivation and anticancer treatment. The various methods to detect glycogen in tumours in vivo as well as pharmacological modulators of glycogen metabolism are also reviewed. Finally, we discuss the therapeutic value of targeting glycogen metabolism as a strategy for combinational approaches in cancer treatment.

  13. The TvLEGU-1, a Legumain-Like Cysteine Proteinase, Plays a Key Role in Trichomonas vaginalis Cytoadherence

    Directory of Open Access Journals (Sweden)

    Francisco Javier Rendón-Gandarilla

    2013-01-01

    Full Text Available The goal of this paper was to characterize a Trichomonas vaginalis cysteine proteinase (CP legumain-1 (TvLEGU-1 and determine its potential role as a virulence factor during T. vaginalis infection. A 30-kDa band, which migrates in three protein spots (pI~6.3, ~6.5, and ~6.7 with a different type and level of phosphorylation, was identified as TvLEGU-1 by one- and two-dimensional Western blot (WB assays, using a protease-rich trichomonad extract and polyclonal antibodies produced against the recombinant TvLEGU-1 (anti-TvLEGU-1r. Its identification was confirmed by mass spectrometry. Immunofluorescence, cell binding, and WB assays showed that TvLEGU-1 is upregulated by iron at the protein level, localized on the trichomonad surface and in lysosomes and Golgi complex, bound to the surface of HeLa cells, and was found in vaginal secretions. Additionally, the IgG and Fab fractions of the anti-TvLEGU-1r antibody inhibited trichomonal cytoadherence up to 45%. Moreover, the Aza-Peptidyl Michael Acceptor that inhibited legumain proteolytic activity in live parasites also reduced levels of trichomonal cytoadherence up to 80%. In conclusion, our data show that the proteolytic activity of TvLEGU-1 is necessary for trichomonal adherence. Thus, TvLEGU-1 is a novel virulence factor upregulated by iron. This is the first report that a legumain-like CP plays a role in a pathogen cytoadherence.

  14. IgG receptor FcγRIIB plays a key role in obesity-induced hypertension.

    Science.gov (United States)

    Sundgren, Nathan C; Vongpatanasin, Wanpen; Boggan, Brigid-Meghan D; Tanigaki, Keiji; Yuhanna, Ivan S; Chambliss, Ken L; Mineo, Chieko; Shaul, Philip W

    2015-02-01

    There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fcγ receptor IIB (FcγRIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that FcγRIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that FcγRIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas FcγRIIB(+/+) mice developed obesity-induced hypertension, FcγRIIB(-/-) mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; FcγRIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet-fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an FcγRIIB-dependent process. Thus, we have identified a novel role for FcγRIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting FcγRIIB may potentially offer new means to treat hypertension in obese individuals. © 2014 American Heart Association, Inc.

  15. A molecular key for building hyphae aggregates: the role of the newly identified Streptomyces protein HyaS.

    Science.gov (United States)

    Koebsch, Ilona; Overbeck, Jens; Piepmeyer, Sophie; Meschke, Holger; Schrempf, Hildgund

    2009-05-01

    Streptomycetes produce many metabolites with medical and biotechnological applications. During fermentations, their hyphae build aggregates, a process in which the newly identified protein HyaS plays an important role. The corresponding hyaS gene is present within all investigated Streptomyces species. Reporter fusions indicate that transcription of hyaS occurs within substrate hyphae of the Streptomyces lividans wild type (WT). The HyaS protein is dominantly associated with the substrate hyphae. The WT strain forms cylindrically shaped clumps of densely packed substrate hyphae, often fusing to higher aggregates (pellets), which remain stably associated during shaking. Investigations by electron microscopy suggest that HyaS induces tight fusion-like contacts among substrate hyphae. In contrast, the pellets of the designed hyaS disruption mutant ΔH are irregular in shape, contain frequently outgrowing bunches of hyphae, and fuse less frequently. ΔH complemented with a plasmid carrying hyaS resembles the WT phenotype. Biochemical studies indicate that the C-terminal region of HyaS has amine oxidase activity. Investigations of ΔH transformants, each carrying a specifically mutated gene, lead to the conclusion that the in situ oxidase activity correlates with the pellet-inducing role of HyaS, and depends on the presence of certain histidine residues. Furthermore, the level of undecylprodigiosin, a red pigment with antibiotic activity, is influenced by the engineered hyaS subtype within a strain. These data present the first molecular basis for future manipulation of pellets, and concomitant production of secondary metabolites during biotechnological processes. © 2009 The Authors. Journal compilation © 2009 Society for Applied Microbiology and Blackwell Publishing Ltd.

  16. IgG Receptor FcγRIIB Plays a Key Role in Obesity-Induced Hypertension

    Science.gov (United States)

    Sundgren, Nathan C.; Vongpatanasin, Wanpen; Boggan, Brigid-Meghan D.; Tanigaki, Keiji; Yuhanna, Ivan S.; Chambliss, Ken L.; Mineo, Chieko; Shaul, Philip W.

    2015-01-01

    There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fcγ receptor IIB (FcγRIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that FcγRIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that FcγRIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas FcγRIIB+/+ mice developed obesity-induced hypertension, FcγRIIB−/− mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; FcγRIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet–fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an FcγRIIB-dependent process. Thus, we have identified a novel role for FcγRIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting FcγRIIB may potentially offer new means to treat hypertension in obese individuals. PMID:25368023

  17. Systematic Analysis of White Pox Disease in Acropora palmata of the Florida Keys and Role of Serratia marcescens.

    Science.gov (United States)

    Joyner, Jessica L; Sutherland, Kathryn P; Kemp, Dustin W; Berry, Brett; Griffin, Ashton; Porter, James W; Amador, Molly H B; Noren, Hunter K G; Lipp, Erin K

    2015-07-01

    White pox disease (WPD) affects the threatened elkhorn coral, Acropora palmata. Owing in part to the lack of a rapid and simple diagnostic test, there have been few systematic assessments of the prevalence of acroporid serratiosis (caused specifically by Serratia marcescens) versus general WPD signs. Six reefs in the Florida Keys were surveyed between 2011 and 2013 to determine the disease status of A. palmata and the prevalence of S. marcescens. WPD was noted at four of the six reefs, with WPD lesions found on 8 to 40% of the colonies surveyed. S. marcescens was detected in 26.9% (7/26) of the WPD lesions and in mucus from apparently healthy colonies both during and outside of disease events (9%; 18/201). S. marcescens was detected with greater frequency in A. palmata than in the overlying water column, regardless of disease status (P = 0.0177). S. marcescens could not be cultured from A. palmata but was isolated from healthy colonies of other coral species and was identified as pathogenic pulsed-field gel electrophoresis type PDR60. WPD lesions were frequently observed on the reef, but unlike in prior outbreaks, no whole-colony death was observed. Pathogenic S. marcescens was circulating on the reef but did not appear to be the primary pathogen in these recent WPD episodes, suggesting that other pathogens or stressors may contribute to signs of WPD. Results highlight the critical importance of diagnostics in coral disease investigations, especially given that field manifestation of disease may be similar, regardless of the etiological agent. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Radical change of Zn speciation in pig slurry amended soil: Key role of nano-sized sulfide particles.

    Science.gov (United States)

    Formentini, Thiago Augusto; Legros, Samuel; Fernandes, Cristovão Vicente Scapulatempo; Pinheiro, Adilson; Le Bars, Maureen; Levard, Clément; Mallmann, Fábio Joel Kochem; da Veiga, Milton; Doelsch, Emmanuel

    2017-03-01

    Spreading livestock manure as fertilizer on farmlands is a widespread practice. It represents the major source of heavy metal(loid)s (HM) input in agricultural soils. Since zinc (Zn) is present at high concentrations in manure, it poses special environmental concerns related to phytotoxicity, groundwater contamination, and introduction in the food chain. Therefore, investigations on the fate and behavior of manure-borne Zn, when it enters the soil environment, are necessary to predict the environmental effects. Nevertheless, long-term field studies assessing Zn speciation in the organic waste matrix, as well as within the soil after manure application, are lacking. This study was designed to fill this gap. Using SEM-EDS and XAS analysis, we reported the following new results: (i) ZnS made up 100% of the Zn speciation in the pig slurry (the highest proportion of ZnS ever observed in organic waste); and (ii) ZnS aggregates were about 1-μm diameter (the smallest particle size ever reported in pig slurry). Moreover, the pig slurry containing ZnS was spread on the soil over an 11-year period, totaling 22 applications, and the resulting Zn speciation within the amended soil was analyzed. Surprisingly, ZnS, i.e. the only species responsible for a nearly 2-fold increase in the Zn concentration within the amended soil, was not detected in this soil. Based on SEM-EDS and XAS observations, we put forward the hypothesis that Zn in the pig slurry consisted of nano-sized ZnS crystallites that further aggregated. The low stability of ZnS nanoparticles within oxic and complex environments such as the studied soil was the key explanation for the radical change in pig slurry-borne Zn speciation after long-term amendments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti

    2011-01-01

    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that g...

  20. The role of microcredit in reducing women's vulnerabilities to multiple disasters.

    Science.gov (United States)

    Ray-Bennett, Nibedita S

    2010-01-01

    This article explores the relationship between microcredit and vulnerability reduction for women-headed households in'multiple disasters'. Here multiple disasters are understood as disasters that occur in one specific place and cause severe devastation. The case study covers the super-cyclone in 1999, floods in 2001 and 2003, and drought in 2002 in Orissa, India. The study entailed eight months fieldwork and interviews with several governmental and non-governmental officials and 12 women-headed households from different social castes. The findings suggest that microcredit is a useful tool to replace women's livelihood assets that have been lost in multiple disasters. But inefficient microcredit delivery can cause microdebts and exacerbate caste, class and gender inequalities. It is posited that microcredit delivery cannot achieve vulnerability reduction for women in multiple disasters unless it is complemented by effective financial services, integrated policy planning and disaster management between government, non-governmental organisations and the community.

  1. The role of the general practitioner in the Australian approach to HIV care: interviews with 'key informants' from government, non-government and professional organisations.

    Science.gov (United States)

    Newman, Christy E; de Wit, John B F; Kippax, Susan C; Reynolds, Robert H; Canavan, Peter G; Kidd, Michael R

    2012-03-01

    HIV care is provided in a range of settings in Australia, but advances in HIV treatment and demographic and geographic changes in the affected population and general practitioner (GP) workforce are testing the sustainability of the special role for GPs. This paper explores how a group of 'key informants' described the role of the GP in the Australian approach to HIV care, and conceptualised the challenges currently inspiring debate around future models of care. A thematic analysis was conducted of semistructured interviews carried out in 2010 with 24 professionals holding senior roles in government, non-government and professional organisations that influence Australian HIV care policy. The strengths of the role of the GP were described as their community setting, collaborative partnership with other medical and health professions, and focus on patient needs. A number of associated challenges were also identified including the different needs of GPs with high and low HIV caseloads, the changing expectations of professional roles in general practice, and barriers to service accessibility for people living with HIV. While there are many advantages to delivering HIV services in primary care, GPs need flexible models of training and accreditation, support in strengthening relationships with other health and medical professionals, and assistance in achieving service accessibility. Consideration of how to support the GP workforce so that care can be made available in the broadest range of geographical and service settings is also critical if systems of HIV care delivery are to be realistic and cost-effective and meet consumer needs.

  2. Old Yellow Enzyme from Trypanosoma cruzi Exhibits In Vivo Prostaglandin F2α Synthase Activity and Has a Key Role in Parasite Infection and Drug Susceptibility

    Directory of Open Access Journals (Sweden)

    Florencia Díaz-Viraqué

    2018-03-01

    Full Text Available The discovery that trypanosomatids, unicellular organisms of the order Kinetoplastida, are capable of synthesizing prostaglandins raised questions about the role of these molecules during parasitic infections. Multiple studies indicate that prostaglandins could be related to the infection processes and pathogenesis in trypanosomatids. This work aimed to unveil the role of the prostaglandin F2α synthase TcOYE in the establishment of Trypanosoma cruzi infection, the causative agent of Chagas disease. This chronic disease affects several million people in Latin America causing high morbidity and mortality. Here, we propose a prokaryotic evolutionary origin for TcOYE, and then we used in vitro and in vivo experiments to show that T. cruzi prostaglandin F2α synthase plays an important role in modulating the infection process. TcOYE overexpressing parasites were less able to complete the infective cycle in cell culture infections and increased cardiac tissue parasitic load in infected mice. Additionally, parasites overexpressing the enzyme increased PGF2α synthesis from arachidonic acid. Finally, an increase in benznidazole and nifurtimox susceptibility in TcOYE overexpressing parasites showed its participation in activating the currently anti-chagasic drugs, which added to its observed ability to confer resistance to hydrogen peroxide, highlights the relevance of this enzyme in multiple events including host–parasite interaction.

  3. Elder Care, Multiple Role Involvement, and Well-Being Among Middle-Aged Men and Women in Japan.

    Science.gov (United States)

    Kikuzawa, Saeko

    2015-12-01

    Japan's population is aging at an unprecedented rate. Combined with the tradition of family responsibility for elder care, this rapid population aging has resulted in middle-aged Japanese people being much more likely today than in past decades to face the responsibility of caring for their elderly parents alongside their other major roles. Using nationally representative Japanese data, this study assessed the individual and combined implications of caregiving and other role involvements for the well-being of middle-aged men and women. Some evidence was found for deleterious psychological consequences of the caregiver role. However, in contrast to expectations, the interaction between the roles of caregiver and worker was positively associated with well-being among both men and women. The results suggest the importance of middle-aged adults being able to keep working when they have to care for their aging parents. Another important finding was significant gender differences in the psychological consequences of holding multiple family- and work-related roles and in combining these with the caregiver role. Further analysis showed that the spousal role was also negatively associated with depressive symptoms and positively associated with satisfaction for men but not for women. Gender differences in the findings appear to reflect the significant gender asymmetry in role experiences in Japan.

  4. Elevated risk of type 2 diabetes for development of Alzheimer disease: a key role for oxidative stress in brain.

    Science.gov (United States)

    Butterfield, D Allan; Di Domenico, Fabio; Barone, Eugenio

    2014-09-01

    Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological data show that the incidence of AD increases with age and doubles every 5 years after 65 years of age. From a neuropathological point of view, amyloid-β-peptide (Aβ) leads to senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of AD. Aβ is associated with the formation of reactive oxygen (ROS) and nitrogen (RNS) species, and induces calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions associated with learning and memory. Oxidative stress was found to be associated with type 2 diabetes mellitus (T2DM), which (i) represents another prevalent disease associated with obesity and often aging, and (ii) is considered to be a risk factor for AD development. T2DM is characterized by high blood glucose levels resulting from increased hepatic glucose production, impaired insulin production and peripheral insulin resistance, which close resemble to the brain insulin resistance observed in AD patients. Furthermore, growing evidence suggests that oxidative stress plays a pivotal role in the development of insulin resistance and vice versa. This review article provides molecular aspects and the pharmacological approaches from both preclinical and clinical data interpreted from the point of view of oxidative stress with the aim of highlighting progresses in this field. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Alternative splicing: the pledge, the turn, and the prestige : The key role of alternative splicing in human biological systems.

    Science.gov (United States)

    Gallego-Paez, L M; Bordone, M C; Leote, A C; Saraiva-Agostinho, N; Ascensão-Ferreira, M; Barbosa-Morais, N L

    2017-09-01

    Alternative pre-mRNA splicing is a tightly controlled process conducted by the spliceosome, with the assistance of several regulators, resulting in the expression of different transcript isoforms from the same gene and increasing both transcriptome and proteome complexity. The differences between alternative isoforms may be subtle but enough to change the function or localization of the translated proteins. A fine control of the isoform balance is, therefore, needed throughout developmental stages and adult tissues or physiological conditions and it does not come as a surprise that several diseases are caused by its deregulation. In this review, we aim to bring the splicing machinery on stage and raise the curtain on its mechanisms and regulation throughout several systems and tissues of the human body, from neurodevelopment to the interactions with the human microbiome. We discuss, on one hand, the essential role of alternative splicing in assuring tissue function, diversity, and swiftness of response in these systems or tissues, and on the other hand, what goes wrong when its regulatory mechanisms fail. We also focus on the possibilities that splicing modulation therapies open for the future of personalized medicine, along with the leading techniques in this field. The final act of the spliceosome, however, is yet to be fully revealed, as more knowledge is needed regarding the complex regulatory network that coordinates alternative splicing and how its dysfunction leads to disease.

  6. The maternal nucleolus plays a key role in centromere satellite maintenance during the oocyte to embryo transition.

    Science.gov (United States)

    Fulka, Helena; Langerova, Alena

    2014-04-01

    The oocyte (maternal) nucleolus is essential for early embryonic development and embryos originating from enucleolated oocytes arrest at the 2-cell stage. The reason for this is unclear. Surprisingly, RNA polymerase I activity in nucleolus-less mouse embryos, as manifested by pre-rRNA synthesis, and pre-rRNA processing are not affected, indicating an unusual role of the nucleolus. We report here that the maternal nucleolus is indispensable for the regulation of major and minor satellite repeats soon after fertilisation. During the first embryonic cell cycle, absence of the nucleolus causes a significant reduction in major and minor satellite DNA by 12% and 18%, respectively. The expression of satellite transcripts is also affected, being reduced by more than half. Moreover, extensive chromosome bridging of the major and minor satellite sequences was observed during the first mitosis. Finally, we show that the absence of the maternal nucleolus alters S-phase dynamics and causes abnormal deposition of the H3.3 histone chaperone DAXX in pronuclei of nucleolus-less zygotes.

  7. The Preferential Infection of Astrocytes by Enterovirus 71 Plays a Key Role in the Viral Neurogenic Pathogenesis.

    Science.gov (United States)

    Feng, Min; Guo, Sujie; Fan, Shengtao; Zeng, Xiaofeng; Zhang, Ying; Liao, Yun; Wang, Jianbin; Zhao, Ting; Wang, Lichun; Che, Yanchun; Wang, Jingjing; Ma, Na; Liu, Longding; Yue, Lei; Li, Qihan

    2016-01-01

    The pathological manifestations of fatal cases of human hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) are characterized by inflammatory damage to the central nervous system (CNS). Here, the dynamic distribution of EV71 in the CNS and the subsequent pathological characteristics within different regions of neonatal rhesus macaque brain tissue were studied using a chimeric EV71 expressing green fluorescence protein. The results were compared with brain tissue obtained from the autopsies of deceased EV71-infected HFMD patients. These observations suggested that the virus was prevalent in areas around the blood vessels and nerve nuclei in the brain stem and showed a preference for astrocytes in the CNS. Interestingly, infected astrocytes within the in vivo and in vitro human and macaque systems exhibited increased expression of excitatory neurotransmitters and cytokines that also stimulated the neuronal secretion of the excitatory neurotransmitters noradrenalin and adrenalin, and this process most likely plays a role in the pathophysiological events that occur during EV71 infection.

  8. Health Behavior Among Men Occupying Multiple Family Roles and the Moderating Effects of Perceived Partner Relationship Quality

    Science.gov (United States)

    DePasquale, Nicole; Polenick, Courtney A.; Hinde, Jesse; Bray, Jeremy W.; Zarit, Steven H.; Moen, Phyllis; Hammer, Leslie B.; Almeida, David M.

    2016-01-01

    Men in the U.S. are increasingly involved in their children’s lives and currently represent 40% of informal caregivers to dependent relatives or friends aged 18 years or older. Yet, much more is known about the health effects of varying family role occupancies for women relative to men. The present research sought to fill this empirical gap by first comparing the health behavior (sleep duration, cigarette smoking, alcohol consumption, exercise, fast food consumption) of men who only occupy partner roles and partnered men who also fill father, informal caregiver, or both father and informal caregiver (i.e., sandwiched) roles. The moderating effects of perceived partner relationship quality, conceptualized here as partner support and strain, on direct family role-health behavior linkages were also examined. Secondary analysis of survey data from 366 cohabiting and married men in the Work, Family and Health Study indicated that men’s multiple family role occupancies were generally not associated with health behavior. With men continuing to take on more family responsibilities, as well as the serious health consequences of unhealthy behavior, the implications of these null effects are encouraging: additional family roles can be integrated into cohabiting and married men’s role repertoires without health behavior risks. Moderation analysis revealed, however, that men’s perceived partner relationship constituted a significant factor in determining whether multiple family role occupancies had positive or negative consequences for their sleep duration, alcohol consumption, and fast food consumption. These findings are discussed in terms of their empirical and practical implications for partnered men and their families. PMID:27449994

  9. Gratitude and Adolescents' Subjective Well-Being in School: The Multiple Mediating Roles of Basic Psychological Needs Satisfaction at School.

    Science.gov (United States)

    Tian, Lili; Pi, Luyang; Huebner, E S; Du, Minmin

    2016-01-01

    Based on the relation between gratitude and general subjective well-being (SWB), and Basic Psychological Needs Theory (Ryan and Deci, 2000), the present study's aim was to use structural equation modeling to test the multiple mediational roles of the satisfaction of three basic psychological needs at school in accounting for the association between gratitude and SWB in school (school satisfaction, school affect) in adolescents. A total of 881 Chinese adolescents (427 males; Mean age = 12.97) completed a multi-measure questionnaire that tapped the targeted variables. Findings revealed that gratitude related significantly, positively to adolescents' SWB in school. Moreover, a multiple-mediators analysis suggested that relatedness and competence needs satisfaction at school mediated the relation between gratitude and SWB in school. Lastly, a multiple-mediators analysis also indicated that autonomy needs satisfaction mediated the relation between relatedness and competence needs and SWB in school. Limitations and practical applications of the study were discussed.

  10. Gratitude and Adolescents’ Subjective Well-Being in School: The Multiple Mediating Roles of Basic Psychological Needs Satisfaction at School

    Science.gov (United States)

    Tian, Lili; Pi, Luyang; Huebner, E. S.; Du, Minmin

    2016-01-01

    Based on the relation between gratitude and general subjective well-being (SWB), and Basic Psychological Needs Theory (Ryan and Deci, 2000), the present study’s aim was to use structural equation modeling to test the multiple mediational roles of the satisfaction of three basic psychological needs at school in accounting for the association between gratitude and SWB in school (school satisfaction, school affect) in adolescents. A total of 881 Chinese adolescents (427 males; Mean age = 12.97) completed a multi-measure questionnaire that tapped the targeted variables. Findings revealed that gratitude related significantly, positively to adolescents’ SWB in school. Moreover, a multiple-mediators analysis suggested that relatedness and competence needs satisfaction at school mediated the relation between gratitude and SWB in school. Lastly, a multiple-mediators analysis also indicated that autonomy needs satisfaction mediated the relation between relatedness and competence needs and SWB in school. Limitations and practical applications of the study were discussed. PMID:27708601

  11. Photoreduction of Hg(II) and photodemethylation of methylmercury: the key role of thiol sites on dissolved organic matter

    Science.gov (United States)

    Jeremiason, Jeffrey D.; Portner, Joshua C.; Aiken, George R.; Hiranaka, Amber J.; Dvorak, Michelle T.; Tran, Khuyen T.; Latch, Douglas E.

    2015-01-01

    This study examined the kinetics of photoreduction of Hg(II) and photodemethylation of methylmercury (MeHg+) attached to, or in the presence of, dissolved organic matter (DOM). Both Hg(II) and MeHg+ are principally bound to reduced sulfur groups associated with DOM in many freshwater systems. We propose that a direct photolysis mechanism is plausible for reduction of Hg(II) bound to reduced sulfur groups on DOM while an indirect mechanism is supported for photodemethylation of MeHg+ bound to DOM. UV spectra of Hg(II) and MeHg+ bound to thiol containing molecules demonstrate that the Hg(II)–S bond is capable of absorbing UV-light in the solar spectrum to a much greater extent than MeHg+–S bonds. Experiments with chemically distinct DOM isolates suggest that concentration of DOM matters little in the photochemistry if there are enough reduced S sites present to strongly bind MeHg+ and Hg(II); DOM concentration does not play a prominent role in photodemethylation other than to screen light, which was demonstrated in a field experiment in the highly colored St. Louis River where photodemethylation was not observed at depths ≥10 cm. Experiments with thiol ligands yielded slower photodegradation rates for MeHg+ than in experiments with DOM and thiols; rates in the presence of DOM alone were the fastest supporting an intra-DOM mechanism. Hg(II) photoreduction rates, however, were similar in experiments with only DOM, thiols plus DOM, or only thiols suggesting a direct photolysis mechanism. Quenching experiments also support the existence of an intra-DOM photodemethylation mechanism for MeHg+. Utilizing the difference in photodemethylation rates measured for MeHg+ attached to DOM or thiol ligands, the binding constant for MeHg+ attached to thiol groups on DOM was estimated to be 1016.7.

  12. Catalytic Ozonation of Toluene Using Chilean Natural Zeolite: The Key Role of Brønsted and Lewis Acid Sites

    Directory of Open Access Journals (Sweden)

    Serguei Alejandro-Martín

    2018-05-01

    Full Text Available The influence of surface physical-chemical characteristics of Chilean natural zeolite on the catalytic ozonation of toluene is presented in this article. Surface characteristics of natural zeolite were modified by acid treatment with hydrochloric acid and ion-exchange with ammonium sulphate. Prior to catalytic ozonation assays, natural and chemically modified zeolite samples were thermally treated at 623 and 823 K in order to enhance Brønsted and Lewis acid sites formation, respectively. Natural and modified zeolite samples were characterised by N2 adsorption at 77 K, elemental analysis, X-ray fluorescence, and Fourier transform infrared (FTIR spectroscopy, using pyridine as a probe molecule. The highest values of the reaction rate of toluene oxidation were observed when NH4Z1 and 2NH4Z1 zeolite samples were used. Those samples registered the highest density values of Lewis acid sites compared to other samples used here. Results indicate that the presence of strong Lewis acid sites at the 2NH4Z1 zeolite surface causes an increase in the reaction rate of toluene oxidation, confirming the role of Lewis acid sites during the catalytic ozonation of toluene at room temperature. Lewis acid sites decompose gaseous ozone into atomic oxygen, which reacts with the adsorbed toluene at Brønsted acid sites. On the other hand, no significant contribution of Brønsted acid sites on the reaction rate was registered when NH4Z1 and 2NH4Z1 zeolite samples were used.

  13. Key Role of Alphaproteobacteria and Cyanobacteria in the Formation of Stromatolites of Lake Dziani Dzaha (Mayotte, Western Indian Ocean

    Directory of Open Access Journals (Sweden)

    Emmanuelle Gérard

    2018-05-01

    , respectively. These results point out the role of phototrophic Alphaproteobacteria in the formation of stromatolites, which may open new perspective for the analysis of the fossil record.

  14. The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin plays a key role in adipocyte differentiation.

    Science.gov (United States)

    Chen, Weiqin; Yechoor, Vijay K; Chang, Benny Hung-Junn; Li, Ming V; March, Keith L; Chan, Lawrence

    2009-10-01

    Mutations in the Berardinelli-Seip congenital lipodystrophy 2 gene (BSCL2) are the underlying defect in patients with congenital generalized lipodystrophy type 2. BSCL2 encodes a protein called seipin, whose function is largely unknown. In this study, we investigated the role of Bscl2 in the regulation of adipocyte differentiation. Bscl2 mRNA is highly up-regulated during standard hormone-induced adipogenesis in 3T3-L1 cells in vitro. However, this up-regulation does not occur during mesenchymal stem cell (C3H10T1/2 cells) commitment to the preadipocyte lineage. Knockdown of Bscl2 by short hairpin RNA in C3H10T1/2 cells has no effect on bone morphogenetic protein-4-induced preadipocyte commitment. However, knockdown in 3T3-L1 cells prevents adipogenesis induced by a standard hormone cocktail, but adipogenesis can be rescued by the addition of peroxisome proliferator-activated receptor-gamma agonist pioglitazone at an early stage of differentiation. Interestingly, pioglitazone-induced differentiation in the absence of standard hormone is not associated with up-regulated Bscl2 expression. On the other hand, short hairpin RNA-knockdown of Bscl2 largely blocks pioglitazone-induced adipose differentiation. These experiments suggest that Bscl2 may be essential for normal adipogenesis; it works upstream or at the level of peroxisome proliferator-activated receptor-gamma, enabling the latter to exert its full activity during adipogenesis. Loss of Bscl2 function thus interferes with the normal transcriptional cascade of adipogenesis during fat cell differentiation, resulting in near total loss of fat or lipodystrophy.

  15. Cultural scripts, memories of childhood abuse, and multiple identities: a study of role-played enactments.

    Science.gov (United States)

    Stafford, Jane; Lynn, Steven Jay

    2002-01-01

    This study compared the reports of satanic, sexual, and physical abuse of persons instructed to role-play either dissociative identity disorder (DID) (n = 33), major depression (n = 33), or a college student who experienced minor adjustment problems ("normal") (n = 33) across a number of trials that included role-played hypnosis. As hypothesized, more of the participants who were asked to role-play DID reported at least one instance of satanic ritual abuse and sexual abuse compared with those who role-played depression or a college student with minor adjustment problems. DID role-players reported more incidents of sexual abuse and more severe physical and sexual abuse than did the major depression role-players. Further, the DID role-players differed from the normal role-players on all the measures of frequency and severity of physical and sexual abuse. Participants in all groups reported more frequent and severe incidents of physical abuse after role-played hypnosis than they did prior to it.

  16. Affective disorders and Health-Related Quality of Life (HRQoL) in adolescents and young adults with Multiple Sclerosis (MS): the moderating role of resilience.

    Science.gov (United States)

    Rainone, Nunzia; Chiodi, Alessandro; Lanzillo, Roberta; Magri, Valeria; Napolitano, Anna; Morra, Vincenzo Brescia; Valerio, Paolo; Freda, Maria Francesca

    2017-03-01

    To investigate the moderating role of resilience in the relationship between affective disorders and Health-Related Quality of Life (HRQoL) for adolescents and young adults with multiple sclerosis (MS). A quantitative methodology was adopted. Fifty-three adolescents and young adults were interviewed to assess resilience as a personality trait (Ego-Resiliency Scale) and resilience as an interactive competence (CYRM-28), Health-Related Quality of Life (PedsQL 4.0), depression and anxiety (BDI-II and STAI-Y). Affective disorders, both depression (β = -.38, p moderating role of resilience competence using individual resources on the relationship between the Depression Cognitive Factor and Emotional Functioning. Data show that in step 2 of the regression analysis, we obtained a variation of β = -.45 (p moderating effect of resilience was significant regarding the increase in R 2 (p moderates the relationship between the Depression Cognitive Factor and Emotional Functioning in adolescents with MS. Our study suggests that to improve well-being for adolescents with MS resilience could play a key role.

  17. Language Learning Enhanced by Massive Multiple Online Role-Playing Games (MMORPGs) and the Underlying Behavioral and Neural Mechanisms

    OpenAIRE

    Zhang, Yongjun; Song, Hongwen; Liu, Xiaoming; Tang, Dinghong; Chen, Yue-e; Zhang, Xiaochu

    2017-01-01

    Massive Multiple Online Role-Playing Games (MMORPGs) have increased in popularity among children, juveniles, and adults since MMORPGs’ appearance in this digital age. MMORPGs can be applied to enhancing language learning, which is drawing researchers’ attention from different fields and many studies have validated MMORPGs’ positive effect on language learning. However, there are few studies on the underlying behavioral or neural mechanism of such effect. This paper reviews the educational app...

  18. Adaptation Mechanism of the Aspartate Receptor: Electrostatics of the Adaptation Subdomain Play a Key Role in Modulating Kinase Activity†

    Science.gov (United States)

    Starrett, Diane J.; Falke, Joseph J.

    2010-01-01

    The aspartate receptor of the Escherichia coli and Salmonella typhimurium chemotaxis pathway generates a transmembrane signal that regulates the activity of the cytoplasmic kinase CheA. Previous studies have identified a region of the cytoplasmic domain that is critical to receptor adaptation and kinase regulation. This region, termed the adaptation subdomain, contains a high density of acidic residues, including specific glutamate residues that serve as receptor adaptation sites. However, the mechanism of signal propagation through this region remains poorly understood. This study uses site-directed mutagenesis to neutralize each acidic residue within the subdomain to probe the hypothesis that electrostatics in this region play a significant role in the mechanism of kinase activation and modulation. Each point mutant was tested for its ability to regulate chemotaxis in vivo and kinase activity in vitro. Four point mutants (D273N, E281Q, D288N, and E477Q) were found to superactivate the kinase relative to the wild-type receptor, and all four of these kinase-activating substitutions are located along the same intersubunit interface as the adaptation sites. These activating substitutions retained the wild-type ability of the attractant-occupied receptor to inhibit kinase activity. When combined in a quadruple mutant (D273N/E281Q/D288N/E477Q), the four charge-neutralizing substitutions locked the receptor in a kinase-superactivating state that could not be fully inactivated by the attractant. Similar lock-on character was observed for a charge reversal substitution, D273R. Together, these results implicate the electrostatic interactions at the intersubunit interface as a major player in signal transduction and kinase regulation. The negative charge in this region destabilizes the local structure in a way that enhances conformational dynamics, as detected by disulfide trapping, and this effect is reversed by charge neutralization of the adaptation sites. Finally, two

  19. The Role of Gender on Consumer Attitudes toward Multiple Celebrity Advertisements

    Directory of Open Access Journals (Sweden)

    Işık Özge YUMURTACI

    2013-12-01

    Full Text Available Although its has been widely used in advertising, the impact of multiple celebrity endorsement on consumers has not been known. Therefore, the aim of this study is to examine whether consumers’ attitudes towards advertisement and brand, and their purchase intention differ regarding to the gender of consumers in multiple celebrity endorsement. Hence, survey study was conducted with 256 individuals. The findings of this study indicates that when two celebrities are used in an advertisement, based on the consumers’ attitudes towards the celebrities, the attitudes towards advertisement and brand, and purchase intentions may show discrepancies according to the gender of consumers. This study may shed light on how to use multiple celebrities in companies’ marketing strategies in a more accurate and effective way while considering consumer gender differences

  20. Role-Playing in Science Education: An Effective Strategy for Developing Multiple Perspectives

    Science.gov (United States)

    Howes, Elaine V.; Cruz, Barbara C.

    2009-01-01

    Role-playing can be an engaging and creative strategy to use in the college classroom. Using official accounts, personal narratives, and diaries to recreate a particular time period, event, or personality, the instructional strategy alternately referred to as role-playing, dramatic improvisation, or first-person characterization can be an…

  1. The Role of Metacognitive Strategies in Learning Music: A Multiple Case Study

    Science.gov (United States)

    Colombo, Barbara; Antonietti, Alessandro

    2017-01-01

    The positive role of metacognition in music learning and practice is well assessed, but the role of musicians' metacognitive skills in such a context is not yet clear. Teachers often state that they apply a metacognitive approach during their lessons, but students fail to acknowledge it and report that they become metacognitive learners thanks to…

  2. The Emerging Role of Zinc in the Pathogenesis of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Bo Young Choi

    2017-09-01

    Full Text Available Our lab has previously demonstrated that multiple sclerosis-induced spinal cord white matter damage and motor deficits are mediated by the pathological disruption of zinc homeostasis. Abnormal vesicular zinc release and intracellular zinc accumulation may mediate several steps in the pathophysiological processes of multiple sclerosis (MS, such as matrix metallopeptidase 9 (MMP-9 activation, blood-brain barrier (BBB disruption, and subsequent immune cell infiltration from peripheral systems. Oral administration of a zinc chelator decreased BBB disruption, immune cell infiltration, and spinal white matter myelin destruction. Therefore, we hypothesized that zinc released into the extracellular space during MS progression is involved in destruction of the myelin sheath in spinal cord white mater and in generation of motor deficits. To confirm our previous study, we employed zinc transporter 3 (ZnT3 knockout mice to test whether vesicular zinc depletion shows protective effects on multiple sclerosis-induced white matter damage and motor deficits. ZnT3 gene deletion profoundly reduced the daily clinical score of experimental autoimmune encephalomyelitis (EAE by suppression of inflammation and demyelination in the spinal cord. ZnT3 gene deletion also remarkably inhibited formation of multiple sclerosis-associated aberrant synaptic zinc patches, MMP-9 activation, and BBB disruption. These two studies strongly support our hypothesis that zinc release from presynaptic terminals may be involved in multiple sclerosis pathogenesis. Further studies will no doubt continue to add mechanistic detail to this process and with luck, clarify how these observations may lead to development of novel therapeutic approaches for the treatment of multiple sclerosis.

  3. The Emerging Role of Zinc in the Pathogenesis of Multiple Sclerosis.

    Science.gov (United States)

    Choi, Bo Young; Jung, Jong Won; Suh, Sang Won

    2017-09-28

    Our lab has previously demonstrated that multiple sclerosis-induced spinal cord white matter damage and motor deficits are mediated by the pathological disruption of zinc homeostasis. Abnormal vesicular zinc release and intracellular zinc accumulation may mediate several steps in the pathophysiological processes of multiple sclerosis (MS), such as matrix metallopeptidase 9 (MMP-9) activation, blood-brain barrier (BBB) disruption, and subsequent immune cell infiltration from peripheral systems. Oral administration of a zinc chelator decreased BBB disruption, immune cell infiltration, and spinal white matter myelin destruction. Therefore, we hypothesized that zinc released into the extracellular space during MS progression is involved in destruction of the myelin sheath in spinal cord white mater and in generation of motor deficits. To confirm our previous study, we employed zinc transporter 3 ( ZnT3 ) knockout mice to test whether vesicular zinc depletion shows protective effects on multiple sclerosis-induced white matter damage and motor deficits. ZnT3 gene deletion profoundly reduced the daily clinical score of experimental autoimmune encephalomyelitis (EAE) by suppression of inflammation and demyelination in the spinal cord. ZnT3 gene deletion also remarkably inhibited formation of multiple sclerosis-associated aberrant synaptic zinc patches, MMP-9 activation, and BBB disruption. These two studies strongly support our hypothesis that zinc release from presynaptic terminals may be involved in multiple sclerosis pathogenesis. Further studies will no doubt continue to add mechanistic detail to this process and with luck, clarify how these observations may lead to development of novel therapeutic approaches for the treatment of multiple sclerosis.

  4. Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Qi Xu

    2016-01-01

    Full Text Available Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD. However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, P<0.0001 upregulated ferroportin 1 expression and significantly (P<0.05 decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P<0.05 and DNA fragmentation by 29% (P=0.086 and increased cell viability by 22% (P<0.05. In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P<0.05 and intracellular iron by 28% (P<0.01, indicating the role of hepcidin in oxidative stress. Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1.

  5. The physical and mental health of lesbian, gay male, and bisexual (LGB) older adults: the role of key health indicators and risk and protective factors.

    Science.gov (United States)

    Fredriksen-Goldsen, Karen I; Emlet, Charles A; Kim, Hyun-Jun; Muraco, Anna; Erosheva, Elena A; Goldsen, Jayn; Hoy-Ellis, Charles P

    2013-08-01

    Based on resilience theory, this paper investigates the influence of key health indicators and risk and protective factors on health outcomes (including general health, disability, and depression) among lesbian, gay male, and bisexual (LGB) older adults. A cross-sectional survey was conducted with LGB older adults, aged 50 and older (N = 2,439). Logistic regressions were conducted to examine the contributions of key health indicators (access to health care and health behaviors), risk factors (lifetime victimization, internalized stigma, and sexual identity concealment), and protective factors (social support and social network size) to health outcomes, when controlling for background characteristics. The findings revealed that lifetime victimization, financial barriers to health care, obesity, and limited physical activity independently and significantly accounted for poor general health, disability, and depression among LGB older adults. Internalized stigma was also a significant predictor of disability and depression. Social support and social network size served as protective factors, decreasing the odds of poor general health, disability, and depression. Some distinct differences by gender and sexual orientation were also observed. High levels of poor general health, disability, and depression among LGB older adults are of major concern. These findings highlight the important role of key risk and protective factors, which significantly influences health outcomes among LGB older adults. Tailored interventions must be developed to address the distinct health issues facing this historically disadvantaged population.

  6. Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs

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    David Juan

    2016-02-01

    Full Text Available Summary: Epigenetic communication through histone and cytosine modifications is essential for gene regulation and cell identity. Here, we propose a framework that is based on a chromatin communication model to get insight on the function of epigenetic modifications in ESCs. The epigenetic communication network was inferred from genome-wide location data plus extensive manual annotation. Notably, we found that 5-hydroxymethylcytosine (5hmC is the most-influential hub of this network, connecting DNA demethylation to nucleosome remodeling complexes and to key transcription factors of pluripotency. Moreover, an evolutionary analysis revealed a central role of 5hmC in the co-evolution of chromatin-related proteins. Further analysis of regions where 5hmC co-localizes with specific interactors shows that each interaction points to chromatin remodeling, stemness, differentiation, or metabolism. Our results highlight the importance of cytosine modifications in the epigenetic communication of ESCs. : 5-hydroxymethylcytosine (5hmC plays a key role in the epigenomic communication network of embryonic stem cells. Juan et al. build a communication network based in co-localization of epigenomic data and literature. The analysis of the network and its components reveals that proteins reading and editing 5hmC co-evolve and serve as links between diverse molecular processes.

  7. The Role of Sound in Residential Facilities for People With Profound Intellectual and Multiple Disabilities

    NARCIS (Netherlands)

    van den Bosch, Kirsten A.; Andringa, Tjeerd C.; Baskent, Deniz; Vlaskamp, Carla

    2016-01-01

    Attention to the auditory environment of people with profound intellectual and multiple disabilities (PIMD) is limited, both in research and practice. As there is a dynamic interplay between the quality of the auditory environment and well-being, a study was undertaken to test the validity of the

  8. Resonance properties of tidal channels with multiple retention basisn: role of adjacent sea

    NARCIS (Netherlands)

    Roos, Pieter C.; Schuttelaars, H.M.

    2015-01-01

    We present an idealised model of the tidal response in a main channel with multiple secondary basins, co-oscillating with an adjacent sea. The sea is represented as a semi-infinite strip of finite width, anywhere between the limits of a channel extension (narrow) and a half-plane (wide). The sea

  9. Partial replicas of uv-irradiated bacteriophage T4 genomes and their role in multiplicity reactivation

    International Nuclear Information System (INIS)

    Rayssiguier, C.; Kozinski, A.W.; Doermann, A.H.

    1980-01-01

    A physicochemical study was made of the replication and transmission of uv-irradiated T4 genomes. The data presented in this paper justify the following conclusions. (i) For both low and high multiplicity of infection there was abundant replication from uv-irradiated parental templates. It exceeded by far the efficiency predicted by the hypothesis that a single lethal hit completely prevents replication of the killed phage DNA: i.e., some dead phage particles must replicate parts of their DNA. (ii) Replication of the uv-irradiated DNA was repetitive as shown by density reversal experiments. (iii) Newly synthesized progeny DNA originating from uv-irradiated templates appeared as significantly shorter segments of the genomes than progeny DNA produced from non-uv-irradiated templates. A good correlation existed between the number of uv hits and the number of random cuts that would be needed to reduce replication fragments to the length observed. (iv) The contribution of uv-irradiated parental DNA among progeny phage in multiplicity reactivation was disposed in shorter subunits than was the DNA from unirradiated parental phage. It is important to emphasize that it was mainly in the form of replicative hybrid. These conclusions appear to justify excluding interparental recombination as a prerequisite for multiplicity reactivation. They lead directly to some form of partial replica hypothesis for multiplicity reactivation

  10. Investigating the Role of Multiple Intelligences in Determining Vocabulary Learning Strategies for L2 Learners

    Science.gov (United States)

    Sistani, Mahsa; Hashemian, Mahmood

    2016-01-01

    This study, first, examined whether there was any relationship between Iranian L2 learners' vocabulary learning strategies (VLSs), on the one hand, and their multiple intelligences (MI) types, on the other hand. In so doing, it explored the extent to which MI would predict L2 learners' VLSs. To these ends, 40 L2 learners from Isfahan University of…

  11. Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

    Directory of Open Access Journals (Sweden)

    Michele Mussap

    2014-01-01

    Full Text Available The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function.

  12. Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

    Science.gov (United States)

    Mussap, Michele; Merlini, Giampaolo

    2014-01-01

    The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function. PMID:24877060

  13. The Role of CLEAR Thinking in Learning Science from Multiple-Document Inquiry Tasks

    Science.gov (United States)

    Griffin, Thomas D.; Wiley, Jennifer; Britt, M. Anne; Salas, Carlos R.

    2012-01-01

    The main goal for the current study was to investigate whether individual differences in domain-general thinking dispositions might affect learning from multiple-document inquiry tasks in science. Middle school students were given a set of documents and were tasked with understanding how and why recent patterns in global temperature might be…

  14. Community health workers in rural India: analysing the opportunities and challenges Accredited Social Health Activists (ASHAs) face in realising their multiple roles.

    Science.gov (United States)

    Saprii, Lipekho; Richards, Esther; Kokho, Puni; Theobald, Sally

    2015-12-09

    Globally, there is increasing interest in community health worker's (CHW) performance; however, there are gaps in the evidence with respect to CHWs' role in community participation and empowerment. Accredited Social Health Activists (ASHAs), whose roles include social activism, are the key cadre in India's CHW programme which is designed to improve maternal and child health. In a diverse country like India, there is a need to understand how the ASHA programme operates in different underserved Indian contexts, such as rural Manipur. We undertook qualitative research to explore stakeholders' perceptions and experiences of the ASHA scheme in strengthening maternal health and uncover the opportunities and challenges ASHAs face in realising their multiple roles in rural Manipur, India. Data was collected through in-depth interviews (n = 18) and focus group discussions (n = 3 FGDs, 18 participants). Participants included ASHAs, key stakeholders and community members. They were purposively sampled based on remoteness of villages and primary health centres to capture diverse and relevant constituencies, as we believed experiences of ASHAs can be shaped by remoteness. Data were analysed using the thematic framework approach. Findings suggested that ASHAs are mostly understood as link workers. ASHA's ability to address the immediate needs of rural and marginalised communities meant that they were valued as service providers. The programme is perceived to be beneficial as it improves awareness and behaviour change towards maternal care. However, there are a number of challenges; the selection of ASHAs is influenced by power structures and poor community sensitisation of the ASHA programme presents a major risk to success and sustainability. The primary health centres which ASHAs link to are ill-equipped. Thus, ASHAs experience adverse consequences in their ability to inspire trust and credibility in the community. Small and irregular monetary incentives demotivate

  15. The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor

    Directory of Open Access Journals (Sweden)

    Sunmi Song

    2015-06-01

    Full Text Available The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood.

  16. Pooling Data from Multiple Longitudinal Studies: The Role of Item Response Theory in Integrative Data Analysis

    Science.gov (United States)

    Curran, Patrick J.; Hussong, Andrea M.; Cai, Li; Huang, Wenjing; Chassin, Laurie; Sher, Kenneth J.; Zucker, Robert A.

    2010-01-01

    There are a number of significant challenges encountered when studying development over an extended period of time including subject attrition, changing measurement structures across group and developmental period, and the need to invest substantial time and money. Integrative data analysis is an emerging set of methodologies that overcomes many of the challenges of single sample designs through the pooling of data drawn from multiple existing developmental studies. This approach is characterized by a host of advantages, but this also introduces several new complexities that must be addressed prior to broad adoption by developmental researchers. In this paper we focus on methods for fitting measurement models and creating scale scores using data drawn from multiple longitudinal studies. We present findings from the analysis of repeated measures of internalizing symptomatology that were pooled from three existing developmental studies. We describe and demonstrate each step in the analysis and we conclude with a discussion of potential limitations and directions for future research. PMID:18331129

  17. The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor.

    Science.gov (United States)

    Song, Sunmi; Graham-Engeland, Jennifer E; Corwin, Elizabeth J; Ceballos, Rachel M; Taylor, Shelley E; Seeman, Teresa; Klein, Laura Cousino

    2015-01-01

    The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood.

  18. Quality of Care for Patients with Multiple Chronic Conditions: The Role of Comorbidity Interrelatedness

    OpenAIRE

    Zulman, Donna M.; Asch, Steven M.; Martins, Susana B.; Kerr, Eve A.; Hoffman, Brian B.; Goldstein, Mary K.

    2013-01-01

    Multimorbidity—the presence of multiple chronic conditions in a patient—has a profound impact on health, health care utilization, and associated costs. Definitions of multimorbidity in clinical care and research have evolved over time, initially focusing on a patient’s number of comorbidities and the associated magnitude of required care processes, and later recognizing the potential influence of comorbidity characteristics on patient care and outcomes. In this article, we review the relation...

  19. The role of assessment in enhancing the vocational success of people with multiple sclerosis.

    Science.gov (United States)

    Roessler, R T

    1996-01-01

    The person/environment or ecological perspective on vocational evaluation provides a comprehensive assessment strategy for people with multiple sclerosis. The ecological model requires assessment of both personal variables such as rehabilitation outlook and MS symptoms and environmental variables such as barriers to workplace accessibility and performance of essential job functions. Measures of person and environment constructs are presented as are applications of the resulting information in vocational counseling and disability management services.

  20. Rapid invasion of the Indo-Pacific lionfishes (Pterois volitans and Pterois miles) in the Florida Keys, USA: evidence from multiple pre-and post-invasion data sets

    Science.gov (United States)

    Ruttenberg, Benjamin I.; Schofield, Pamela J.; Akins, J. Lad; Acosta, Alejandro; Feeley, Michael W.; Blondeau, Jeremiah; Smith, Steven G.; Ault, Jerald S.

    2012-01-01

    Over the past decade, Indo-Pacific lionfishes, Pterois volitans (Linnaeus, 1758) and Pterois miles (Bennett, 1828), venomous members of the scorpionfish family (Scorpaenidae), have invaded and spread throughout much of the tropical and subtropical northwestern Atlantic Ocean and Caribbean Sea. These species are generalist predators of fishes and invertebrates with the potential to disrupt the ecology of the invaded range. Lionfishes have been present in low numbers along the east coast of Florida since the 1980s, but were not reported in the Florida Keys until 2009. We document the appearance and rapid spread of lionfishes in the Florida Keys using multiple long-term data sets that include both pre- and post-invasion sampling. Our results are the first to quantify the invasion of lionfishes in a new area using multiple independent, ongoing monitoring data sets, two of which have explicit estimates of sampling effort. Between 2009 and 2011, lionfish frequency of occurrence, abundance, and biomass increased rapidly, increasing three- to six-fold between 2010 and 2011 alone. In addition, individuals were detected on a variety of reef and non-reef habitats throughout the Florida Keys. Because lionfish occurrence, abundance, and impacts are expected to continue to increase throughout the region, monitoring programs like those used in this study will be essential to document ecosystem changes that may result from this invasion.

  1. Abscisic acid (ABA) and key proteins in its perception and signaling pathways are ancient, but their roles have changed through time.

    Science.gov (United States)

    Sussmilch, Frances C; Atallah, Nadia M; Brodribb, Timothy J; Banks, Jo Ann; McAdam, Scott A M

    2017-09-02

    Homologs of the Arabidopsis core abscisic acid (ABA) signaling component OPEN STOMATA1 (OST1) are best known for their role in closing stomata in angiosperm species. We recently characterized a fern OST1 homolog, GAMETOPHYTES ABA INSENSITIVE ON ANTHERDIOGEN 1 (GAIA1), which is not required for stomatal closure in ferns, consistent with physiologic evidence that shows the stomata of these plants respond passively to changes in leaf water status. Instead, gaia1 mutants reveal a critical role in ABA signaling for spore dormancy and sex determination, in a system regulated by antagonism between ABA and the gibberellin (GA)-derived fern hormone antheridiogen (A CE ). ABA and key proteins, including ABA receptors from the PYR/PYL/RCAR family and negative regulators of ABA-signaling from Group A of the type-2C protein phosphatases (PP2Cs), in addition to OST1 homologs, can be found in all terrestrial land plant lineages, ranging from liverworts that lack stomata, to angiosperms. As land plants have evolved and diversified over the past 450 million years, so too have the roles of this important plant hormone and the genes involved in its signaling and perception.

  2. HMGB1 and Histones Play a Significant Role in Inducing Systemic Inflammation and Multiple Organ Dysfunctions in Severe Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Runkuan Yang

    2017-01-01

    Full Text Available Severe acute pancreatitis (SAP starts as a local inflammation of pancreatic tissue that induces the development of multiple extrapancreatic organs dysfunction; however, the underlying mechanisms are still not clear. Ischemia-reperfusion, circulating inflammatory cytokines, and possible bile cytokines significantly contribute to gut mucosal injury and intestinal bacterial translocation (BT during SAP. Circulating HMGB1 level is significantly increased in SAP patients and HMGB1 is an important factor that mediates (at least partly gut BT during SAP. Gut BT plays a critical role in triggering/inducing systemic inflammation/sepsis in critical illness, and profound systemic inflammatory response syndrome (SIRS can lead to multiple organ dysfunction syndrome (MODS during SAP, and systemic inflammation with multiorgan dysfunction is the cause of death in experimental SAP. Therefore, HMGB1 is an important factor that links gut BT and systemic inflammation. Furthermore, HMGB1 significantly contributes to multiple organ injuries. The SAP patients also have significantly increased circulating histones and cell-free DNAs levels, which can reflect the disease severity and contribute to multiple organ injuries in SAP. Hepatic Kupffer cells (KCs are the predominant source of circulating inflammatory cytokines in SAP, and new evidence indicates that hepatocyte is another important source of circulating HMGB1 in SAP; therefore, treating the liver injury is important in SAP.

  3. The Swiss Multiple Sclerosis Cohort-Study (SMSC: A Prospective Swiss Wide Investigation of Key Phases in Disease Evolution and New Treatment Options.

    Directory of Open Access Journals (Sweden)

    Giulio Disanto

    Full Text Available The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs (DMDs in multiple sclerosis (MS are unclear. We aimed at building a prospective cohort of MS patients with standardized collection of demographic, clinical, MRI data and body fluids that can be used to develop prognostic indicators and biomarkers of disease evolution and therapeutic response. The Swiss MS Cohort (SMSC is a prospective observational study performed across seven Swiss MS centers including patients with MS, clinically isolated syndrome (CIS, radiologically isolated syndrome or neuromyelitis optica. Neurological and radiological assessments and biological samples are collected every 6-12 months. We recruited 872 patients (clinically isolated syndrome [CIS] 5.5%, relapsing-remitting MS [RRMS] 85.8%, primary progressive MS [PPMS] 3.5%, secondary progressive MS [SPMS] 5.2% between June 2012 and July 2015. We performed 2,286 visits (median follow-up 398 days and collected 2,274 serum, plasma and blood samples, 152 cerebrospinal fluid samples and 1,276 brain MRI scans. 158 relapses occurred and expanded disability status scale (EDSS scores increased in PPMS, SPMS and RRMS patients experiencing relapses. Most RRMS patients were treated with fingolimod (33.4%, natalizumab (24.5% or injectable DMDs (13.6%. The SMSC will provide relevant information regarding DMDs efficacy and safety and will serve as a comprehensive infrastructure available for nested research projects.

  4. Multiple Role Balance, Job Satisfaction, and Life Satisfaction in Women School Counselors

    Science.gov (United States)

    Bryant, Rhonda M.; Constantine, Madonna G.

    2006-01-01

    Many prior studies have reported that school counselors are at risk for experiencing mental health difficulties (e.g., professional burnout) as a result of their participation in a wide variety of service-oriented roles. The majority of school counselors are women, which underscores the importance of examining these individuals' unique…

  5. Neurodegeneration in ataxia-telangiectasia: Multiple roles of ATM kinase in cellular homeostasis.

    Science.gov (United States)

    Choy, Kay Rui; Watters, Dianne J

    2018-01-01

    Ataxia-telangiectasia (A-T) is characterized by neuronal degeneration, cancer, diabetes, immune deficiency, and increased sensitivity to ionizing radiation. A-T is attributed to the deficiency of the protein kinase coded by the ATM (ataxia-telangiectasia mutated) gene. ATM is a sensor of DNA double-strand breaks (DSBs) and signals to cell cycle checkpoints and the DNA repair machinery. ATM phosphorylates numerous substrates and activates many cell-signaling pathways. There has been considerable debate about whether a defective DNA damage response is causative of the neurological aspects of the disease. In proliferating cells, ATM is localized mainly in the nucleus; however, in postmitotic cells such as neurons, ATM is mostly cytoplasmic. Recent studies reveal an increasing number of roles for ATM in the cytoplasm, including activation by oxidative stress. ATM associates with organelles including mitochondria and peroxisomes, both sources of reactive oxygen species (ROS), which have been implicated in neurodegenerative diseases and aging. ATM is also associated with synaptic vesicles and has a role in regulating cellular homeostasis and autophagy. The cytoplasmic roles of ATM provide a new perspective on the neurodegenerative process in A-T. This review will examine the expanding roles of ATM in cellular homeostasis and relate these functions to the complex A-T phenotype. Developmental Dynamics 247:33-46, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Young Children's Role-Playing for Enhancing Personal Intelligences in Multiple Intelligences Theory

    Science.gov (United States)

    Wee, Su-Jeong; Shin, Hwa-Sik; Kim, Myung-Hee

    2013-01-01

    This article examines young children's role-play in an effort to develop methods with which teachers can enhance children's interpersonal and intrapersonal intelligences. Examining how MI practice is applied in different cultural and social contexts is important because it can provide new insights on enriching and enhancing curricula and…

  7. Multiple roles of the prostaglandin D2 signaling pathway in reproduction.

    Science.gov (United States)

    Rossitto, Moïra; Ujjan, Safdar; Poulat, Francis; Boizet-Bonhoure, Brigitte

    2015-01-01

    Prostaglandins signaling molecules are involved in numerous physiological processes. They are produced by several enzyme-limited reactions upon fatty acids, which are catalyzed by two cyclooxygenases and prostaglandin synthases. In particular, the prostaglandins E2 (PGE2), D2 (PGD2), and F2 (PGF2 α) have been shown to be involved in female reproductive mechanisms. Furthermore, widespread expression of lipocalin- and hematopoietic-PGD2 synthases in the male reproductive tract supports the purported roles of PGD2 in the development of both embryonic and adult testes, sperm maturation, and spermatogenesis. In this review, we summarize the putative roles of PGD2 signaling and the roles of both PGD2 synthases in testicular formation and function. We review the data reporting the involvement of PGD2 signaling in the differentiation of Sertoli and germ cells of the embryonic testis. Furthermore, we discuss the roles of lipocalin-PGD2 synthase in steroidogenesis and spermatogenesis, in terms of lipid molecule transport and PGD2 production. Finally, we discuss the hypothesis that PGD2 signaling may be affected in certain reproductive diseases, such as infertility, cryptorchidism, and testicular cancer. © 2015 Society for Reproduction and Fertility.

  8. Comparison is key.

    Science.gov (United States)

    Stone, Mark H; Stenner, A Jackson

    2014-01-01

    Several concepts from Georg Rasch's last papers are discussed. The key one is comparison because Rasch considered the method of comparison fundamental to science. From the role of comparison stems scientific inference made operational by a properly developed frame of reference producing specific objectivity. The exact specifications Rasch outlined for making comparisons are explicated from quotes, and the role of causality derived from making comparisons is also examined. Understanding causality has implications for what can and cannot be produced via Rasch measurement. His simple examples were instructive, but the implications are far reaching upon first establishing the key role of comparison.

  9. Role of sequential hemi-body irradiation in multiple myeloma: preliminary observations

    International Nuclear Information System (INIS)

    Kumar, H.S.; Chaudhary, R.K.; Kumar, Vanita

    1993-01-01

    Ten patients with multiple myeloma presenting in a highly painful condition were included in the study. They were treated by sequential hemi-body irradiation. A dose of 600 cGy was delivered to the upper hemi-body and 800 c Gy to the lower hemi-body. All patients has appreciable relief from pain. The maximum effect was achieved within 24 to 48 hours of treatment. 9 out of the 10 patients has an improvement in the performance status. All these patients were later subjected to combination chemotherapy. (author). 9 refs., 3 tabs

  10. Return of the pulmonary nodule: the radiologist's key role in implementing the 2015 BTS guidelines on the investigation and management of pulmonary nodules.

    Science.gov (United States)

    Graham, Richard N J; Baldwin, David R; Callister, Matthew E J; Gleeson, Fergus V

    2016-01-01

    The British Thoracic Society has published new comprehensive guidelines for the management of pulmonary nodules. These guidelines are significantly different from those previously published, as they use two malignancy prediction calculators to better characterize the risk of malignancy. There are recommendations for a higher nodule size threshold for follow-up (≥5 mm or ≥80 mm(3)) and a reduction of the follow-up period to 1 year for solid pulmonary nodules; both of these will reduce the number of follow-up CT scans. PET-CT plays a crucial role in characterization also, with an ordinal scale being recommended for reporting. Radiologists will be the key in implementing these guidelines, and routine use of volumetric image-analysis software will be required to manage patients with pulmonary nodules correctly.

  11. Metabolomics: A potential way to know the role of vitamin D on multiple sclerosis.

    Science.gov (United States)

    Luque-Córdoba, Diego; Luque de Castro, María D

    2017-03-20

    The literature about the influence of vitamin D on multiple sclerosis (MS) is very controversial, possibly as a result of the way through which the research on the subject has been conducted. The studies developed so far have been focused exclusively on gene expression: the effect of a given vitamin D metabolite on target receptors. The influence of the vitamin D status (either natural or after supplementation) on MS has been studied by measurement of the 25 monohydroxylated metabolite (also known as circulating form), despite the 1,25 dihydroxylated metabolite is considered the active form. In the light of the multiple metabolic pathways in which both forms of vitamin D (D 2 and D 3 ) are involved, monitoring of the metabolites is crucial to know the activity of the target enzymes as a function of both the state of the MS patient and the clinical treatment applied. The study of metabolomics aspects is here proposed to clarify the present controversy. In "omics" terms, our proposal is to take profit from up-stream information-thus is, from metabolomics to genomics-with a potential subsequent step to systems biology, if required. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. The role of NIGMS P50 sponsored team science in our understanding of multiple organ failure.

    Science.gov (United States)

    Moore, Frederick A; Moore, Ernest E; Billiar, Timothy R; Vodovotz, Yoram; Banerjee, Anirban; Moldawer, Lyle L

    2017-09-01

    The history of the National Institute of General Medical Sciences (NIGMS) Research Centers in Peri-operative Sciences (RCIPS) is the history of clinical, translational, and basic science research into the etiology and treatment of posttraumatic multiple organ failure (MOF). Born out of the activism of trauma and burn surgeons after the Viet Nam War, the P50 trauma research centers have been a nidus of research advances in the field and the training of future academic physician-scientists in the fields of trauma, burns, sepsis, and critical illness. For over 40 years, research conducted under the aegis of this funding program has led to numerous contributions at both the bedside and at the bench. In fact, it has been this requirement for team science with a clinician-scientist working closely with basic scientists from multiple disciplines that has led the RCIPS to its unrivaled success in the field. This review will briefly highlight some of the major accomplishments of the RCIPS program since its inception, how they have both led and evolved as the field moved steadily forward, and how they are responsible for much of our current understanding of the etiology and pathology of MOF. This review is not intended to be all encompassing nor a historical reference. Rather, it serves as recognition to the foresight and support of many past and present individuals at the NIGMS and at academic institutions who have understood the cost of critical illness and MOF to the individual and to society.

  13. The dual role of multiple-transistor charge sharing collection in single-event transients

    International Nuclear Information System (INIS)

    Guo Yang; Chen Jian-Jun; He Yi-Bai; Liang Bin; Liu Bi-Wei

    2013-01-01

    As technologies scale down in size, multiple-transistors being affected by a single ion has become a universal phenomenon, and some new effects are present in single event transients (SETs) due to the charge sharing collection of the adjacent multiple-transistors. In this paper, not only the off-state p-channel metal—oxide semiconductor field-effect transistor (PMOS FET), but also the on-state PMOS is struck by a heavy-ion in the two-transistor inverter chain, due to the charge sharing collection and the electrical interaction. The SET induced by striking the off-state PMOS is efficiently mitigated by the pulse quenching effect, but the SET induced by striking the on-state PMOS becomes dominant. It is indicated in this study that in the advanced technologies, the SET will no longer just be induced by an ion striking the off-state transistor, and the SET sensitive region will no longer just surround the off-state transistor either, as it is in the older technologies. We also discuss this issue in a three-transistor inverter in depth, and the study illustrates that the three-transistor inverter is still a better replacement for spaceborne integrated circuit design in advanced technologies. (condensed matter: structural, mechanical, and thermal properties)

  14. New approaches in the management of spasticity in multiple sclerosis patients: role of cannabinoids

    Directory of Open Access Journals (Sweden)

    Paul F Smith

    2010-02-01

    Full Text Available Paul F SmithDepartment of Pharmacology and Toxicology, School of Medical Sciences, University of Otago, Dunedin, New ZealandAbstract: Cannabinoids such as Cannabis-based medicinal extracts (CBMEs are increasingly being used in the treatment of spasticity associated with multiple sclerosis (MS. They have been shown to have a beneficial effect on spasticity; however, this evidence is largely based on subjective rating scales. Objective measurements using the Ashworth scale have tended to show no significant effect; however, the validity of this scale has been questioned. The available clinical trial data suggest that the adverse side effects associated with using CBMEs are generally mild, such as dry mouth, dizziness, somnolence, nausea and intoxication. However, most of these trials were run over a period of months and it is possible that other adverse side effects could develop with long-term use. There may be reason to be concerned about the use of therapeutic cannabinoids by adolescents, people predisposed to psychosis and pregnant women.Keywords: multiple sclerosis, spasticity, cannabinoids, Cannabis

  15. The role of backward associative strength in false recognition of DRM lists with multiple critical words.

    Science.gov (United States)

    Beato, María S; Arndt, Jason

    2017-08-01

    Memory is a reconstruction of the past and is prone to errors. One of the most widely-used paradigms to examine false memory is the Deese/Roediger-McDermott (DRM) paradigm. In this paradigm, participants studied words associatively related to a non-presented critical word. In a subsequent memory test critical words are often falsely recalled and/or recognized. In the present study, we examined the influence of backward associative strength (BAS) on false recognition using DRM lists with multiple critical words. In forty-eight English DRM lists, we manipulated BAS while controlling forward associative strength (FAS). Lists included four words (e.g., prison, convict, suspect, fugitive) simultaneously associated with two critical words (e.g., CRIMINAL, JAIL). The results indicated that true recognition was similar in high-BAS and low-BAS lists, while false recognition was greater in high-BAS lists than in low-BAS lists. Furthermore, there was a positive correlation between false recognition and the probability of a resonant connection between the studied words and their associates. These findings suggest that BAS and resonant connections influence false recognition, and extend prior research using DRM lists associated with a single critical word to studies of DRM lists associated with multiple critical words.

  16. Human CD134 (OX40) expressed on T cells plays a key role for human herpesvirus 6B replication after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Nagamata, Satoshi; Nagasaka, Miwako; Kawabata, Akiko; Kishimoto, Kenji; Hasegawa, Daiichiro; Kosaka, Yoshiyuki; Mori, Takeshi; Morioka, Ichiro; Nishimura, Noriyuki; Iijima, Kazumoto; Yamada, Hideto; Kawamoto, Shinichiro; Yakushijin, Kimikazu; Matsuoka, Hiroshi; Mori, Yasuko

    2018-05-01

    CD134 (OX40), which is a cellular receptor for human herpesvirus-6B (HHV-6B) and expresses on activated T cells, may play a key role for HHV-6B replication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, we examined the CD134 expression on T cells and HHV-6B replication after allo-HSCT, and analyzed the correlation between them. Twenty-three patients after allo-HSCT were enrolled. The percentages of CD134-positive cells within the CD4 + and CD8 + cell populations were measured by flow cytometry, and the viral copy number of HHV-6B was simultaneously quantified by real-time PCR. The correlation between CD134 and HHV-6B viral load was then statistically analyzed. HHV-6B reactivation occurred in 11 of 23 patients (47.8%). CD134 expression was seen on T cells and was coincident with the time of peak viral load. The percentage of CD134-positive cells decreased significantly when HHV-6B DNA disappeared (p = .005 in CD4 + T cells, p = .02 in CD8 + T cells). In the 4 patients who underwent umbilical cord blood transplantation (UCBT), the viral load varied with the percentage of CD134-positive cells. In the comparison between the HHV-6B reactivation group and non-reactivation group, maximum percentages of CD134-positive cells among CD4 + T cells in reactivation group were significantly higher than those in non-reactivation group (p = .04). This is the first study to show that a correlation of CD134 expression on T cells with HHV-6B replication after allo-HSCT, especially in UCBT. The results possibly indicate that CD134 on T cells plays a key role for HHV-6B replication after allo-HSCT. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Multiple roles of biosurfactants in structural biofilm development by Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Pamp, Sünje Johanna; Tolker-Nielsen, Tim

    2007-01-01

    Recent studies have indicated that biosurfactants produced by Pseudomonas aeruginosa play a role both in maintaining channels between multicellular structures in biofilms and in dispersal of cells from biofilms. Through the use of flow cell technology and enhanced confocal laser scanning microscopy......, we have obtained results which suggest that the biosurfactants produced by P. aeruginosa play additional roles in structural biofilm development. We present genetic evidence that during biofilm development by P. aeruginosa, biosurfactants promote microcolony formation in the initial phase...... and facilitate migration-dependent structural development in the later phase. P. aeruginosa rhl4 mutants, deficient in synthesis of biosurfactants, were not capable of forming microcolonies in the initial phase of biofilm formation. Experiments involving two-color-coded mixed-strain biofilms showed that P...

  18. Facebook Role Play Addiction - A Comorbidity with Multiple Compulsive-Impulsive Spectrum Disorders.

    Science.gov (United States)

    Nathan, Deeepa; Shukla, Lekhansh; Kandasamy, Arun; Benegal, Vivek

    2016-06-01

    Background Problematic Internet use (PIU) is an emerging entity with varied contents. Behavioral addictions have high comorbidity of attention deficit hyperactivity disorder and obsessive-compulsive spectrum disorders. Social networking site (SNS) addiction and role playing game (RPG) addiction are traditionally studied as separate entities. We present a case with excessive Internet use, with a particular focus on phenomenology and psychiatric comorbidities. Case presentation Fifteen-year-old girl with childhood onset attention deficit disorder, obsessive-compulsive disorder, adolescent onset trichotillomania, and disturbed family environment presented with excessive Facebook use. Main online activity was creating profiles in names of mainstream fictional characters and assuming their identity (background, linguistic attributes, etc.). This was a group activity with significant socialization in the virtual world. Craving, salience, withdrawal, mood modification, and conflict were clearly elucidated and significant social and occupational dysfunction was evident. Discussion This case highlights various vulnerability and sociofamilial factors contributing to behavioral addiction. It also highlights the presence of untreated comorbidities in such cases. The difference from contemporary RPGs and uniqueness of role playing on SNS is discussed. SNS role playing as a separate genre of PIU and its potential to reach epidemic proportions are discussed. Conclusions Individuals with temperamental vulnerability are likely to develop behavioral addictions. Identification and management of comorbid conditions are important. The content of PIU continues to evolve and needs further study.

  19. Electrophysiology and Beyond: Multiple roles of Na+ channel β subunits in development and disease

    Science.gov (United States)

    Patino, Gustavo A.; Isom, Lori L.

    2010-01-01

    Voltage-gated Na+ channel (VGSC) β subunits are not “auxiliary.” These multifunctional molecules not only modulate Na+ current (INa), but also function as cell adhesion molecules (CAMs) – playing roles in aggregation, migration, invasion, neurite outgrowth, and axonal fasciculation. β subunits are integral members of VGSC signaling complexes at nodes of Ranvier, axon initial segments, and cardiac intercalated disks, regulating action potential propagation through critical intermolecular and cell-cell communication events. At least in vitro, many β subunit cell adhesive functions occur both in the presence and absence of pore-forming VGSC α subunits, and in vivo β subunits are expressed in excitable as well as non-excitable cells, thus β subunits may play important functional roles on their own, in the absence of α subunits. VGSC β1 subunits are essential for life and appear to be especially important during brain development. Mutations in β subunit genes result in a variety of human neurological and cardiovascular diseases. Moreover, some cancer cells exhibit alterations in β subunit expression during metastasis. In short, these proteins, originally thought of as merely accessory to α subunits, are critical players in their own right in human health and disease. Here we discuss the role of VGSC β subunits in the nervous system. PMID:20600605

  20. Facebook Role Play Addiction – A Comorbidity with Multiple Compulsive–Impulsive Spectrum Disorders

    Science.gov (United States)

    Nathan, Deeepa; Shukla, Lekhansh; Kandasamy, Arun; Benegal, Vivek

    2016-01-01

    Background Problematic Internet use (PIU) is an emerging entity with varied contents. Behavioral addictions have high comorbidity of attention deficit hyperactivity disorder and obsessive–compulsive spectrum disorders. Social networking site (SNS) addiction and role playing game (RPG) addiction are traditionally studied as separate entities. We present a case with excessive Internet use, with a particular focus on phenomenology and psychiatric comorbidities. Case presentation Fifteen-year-old girl with childhood onset attention deficit disorder, obsessive–compulsive disorder, adolescent onset trichotillomania, and disturbed family environment presented with excessive Facebook use. Main online activity was creating profiles in names of mainstream fictional characters and assuming their identity (background, linguistic attributes, etc.). This was a group activity with significant socialization in the virtual world. Craving, salience, withdrawal, mood modification, and conflict were clearly elucidated and significant social and occupational dysfunction was evident. Discussion This case highlights various vulnerability and sociofamilial factors contributing to behavioral addiction. It also highlights the presence of untreated comorbidities in such cases. The difference from contemporary RPGs and uniqueness of role playing on SNS is discussed. SNS role playing as a separate genre of PIU and its potential to reach epidemic proportions are discussed. Conclusions Individuals with temperamental vulnerability are likely to develop behavioral addictions. Identification and management of comorbid conditions are important. The content of PIU continues to evolve and needs further study. PMID:27156380

  1. B cell follicle-like structures in multiple sclerosis-with focus on the role of B cell activating factor

    DEFF Research Database (Denmark)

    Morten, Haugen; Frederiksen, Jette L; Vinter, Matilda Degn

    2014-01-01

    B lymphocytes play an important role in the pathogenesis of multiple sclerosis (MS). Follicle-like structures (FLS) have recently been found in the subarachnoid space in the leptomeninges in some patients with secondary progressive MS (SPMS). They contain proliferating B lymphocytes, plasma cells......, helper T lymphocytes and a network of follicular dendritic cells. FLS have been shown to correlate with increased cortical demyelination, neuronal loss, meningeal infiltration and central nervous system inflammation, as well as lower age at disease onset and progression to severe disability and death....... In this review, we will discuss the role of FLS in MS pathogenesis and disease course and the possible influence by B cell activating factor (BAFF) and C-X-C motif chemokine 13 (CXCL13)....

  2. Role of socio-economic and reproductive factors in the risk of multiple sclerosis

    DEFF Research Database (Denmark)

    Magyari, Melinda

    2015-01-01

    rapid to be explained by gene alterations. We investigated the effect of numerous biological social physical and chemical environmental exposures in different periods of life. These data were available from population-based registries and were used in a case-control approach. This study database...... children reduced the risk of multiple sclerosis (MS) in women but not in men. Childbirths reduced the risk of MS by about 46% during the following 5 years. Even pregnancies terminated early had a protective effect on the risk of developing MS suggesting a temporary immunosuppression during pregnancy. Our...... data on social behaviour regarding educational level income and relationship stability did not indicate reverse causality. A greater likelihood to be exposed to common infections did not show any effect on the risk of MS neither in puberty nor in adulthood. Socio-economic status and lifestyle expressed...

  3. The role of the thalamus and hippocampus in episodic memory performance in patients with multiple sclerosis.

    Science.gov (United States)

    Koenig, Katherine A; Rao, Stephen M; Lowe, Mark J; Lin, Jian; Sakaie, Ken E; Stone, Lael; Bermel, Robert A; Trapp, Bruce D; Phillips, Micheal D

    2018-03-01

    Episodic memory loss is one of the most common cognitive symptoms in patients with multiple sclerosis (MS), but the pathophysiology of this symptom remains unclear. Both the hippocampus and thalamus have been implicated in episodic memory and show regional atrophy in patients with MS. In this work, we used functional magnetic resonance imaging (fMRI) during a verbal episodic memory task, lesion load, and volumetric measures of the hippocampus and thalamus to assess the relative contributions to verbal and visual-spatial episodic memory. Functional activation, lesion load, and volumetric measures from 32 patients with MS and 16 healthy controls were used in a predictive analysis of episodic memory function. After adjusting for disease duration, immediate recall performance on a visual-spatial episodic memory task was significantly predicted by hippocampal volume ( p memory measures, functional activation of the thalamus during encoding was more predictive than that of volume measures ( p episodic memory loss in patients with MS.

  4. The "Gut Feeling": Breaking Down the Role of Gut Microbiome in Multiple Sclerosis.

    Science.gov (United States)

    Freedman, Samantha N; Shahi, Shailesh K; Mangalam, Ashutosh K

    2018-01-01

    Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system with unknown etiology. Recently, the gut microbiota has emerged as a potential factor in the development of MS, with a number of studies having shown that patients with MS exhibit gut dysbiosis. The gut microbiota helps the host remain healthy by regulating various functions, including food metabolism, energy homeostasis, maintenance of the intestinal barrier, inhibition of colonization by pathogenic organisms, and shaping of both mucosal and systemic immune responses. Alteration of the gut microbiota, and subsequent changes in its metabolic network that perturb this homeostasis, may lead to intestinal and systemic disorders such as MS. Here we discuss the findings of recent MS microbiome studies and potential mechanisms through which gut microbiota can predispose to, or protect against, MS. These findings highlight the need of an improved understanding of the interactions between the microbiota and host for developing therapies based on gut commensals with which to treat MS.

  5. A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility

    DEFF Research Database (Denmark)

    Damotte, V; Guillot-Noel, L; Patsopoulos, N A

    2014-01-01

    adhesion molecule (CAMs) biological pathway using Cytoscape software. This network is a strong candidate, as it is involved in the crossing of the blood-brain barrier by the T cells, an early event in MS pathophysiology, and is used as an efficient therapeutic target. We drew up a list of 76 genes...... in interaction with other genes as a group. Pathway analysis is an alternative way to highlight such group of genes. Using SNP association P-values from eight multiple sclerosis (MS) GWAS data sets, we performed a candidate pathway analysis for MS susceptibility by considering genes interacting in the cell...... belonging to the CAM network. We highlighted 64 networks enriched with CAM genes with low P-values. Filtering by a percentage of CAM genes up to 50% and rejecting enriched signals mainly driven by transcription factors, we highlighted five networks associated with MS susceptibility. One of them, constituted...

  6. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

    Directory of Open Access Journals (Sweden)

    Patrizia Tosi

    2012-11-01

    Full Text Available Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

  7. Exposure to predator odor influences the relative use of multiple memory systems: role of basolateral amygdala.

    Science.gov (United States)

    Leong, Kah-Chung; Packard, Mark G

    2014-03-01

    In a dual-solution plus-maze task in which both hippocampus-dependent place learning and dorsolateral striatal-dependent response learning provide an adequate solution, the relative use of multiple memory systems can be influenced by emotional state. Specifically, pre-training peripheral or intra-basolateral (BLA) administration of anxiogenic drugs result in the predominant use of response learning. The present experiments were designed to extend these findings by examining whether exposure to a putatively ethologically valid stressor would also produce a predominant use of response learning. In experiment 1, adult male Long-Evans rats were exposed to either a predator odor (trimethylthiazoline [TMT], a component of fox feces) or distilled water prior to training in a dual-solution water plus maze task. On a probe trial 24h following task acquisition, rats previously exposed to TMT predominantly displayed response learning relative to control animals. In experiment 2, rats trained on a single-solution plus maze task that required the use of response learning displayed enhanced acquisition following pre-training TMT exposure. In experiment 3, rats exposed to TMT or distilled water were trained in the dual-solution task and received post-training intra-BLA injections of the sodium channel blocker bupivacaine (1.0% solution, 0.5 μl) or saline. Relative to control animals, rats exposed to TMT predominantly displayed response learning on the probe trial, and this effect was blocked by neural inactivation of the BLA. The findings indicate that (1) the use of dorsal striatal-dependent habit memory produced by emotional arousal generalizes from anxiogenic drug administration to a putatively ecologically valid stressor (i.e. predator odor), and (2) the BLA mediates the modulatory effect of exposure to predator odor on the relative use of multiple memory systems. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Factors predicting work outcome in Japanese patients with schizophrenia: role of multiple functioning levels

    Directory of Open Access Journals (Sweden)

    Chika Sumiyoshi

    2015-09-01

    Full Text Available Functional outcomes in individuals with schizophrenia suggest recovery of cognitive, everyday, and social functioning. Specifically improvement of work status is considered to be most important for their independent living and self-efficacy. The main purposes of the present study were 1 to identify which outcome factors predict occupational functioning, quantified as work hours, and 2 to provide cut-offs on the scales for those factors to attain better work status. Forty-five Japanese patients with schizophrenia and 111 healthy controls entered the study. Cognition, capacity for everyday activities, and social functioning were assessed by the Japanese versions of the MATRICS Cognitive Consensus Battery (MCCB, the UCSD Performance-based Skills Assessment-Brief (UPSA-B, and the Social Functioning Scale Individuals’ version modified for the MATRICS-PASS (Modified SFS for PASS, respectively. Potential factors for work outcome were estimated by multiple linear regression analyses (predicting work hours directly and a multiple logistic regression analyses (predicting dichotomized work status based on work hours. ROC curve analyses were performed to determine cut-off points for differentiating between the better- and poor work status. The results showed that a cognitive component, comprising visual/verbal learning and emotional management, and a social functioning component, comprising independent living and vocational functioning, were potential factors for predicting work hours/status. Cut-off points obtained in ROC analyses indicated that 60–70% achievements on the measures of those factors were expected to maintain the better work status. Our findings suggest that improvement on specific aspects of cognitive and social functioning are important for work outcome in patients with schizophrenia.

  9. Factors predicting work outcome in Japanese patients with schizophrenia: role of multiple functioning levels.

    Science.gov (United States)

    Sumiyoshi, Chika; Harvey, Philip D; Takaki, Manabu; Okahisa, Yuko; Sato, Taku; Sora, Ichiro; Nuechterlein, Keith H; Subotnik, Kenneth L; Sumiyoshi, Tomiki

    2015-09-01

    Functional outcomes in individuals with schizophrenia suggest recovery of cognitive, everyday, and social functioning. Specifically improvement of work status is considered to be most important for their independent living and self-efficacy. The main purposes of the present study were 1) to identify which outcome factors predict occupational functioning, quantified as work hours, and 2) to provide cut-offs on the scales for those factors to attain better work status. Forty-five Japanese patients with schizophrenia and 111 healthy controls entered the study. Cognition, capacity for everyday activities, and social functioning were assessed by the Japanese versions of the MATRICS Cognitive Consensus Battery (MCCB), the UCSD Performance-based Skills Assessment-Brief (UPSA-B), and the Social Functioning Scale Individuals' version modified for the MATRICS-PASS (Modified SFS for PASS), respectively. Potential factors for work outcome were estimated by multiple linear regression analyses (predicting work hours directly) and a multiple logistic regression analyses (predicting dichotomized work status based on work hours). ROC curve analyses were performed to determine cut-off points for differentiating between the better- and poor work status. The results showed that a cognitive component, comprising visual/verbal learning and emotional management, and a social functioning component, comprising independent living and vocational functioning, were potential factors for predicting work hours/status. Cut-off points obtained in ROC analyses indicated that 60-70% achievements on the measures of those factors were expected to maintain the better work status. Our findings suggest that improvement on specific aspects of cognitive and social functioning are important for work outcome in patients with schizophrenia.

  10. Role of thalamic diffusion for disease differentiation between multiple sclerosis and ischemic cerebral small vessel disease

    International Nuclear Information System (INIS)

    Oeztoprak, Bilge; Oeztoprak, Ibrahim; Salk, Ismail; Topalkara, Kamil; Erkoc, Mustafa F.

    2015-01-01

    Cerebral small vessel disease (CSVD) and multiple sclerosis (MS) both harbor multiple, T2-hyperintense white matter lesions on conventional magnetic resonance imaging (MRI).We aimed to determine the microstructural changes via diffusion-weighted imaging (DWI) in normal appearing thalami. We hypothesized that the apparent diffusion coefficient (ADC) values would be different in CSVD and MS, since the extent of arterial involvement is different in these two diseases. DWI was performed for 50 patients with CSVD and 35 patients with MS along with gender- and age-matched controls whose conventional MRI revealed normal findings. DWI was done with 1.5 Tesla MR devices using echo planar imaging (EPI) for b = 0, 1000 s/mm 2 . ADC values were obtained from the thalami which appeared normal on T2-weighted and FLAIR images. Standard oval regions of interest (ROIs) of 0.5 cm 2 which were oriented parallel to the long axis of the thalamus were used for this purpose. The mean ADC value of the thalamus was (0.99 ± 0.16) x 10 -3 mm 2 /s in patients with CSVD, whereas the mean ADC value was (0.78 ± 0.06) x 10 -3 mm 2 /s in the control group. The mean ADC value was significantly higher in patients with CSVD compared to the controls (p < 0.001). The mean ADC values of the thalamus were (0.78 ± 0.08) x 10 -3 mm 2 /s in MS patients, and (0.75 ± 0.08) x 10 -3 mm 2 /s in the control group, which are not significantly different (p > 0.05). Our study revealed a difference in the diffusion of the thalami between CSVD and MS. DWI may aid in the radiological disease differentiation. (orig.)

  11. Role of thalamic diffusion for disease differentiation between multiple sclerosis and ischemic cerebral small vessel disease

    Energy Technology Data Exchange (ETDEWEB)

    Oeztoprak, Bilge; Oeztoprak, Ibrahim; Salk, Ismail [Cumhuriyet University School of Medicine, Department of Radiology, Sivas (Turkey); Topalkara, Kamil [Bayindir Hospital, Department of Neurology, Ankara (Turkey); Erkoc, Mustafa F. [Bozok University School of Medicine, Department of Radiology, Yozgat (Turkey)

    2015-04-01

    Cerebral small vessel disease (CSVD) and multiple sclerosis (MS) both harbor multiple, T2-hyperintense white matter lesions on conventional magnetic resonance imaging (MRI).We aimed to determine the microstructural changes via diffusion-weighted imaging (DWI) in normal appearing thalami. We hypothesized that the apparent diffusion coefficient (ADC) values would be different in CSVD and MS, since the extent of arterial involvement is different in these two diseases. DWI was performed for 50 patients with CSVD and 35 patients with MS along with gender- and age-matched controls whose conventional MRI revealed normal findings. DWI was done with 1.5 Tesla MR devices using echo planar imaging (EPI) for b = 0, 1000 s/mm{sup 2}. ADC values were obtained from the thalami which appeared normal on T2-weighted and FLAIR images. Standard oval regions of interest (ROIs) of 0.5 cm{sup 2} which were oriented parallel to the long axis of the thalamus were used for this purpose. The mean ADC value of the thalamus was (0.99 ± 0.16) x 10{sup -3} mm{sup 2}/s in patients with CSVD, whereas the mean ADC value was (0.78 ± 0.06) x 10{sup -3} mm{sup 2}/s in the control group. The mean ADC value was significantly higher in patients with CSVD compared to the controls (p < 0.001). The mean ADC values of the thalamus were (0.78 ± 0.08) x 10{sup -3} mm{sup 2}/s in MS patients, and (0.75 ± 0.08) x 10{sup -3} mm{sup 2}/s in the control group, which are not significantly different (p > 0.05). Our study revealed a difference in the diffusion of the thalami between CSVD and MS. DWI may aid in the radiological disease differentiation. (orig.)

  12. The MqsRA Toxin-Antitoxin System from Xylella fastidiosa Plays a Key Role in Bacterial Fitness, Pathogenicity, and Persister Cell Formation

    Science.gov (United States)

    Merfa, Marcus V.; Niza, Bárbara; Takita, Marco A.; De Souza, Alessandra A.

    2016-01-01

    Through the formation of persister cells, bacteria exhibit tolerance to multidrug and other environmental stresses without undergoing genetic changes. The toxin-antitoxin (TA) systems are involved in the formation of persister cells because they are able to induce cell dormancy. Among the TA systems, the MqsRA system has been observed to be highly induced in persister cells of Xylella fastidiosa (causal agent of citrus variegated chlorosis—CVC) activated by copper stress, and has been described in Escherichia coli as related to the formation of persister cells and biofilms. Thus, we evaluated the role of this TA system in X. fastidiosa by overexpressing the MqsR toxin, and verified that the toxin positively regulated biofilm formation and negatively cell movement, resulting in reduced pathogenicity in citrus plants. The overexpression of MqsR also increased the formation of persister cells under copper stress. Analysis of the gene and protein expression showed that this system likely has an autoregulation mechanism to express the toxin and antitoxin in the most beneficial ratio for the cell to oppose stress. Our results suggest that this TA system plays a key role in the adaptation and survival of X. fastidiosa and reveal new insights into the physiology of phytopathogen-host interactions. PMID:27375608

  13. The RNA chaperone, Hfq, controls two luxR-type regulators and plays a key role in pathogenesis and production of antibiotics in Serratia sp. ATCC 39006.

    Science.gov (United States)

    Wilf, Nabil M; Williamson, Neil R; Ramsay, Joshua P; Poulter, Simon; Bandyra, Kasia J; Salmond, George P C

    2011-10-01

    Serratia sp. ATCC 39006 (S39006) is a Gram-negative bacterium that is virulent in plant (potato) and animal (Caenorhabditis elegans) models. It produces two secondary metabolite antibiotics, a prodigiosin and a carbapenem, and the exoenzymes, pectate lyase and cellulase. A complex regulatory network that includes quorum sensing (QS) controls production of prodigiosin. While many aspects of the regulation of the metabolites and exoenzymes are well understood, the potential role in this network of the RNA chaperone Hfq and dependent small regulatory RNAs has not been characterized. Hfq is an RNA chaperone involved in post-transcriptional regulation that plays a key role in stress response and virulence in diverse bacterial species. To explore whether Hfq-dependent processes might contribute to the regulation of antibiotic production we constructed an S39006 Δhfq mutant. Production of prodigiosin and carbapenem was abolished in this mutant strain, while production of the QS signalling molecule, butanoyl homoserine lactone (BHL), was unaffected. Using transcriptional fusions, we found that Hfq regulates the QS response regulators, SmaR and CarR. Additionally, exoenzyme production and swimming motility were decreased in a Δhfq mutant, and virulence was attenuated in potato and C. elegans models. These results suggest that an Hfq-dependent pathway is involved in the regulation of virulence and secondary metabolite production in S39006. © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.

  14. Impact of light on Hypocrea jecorina and the multiple cellular roles of ENVOY in this process

    Directory of Open Access Journals (Sweden)

    Druzhinina Irina S

    2007-12-01

    Full Text Available Abstract Background In fungi, light is primarily known to influence general morphogenesis and both sexual and asexual sporulation. In order to expand the knowledge on the effect of light in fungi and to determine the role of the light regulatory protein ENVOY in the implementation of this effect, we performed a global screen for genes, which are specifically effected by light in the fungus Hypocrea jecorina (anamorph Trichoderma reesei using Rapid Subtraction Hybridization (RaSH. Based on these data, we analyzed whether these genes are influenced by ENVOY and if overexpression of ENVOY in darkness would be sufficient to execute its function. Results The cellular functions of the detected light responsive genes comprised a variety of roles in transcription, translation, signal transduction, metabolism, and transport. Their response to light with respect to the involvement of ENVOY could be classified as follows: (i ENVOY-mediated upregulation by light; (ii ENVOY-independent upregulation by light; (iii ENVOY-antagonized upregulation by light; ENVOY-dependent repression by light; (iv ENVOY-independent repression by light; and (v both positive and negative regulation by ENVOY of genes not responsive to light in the wild-type. ENVOY was found to be crucial for normal growth in light on various carbon sources and is not able to execute its regulatory function if overexpressed in the darkness. Conclusion The different responses indicate that light impacts fungi like H. jecorina at several cellular processes, and that it has both positive and negative effects. The data also emphasize that ENVOY has an apparently more widespread cellular role in this process than only in modulating the response to light.

  15. Multiple roles of putrescine and spermidine in stress resistance and virulence of Salmonella enterica serovar Typhimurium

    DEFF Research Database (Denmark)

    Cartas Espinel, Irene; Guerra, Priscila Regina; Jelsbak, Lotte

    2016-01-01

    . Typhimurium virulence is the ability to survive and replicate inside macrophages and resisting the antimicrobial attacks in the form of oxidative and nitrosative stress elicited from these cells. In the present study, we have investigated the role of polyamines in intracellular survival and systemic...... infections of mice. Using a S. Typhimurium mutant defective for putrescine and spermidine biosynthesis, we show that polyamines are essential for coping with reactive nitrogen species, possibly linking polyamines to increased intracellular stress resistance. However, using a mouse model defective for nitric...

  16. The Arabidopsis thaliana Homolog of the Helicase RTEL1 Plays Multiple Roles in Preserving Genome Stability[C][W

    Science.gov (United States)

    Recker, Julia; Knoll, Alexander; Puchta, Holger

    2014-01-01

    In humans, mutations in the DNA helicase Regulator of Telomere Elongation Helicase1 (RTEL1) lead to Hoyeraal-Hreidarsson syndrome, a severe, multisystem disorder. Here, we demonstrate that the RTEL1 homolog in Arabidopsis thaliana plays multiple roles in preserving genome stability. RTEL1 suppresses homologous recombination in a pathway parallel to that of the DNA translocase FANCM. Cytological analyses of root meristems indicate that RTEL1 is involved in processing DNA replication intermediates independently from FANCM and the nuclease MUS81. Moreover, RTEL1 is involved in interstrand and intrastrand DNA cross-link repair independently from FANCM and (in intrastrand cross-link repair) parallel to MUS81. RTEL1 contributes to telomere homeostasis; the concurrent loss of RTEL1 and the telomerase TERT leads to rapid, severe telomere shortening, which occurs much more rapidly than it does in the single-mutant line tert, resulting in developmental arrest after four generations. The double mutant rtel1-1 recq4A-4 exhibits massive growth defects, indicating that this RecQ family helicase, which is also involved in the suppression of homologous recombination and the repair of DNA lesions, can partially replace RTEL1 in the processing of DNA intermediates. The requirement for RTEL1 in multiple pathways to preserve genome stability in plants can be explained by its putative role in the destabilization of DNA loop structures, such as D-loops and T-loops. PMID:25516598

  17. Protein Kinase C-Related Kinase (PKN/PRK). Potential Key-Role for PKN1 in Protection of Hypoxic Neurons.

    Science.gov (United States)

    Thauerer, Bettina; Zur Nedden, Stephanie; Baier-Bitterlich, Gabriele

    2014-05-01

    Serine/threonine protein kinase C-related kinase (PKN/PRK) is a family of three isoenzymes (PKN1, PKN2, PKN3), which are widely distributed in eukaryotic organisms and share the same overall domain structure. The Nterminal region encompasses a conserved repeated domain, termed HR1a-c as well as a HR2/C2 domain. The serine/threonine kinase domain is found in the C-terminal region of the protein and shows high sequence homology to other members of the PKC superfamily. In neurons, PKN1 is the most abundant isoform and has been implicated in a variety of functions including cytoskeletal organization and neuronal differentiation and its deregulation may contribute to neuropathological processes such as amyotrophic lateral sclerosis and Alzheimer's disease. We have recently identified a candidate role of PKN1 in the regulation of neuroprotective processes during hypoxic stress. Our key findings were that: 1) the activity of PKN1 was significantly increased by hypoxia (1% O2) and neurotrophins (nerve growth factor and purine nucleosides); 2) Neuronal cells, deficient of PKN1 showed a decrease of cell viability and neurite formation along with a disturbance of the F-actinassociated cytoskeleton; 3) Purine nucleoside-mediated neuroprotection during hypoxia was severely hampered in PKN1 deficient neuronal cells, altogether suggesting a potentially critical role of PKN1 in neuroprotective processes. This review gives an up-to-date overview of the PKN family with a special focus on the neuroprotective role of PKN1 in hypoxia.

  18. A defined role for multiple Fanconi anemia gene products in DNA-damage-associated ubiquitination.

    Science.gov (United States)

    Tan, Winnie; Deans, Andrew J

    2017-06-01

    Fanconi anemia (FA) is an inherited blood disorder that causes bone marrow failure and high predisposition to cancers. The FA pathway guards the cell's genome stability by orchestrating the repair of interstrand cross-linking during the S phase of the cell cycle, preventing the chromosomal instability that is a key event in bone marrow failure syndrome. Central to the FA pathway is loss of monoubiquitinated forms of the Fanconi proteins FANCI and FANCD2, a process that is normally mediated by a "core complex" of seven other Fanconi proteins. Each protein, when mutated, can cause FA. The FA core-complex-catalyzed reaction is critical for signaling DNA cross-link damage such as that induced by chemotherapies. Here, we present a perspective on the current understanding of FANCI and FANCD2 monoubiquitination-mediated DNA repair. Our recent biochemical reconstitution of the monoubiquitination (and deubiquitination) reactions creates a paradigm for understanding FA. Further biochemical analysis will create new opportunities to address the leukemic phenotype of FA patients. Copyright © 2017 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  19. The main component of an alarm pheromone of kissing bugs plays multiple roles in the cognitive modulation of the escape response

    Directory of Open Access Journals (Sweden)

    Sebastián eMinoli

    2013-07-01

    Full Text Available Innate responses in animals can be modulated by experience. Disturbed adults of the triatomine bug Triatoma infestans release an alarm pheromone (AP that elicits an escape response in conspecific larvae. The main component of this AP, the isobutyric acid (IsoAc, alone has already shown to generate an escape response in this species. However, not much is known about the modulation of this behavior by non-associative and associative cognitive processes. We present here evidences of the cognitive capacities of T. infestans larvae in an escape context under different conditioning paradigms, including IsoAc in different roles. We show that: 1 the duration of a pre-exposure to IsoAc plays a main role in determining the type of non-associative learning expressed: short time pre-exposures elicit a sensitization while a longer pre-exposure time triggers a switch from repellence to attractiveness; 2 a simple pre-exposure event is enough to modulate the escape response of larvae to the AP and to its main component: IsoAc; 3 IsoAc and the AP are perceived as different chemical entities; 4 an association between IsoAc and an aversive stimulus can be created under a classical conditioning paradigm; 5 an association between IsoAc and a self-action can be generated under an operant conditioning. These results evince that IsoAc can attain multiple and different cognitive roles in the modulation of the escape response of triatomines and show how cognitive processes can modulate a key behavior for surviving, as it is the escaping response in presence of a potential danger in insects.

  20. Fatigue in multiple sclerosis: neural correlates and the role of non-invasive brain stimulation

    Directory of Open Access Journals (Sweden)

    Moussa A. Chalah

    2015-11-01

    Full Text Available Multiple sclerosis (MS is a chronic progressive inflammatory disease of the central nervous system and the major cause of non-traumatic disability in young adults. Fatigue is a frequent symptom reported by the majority of MS patients during their disease course and drastically af-fects their quality of life. Despite its significant prevalence and impact, the underlying patho-physiological mechanisms are not well elucidated. MS fatigue is still considered the result of multifactorial and complex constellations, and is commonly classified into primary fatigue related to the pathological changes of the disease itself, and secondary fatigue attributed to mimicking symptoms, comorbid sleep and mood disorders, and medications side effects. Data from neuroimaging, neurophysiology, neuroendocrine and neuroimmune studies have raised hypotheses regarding the origin of this symptom, some of which have succeeded in identifying an association between MS fatigue and structural or functional abnormalities within various brain networks. Hence, the aim of this work is to reappraise the neural correlates of MS fatigue and to discuss the rationale for the emergent use of noninvasive brain stimulation (NIBS techniques as potential treatments. This will include a presentation of the various NIBS modalities and a proposition of their potential mechanisms of action in this context. Specific issues related to the value of transcranial direct current stimulation will be addressed.

  1. Multiple Climate States of Habitable Exoplanets: The Role of Obliquity and Irradiance

    International Nuclear Information System (INIS)

    Kilic, C.; Raible, C. C.; Stocker, T. F.

    2017-01-01

    Stable, steady climate states on an Earth-size planet with no continents are determined as a function of the tilt of the planet’s rotation axis (obliquity) and stellar irradiance. Using a general circulation model of the atmosphere coupled to a slab ocean and a thermodynamic sea ice model, two states, the Aquaplanet and the Cryoplanet, are found for high and low stellar irradiance, respectively. In addition, four stable states with seasonally and perennially open water are discovered if comprehensively exploring a parameter space of obliquity from 0° to 90° and stellar irradiance from 70% to 135% of the present-day solar constant. Within 11% of today’s solar irradiance, we find a rich structure of stable states that extends the area of habitability considerably. For the same set of parameters, different stable states result if simulations are initialized from an aquaplanet or a cryoplanet state. This demonstrates the possibility of multiple equilibria, hysteresis, and potentially rapid climate change in response to small changes in the orbital parameters. The dynamics of the atmosphere of an aquaplanet or a cryoplanet state is investigated for similar values of obliquity and stellar irradiance. The atmospheric circulation substantially differs in the two states owing to the relative strength of the primary drivers of the meridional transport of heat and momentum. At 90° obliquity and present-day solar constant, the atmospheric dynamics of an Aquaplanet state and one with an equatorial ice cover is analyzed.

  2. Resonance properties of tidal channels with multiple retention basins: role of adjacent sea

    Science.gov (United States)

    Roos, Pieter C.; Schuttelaars, Henk M.

    2015-03-01

    We present an idealised model of the tidal response in a main channel with multiple secondary basins, co-oscillating with an adjacent sea. The sea is represented as a semi-infinite strip of finite width, anywhere between the limits of a channel extension (narrow) and a half-plane (wide). The sea geometry controls the extent to which radiative damping takes place and hence the type of conditions that effectively apply at the channel mouth. These conditions range between the two extremes of prescribing elevation (deep sea limit) and prescribing the incoming wave (sea as channel extension of the same depth, as done in an earlier study). The closer to this first extreme, the stronger the oscillations in the secondary basins may feed back onto the channel mouth and thus produce an amplified or weakened response in the system as a whole. The possibly resonant response is explained by analysing the additional waves that emerge on either side of the entrance of the secondary basin. Finally, we show that the simultaneous presence of two secondary basins may amplify or weaken the accumulated responses to these basins individually.

  3. The Role of Allogeneic Transplantation in the Treatment of Multiple Myeloma.

    Science.gov (United States)

    Majolino, I

    1998-01-01

    In multiple myeloma (MM) attempts to improve upon the results of standard melphalanpredisone with other conventional dose drug combinations, have generally been unsuccessful, producing only minor improvements in response rate, with little effect on survival. The only treatment capable of producing a dramatic change in response and life expectancy is high-dose chemo-radiotherapy followed by stem cell transplantation. However, after autologous transplant relapse will almost inevitably occur, and freedom from recurrence curves show no plateau in most studies. Besides the resistance of the disease to chemotherapy, another possible explanation is tumor contamination of the graft. This is one major advantage of allogeneic transplantation over autologous, the other being an immune mediated mechanism of tumor suppression in part related to GVHD. Application of allogeneic transplantation to MM has met a number of obstacles, but is now entering a phase of reappraisal, due in part to a tendency to earlier transplantation, in part to the use of novel technologies such as allogeneic peripheral blood stem cells instead of marrow. The goal should be the reduction of transplant related deaths, to better exploit the higher eradication potential of allogeneic cell therapies. The most intriguing perspectives are those related to immune manipulation of recipient and/or donor.

  4. The Mechanisms of Water Exchange: The Regulatory Roles of Multiple Interactions in Social Wasps.

    Science.gov (United States)

    Agrawal, Devanshu; Karsai, Istvan

    2016-01-01

    Evolutionary benefits of task fidelity and improving information acquisition via multiple transfers of materials between individuals in a task partitioned system have been shown before, but in this paper we provide a mechanistic explanation of these phenomena. Using a simple mathematical model describing the individual interactions of the wasps, we explain the functioning of the common stomach, an information center, which governs construction behavior and task change. Our central hypothesis is a symmetry between foragers who deposit water and foragers who withdraw water into and out of the common stomach. We combine this with a trade-off between acceptance and resistance to water transfer. We ultimately derive a mathematical function that relates the number of interactions that foragers complete with common stomach wasps during a foraging cycle. We use field data and additional model assumptions to calculate values of our model parameters, and we use these to explain why the fullness of the common stomach stabilizes just below 50 percent, why the average number of successful interactions between foragers and the wasps forming the common stomach is between 5 and 7, and why there is a variation in this number of interactions over time. Our explanation is that our proposed water exchange mechanism places natural bounds on the number of successful interactions possible, water exchange is set to optimize mediation of water through the common stomach, and the chance that foragers abort their task prematurely is very low.

  5. Examination of the role of magnetic resonance imaging in multiple sclerosis: A problem-orientated approach

    Directory of Open Access Journals (Sweden)

    McFarland Henry

    2009-01-01

    Full Text Available Magnetic Resonance Imaging (MRI has brought in several benefits to the study of Multiple Sclerosis (MS. It provides accurate measurement of disease activity, facilitates precise diagnosis, and aid in the assessment of newer therapies. The imaging guidelines for MS are broadly divided in to approaches for imaging patients with suspected MS or clinically isolated syndromes (CIS or for monitoring patients with established MS. In this review, the technical aspects of MR imaging for MS are briefly discussed. The imaging process need to capture the twin aspects of acute MS viz. the autoimmune acute inflammatory process and the neurodegenerative process. Gadolinium enhanced MRI can identify acute inflammatory lesions precisely. The commonly applied MRI marker of disease progression is brain atrophy. Whole brain magnetization Transfer Ratio (MTR and Magnetic Resonance Spectroscopy (MRS are two other techniques use to monitor disease progression. A variety of imaging techniques such as Double Inversion Recovery (DIR, Spoiled Gradient Recalled (SPGR acquisition, and Fluid Attenuated Inversion Recovery (FLAIR have been utilized to study the cortical changes in MS. MRI is now extensively used in the Phase I, II and III clinical trials of new therapies. As the technical aspects of MRI advance rapidly, and higher field strengths become available, it is hoped that the impact of MRI on our understanding of MS will be even more profound in the next decade.

  6. Multiple Climate States of Habitable Exoplanets: The Role of Obliquity and Irradiance

    Energy Technology Data Exchange (ETDEWEB)

    Kilic, C.; Raible, C. C.; Stocker, T. F., E-mail: stocker@climate.unibe.ch [Climate and Environmental Physics, Physics Institute, University of Bern (Switzerland)

    2017-08-01

    Stable, steady climate states on an Earth-size planet with no continents are determined as a function of the tilt of the planet’s rotation axis (obliquity) and stellar irradiance. Using a general circulation model of the atmosphere coupled to a slab ocean and a thermodynamic sea ice model, two states, the Aquaplanet and the Cryoplanet, are found for high and low stellar irradiance, respectively. In addition, four stable states with seasonally and perennially open water are discovered if comprehensively exploring a parameter space of obliquity from 0° to 90° and stellar irradiance from 70% to 135% of the present-day solar constant. Within 11% of today’s solar irradiance, we find a rich structure of stable states that extends the area of habitability considerably. For the same set of parameters, different stable states result if simulations are initialized from an aquaplanet or a cryoplanet state. This demonstrates the possibility of multiple equilibria, hysteresis, and potentially rapid climate change in response to small changes in the orbital parameters. The dynamics of the atmosphere of an aquaplanet or a cryoplanet state is investigated for similar values of obliquity and stellar irradiance. The atmospheric circulation substantially differs in the two states owing to the relative strength of the primary drivers of the meridional transport of heat and momentum. At 90° obliquity and present-day solar constant, the atmospheric dynamics of an Aquaplanet state and one with an equatorial ice cover is analyzed.

  7. The role of multiple-group measurement invariance in family psychology research.

    Science.gov (United States)

    Kern, Justin L; McBride, Brent A; Laxman, Daniel J; Dyer, W Justin; Santos, Rosa M; Jeans, Laurie M

    2016-04-01

    Measurement invariance (MI) is a property of measurement that is often implicitly assumed, but in many cases, not tested. When the assumption of MI is tested, it generally involves determining if the measurement holds longitudinally or cross-culturally. A growing literature shows that other groupings can, and should, be considered as well. Additionally, it is noted that the standard techniques for investigating MI have been focused almost exclusively on the case of 2 groups, with very little work on the case of more than 2 groups, even though the need for such techniques is apparent in many fields of research. This paper introduces and illustrates a model building technique to investigating MI for more than 2 groups. This technique is an extension of the already-existing hierarchy for testing MI introduced by Meredith (1993). An example using data on father involvement in 5 different groups of families of children with and without developmental disabilities from the Early Childhood Longitudinal Study-Birth Cohort dataset will be given. We show that without considering the possible differential functioning of the measurements on multiple developmental groups, the differences present between the groups in terms of the measurements may be obscured. This could lead to incorrect conclusions. (c) 2016 APA, all rights reserved).

  8. The Role of Clinical and Instrumented Outcome Measures in Balance Control of Individuals with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Neeta Kanekar

    2013-01-01

    Full Text Available Purpose. The aim of the study was to investigate differences in balance control between individuals with multiple sclerosis (MS and healthy control subjects using clinical scales and instrumented measures of balance and determine relationships between balance measures, fatigue, and disability levels in individuals with MS with and without a history of falls. Method. Twelve individuals with MS and twelve healthy controls were evaluated using the Berg Balance and Activities-specific Balance Confidence Scales, Modified Clinical Test of Sensory Interaction on Balance, and Limits of Stability Tests as well as Fatigue Severity Scale and Barthel Index. Results. Mildly affected individuals with MS had significant balance performance deficits and poor balance confidence levels (P<0.05. MS group had higher sway velocities and diminished stability limits (P<0.05, significant sensory impairments, high fatigue and disability levels (P<0.05. Sway velocity was a significant predictor of balance performance and the ability to move towards stability limits for the MS group. For the MS-fallers group, those with lower disability levels had faster movement velocities and better balance performance. Conclusion. Implementation of both clinical and instrumented tests of balance is important for the planning and evaluation of treatment outcomes in balance rehabilitation of people with MS.

  9. Management of multiple sclerosis: the role of coping self-efficacy and self-esteem.

    Science.gov (United States)

    Mikula, Pavol; Nagyova, Iveta; Vitkova, Marianna; Szilasiova, Jarmila

    2018-02-07

    Patients with multiple sclerosis (MS) engage in various coping behaviours in order to manage their disease. The aim of this study is to find out if the self-esteem of patients is associated with coping strategies - problem-focused (e.g. making a plan of action when confronted with a problem); emotion focused (e.g. get emotional support from community); and focused on stopping unpleasant emotions and thoughts (e.g. keeping oneself from feeling sad), and if it can enhance or hinder coping efforts in the disease management. We collected data from 155 consecutive MS patients who completed the Coping Self-Efficacy Scale (CSE) and the Rosenberg Self-esteem Scale (RSE). Explained variance for problem-focused coping, emotion-focused coping, and coping focused on stopping unpleasant emotions and thoughts was 33, 24, and 31%, respectively. Self-esteem seems to be associated with coping strategies indicating that feelings of self-worth are linked with the ability to handle difficult life situations and can be helpful in chronic disease management.

  10. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

    Directory of Open Access Journals (Sweden)

    Patrizia Tosi

    2012-01-01

    Full Text Available

    Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

  11. Cortical injury in multiple sclerosis; the role of the immune system

    Directory of Open Access Journals (Sweden)

    Walker Caroline A

    2011-12-01

    Full Text Available Abstract The easily identifiable, ubiquitous demyelination and neuronal damage that occurs within the cerebral white matter of patients with multiple sclerosis (MS has been the subject of extensive study. Accordingly, MS has historically been described as a disease of the white matter. Recently, the cerebral cortex (gray matter of patients with MS has been recognized as an additional and major site of disease pathogenesis. This acknowledgement of cortical tissue damage is due, in part, to more powerful MRI that allows detection of such injury and to focused neuropathology-based investigations. Cortical tissue damage has been associated with inflammation that is less pronounced to that which is associated with damage in the white matter. There is, however, emerging evidence that suggests cortical damage can be closely associated with robust inflammation not only in the parenchyma, but also in the neighboring meninges. This manuscript will highlight the current knowledge of inflammation associated with cortical tissue injury. Historical literature along with contemporary work that focuses on both the absence and presence of inflammation in the cerebral cortex and in the cerebral meninges will be reviewed.

  12. Multiple roles of the Y chromosome in the biology of Drosophila melanogaster.

    Science.gov (United States)

    Piergentili, Roberto

    2010-09-01

    The X and Y chromosomes of Drosophila melanogaster were the first examples of chromosomes associated with genetic information. Thanks to the serendipitous discovery of a male with white eyes in 1910, T.H. Morgan was able to associate the X chromosome of the fruit fly with a phenotypic character (the eye color) for the first time. A few years later, his student, C.B. Bridges, demonstrated that X0 males, although phenotypically normal, are completely sterile. This means that the X chromosome, like the autosomes, harbors genes that control several phenotypic traits, while the Y chromosome is important for male fertility only. Notwithstanding its long history--almost 100 years in terms of genetic studies--most of the features of the Y chromosome are still a mystery. This is due to the intrinsic nature of this genetic element, namely, (1) its molecular composition (mainly transposable elements and satellite DNA), (2) its genetic inertia (lack of recombination due to its heterochromatic nature), (3) the absence of homology with the X (with the only exception of the nucleolar organizer), (4) the lack of visible phenotypes when it is missing (indeed, except for their sterility, X0 flies are normal males), and (5) its low density as for protein-coding sequences (to date, only 13 genes out of approximately 14,000 have been mapped on this chromosome in D. melanogaster, i.e., ~0.1% of the total). Nonetheless, a more accurate analysis reveals that this chromosome can influence several complex phenotypes: (1) it has a role in the fertility of both sexes and viability of males when over-represented; (2) it can unbalance the intracellular nucleotide pool; (3) it can interfere with the gene expression either by recruiting proteins involved in chromatin remodeling (PEV) or, to a higher extent, by influencing the expression of up to 1,000 different genes, probably by changing the availability of transcription factors; (4) it plays a major role (up to 50%) in the resistance to heat

  13. Brd4 and HEXIM1: Multiple Roles in P-TEFb Regulation and Cancer

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    Ruichuan Chen

    2014-01-01

    Full Text Available Bromodomain-containing protein 4 (Brd4 and hexamethylene bisacetamide (HMBA inducible protein 1 (HEXIM1 are two opposing regulators of the positive transcription elongation factor b (P-TEFb, which is the master modulator of RNA polymerase II during transcriptional elongation. While Brd4 recruits P-TEFb to promoter-proximal chromatins to activate transcription, HEXIM1 sequesters P-TEFb into an inactive complex containing the 7SK small nuclear RNA. Besides regulating P-TEFb’s transcriptional activity, recent evidence demonstrates that both Brd4 and HEXIM1 also play novel roles in cell cycle progression and tumorigenesis. Here we will discuss the current knowledge on Brd4 and HEXIM1 and their implication as novel therapeutic options against cancer.

  14. Multiple Roles of Soluble Sugars in the Establishment of Gunnera-Nostoc Endosymbiosis1[OA

    Science.gov (United States)

    Khamar, Hima J.; Breathwaite, Erick K.; Prasse, Christine E.; Fraley, Elizabeth R.; Secor, Craig R.; Chibane, Fairouz L.; Elhai, Jeff; Chiu, Wan-Ling

    2010-01-01

    Gunnera plants have the unique ability to form endosymbioses with N2-fixing cyanobacteria, primarily Nostoc. Cyanobacteria enter Gunnera through transiently active mucilage-secreting glands on stems. We took advantage of the nitrogen (N)-limitation-induced gland development in Gunnera manicata to identify factors that may enable plant tissue to attract and maintain cyanobacteria colonies. Cortical cells in stems of N-stressed Gunnera plants were found to accumulate a copious amount of starch, while starch in the neighboring mature glands was nearly undetectable. Instead, mature glands accumulated millimolar concentrations of glucose (Glc) and fructose (Fru). Successful colonization by Nostoc drastically reduced sugar accumulation in the surrounding tissue. Consistent with the abundance of Glc and Fru in the gland prior to Nostoc colonization, genes encoding key enzymes for sucrose and starch hydrolysis (e.g. cell wall invertase, α-amylase, and starch phosphorylase) were expressed at higher levels in stem segments with glands than those without. In contrast, soluble sugars were barely detectable in mucilage freshly secreted from glands. Different sugars affected Nostoc’s ability to differentiate motile hormogonia in a manner consistent with their locations. Galactose and arabinose, the predominant constituents of polysaccharides in the mucilage, had little or no inhibitory effect on hormogonia differentiation. On the other hand, soluble sugars that accumulated in gland tissue, namely sucrose, Glc, and Fru, inhibited hormogonia differentiation and enhanced vegetative growth. Results from this study suggest that, in an N-limited environment, mature Gunnera stem glands may employ different soluble sugars to attract Nostoc and, once the cyanobacteria are internalized, to maintain them in the N2-fixing vegetative state. PMID:20833727

  15. The role of stem cell mobilization regimen on lymphocyte collection yield in patients with multiple myeloma.

    Science.gov (United States)

    Hiwase, D K; Hiwase, S; Bailey, M; Bollard, G; Schwarer, A P

    2008-01-01

    The lymphocyte dose (LY-DO) infused during an autograft influences absolute lymphocyte (ALC) recovery and survival following autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Factors influencing lymphocyte yield (LY-C) during leukapheresis have been poorly studied. Factors that could influence survival, LY-C and CD34(+) cell yield were analyzed in 122 MM patients. Three mobilization regimens were used, granulocyte-colony-stimulating factor (G-CSF) alone (n=13), cyclophosphamide 1-2 g/m(2) plus G-CSF (LD-CY, n=62) and cyclophosphamide 3-4 g/m(2) and G-CSF (ID-CY, n=47). Using multivariate analysis, age, LY-C, ALC on day 30 (ALC-30) and International Staging System stage significantly influenced overall (OS) and progression-free survival (PFS) following ASCT. PFS (56 versus 29 months, P=0.05) and OS (72 versus 49 months; P=0.07) were longer in the LY-C>or=0.12x10(9)/kg group than the LY-Cradiotherapy and number of leukaphereses significantly influenced LY-C. Significantly higher LY-C was obtained with G-CSF alone compared with the LD-CY and ID-CY groups. CD34(+) count on the day of leukapheresis, prior chemotherapy with prednisone, cyclophosphamide, adriamycin and BCNU or melphalan, and stem cell mobilization regimen significantly influenced CD34(+) cell yield. LY-C influenced ALC-15 and survival following ASCT. Factors that influenced CD34(+) cell yield and LY-C during leukapheresis were different. Mobilization should be tailored to maximize the LY-C and CD34(+) cell yield.

  16. Critical appraisal of the role of fingolimod in the treatment of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Warnke C

    2011-09-01

    Full Text Available Clemens Warnke1,2, Olaf Stüve3,4, Hans-Peter Hartung1, Anna Fogdell-Hahn2, Bernd C Kieseier11Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany; 2Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; 3Department of Neurology, Dallas Veterans Affairs Medical Center, TX, USA; 4Department of Neurology, University of Texas Southwestern Medical Center at Dallas, TX, USAAbstract: This review summarizes Phase III clinical trial data available for fingolimod. The main purpose is to evaluate the benefit-risk profile of fingolimod, the first oral compound available for treatment of multiple sclerosis (MS and just recently approved by the European authorities. The authors place this evaluation in the context of the known safety and efficacy profile of established compounds for therapy of MS to outline the current and future potential of fingolimod. The authors conclude that only long-term safety data from post-marketing surveillance plans, together with additional head-to-head studies, would allow evidence-based treatment decisions. Furthermore, risk-profile analyses including patient history, exposure data to certain pathogens, and genetic analyses may potentially help to choose the right drug for individual patients in the future. Until these approaches toward an individualized medicine have been validated, treatment decisions for one or the other compound will have to be based partly on class IV evidence. Therefore, a close dialog with the well-informed patient, secured by effective risk mitigation plans, is required to choose the compound.Keywords: FTY720, oral drug, spingosine 1-phosphate receptor

  17. On the role of the amygdala for experiencing fatigue in patients with multiple sclerosis.

    Science.gov (United States)

    Hanken, Katrin; Francis, Yoselin; Kastrup, Andreas; Eling, Paul; Klein, Jan; Hildebrandt, Helmut

    2018-02-01

    Recently, we proposed a model explaining the origin of fatigue in multiple sclerosis (MS) patients. This model assumes that the feeling of fatigue results from inflammation-induced information processing within interoceptive brain areas. To investigate the association between self-reported cognitive fatigue and structural integrity of interoceptive brain areas in MS patients. 95 MS patients and 28 healthy controls participated in this study. All participants underwent diffusion tensor MRI and fractional anisotropy data were calculated for the amygdala, the stria terminalis and the corpus callosum, a non-interoceptive brain area. Based on the cognitive fatigue score of the Fatigue Scale for Motor and Cognition, patients were divided into moderately cognitively fatigued (cognitive fatigue score ≥ 28) and cognitively non-fatigued (cognitive fatigue score < 28) MS patients. Healthy controls were recruited as a third group. Repeated measures analyses of covariance, controlling for age, depression and brain atrophy, were performed to investigate whether the factor Group had a significant effect on the fractional anisotropy data. A significant effect of Group was observed for the amygdala (F = 3.389, p = 0.037). MS patients without cognitive fatigue presented lower values of the amygdala than MS patients with cognitive fatigue and healthy controls. For the stria terminalis and the corpus callosum, no main effect of Group was observed. The structural integrity of the amygdala in non-fatigued MS patients appears to be reduced. According to our model this might indicate that the absence of fatigue in non-fatigued MS patients might result from disturbed inflammation-induced information processing in the amygdala. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis.

    Science.gov (United States)

    Calvo-Barreiro, Laura; Eixarch, Herena; Montalban, Xavier; Espejo, Carmen

    2018-02-01

    The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity

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    Alexander Tallner

    2015-07-01

    Full Text Available Multiple sclerosis (MS patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36, and Beck Depression Inventory (BDI. We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL. Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients.

  20. Multiple Roles of Autophagy in the Sorafenib Resistance of Hepatocellular Carcinoma

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    Ting Sun

    2017-11-01

    Full Text Available Hepatocellular carcinoma (HCC is the second leading cause of cancer-related death worldwide, and prognosis remains unsatisfactory since the disease is often diagnosed at the advanced stages. Currently, the multikinase inhibitor sorafenib is the only drug approved for the treatment of advanced HCC. However, primary or acquired resistance to sorafenib develops, generating a roadblock in HCC therapy. Autophagy is an intracellular lysosomal pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. Current understanding of the role of autophagy in the progression of cancer and the response to cancer therapy remains controversial. Sorafenib is able to induce autophagy in HCC, but the effect of autophagy is indistinct. Some studies established that sorafenib-induced autophagy serves as a pro-survival response. However, other studies found that sorafenib-induced autophagy improves the lethality of sorafenib against HCC cells. The mechanisms underlying autophagy and sorafenib resistance remain elusive. The purpose of this review is to summarize the progress of research focused on autophagy and sorafenib resistance and to update current knowledge of how cellular autophagy impacts sorafenib sensitivity in HCC treatment.

  1. From "Cellular" RNA to "Smart" RNA: Multiple Roles of RNA in Genome Stability and Beyond.

    Science.gov (United States)

    Michelini, Flavia; Jalihal, Ameya P; Francia, Sofia; Meers, Chance; Neeb, Zachary T; Rossiello, Francesca; Gioia, Ubaldo; Aguado, Julio; Jones-Weinert, Corey; Luke, Brian; Biamonti, Giuseppe; Nowacki, Mariusz; Storici, Francesca; Carninci, Piero; Walter, Nils G; Fagagna, Fabrizio d'Adda di

    2018-03-30

    Coding for proteins has been considered the main function of RNA since the "central dogma" of biology was proposed. The discovery of noncoding transcripts shed light on additional roles of RNA, ranging from the support of polypeptide synthesis, to the assembly of subnuclear structures, to gene expression modulation. Cellular RNA has therefore been recognized as a central player in often unanticipated biological processes, including genomic stability. This ever-expanding list of functions inspired us to think of RNA as a "smart" phone, which has replaced the older obsolete "cellular" phone. In this review, we summarize the last two decades of advances in research on the interface between RNA biology and genome stability. We start with an account of the emergence of noncoding RNA, and then we discuss the involvement of RNA in DNA damage signaling and repair, telomere maintenance, and genomic rearrangements. We continue with the depiction of single-molecule RNA detection techniques, and we conclude by illustrating the possibilities of RNA modulation in hopes of creating or improving new therapies. The widespread biological functions of RNA have made this molecule a reoccurring theme in basic and translational research, warranting it the transcendence from classically studied "cellular" RNA to "smart" RNA.

  2. Role of multiple hosts in the cross-species transmission and emergence of a pandemic parvovirus.

    Science.gov (United States)

    Allison, Andrew B; Harbison, Carole E; Pagan, Israel; Stucker, Karla M; Kaelber, Jason T; Brown, Justin D; Ruder, Mark G; Keel, M Kevin; Dubovi, Edward J; Holmes, Edward C; Parrish, Colin R

    2012-01-01

    Understanding the mechanisms of cross-species virus transmission is critical to anticipating emerging infectious diseases. Canine parvovirus type 2 (CPV-2) emerged as a variant of a feline parvovirus when it acquired mutations that allowed binding to the canine transferrin receptor type 1 (TfR). However, CPV-2 was soon replaced by a variant virus (CPV-2a) that differed in antigenicity and receptor binding. Here we show that the emergence of CPV involved an additional host range variant virus that has circulated undetected in raccoons for at least 24 years, with transfers to and from dogs. Raccoon virus capsids showed little binding to the canine TfR, showed little infection of canine cells, and had altered antigenic structures. Remarkably, in capsid protein (VP2) phylogenies, most raccoon viruses fell as evolutionary intermediates between the CPV-2 and CPV-2a strains, suggesting that passage through raccoons assisted in the evolution of CPV-2a. This highlights the potential role of alternative hosts in viral emergence.

  3. Role of Multiple Hosts in the Cross-Species Transmission and Emergence of a Pandemic Parvovirus

    Science.gov (United States)

    Allison, Andrew B.; Harbison, Carole E.; Pagan, Israel; Stucker, Karla M.; Kaelber, Jason T.; Brown, Justin D.; Ruder, Mark G.; Keel, M. Kevin; Dubovi, Edward J.; Holmes, Edward C.

    2012-01-01

    Understanding the mechanisms of cross-species virus transmission is critical to anticipating emerging infectious diseases. Canine parvovirus type 2 (CPV-2) emerged as a variant of a feline parvovirus when it acquired mutations that allowed binding to the canine transferrin receptor type 1 (TfR). However, CPV-2 was soon replaced by a variant virus (CPV-2a) that differed in antigenicity and receptor binding. Here we show that the emergence of CPV involved an additional host range variant virus that has circulated undetected in raccoons for at least 24 years, with transfers to and from dogs. Raccoon virus capsids showed little binding to the canine TfR, showed little infection of canine cells, and had altered antigenic structures. Remarkably, in capsid protein (VP2) phylogenies, most raccoon viruses fell as evolutionary intermediates between the CPV-2 and CPV-2a strains, suggesting that passage through raccoons assisted in the evolution of CPV-2a. This highlights the potential role of alternative hosts in viral emergence. PMID:22072763

  4. The Role of Environment and Lifestyle in Determining the Risk of Multiple Sclerosis.

    Science.gov (United States)

    Hedström, Anna Karin; Olsson, Tomas; Alfredsson, Lars

    2015-01-01

    MS is a complex disease where both genetic and environmental factors contribute to disease susceptibility. The substantially increased risk of developing MS in relatives of affected individuals gives solid evidence for a genetic base for susceptibility, whereas the modest familial risk, most strikingly demonstrated in the twin studies, is a very strong argument for an important role of lifestyle/environmental factors in determining the risk of MS, sometimes interacting with MS risk genes. Lifestyle factors and environmental exposures are harder to accurately study and quantify than genetic factors. However, it is important to identify these factors since they, as opposed to risk genes, are potentially preventable. We have reviewed the evidence for environmental factors that have been repeatedly shown to influence the risk of MS: Epstein-Barr virus (EBV) infection, ultraviolet radiation (UVR) exposure habits /vitamin D status, and smoking. We have also reviewed a number of additional environmental factors, published in the past 5 years, that have been described to influence MS risk. Independent replication, preferably by a variety of methods, may give still more firm evidence for their involvement.

  5. The multiple roles of computational chemistry in fragment-based drug design

    Science.gov (United States)

    Law, Richard; Barker, Oliver; Barker, John J.; Hesterkamp, Thomas; Godemann, Robert; Andersen, Ole; Fryatt, Tara; Courtney, Steve; Hallett, Dave; Whittaker, Mark

    2009-08-01

    Fragment-based drug discovery (FBDD) represents a change in strategy from the screening of molecules with higher molecular weights and physical properties more akin to fully drug-like compounds, to the screening of smaller, less complex molecules. This is because it has been recognised that fragment hit molecules can be efficiently grown and optimised into leads, particularly after the binding mode to the target protein has been first determined by 3D structural elucidation, e.g. by NMR or X-ray crystallography. Several studies have shown that medicinal chemistry optimisation of an already drug-like hit or lead compound can result in a final compound with too high molecular weight and lipophilicity. The evolution of a lower molecular weight fragment hit therefore represents an attractive alternative approach to optimisation as it allows better control of compound properties. Computational chemistry can play an important role both prior to a fragment screen, in producing a target focussed fragment library, and post-screening in the evolution of a drug-like molecule from a fragment hit, both with and without the available fragment-target co-complex structure. We will review many of the current developments in the area and illustrate with some recent examples from successful FBDD discovery projects that we have conducted.

  6. Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors

    Directory of Open Access Journals (Sweden)

    Eduardo Pimenta

    2009-05-01

    Full Text Available Eduardo Pimenta1, Suzanne Oparil21Endocrine Hypertension Research Center and Clinical Center of Research Excellence in Cardiovascular Disease and Metabolic Disorders, University of Queensland School of Medicine, Princess Alexandra Hospital, Brisbane, QLD, Australia; 2Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham, AL, USAbstract: The renin-angiotensin-aldosterone system (RAAS is an important mediator of blood pressure (BP and volume regulation in both normotensive and hypertensive persons and is a major contributor to hypertension-related target organ damage. The concept of renin inhibition for managing hypertension by blocking the RAAS pathway at its point of activation is very attractive since the renin-angiotensinogen reaction is the first and rate-limiting step in the generation of angiotensin II (Ang II. Aliskiren, the first in a new class of orally effective direct renin inhibitors (DRIs, is approved for the treatment of hypertension. It is effective in reducing BP in the general population of hypertensive patients and in special patient groups such as obese persons, and has a tolerability and safety profile similar to placebo. Aliskiren has renoprotective, cardioprotective and anti-atherosclerotic effects in animal models that appear to be independent of BP lowering. It reduces proteinuria in diabetic patients and has favorable neurohumoral effects in patients with symptomatic heart failure. Additional outcome trials are needed to establish the role of this novel class of antihypertensive medication in the therapeutic armamentarium.Keywords: hypertension, renin inhibitors, renin-angiotensin-aldosterone system

  7. Multiple roles for apoptosis facilitating condensation of the Drosophila ventral nerve cord.

    Science.gov (United States)

    Page, Damon T; Olofsson, Birgitta

    2008-02-01

    At the end of embryogenesis, the ventral nerve cord (VNC) of Drosophila undergoes a shape change, termed condensation. During condensation the length of the VNC shortens by 25%, a process dependent on extracellular matrix deposited by hemocytes, an intact cytoskeleton of glia and neurons and neural activity. Here we show that cell death contributes to nerve cord shortening. Firstly, apoptosis occurs at the interface of the epidermis and the nerve cord where it plays a role in the separation of these two tissues. Separation precedes condensation and in conditions where separation is prevented, condensation fails. Secondly, many cells undergo apoptosis within VNC during condensation. This cell death is localized mainly to the posterior part of the nerve cord where more than half of all cell death occurs. Preventing apoptosis either in neurons or glia partially inhibits VNC shortening during condensation. Despite the importance of midline glia in axon tract development, preventing midline glia cell death results in normal hatching and adult formation. We find that undead midline glia are eliminated from the midline and become mispositioned or expelled from the nervous system. We suggest that this represent a form of pattern repair that operates to reduce the impact of the additional cells. (c) 2008 Wiley-Liss, Inc.

  8. Emotional and behavioural resilience to multiple risk exposure in early life: the role of parenting.

    Science.gov (United States)

    Flouri, Eirini; Midouhas, Emily; Joshi, Heather; Tzavidis, Nikos

    2015-07-01

    Ecological and transactional theories link child outcomes to neighbourhood disadvantage, family poverty and adverse life events. Traditionally, these three types of risk factors have been examined independently of one another or combined into one cumulative risk index. The first approach results in poor prediction of child outcomes, and the second is not well rooted in ecological theory as it does not consider that distal risk factors (such as poverty) may indirectly impact children through proximal risk factors (such as adverse life events). In this study, we modelled simultaneously the longitudinal effects of these three risk factors on children's internalising and externalising problems, exploring the role of parenting in moderating these effects. Our sample followed 16,916 children (at ages 3, 5 and 7 years; N = 16,916; 49% girls) from the UK Millennium Cohort Study. Parenting was characterised by quality of parent-child relationship, parental involvement in learning and parental discipline. Neighbourhood disadvantage, family poverty and adverse events were all simultaneously related to the trajectories of both outcomes. As expected, parenting moderated risk effects. Positive parent-child relationship, rather than greater involvement or authoritative discipline, most consistently 'buffered' risk effects. These findings suggest that a good parent-child relationship may promote young children's emotional and behavioural resilience to different types of environmental risk.

  9. The multiple roles of titin in muscle contraction and force production.

    Science.gov (United States)

    Herzog, Walter

    2018-01-20

    Titin is a filamentous protein spanning the half-sarcomere, with spring-like properties in the I-band region. Various structural, signaling, and mechanical functions have been associated with titin, but not all of these are fully elucidated and accepted in the scientific community. Here, I discuss the primary mechanical functions of titin, including its accepted role in passive force production, stabilization of half-sarcomeres and sarcomeres, and its controversial contribution to residual force enhancement, passive force enhancement, energetics, and work production in shortening muscle. Finally, I provide evidence that titin is a molecular spring whose stiffness changes with muscle activation and actin-myosin-based force production, suggesting a novel model of force production that, aside from actin and myosin, includes titin as a "third contractile" filament. Using this three-filament model of sarcomeres, the stability of (half-) sarcomeres, passive force enhancement, residual force enhancement, and the decrease in metabolic energy during and following eccentric contractions can be explained readily.

  10. Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kwang-Soo, E-mail: shinks@dju.kr [Division of Life Science, Daejeon University, Daejeon, 300-716 (Korea, Republic of); Kim, Young Hwan [Biomedical Omics Team, Korea Basic Science Institute (KBSI), Ohcang, 368-883 (Korea, Republic of); Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Department of Bio-Analytical Science, University of Science and Technology, Daejeon, 305-333 (Korea, Republic of); Yu, Jae-Hyuk, E-mail: jyu1@wisc.edu [Departments of Bacteriology and Genetics, The University of Wisconsin–Madison, Madison, WI, 53706 (United States)

    2015-07-31

    The opportunistic human pathogenic fungus Aspergillus fumigatus primarily reproduces by forming a large number of asexual spores (conidia). Sequential activation of the central regulators BrlA, AbaA and WetA is necessary for the fungus to undergo asexual development. In this study, to address the presumed roles of these key developmental regulators during proliferation of the fungus, we analyzed and compared the proteomes of vegetative cells of wild type (WT) and individual mutant strains. Approximately 1300 protein spots were detectable from 2-D electrophoresis gels. Among these, 13 proteins exhibiting significantly altered accumulation levels were further identified by ESI-MS/MS. Markedly, we found that the GliM and GliT proteins associated with gliotoxin (GT) biosynthesis and self-protection of the fungus from GT were significantly down-regulated in the ΔabaA and ΔbrlA mutants. Moreover, mRNA levels of other GT biosynthetic genes including gliM, gliP, gliT, and gliZ were significantly reduced in both mutant strains, and no and low levels of GT were detectable in the ΔbrlA and ΔabaA mutant strains, respectively. As GliT is required for the protection of the fungus from GT, growth of the ΔbrlA mutant with reduced levels of GliT was severely impaired by exogenous GT. Our studies demonstrate that AbaA and BrlA positively regulate expression of the GT biosynthetic gene cluster in actively growing vegetative cells, and likely bridge morphological and chemical development during the life-cycle of A. fumigatus. - Highlights: • Proteome analyses of WT and mutants reveal 13 differentially expressed proteins. • The GliT and GliM proteins are significantly down-regulated by ΔabaA and ΔbrlA. • Expression of other gliotoxin biosynthetic genes is lowered by ΔabaA and ΔbrlA. • Growth of ΔbrlA strain lacking GliT is completely inhibited by exogenous gliotoxin. • BrlA and AbaA play key roles in biogenesis of gliotoxin in Aspergillus fumigatus.

  11. Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus

    International Nuclear Information System (INIS)

    Shin, Kwang-Soo; Kim, Young Hwan; Yu, Jae-Hyuk

    2015-01-01

    The opportunistic human pathogenic fungus Aspergillus fumigatus primarily reproduces by forming a large number of asexual spores (conidia). Sequential activation of the central regulators BrlA, AbaA and WetA is necessary for the fungus to undergo asexual development. In this study, to address the presumed roles of these key developmental regulators during proliferation of the fungus, we analyzed and compared the proteomes of vegetative cells of wild type (WT) and individual mutant strains. Approximately 1300 protein spots were detectable from 2-D electrophoresis gels. Among these, 13 proteins exhibiting significantly altered accumulation levels were further identified by ESI-MS/MS. Markedly, we found that the GliM and GliT proteins associated with gliotoxin (GT) biosynthesis and self-protection of the fungus from GT were significantly down-regulated in the ΔabaA and ΔbrlA mutants. Moreover, mRNA levels of other GT biosynthetic genes including gliM, gliP, gliT, and gliZ were significantly reduced in both mutant strains, and no and low levels of GT were detectable in the ΔbrlA and ΔabaA mutant strains, respectively. As GliT is required for the protection of the fungus from GT, growth of the ΔbrlA mutant with reduced levels of GliT was severely impaired by exogenous GT. Our studies demonstrate that AbaA and BrlA positively regulate expression of the GT biosynthetic gene cluster in actively growing vegetative cells, and likely bridge morphological and chemical development during the life-cycle of A. fumigatus. - Highlights: • Proteome analyses of WT and mutants reveal 13 differentially expressed proteins. • The GliT and GliM proteins are significantly down-regulated by ΔabaA and ΔbrlA. • Expression of other gliotoxin biosynthetic genes is lowered by ΔabaA and ΔbrlA. • Growth of ΔbrlA strain lacking GliT is completely inhibited by exogenous gliotoxin. • BrlA and AbaA play key roles in biogenesis of gliotoxin in Aspergillus fumigatus

  12. Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity.

    Science.gov (United States)

    Yeves, A M; Burgos, J I; Medina, A J; Villa-Abrille, M C; Ennis, I L

    2018-05-13

    Myocardial Na + /H + exchanger-1 (NHE-1) hyperactivity and oxidative stress are interrelated phenomena playing pivotal roles in the development of pathological cardiac hypertrophy and heart failure. Exercise training is effective to convert pathological into physiological hypertrophy in the spontaneously hypertensive rats (SHR), and IGF-1-key humoral mediator of exercise training-inhibits myocardial NHE-1, at least in normotensive rats. Therefore, we hypothesize that IGF-1 by hampering NHE-1 hyperactivity and oxidative stress should exert a cardioprotective effect in the SHR. NHE-1 activity [proton efflux (JH+) mmol L -1  min -1 ], expression and phosphorylation; H 2 O 2 production; superoxide dismutase (SOD) activity; contractility and calcium transients were measured in SHR hearts in the presence/absence of IGF-1. IGF-1 significantly decreased NHE-1 activity (JH+ at pH i 6.95: 1.39 ± 0.32, n = 9 vs C 3.27 ± 0.3, n = 20, P IGF-1 receptor (2.7 ± 0.4, n = 7); by the PI3K inhibitor wortmannin (3.14 ± 0.41, n = 7); and the AKT inhibitor MK2206 (3.37 ± 0.43, n = 14). Moreover, IGF-1 exerted an antioxidant effect revealed by a significant reduction in H 2 O 2 production accompanied by an increase in SOD activity. In addition, IGF-1 improved cardiomyocyte contractility as evidenced by an increase in sarcomere shortening and a decrease in the relaxation constant, underlined by an increase in the amplitude and rate of decay of the calcium transients. IGF-1 exerts a cardioprotective role on the hypertrophied hearts of the SHR, in which the inhibition of NHE-1 hyperactivity, as well as the positive inotropic and antioxidant effects, emerges as key players. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  13. The role of multiple partners in a digestive mutualism with a protocarnivorous plant.

    Science.gov (United States)

    Nishi, Aline Hiroko; Vasconcellos-Neto, João; Romero, Gustavo Quevedo

    2013-01-01

    ). This is the first study that demonstrates partitioning effects from multiple partners in a digestion-based mutualism. Despite most of the nitrogen being absorbed through their roots (via termites), P. bromelioides has all the attributes necessary to be considered as a carnivorous plant in the context of digestive mutualism.

  14. The role of specialist nurses in multiple sclerosis: a rapid and systematic review.

    Science.gov (United States)

    De Broe, S; Christopher, F; Waugh, N

    2001-01-01

    Multiple sclerosis (MS) is a disease of the central nervous system. The cause is unknown. There are about 80-160 people with MS per 100,000 population, with twice as many women affected as men. The management of individuals with MS includes treatment of acute relapses and chronic symptoms. The care of MS patients is provided by various healthcare professionals, such as general practitioners (GPs), neurologists, physiotherapists, occupational therapists and nurses. Some MS patients have access to an MS specialist nurse, although this provision varies geographically. The aim of this report is to assess the effectiveness and relative cost-effectiveness of MS specialist nurses in improving care and outcomes for patients with MS. A systematic review of the literature, involving a range of databases, was performed. Full details are described in the main report. Only one study was identified that tried to evaluate the benefit of MS specialist nurses. The study concluded that MS patients and their carers found the MS specialist nurse to be helpful, particularly in improving their knowledge of MS, ability to cope, mood and confidence about the future. GPs also reported finding the nurse to be helpful with their MS patients, and 40% of the GPs stated they would purchase the services of an MS specialist nurse if their practices became fundholding. However, there were considerable methodological weaknesses inherent in the study design, and it was unclear whether the results of the study could be extrapolated to other settings or to other MS patient groups. RESULTS - ONGOING RESEARCH: There are two ongoing research studies regarding MS specialist nurses. One of these studies involves the provision of MS nurses to several areas, but also has two control populations to allow evaluation of the health benefits of the nurses to MS patients and their carers. This study will help to fill the evidence gap. RESULTS - COSTS: The costs of providing MS specialist nurses consist of their

  15. Language Learning Enhanced by Massive Multiple Online Role-Playing Games (MMORPGs) and the Underlying Behavioral and Neural Mechanisms

    Science.gov (United States)

    Zhang, Yongjun; Song, Hongwen; Liu, Xiaoming; Tang, Dinghong; Chen, Yue-e; Zhang, Xiaochu

    2017-01-01

    Massive Multiple Online Role-Playing Games (MMORPGs) have increased in popularity among children, juveniles, and adults since MMORPGs’ appearance in this digital age. MMORPGs can be applied to enhancing language learning, which is drawing researchers’ attention from different fields and many studies have validated MMORPGs’ positive effect on language learning. However, there are few studies on the underlying behavioral or neural mechanism of such effect. This paper reviews the educational application of the MMORPGs based on relevant macroscopic and microscopic studies, showing that gamers’ overall language proficiency or some specific language skills can be enhanced by real-time online interaction with peers and game narratives or instructions embedded in the MMORPGs. Mechanisms underlying the educational assistant role of MMORPGs in second language learning are discussed from both behavioral and neural perspectives. We suggest that attentional bias makes gamers/learners allocate more cognitive resources toward task-related stimuli in a controlled or an automatic way. Moreover, with a moderating role played by activation of reward circuit, playing the MMORPGs may strengthen or increase functional connectivity from seed regions such as left anterior insular/frontal operculum (AI/FO) and visual word form area to other language-related brain areas. PMID:28303097

  16. The Calibration Target for the Mars 2020 SHERLOC Instrument: Multiple Science Roles for Future Manned and Unmanned Mars Exploration

    Science.gov (United States)

    Fries, M.; Bhartia, R.; Beegle, L.; Burton, A.; Ross, A.; Shahar, A.

    2014-01-01

    The Scanning Habitable Environments with Raman & Luminescence for Organics & Chemicals (SHERLOC) instrument is a deep ultraviolet (UV) Raman/fluorescence instrument selected as part of the Mars 2020 rover instrument suite. SHERLOC will be mounted on the rover arm and its primary role is to identify carbonaceous species in martian samples, which may be selected for inclusion into a returnable sample cache. The SHERLOC instrument will require the use of a calibration target, and by design, multiple science roles will be addressed in the design of the target. Samples of materials used in NASA Extravehicular Mobility unit (EMU, or "space suit") manufacture have been included in the target to serve as both solid polymer calibration targets for SHERLOC instrument function, as well as for testing the resiliency of those materials under martian ambient conditions. A martian meteorite will also be included in the target to serve as a well-characterized example of a martian rock that contains trace carbonaceous material. This rock will be the first rock that we know of that has completed a round trip between planets and will therefore serve an EPO role to attract public attention to science and planetary exploration. The SHERLOC calibration target will address a wide range of NASA goals to include basic science of interest to both the Science Mission Directorate (SMD) and Human Exploration and Operations Mission Directorate (HEOMD).

  17. Language Learning Enhanced by Massive Multiple Online Role-Playing Games (MMORPGs) and the Underlying Behavioral and Neural Mechanisms.

    Science.gov (United States)

    Zhang, Yongjun; Song, Hongwen; Liu, Xiaoming; Tang, Dinghong; Chen, Yue-E; Zhang, Xiaochu

    2017-01-01

    Massive Multiple Online Role-Playing Games (MMORPGs) have increased in popularity among children, juveniles, and adults since MMORPGs' appearance in this digital age. MMORPGs can be applied to enhancing language learning, which is drawing researchers' attention from different fields and many studies have validated MMORPGs' positive effect on language learning. However, there are few studies on the underlying behavioral or neural mechanism of such effect. This paper reviews the educational application of the MMORPGs based on relevant macroscopic and microscopic studies, showing that gamers' overall language proficiency or some specific language skills can be enhanced by real-time online interaction with peers and game narratives or instructions embedded in the MMORPGs. Mechanisms underlying the educational assistant role of MMORPGs in second language learning are discussed from both behavioral and neural perspectives. We suggest that attentional bias makes gamers/learners allocate more cognitive resources toward task-related stimuli in a controlled or an automatic way. Moreover, with a moderating role played by activation of reward circuit, playing the MMORPGs may strengthen or increase functional connectivity from seed regions such as left anterior insular/frontal operculum (AI/FO) and visual word form area to other language-related brain areas.

  18. Determination of Key Risk Supervision Areas around River-Type Water Sources Affected by Multiple Risk Sources: A Case Study of Water Sources along the Yangtze’s Nanjing Section

    Directory of Open Access Journals (Sweden)

    Qi Zhou

    2017-02-01

    Full Text Available To provide a reference for risk management of water sources, this study screens the key risk supervision areas around river-type water sources (hereinafter referred to as the water sources threatened by multiple fixed risk sources (the risk sources, and establishes a comprehensive methodological system. Specifically, it comprises: (1 method of partitioning risk source concentrated sub-regions for screening water source perimeter key risk supervision areas; (2 approach of determining sub-regional risk indexes (SrRI, which characterizes the scale of sub-regional risks considering factors like risk distribution intensity within sub-regions, risk indexes of risk sources (RIRS, characterizing the risk scale of risk sources and the number of risk sources; and (3 method of calculating sub-region’s risk threats to the water sources (SrTWS which considers the positional relationship between water sources and sub-regions as well as SrRI, and the criteria for determining key supervision sub-regions. Favorable effects are achieved by applying this methodological system in determining water source perimeter sub-regions distributed along the Yangtze’s Nanjing section. Results revealed that for water sources, the key sub-regions needing supervision were SD16, SD06, SD21, SD26, SD15, SD03, SD02, SD32, SD10, SD11, SD14, SD05, SD27, etc., in the order of criticality. The sub-region with the greatest risk threats on the water sources was SD16, which was located in the middle reaches of Yangtze River. In general, sub-regions along the upper Yangtze reaches had greater threats to water sources than the lower reach sub-regions other than SD26 and SD21. Upstream water sources were less subject to the threats of sub-regions than the downstream sources other than NJ09B and NJ03.

  19. Deconstructing the symbol digit modalities test in multiple sclerosis: The role of memory.

    Science.gov (United States)

    Patel, Viral P; Walker, Lisa A S; Feinstein, Anthony

    2017-10-01

    The Symbol Digit Modalities Test (SDMT) is a sensitive measure of impaired cognition in people with MS. While the SDMT is primarily considered a test of information processing speed, other components such as visual scanning and oral-motor ability have also been linked to performance. The objective of this study was to determine the role of memory in the performance of the SDMT. Two version of a modified computerized SDMT (c-SDMT) were employed, a fixed and a variable. For each group 50 MS and 33 healthy control (HC) participants were recruited. In the fixed c-SDMT, the symbol-digit code is kept constant for the entire test whereas in the variable version, it changes eight times. Unlike the traditional SDMT which records the correct number of responses, the c-SDMT presented here measures the mean response time (in seconds) for the eight trials. MS participants were slower than HC on the fixed (p < 0.001) and variable (p = 0.005) c-SDMT. Trend analysis showed performance improvement on the fixed, but not on the variable c-SDMT in both MS and HC groups. Furthermore, immediate visual memory recall was associated with the fixed (β = -0.299, p = 0.017), but not variable (B = -0.057, p = 0.260) c-SDMT. Immediate verbal memory was not associated with either versions of the c-SDMT. Given that the fixed and variable c-SDMTs are identical in every way apart from the fixity of the code, the ability of participants to speed up responses over the course of the fixed version only points to the contribution of incidental visual memory in test performance. Copyright © 2017. Published by Elsevier B.V.

  20. Gamma-Klotho exhibits multiple roles in tumor growth of human bladder cancer.

    Science.gov (United States)

    Hori, Shunta; Miyake, Makito; Tatsumi, Yoshihiro; Morizawa, Yosuke; Nakai, Yasushi; Onishi, Sayuri; Onishi, Kenta; Iida, Kota; Gotoh, Daisuke; Tanaka, Nobumichi; Fujimoto, Kiyohide

    2018-04-13

    Alpha-Klotho (KLα) and beta-Klotho (KLβ) have recently been reported to correlate with cancer prognosis in some malignancies and we previously reported the association between KLα, KLβ, and urothelial carcinoma of the bladder (UCB), indicating that KLβ acts as a tumor promoter. However, the association between gamma-Klotho (KLγ) and cancer prognosis remains unclear. In the present study, we evaluated the association between KLγ and UCB. To evaluate the effect of KLγ on human bladder cancer cell lines in vitro assays were performed. Exogenous KLγ increased the ability of human bladder cancer cells to proliferate, migrate, invade, form colonies, and provide anchorage-independent growth potential. In in vivo assays, eighteen mice bearing xenografts inoculated using UM-UC-3, were randomly divided into three groups and treated with a small interfering RNA (siRNA) by intratumoral administration once a week for four weeks. Knockdown of KLγ with siRNA led to a dramatic change in tumor growth and suggested that KLγ had effects on tumor growth, including promotion of cell proliferation, inhibition of apoptosis, and enhancement of the epithelial-mesenchymal transition. To confirm the study, human tissue samples were used and patients were divided into two groups according to KLγ expression level. High expression of KLγ was significantly associated with higher stage and grade cancer and the presence of lymphovascular invasion compared to patients with lower expression of KLγ. Our results suggest that KLγ plays an important role in tumor invasion and progression and these results may lead to the development of new therapies and diagnostic methods for UCB.

  1. Nitric Oxide Plays a Key Role in Ovariectomy-Induced Apoptosis in Anterior Pituitary: Interplay between Nitric Oxide Pathway and Estrogen

    Science.gov (United States)

    Quinteros, Fernanda A.; Duvilanski, Beatriz H.; Cabilla, Jimena P.

    2016-01-01

    Changes in the estrogenic status produce deep changes in pituitary physiology, mainly because estrogens (E2) are one of the main regulators of pituitary cell population. Also, E2 negatively regulate pituitary neuronal nitric oxide synthase (nNOS) activity and expression and may thereby modulate the production of nitric oxide (NO), an important regulator of cell death and survival. Little is known about how ovary ablation affects anterior pituitary cell remodelling and molecular mechanisms that regulate this process have not yet been elucidated. In this work we used freshly dispersed anterior pituitaries as well as cell cultures from ovariectomized female rats in order to study whether E2 deficiency induces apoptosis in the anterior pituitary cells, the role of NO in this process and effects of E2 on the NO pathway. Our results showed that cell activity gradually decreases after ovariectomy (OVX) as a consequence of cell death, which is completely prevented by a pan-caspase inhibitor. Furthermore, there is an increase of fragmented nuclei and DNA cleavage thereby presenting the first direct evidence of the existence of apoptosis in the anterior pituitary gland after OVX. NO production and soluble guanylyl cyclase (sGC) expression in anterior pituitary cells increased concomitantly to the apoptosis. Inhibition of both, NO synthase (NOS) and sGC activities prevented the drop of cell viability after OVX, showing for the first time that increased NO levels and sGC activity observed post-OVX play a key role in the induction of apoptosis. Conversely, E2 and prolactin treatments decreased nNOS expression and activity in pituitary cells from OVX rats in a time- and E2 receptor-dependent manner, thus suggesting interplay between NO and E2 pathways in anterior pituitary. PMID:27611913

  2. Nitric Oxide Plays a Key Role in Ovariectomy-Induced Apoptosis in Anterior Pituitary: Interplay between Nitric Oxide Pathway and Estrogen.

    Directory of Open Access Journals (Sweden)

    Sonia A Ronchetti

    Full Text Available Changes in the estrogenic status produce deep changes in pituitary physiology, mainly because estrogens (E2 are one of the main regulators of pituitary cell population. Also, E2 negatively regulate pituitary neuronal nitric oxide synthase (nNOS activity and expression and may thereby modulate the production of nitric oxide (NO, an important regulator of cell death and survival. Little is known about how ovary ablation affects anterior pituitary cell remodelling and molecular mechanisms that regulate this process have not yet been elucidated. In this work we used freshly dispersed anterior pituitaries as well as cell cultures from ovariectomized female rats in order to study whether E2 deficiency induces apoptosis in the anterior pituitary cells, the role of NO in this process and effects of E2 on the NO pathway. Our results showed that cell activity gradually decreases after ovariectomy (OVX as a consequence of cell death, which is completely prevented by a pan-caspase inhibitor. Furthermore, there is an increase of fragmented nuclei and DNA cleavage thereby presenting the first direct evidence of the existence of apoptosis in the anterior pituitary gland after OVX. NO production and soluble guanylyl cyclase (sGC expression in anterior pituitary cells increased concomitantly to the apoptosis. Inhibition of both, NO synthase (NOS and sGC activities prevented the drop of cell viability after OVX, showing for the first time that increased NO levels and sGC activity observed post-OVX play a key role in the induction of apoptosis. Conversely, E2 and prolactin treatments decreased nNOS expression and activity in pituitary cells from OVX rats in a time- and E2 receptor-dependent manner, thus suggesting interplay between NO and E2 pathways in anterior pituitary.

  3. Nitric Oxide Plays a Key Role in Ovariectomy-Induced Apoptosis in Anterior Pituitary: Interplay between Nitric Oxide Pathway and Estrogen.

    Science.gov (United States)

    Ronchetti, Sonia A; Machiavelli, Leticia I; Quinteros, Fernanda A; Duvilanski, Beatriz H; Cabilla, Jimena P

    2016-01-01

    Changes in the estrogenic status produce deep changes in pituitary physiology, mainly because estrogens (E2) are one of the main regulators of pituitary cell population. Also, E2 negatively regulate pituitary neuronal nitric oxide synthase (nNOS) activity and expression and may thereby modulate the production of nitric oxide (NO), an important regulator of cell death and survival. Little is known about how ovary ablation affects anterior pituitary cell remodelling and molecular mechanisms that regulate this process have not yet been elucidated. In this work we used freshly dispersed anterior pituitaries as well as cell cultures from ovariectomized female rats in order to study whether E2 deficiency induces apoptosis in the anterior pituitary cells, the role of NO in this process and effects of E2 on the NO pathway. Our results showed that cell activity gradually decreases after ovariectomy (OVX) as a consequence of cell death, which is completely prevented by a pan-caspase inhibitor. Furthermore, there is an increase of fragmented nuclei and DNA cleavage thereby presenting the first direct evidence of the existence of apoptosis in the anterior pituitary gland after OVX. NO production and soluble guanylyl cyclase (sGC) expression in anterior pituitary cells increased concomitantly to the apoptosis. Inhibition of both, NO synthase (NOS) and sGC activities prevented the drop of cell viability after OVX, showing for the first time that increased NO levels and sGC activity observed post-OVX play a key role in the induction of apoptosis. Conversely, E2 and prolactin treatments decreased nNOS expression and activity in pituitary cells from OVX rats in a time- and E2 receptor-dependent manner, thus suggesting interplay between NO and E2 pathways in anterior pituitary.

  4. Study of 'Redhaven' peach and its white-fleshed mutant suggests a key role of CCD4 carotenoid dioxygenase in carotenoid and norisoprenoid volatile metabolism

    Directory of Open Access Journals (Sweden)

    Tartarini Stefano

    2011-01-01

    Full Text Available Abstract Background Carotenoids are plant metabolites which are not only essential in photosynthesis but also important quality factors in determining the pigmentation and aroma of flowers and fruits. To investigate the regulation of carotenoid metabolism, as related to norisoprenoids and other volatile compounds in peach (Prunus persica L. Batsch., and the role of carotenoid dioxygenases in determining differences in flesh color phenotype and volatile composition, the expression patterns of relevant carotenoid genes and metabolites were studied during fruit development along with volatile compound content. Two contrasted cultivars, the yellow-fleshed 'Redhaven' (RH and its white-fleshed mutant 'Redhaven Bianca' (RHB were examined. Results The two genotypes displayed marked differences in the accumulation of carotenoid pigments in mesocarp tissues. Lower carotenoid levels and higher levels of norisoprenoid volatiles were observed in RHB, which might be explained by differential activity of carotenoid cleavage dioxygenase (CCD enzymes. In fact, the ccd4 transcript levels were dramatically higher at late ripening stages in RHB with respect to RH. The two genotypes also showed differences in the expression patterns of several carotenoid and isoprenoid transcripts, compatible with a feed-back regulation of these transcripts. Abamine SG - an inhibitor of CCD enzymes - decreased the levels of both isoprenoid and non-isoprenoid volatiles in RHB fruits, indicating a complex regulation of volatile production. Conclusions Differential expression of ccd4 is likely to be the major determinant in the accumulation of carotenoids and carotenoid-derived volatiles in peach fruit flesh. More in general, dioxygenases appear to be key factors controlling volatile composition in peach fruit, since abamine SG-treated 'Redhaven Bianca' fruits had strongly reduced levels of norisoprenoids and other volatile classes. Comparative functional studies of peach carotenoid

  5. Qualitative aspects of representational competence among college chemistry students: Multiple representations and their role in the understanding of ideal gases

    Science.gov (United States)

    Madden, Sean Patrick

    This study examined the role of multiple representations of chemical phenomena, specifically, the temperature-pressure relationship of ideal gases, in the problem solving strategies of college chemistry students. Volunteers included students enrolled in a first semester general chemistry course at a western university. Two additional volunteers from the same university were asked to participate and serve as models of greater sophistication. One was a senior chemistry major; another was a junior science writing major. Volunteers completed an initial screening task involving multiple representations of concentration and dilution concepts. Based on the results of this screening instrument a smaller set of subjects were asked to complete a think aloud session involving multiple representations of the temperature-pressure relationship. Data consisted of the written work of the volunteers and transcripts from videotaped think aloud sessions. The data were evaluated by the researcher and two other graduate students in chemical education using a coding scheme (Kozma, Schank, Coppola, Michalchik, and Allen. 2000). This coding scheme was designed to identify essential features of representational competence and differences in uses of multiple representations. The results indicate that students tend to have a strong preference for one type of representation. Students scoring low on representational competence, as measured by the rubric, ignored important features of some representations or acknowledged them only superficially. Students scoring higher on representational competence made meaningful connections among representations. The more advanced students, those who rated highly on representational competence, tended to use their preferred representation in a heuristic manner to establish meaning for other representations. The more advanced students also reflected upon the problem at greater length before beginning work. Molecular level sketches seemed to be the most

  6. Efficiently outsourcing multiparty computation under multiple keys

    NARCIS (Netherlands)

    Peter, Andreas; Tews, Erik; Tews, Erik; Katzenbeisser, Stefan

    2013-01-01

    Secure multiparty computation enables a set of users to evaluate certain functionalities on their respective inputs while keeping these inputs encrypted throughout the computation. In many applications, however, outsourcing these computations to an untrusted server is desirable, so that the server

  7. ZIP8 zinc transporter: indispensable role for both multiple-organ organogenesis and hematopoiesis in utero.

    Directory of Open Access Journals (Sweden)

    Marina Gálvez-Peralta

    Full Text Available Previously this laboratory characterized Slc39a8-encoded ZIP8 as a Zn(2+/(HCO(3(-(2 symporter; yet, the overall physiological importance of ZIP8 at the whole-organism level remains unclear. Herein we describe the phenotype of the hypomorphic Slc39a8(neo/neo mouse which has retained the neomycin-resistance gene in intron 3, hence causing significantly decreased ZIP8 mRNA and protein levels in embryo, fetus, placenta, yolk sac, and several tissues of neonates. The Slc39a8(neo allele is associated with diminished zinc and iron uptake in mouse fetal fibroblast and liver-derived cultures; consequently, Slc39a8(neo/neo newborns exhibit diminished zinc and iron levels in several tissues. Slc39a8(neo/neo homozygotes from gestational day(GD-11.5 onward are pale, growth-stunted, and die between GD18.5 and 48 h postnatally. Defects include: severely hypoplastic spleen; hypoplasia of liver, kidney, lung, and lower limbs. Histologically, Slc39a8(neo/neo neonates show decreased numbers of hematopoietic islands in yolk sac and liver. Low hemoglobin, hematocrit, red cell count, serum iron, and total iron-binding capacity confirmed severe anemia. Flow cytometry of fetal liver cells revealed the erythroid series strikingly affected in the hypomorph. Zinc-dependent 5-aminolevulinic acid dehydratase, required for heme synthesis, was not different between Slc39a8(+/+ and Slc39a8(neo/neo offspring. To demonstrate further that the mouse phenotype is due to ZIP8 deficiency, we bred Slc39a8(+/neo with BAC-transgenic BTZIP8-3 line (carrying three extra copies of the Slc39a8 allele; this cross generated viable Slc39a8(neo/neo_BTZIP8-3(+/+ pups showing none of the above-mentioned congenital defects-proving Slc39a8(neo/neo causes the described phenotype. Our study demonstrates that ZIP8-mediated zinc transport plays an unappreciated critical role during in utero and neonatal growth, organ morphogenesis, and hematopoiesis.

  8. Drought-induced defoliation and long periods of near-zero gas exchange play a key role in accentuating metabolic decline of Scots pine.

    Science.gov (United States)

    Poyatos, Rafael; Aguadé, David; Galiano, Lucía; Mencuccini, Maurizio; Martínez-Vilalta, Jordi

    2013-10-01

    Drought-induced defoliation has recently been associated with the depletion of carbon reserves and increased mortality risk in Scots pine (Pinus sylvestris). We hypothesize that defoliated individuals are more sensitive to drought, implying that potentially higher gas exchange (per unit of leaf area) during wet periods may not compensate for their reduced photosynthetic area. We measured sap flow, needle water potentials and whole-tree hydraulic conductance to analyse the drought responses of co-occurring defoliated and nondefoliated Scots pines in northeast Spain during typical (2010) and extreme (2011) drought conditions. Defoliated Scots pines showed higher sap flow per unit leaf area during spring, but were more sensitive to summer drought, relative to nondefoliated pines. This pattern was associated with a steeper decline in soil-to-leaf hydraulic conductance with drought and an enhanced sensitivity of canopy conductance to soil water availability. Near-homeostasis in midday water potentials was observed across years and defoliation classes, with minimum values of -2.5 MPa. Enhanced sensitivity to drought and prolonged periods of near-zero gas exchange were consistent with low levels of carbohydrate reserves in defoliated trees. Our results support the critical links between defoliation, water and carbon availability, and their key roles in determining tree survival and recovery under drought. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  9. Quantitative cell polarity imaging defines leader-to-follower transitions during collective migration and the key role of microtubule-dependent adherens junction formation.

    Science.gov (United States)

    Revenu, Céline; Streichan, Sebastian; Donà, Erika; Lecaudey, Virginie; Hufnagel, Lars; Gilmour, Darren

    2014-03-01

    The directed migration of cell collectives drives the formation of complex organ systems. A characteristic feature of many migrating collectives is a 'tissue-scale' polarity, whereby 'leader' cells at the edge of the tissue guide trailing 'followers' that become assembled into polarised epithelial tissues en route. Here, we combine quantitative imaging and perturbation approaches to investigate epithelial cell state transitions during collective migration and organogenesis, using the zebrafish lateral line primordium as an in vivo model. A readout of three-dimensional cell polarity, based on centrosomal-nucleus axes, allows the transition from migrating leaders to assembled followers to be quantitatively resolved for the first time in vivo. Using live reporters and a novel fluorescent protein timer approach, we investigate changes in cell-cell adhesion underlying this transition by monitoring cadherin receptor localisation and stability. This reveals that while cadherin 2 is expressed across the entire tissue, functional apical junctions are first assembled in the transition zone and become progressively more stable across the leader-follower axis of the tissue. Perturbation experiments demonstrate that the formation of these apical adherens junctions requires dynamic microtubules. However, once stabilised, adherens junction maintenance is microtubule independent. Combined, these data identify a mechanism for regulating leader-to-follower transitions within migrating collectives, based on the relocation and stabilisation of cadherins, and reveal a key role for dynamic microtubules in this process.

  10. A Key Role for NF-κB Transcription Factor c-Rel in T-Lymphocyte-Differentiation and Effector Functions

    Directory of Open Access Journals (Sweden)

    Alexander Visekruna

    2012-01-01

    Full Text Available The transcription factors of the Rel/NF-κB family function as key regulators of innate and adoptive immunity. Tightly and temporally controlled activation of NF-κB-signalling pathways ensures prevention of harmful immune cell dysregulation, whereas a loss of control leads to pathological conditions such as severe inflammation, autoimmune disease, and inflammation-associated oncogenesis. Five family members have been identified in mammals: RelA (p65, c-Rel, RelB, and the precursor proteins NF-κB1 (p105 and NF-κB2 (p100, that are processed into p50 and p52, respectively. While RelA-containing dimers are present in most cell types, c-Rel complexes are predominately found in cells of hematopoietic origin. In T-cell lymphocytes, certain genes essential for immune function such as Il2 and Foxp3 are directly regulated by c-Rel. Additionally, c-Rel-dependent IL-12 and IL-23 transcription by macrophages and dendritic cells is crucial for T-cell differentiation and effector functions. Accordingly, c-Rel expression in T cells and antigen-presenting cells (APCs controls a delicate balance between tolerance and immunity. This review gives a selective overview on recent progress in understanding of diverse roles of c-Rel in regulating adaptive immunity.

  11. Multiple regulatory roles of the mouse transmembrane adaptor protein NTAL in gene transcription and mast cell physiology.

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    Iva Polakovicova

    Full Text Available Non-T cell activation linker (NTAL; also called LAB or LAT2 is a transmembrane adaptor protein that is expressed in a subset of hematopoietic cells, including mast cells. There are conflicting reports on the role of NTAL in the high affinity immunoglobulin E receptor (FcεRI signaling. Studies carried out on mast cells derived from mice with NTAL knock out (KO and wild type mice suggested that NTAL is a negative regulator of FcεRI signaling, while experiments with RNAi-mediated NTAL knockdown (KD in human mast cells and rat basophilic leukemia cells suggested its positive regulatory role. To determine whether different methodologies of NTAL ablation (KO vs KD have different physiological consequences, we compared under well defined conditions FcεRI-mediated signaling events in mouse bone marrow-derived mast cells (BMMCs with NTAL KO or KD. BMMCs with both NTAL KO and KD exhibited enhanced degranulation, calcium mobilization, chemotaxis, tyrosine phosphorylation of LAT and ERK, and depolymerization of filamentous actin. These data provide clear evidence that NTAL is a negative regulator of FcεRI activation events in murine BMMCs, independently of possible compensatory developmental alterations. To gain further insight into the role of NTAL in mast cells, we examined the transcriptome profiles of resting and antigen-activated NTAL KO, NTAL KD, and corresponding control BMMCs. Through this analysis we identified several genes that were differentially regulated in nonactivated and antigen-activated NTAL-deficient cells, when compared to the corresponding control cells. Some of the genes seem to be involved in regulation of cholesterol-dependent events in antigen-mediated chemotaxis. The combined data indicate multiple regulatory roles of NTAL in gene expression and mast cell physiology.

  12. Roles sociales de la sociedad contemporánea en la película 'Multiplicity' de Harold Ramis

    Directory of Open Access Journals (Sweden)

    Raquel Fernández Cobo

    2015-10-01

    Full Text Available Multiplicity (2010, dirigida por Harold Ramis, plasma en pantalla a través del motivo del doble los elementos que constituyen la crisis del sujeto y que representan al individuo bajo el signo de la disipación. Mediante un análisis temático y discursivo del motivo del doble examinamos cómo el protagonista, al intentar llevar a cabo la totalidad de los roles sociales, se ve abocada a las contradicciones más agudas de la sociedad, manifestadas, sobre todo, a nivel del cuerpo, tanto en el manifiesto simbolismo del motivo del doble como en el “terror biológico” que de forma absolutamente irónica y humorística se representa en el último clon del protagonista.

  13. Ethnic and racial socialization and self-esteem of Asian adoptees: the mediating role of multiple identities.

    Science.gov (United States)

    Mohanty, Jayashree

    2013-02-01

    Positive identity development during adolescence in general is a complex process and may pose additional challenges for adolescents adopted from a different culture. Using a web-based survey design with a sample of 100 internationally adopted Asian adolescent and young adults, the present study examined the mediating role of multiple identities (i.e., ethnic, adoptive and interpersonal ego identities) in explaining the relationship between ethnic and racial socializations, ethnic neighborhood, and self-esteem. The results showed that (a) adoptive identity mediated the influence of racial socialization on psychological well-being, and (b) ethnic affirmation mediated the influence of ethnic socialization on adoptees' well-being. This study illustrates the importance of providing supportive counseling services for adoptees who are exploring their adoptive identity. Copyright © 2012 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  14. Podocalyxin Is a Novel Polysialylated Neural Adhesion Protein with Multiple Roles in Neural Development and Synapse Formation

    Science.gov (United States)

    Vitureira, Nathalia; Andrés, Rosa; Pérez-Martínez, Esther; Martínez, Albert; Bribián, Ana; Blasi, Juan; Chelliah, Shierley; López-Doménech, Guillermo; De Castro, Fernando; Burgaya, Ferran; McNagny, Kelly; Soriano, Eduardo

    2010-01-01

    Neural development and plasticity are regulated by neural adhesion proteins, including the polysialylated form of NCAM (PSA-NCAM). Podocalyxin (PC) is a renal PSA-containing protein that has been reported to function as an anti-adhesin in kidney podocytes. Here we show that PC is widely expressed in neurons during neural development. Neural PC interacts with the ERM protein family, and with NHERF1/2 and RhoA/G. Experiments in vitro and phenotypic analyses of podxl-deficient mice indicate that PC is involved in neurite growth, branching and axonal fasciculation, and that PC loss-of-function reduces the number of synapses in the CNS and in the neuromuscular system. We also show that whereas some of the brain PC functions require PSA, others depend on PC per se. Our results show that PC, the second highly sialylated neural adhesion protein, plays multiple roles in neural development. PMID:20706633

  15. Techno-economic assessment and policy of gas power generation considering the role of multiple stakeholders in China

    International Nuclear Information System (INIS)

    Dong Jun; Zhang Xu; Xu Xiaolin

    2012-01-01

    In accordance with the energy planning in China, within the “Twelfth Five-Year” period (2011–2015), the proportion of natural gas among primary energy consumption is expected to increase from the current 4% to 8%. In 2015, about 17 natural gas pipelines will be completed. This paper reviews the current situation of gas power generation, analyzes the main opportunities and obstacles of gas power generation development in China, and conducts a techno-economic assessment of the natural gas power generation, taking into account the role and the interaction of the multiple stakeholders in the natural gas industry chain. Taking a power plant fueled with the natural gas transported by the second West-to-East Pipeline as an example, it is found that the on-grid power price fluctuates upward with the rise of gas price and downward with the increase of annual utilization hours, and the influences of tax policies on the on-grid power price prove to be highly significant. As the analysis and calculation indicate, the environmental benefits of natural gas power generation ought to be strongly emphasized, compared with coal-fired power generation. Finally, this paper puts forward specific policy recommendations, from the perspectives of electricity price, gas price, tax, power grid dispatching, etc. - Highlights: ► Presents the opportunities and obstacles of gas power generation development in China. ► Analyzes the interactions of multiple stakeholders in the natural gas industry chain. ► Conducts a techno-economic assessment on the natural gas power generation. ► Discusses the responsibilities and risks of multiple stakeholders. ► Puts forward policy recommendations, from electricity price, gas price, tax, etc.

  16. The key role of {sup 99m}Tc-MIBI SPECT/CT in the diagnosis of parathyroid adenoma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qing; Pan, Jiemin; Luo, Quanyong; Wang, Yan; Bao, Yuqian; Jia, Weiping, E-mail: wpjia@sjtu.edu.cn, E-mail: wpjia@yahoo.com [Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai (China)

    2015-06-15

    The concomitant occurrence of primary hyperparathyroidism (PHPT) due to parathyroid adenoma and papillary thyroid carcinoma (PTC) is not common. The co-occurrence of parathyroid tumors and thyroid diseases can lead to misdiagnosis owing to mutual interference of imaging in the early period of disease. The most commonly used imaging techniques for the preoperative localization of parathyroid and thyroid adenomas are technetium-99m sestamibi ({sup 99m}Tc-MIBI) scintigraphy and ultrasonography of the neck. Recently, {sup 99m}Tc-MIBI single-photon emission computed tomography associated with computed tomography scintigraphy (SPECT/CT) has been used to detect PHPT, and its diagnostic value is being evaluated. Herein, we report a patient with an unusual co-occurrence of parathyroid adenoma and multiple thyroid diseases, including papillary thyroid carcinoma, thyroid adenoma and lymphocytic thyroiditis, which were localized with {sup 99}mTc-MIBI SPECT/CT and confirmed surgically. We suggest that {sup 99m}Tc-MIBI SPECT/CT can play an important role in the diagnosis of parathyroid and thyroid lesions. (author)

  17. The Role of Coping Styles in the Relationship between Personality Traits and Quality of Life of Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Seyed Amir Hejazi Taghanaki

    2016-06-01

    Full Text Available Background and Objectives: Individuals with multiple sclerosis (MS show different reactions to the disease according to their personality traits, which can affect their quality of life. In this research, the mediator role of coping styles was investigated in the relationship between personality traits and quality of life in individuals with multiple sclerosis (MS. Methods: Of all individuals with MS, who were member of MS Society of Qom province, 170 persons were selected using probability convenient sampling. All the patients were investigated using a general questionnaire in addition to 3 international approved standard tools (including Stress Coping Styles, Quality of life, and Personality Traits questionnaires. Data analysis was performed by descriptive-analytical statistics, Pearson’s correlation coefficient. The significance level was considered as p<0.05. Results: The mean age of the patients was in the range of 18-59 years, 32.34±8.71, of whom 138 subjects (83.2% were female. In this research, there was a significant correlation between coping styles and quality of life and its dimensions in MS patients. The correlation between coping styles and personality traits, was significant. There was a significant correlation between personality traits and quality of life and its dimensions in MS patients. In this study, path analysis results proved the mediator role of coping styles in the relationship between variables of quality of life and personality traits. Conclusion: According to the results of this study, there is a significant correlation between personality traits of the individuals with MS and type of the used coping styles, which can affect the quality of life in these patients.

  18. The role of multiple ionization and subshell coupling effects in L-shell ionization of Au by oxygen ions

    International Nuclear Information System (INIS)

    Banas, D.; Braziewicz, J.; Pajek, M.; Semaniak, J.; Czyzewski, T.; Fijal, I.; Jaskola, M.; Kretschmer, W.; Mukoyama, T.; Trautmann, D.

    2002-01-01

    The ionization of L-subshell electrons in gold by the impact of 0.4-2.2 MeV amu -1 O ions was studied by observing excited Lγ(L-N, O) x-rays. We demonstrate that both the multiple ionization in outer M- and N-shells as well as the coupling effects in the L-shell play an important role in understanding the measured L-subshell ionization cross sections. The multiple ionization was found to be important in two aspects: first, the analysis of x-ray energy shifts and line broadening was crucial for proper interpretation of measured x-ray spectra; second, the additional vacancies in the M- and N-shells substantially influenced the L 1 -subshell fluorescence and Coster-Kronig (CK) yields, mainly by closing strong L 1 -L 3 M 4,5 CK transitions. The data are compared with the simplified coupled-channels calculations using the 'coupled-subshell model' (CSM) based on the semiclassical approximation (SCA), which describes both direct Coulomb ionization as well as the L-subshell couplings within the same theoretical approach. A good agreement of the present data with the theoretical predictions based on the discussed SCA-CSM approach is observed. Present findings partly explain the long-standing problem of inadequate theoretical description of L-shell ionization by heavy ion impact. (author)

  19. Transcriptome Analysis Reveals Novel Entry Mechanisms and a Central Role of SRC in Host Defense during High Multiplicity Mycobacterial Infection.

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    Jay Zhang

    Full Text Available Mycobacterium tuberculosis (MTB infects an estimated one-third of the global population and is one of the main causes of mortality from an infectious agent. The characteristics of macrophages challenged by MTB with a high multiplicity of infection (MOI, which mimics both clinical disseminated infection and granuloma formation, are distinct from macrophages challenged with a low MOI. To better understand the cross talk between macrophage host cells and mycobacteria, we compared the transcription patterns of mouse macrophages infected with bacille Calmette-Guérin, H37Ra and M. smegmatis. Attention was focused on the changes in the abundance of transcripts related to immune system function. From the results of a transcriptome profiling study with a high mycobacterial MOI, we defined a pathogen-specific host gene expression pattern. The present study suggests that two integrins, ITGA5 and ITGAV, are novel cell surface receptors mediating mycobacterium entry into macrophages challenged with high MOI. Our results indicate that SRC likely plays a central role in regulating multiple unique signaling pathways activated by MTB infection. The integrated results increase our understanding of the molecular networks behind the host innate immune response and identify important targets that might be useful for the development of tuberculosis therapy.

  20. The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis

    Science.gov (United States)

    Živković, Maja; Starčević Čizmarević, Nada; Lovrečić, Luca; Klupka-Sarić, Inge; Stanković, Aleksandra; Gašparović, Iva; Dinčić, Evica; Stojković, Ljiljana; Rudolf, Gorazd; Šega Jazbec, Saša; Perković, Olivio; Sinanović, Osman; Sepčić, Juraj; Kapović, Miljenko; Peterlin, Borut

    2014-01-01

    Background. Previous studies have shown impaired fibrinolysis in multiple sclerosis (MS) and implicated extracellular proteolytic enzymes as important factors in demyelinating neuroinflammatory disorders. Tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1) are key molecules in both fibrinolysis and extracellular proteolysis. In the present study, an association of the TPA Alu I/D and PAI-1 4G/5G polymorphisms with MS was analyzed within the Genomic Network for Multiple Sclerosis (GENoMS). Methods. The GENoMS includes four populations (Croatian, Slovenian, Serbian, and Bosnian and Herzegovinian) sharing the same geographic location and a similar ethnic background. A total of 885 patients and 656 ethnically matched healthy blood donors with no history of MS in their families were genotyped using PCR-RFLP. Results. TPA DD homozygosity was protective (OR = 0.79, 95% CI 0.63–0.99, P = 0.037) and PAI 5G5G was a risk factor for MS (OR = 1.30, 95% CI 1.01–1.66, P = 0.038). A significant effect of the genotype/carrier combination was detected in 5G5G/I carriers (OR = 1.39 95% CI 1.06–1.82, P = 0.017). Conclusions. We found a significantly harmful effect of the combination of the PAI-1 5G/5G genotype and TPA I allele on MS susceptibility, which indicates the importance of gene-gene interactions in complex diseases such as MS. PMID:24825926

  1. An amphipathic alpha-helix controls multiple roles of brome mosaic virus protein 1a in RNA replication complex assembly and function.

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    Ling Liu

    2009-03-01

    Full Text Available Brome mosaic virus (BMV protein 1a has multiple key roles in viral RNA replication. 1a localizes to perinuclear endoplasmic reticulum (ER membranes as a peripheral membrane protein, induces ER membrane invaginations in which RNA replication complexes form, and recruits and stabilizes BMV 2a polymerase (2a(Pol and RNA replication templates at these sites to establish active replication complexes. During replication, 1a provides RNA capping, NTPase and possibly RNA helicase functions. Here we identify in BMV 1a an amphipathic alpha-helix, helix A, and use NMR analysis to define its structure and propensity to insert in hydrophobic membrane-mimicking micelles. We show that helix A is essential for efficient 1a-ER membrane association and normal perinuclear ER localization, and that deletion or mutation of helix A abolishes RNA replication. Strikingly, mutations in helix A give rise to two dramatically opposite 1a function phenotypes, implying that helix A acts as a molecular switch regulating the intricate balance between separable 1a functions. One class of helix A deletions and amino acid substitutions markedly inhibits 1a-membrane association and abolishes ER membrane invagination, viral RNA template recruitment, and replication, but doubles the 1a-mediated increase in 2a(Pol accumulation. The second class of helix A mutations not only maintains efficient 1a-membrane association but also amplifies the number of 1a-induced membrane invaginations 5- to 8-fold and enhances viral RNA template recruitment, while failing to stimulate 2a(Pol accumulation. The results provide new insights into the pathways of RNA replication complex assembly and show that helix A is critical for assembly and function of the viral RNA replication complex, including its central role in targeting replication components and controlling modes of 1a action.

  2. Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations

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    Yusuke Nakatsu

    2016-09-01

    Full Text Available Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14. Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer’s disease. On the other hand, recent studies have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-κB p65. In this review, we focus on recent advances in elucidating the physiological roles of Pin1 as well as the pathogenesis of disorders involving this isomerase, from the viewpoint of the relationships between signal transductions and metabolic functions.

  3. Key Decision Points in the Careers of Geoscientists: The Role of the YES Network in Facilitating Successful Career Transitions for Early Career Geoscientists (Invited)

    Science.gov (United States)

    Venus, J. H.; Gonzales, L. M.; Yes Network

    2010-12-01

    The external influences on the decisions that geoscientists make pertaining to their careers are often assumed but not quantified. The YES Network is conducting an international study to determine the Key Decision points in the career pathways of early career geoscientists. The study aims to identify factors contributing to individual career decisions and to monitor these over a ten year period. The Initial phase of the study is now underway enabling preliminary conclusions to be drawn and will identify a group of individuals that will be tracked over the 10 year programme. The Survey will highlight reoccurring areas where Early Career Geoscientists are experiencing progression difficulties and, importantly, provide respondents with an opportunity to suggest solutions whilst also allowing general resource needs to be identified from the results as a whole. Early results show an overwhelming majority expressing job satisfaction most or all of the time (only 2 candidates reporting none). Respondents rate job satisfaction and respect highly, returning more responses than good salaries. A general frustration with administration, paper work and bureaucracy is particularly evident in those employed by government organisations. Early Career geoscientists express a frustration concerning a lack of involvement in decision making processes; interestingly several later career respondents also acknowledge a need to properly train, nurture and encourage new recruits to retain good graduates who may otherwise become disillusioned and leave the profession. The role of family in career choices has been highlighted both in survey and general feedback responses particularly by female geoscientists and those working in jobs wit