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Sample records for challenge reveal potential

  1. Mammary gene expression profiles during an intramammary challenge reveal potential mechanisms linking negative energy balance with impaired immune response

    DEFF Research Database (Denmark)

    Moyes, Kasey; Drackley, J K; Morin, D E;

    2010-01-01

    Our objective was to compare mammary tissue gene expression profiles during a Streptococcus uberis (S. uberis) mastitis challenge between lactating cows subjected to dietary-induced negative energy balance (NEB; n = 5) and cows fed ad libitum to maintain positive energy balance (PEB; n = 5......) in order to better understand the mechanisms associated with NEB and risk of mastitis during the transition period. The NEB cows were feed-restricted to 60% of calculated net energy for lactation requirements for 7 d, and cows assigned to PEB were fed the same diet for ad libitum intake. Five days after...... feed restriction, one rear mammary quarter of each cow was inoculated with 5,000 cfu of S. uberis (O140J). At 20 h post-inoculation, S. uberis-infected mammary quarters from all cows were biopsied for RNA extraction. Energy balance (NEB vs. PEB) resulted in 287 differentially expressed genes (DEG; FDR...

  2. Mammary gene expression profiles during an intramammary challenge reveal potential mechanisms linking negative energy balance with impaired immune response.

    Science.gov (United States)

    Moyes, Kasey M; Drackley, James K; Morin, Dawn E; Rodriguez-Zas, Sandra L; Everts, Robin E; Lewin, Harris A; Loor, Juan J

    2010-04-01

    Our objective was to compare mammary tissue gene expression profiles during a Streptococcus uberis (S. uberis) mastitis challenge between lactating cows subjected to dietary-induced negative energy balance (NEB; n = 5) and cows fed ad libitum to maintain positive energy balance (PEB; n = 5) to better understand the mechanisms associated with NEB and risk of mastitis during the transition period. The NEB cows were feed-restricted to 60% of calculated net energy for lactation requirements for 7 days, and cows assigned to PEB were fed the same diet for ad libitum intake. Five days after feed restriction, one rear mammary quarter of each cow was inoculated with 5,000 cfu of S. uberis (O140J). At 20 h postinoculation, S. uberis-infected mammary quarters from all cows were biopsied for RNA extraction. Negative energy balance resulted in 287 differentially expressed genes (DEG; false discovery rate ≤ 0.05), with 86 DEG upregulated and 201 DEG downregulated in NEB vs. PEB. Canonical pathways most affected by NEB were IL-8 signaling (10 genes), glucocorticoid receptor signaling (13), and NRF2-mediated oxidative stress response (10). Among the genes differentially expressed by NEB, cell growth and proliferation (48) and cellular development (36) were the most enriched functions. Regarding immune response, HLA-A was upregulated due to NEB, whereas the majority of genes involved in immune response were downregulated (e.g., AKT1, IRAK1, MAPK9, and TRAF6). This study provided new avenues for investigation into the mechanisms relating NEB and susceptibility to mastitis in lactating dairy cows.

  3. Paraganglioma: a potentially challenging tumor.

    Science.gov (United States)

    Trombetta, Mark; Silverman, Jan; Colonias, Athanasios; Lee, Vincent; Mohanty, Alok; Parda, David

    2008-03-01

    Paragangliomas are usually low-grade neoplasms with a benign natural history. While the treatment of paraganglioma has historically been controversial, surgery and radiotherapy have become standardized as therapies of choice for primary therapy. More recently, stereotactic radiosurgery has been used effectively against this rare tumor. The development of metastatic disease in patients with paraganglioma is an unusual and challenging event. This case report and review describes the specific features of this disease and the multiple therapeutic options.

  4. Perovskite Solar Cells: Potentials, Challenges, and Opportunities

    Directory of Open Access Journals (Sweden)

    Muhammad Imran Ahmed

    2015-01-01

    Full Text Available Heralded as a major scientific breakthrough of 2013, organic/inorganic lead halide perovskite solar cells have ushered in a new era of renewed efforts at increasing the efficiency and lowering the cost of solar energy. As a potential game changer in the mix of technologies for alternate energy, it has emerged from a modest beginning in 2012 to efficiencies being claimed at 20.1% in a span of just two years. This remarkable progress, encouraging at one end, also points to the possibility that the potential may still be far from being fully realized. With greater insight into the photophysics involved and optimization of materials and methods, this technology stands to match or even exceed the efficiencies for single crystal silicon solar cells. With thin film solution processability, applicability to flexible substrates, and being free of liquid electrolyte, this technology combines the benefits of Dye Sensitized Solar Cells (DSSCs, Organic Photovoltaics (OPVs, and thin film solar cells. In this review we present a brief historic perspective to this development, take a cognizance of the current state of the art, and highlight challenges and the opportunities.

  5. Gene network and pathway analysis of bovine mammary tissue challenged with Streptococcus uberis reveals induction of cell proliferation and inhibition of PPARγ signaling as potential mechanism for the negative relationships between immune response and lipid metabolism

    Directory of Open Access Journals (Sweden)

    Rodriguez-Zas Sandra L

    2009-11-01

    Full Text Available Abstract Background Information generated via microarrays might uncover interactions between the mammary gland and Streptococcus uberis (S. uberis that could help identify control measures for the prevention and spread of S. uberis mastitis, as well as improve overall animal health and welfare, and decrease economic losses to dairy farmers. The main objective of this study was to determine the most affected gene networks and pathways in mammary tissue in response to an intramammary infection (IMI with S. uberis and relate these with other physiological measurements associated with immune and/or metabolic responses to mastitis challenge with S. uberis O140J. Results Streptococcus uberis IMI resulted in 2,102 (1,939 annotated differentially expressed genes (DEG. Within this set of DEG, we uncovered 20 significantly enriched canonical pathways (with 20 to 61 genes each, the majority of which were signaling pathways. Among the most inhibited were LXR/RXR Signaling and PPARα/RXRα Signaling. Pathways activated by IMI were IL-10 Signaling and IL-6 Signaling which likely reflected counter mechanisms of mammary tissue to respond to infection. Of the 2,102 DEG, 1,082 were up-regulated during IMI and were primarily involved with the immune response, e.g., IL6, TNF, IL8, IL10, SELL, LYZ, and SAA3. Genes down-regulated (1,020 included those associated with milk fat synthesis, e.g., LPIN1, LPL, CD36, and BTN1A1. Network analysis of DEG indicated that TNF had positive relationships with genes involved with immune system function (e.g., CD14, IL8, IL1B, and TLR2 and negative relationships with genes involved with lipid metabolism (e.g., GPAM, SCD, FABP4, CD36, and LPL and antioxidant activity (SOD1. Conclusion Results provided novel information into the early signaling and metabolic pathways in mammary tissue that are associated with the innate immune response to S. uberis infection. Our study indicated that IMI challenge with S. uberis (strain O140J elicited

  6. Lubrication of space systems: Challenges and potential solutions

    Science.gov (United States)

    Fusaro, Robert L.

    1992-01-01

    Future space missions will all require advanced mechanical moving components which will require wear protection and lubrication. The tribology practices used today are primarily based upon a technology base that is more than 20 years old. This paper will discuss NASA's future space missions and some of the mechanism tribology challenges that will be encountered. Potential solutions to these challenges using coatings technology will be assessed.

  7. Methods, Challenges and Potentials of Single Cell RNA-seq

    OpenAIRE

    Daniel Hebenstreit

    2012-01-01

    RNA-sequencing (RNA-seq) has become the tool of choice for transcriptomics. Several recent studies demonstrate its successful adaption to single cell analysis. This allows new biological insights into cell differentiation, cell-to-cell variation and gene regulation, and how these aspects depend on each other. Here, I review the current single cell RNA-seq (scRNA-seq) efforts and discuss experimental protocols, challenges and potentials.

  8. Methods, challenges and potentials of single cell RNA-seq

    OpenAIRE

    Hebenstreit, Daniel

    2012-01-01

    RNA-sequencing (RNA-seq) has become the tool of choice for transcriptomics. Several recent studies demonstrate its successful adaption to single cell analysis. This allows new biological insights into cell differentiation, cell-to-cell variation and gene regulation, and how these aspects depend on each other. Here, I review the current single cell RNA-seq (scRNA-seq) efforts and discuss experimental protocols, challenges and potentials.

  9. The potential biomarkers of drug addiction: proteomic and metabolomics challenges.

    Science.gov (United States)

    Wang, Lv; Wu, Ning; Zhao, Tai-Yun; Li, Jin

    2016-07-28

    Drug addiction places a significant burden on society and individuals. Proteomics and metabolomics approaches pave the road for searching potential biomarkers to assist the diagnosis and treatment. This review summarized putative drug addiction-related biomarkers in proteomics and metabolomics studies and discussed challenges and prospects in future studies. Alterations of several hundred proteins and metabolites were reported when exposure to abused drug, which enriched in energy metabolism, oxidative stress response, protein modification and degradation, synaptic function and neurotrasmission, etc. Hsp70, peroxiredoxin-6 and α- and β-synuclein, as well as n-methylserotonin and purine metabolites, were promising as potential biomarker for drug addiction.

  10. Innovation inspired by nature: capabilities, potentials, and challenges

    Science.gov (United States)

    Bar-Cohen, Yoseph

    2012-10-01

    Through evolution, nature came up with many effective solutions to its challenges and continually improving them. By mimicking, coping and being inspired, humans have been using Nature's solutions to address their own challenges. In recent years, the implementation of nature's capabilities has intensified with our growing understanding of the various biological and nastic mechanisms and processes. Successes include even the making of humanlike robots that perform such lifelike tasks as walking, talking, making eye-contact, interpreting speech and facial expressions, as well as many other humanlike functions. Generally, once humans are able to implement a function then, thru rapid advances in technology, capabilities are developed that can significantly exceed the original source of inspiration in Nature. Examples include flight where there is no species that can fly as high, carry so much mass, has so large dimensions and fly so fast, and operate at as such extreme conditions as our aircraft and other aerospace systems. However, using the capabilities of today's technology, there are many challenges that are not feasible to address in mimicking characteristics of species and plants. In this manuscript, state-of-the-art of biomimetic capabilities, potentials and challenges are reviewed.

  11. Innovation Inspired by Nature: Capabilities, Potentials and Challenges

    Science.gov (United States)

    Bar-Cohen, Yoseph

    2012-01-01

    Through evolution, nature came up with many effective solutions to its challenges and continually improving them. By mimicking, coping and being inspired, humans have been using Nature's solutions to address their own challenges. In recent years, the implementation of nature's capabilities has intensified with our growing understanding of the various biological and nastic mechanisms and processes. Successes include even the making of humanlike robots that perform such lifelike tasks as walking, talking, making eye-contact, interpreting speech and facial expressions, as well as many other humanlike functions. Generally, once humans are able to implement a function then, thru rapid advances in technology, capabilities are developed that can significantly exceed the original source of inspiration in Nature. Examples include flight where there is no species that can fly as high, carry so much mass, has so large dimensions and fly so fast, and operate at as such extreme conditions as our aircraft and other aerospace systems. However, using the capabilities of today's technology, there are many challenges that are not feasible to address in mimicking characteristics of species and plants. In this manuscript, state-of-the-art of biomimetic capabilities, potentials and challenges are reviewed.

  12. [Biomass energy utilization in microbial fuel cells: potentials and challenges].

    Science.gov (United States)

    Huang, Liping; Cheng, Shaoan

    2010-07-01

    Microbial fuel cells (MFCs) that can harvest biomass energy from organic wastes through microbial catalysis have garnered more and more attention within the past decade due to its potential benefits to ecological environment. In this article, the updated progress in MFCs is reviewed, with a focus on frontier technologies such as chamber configurations, feedstock varieties and the integration of MFCs with microbial electrolysis cells for hydrogen production. And on the other hand, the challenges like development of cost-effective electrode materials, improvement of biomass energy recovery and power output, design and optimization of commercial MFC devices are presented.

  13. Bioprospection of marine microorganisms: potential and challenges for Argentina.

    Science.gov (United States)

    Dionisi, Hebe M; Lozada, Mariana; Olivera, Nelda L

    2012-01-01

    The marine environments of Argentina have a remarkable extension, as well as high biological productivity and biodiversity of both macro- and microorganisms. Despite having a great potential for biotechnological applications, the microorganisms inhabiting these ecosystems remain mostly unexplored and unexploited. In this review, we study the research topics and the interactions among Argentinean laboratories, by analyzing current articles published on biotechnology-related marine microbiology by researchers of this country. In addition, we identify the challenges and opportunities for Argentina to take advantage of the genetic potential of its marine microorganisms. Finally, we suggest possible actions that could improve the development of this research field, as well as the utilization of this knowledge to solve societal needs.

  14. Animal models of protein allergenicity: potential benefits, pitfalls and challenges.

    Science.gov (United States)

    Dearman, R J; Kimber, I

    2009-04-01

    Food allergy is an important health issue. With an increasing interest in novel foods derived from transgenic crop plants, there is a growing need for the development of approaches suitable for the characterization of the allergenic potential of proteins. There are methods available currently (such as homology searches and serological testing) that are very effective at identifying proteins that are likely to cross-react with known allergens. However, animal models may play a role in the identification of truly novel proteins, such as bacterial or fungal proteins, that have not been experienced previously in the diet. We consider here the potential benefits, pitfalls and challenges of the selection of various animal models, including the mouse, the rat, the dog and the neonatal swine. The advantages and disadvantages of various experimental end-points are discussed, including the measurement of specific IgE by ELISA, Western blotting or functional tests such as the passive cutaneous anaphylaxis assay, and the assessment of challenge-induced clinical symptoms in previously sensitized animals. The experimental variables of route of exposure to test proteins and the incorporation of adjuvant to increase the sensitivity of the responses are considered also. It is important to emphasize that currently none of these approaches has been validated for the purposes of hazard identification in the context of a safety assessment. However, the available evidence suggests that the judicious use of an accurate and robust animal model could provide important additional data that would contribute significantly to the assessment of the potential allergenicity of novel proteins.

  15. The Health Challenges of Urban Latino College Students as Revealed through Student Journaling

    Science.gov (United States)

    Rowland, Amy L.

    2008-01-01

    Because of the unique health risks faced by the Hispanic population and the notoriously poor health habits of college students, this study examines the health challenges faced by Latino college students enrolled at an urban commuter institution. A thematic analysis reveals the top themes for males and females as healthy eating, weight management,…

  16. Potential and challenges for the Black Sea regional cooperation

    Directory of Open Access Journals (Sweden)

    Galya VLADOVA

    2014-06-01

    Full Text Available Since the early nineties, the Black Sea region has witnessed fundamental geopolitical changes and significant shifts in its regional context and dynamics. In an attempt to react to the altered circumstances after the collapse of the Soviet Union and to address an increasing number of common challenges, the Black Sea states have jointed efforts in various regional cooperation activities. Throughout the years, the Black Sea cooperation has evolved with different speed and success, reflecting the difficult regional circumstances and attracting increasing external involvement. Today, more than twenty years after the first cooperation activities have been launched, the Black Sea cooperation is still shadowed by persisting historical rivalries, unrecognized territorial entities, ‘frozen conflicts’ and security threats. As a result, despite the many pressing problems of regional character, the cooperation efforts are currently showing rather limited outcomes. Seen against this background, the current paper presents a study of the main challenges and the existing potential for further development of the Black Sea regional cooperation.

  17. Protection of Renewable-dominated Microgrids: Challenges and Potential Solutions

    Energy Technology Data Exchange (ETDEWEB)

    Elkhatib, Mohamed [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ellis, Abraham [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Biswal, Milan [New Mexico State Univ., Las Cruces, NM (United States); Brahma, Sukumar [New Mexico State Univ., Las Cruces, NM (United States); Ranade, Satish [New Mexico State Univ., Las Cruces, NM (United States)

    2016-11-01

    In this report we address the challenge of designing efficient protection system for inverter- dominated microgrids. These microgrids are characterised with limited fault current capacity as a result of current-limiting protection functions of inverters. Typically, inverters limit their fault contribution in sub-cycle time frame to as low as 1.1 per unit. As a result, overcurrent protection could fail completely to detect faults in inverter-dominated microgrids. As part of this project a detailed literature survey of existing and proposed microgrid protection schemes were conducted. The survey concluded that there is a gap in the available microgrid protection methods. The only credible protection solution available in literature for low- fault inverter-dominated microgrids is the differential protection scheme which represents a robust transmission-grade protection solution but at a very high cost. Two non-overcurrent protection schemes were investigated as part of this project; impedance-based protection and transient-based protection. Impedance-based protection depends on monitoring impedance trajectories at feeder relays to detect faults. Two communication-based impedance-based protection schemes were developed. the first scheme utilizes directional elements and pilot signals to locate the fault. The second scheme depends on a Central Protection Unit that communicates with all feeder relays to locate the fault based on directional flags received from feeder relays. The later approach could potentially be adapted to protect networked microgrids and dynamic topology microgrids. Transient-based protection relies on analyzing high frequency transients to detect and locate faults. This approach is very promising but its implementation in the filed faces several challenges. For example, high frequency transients due to faults can be confused with transients due to other events such as capacitor switching. Additionally, while detecting faults by analyzing transients

  18. Molecularly imprinted polymers--potential and challenges in analytical chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Mahony, J.O. [Dublin City University, School of Chemical Sciences, Glasnevin, Dublin 9 (Ireland); Nolan, K. [Dublin City University, School of Chemical Sciences, Glasnevin, Dublin 9 (Ireland); Smyth, M.R. [Dublin City University, School of Chemical Sciences, Glasnevin, Dublin 9 (Ireland); Mizaikoff, B. [Georgia Institute of Technology, School of Chemistry and Biochemistry, 770 State Street, Boggs Building, Atlanta, GA 30332-0400 (United States)]. E-mail: boris.mizaikoff@chemistry.gatech.edu

    2005-04-04

    Among the variety of biomimetic recognition schemes utilizing supramolecular approaches molecularly imprinted polymers (MIPs) have proven their potential as synthetic receptors in numerous applications ranging from liquid chromatography to assays and sensor technology. Their inherent advantages compared to biochemical/biological recognition systems include robustness, storage endurance and lower costs. However, until recently only few contributions throughout the relevant literature describe quantitative analytical applications of MIPs for practically relevant analyte molecules and real-world samples. Increased motivation to thoroughly evaluate the true potential of MIP technology is clearly attributed to the demands of modern analytical chemistry, which include enhanced sensitivity, selectivity and applicability of molecular recognition building blocks at decreasing costs. In particular, the areas of environmental monitoring, food and beverage analysis and industrial process surveillance require analytical tools capable of discriminating chemicals with high molecular specificity considering increasing numbers of complex environmental contaminants, pollution of raw products and rigorous quality control requested by legislation and consumer protection. Furthermore, efficient product improvement and development of new products requires precise qualitative and quantitative analytical methods. Finally, environmental, food and process safety control issues favor the application of on-line in situ analytical methods with high molecular selectivity. While biorecognition schemes frequently suffer from degrading bioactivity and long-term stability when applied in real-world sample environments, MIPs serving as synthetic antibodies have successfully been applied as stationary phase separation matrix (e.g. HPLC and SPE), recognition component in bioassays (e.g. ELISA) or biomimetic recognition layer in chemical sensor systems. Examples such as MIP-based selective analysis of

  19. Research recruitment using Facebook advertising: big potential, big challenges.

    Science.gov (United States)

    Kapp, Julie M; Peters, Colleen; Oliver, Debra Parker

    2013-03-01

    To our knowledge, ours is the first study to report on Facebook advertising as an exclusive mechanism for recruiting women ages 35-49 years residing in the USA into a health-related research study. We directed our survey to women ages 35-49 years who resided in the USA exclusively using three Facebook advertisements. Women were then redirected to our survey site. There were 20,568,960 women on Facebook that met the eligibility criteria. The three ads resulted in 899,998 impressions with a reach of 374,225 women. Of the women reached, 280 women (0.075 %) clicked the ad. Of the women who clicked the ad, nine women (3.2 %) proceeded past the introductory page. Social networking, and in particular Facebook, is an innovative venue for recruiting participants for research studies. Challenges include developing an ad to foster interest without biasing the sample, and motivating women who click the ad to complete the survey. There is still much to learn about this potential method of recruitment.

  20. Big data challenges: Impact, potential responses and research needs

    OpenAIRE

    Bachlechner , Daniel; Leimbach, Timo

    2016-01-01

    Although reports on big data success stories have been accumulating in the media, most organizations dealing with high-volume, high-velocity and high-variety information assets still face challenges. Only a thorough understanding of these challenges puts organizations into a position in which they can make an informed decision for or against big data, and, if the decision is positive, overcome the challenges smoothly. The combination of a series of interviews with leading experts from enterpr...

  1. Biophysical characteristics reveal neural stem cell differentiation potential.

    Directory of Open Access Journals (Sweden)

    Fatima H Labeed

    Full Text Available BACKGROUND: Distinguishing human neural stem/progenitor cell (huNSPC populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers. METHODOLOGY/PRINCIPAL FINDINGS: We used dielectrophoresis (DEP to analyze the biophysical, specifically electrophysiological, properties of cortical human and mouse NSPCs that vary in differentiation potential. Our data demonstrate that the electrophysiological property membrane capacitance inversely correlates with the neurogenic potential of NSPCs. Furthermore, as huNSPCs are continually passaged they decrease neuron generation and increase membrane capacitance, confirming that this parameter dynamically predicts and negatively correlates with neurogenic potential. In contrast, differences in membrane conductance between NSPCs do not consistently correlate with the ability of the cells to generate neurons. DEP crossover frequency, which is a quantitative measure of cell behavior in DEP, directly correlates with neuron generation of NSPCs, indicating a potential mechanism to separate stem cells biased to particular differentiated cell fates. CONCLUSIONS/SIGNIFICANCE: We show here that whole cell membrane capacitance, but not membrane conductance, reflects and predicts the neurogenic potential of human and mouse NSPCs. Stem cell biophysical characteristics therefore provide a completely novel and quantitative measure of stem cell fate potential and a label-free means to identify neuron- or glial-biased progenitors.

  2. Big data challenges: impact, potential responses and research needs

    DEFF Research Database (Denmark)

    Leimbach, Timo; Bachlechner, Daniel

    2016-01-01

    Although reports on big data success stories have been accumulating in the media, most organizations dealing with high-volume, high-velocity and high-variety information assets still face challenges. Only a thorough understanding of these challenges puts organizations into a position in which...... they can make an informed decision for or against big data, and, if the decision is positive, overcome the challenges smoothly. The combination of a series of interviews with leading experts from enterprises, associations and research institutions, and focused literature reviews allowed not only...... framework are also relevant. For large enterprises and startups specialized in big data, it is typically easier to overcome the challenges than it is for other enterprises and public administration bodies....

  3. Brain potentials reveal unconscious translation during foreign-language comprehension.

    Science.gov (United States)

    Thierry, Guillaume; Wu, Yan Jing

    2007-07-24

    Whether the native language of bilingual individuals is active during second-language comprehension is the subject of lively debate. Studies of bilingualism have often used a mix of first- and second-language words, thereby creating an artificial "dual-language" context. Here, using event-related brain potentials, we demonstrate implicit access to the first language when bilinguals read words exclusively in their second language. Chinese-English bilinguals were required to decide whether English words presented in pairs were related in meaning or not; they were unaware of the fact that half of the words concealed a character repetition when translated into Chinese. Whereas the hidden factor failed to affect behavioral performance, it significantly modulated brain potentials in the expected direction, establishing that English words were automatically and unconsciously translated into Chinese. Critically, the same modulation was found in Chinese monolinguals reading the same words in Chinese, i.e., when Chinese character repetition was evident. Finally, we replicated this pattern of results in the auditory modality by using a listening comprehension task. These findings demonstrate that native-language activation is an unconscious correlate of second-language comprehension.

  4. Democratic challenges and potentials in pre-schools

    DEFF Research Database (Denmark)

    Kampmann, Jan; Ahrenkiel, Annegrethe; Røn Larsen, Maja;

    This paper takes point of departure in research approaching both empirical and theoretical challenges related to the study of very young children’s everyday lives in institutional settings. In this paper, we present an analysis of pedagogical practice about developing democracy and influence for ...

  5. OIL PALM FIBERS AS PAPERMAKING MATERIAL: POTENTIALS AND CHALLENGES

    Directory of Open Access Journals (Sweden)

    Wan Rosli Wan Daud

    2011-02-01

    Full Text Available This paper reviews the physical and chemical characteristics of fibers from the stem, fronds, and empty fruit bunches of oil palm tree in relation to their papermaking properties. Challenges regarding the use of this nonwood material for papermaking are raised, and possible solutions to them are given. A vision for the complete utilization of oil palm biomass is also outlined.

  6. Implementing Ecopharmacovigilance in Practice: Challenges and Potential Opportunities

    OpenAIRE

    Holm, Gisela; Snape, Jason R.; Murray-Smith, Richard; Talbot, John; Taylor, David; Sörme, Pernilla

    2013-01-01

    Ecopharmacovigilance (EPV) is a developing science and it is currently very unclear what it might mean in practice. We have performed a comparison between pharmacovigilance (PV) and EPV and have identified that there are similarities, but also some important differences that must be considered before any practical implementation of EPV. The biggest difference and greatest challenge concerns signal detection in the environment and the difficulty of identifying cause and effect. We reflect on t...

  7. Development and application of modern agricultural biotechnology in Botswana: the potentials, opportunities and challenges.

    Science.gov (United States)

    Batlang, Utlwang; Tsurupe, Gorata; Segwagwe, Amogelang; Obopile, Motshwari

    2014-07-03

    In Botswana, approximately 40% of the population live in rural areas and derive most of their livelihood from agriculture by keeping livestock and practising arable farming. Due to the nature of their farming practises livestock and crops are exposed to diseases and environmental stresses. These challenges offer opportunities for application of biotechnology to develop adaptable materials to the country's environment. On the other hand, the perceived risk of genetically modified organisms (GMOs) has dimmed the promise of the technology for its application in agriculture. This calls for a holistic approach to the application of biotechnology to address issues of biosafety of GMOs. We have therefore assessed the potentials, challenges and opportunities to apply biotechnology with specific emphasis on agriculture, taking cognisance of requirement for its research, development and application in research and teaching institutions. In order to achieve this, resource availability, infrastructure, human and laboratory requirements were analyzed. The analysis revealed that the country has the capacity to carry out research in biotechnology in the development and production of genetically modified crops for food and fodder crops. These will include gene discovery, genetic transformation and development of systems to comply with the world regulatory framework on biosafety. In view of the challenges facing the country in agriculture, first generation biotech crops could be released for production. Novel GM products for development may include disease diagnosis kits, animal disease vaccines, and nutrient use efficiency, drought, and pest and disease resistant food and fodder crops.

  8. THE POTENTIAL AND CHALLENGES OF SUSTAINABLE TOURISM IN ROMANIA

    OpenAIRE

    Flaviu Doru Neaga

    2015-01-01

    When talking about the concepts of tourism potential and heritage tourism, tourism professionals are using different terminologies and concepts, both in form and content. The tourism potential of a given space is defined as "all natural components, cultural-historical, socio-demographic, technical and economic, scientifically recognized, quantitatively, qualitatively, proven through practice and showing the possibilities for tourism and give specific functionality for tourism, to the extent t...

  9. Oxygen restriction as challenge test reveals early high-fat-diet-induced changes in glucose and lipid metabolism

    NARCIS (Netherlands)

    Duivenvoorde, L.P.M.; Schothorst, van E.M.; Derous, D.; Stelt, van der I.; Masania, J.; Rabbani, N.; Thornalley, P.J.; Keijer, J.

    2015-01-01

    Challenge tests stress homeostasis and may reveal deviations in health that remain masked under unchallenged conditions. Ideally, challenge tests are non-invasive and applicable in an early phase of an animal experiment. Oxygen restriction (OxR; based on ambient, mild normobaric hypoxia) is a non-in

  10. Transdermal Delivery of Drugs with Microneedles—Potential and Challenges

    Science.gov (United States)

    Ita, Kevin

    2015-01-01

    Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use. PMID:26131647

  11. Transdermal Delivery of Drugs with Microneedles—Potential and Challenges

    Directory of Open Access Journals (Sweden)

    Kevin Ita

    2015-06-01

    Full Text Available Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use.

  12. Organic livestock production in Uganda: potentials, challenges and prospects

    DEFF Research Database (Denmark)

    Nalubwama, Sylvia Muwanga; Mugisha, Anthony; Vaarst, Mette

    2011-01-01

    Development in organic farming has been stimulated by farmers and consumers becoming interested in healthy food products and sustainable environment. Organic agriculture is a holistic production management system which is based on the principles of health, ecology, care, and fairness. Organic dev...... production. The prospects of organic livestock development in Uganda can be enhanced with more scientific research in organic livestock production under local conditions and strengthening institutional support....... to the current low-input/low-output systems. Traditional farming should not be confused with organic farming because in some cases, the existing traditional practices have consequences like overstocking and less attention to soil improvement as well as to animal health and welfare, which is contrary to organic...... principles of ecology, fairness, health, and care. Challenges of implementing sustainable organic practices in the Ugandan livestock sector threaten its future development, such as vectors and vector-borne diseases, organic feed insufficiency, limited education, research, and support to organic livestock...

  13. Bending and Focusing with Plasmas and Crystals - Potential and Challenges

    CERN Document Server

    Zimmermann, F

    2013-01-01

    This talk review the potential of plasmas and crystals for focusing and bending high-energy charged particle beams. It covers topics like plasma lenses, plasma wigglers, plasma dipoles, crystal channeling & reflection, radiation in crystals, crystal accelerators, crystalline beams and ultimate limitations. Past, ongoing or required R&D efforts are highlighted. Invited presentation at EuCARD'13 "Visions for the Future of Particle Accelerators," CERN, 11 June 2013.

  14. Implementing ecopharmacovigilance in practice: challenges and potential opportunities.

    Science.gov (United States)

    Holm, Gisela; Snape, Jason R; Murray-Smith, Richard; Talbot, John; Taylor, David; Sörme, Pernilla

    2013-07-01

    Ecopharmacovigilance (EPV) is a developing science and it is currently very unclear what it might mean in practice. We have performed a comparison between pharmacovigilance (PV) and EPV and have identified that there are similarities, but also some important differences that must be considered before any practical implementation of EPV. The biggest difference and greatest challenge concerns signal detection in the environment and the difficulty of identifying cause and effect. We reflect on the dramatic vulture decline in Asia, which was caused by the veterinary use of diclofenac, versus the relative difficulty in identifying the specific causes of intersex fish in European rivers. We explore what EPV might mean in practice and have identified that there are some practical measures that can be taken to assess environmental risks across product life cycle, particularly after launch of a new drug, to ensure that our risk assessments and scientific understanding of pharmaceuticals in the environment remain scientifically and ecologically relevant. These include: Tracking environmental risks after launch of the product, via literature monitoring for emerging data on exposure and effects Using Environmental Risk Management Plans (ERMPs) as a centralized resource to assess and manage the risks of a drug throughout its life cycle Further research, testing or monitoring in the environment when a risk is identified Keeping a global EPV perspective Increasing transparency and availability of environmental data for medicinal products. These measures will help to ensure that any significant environmental issues associated with pharmaceuticals in the environment (PIE) are identified in a timely way, and can be managed appropriately.

  15. Resource potential of bamboo, challenges and future directions towards sustainable management and utilization in Ethiopia

    Directory of Open Access Journals (Sweden)

    Getachew Desalegn

    2014-08-01

    Full Text Available Aim of study: Bamboo, the fastest growing and high yielding perennial plant of the world has more than 1500 species and 1500 versatile socio-economic uses and ecological services. Ethiopia has two indigenous bamboo species namely Yushania alpina and Oxytenantheria abyssinica, covering about one million ha with a wide distribution. The objective of this paper is to highlight the potential of bamboo resources, challenges including biodeterioration damage, opportunities and future research directions towards its sustainable management and rational utilization.Area of study: Bamboo resources of EthiopiaMaterial and Methods: Reconnaissance survey was done to some parts of the bamboo growing potential areas in Ethiopia besides the literature review. Main results: The bamboo resource, despite its socio-economic and environmental benefits, currently, in most areas has been under high pressure due to land use changes, bamboo mass- flowering, poor processing with low value addition, and damage by biodeteriorating agents (termites, beetles and fungi. The preservative tests on Ethiopian bamboos revealed low natural durability and highlighted the paramount importance of appropriate protection measures such as Tanalith and vehicles used motor oil to increase durability, service life and rational utilization of bamboo-based products and structures as potential alternative construction and furniture material.Research highlights: Therefore, integrated research and development interventions involving different propagation and managements techniques, harvesting season, processing, value addition including proper seasoning and preservation technologies and marketing are recommended to fill the information and technological gaps on sustainable management and rational utilization of this fast growing and multipurpose bamboo resources in Ethiopia.Key words: Bamboo; challenges; management; socio-economic and environmental significance; utilization.

  16. Soil Degradation in India: Challenges and Potential Solutions

    Directory of Open Access Journals (Sweden)

    Ranjan Bhattacharyya

    2015-03-01

    Full Text Available Soil degradation in India is estimated to be occurring on 147 million hectares (Mha of land, including 94 Mha from water erosion, 16 Mha from acidification, 14 Mha from flooding, 9 Mha from wind erosion, 6 Mha from salinity, and 7 Mha from a combination of factors. This is extremely serious because India supports 18% of the world’s human population and 15% of the world’s livestock population, but has only 2.4% of the world’s land area. Despite its low proportional land area, India ranks second worldwide in farm output. Agriculture, forestry, and fisheries account for 17% of the gross domestic product and employs about 50% of the total workforce of the country. Causes of soil degradation are both natural and human-induced. Natural causes include earthquakes, tsunamis, droughts, avalanches, landslides, volcanic eruptions, floods, tornadoes, and wildfires. Human-induced soil degradation results from land clearing and deforestation, inappropriate agricultural practices, improper management of industrial effluents and wastes, over-grazing, careless management of forests, surface mining, urban sprawl, and commercial/industrial development. Inappropriate agricultural practices include excessive tillage and use of heavy machinery, excessive and unbalanced use of inorganic fertilizers, poor irrigation and water management techniques, pesticide overuse, inadequate crop residue and/or organic carbon inputs, and poor crop cycle planning. Some underlying social causes of soil degradation in India are land shortage, decline in per capita land availability, economic pressure on land, land tenancy, poverty, and population increase. In this review of land degradation in India, we summarize (1 the main causes of soil degradation in different agro-climatic regions; (2 research results documenting both soil degradation and soil health improvement in various agricultural systems; and (3 potential solutions to improve soil health in different regions using a

  17. Respiratory Challenges in Breast Cancer: Potential for Enhanced Diagnostics and Therapy

    Science.gov (United States)

    2010-07-01

    of cancer cachexia and abnormal glucose metabolism in humans with cancer J Am Coll Nutr 11 445-56 Teicher B A, Lazo J S and Sartorelli A C 1981...AD_________________ Award Number: W81XWH-08-1-0447 TITLE: Respiratory Challenges in Breast Cancer : Potential for Enhanced...07-2010 2. REPORT TYPE Annual 3. DATES COVERED (From - To) (1 JUL 2009-30 JUN 2010 4. TITLE AND SUBTITLE Respiratory Challenges in Breast Cancer

  18. BRAIN DYSFUNCTION OF PATIENTS WITH QIGONG INDUCED MENTAL DISORDER REVEALED BY EVOKED POTENTIALS RECORDING

    Institute of Scientific and Technical Information of China (English)

    LU Yingzhi; ZONG Wenbin; CHEN Xingshi

    2003-01-01

    Objective: In order to investigate the brain function of patients with Qigong induced mental disorder (QIMD), this study was carried out. Methods: Four kinds of evoked potentials, including contingent negative variation (CNV), auditory evoked potentials (AEP), visual evoked potentials (VEP), and somatosensory evoked potentials (SEP), were recorded from 12 patients with Qigong induced mental disorder.Comparison of their evoked potentials with the data from some normal controls was made. Results: The results revealed that there were 3 kinds of abnormal changes in evoked potentials of patients with QIMD that is latency prolongation, amplitude increase and amplitude decrease, as compared with normal controls. Conclusion: Brain dysfunction of patients with QIMD was confirmed. Its biological mechanism needs further studying.

  19. Introducing GaLA: Serious Game potentials, challenges and TEL-related issues

    NARCIS (Netherlands)

    Earp, Jeffrey; Klemke, Roland

    2011-01-01

    Earp, J., & Klemke, R. (2011, 21 September). Introducing GaLA: Serious Game potentials, challenges and TEL-related issues. Presented at TEL-Think-Tank Workshop at the 6th European conference on Technology enhanced learning: towards ubiquitous learning (EC-TEL 2011), Palermo, Italy.

  20. Assets, Challenges, and the Potential of Technology for Nutrition Education in Rural Communities

    Science.gov (United States)

    Atkinson, Nancy L.; Desmond, Sharon M.; Saperstein, Sandra L.; Billing, Amy S.; Gold, Robert S.; Tournas-Hardt, Amy

    2010-01-01

    Objective: To examine assets of and challenges to getting adequate nutrition and physical activity among low-income rural residents, and the potential for technology to provide health education. Methods: Environmental scans and community stakeholder interviews were conducted in 5 rural counties in Maryland. During environmental scans, stakeholders…

  1. Zero-Acreage Farming in the City of Berlin: An Aggregated Stakeholder Perspective on Potential Benefits and Challenges

    Directory of Open Access Journals (Sweden)

    Kathrin Specht

    2015-04-01

    Full Text Available How can buildings be combined with agricultural production and what are the major potential benefits and challenges for the introduction of zero-acreage farming (ZFarming in Berlin from the relevant stakeholders’ perspectives? These questions were explored through a series of interviews and stakeholder workshops held between 2011 and 2013. The aim was to identify the most suitable building-integrated farming model for the Berlin metropolitan area and to develop guidelines for the model’s successful and sustainable implementation through a stakeholder-driven approach. This paper provides an aggregated synthesis of the outcomes derived from the qualitative interviews and stakeholder workshops. As the results reveal, the stakeholders perceive potential benefits and challenges related to the issue of ZFarming in all dimensions (economic, social, environmental and political. They largely agreed on the importance of focusing on local resources, using energy-efficient production—including social and educational aspects—and developing new market structures when introducing ZFarming to the city of Berlin. The stakeholders identified urban rooftop greenhouses (RTG as the most promising farming model for Berlin. In a joint collaboration of all stakeholders, a manual for RTG was developed within the participatory innovation process that addresses the identified problems and challenges associated with future implementation and governance of RTG in Berlin and beyond.

  2. Part-Load Performance Characterization and Energy Savings Potential of the RTU Challenge Unit: Daikin Rebel

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Weimin; Katipamula, Srinivas

    2013-09-30

    In 2011, the U.S. Department of Energy’s Building Technology Office (DOE’s BTO), with help from the Better Buildings Alliance (BBA) members, developed a specification for high performance rooftop air-conditioning units (RTU Challenge) with capacity ranges between 10 and 20 tons (DOE 2013). Daikin’s Rebel for the first rooftop unit system that was recognized by DOE in May 2012 as meeting the RTU Challenge specifications. This report documents the development of part-load performance curves and its use with EnergyPlus simulation tool to estimate the potential savings from use of Rebel compared to other standard options.

  3. Reciprocal osmotic challenges reveal mechanisms of divergence in phenotypic plasticity in the killifish Fundulus heteroclitus.

    Science.gov (United States)

    Brennan, Reid S; Galvez, Fernando; Whitehead, Andrew

    2015-04-15

    The killifish Fundulus heteroclitus is an estuarine species with broad physiological plasticity, enabling acclimation to diverse stressors. Previous work suggests that freshwater populations expanded their physiology to accommodate low salinity environments; however, it is unknown whether this compromises their tolerance to high salinity. We used a comparative approach to investigate the mechanisms of a derived freshwater phenotype and the fate of an ancestral euryhaline phenotype after invasion of a freshwater environment. We compared physiological and transcriptomic responses to high- and low-salinity stress in fresh and brackish water populations and found an enhanced plasticity to low salinity in the freshwater population coupled with a reduced ability to acclimate to high salinity. Transcriptomic data identified genes with a conserved common response, a conserved salinity-dependent response and responses associated with population divergence. Conserved common acclimation responses revealed stress responses and alterations in cell-cycle regulation as important mechanisms in the general osmotic response. Salinity-specific responses included the regulation of genes involved in ion transport, intracellular calcium, energetic processes and cellular remodeling. Genes diverged between populations were primarily those showing salinity-specific expression and included those regulating polyamine homeostasis and the cell cycle. Additionally, when populations were matched with their native salinity, expression patterns were consistent with the concept of 'transcriptomic resilience', suggesting local adaptation. These findings provide insight into the fate of a plastic phenotype after a shift in environmental salinity and help to reveal mechanisms allowing for euryhalinity.

  4. A nonlinear strategy to reveal seismic precursory signatures in earthquake-related self-potential signals

    Science.gov (United States)

    Telesca, Luciano; Lovallo, Michele; Ramirez-Rojas, Alejandro; Angulo-Brown, Fernando

    2009-05-01

    The time fluctuations of self-potential data, recorded at the monitoring station Acapulco (Mexico) during 1994-1996 in the seismic area of Guerrero-Oaxaca, are analyzed by means of the Fisher Information Measure (FIM), a nonlinear powerful method to investigate complex dynamics in time series. The time evolution of the FIM shows a clear correlation with the largest earthquakes that occurred in the monitored area during the observation period. Seismic precursory patterns in the FIM evolution are also revealed.

  5. Organic agriculture and undernourishment in developing countries: main potentials and challenges.

    Science.gov (United States)

    Schoonbeek, Sanne; Azadi, Hossein; Mahmoudi, Hossein; Derudder, Ben; De Maeyer, Philippe; Witlox, Frank

    2013-01-01

    While much has been published on the advantages of organic agriculture, less has addressed its potentials and challenges to fight undernourishment in developing countries. This article aims at reviewing the main potentials and challenges of this approach when dealing with "undernourishment" as a multifaceted concept in developing countries. Accordingly, 2 main issues of the concept which are "food security" and "food safety" are discussed in the context of both developed and developing countries to understand their different food policies' priorities. Next, the main potentials, challenges and tradeoffs of the organic approach are analyzed to understand whether the approach is capable to provide a secure or a safe food-production system which can meet the food policy priorities in developing countries. With respect to food security, the article concludes that conventional and biotechnological approaches still produce higher yields than organic agriculture. However, considering the many advantages of organic agriculture, it can in a long run, be more conducive than now to meet food security. Thus, conventional approach is still needed to feed the hungers in developing countries [corrected]. Accordingly, the article emphasizes on the importance of providing farmers in developing countries with the possibility of implementing different approaches. Therefore, policy makers should be aware of a realistic and gradual transition from the other approaches to the organic that should be projected only in "long run," and after conducting a series of risk assessment studies on the bases of both "crop-case" and "region-case."

  6. Educational games for brain health: revealing their unexplored potential through a neurocognitive approach

    Directory of Open Access Journals (Sweden)

    Patrick eFissler

    2015-07-01

    Full Text Available Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control, and second, educational learning experiences (e.g., studying foreign languages improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research.

  7. Educational games for brain health: revealing their unexplored potential through a neurocognitive approach.

    Science.gov (United States)

    Fissler, Patrick; Kolassa, Iris-Tatjana; Schrader, Claudia

    2015-01-01

    Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control), and second, educational learning experiences (e.g., studying foreign languages) improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research.

  8. Social Network Analysis Reveals Potential Fission-Fusion Behavior in a Shark

    Science.gov (United States)

    Haulsee, Danielle E.; Fox, Dewayne A.; Breece, Matthew W.; Brown, Lori M.; Kneebone, Jeff; Skomal, Gregory B.; Oliver, Matthew J.

    2016-09-01

    Complex social networks and behaviors are difficult to observe for free-living marine species, especially those that move great distances. Using implanted acoustic transceivers to study the inter- and intraspecific interactions of sand tiger sharks Carcharias taurus, we observed group behavior that has historically been associated with higher order mammals. We found evidence strongly suggestive of fission-fusion behavior, or changes in group size and composition of sand tigers, related to five behavioral modes (summering, south migration, community bottleneck, dispersal, north migration). Our study shows sexually dimorphic behavior during migration, in addition to presenting evidence of a potential solitary phase for these typically gregarious sharks. Sand tigers spent up to 95 consecutive and 335 cumulative hours together, with the strongest relationships occurring between males. Species that exhibit fission-fusion group dynamics pose a particularly challenging issue for conservation and management because changes in group size and composition affect population estimates and amplify anthropogenic impacts.

  9. Social Network Analysis Reveals Potential Fission-Fusion Behavior in a Shark

    Science.gov (United States)

    Haulsee, Danielle E.; Fox, Dewayne A.; Breece, Matthew W.; Brown, Lori M.; Kneebone, Jeff; Skomal, Gregory B.; Oliver, Matthew J.

    2016-01-01

    Complex social networks and behaviors are difficult to observe for free-living marine species, especially those that move great distances. Using implanted acoustic transceivers to study the inter- and intraspecific interactions of sand tiger sharks Carcharias taurus, we observed group behavior that has historically been associated with higher order mammals. We found evidence strongly suggestive of fission-fusion behavior, or changes in group size and composition of sand tigers, related to five behavioral modes (summering, south migration, community bottleneck, dispersal, north migration). Our study shows sexually dimorphic behavior during migration, in addition to presenting evidence of a potential solitary phase for these typically gregarious sharks. Sand tigers spent up to 95 consecutive and 335 cumulative hours together, with the strongest relationships occurring between males. Species that exhibit fission-fusion group dynamics pose a particularly challenging issue for conservation and management because changes in group size and composition affect population estimates and amplify anthropogenic impacts. PMID:27686155

  10. Potential and challenges of zeolite chemistry in the catalytic conversion of biomass.

    Science.gov (United States)

    Ennaert, Thijs; Van Aelst, Joost; Dijkmans, Jan; De Clercq, Rik; Schutyser, Wouter; Dusselier, Michiel; Verboekend, Danny; Sels, Bert F

    2016-02-01

    Increasing demand for sustainable chemicals and fuels has pushed academia and industry to search for alternative feedstocks replacing crude oil in traditional refineries. As a result, an immense academic attention has focused on the valorisation of biomass (components) and derived intermediates to generate valuable platform chemicals and fuels. Zeolite catalysis plays a distinct role in many of these biomass conversion routes. This contribution emphasizes the progress and potential in zeolite catalysed biomass conversions and relates these to concepts established in existing petrochemical processes. The application of zeolites, equipped with a variety of active sites, in Brønsted acid, Lewis acid, or multifunctional catalysed reactions is discussed and generalised to provide a comprehensive overview. In addition, the feedstock shift from crude oil to biomass involves new challenges in developing fields, like mesoporosity and pore interconnectivity of zeolites and stability of zeolites in liquid phase. Finally, the future challenges and perspectives of zeolites in the processing of biomass conversion are discussed.

  11. Potential probiotic yeasts isolated from the fish gut protect zebrafish (Danio rerio from a Vibrio anguillarum challenge

    Directory of Open Access Journals (Sweden)

    Mario eCaruffo

    2015-10-01

    Full Text Available Due to the negative consequences associated with the use of antibiotics, researchers and food producers have studied alternatives, such as probiotics, for the control of fish diseases. The probiotic properties of yeasts in aquaculture have been scarcely considered. The present study investigated the probiotic properties of local yeast strains for aquaculture application in the protection of bacterial diseases. Yeast strains (n=15, previously isolated from the intestinal gut of healthy salmonids, yellowtail and croaker, were evaluated for their protection of zebrafish larvae following a Vibrio anguillarum challenge. We developed an infection model on zebrafish larvae with V. anguillarum, observing rapid mortality (≥50% 5 days post immersion challenge. Infection of Tg(Lyz:DsRednz50 larvae with fluorescent-marked V. anguillarum showed the oro-intestinal as the natural route of infection concomitant with an inflammatory response of the larvae reflected by neutrophil migration outside the hematopoietic tissue. Thirteen of 15 strains increased the percentage of larvae survival after the V. anguillarum challenge, although no yeast showed in vitro anti-V. anguillarum activity. In a subset of yeasts, we explored yeast-larvae interactions using fluorescent yeast and evaluated larvae colonization by culture analysis. All fluorescent yeasts were located in the gastrointestinal tract until 5 days post inoculation (dpi. Yeasts reached 103 CFU/larvae at 0 dpi, although the persistence until 5 dpi of the viable yeast in the gut was different among the strains. These results reveal that some yeasts isolated from the gut of fish could be potential probiotics, reducing the mortality associated to V. anguillarum challenge, and suggest that gut colonization could be involved in the protective effect. Future studies should elucidate other mechanisms involved in yeast protection and verify the beneficial effects of probiotic use in commercial fish species.

  12. Potential and Challenges of Web-based Collective Intelligence to Tackle Societal Problems

    Directory of Open Access Journals (Sweden)

    Birutė Pitrėnaitė-Žilėnienė

    2014-03-01

    characteristics of diverse web-based projects, which include attributes of CI, and came up with relatively small number of common elements calling them CI genes, and combination of different genes was called genome. The genes were classified using two pairs of questions: who are performing tasks? Why they are doing it? And what is being done? How it is being performed? Responses to these questions gives information on what principles are followed when CI is emerging in a particular web-based project. This information is crucial when systems, which are oriented to emergence and application of CI, are being designed.Different research evidence the potential of CI to contribute to solving of public issues. Specific virtual communication platforms are being designed for this purpose. Exploratory review of Lithuanian virtual community projects demonstrates a growing number of such projects and an increasing number of users joining these platforms. It is important that such projects enable identification of problems, discussion on them, search alternatives for problem solving, evaluate these alternatives and make decisions. The authors analyzed Lithuanian examples conforming to these requirements, such as virtual community projects Aš Lietuvai (I for Lithuania ir Lietuva 2.0. (Lithuania 2.0. These projects encompass all the elements attributed to CI and its application for tackling social issues: the projects can attract geographically dispersed crowds, they have technological solutions allowing identification and discussion of problems, suggesting and voting on possible solutions, and decision making. However, the current research has not revealed if CI emergence in virtual community projects is acceptable and applicable in practice and actually influences policies.Research limitations – case studies, which are presented in this paper, could be evaluated as synoptical and requiring broader and deeper research. In order to have explicit mosaic of web-based CI application for

  13. THE IPICS «OLDEST ICE» CHALLENGE: A NEW TECHNOLOGY TO QUALIFY POTENTIAL SITES

    Directory of Open Access Journals (Sweden)

    J. Chappellaz

    2012-01-01

    Full Text Available Among the priorities of the International Partnerships in Ice Core Sciences (IPICS core project of Past Global Changes (IGBP/PAGES, drilling ice as old as 1.5 million years is probably the most emblematic challenge. The search for a potential site in Antarcticahosting such old ice in good stratigraphic order is under way. Here we propose an innovative way to rapidly qualify potential sites. We plan to build a probe able to drill down to bedrock within one field season. The probe will embed a laser optical instrument measuring in real time key parameters such as the water isotopic composition of the ice and the concentration of one or more greenhouse gases.

  14. The emerging era of pharmacogenomics: current successes, future potential, and challenges.

    Science.gov (United States)

    Lee, J W; Aminkeng, F; Bhavsar, A P; Shaw, K; Carleton, B C; Hayden, M R; Ross, C J D

    2014-07-01

    The vast range of genetic diversity contributes to a wonderful array of human traits and characteristics. Unfortunately, a consequence of this genetic diversity is large variability in drug response between people, meaning that no single medication is safe and effective in everyone. The debilitating and sometimes deadly consequences of adverse drug reactions (ADRs) are a major and unmet problem of modern medicine. Pharmacogenomics can uncover associations between genetic variation and drug safety and has the potential to predict ADRs in individual patients. Here we review pharmacogenomic successes leading to changes in clinical practice, as well as clinical areas probably to be impacted by pharmacogenomics in the near future. We also discuss some of the challenges, and potential solutions, that remain for the implementation of pharmacogenomic testing into clinical practice for the significant improvement of drug safety.

  15. Incorporating intersectionality theory into population health research methodology: challenges and the potential to advance health equity.

    Science.gov (United States)

    Bauer, Greta R

    2014-06-01

    Intersectionality theory, developed to address the non-additivity of effects of sex/gender and race/ethnicity but extendable to other domains, allows for the potential to study health and disease at different intersections of identity, social position, processes of oppression or privilege, and policies or institutional practices. Intersectionality has the potential to enrich population health research through improved validity and greater attention to both heterogeneity of effects and causal processes producing health inequalities. Moreover, intersectional population health research may serve to both test and generate new theories. Nevertheless, its implementation within health research to date has been primarily through qualitative research. In this paper, challenges to incorporation of intersectionality into population health research are identified or expanded upon. These include: 1) confusion of quantitative terms used metaphorically in theoretical work with similar-sounding statistical methods; 2) the question of whether all intersectional positions are of equal value, or even of sufficient value for study; 3) distinguishing between intersecting identities, social positions, processes, and policies or other structural factors; 4) reflecting embodiment in how processes of oppression and privilege are measured and analysed; 5) understanding and utilizing appropriate scale for interactions in regression models; 6) structuring interaction or risk modification to best convey effects, and; 7) avoiding assumptions of equidistance or single level in the design of analyses. Addressing these challenges throughout the processes of conceptualizing and planning research and in conducting analyses has the potential to improve researchers' ability to more specifically document inequalities at varying intersectional positions, and to study the potential individual- and group-level causes that may drive these observed inequalities. A greater and more thoughtful incorporation

  16. An integrative systems genetics approach reveals potential causal genes and pathways related to obesity

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Zhernakova, Daria V.; Westra, Harm-Jan

    2015-01-01

    BACKGROUND: Obesity is a multi-factorial health problem in which genetic factors play an important role. Limited results have been obtained in single-gene studies using either genomic or transcriptomic data. RNA sequencing technology has shown its potential in gaining accurate knowledge about...... the transcriptome, and may reveal novel genes affecting complex diseases. Integration of genomic and transcriptomic variation (expression quantitative trait loci [eQTL] mapping) has identified causal variants that affect complex diseases. We integrated transcriptomic data from adipose tissue and genomic data from...... a porcine model to investigate the mechanisms involved in obesity using a systems genetics approach. METHODS: Using a selective gene expression profiling approach, we selected 36 animals based on a previously created genomic Obesity Index for RNA sequencing of subcutaneous adipose tissue. Differential...

  17. Functional splicing network reveals extensive regulatory potential of the core spliceosomal machinery.

    Science.gov (United States)

    Papasaikas, Panagiotis; Tejedor, J Ramón; Vigevani, Luisa; Valcárcel, Juan

    2015-01-08

    Pre-mRNA splicing relies on the poorly understood dynamic interplay between >150 protein components of the spliceosome. The steps at which splicing can be regulated remain largely unknown. We systematically analyzed the effect of knocking down the components of the splicing machinery on alternative splicing events relevant for cell proliferation and apoptosis and used this information to reconstruct a network of functional interactions. The network accurately captures known physical and functional associations and identifies new ones, revealing remarkable regulatory potential of core spliceosomal components, related to the order and duration of their recruitment during spliceosome assembly. In contrast with standard models of regulation at early steps of splice site recognition, factors involved in catalytic activation of the spliceosome display regulatory properties. The network also sheds light on the antagonism between hnRNP C and U2AF, and on targets of antitumor drugs, and can be widely used to identify mechanisms of splicing regulation.

  18. Early somatosensory event-related potentials reveal attentional bias for internal stimuli in social anxiety.

    Science.gov (United States)

    Kanai, Yoshihiro; Nittono, Hiroshi; Kubo, Kenta; Sasaki-Aoki, Shoko; Iwanaga, Makoto

    2012-03-01

    The present study used event-related brain potentials (ERPs) to investigate allocation of attentional resources to internal and external stimuli in individuals with social anxiety. High and low socially anxious individuals were presented with depictions of various facial expressions or household objects, followed by an internal (vibration presented to the finger) or external probe (the letter "E"). Participants were told that the vibration signals physiological changes and were asked to detect both probes. High socially anxious individuals showed larger front-central N140 amplitudes in response to vibratory internal probes as compared to non-anxious controls. ERPs elicited by picture stimuli and external probes and reaction times in response to both probe types did not differ between high and low social anxiety individuals. Early somatosensory ERPs reveal an attentional bias for internal stimuli that does not appear in overt behavior.

  19. Event-related potentials can reveal differences between two decision-making groups.

    Science.gov (United States)

    Cutmore, T R; Muckert, T D

    1998-02-01

    Previous research has shown that a complex decision is dependent on an underlying utility metric that is used by decision making processes to accumulate preference for one alternative. This study postulated that a state of indecision may arise if this underlying metric is poorly organized. The underlying metric was examined with a paired comparison task while measuring event-related potentials (ERP) for subjects classified as 'career decided' and 'career undecided'. Stimuli for comparison were presented either sequentially or simultaneously. The simultaneous condition produced results consistent with the hypothesis that undecided subjects have a poorly organized value metric as revealed in both the behavioral data and the P3 component. A relationship between P3 amplitude and word distance on the underlying metric was found only for the decided group. This was interpreted in terms of the previously documented relationship between P3 and the constructs of decision confidence and task difficulty.

  20. An assessment of BWR (boiling water reactor) Mark III containment challenges, failure modes, and potential improvements in performance

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, J.A.; Pafford, D.J.; Kelly, D.L.; Jones, K.R.; Dallman, F.J. (EG and G Idaho, Inc., Idaho Falls, ID (USA))

    1991-01-01

    This report describes risk-significant challenges posed to Mark III containment systems by severe accidents as identified for Grand Gulf. Design similarities and differences between the Mark III plants that are important to containment performance are summarized. The accident sequences responsible for the challenges and the postulated containment failure modes associated with each challenge are identified and described. Improvements are discussed that have the potential either to prevent or delay containment failure, or to mitigate the offsite consequences of a fission product release. For each of these potential improvements, a qualitative analysis is provided. A limited quantitative risk analysis is provided for selected potential improvements. 21 refs., 5 figs., 46 tabs.

  1. Revealing the potential of squid chitosan-based structures for biomedical applications.

    Science.gov (United States)

    Reys, L L; Silva, S S; Oliveira, J M; Caridade, S G; Mano, J F; Silva, T H; Reis, R L

    2013-08-01

    In recent years, much attention has been given to different marine organisms, namely as potential sources of valuable materials with a vast range of properties and characteristics. In this work, β-chitin was isolated from the endoskeleton of the giant squid Dosidicus gigas and further deacetylated to produce chitosan. Then, the squid chitosan was processed into membranes and scaffolds using solvent casting and freeze-drying, respectively, to assess their potential biomedical application. The developed membranes have shown to be stiffer and less hydrophobic than those obtained with commercial chitosan. On the other hand, the morphological characterization of the developed scaffolds, by SEM and micro-computed tomography, revealed that the matrices were formed with a lamellar structure. The findings also indicated that the treatment with ethanol prior to neutralization with sodium hydroxide caused the formation of larger pores and loss of some lamellar features. The in vitro cell culture study has shown that all chitosan scaffolds exhibited a non-cytotoxic effect over the mouse fibroblast-like cell line, L929 cells. Thus, chitosan produced from the endoskeletons of the giant squid Dosidicus gigas has proven to be a valuable alternative to existing commercial materials when considering its use as biomaterial.

  2. Revealing the potential of Didodecyldimethylammonium bromide as efficient scaffold for fabrication of nano liquid crystalline structures.

    Science.gov (United States)

    Kanwar, Rohini; Kaur, Gurpreet; Mehta, S K

    2016-03-01

    To exploit the potential of Didodecyldimethylammonium bromide (D12DAB) as a core lipidic constituent, an attempt was made to fabricate and optimize cationic nanostructured lipid carriers (cNLCs) using a cost-effective microemulsification methodology. Designed composition was optimized by studying the effect of different microemulsion components on D12DAB cNLCs characteristics. ​Spherical shaped D12DAB cNLCs were obtained with an average size of ∼160 nm and zeta potential of +30.2 mV. Differential Scanning Calorimetry (DSC) depicted the presence of thermotropic character, whereas polarized optical microscopy confirmed the mesophase like behavior of D12DAB based cNLCs. In addition, hemolysis analysis revealed that the toxicity was concentration dependent as LC50 was reached at a concentration of 50 μg/mL of cNLCs. This class of cNLCs is expected to become a potent candidate for a broad spectrum of medicaments as carriers, targeting for pharmaceutical and medicinal purposes, due to the combination of a hard lipid with a soft lipid, where the liquid crystalline structure of the lipid co-exists.

  3. Dynamic chromatin states in human ES cells reveal potential regulatory sequences and genes involved in pluripotency

    Institute of Scientific and Technical Information of China (English)

    R David Hawkins; Zhen Ye; Samantha Kuan; Pengzhi Yu; Hui Liu; Xinmin Zhang; Roland D Green; Victor V Lobanenkov; Ron Stewart; James A Thomson; Bing Ren; Gary C Hon; Chuhu Yang; Jessica E Antosiewicz-Bourget; LeonardKLee; Que-Minh Ngo; Sarit Klugman; Keith A Ching; Lee E Edsall

    2011-01-01

    Pluripotency,the ability of a cell to differentiate and give rise to all embryonic lineages,defines a small number of mammalian cell types such as embryonic stem (ES) cells.While it has been generally held that pluripotency is the product of a transcriptional regulatory network that activates and maintains the expression of key stem cell genes,accumulating evidence is pointing to a critical role for epigenetic processes in establishing and safeguarding the pluripotency of ES cells,as well as maintaining the identity of differentiated cell types.In order to better understand the role of epigenetic mechanisms in pluripotency,we have examined the dynamics of chromatin modifications genomewide in human ES cells (hESCs) undergoing differentiation into a mesendodermal lineage.We found that chromatin modifications at promoters remain largely invariant during differentiation,except at a small number of promoters where a dynamic switch between acetylation and methylation at H3K27 marks the transition between activation and silencing of gene expression,suggesting a hierarchy in cell fate commitment over most differentially expressed genes.We also mapped over 50 000 potential enhancers,and observed much greater dynamics in chromatin modifications,especially H3K4mel and H3K27ac,which correlate with expression of their potential target genes.Further analysis of these enhancers revealed potentially key transcriptional regulators of pluripotency and a chromatin signature indicative of a poised state that may confer developmental competence in hESCs.Our results provide new evidence supporting the role of chromatin modifications in defining enhancers and pluripotency.

  4. ECONOMIC POTENTIAL RECOVERY – A EUROPEAN CHALLENGE IN THE MEDIUM TERM

    Directory of Open Access Journals (Sweden)

    Rãdulescu Andrei

    2012-12-01

    Full Text Available The waves of the worst global financial and economic crisis since World War II have seriously affected the economy of the Euro Area. The first wave of the global crisis determined the worst recession in decades for the member states of the region. At present, the Monetary Union is confronted with the second wave of the crisis – the public debt problem. Despite the efforts adopted and implemented by the European policymakers over the past quarters, the sovereign debt crisis is far from over. Spain has recently become the “favourite target” of the financial markets. Among the consequences of the waves of the crisis for the Euro Area one can mention the potential output decline and the economic divergence (asymmetric evolution of member countries. In this context, the potential output recovery and the relaunch of the real economic convergence process represent the main challenges for the policymakers in the medium run. This paper analyses the evolution of potential GDP of the member countries of European Monetary Union (12. I employ the Hodrick-Prescott methodology on data from the World Bank Database. According to the results, the economic potential of the member states of the Euro Area (12 decreased to the lowest level of the past decades. At the same time, the analysis presents the differences exiting across the member states in terms of potential output. Some countries suffered an important potential output loss over the past quarters (it seems that Greece and Portugal have become asymmetric shocks in the Monetary Union. For these countries, the first wave of the global crisis transformed in a permanent shock. The decline of investments and the depreciation of human capital over the past quarters express a huge probability that potential output is going to maintain at a low level in the Euro Area over the following years. The recovery of potential GDP towards the pre-crisis levels is dependent on a higher participation rate

  5. Extroversion-related differences in speed of premotor and motor processing as revealed by lateralized readiness potentials.

    Science.gov (United States)

    Stahl, Jutta; Rammsayer, Thomas

    2008-03-01

    To further elucidate extroversion-related differences in speed of sensorimotor processing, the authors obtained behavioral and psychophysiological measures as participants (16 introverts and 16 extroverts) performed a visual go/no-go task. Although no extroversion-related differences in reaction time emerged, introverts showed faster premotor processing but slower central and peripheral motor processing--as indicated by latencies of the lateralized readiness potential (LRP) and electromyographic (EMG) data, respectively--than extroverts did. Additional regression analyses revealed that stimulus-locked LRP latency, response-locked LRP latency, and Nl EMG amplitude accounted for 40% of overall variability in individual extroversion scores. On the basis of the present results, the authors introduce a compensation hypothesis that accounts for the common failure of researchers to demonstrate extroversion-related differences in reaction time. The present results challenge J. Brebner and C. Cooper's (1985) model of extroversion in which stimulus analysis is not slower in introverts than in extroverts. However, the present findings support the assumption of faster motor processing in extroverts.

  6. Near-Space Microwave Radar Remote Sensing: Potentials and Challenge Analysis

    Directory of Open Access Journals (Sweden)

    Qicong Peng

    2010-03-01

    Full Text Available Near-space, defined as the region between 20 km and 100 km, offers many new capabilities that are not accessible to low earth orbit (LEO satellites and airplanes, because it is above storm and not constrained by either the orbital mechanics of satellites or the high fuel consumption of airplanes. By placing radar transmitter/receiver in near-space platforms, many functions that are currently performed with satellites or airplanes could be performed in a cheaper way. Inspired by these advantages, this paper introduces several near-space vehicle-based radar configurations, such as near-space passive bistatic radar and high-resolution wide-swath (HRWS synthetic aperture radar (SAR. Their potential applications, technical challenges and possible solutions are investigated. It is shown that near-space is a satisfactory solution to some specific remote sensing applications. Firstly, near-space passive bistatic radar using opportunistic illuminators offers a solution to persistent regional remote sensing, which is particularly interest for protecting homeland security or monitoring regional environment. Secondly, near-space provides an optimal solution to relative HRWS SAR imaging. Moreover, as motion compensation is a common technical challenge for the described radars, an active transponder-based motion compensation is also described.

  7. Computational Challenge of Fractional Differential Equations and the Potential Solutions: A Survey

    Directory of Open Access Journals (Sweden)

    Chunye Gong

    2015-01-01

    Full Text Available We present a survey of fractional differential equations and in particular of the computational cost for their numerical solutions from the view of computer science. The computational complexities of time fractional, space fractional, and space-time fractional equations are O(N2M, O(NM2, and O(NM(M + N compared with O(MN for the classical partial differential equations with finite difference methods, where M, N are the number of space grid points and time steps. The potential solutions for this challenge include, but are not limited to, parallel computing, memory access optimization (fractional precomputing operator, short memory principle, fast Fourier transform (FFT based solutions, alternating direction implicit method, multigrid method, and preconditioner technology. The relationships of these solutions for both space fractional derivative and time fractional derivative are discussed. The authors pointed out that the technologies of parallel computing should be regarded as a basic method to overcome this challenge, and some attention should be paid to the fractional killer applications, high performance iteration methods, high order schemes, and Monte Carlo methods. Since the computation of fractional equations with high dimension and variable order is even heavier, the researchers from the area of mathematics and computer science have opportunity to invent cornerstones in the area of fractional calculus.

  8. Electrophysiological potentials reveal cortical mechanisms for mental imagery, mental simulation, and grounded (embodied cognition

    Directory of Open Access Journals (Sweden)

    Haline E. Schendan

    2012-09-01

    Full Text Available Grounded cognition theory proposes that cognition, including meaning, is grounded in sensorimotor processing. The mechanism for grounding cognition is mental simulation, which is a type of mental imagery that re-enacts modal processing. To reveal top-down, cortical mechanisms for mental simulation of shape, event-related potentials were recorded to face and object pictures preceded by mental imagery of a picture. Mental imagery of the identical face or object (congruous condition facilitated not only categorical perception (VPP/N170 but also later visual knowledge (N3[00] complex and linguistic knowledge (N400 for faces more than objects, and strategic semantic analysis (late positive complex between 200 and 700 ms. The later effects resembled semantic congruity effects with pictures. Mental imagery also facilitated category decisions, as a P3(00 peaked earlier for congruous than incongruous (other category pictures, resembling the case when identical pictures repeat immediately. Thus mental imagery mimics semantic congruity and immediate repetition priming processes with pictures. Perception control results showed the opposite for faces and were in the same direction for objects: Perceptual repetition adapts (and so impairs processing of perceived faces from categorical perception onwards, but primes processing of objects during categorical perception, visual knowledge processes, and strategic semantic analysis. For both imagery and perception, differences between faces and objects support domain-specificity and indicate that cognition is grounded in modal processing. Altogether, this direct neural evidence reveals that top-down processes of mental imagery sustain an imagistic representation that mimics perception well enough to prime subsequent perception and cognition. This also suggests that automatic mental simulation of the visual shape of faces and objects operates between 200 and 400 ms, and strategic mental simulation operates between

  9. Therapeutic potentials of gene silencing by RNA interference: principles, challenges, and new strategies.

    Science.gov (United States)

    Deng, Yan; Wang, Chi Chiu; Choy, Kwong Wai; Du, Quan; Chen, Jiao; Wang, Qin; Li, Lu; Chung, Tony Kwok Hung; Tang, Tao

    2014-04-01

    During recent decades there have been remarkable advances in biology, in which one of the most important discoveries is RNA interference (RNAi). RNAi is a specific post-transcriptional regulatory pathway that can result in silencing gene functions. Efforts have been done to translate this new discovery into clinical applications for disease treatment. However, technical difficulties restrict the development of RNAi, including stability, off-target effects, immunostimulation and delivery problems. Researchers have attempted to surmount these barriers and improve the bioavailability and safety of RNAi-based therapeutics by optimizing the chemistry and structure of these molecules. This paper aimed to describe the principles of RNA interference, review the therapeutic potential in various diseases and discuss the new strategies for in vivo delivery of RNAi to overcome the challenges.

  10. Statistical challenges in assessing potential efficacy of complex interventions in pilot or feasibility studies.

    Science.gov (United States)

    Wilson, Duncan T; Walwyn, Rebecca Ea; Brown, Julia; Farrin, Amanda J; Brown, Sarah R

    2016-06-01

    Early phase trials of complex interventions currently focus on assessing the feasibility of a large randomised control trial and on conducting pilot work. Assessing the efficacy of the proposed intervention is generally discouraged, due to concerns of underpowered hypothesis testing. In contrast, early assessment of efficacy is common for drug therapies, where phase II trials are often used as a screening mechanism to identify promising treatments. In this paper, we outline the challenges encountered in extending ideas developed in the phase II drug trial literature to the complex intervention setting. The prevalence of multiple endpoints and clustering of outcome data are identified as important considerations, having implications for timely and robust determination of optimal trial design parameters. The potential for Bayesian methods to help to identify robust trial designs and optimal decision rules is also explored.

  11. H7N9 avian influenza A virus and the perpetual challenge of potential human pandemicity.

    Science.gov (United States)

    Morens, David M; Taubenberger, Jeffery K; Fauci, Anthony S

    2013-07-09

    ABSTRACT The ongoing H7N9 influenza epizootic in China once again presents us questions about the origin of pandemics and how to recognize them in early stages of development. Over the past ~135 years, H7 influenza viruses have neither caused pandemics nor been recognized as having undergone human adaptation. Yet several unusual properties of these viruses, including their poultry epizootic potential, mammalian adaptation, and atypical clinical syndromes in rarely infected humans, suggest that they may be different from other avian influenza viruses, thus questioning any assurance that the likelihood of human adaptation is low. At the same time, the H7N9 epizootic provides an opportunity to learn more about the mammalian/human adaptational capabilities of avian influenza viruses and challenges us to integrate virologic and public health research and surveillance at the animal-human interface.

  12. Low-Temperature Biodiesel Research Reveals Potential Key to Successful Blend Performance (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2012-02-01

    Relatively low-cost solutions could improve reliability while making biodiesel blends an affordable option. While biodiesel has very low production costs and the potential to displace up to 10% of petroleum diesel, until now, issues with cold weather performance have prevented biodiesel blends from being widely adopted. Some biodiesel blends have exhibited unexplained low-temperature performance problems even at blend levels as low as 2% by volume. The most common low-temperature performance issue is vehicle stalling caused by fuel filter clogging, which prevents fuel from reaching the engine. Research at the National Renewable Energy Laboratory (NREL) reveals the properties responsible for these problems, clearing a path for the development of solutions and expanded use of energy-conserving and low-emissions alternative fuel. NREL researchers set out to study the unpredictable nature of biodiesel crystallization, the condition that impedes the flow of fuel in cold weather. Their research revealed for the first time that saturated monoglyceride impurities common to the biodiesel manufacturing process create crystals that can cause fuel filter clogging and other problems when cooling at slow rates. Biodiesel low-temperature operational problems are commonly referred to as 'precipitates above the cloud point (CP).' NREL's Advanced Biofuels team spiked distilled soy and animal fat-derived B100, as well as B20, B10, and B5 biodiesel blends with three saturated monoglycerides (SMGs) at concentration levels comparable to those of real-world fuels. Above a threshold or eutectic concentration, the SMGs (monomyristin, monopalmitin, and monostearin) were shown to significantly raise the biodiesel CP, and had an even greater impact on the final melting temperature. Researchers discovered that upon cooling, monoglyceride initially precipitates as a metastable crystal, but it transforms over time or upon slight heating into a more stable crystal with a much lower

  13. The Challenges and Potential of Nuclear Energy for Addressing Climate Change

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Son H.; Edmonds, James A.

    2007-10-24

    The response to climate change and the stabilization of atmospheric greenhouse gas concentrations has major implications for the global energy system. Stabilization of atmospheric carbon dioxide (CO2) concentrations requires a peak and an indefinite decline of global CO2 emissions. Nuclear energy, along with other technologies, has the potential to contribute to the growing demand for energy without emitting CO2. Nuclear energy is of particular interest because of its global prevalence and its current significant contribution, nearly 20%, to the world’s electricity supply. We have investigated the value of nuclear energy in addressing climate change, and have explored the potential challenges for the rapid and large-scale expansion of nuclear energy as a response to climate change. The scope of this study is long-term and the modeling time frame extends out a century because the nature of nuclear energy and climate change dictate that perspective. Our results indicate that the value of the nuclear technology option for addressing climate change is denominated in trillions of dollars. Several-fold increases to the value of the nuclear option can be expected if there is limited availability of competing carbon-free technologies, particularly fossil-fuel based technologies that can capture and sequester carbon. Challenges for the expanded global use of nuclear energy include the global capacity for nuclear construction, proliferation, uranium availability, and waste disposal. While the economic costs of nuclear fuel and power are important, non-economic issues transcend the issues of costs. In this regard, advanced nuclear technologies and new vision for the global use of nuclear energy are important considerations for the future of nuclear power and climate change.

  14. Potential brain death organ donors - challenges and prospects: A single center retrospective review

    Directory of Open Access Journals (Sweden)

    Yousef Al-Maslamani

    2014-01-01

    Full Text Available Organ donation after brain death (BD is a major source for obtaining transplantable organs for patients with end-stage organ disease (ESOD. This retrospective, descriptive study was carried out on all potential BD patients admitted in different intensive care units (ICUs of the Hamad medical Corporation (HMC, Doha, Qatar during a period from January 2011 to April 2012. Our aim was to evaluate various demographic criteria and challenges of organ donation among potential BD organ donors and plan a strategy to improve the rate of organ donation in Qatar. Various aspects of BD patients in the ICUs and their possible effects on organ donation were studied. The time intervals analyzed to determine the possible causes of delay of organ retrieval were: time of diagnosing fixed dilated pupils in the ICU, to performing the first BD test, then to the second BD test, to family approach, to organ retrieval and/or circulatory death (CD without organ retrieval. There were a total of 116 potential BD organ donors of whom 96 (82.75% were males and 20 (17.25% were females. Brain hemorrhage and head injury contributed to 37 (31.9% and 32 (27.6% BD cases, respectively. Time interval between diagnosing fixed dilated pupil and performing the first test of BD was delayed >24 h in 79% of the cases and between the first and second BD tests was >6 h in 70.8% of the cases. This delay is not compatible with the Hamad Medical Corporation (HMC policy for BD diagnosis and resulted in a low number of organs retrieved. BD organ donation, a potential source for organs to save patients with ESOD has several pitfalls and every effort should be made to increase the awareness of the public as well as medical personnel to optimize donation efficacy.

  15. Exome sequencing reveals a potential mutational trajectory and treatments for a specific pancreatic cancer patient

    Directory of Open Access Journals (Sweden)

    Cotterell J

    2014-05-01

    Full Text Available James Cotterell1,21Center for Genomic Regulation, Barcelona, Spain; 2Garvan Institute for Medical Research, Sydney, NSW, AustraliaAbstract: Pancreatic cancer is the fourth biggest killer, and has one of the worst prognoses, of any cancer type. Approximately 95% of patients diagnosed with pancreatic cancer will not survive beyond 5 years post diagnosis, and these statistics have barely improved in over 40 years. Here, genomic changes in one particular patient with stage IV metastatic pancreatic cancer were explored to suggest a potential personalized treatment. In particular, exome sequencing of genomic DNA extracted from blood and the cancer biopsy was utilized with the aim of identifying mutational drivers of the cancer. This analysis revealed a splice site mutation in RBCK1 as the most promising driver of the cancer and a therapy based on a pan-cyclin-dependent kinase (pan-CDK inhibitor, flavopiridol. This study suggests that drugs whose effectiveness is unclear for general populations of cancer sufferers should possibly be reconsidered for specific patients where the drug could be rationally argued to improve outcome.Keyword: personalized medicine, driver mutation identification, next generation sequencing

  16. Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study

    Directory of Open Access Journals (Sweden)

    Hua Wan

    2016-01-01

    Full Text Available TAL effectors (TALEs contain a modular DNA-binding domain that is composed of tandem repeats. In all naturally occurring TALEs, the end of tandem repeats is invariantly a truncated half repeat. To investigate the potential role of the last half repeat in TALEs, we performed comparative molecular dynamics simulations for the crystal structure of DNA-bound TALE AvrBs3 lacking the last half repeat and its modeled structure having the last half repeat. The structural stability analysis indicates that the modeled system is more stable than the nonmodeled system. Based on the principle component analysis, it is found that the AvrBs3 increases its structural compactness in the presence of the last half repeat. The comparison of DNA groove parameters of the two systems implies that the last half repeat also causes the change of DNA major groove binding efficiency. The following calculation of hydrogen bond reveals that, by stabilizing the phosphate binding with DNA at the C-terminus, the last half repeat helps to adopt a compact conformation at the protein-DNA interface. It further mediates more contacts between TAL repeats and DNA nucleotide bases. Finally, we suggest that the last half repeat is required for the high-efficient recognition of DNA by TALE.

  17. Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study

    Science.gov (United States)

    Wan, Hua; Chang, Shan; Hu, Jian-ping; Tian, Xu-hong

    2016-01-01

    TAL effectors (TALEs) contain a modular DNA-binding domain that is composed of tandem repeats. In all naturally occurring TALEs, the end of tandem repeats is invariantly a truncated half repeat. To investigate the potential role of the last half repeat in TALEs, we performed comparative molecular dynamics simulations for the crystal structure of DNA-bound TALE AvrBs3 lacking the last half repeat and its modeled structure having the last half repeat. The structural stability analysis indicates that the modeled system is more stable than the nonmodeled system. Based on the principle component analysis, it is found that the AvrBs3 increases its structural compactness in the presence of the last half repeat. The comparison of DNA groove parameters of the two systems implies that the last half repeat also causes the change of DNA major groove binding efficiency. The following calculation of hydrogen bond reveals that, by stabilizing the phosphate binding with DNA at the C-terminus, the last half repeat helps to adopt a compact conformation at the protein-DNA interface. It further mediates more contacts between TAL repeats and DNA nucleotide bases. Finally, we suggest that the last half repeat is required for the high-efficient recognition of DNA by TALE. PMID:27803930

  18. The time course of word retrieval revealed by event-related brain potentials during overt speech.

    Science.gov (United States)

    Costa, Albert; Strijkers, Kristof; Martin, Clara; Thierry, Guillaume

    2009-12-15

    Speech production is one of the most fundamental activities of humans. A core cognitive operation involved in this skill is the retrieval of words from long-term memory, that is, from the mental lexicon. In this article, we establish the time course of lexical access by recording the brain electrical activity of participants while they named pictures aloud. By manipulating the ordinal position of pictures belonging to the same semantic categories, the cumulative semantic interference effect, we were able to measure the exact time at which lexical access takes place. We found significant correlations between naming latencies, ordinal position of pictures, and event-related potential mean amplitudes starting 200 ms after picture presentation and lasting for 180 ms. The study reveals that the brain engages extremely fast in the retrieval of words one wishes to utter and offers a clear time frame of how long it takes for the competitive process of activating and selecting words in the course of speech to be resolved.

  19. Metagenomic analysis reveals that modern microbialites and polar microbial mats have similar taxonomic and functional potential.

    Science.gov (United States)

    White, Richard Allen; Power, Ian M; Dipple, Gregory M; Southam, Gordon; Suttle, Curtis A

    2015-01-01

    Within the subarctic climate of Clinton Creek, Yukon, Canada, lies an abandoned and flooded open-pit asbestos mine that harbors rapidly growing microbialites. To understand their formation we completed a metagenomic community profile of the microbialites and their surrounding sediments. Assembled metagenomic data revealed that bacteria within the phylum Proteobacteria numerically dominated this system, although the relative abundances of taxa within the phylum varied among environments. Bacteria belonging to Alphaproteobacteria and Gammaproteobacteria were dominant in the microbialites and sediments, respectively. The microbialites were also home to many other groups associated with microbialite formation including filamentous cyanobacteria and dissimilatory sulfate-reducing Deltaproteobacteria, consistent with the idea of a shared global microbialite microbiome. Other members were present that are typically not associated with microbialites including Gemmatimonadetes and iron-oxidizing Betaproteobacteria, which participate in carbon metabolism and iron cycling. Compared to the sediments, the microbialite microbiome has significantly more genes associated with photosynthetic processes (e.g., photosystem II reaction centers, carotenoid, and chlorophyll biosynthesis) and carbon fixation (e.g., CO dehydrogenase). The Clinton Creek microbialite communities had strikingly similar functional potentials to non-lithifying microbial mats from the Canadian High Arctic and Antarctica, but are functionally distinct, from non-lithifying mats or biofilms from Yellowstone. Clinton Creek microbialites also share metabolic genes (R (2) Mexico, but are more similar to polar Arctic mats (R (2) > 0.900). These metagenomic profiles from an anthropogenic microbialite-forming ecosystem provide context to microbialite formation on a human-relevant timescale.

  20. Metagenomic analysis reveals that modern microbialites and polar microbial mats have similar taxonomic and functional potential

    Directory of Open Access Journals (Sweden)

    Richard Allen White III

    2015-09-01

    Full Text Available Within the subarctic climate of Clinton Creek, Yukon, Canada, lies an abandoned and flooded open-pit asbestos mine that harbors rapidly growing microbialites. To understand their formation we completed a metagenomic community profile of the microbialites and their surrounding sediments. Assembled metagenomic data revealed that bacteria within the phylum Proteobacteria numerically dominated this system, although the relative abundances of taxa within the phylum varied among environments. Bacteria belonging to Alphaproteobacteria and Gammaproteobacteria were dominant in the microbialites and sediments, respectively. The microbialites were also home to many other groups associated with microbialite formation including filamentous cyanobacteria and dissimilatory sulfate-reducing Deltaproteobacteria, consistent with the idea of a shared global microbialite microbiome. Other members were present that are typically not associated with microbialites including Gemmatimonadetes and iron-oxidizing Betaproteobacteria, which participate in carbon metabolism and iron cycling. Compared to the sediments, the microbialite microbiome has significantly more genes associated with photosynthetic processes (e.g., photosystem II reaction centers, carotenoid and chlorophyll biosynthesis and carbon fixation (e.g., CO dehydrogenase. The Clinton Creek microbialite communities had strikingly similar functional potentials to non-lithifying microbial mats from the Canadian High Arctic and Antarctica, but are functionally distinct, from non-lithifying mats or biofilms from Yellowstone. Clinton Creek microbialites also share metabolic genes (R2 0.900. These metagenomic profiles from an anthropogenic microbialite-forming ecosystem provide context to microbialite formation on a human-relevant timescale.

  1. Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species.

    Science.gov (United States)

    Lee, Kim-Chung; Tam, Emily W T; Lo, Ka-Ching; Tsang, Alan K L; Lau, Candy C Y; To, Kelvin K W; Chan, Jasper F W; Lam, Ching-Wan; Yuen, Kwok-Yung; Lau, Susanna K P; Woo, Patrick C Y

    2015-06-17

    Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii) and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu-Glu-Leu-Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxy)benzoic acid possesses a structure similar to those of aspirin [2-(acetoxy)benzoic acid] and salicylic acid (2-hydroxybenzoic acid). Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu-Glu-Leu-Glu, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid are virulent factors of the pathogenic Aspergillus species.

  2. Potential translational targets revealed by linking mouse grooming behavioral phenotypes to gene expression using public databases.

    Science.gov (United States)

    Roth, Andrew; Kyzar, Evan J; Cachat, Jonathan; Stewart, Adam Michael; Green, Jeremy; Gaikwad, Siddharth; O'Leary, Timothy P; Tabakoff, Boris; Brown, Richard E; Kalueff, Allan V

    2013-01-10

    Rodent self-grooming is an important, evolutionarily conserved behavior, highly sensitive to pharmacological and genetic manipulations. Mice with aberrant grooming phenotypes are currently used to model various human disorders. Therefore, it is critical to understand the biology of grooming behavior, and to assess its translational validity to humans. The present in-silico study used publicly available gene expression and behavioral data obtained from several inbred mouse strains in the open-field, light-dark box, elevated plus- and elevated zero-maze tests. As grooming duration differed between strains, our analysis revealed several candidate genes with significant correlations between gene expression in the brain and grooming duration. The Allen Brain Atlas, STRING, GoMiner and Mouse Genome Informatics databases were used to functionally map and analyze these candidate mouse genes against their human orthologs, assessing the strain ranking of their expression and the regional distribution of expression in the mouse brain. This allowed us to identify an interconnected network of candidate genes (which have expression levels that correlate with grooming behavior), display altered patterns of expression in key brain areas related to grooming, and underlie important functions in the brain. Collectively, our results demonstrate the utility of large-scale, high-throughput data-mining and in-silico modeling for linking genomic and behavioral data, as well as their potential to identify novel neural targets for complex neurobehavioral phenotypes, including grooming.

  3. Genetic diversity and population structure of endangered Aquilaria malaccensis revealed potential for future conservation.

    Science.gov (United States)

    Singh, Pradeep; Nag, Akshay; Parmar, Rajni; Ghosh, Sneha; Bhau, Brijmohan Singh; Sharma, Ram Kumar

    2015-12-01

    The endangered Aquilaria malaccensis,is an important plant with high economic values. Characterization of genetic diversity and population structure is receiving tremendous attention for effective conservation of genetic resources. Considering important repositories of biological diversity, the genetic relationships of 127 A. malaccensis accessions from 10 home gardens of three states of northeast India were assessed using amplified fragment length polymorphism (AFLP). Of the 1153 fragments amplified with four AFLP primer combinations, 916 (79.4%) were found to be polymorphic. Polymorphic information content (PIC) and marker index (MI) of each primer combination correlate significantly with the number of genotypes resolved. Overall, a high genetic diversity (avg. 71.85%) was recorded. Further, high gene flow (Nm: 3.37), low genetic differentiation (FST: 0.069) and high within population genetic variation (93%) suggests that most of the genetic diversity is restricted within population. Neighbour joining (NJ), principal coordinate analysis (PCoA) and Bayesian-based STRUCTURE grouped all the accessions in two clusters with significant intermixing between populations, therefore, revealed that two genetically distinct gene pools are operating in the A. malaccensis populations cultivated in home gardens. Based on the various diversity inferences, five diverse populations (JOH, FN, HLF, DHM and ITN) were identified, which can be potentially exploited to develop conservation strategies for A. malaccensis.

  4. A fibrolytic potential in the human ileum mucosal microbiota revealed by functional metagenomic

    Science.gov (United States)

    Patrascu, Orlane; Béguet-Crespel, Fabienne; Marinelli, Ludovica; Le Chatelier, Emmanuelle; Abraham, Anne-Laure; Leclerc, Marion; Klopp, Christophe; Terrapon, Nicolas; Henrissat, Bernard; Blottière, Hervé M.; Doré, Joël; Béra-Maillet, Christel

    2017-01-01

    The digestion of dietary fibers is a major function of the human intestinal microbiota. So far this function has been attributed to the microorganisms inhabiting the colon, and many studies have focused on this distal part of the gastrointestinal tract using easily accessible fecal material. However, microbial fermentations, supported by the presence of short-chain fatty acids, are suspected to occur in the upper small intestine, particularly in the ileum. Using a fosmid library from the human ileal mucosa, we screened 20,000 clones for their activities against carboxymethylcellulose and xylans chosen as models of the major plant cell wall (PCW) polysaccharides from dietary fibres. Eleven positive clones revealed a broad range of CAZyme encoding genes from Bacteroides and Clostridiales species, as well as Polysaccharide Utilization Loci (PULs). The functional glycoside hydrolase genes were identified, and oligosaccharide break-down products examined from different polysaccharides including mixed-linkage β-glucans. CAZymes and PULs were also examined for their prevalence in human gut microbiome. Several clusters of genes of low prevalence in fecal microbiome suggested they belong to unidentified strains rather specifically established upstream the colon, in the ileum. Thus, the ileal mucosa-associated microbiota encompasses the enzymatic potential for PCW polysaccharide degradation in the small intestine. PMID:28091525

  5. Zero-expansion glass ceramic ZERODUR: recent developments reveal high potential

    Science.gov (United States)

    Hartmann, Peter; Jedamzik, Ralf; Westerhoff, Thomas

    2012-09-01

    ZERODUR® is a well-established material in astronomy and all fields of applications where temperature gradients might limit extreme precision and stability. Together with its rich heritage come a series of recent developments, which reveal the potential of the material for broader and more demanding applications. The outstanding degree of light-weighting achieved with progress in CNC grinding in the last two years shows its high suitability for space telescope mirrors. This is supported by new data on strength enabling higher mechanical loads. Also ground based telescopes benefit from the improved light-weight processing such as solar telescopes and downstream mirrors of extremely large telescopes. More and better data have been collected demonstrating the unique CTE homogeneity of ZERODUR® and its very high reproducibility a necessary precondition for large series mirror production. Deliveries of more than 250 ZERODUR mirrors of 1.5 m in diameter prove the availability of robust industrial serial production capability inevitable for ELT mirror segment production.

  6. Biosurfactant/s from Lactobacilli species: Properties, challenges and potential biomedical applications.

    Science.gov (United States)

    Satpute, Surekha K; Kulkarni, Gauri R; Banpurkar, Arun G; Banat, Ibrahim M; Mone, Nishigandha S; Patil, Rajendra H; Cameotra, Swaranjit Singh

    2016-11-01

    Lactic acid bacteria are generally believed to have positive roles in maintaining good health and immune system in humans. A number of Lactobacilli spp. are known to produce important metabolites, among which biosurfactants in particular have shown antimicrobial activity against several pathogens in the intestinal tract and female urogenital tract partly through interfering with biofilm formation and adhesion to the epithelial cells surfaces. Around 46 reports are documented on biosurfactant production from Lactobacillus spp. of which six can be broadly classified as cell free biosurfactant and 40 as cell associated biosurfactants and only approximately 50% of those have reported on the structural composition which, in order of occurrence were mainly proteinaceous, glycolipidic, glycoproteins, or glycolipopeptides in nature. Due to the proteinaceous nature, most biosurfactant produced by strains of Lactobacillus are generally believed to be surlactin type with high potential toward impeding pathogens adherence. Researchers have recently focused on the anti-adhesive and antibiofilm properties of Lactobacilli-derived biosurfactants. This review briefly discusses the significance of Lactobacilli-derived biosurfactants and their potential applications in various fields. In addition, we highlight the exceptional prospects and challenges in fermentation economics of Lactobacillus spp.-derived biosurfactants' production processes.

  7. Therapeutic potential and challenges of Natural killer cells in treatment of solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea eGras Navarro

    2015-04-01

    Full Text Available Natural killer (NK cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing requiring one–to-one target engagement and site directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME and augment adaptive immune responses by promoting differentiation, activation and/ or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach.

  8. Current Challenges in Volatile Organic Compounds Analysis as Potential Biomarkers of Cancer

    Directory of Open Access Journals (Sweden)

    Kamila Schmidt

    2015-01-01

    Full Text Available An early diagnosis and appropriate treatment are crucial in reducing mortality among people suffering from cancer. There is a lack of characteristic early clinical symptoms in most forms of cancer, which highlights the importance of investigating new methods for its early detection. One of the most promising methods is the analysis of volatile organic compounds (VOCs. VOCs are a diverse group of carbon-based chemicals that are present in exhaled breath and biofluids and may be collected from the headspace of these matrices. Different patterns of VOCs have been correlated with various diseases, cancer among them. Studies have also shown that cancer cells in vitro produce or consume specific VOCs that can serve as potential biomarkers that differentiate them from noncancerous cells. This review identifies the current challenges in the investigation of VOCs as potential cancer biomarkers, by the critical evaluation of available matrices for the in vivo and in vitro approaches in this field and by comparison of the main extraction and detection techniques that have been applied to date in this area of study. It also summarises complementary in vivo, ex vivo, and in vitro studies conducted to date in order to try to identify volatile biomarkers of cancer.

  9. The challenge of treating obesity: the endocannabinoid system as a potential target.

    Science.gov (United States)

    Isoldi, Kathy Keenan; Aronne, Louis J

    2008-05-01

    Obesity and cardiometabolic risk, or the metabolic syndrome, continue to be major public health concerns. To date, treatment with lifestyle and pharmacotherapy interventions has resulted in limited efficacy in reversing the upward trend in this present-day health crisis. Research reveals that a modest 5% to 10% weight loss results in substantial improvement in health. While obtaining modest weight loss is often achievable, maintaining lost weight is challenging. Research has recently improved our understanding of several endogenous pathways that influence body weight regulation and disease risk. The endocannabinoid system has been found to regulate appetite and energy expenditure, as well as lipid and glucose metabolism. Interest in blocking stimulation of this pathway to aid weight loss and reduce cardiometabolic risk factor development is an area of interest and research. This article reviews the mechanisms by which the endocannabinoid system is believed to influence body weight regulation and cardiometabolic risk factors, as well as the results of clinical trials investigating the safety and efficacy of a selective cannabinoid-1 receptor antagonist (rimonabant). Clinical trials investigating rimonabant treatment resulted in substantial reductions in body weight and markers for cardiometabolic risk in study participants. However, increases in adverse events were reported in the drug-treated group. Data regarding long-term benefit and adverse events from rimonabant treatment are being collected in several ongoing clinical trials. Rimonabant is currently available in 42 countries, but has not received United States Food and Drug Administration approval. Food and nutrition professionals play a pivotal role in tackling the current obesity crisis; it is essential that they understand the many physiological mechanisms regulating body weight. Emerging research data reveals pathways that influence appetite and energy metabolism, and this knowledge may form the foundation

  10. Projected Scenarios for Coastal First Nations' Fisheries Catch Potential under Climate Change: Management Challenges and Opportunities.

    Science.gov (United States)

    Weatherdon, Lauren V; Ota, Yoshitaka; Jones, Miranda C; Close, David A; Cheung, William W L

    2016-01-01

    Studies have demonstrated ways in which climate-related shifts in the distributions and relative abundances of marine species are expected to alter the dynamics and catch potential of global fisheries. While these studies assess impacts on large-scale commercial fisheries, few efforts have been made to quantitatively project impacts on small-scale subsistence and commercial fisheries that are economically, socially and culturally important to many coastal communities. This study uses a dynamic bioclimate envelope model to project scenarios of climate-related changes in the relative abundance, distribution and richness of 98 exploited marine fishes and invertebrates of commercial and cultural importance to First Nations in coastal British Columbia, Canada. Declines in abundance are projected for most of the sampled species under both the lower (Representative Concentration Pathway [RCP] 2.6) and higher (RCP 8.5) emission scenarios (-15.0% to -20.8%, respectively), with poleward range shifts occurring at a median rate of 10.3 to 18.0 km decade(-1) by 2050 relative to 2000. While a cumulative decline in catch potential is projected coastwide (-4.5 to -10.7%), estimates suggest a strong positive correlation between the change in relative catch potential and latitude, with First Nations' territories along the northern and central coasts of British Columbia likely to experience less severe declines than those to the south. Furthermore, a strong negative correlation is projected between latitude and the number of species exhibiting declining abundance. These trends are shown to be robust to alternative species distribution models. This study concludes by discussing corresponding management challenges that are likely to be encountered under climate change, and by highlighting the value of joint-management frameworks and traditional fisheries management approaches that could aid in offsetting impacts and developing site-specific mitigation and adaptation strategies derived

  11. Projections of Biofuel Growth Patterns Reveal the Potential Importance of Nitrogen Fixation for Miscanthus Productivity

    Science.gov (United States)

    Davis, S. C.; Parton, W. J.; Dohleman, F. G.; Gottel, N. R.; Smith, C. M.; Kent, A. D.; Delucia, E. H.

    2008-12-01

    Demand for liquid biofuels is increasing because of the disparity between fuel demand and supply. Relative to grain crops, the more intensive harvest required for second generation liquid biofuel production leads to the removal of significantly more carbon and nitrogen from the soil. These elements are conventionally litter products of crops that are returned to the soil and can accumulate over time. This loss of organic matter represents a management challenge because the energy cost associated with fertilizers or external sources of organic matter reduce the net energy value of the biofuel crops. Plants that have exceptional strategies for exploiting nutrients may be the most viable options for sustainable biofuel yields because of low management and energy cost. Miscanthus x giganteus has high N retranslocation rates, maintains high photosynthetic rates over a large temperature range, exploits a longer-than-average growing season, and yields at least twice the biomass of other candidate biofuel grass crops (i.e. switchgrass). We employed the DAYCENT model to project potential productivity of Miscanthus, corn, switchgrass, and mixed prairie communities based on our current knowledge of these species. Ecosystem process descriptions that have been validated for many crop species did not accurately predict Miscanthus yields and lead to new hypotheses about unknown N cycling mechanisms for this species. We tested the hypothesis that Miscanthus hosts N-fixing bacteria in several ways. First, we used enrichment culture and molecular methods to detect N-fixing bacteria in Miscanthus. Then, we demonstrated the plant-growth promoting effect of diazotrophs isolated from Miscanthus rhizomes on a model grass. And finally, we applied 15N2 to the soil and rooting zone of field grown Miscanthus plants to determine if atmospheric N2 was incorporated into plant tissue, a process that requires N-fixation. These experiments are the first tests of N-fixation in Miscanthus x

  12. The development of control processes supporting source memory discrimination as revealed by event-related potentials.

    Science.gov (United States)

    de Chastelaine, Marianne; Friedman, David; Cycowicz, Yael M

    2007-08-01

    Improvement in source memory performance throughout childhood is thought to be mediated by the development of executive control. As postretrieval control processes may be better time-locked to the recognition response rather than the retrieval cue, the development of processes underlying source memory was investigated with both stimulus- and response-locked event-related potentials (ERPs). These were recorded in children, adolescents, and adults during a recognition memory exclusion task. Green- and red-outlined pictures were studied, but were tested in black outline. The test requirement was to endorse old items shown in one study color ("targets") and to reject new items along with old items shown in the alternative study color ("nontargets"). Source memory improved with age. All age groups retrieved target and nontarget memories as reflected by reliable parietal episodic memory (EM) effects, a stimulus-locked ERP correlate of recollection. Response-locked ERPs to targets and nontargets diverged in all groups prior to the response, although this occurred at an increasingly earlier time point with age. We suggest these findings reflect the implementation of attentional control mechanisms to enhance target memories and facilitate response selection with the greatest and least success, respectively, in adults and children. In adults only, response-locked ERPs revealed an early-onsetting parietal negativity for nontargets, but not for targets. This was suggested to reflect adults' ability to consistently inhibit prepotent target responses for nontargets. The findings support the notion that the development of source memory relies on the maturation of control processes that serve to enhance accurate selection of task-relevant memories.

  13. Metal oxide-based nanoparticles: revealing their potential to enhance oil recovery in different wettability systems

    Science.gov (United States)

    Hendraningrat, Luky; Torsæter, Ole

    2015-02-01

    This paper presents systematic studies of hydrophilic metal oxide nanoparticles (NPs) dispersed in brine intended to reveal their potential to enhance oil recovery (EOR) in various rock wettability systems. The stability in suspension (nanofluid) of the NPs has been identified as a key factor related to their use as an EOR agent. Experimental techniques have been developed for nanofluid stability using three coupled methods: direct visual observation, surface conductivity and particle size measurements. The use of a dispersant has been investigated and has been shown to successfully improve metal oxide nanofluid stability as a function of its concentration. The dispersant alters the nanofluid properties, i.e. surface conductivity, pH and particle size distribution. A two-phase coreflood experiment was conducted by injecting the stable nanofluids as a tertiary process (nano-EOR) through core plugs with various wettabilities ranging from water-wet to oil-wet. The combination of metal oxide nanofluid and dispersant improved the oil recovery to a greater extent than either silica-based nanofluid or dispersant alone in all wettability systems. The contact angle, interfacial tension (IFT) and effluent were also measured. It was observed that metal oxide-based nanofluids altered the quartz plates to become more water-wet, and the results are consistent with those of the coreflood experiment. The particle adsorption during the transport process was identified from effluent analysis. The presence of NPs and dispersant reduced the IFT, but its reduction is sufficient to yield significant additional oil recovery. Hence, wettability alteration plays a dominant role in the oil displacement mechanism using nano-EOR.

  14. Microbial P450 enzymes in bioremediation and drug discovery: Emerging potentials and challenges.

    Science.gov (United States)

    Bhattacharya, Sukanta S; Yadav, Jagjit S

    2016-11-21

    Cytochrome P450 enzymes are a structurally conserved but functionally diverse group of heme-containing mixed function oxidases found across both prokaryotic and eukaryotic forms of the microbial world. Microbial P450s are known to perform diverse functions ranging from the synthesis of cell wall components to xenobiotic/drug metabolism to biodegradation of environmental chemicals. Conventionally, many microbial systems have been reported to mimic mammalian P450-like activation of drugs and were proposed as the in-vitro models of mammalian drug metabolism. Recent reports suggest that native or engineered forms of specific microbial P450s from these and other microbial systems could be employed for desired specific biotransformation reactions toward natural and synthetic (drug) compounds underscoring their emerging potential in drug improvement and discovery. On the other hand, microorganisms particularly fungi and actinomycetes have been shown to possess catabolic P450s with unusual potential to degrade toxic environmental chemicals including persistent organic pollutants (POPs). Wood-rotting basidiomycete fungi in particular have revealed the presence of exceptionally large P450 repertoire (P450ome) in their genomes, majority of which are however orphan (with no known function). Our pre- and post-genomic studies have led to functional characterization of several fungal P450s inducible in response to exposure to several environmental toxicants and their potential in bioremediation of these chemicals. This review is an attempt to summarize the post-genomic unveiling of this versatile enzyme superfamily in microbial systems and investigation of their potential to synthesize new drugs and degrade persistent pollutants, among other biotechnological applications.

  15. microRNAs as Potential Biomarkers in Adrenocortical Cancer: Progress and Challenges

    Science.gov (United States)

    Cherradi, Nadia

    2016-01-01

    Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis and limited therapeutic options. Over the last decade, pan-genomic analyses of genetic and epigenetic alterations and genome-wide expression profile studies allowed major advances in the understanding of the molecular genetics of ACC. Besides the well-known dysfunctional molecular pathways in adrenocortical tumors, such as the IGF2 pathway, the Wnt pathway, and TP53, high-throughput technologies enabled a more comprehensive genomic characterization of adrenocortical cancer. Integration of expression profile data with exome sequencing, SNP array analysis, methylation, and microRNA (miRNA) profiling led to the identification of subgroups of malignant tumors with distinct molecular alterations and clinical outcomes. miRNAs post-transcriptionally silence their target gene expression either by degrading mRNA or by inhibiting translation. Although our knowledge of the contribution of deregulated miRNAs to the pathogenesis of ACC is still in its infancy, recent studies support their relevance in gene expression alterations in these tumors. Some miRNAs have been shown to carry potential diagnostic and prognostic values, while others may be good candidates for therapeutic interventions. With the emergence of disease-specific blood-borne miRNAs signatures, analyses of small cohorts of patients with ACC suggest that circulating miRNAs represent promising non-invasive biomarkers of malignancy or recurrence. However, some technical challenges still remain, and most of the miRNAs reported in the literature have not yet been validated in sufficiently powered and longitudinal studies. In this review, we discuss the current knowledge regarding the deregulation of tumor-associated and circulating miRNAs in ACC patients, while emphasizing their potential significance in pathogenic pathways in light of recent insights into the role of miRNAs in shaping the tumor microenvironment. PMID:26834703

  16. MicroRNAs as potential biomarkers in adrenocortical cancer: progress and challenges

    Directory of Open Access Journals (Sweden)

    Nadia eCHERRADI

    2016-01-01

    Full Text Available Adrenocortical carcinoma is a rare malignancy with poor prognosis and limited therapeutic options. Over the last decade, pan-genomic analyses of genetic and epigenetic alterations and genome-wide expression profile studies allowed major advances in the understanding of the molecular genetics of adrenocortical carcinoma. Besides the well-known dysfunctional molecular pathways in adrenocortical tumors such as the IGF2 pathway, the Wnt pathway and TP53, high-throughput technologies enabled a more comprehensive genomic characterization of adrenocortical cancer. Integration of expression profile data with exome sequencing, SNP array analysis, methylation and microRNA profiling led to the identification of subgroups of malignant tumors with distinct molecular alterations and clinical outcomes. MicroRNAs post-transcriptionally silence their target gene expression either by degrading mRNA or by inhibiting translation. Although our knowledge of the contribution of deregulated microRNAs to the pathogenesis of adrenocortical carcinoma is still in its infancy, recent studies support their relevance in gene expression alterations in these tumors. Some microRNAs have been shown to carry potential diagnostic and prognostic values while others may be good candidates for therapeutic interventions. With the emergence of disease-specific blood-borne microRNAs signatures, analyses of small cohorts of patients with adrenocortical carcinoma suggest that circulating microRNAs represent promising non-invasive biomarkers of malignancy or recurrence. However, some technical challenges still remain, and most of the microRNAs reported in the literature have not yet been validated in sufficiently powered and longitudinal studies. In this review, we discuss the current knowledge regarding the deregulation of tumor-associated and circulating microRNAs in adrenocortical carcinoma patients, while emphasizing their potential significance in adrenocortical carcinoma pathogenic

  17. Forward and pressure retarded osmosis: potential solutions for global challenges in energy and water supply.

    Science.gov (United States)

    Klaysom, Chalida; Cath, Tazhi Y; Depuydt, Tom; Vankelecom, Ivo F J

    2013-08-21

    Osmotically driven membrane processes (ODMP) have gained renewed interest in recent years and they might become a potential solution for the world's most challenging problems of water and energy scarcity. Though the concept of utilizing osmotic pressure difference between high and low salinity streams across semipermeable membranes has been explored for several decades, lack of optimal membranes and draw solutions hindered competition between forward osmosis (FO) and pressure retarded osmosis (PRO) with existing water purification and power generation technologies, respectively. Driven by growing global water scarcity and by energy cost and negative environmental impacts, novel membranes and draw solutions are being developed for ODMPs, mass and heat transfer in osmotic process are becoming better understood, and new applications of ODMPs are emerging. Therefore, OMDPs might become promising green technologies to provide clean water and clean energy from abundantly available renewable resources. This review focuses primarily on new insights into osmotic membrane transport mechanisms and on novel membranes and draw solutions that are currently being developed. Furthermore, the effects of operating conditions on the overall performance of osmotic membranes will be highlighted and future perspectives will be presented.

  18. Therapeutic Potential, Challenges and Future Perspective of Cancer Stem Cells in Translational Oncology: A Critical Review.

    Science.gov (United States)

    Shukla, Gaurav; Khera, Harvinder Kour; Srivastava, Amit Kumar; Khare, Piush; Patidar, Rahul; Saxena, Rajiv

    2017-01-01

    Stem cell research is a rapidly developing field that offers effective treatment for a variety of malignant and non-malignant diseases. Stem cell is a regenerative medicine associated with the replacement, repair, and restoration of injured tissue. Stem cell research is a promising field having maximum therapeutic potential. Cancer stem cells (CSCs) are the cells within the tumor that posses capacity of selfrenewal and have a root cause for the failure of traditional therapies leading to re-occurrence of cancer. CSCs have been identified in blood, breast, brain, and colon cancer. Traditional therapies target only fast growing tumor mass, but not slow-dividing cancer stem cells. It has been shown that embryonic pathways such as Wnt, Hedgehog and Notch, control self-renewal capacity and involved in cancer stem cell maintenance. Targeting of these pathways may be effective in eradicating cancer stem cells and preventing chemotherapy and radiotherapy resistance. Targeting CSCs has become one of the most effective approaches to improve the cancer survival by eradicating the main root cause of cancer. The present review will address, in brief, the importance of cancer stem cells in targeting cancer as better and effective treatment along with a concluding outlook on the scope and challenges in the implication of cancer stem cells in translational oncology.

  19. Potential challenges facing distributed leadership in health care: evidence from the UK National Health Service.

    Science.gov (United States)

    Martin, Graeme; Beech, Nic; MacIntosh, Robert; Bushfield, Stacey

    2015-01-01

    The discourse of leaderism in health care has been a subject of much academic and practical debate. Recently, distributed leadership (DL) has been adopted as a key strand of policy in the UK National Health Service (NHS). However, there is some confusion over the meaning of DL and uncertainty over its application to clinical and non-clinical staff. This article examines the potential for DL in the NHS by drawing on qualitative data from three co-located health-care organisations that embraced DL as part of their organisational strategy. Recent theorising positions DL as a hybrid model combining focused and dispersed leadership; however, our data raise important challenges for policymakers and senior managers who are implementing such a leadership policy. We show that there are three distinct forms of disconnect and that these pose a significant problem for DL. However, we argue that instead of these disconnects posing a significant problem for the discourse of leaderism, they enable a fantasy of leadership that draws on and supports the discourse.

  20. A REVIEW OF OIL PALM BIOCOMPOSITES FOR FURNITURE DESIGN AND APPLICATIONS: POTENTIAL AND CHALLENGES

    Directory of Open Access Journals (Sweden)

    Siti Suhaily,

    2012-07-01

    Full Text Available This review considers the potential and challenges of using agro-based oil palm biomasses, including the trunk, frond, empty fruit bunch, and palm press fiber biocomposites, for furniture applications. Currently, design and quality rather than price are becoming the primary concern for consumers when buying new furniture. Within this context, this paper focuses on the design of innovative, sustainable furniture from agro-based biocomposites to meet the needs of future population growth and technology. This research also discusses the need for biocomposite materials that do not depend on the growth of populations, but on the growth and development of the economy. This study focuses on globally available agro-based biocomposites, especially those from oil palm biomass: plywood, medium density fiberboard (MDF, wood plastic composite (WPC, laminated veneer lumber (LVL, oriented strand board (OSB, hardboards, and particleboard. Additional positive aspects of biocomposites are their environmentally friendly character, high quality, competitive design, and capacity to improve the value proposition of high-end products. These attributes increase the demand for agro-based biocomposite furniture on the international market.

  1. Salmonella challenges: prevalence in swine and poultry and potential pathogenicity of such isolates.

    Science.gov (United States)

    Foley, S L; Lynne, A M; Nayak, R

    2008-04-01

    Salmonellosis is the second leading cause of bacterial foodborne illness in the United States, and the great majority of these infections are associated with the consumption of products such as meat, poultry, eggs, milk, seafood, and fresh produce contaminated with Salmonella. The per capita consumption of meat and poultry in United States has increased significantly over the past century. This increase is especially evident with poultry products, where there has been a nearly 6-fold increase in chicken consumption and 17-fold increase in turkey consumption since 1909. The per capita consumption of pork has also increased over this time from 18.7 to 21.7 kg/yr. With this increase in meat and poultry consumption, the dynamics of animal production and consumer exposure have changed leading to new challenges in limiting salmonellosis. To meet the demands of consumers, more intensive agricultural practices have been adopted, which has likely changed the population characteristics of Salmonella present among poultry flocks and swine populations. In Salmonella isolated from swine in the United States, S. Typhimurium has replaced S. Choleraesuis as the predominant serovar in recent years. Among isolates from turkeys collected in 2004, serovars S. Senftenberg and S. Hadar were most common overall; however, S. Heidelberg was most common from clinical diagnostic sources, potentially indicating increased virulence. Salmonella Heidelberg was also the most commonly detected serovar among chicken isolates from clinically ill birds and Salmonella surveillance samples. Overall among the 10 serovars most commonly associated with human infections, 6 are also found in the top serovars of swine and poultry. These include S. Typhimurium, S. Enteritidis, S. Heidelberg, S. Montevideo, S. Saintpaul, and S. I 4,[5],12:i:-.

  2. Phytogenic Compounds as Alternatives to In-Feed Antibiotics: Potentials and Challenges in Application

    Directory of Open Access Journals (Sweden)

    Chengbo Yang

    2015-03-01

    Full Text Available This article summarizes current experimental knowledge on the efficacy, possible mechanisms and feasibility in the application of phytogenic products as feed additives for food-producing animals. Phytogenic compounds comprise a wide range of plant-derived natural bioactive compounds and essential oils are a major group. Numerous studies have demonstrated that phytogenic compounds have a variety of functions, including antimicrobial/antiviral, antioxidative and anti-inflammation effects and improvement in the palatability of feed and gut development/health. However, the mechanisms underlying their functions are still largely unclear. In the past, there has been a lack of consistency in the results from both laboratory and field studies, largely due to the varied composition of products, dosages, purities and growing conditions of animals used. The minimal inhibitory concentration (MIC of phytogenic compounds required for controlling enteric pathogens may not guarantee the best feed intake, balanced immunity of animals and cost-effectiveness in animal production. The lipophilic nature of photogenic compounds also presents a challenge in effective delivery to the animal gut and this can partially be resolved by microencapsulation and combination with other compounds (synergistic effect. Interestingly, the effects of photogenic compounds on anti-inflammation, gut chemosensing and possible disruption of bacterial quorum sensing could explain a certain number of studies with different animal species for the better production performance of animals that have received phytogenic feed additives. It is obvious that phytogenic compounds have good potential as an alternative to antibiotics in feed for food animal production and the combination of different phytogenic compounds appears to be an approach to improve the efficacy and safety of phytogenic compounds in the application. It is our expectation that the recent development of high-throughput and

  3. Donation after circulatory death: current practices, ongoing challenges, and potential improvements.

    Science.gov (United States)

    Morrissey, Paul E; Monaco, Anthony P

    2014-02-15

    Organ donation after circulatory death (DCD) has been endorsed by the World Health Organization and is practiced worldwide. This overview examines current DCD practices, identifies problems and challenges, and suggests clinical strategies for possible improvement. Although there is uniform agreement on DCD donor candidacy (ventilator-dependent individuals with nonrecoverable or irreversible neurologic injury not meeting brain death criteria), there are variations in all aspects of DCD practice. Utilization of DCD organs is limited by hypoxia, hypotension, reduced--then absent--organ perfusion, and ischemia/reperfusion syndrome. Nevertheless, DCD kidneys exhibit comparable function and survival to donors with brain death kidneys, although they have higher rates of primary graft nonfunction, delayed graft function, discard, and retrieval associated injury. Concern over ischemic organ injury underscores the reluctance to recover extrarenal DCD organs since lack of medical therapy to support inadequate allograft function limits their acceptability. Nevertheless, limited results with DCD pancreas, liver, and lung allografts (but not heart) are now approaching that of donors with brain death organs. Pretransplant machine perfusion of DCD kidneys (vs. static storage) may reduce delayed graft function but has no effect on long-term organ function and survival. Normothermic regional perfusion used during DCD abdominal organ retrieval may reduce ischemic organ injury and increase the number of usable organs, although critical confirmative studies have yet to be done. Minor increases in usable DCD kidneys could accrue from increased use of pediatric DCD kidneys and from selective use of DCD/ECD kidneys, whereas a modest increase could result through utilization of donors declared dead beyond 1 hr from withdrawal of life support therapy. A significant increase in transplantable kidneys could be achieved by extension of the concept of living kidney donation in relation to

  4. Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

    Science.gov (United States)

    McKenna, Dennis J

    2004-05-01

    Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.

  5. Challenges and issues with building a potential railroad to Yucca Mountain

    Energy Technology Data Exchange (ETDEWEB)

    Sweeney, R.L.

    2004-07-01

    On July 23, 2002, the President of the United States signed into law a joint resolution of the United States Congress designating the Yucca Mountain site in Nye County, Nevada, for development as a geologic repository for the disposal of spent nuclear fuel and high-level radioactive waste. If the U.S. Nuclear Regulatory Commission authorizes construction of the repository and receipt and possession of spent nuclear fuel and high-level radioactive at Yucca Mountain, the U.S. Department of Energy (DOE) would be responsible for transporting these materials to the Yucca Mountain repository as part of its obligation under the Nuclear Waste Policy Act. Part of the site recommendation decision included the analysis of a nation-wide shipping campaign to the proposed repository site. The Final Environmental Impact Statement for a Geologic Repository for the Disposal of Spent Nuclear Fuel and High-Level Radioactive Waste at Yucca Mountain, Nye County, Nevada'' (February 2002) (Repository EIS) evaluated the potential impacts of the transportation of 70,000 Metric Tons of Heavy Metal spent nuclear fuel and high-level radioactive waste from 77 locations around the nation to the potential repository in Nevada over a 24 year shipping campaign. DOE believes that the Repository EIS provides the environmental impact information necessary to make certain broad transportation-related decisions, namely the choice of a national mode of transportation outside Nevada (mostly rail or mostly legal-weight truck), the choice among alternative transportation modes in Nevada (mostly rail, mostly legal-weight truck, or heavy-haul truck with use of an associated intermodal transfer station), and the choice among alternative rail corridors or heavy-haul truck routes with use of an associated intermodal transfer station in Nevada. In the Repository EIS, DOE identified mostly rail as its preferred mode of transportation, both nationally and in the State of Nevada. In December 2003, based

  6. IRETHERM: Research and Exploration Challenges in Assessing Ireland's Deep Low-Enthalpy Geothermal Energy Potential

    Science.gov (United States)

    Jones, A. G.; Muller, M. R.; Fullea, J.; Vozar, J.; Blake, S.; Delhaye, R.; Farrell, T.; Yeomans, C.; Loewer, M.; Reay, D.

    2012-12-01

    IRETHERM (www.iretherm.ie) is a new, academic-government-industry, collaborative research project, funded by Science Foundation Ireland, with the overarching objective of developing a holistic understanding of Ireland's low-enthalpy geothermal energy potential through integrated modelling of new and existing geophysical and geological data. A regional south-to-north trend in surface heat-flow is mapped across Ireland, ~40 to >80 mWm-2, but the source of the heat variation (whether crustal and/or lithospheric-mantle in origin) is unknown. With the exception of Permo-Triassic basins in Northern Ireland, hosting geothermal aquifers of promising but currently poorly-defined potential, rocks with high primary porosity have not been identified elsewhere. Whether any major Irish shear zones/faults might host a geothermal aquifer at depth is also unknown, although clusters of warm-springs in the vicinity of two major shear zones are promising. Our paper discusses the approaches and strategies that IRETHERM has adopted to meet the challenges of exploring for unknown deep geothermal resources (either hydrothermal aquifers or hot, dry rock) starting from a limited knowledge-base. IRETHERM's objectives over a four-year period are to: (i) Develop multi-parameter geophysical modelling and interpretation software tools that will enhance our ability to explore for and assess deep aquifers and granitic intrusions. (ii) Model and understand temperature variations in the upper-crust. Firstly, by building a 3-D model of crustal heat-production based on geochemical analysis of surface, borehole and mid- to lower-crustal xenolith samples. Secondly, by modelling, using a fully self-consistent 3-D approach, observed surface heat-flow variation as a function of variation in the structure and thermal properties of the crust and lithosphere, additionally constrained by surface elevation, geoid, gravity, seismic and magnetotelluric (MT) data. (iii) Test a strategic set of eight "type

  7. Proteomic and genomic analysis reveals novel Campylobacter jejuni outer membrane proteins and potential heterogeneity.

    Science.gov (United States)

    Watson, Eleanor; Sherry, Aileen; Inglis, Neil F; Lainson, Alex; Jyothi, Dushyanth; Yaga, Raja; Manson, Erin; Imrie, Lisa; Everest, Paul; Smith, David G E

    2014-09-01

    Gram-negative bacterial outer membrane proteins play important roles in the interaction of bacteria with their environment including nutrient acquisition, adhesion and invasion, and antibiotic resistance. In this study we identified 47 proteins within the Sarkosyl-insoluble fraction of Campylobacter jejuni 81-176, using LC-ESI-MS/MS. Comparative analysis of outer membrane protein sequences was visualised to reveal protein distribution within a panel of Campylobacter spp., identifying several C. jejuni-specific proteins. Smith-Waterman analyses of C. jejuni homologues revealed high sequence conservation amongst a number of hypothetical proteins, sequence heterogeneity of other proteins and several proteins which are absent in a proportion of strains.

  8. Gene co-expression networks and profiles reveal potential biomarkers of boar taint in pigs

    DEFF Research Database (Denmark)

    Drag, Markus; Skinkyté-Juskiené, Rúta; Do, Duy Ngoc

    Boar taint (BT) is an offensive odour or taste of porcine meat which may occur in entire male pigs due to skatole and androstenone accumulation. To avoid BT, castration of young piglets is performed but this strategy is under debate due to animal welfare concerns. The study aimed to reveal...... synthesis. In testis, >80 DE genes were functionally classified by the PANTHER tool to “Gonadotropin releasing hormone receptor” and “Wnt signaling” pathways which play a role in reproductive maturation and proliferation of spermatogonia, respectively. WGCNA was used to build co-expression modules...... and enrichment analysis and semantic filtering revealed the GO terms “catalytic activity” and “transferase activity” to be overrepresented (p hormones. Extraction of hub...

  9. Proteomic and genomic analysis reveals novel Campylobacter jejuni outer membrane proteins and potential heterogeneity

    Directory of Open Access Journals (Sweden)

    Eleanor Watson

    2014-09-01

    Full Text Available Gram-negative bacterial outer membrane proteins play important roles in the interaction of bacteria with their environment including nutrient acquisition, adhesion and invasion, and antibiotic resistance. In this study we identified 47 proteins within the Sarkosyl-insoluble fraction of Campylobacter jejuni 81-176, using LC–ESI-MS/MS. Comparative analysis of outer membrane protein sequences was visualised to reveal protein distribution within a panel of Campylobacter spp., identifying several C. jejuni-specific proteins. Smith–Waterman analyses of C. jejuni homologues revealed high sequence conservation amongst a number of hypothetical proteins, sequence heterogeneity of other proteins and several proteins which are absent in a proportion of strains.

  10. Metagenomic analysis reveals that modern microbialites and polar microbial mats have similar taxonomic and functional potential

    OpenAIRE

    White, Richard Allen; Power, Ian M.; Dipple, Gregory M.; Southam, Gordon; Suttle, Curtis A.

    2015-01-01

    Within the subarctic climate of Clinton Creek, Yukon, Canada, lies an abandoned and flooded open-pit asbestos mine that harbors rapidly growing microbialites. To understand their formation we completed a metagenomic community profile of the microbialites and their surrounding sediments. Assembled metagenomic data revealed that bacteria within the phylum Proteobacteria numerically dominated this system, although the relative abundances of taxa within the phylum varied among environments. Bacte...

  11. Metagenomic analysis reveals that modern microbialites and polar microbial mats have similar taxonomic and functional potential

    OpenAIRE

    III, Richard Allen White; Ian Malcolm Power; Dipple, Gregory M.; Gordon eSoutham; Suttle, Curtis A.

    2015-01-01

    Within the subarctic climate of Clinton Creek, Yukon, Canada, lies an abandoned and flooded open-pit asbestos mine that harbors rapidly growing microbialites. To understand their formation we completed a metagenomic community profile of the microbialites and their surrounding sediments. Assembled metagenomic data revealed that bacteria within the phylum Proteobacteria numerically dominated this system, although the relative abundances of taxa within the phylum varied among environments. Bact...

  12. Global metabolomics reveals potential urinary biomarkers of esophageal squamous cell carcinoma for diagnosis and staging

    Science.gov (United States)

    Xu, Jing; Chen, Yanhua; Zhang, Ruiping; He, Jiuming; Song, Yongmei; Wang, Jingbo; Wang, Huiqing; Wang, Luhua; Zhan, Qimin; Abliz, Zeper

    2016-10-01

    We performed a metabolomics study using liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis (MVDA) to discriminate global urine profiles in urine samples from esophageal squamous cell carcinoma (ESCC) patients and healthy controls (NC). Our work evaluated the feasibility of employing urine metabolomics for the diagnosis and staging of ESCC. The satisfactory classification between the healthy controls and ESCC patients was obtained using the MVDA model, and obvious classification of early-stage and advanced-stage patients was also observed. The results suggest that the combination of LC-MS analysis and MVDA may have potential applications for ESCC diagnosis and staging. We then conducted LC-MS/MS experiments to identify the potential biomarkers with large contributions to the discrimination. A total of 83 potential diagnostic biomarkers for ESCC were screened out, and 19 potential biomarkers were identified; the variations between the differences in staging using these potential biomarkers were further analyzed. These biomarkers may not be unique to ESCCs, but instead result from any malignant disease. To further elucidate the pathophysiology of ESCC, we studied related metabolic pathways and found that ESCC is associated with perturbations of fatty acid β-oxidation and the metabolism of amino acids, purines, and pyrimidines.

  13. Plasma metabolomics and proteomics profiling after a postprandial challenge reveal subtle diet effects on human metabolic status

    NARCIS (Netherlands)

    Pellis, L.; Erk, M.J. van; Ommen, B. van; Bakker, G.C.M.; Hendriks, H.F.J.; Cnubben, N.H.P.; Kleemann, R.; Someren, E.P. van; Bobeldijk, I.; Rubingh, C.M.; Wopereis, S.

    2012-01-01

    We introduce the metabolomics and proteomics based Postprandial Challenge Test (PCT) to quantify the postprandial response of multiple metabolic processes in humans in a standardized manner. The PCT comprised consumption of a standardized 500 ml dairy shake containing respectively 59, 30 and 12 ener

  14. Genome mining reveals unlocked bioactive potential of marine Gram-negative bacteria

    DEFF Research Database (Denmark)

    Machado, Henrique; Sonnenschein, Eva; Melchiorsen, Jette;

    2015-01-01

    of bioactive compounds leading to successful applications in pharmaceutical and biotech industries. Marine bacteria have so far not been exploited to the same extent; however, they are believed to harbor a multitude of novel bioactive chemistry. To explore this potential, genomes of 21 marine Alpha......- and Gammaproteobacteria collected during the Galathea 3 expedition were sequenced and mined for natural product encoding gene clusters. Results: Independently of genome size, bacteria of all tested genera carried a large number of clusters encoding different potential bioactivities, especially within the Vibrionaceae...... and Pseudoalteromonadaceae families. A very high potential was identified in pigmented pseudoalteromonads with up to 20 clusters in a single strain, mostly NRPSs and NRPS-PKS hybrids. Furthermore, regulatory elements in bioactivity-related pathways including chitin metabolism, quorum sensing and iron scavenging systems were...

  15. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery

    DEFF Research Database (Denmark)

    Poulsen, Michael; Oh, Dong-Chan; Clardy, Jon;

    2011-01-01

    Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social...... of these isolates identified 11 distinct and structurally diverse secondary metabolites, including a novel polyunsaturated and polyoxygenated macrocyclic lactam, which we name sceliphrolactam. By pairing the 15 Streptomyces strains against a collection of fungi and bacteria, we document their antifungal...... and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding...

  16. Potential human pathogenic bacteria in a mixed urban watershed as revealed by pyrosequencing

    Science.gov (United States)

    Current microbial source tracking (MST) methods for water depend on testing for fecal indicator bacterial counts or specific marker gene sequences to identify fecal contamination where potential human pathogenic bacteria could be present. In this study, we applied 454 high-throughput pyrosequencing ...

  17. Perceptual Shift in Bilingualism: Brain Potentials Reveal Plasticity in Pre-Attentive Colour Perception

    Science.gov (United States)

    Athanasopoulos, Panos; Dering, Benjamin; Wiggett, Alison; Kuipers, Jan-Rouke; Thierry, Guillaume

    2010-01-01

    The validity of the linguistic relativity principle continues to stimulate vigorous debate and research. The debate has recently shifted from the behavioural investigation arena to a more biologically grounded field, in which tangible physiological evidence for language effects on perception can be obtained. Using brain potentials in a colour…

  18. Atypical Brain Responses to Reward Cues in Autism as Revealed by Event-Related Potentials

    Science.gov (United States)

    Kohls, Gregor; Peltzer, Judith; Schulte-Ruther, Martin; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2011-01-01

    Social motivation deficit theories suggest that children with autism do not properly anticipate and appreciate the pleasure of social stimuli. In this study, we investigated event-related brain potentials evoked by cues that triggered social versus monetary reward anticipation in children with autism. Children with autism showed attenuated P3…

  19. An integrative systems genetics approach reveals potential causal genes and pathways related to obesity

    NARCIS (Netherlands)

    Kogelman, Lisette J. A.; Zhernakova, Daria V.; Westra, Harm-Jan; Cirera, Susanna; Fredholm, Merete; Franke, Lude; Kadarmideen, Haja N.

    2015-01-01

    Background: Obesity is a multi-factorial health problem in which genetic factors play an important role. Limited results have been obtained in single-gene studies using either genomic or transcriptomic data. RNA sequencing technology has shown its potential in gaining accurate knowledge about the tr

  20. Whole Genome Sequencing Reveals Potential New Targets for Improving Nitrogen Uptake and Utilization in Sorghum bicolor

    Science.gov (United States)

    Massel, Karen; Campbell, Bradley C.; Mace, Emma S.; Tai, Shuaishuai; Tao, Yongfu; Worland, Belinda G.; Jordan, David R.; Botella, Jose R.; Godwin, Ian D.

    2016-01-01

    Nitrogen (N) fertilizers are a major agricultural input where more than 100 million tons are supplied annually. Cereals are particularly inefficient at soil N uptake, where the unrecovered nitrogen causes serious environmental damage. Sorghum bicolor (sorghum) is an important cereal crop, particularly in resource-poor semi-arid regions, and is known to have a high NUE in comparison to other major cereals under limited N conditions. This study provides the first assessment of genetic diversity and signatures of selection across 230 fully sequenced genes putatively involved in the uptake and utilization of N from a diverse panel of sorghum lines. This comprehensive analysis reveals an overall reduction in diversity as a result of domestication and a total of 128 genes displaying signatures of purifying selection, thereby revealing possible gene targets to improve NUE in sorghum and cereals alike. A number of key genes appear to have been involved in selective sweeps, reducing their sequence diversity. The ammonium transporter (AMT) genes generally had low allelic diversity, whereas a substantial number of nitrate/peptide transporter 1 (NRT1/PTR) genes had higher nucleotide diversity in domesticated germplasm. Interestingly, members of the distinct race Guinea margaritiferum contained a number of unique alleles, and along with the wild sorghum species, represent a rich resource of new variation for plant improvement of NUE in sorghum. PMID:27826302

  1. Whole Genome Sequencing Reveals Potential New Targets for Improving Nitrogen Uptake and Utilization in Sorghum bicolor

    Directory of Open Access Journals (Sweden)

    Karen Massel

    2016-10-01

    Full Text Available Nitrogen (N fertilizers are a major agricultural input where more than 100 million tons are supplied annually. Cereals are particularly inefficient at soil N uptake, where the unrecovered nitrogen causes serious environmental damage. Sorghum bicolor (sorghum is an important cereal crop, particularly in resource-poor semi-arid regions, and is known to have a high NUE in comparison to other major cereals under limited N conditions. This study provides the first assessment of genetic diversity and signatures of selection across 230 fully sequenced genes putatively involved in the uptake and mobilization of N from a diverse panel of sorghum lines. This comprehensive analysis reveals an overall reduction in diversity as a result of domestication and a total of 128 genes displaying signatures of purifying selection, thereby revealing possible gene targets to improve NUE in sorghum and cereals alike. A number of key genes appear to have been involved in selective sweeps, reducing their sequence diversity. The ammonium transporter (AMT genes generally had low allelic diversity, whereas a substantial number of nitrate/peptide transporter 1 (NRT1/PTR genes had higher nucleotide diversity in domesticated germplasm. Interestingly, members of the distinct race Guinea margaritiferum contained a number of unique alleles, and along with the wild sorghum species, represent a rich resource of new variation for plant improvement of NUE in sorghum.

  2. An integrative genomic and transcriptomic analysis reveals potential targets associated with cell proliferation in uterine leiomyomas

    DEFF Research Database (Denmark)

    Cirilo, Priscila Daniele Ramos; Marchi, Fábio Albuquerque; Barros Filho, Mateus de Camargo;

    2013-01-01

    proliferation, including FGFR1 and IGFBP5. Transcriptional and protein analyses showed that FGFR1 (P = 0.006 and P... and transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs....

  3. Gene expression profiling of craniofacial fibrous dysplasia reveals ADAMTS2 overexpression as a potential marker

    OpenAIRE

    Zhou, Shang-Hui; Yang, Wen-Jun; Liu, Sheng-Wen; Li, Jiang; Zhang, Chun-Ye; Zhu, Yun; Zhang, Chen-Ping

    2014-01-01

    Fibrous dysplasia (FD) as an abnormal bone growth is one of the common fibro-osseous leasions (FOL) in oral and maxillofacial region, however, its etiology still remains unclear. Here, we performed gene expression profiling of FD using microarray analysis to explore the key molecule events in FD development, and develop potential diagnostic markers or therapeutic targets for FD. We found that 1,881 genes exhibited differential expression with more than two-fold changes in FD compared to norma...

  4. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery

    DEFF Research Database (Denmark)

    Poulsen, Michael; Oh, Dong-Chan; Clardy, Jon;

    2011-01-01

    Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social...... phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest....

  5. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery.

    Directory of Open Access Journals (Sweden)

    Michael Poulsen

    Full Text Available Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15 of these isolates identified 11 distinct and structurally diverse secondary metabolites, including a novel polyunsaturated and polyoxygenated macrocyclic lactam, which we name sceliphrolactam. By pairing the 15 Streptomyces strains against a collection of fungi and bacteria, we document their antifungal and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest.

  6. Set potential regulation reveals additional oxidation peaks of Geobacter sulfurreducens anodic biofilms

    KAUST Repository

    Zhu, Xiuping

    2012-08-01

    Higher current densities produced in microbial fuel cells and other bioelectrochemical systems are associated with the presence of various Geobacter species. A number of electron transfer components are involved in extracellular electron transfer by the model exoelectrogen, Geobacter sulfurreducens. It has previously been shown that 5 main oxidation peaks can be identified in cyclic voltammetry scans. It is shown here that 7 separate oxidation peaks emerged over relatively long periods of time when a larger range of set potentials was used to acclimate electroactive biofilms. The potentials of oxidation peaks obtained with G. sulfurreducens biofilms acclimated at 0.60 V (vs. Ag/AgCl) were different from those that developed at - 0.46 V, and both of their peaks were different from those obtained for biofilms incubated at - 0.30 V, 0 V, and 0.30 V. These results expand the known range of potentials for which G. sulfurreducens produces identifiable oxidation peaks that could be important for extracellular electron transfer. © 2012 Elsevier B.V.

  7. Comprehensive molecular pathology analysis of small bowel adenocarcinoma reveals novel targets with potential for clinical utility.

    Science.gov (United States)

    Alvi, Muhammad A; McArt, Darragh G; Kelly, Paul; Fuchs, Marc-Aurel; Alderdice, Matthew; McCabe, Clare M; Bingham, Victoria; McGready, Claire; Tripathi, Shailesh; Emmert-Streib, Frank; Loughrey, Maurice B; McQuaid, Stephen; Maxwell, Perry; Hamilton, Peter W; Turkington, Richard; James, Jacqueline A; Wilson, Richard H; Salto-Tellez, Manuel

    2015-08-28

    Small bowel accounts for only 0.5% of cancer cases in the US but incidence rates have been rising at 2.4% per year over the past decade. One-third of these are adenocarcinomas but little is known about their molecular pathology and no molecular markers are available for clinical use. Using a retrospective 28 patient matched normal-tumor cohort, next-generation sequencing, gene expression arrays and CpG methylation arrays were used for molecular profiling. Next-generation sequencing identified novel mutations in IDH1, CDH1, KIT, FGFR2, FLT3, NPM1, PTEN, MET, AKT1, RET, NOTCH1 and ERBB4. Array data revealed 17% of CpGs and 5% of RNA transcripts assayed to be differentially methylated and expressed respectively (p clinically exploitable markers.

  8. Membrane bioreactor wastewater treatment plants reveal diverse yeast and protist communities of potential significance in biofouling.

    Science.gov (United States)

    Liébana, Raquel; Arregui, Lucía; Belda, Ignacio; Gamella, Luis; Santos, Antonio; Marquina, Domingo; Serrano, Susana

    2015-01-01

    The yeast community was studied in a municipal full-scale membrane bioreactor wastewater treatment plant (MBR-WWTP). The unexpectedly high diversity of yeasts indicated that the activated sludge formed a suitable environment for them to proliferate, with cellular concentrations of 2.2 ± 0.8 × 10(3) CFU ml(-1). Sixteen species of seven genera were present in the biological reactor, with Ascomycetes being the most prevalent group (93%). Most isolates were able to grow in a synthetic wastewater medium, adhere to polyethylene surfaces, and develop biofilms of variable complexity. The relationship between yeast populations and the protists in the MBR-WWTP was also studied, revealing that some protist species preyed on and ingested yeasts. These results suggest that yeast populations may play a role in the food web of a WWTP and, to some extent, contribute to membrane biofouling in MBR systems.

  9. Challenges in the Use of Social Networking Sites to Trace Potential Research Participants

    Science.gov (United States)

    Marsh, Jackie; Bishop, Julia C.

    2014-01-01

    This paper reports on a number of challenges faced in tracing contributors to research projects that were originally conducted many decades previously. The need to trace contributors in this way arises in projects which focus on involving research participants in previous studies who have not been maintained on a database, or with whom the…

  10. Outreach to internally displaced persons in Bogotá, Colombia: challenges and potential solutions.

    Science.gov (United States)

    Shultz, James M; García, Natalia Muñoz; Ceballos, Ángela Milena Gómez; Florez, Luis Jorge Hernandez; Araya, Ricardo; Verdeli, Helen; Espinel, Zelde; Bolivar, Sandra Patricia Cipagauta; Neria, Yuval

    2014-01-01

    Programs that provide services for internally displaced persons (IDPs) in Colombia, South America face challenges when attempting to engage and enroll the target population of forced migrants they intend to serve. Innovative multi-strategy outreach approaches must be used in order to effectively seek, recruit, provide services, monitor, and retain IDPs.

  11. Openings for Researching Environment and Place in Children's Literature: Ecologies, Potentials, Realities and Challenges

    Science.gov (United States)

    Reid, Alan; Payne, Phillip G.; Cutter-Mackenzie, Amy

    2010-01-01

    This not quite "final" ending of this special issue of "Environmental Education Research" traces a series of hopeful, if somewhat difficult and at times challenging, openings for researching experiences of environment and place through children's literature. In the first instance, we draw inspiration from the contributors who…

  12. Eco-Efficiency Assessments as a Tool for Revealing the Environmental Improvement Potential of New Regulations

    Directory of Open Access Journals (Sweden)

    Ottar Michelsen

    2010-01-01

    Full Text Available Public regulations can result in improved environmental performance of products. In this paper eco-efficiency is used to assess the most likely outcome of potential new regulations. The paper presents a case study of furniture production in Norway where different scenarios for improving the environmental performance of the products are presented. Four regulatory options for imposing environmental improvements are assessed; (1 an introduction of a tax on emissions, (2 an increase of the tax on landfills, (3 an introduction of a tax on raw material consumption, and (4 introduction of take-back legislation.

  13. Exosome proteomics reveals transcriptional regulator proteins with potential to mediate downstream pathways.

    Science.gov (United States)

    Ung, Timothy H; Madsen, Helen J; Hellwinkel, Justin E; Lencioni, Alex M; Graner, Michael W

    2014-11-01

    Exosomes are virus-sized, membrane-enclosed vesicles with origins in the cellular endosomal system, but are released extracellularly. As a population, these tiny vesicles carry relatively enormous amounts of information in their protein, lipid and nucleic acid content, and the vesicles can have profound impacts on recipient cells. This review employs publically-available data combined with gene ontology applications to propose a novel concept, that exosomes transport transcriptional and translational machinery that may have direct impacts on gene expression in recipient cells. Here, we examine the previously published proteomic contents of medulloblastoma-derived exosomes, focusing on transcriptional regulators; we found that there are numerous proteins that may have potential roles in transcriptional and translational regulation with putative influence on downstream, cancer-related pathways. We expanded this search to all of the proteins in the Vesiclepedia database; using gene ontology approaches, we see that these regulatory factors are implicated in many of the processes involved in cancer initiation and progression. This information suggests that some of the effects of exosomes on recipient cells may be due to the delivery of protein factors that can directly and fundamentally change the transcriptional landscape of the cells. Within a tumor environment, this has potential to tilt the advantage towards the cancer.

  14. A five-year survey of dematiaceous fungi in a tropical hospital reveals potential opportunistic species.

    Directory of Open Access Journals (Sweden)

    Su Mei Yew

    Full Text Available Dematiaceous fungi (black fungi are a heterogeneous group of fungi present in diverse environments worldwide. Many species in this group are known to cause allergic reactions and potentially fatal diseases in humans and animals, especially in tropical and subtropical climates. This study represents the first survey of dematiaceous fungi in Malaysia and provides observations on their diversity as well as in vitro response to antifungal drugs. Seventy-five strains isolated from various clinical specimens were identified by morphology as well as an internal transcribed spacer (ITS-based phylogenetic analysis. The combined molecular and conventional approach enabled the identification of three classes of the Ascomycota phylum and 16 genera, the most common being Cladosporium, Cochliobolus and Neoscytalidium. Several of the species identified have not been associated before with human infections. Among 8 antifungal agents tested, the azoles posaconazole (96%, voriconazole (90.7%, ketoconazole (86.7% and itraconazole (85.3% showed in vitro activity (MIC ≤ 1 µg/mL to the largest number of strains, followed by anidulafungin (89.3%, caspofungin (74.7% and amphotericin B (70.7%. Fluconazole appeared to be the least effective with only 10.7% of isolates showing in vitro susceptibility. Overall, almost half (45.3% of the isolates showed reduced susceptibility (MIC >1 µg/mL to at least one antifungal agent, and three strains (one Pyrenochaeta unguis-hominis and two Nigrospora oryzae showed potential multidrug resistance.

  15. Fast calcium and voltage-sensitive dye imaging in enteric neurones reveal calcium peaks associated with single action potential discharge.

    Science.gov (United States)

    Michel, K; Michaelis, M; Mazzuoli, G; Mueller, K; Vanden Berghe, P; Schemann, M

    2011-12-15

    Slow changes in [Ca(2+)](i) reflect increased neuronal activity. Our study demonstrates that single-trial fast [Ca(2+)](i) imaging (≥200 Hz sampling rate) revealed peaks each of which are associated with single spike discharge recorded by consecutive voltage-sensitive dye (VSD) imaging in enteric neurones and nerve fibres. Fast [Ca(2+)](i) imaging also revealed subthreshold fast excitatory postsynaptic potentials. Nicotine-evoked [Ca(2+)](i) peaks were reduced by -conotoxin and blocked by ruthenium red or tetrodotoxin. Fast [Ca(2+)](i) imaging can be used to directly record single action potentials in enteric neurones. [Ca(2+)](i) peaks required opening of voltage-gated sodium and calcium channels as well as Ca(2+) release from intracellular stores.

  16. Potential microRNA-mediated oncogenic intercellular communication revealed by pan-cancer analysis

    Science.gov (United States)

    Li, Yue; Zhang, Zhaolei

    2014-11-01

    Carcinogenesis consists of oncogenesis and metastasis, and intriguingly microRNAs (miRNAs) are involved in both processes. Although aberrant miRNA activities are prevalent in diverse tumor types, the exact mechanisms for how they regulate cancerous processes are not always clear. To this end, we performed a large-scale pan-cancer analysis via a novel probabilistic approach to infer recurrent miRNA-target interactions implicated in 12 cancer types using data from The Cancer Genome Atlas. We discovered ~20,000 recurrent miRNA regulations, which are enriched for cancer-related miRNAs/genes. Notably, miRNA 200 family (miR-200/141/429) is among the most prominent miRNA regulators, which is known to be involved in metastasis. Importantly, the recurrent miRNA regulatory network is not only enriched for cancer pathways but also for extracellular matrix (ECM) organization and ECM-receptor interactions. The results suggest an intriguing cancer mechanism involving miRNA-mediated cell-to-cell communication, which possibly involves delivery of tumorigenic miRNA messengers to adjacent cells via exosomes. Finally, survival analysis revealed 414 recurrent-prognostic associations, where both gene and miRNA involved in each interaction conferred significant prognostic power in one or more cancer types. Together, our comprehensive pan-cancer analysis provided not only biological insights into metastasis but also brought to bear the clinical relevance of the proposed recurrent miRNA-gene associations.

  17. Designing an Index to Reveal the Potential of Multipurpose Landscapes in Southern Africa

    Directory of Open Access Journals (Sweden)

    Emmanuel Torquebiau

    2013-12-01

    Full Text Available Multipurpose mosaic (“ecoagriculture” landscapes can serve the purpose of land sharing to combine objectives of agricultural production and biodiversity conservation. Rewarding the people who shape and maintain those landscapes could act as a mechanism to generate added-value representing an indirect payment for ecosystem services. We investigated the feasibility of such an approach in two areas in Southern Africa differing in spatial configurations, history and socio-economic context. We designed and tested a composite index describing the state of each landscape in terms of ecoagriculture criteria (conservation, production, institutions and livelihood and ecosystem services (provisioning, regulating and cultural services. The resulting index is made up of different sets of data each comprising 40 scores, obtained from stakeholders’ participatory interviews. Ecosystem services are in general assigned more importance than ecoagriculture criteria. In both cases, cultural services receive the highest scores, whereas the lowest ones are attributed to the livelihood and institutions in the Zimbabwean and South African sites, respectively. Index values reveal that the South African site, where there is more integration between land-use units, does better in terms of a landscape performing multiple functions. Provided relevant stakeholders are involved and a certification mechanism is developed, the landscape labelling index can be used to recognize and reward the value of outstanding rural landscapes.

  18. Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism.

    Directory of Open Access Journals (Sweden)

    Barbara Witek

    Full Text Available Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis.

  19. Geological features of the northeastern Canadian Arctic margin revealed from analysis of potential field data

    Science.gov (United States)

    Anudu, Goodluck K.; Stephenson, Randell A.; Macdonald, David I. M.; Oakey, Gordon N.

    2016-11-01

    The northeastern Canadian Arctic margin is bordered to the north by Alpha Ridge, a dominantly magmatic complex within the Amerasia Basin of the Arctic Ocean, which forms part of the High Arctic Large Igneous Province (HALIP). The characteristics of the gravity and magnetic anomaly fields change notably along the Arctic margin, with two main segments recognised. Aeromagnetic and gravity data in the transition zone between these contrasting domains of the Canadian Arctic margin are analysed here in detail. Results obtained using a variety of edge enhancement (derivative) methods highlight several magnetic domains and a major offshore sedimentary basin as well as some known and a number of previously unknown tectonic and magmatic elements. A magmatic intrusion distribution map derived from the edge enhanced magnetic anomaly maps reveals that magmatic rocks are much more widespread in the relatively shallow subsurface than implied by surface geological mapping. Magmatic intrusions (mainly dykes) and other geological structures have NW-SE, NE-SW and N-S major trends. Broad gravity and pseudogravity lows across most of the Sverdrup Basin region are due to thick, less dense sedimentary succession and low magnetised crust. Magnetic and pseudogravity highs observed over Alpha Ridge indicate high crustal magnetisation associated with the occurrence of extensive and voluminous crustal magmatic bodies. Absence of these volcanic and intrusive rocks in the imaged sedimentary basin beneath the northeast Canadian Arctic margin region suggests that the basin probably formed after the cessation of HALIP magmatism.

  20. Event related potentials reveal differences between morphological (prefixes) and phonological (syllables) processing of words.

    Science.gov (United States)

    Domínguez, Alberto; Alija, Maira; Cuetos, Fernando; de Vega, Mauel

    2006-11-06

    Behavioral measures in visual priming tasks show opposite effects for syllables and morphemes, which indicate that they are processed by two independent systems. We used event related potentials (ERPs) to explore two priming situations in Spanish: prefix related words (reacción-REFORMA [reaction-reform]), in which prime and target words shared a first syllable that was also a prefix, and syllable related words (regalo-REFORMA [gift-reform.]), in which the shared first syllable was a pseudoprefix in the prime word. Prefix related pairs, unlike syllable related pairs, evoked a very early positivity in reaction to the target (at 150-250ms window), suggesting that the prefix information is immediately available, at a prelexical stage. By contrast, syllable related pairs showed a larger N400 effect. This late negativity may be caused by lateral inhibition among lexical candidates activated in the lexicon by the prime's first syllable.

  1. An integrative systems genetics approach reveals potential causal genes and pathways related to obesity

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Zhernakova, Daria V.; Westra, Harm-Jan;

    2015-01-01

    expression analysis was performed using the Obesity Index as a continuous variable in a linear model. eQTL mapping was then performed to integrate 60 K porcine SNP chip data with the RNA sequencing data. Results were restricted based on genome-wide significant single nucleotide polymorphisms, detected...... polymorphisms to detect obesity-related genes and pathways. Building a co-expression network using eQTLs resulted in the detection of a module strongly associated with lipid pathways. Furthermore, we detected several obesity candidate genes, for example, ENPP1, CTSL, and ABHD12B. CONCLUSIONS: To our knowledge......BACKGROUND: Obesity is a multi-factorial health problem in which genetic factors play an important role. Limited results have been obtained in single-gene studies using either genomic or transcriptomic data. RNA sequencing technology has shown its potential in gaining accurate knowledge about...

  2. Event-related potentials reveal increased distraction by salient global objects in older adults

    DEFF Research Database (Denmark)

    Wiegand, Iris; Finke, Kathrin; Töllner, Thomas;

    a processing advantage for salient whole-object representations relative to configurations of local elements not inducing a global form. We investigated event-related potential (ERP) correlates of age-related decline in visual abilities, and specifically, distractibility by salient global objects in visual...... search. Older participants detected target stimuli slower and less accurate than younger participants did. ERPs indicated that the general performance decline originated at multiple stages within the information-processing stream, from sensory coding to spatial allocation of attention: The P1...... in global-local asymmetries originates from early processing stages, where the dissociation of hierarchical levels is less distinct, and inhibition of the salient irrelevant global object information is less effective...

  3. Combining genomic sequencing methods to explore viral diversity and reveal potential virus-host interactions

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    Cheryl-Emiliane Tien Chow

    2015-04-01

    Full Text Available Viral diversity and virus-host interactions in oxygen-starved regions of the ocean, also known as oxygen minimum zones (OMZs, remain relatively unexplored. Microbial community metabolism in OMZs alters nutrient and energy flow through marine food webs, resulting in biological nitrogen loss and greenhouse gas production. Thus, viruses infecting OMZ microbes have the potential to modulate community metabolism with resulting feedback on ecosystem function. Here, we describe viral communities inhabiting oxic surface (10m and oxygen-starved basin (200m waters of Saanich Inlet, a seasonally anoxic fjord on the coast of Vancouver Island, British Columbia using viral metagenomics and complete viral fosmid sequencing on samples collected between April 2007 and April 2010. Of 6459 open reading frames (ORFs predicted across all 34 viral fosmids, 77.6% (n=5010 had no homology to reference viral genomes. These fosmids recruited a higher proportion of viral metagenomic sequences from Saanich Inlet than from nearby northeastern subarctic Pacific Ocean (Line P waters, indicating differences in the viral communities between coastal and open ocean locations. While functional annotations of fosmid ORFs were limited, recruitment to NCBI’s non-redundant ‘nr’ database and publicly available single-cell genomes identified putative viruses infecting marine thaumarchaeal and SUP05 proteobacteria to provide potential host linkages with relevance to coupled biogeochemical cycling processes in OMZ waters. Taken together, these results highlight the power of coupled analyses of multiple sequence data types, such as viral metagenomic and fosmid sequence data with prokaryotic single cell genomes, to chart viral diversity, elucidate genomic and ecological contexts for previously unclassifiable viral sequences, and identify novel host interactions in natural and engineered ecosystems.

  4. Genetic and genomic dissection of Prolactin revealed potential association with milk production traits in riverine buffalo.

    Science.gov (United States)

    Nadeem, A; Maryam, J

    2016-08-01

    Milk yield and quality has been a major selection criterion for genetic improvement in livestock species. Role of Prolactin gene in determining milk quality in terms of protein profile, lactose, lipids and other imperative macromolecules is very important. In this context, genetic profiling of Prolactin gene in riverine buffalo of Pakistan was performed and potential genetic markers were identified illustrating worth of this gene in marker-assisted selection of superior dairy buffaloes. Series of wet and dry lab experimentation was performed starting with genomic DNA isolation from true to breed representatives of indigenous river buffalo (Nili-Ravi). After amplification of coding regions of Prolactin gene, products were eluted and sequenced by Sanger's chain termination method and aligned to get variations in genomic region. A total of 15 novel variations were identified and analyzed statistically for their significance at population level, haplotypes were constructed, and association was estimated. Phylogenetic analysis was performed to evaluate the rate of evolution for Prolactin gene in various mammalian species. Lastly, biological networking for this molecule was predicted to get the bigger pictorial of its functional machinery. Pathway analysis was performed to find its physiological mode of action in milk synthesis. This is a first report toward complete genetic screening of Prolactin gene in Pakistani buffaloes. Results of this study not only provide an insight for potential role of Prolactin gene in milk-producing abilities of buffalo but also suggest new directions for exploration of more genes that may have promising role to enhance future milk production capabilities of river buffalo breeds of Asian region through marker-assisted selection.

  5. Revealing the biotechnological potential of Delftia sp. JD2 by a genomic approach

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    María A. Morel

    2016-04-01

    Full Text Available Delftia sp. JD2 is a chromium-resistant bacterium that reduces Cr(VI to Cr(III, accumulates Pb(II, produces the phytohormone indole-3-acetic acid and siderophores, and increases the plant growth performance of rhizobia in co-inoculation experiments. We aimed to analyze the biotechnological potential of JD2 using a genomic approach. JD2 has a genome of 6.76Mb, with 6,051 predicted protein coding sequences and 93 RNA genes (tRNA and rRNA. The indole-acetamide pathway was identified as responsible for the synthesis of indole-3-acetic acid. The genetic information involved in chromium resistance (the gene cluster, chrBACF, was found. At least 40 putative genes encoding for TonB-dependent receptors, probably involved in the utilization of siderophores and biopolymers, and genes for the synthesis, maturation, exportation and uptake of pyoverdine, and acquisition of Fe-pyochelin and Fe-enterobactin were also identified. The information also suggests that JD2 produce polyhydroxybutyrate, a carbon reserve polymer commonly used for manufacturing petrochemical free bioplastics. In addition, JD2 may degrade lignin-derived aromatic compounds to 2-pyrone-4,6-dicarboxylate, a molecule used in the bio-based polymer industry. Finally, a comparative genomic analysis of JD2, Delftia sp. Cs1-4 and Delftia acidovorans SPH-1 is also discussed. The present work provides insights into the physiology and genetics of a microorganism with many potential uses in biotechnology.

  6. Current Challenges and Potential Opportunities for the Pharmaceutical Sciences to Make Global Impact: An FIP Perspective.

    Science.gov (United States)

    Tucker, Geoffrey; DeSilva, Binodh; Dressman, Jennifer; Ito, Michiho; Kumamoto, Takuya; Mager, Don; Mahler, Hanns-Christian; Maitland-van der Zee, Anke H; Pauletti, Giovanni M; Sasaki, Hitoshi; Shah, Vinod; Tang, Daniel; Ward, Michael

    2016-09-01

    The chairs of each of the 8 Special Interest Groups of the Board of Pharmaceutical Sciences of the International Pharmaceutical Federation have compiled opinions with regard to major challenges for the pharmaceutical sciences over the next 5-10 years. Areas covered are drug design and discovery, natural products, formulation design and pharmaceutical technology, pharmacokinetics/pharmacodynamics and systems pharmacology, translational and personalized medicine, biotechnology, analytical sciences and quality control, and regulatory science.

  7. Heterologous expression of the filarial nematode alt gene products reveals their potential to inhibit immune function

    Directory of Open Access Journals (Sweden)

    Aebischer Toni

    2005-03-01

    Full Text Available Abstract Background Parasites exploit sophisticated strategies to evade host immunity that require both adaptation of existing genes and evolution of new gene families. We have addressed this question by testing the immunological function of novel genes from helminth parasites, in which conventional transgenesis is not yet possible. We investigated two such novel genes from Brugia malayi termed abundant larval transcript (alt, expression of which reaches ~5% of total transcript at the time parasites enter the human host. Results To test the hypothesis that ALT proteins modulate host immunity, we adopted an alternative transfection strategy to express these products in the protozoan parasite Leishmania mexicana. We then followed the course of infection in vitro in macrophages and in vivo in mice. Expression of ALT proteins, but not a truncated mutant, conferred greater infectivity of macrophages in vitro, reaching 3-fold higher parasite densities. alt-transfected parasites also caused accelerated disease in vivo, and fewer mice were able to clear infection of organisms expressing ALT. alt-transfected parasites were more resistant to IFN-γ-induced killing by macrophages. Expression profiling of macrophages infected with transgenic L. mexicana revealed consistently higher levels of GATA-3 and SOCS-1 transcripts, both associated with the Th2-type response observed in in vivo filarial infection. Conclusion Leishmania transfection is a tractable and informative approach to determining immunological functions of single genes from heterologous organisms. In the case of the filarial ALT proteins, our data suggest that they may participate in the Th2 bias observed in the response to parasite infection by modulating cytokine-induced signalling within immune system cells.

  8. Genome Analysis of Two Pseudonocardia Phylotypes Associated with Acromyrmex Leafcutter Ants Reveals Their Biosynthetic Potential.

    Science.gov (United States)

    Holmes, Neil A; Innocent, Tabitha M; Heine, Daniel; Bassam, Mahmoud Al; Worsley, Sarah F; Trottmann, Felix; Patrick, Elaine H; Yu, Douglas W; Murrell, J C; Schiøtt, Morten; Wilkinson, Barrie; Boomsma, Jacobus J; Hutchings, Matthew I

    2016-01-01

    The attine ants of South and Central America are ancient farmers, having evolved a symbiosis with a fungal food crop >50 million years ago. The most evolutionarily derived attines are the Atta and Acromyrmex leafcutter ants, which harvest fresh leaves to feed their fungus. Acromyrmex and many other attines vertically transmit a mutualistic strain of Pseudonocardia and use antifungal compounds made by these bacteria to protect their fungal partner against co-evolved fungal pathogens of the genus Escovopsis. Pseudonocardia mutualists associated with the attines Apterostigma dentigerum and Trachymyrmex cornetzi make novel cyclic depsipeptide compounds called gerumycins, while a mutualist strain isolated from derived Acromyrmex octospinosus makes an unusual polyene antifungal called nystatin P1. The novelty of these antimicrobials suggests there is merit in exploring secondary metabolites of Pseudonocardia on a genome-wide scale. Here, we report a genomic analysis of the Pseudonocardia phylotypes Ps1 and Ps2 that are consistently associated with Acromyrmex ants collected in Gamboa, Panama. These were previously distinguished solely on the basis of 16S rRNA gene sequencing but genome sequencing of five Ps1 and five Ps2 strains revealed that the phylotypes are distinct species and each encodes between 11 and 15 secondary metabolite biosynthetic gene clusters (BGCs). There are signature BGCs for Ps1 and Ps2 strains and some that are conserved in both. Ps1 strains all contain BGCs encoding nystatin P1-like antifungals, while the Ps2 strains encode novel nystatin-like molecules. Strains show variations in the arrangement of these BGCs that resemble those seen in gerumycin gene clusters. Genome analyses and invasion assays support our hypothesis that vertically transmitted Ps1 and Ps2 strains have antibacterial activity that could help shape the cuticular microbiome. Thus, our work defines the Pseudonocardia species associated with Acromyrmex ants and supports the hypothesis

  9. Systematically Altering Bacterial SOS Activity under Stress Reveals Therapeutic Strategies for Potentiating Antibiotics.

    Science.gov (United States)

    Mo, Charlie Y; Manning, Sara A; Roggiani, Manuela; Culyba, Matthew J; Samuels, Amanda N; Sniegowski, Paul D; Goulian, Mark; Kohli, Rahul M

    2016-01-01

    The bacterial SOS response is a DNA damage repair network that is strongly implicated in both survival and acquired drug resistance under antimicrobial stress. The two SOS regulators, LexA and RecA, have therefore emerged as potential targets for adjuvant therapies aimed at combating resistance, although many open questions remain. For example, it is not well understood whether SOS hyperactivation is a viable therapeutic approach or whether LexA or RecA is a better target. Furthermore, it is important to determine which antimicrobials could serve as the best treatment partners with SOS-targeting adjuvants. Here we derived Escherichia coli strains that have mutations in either lexA or recA genes in order to cover the full spectrum of possible SOS activity levels. We then systematically analyzed a wide range of antimicrobials by comparing the mean inhibitory concentrations (MICs) and induced mutation rates for each drug-strain combination. We first show that significant changes in MICs are largely confined to DNA-damaging antibiotics, with strains containing a constitutively repressed SOS response impacted to a greater extent than hyperactivated strains. Second, antibiotic-induced mutation rates were suppressed when SOS activity was reduced, and this trend was observed across a wider spectrum of antibiotics. Finally, perturbing either LexA or RecA proved to be equally viable strategies for targeting the SOS response. Our work provides support for multiple adjuvant strategies, while also suggesting that the combination of an SOS inhibitor with a DNA-damaging antibiotic could offer the best potential for lowering MICs and decreasing acquired drug resistance. IMPORTANCE Our antibiotic arsenal is becoming depleted, in part, because bacteria have the ability to rapidly adapt and acquire resistance to our best agents. The SOS pathway, a widely conserved DNA damage stress response in bacteria, is activated by many antibiotics and has been shown to play central role in

  10. In Vivo Differentiation Potential of Epiblast Stem Cells Revealed by Chimeric Embryo Formation

    Directory of Open Access Journals (Sweden)

    Yali Huang

    2012-12-01

    Full Text Available Chimera formation after blastocyst injection or morula aggregation is the principal functional assay of the developmental potential of mouse embryonic stem cells (ESCs. This property, which demonstrates functional equivalence between ESCs and the preimplantation epiblast, is not shared by epiblast stem cell (EpiSC lines. Here, we show that EpiSCs derived either from postimplantation embryos or from ESCs in vitro readily generate chimeras when grafted to postimplantation embryos in whole embryo culture. EpiSC derivatives integrate and differentiate to derivatives of all three embryonic germ layers and primordial germ cells. In contrast, grafted ESCs seldom proliferate in postimplantation embryos, and fail to acquire the identity of their host-derived neighbors. EpiSCs do not incorporate efficiently into embryonic day 8.5 embryos, a stage by which pluripotency has been lost. Thus, chimera formation by EpiSCs requires a permissive environment, the postimplantation epiblast, and demonstrates functional equivalence between this cell type and EpiSCs.

  11. Perilipin Expression Reveals Adipogenic Potential of hADSCs inside Superporous Polymeric Cellular Delivery Systems

    Directory of Open Access Journals (Sweden)

    Sorina Dinescu

    2014-01-01

    Full Text Available Recent progress in tissue engineering and regenerative medicine envisages the use of cell-scaffold bioconstructs to best mimic the natural in vivo microenvironment. Our aim was not only to develop novel 3D porous scaffolds for regenerative applications by the association of gelatin (G, alginate (A, and polyacrylamide (PAA major assets but also to evaluate their in vitro potential to support human adipose-derived stem cells (hADSCs adipogenesis. G-A-PAA biomatrix investigated in this work is an interesting substrate combining the advantages of the three individual constituents, namely, biodegradability of G, hydrophilicity of A and PAA, superior elasticity at compression with respect to the G-A and PAA controls, and the capacity to generate porous scaffolds. hADSCs inside these novel interpenetrating polymer networks (IPNs were able to populate the entire scaffold structure and to display their characteristic spindle-like shape as a consequence of a good interaction with G component of the matrices. Additionally, hADSCs proved to display the capacity to differentiate towards mature adipocytes, to accumulate lipids inside their cytoplasm, and to express perilipin late adipogenic marker inside novel IPNs described in this study. On long term, this newly designed biomatrix aims to represent a stem cell delivery system product dedicated for modern regenerative strategies.

  12. A potential source for cellulolytic enzyme discovery and environmental aspects revealed through metagenomics of Brazilian mangroves.

    Science.gov (United States)

    Thompson, Claudia Elizabeth; Beys-da-Silva, Walter Orlando; Santi, Lucélia; Berger, Markus; Vainstein, Marilene Henning; Guima Rães, Jorge Almeida; Vasconcelos, Ana Tereza Ribeiro

    2013-01-01

    The mangroves are among the most productive and biologically important environments. The possible presence of cellulolytic enzymes and microorganisms useful for biomass degradation as well as taxonomic and functional aspects of two Brazilian mangroves were evaluated using cultivation and metagenomic approaches. From a total of 296 microorganisms with visual differences in colony morphology and growth (including bacteria, yeast and filamentous fungus), 179 (60.5%) and 117 (39.5%) were isolated from the Rio de Janeiro (RJ) and Bahia (BA) samples, respectively. RJ metagenome showed the higher number of microbial isolates, which is consistent with its most conserved state and higher diversity. The metagenomic sequencing data showed similar predominant bacterial phyla in the BA and RJ mangroves with an abundance of Proteobacteria (57.8% and 44.6%), Firmicutes (11% and 12.3%) and Actinobacteria (8.4% and 7.5%). A higher number of enzymes involved in the degradation of polycyclic aromatic compounds were found in the BA mangrove. Specific sequences involved in the cellulolytic degradation, belonging to cellulases, hemicellulases, carbohydrate binding domains, dockerins and cohesins were identified, and it was possible to isolate cultivable fungi and bacteria related to biomass decomposition and with potential applications for the production of biofuels. These results showed that the mangroves possess all fundamental molecular tools required for building the cellulosome, which is required for the efficient degradation of cellulose material and sugar release.

  13. Mycotoxigenic Potentials of Fusarium Species in Various Culture Matrices Revealed by Mycotoxin Profiling

    Directory of Open Access Journals (Sweden)

    Wen Shi

    2016-12-01

    Full Text Available In this study, twenty of the most common Fusarium species were molecularly characterized and inoculated on potato dextrose agar (PDA, rice and maize medium, where thirty three targeted mycotoxins, which might be the secondary metabolites of the identified fungal species, were detected by liquid chromatography–tandem mass spectrometry (LC-MS/MS. Statistical analysis was performed with principal component analysis (PCA to characterize the mycotoxin profiles for the twenty fungi, suggesting that these fungi species could be discriminated and divided into three groups as follows. Group I, the fusaric acid producers, were defined into two subgroups, namely subgroup I as producers of fusaric acid and fumonisins, comprising of F. proliferatum, F. verticillioides, F. fujikuroi and F. solani, and subgroup II considered to only produce fusaric acid, including F. temperatum, F. subglutinans, F. musae, F. tricinctum, F. oxysporum, F. equiseti, F. sacchari, F. concentricum, F. andiyazi. Group II, as type A trichothecenes producers, included F. langsethiae, F. sporotrichioides, F. polyphialidicum, while Group III were found to mainly produce type B trichothecenes, comprising of F. culmorum, F. poae, F. meridionale and F. graminearum. A comprehensive picture, which presents the mycotoxin-producing patterns by the selected fungal species in various matrices, is obtained for the first time, and thus from an application point of view, provides key information to explore mycotoxigenic potentials of Fusarium species and forecast the Fusarium infestation/mycotoxins contamination.

  14. In silico analysis reveals the anti-malarial potential of quinolinyl chalcone derivatives.

    Science.gov (United States)

    Thillainayagam, Mahalakshmi; Pandian, Lavanya; Murugan, Kumar Kalavathy; Vijayaparthasarathi, Vijayakumar; Sundaramoorthy, Sarveswari; Anbarasu, Anand; Ramaiah, Sudha

    2015-01-01

    In this study, the correlation between chemical structures and various parameters such as steric effects and electrostatic interactions to the inhibitory activities of quinolinyl chalcone derivatives is derived to identify the key structural elements required in the rational design of potent and novel anti-malarial compounds. The molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are carried out on 38 chalcones derivatives using Plasmodium falciparum lactate dehydrogenase (PfLDH) as potential target. Surflex-dock is used to determine the probable binding conformations of all the compounds at the active site of pfLDH and to identify the hydrogen bonding interactions which could be used to alter the inhibitory activities. The CoMFA model has provided statistically significant results with the cross-validated correlation coefficient (q(2)) of .850 and the non-cross-validated correlation coefficient (r(2)) of .912. Standard error of estimation (SEE) is .280 and the optimum number of component is five. The predictive ability of the resultant model is evaluated using a test set comprising of 13 molecules and the predicted r(2) value is .885. The results provide valuable insight for optimization of quinolinyl chalcone derivatives for better anti-malarial therapy.

  15. Event-related potentials reveal the relations between feature representations at different levels of abstraction.

    Science.gov (United States)

    Hannah, Samuel D; Shedden, Judith M; Brooks, Lee R; Grundy, John G

    2016-11-01

    In this paper, we use behavioural methods and event-related potentials (ERPs) to explore the relations between informational and instantiated features, as well as the relation between feature abstraction and rule type. Participants are trained to categorize two species of fictitious animals and then identify perceptually novel exemplars. Critically, two groups are given a perfectly predictive counting rule that, according to Hannah and Brooks (2009. Featuring familiarity: How a familiar feature instantiation influences categorization. Canadian Journal of Experimental Psychology/Revue Canadienne de Psychologie Expérimentale, 63, 263-275. Retrieved from http://doi.org/10.1037/a0017919), should orient them to using abstract informational features when categorizing the novel transfer items. A third group is taught a feature list rule, which should orient them to using detailed instantiated features. One counting-rule group were taught their rule before any exposure to the actual stimuli, and the other immediately after training, having learned the instantiations first. The feature-list group were also taught their rule after training. The ERP results suggest that at test, the two counting-rule groups processed items differently, despite their identical rule. This not only supports the distinction that informational and instantiated features are qualitatively different feature representations, but also implies that rules can readily operate over concrete inputs, in contradiction to traditional approaches that assume that rules necessarily act on abstract inputs.

  16. Microarray technology reveals potentially novel genes and pathways involved in non-functioning pituitary adenomas

    Science.gov (United States)

    Qiao, X; Wang, H; Wang, X; Zhao, B

    2016-01-01

    Abstract Microarray data of non-functioning pituitary adenomas (NFPAs) were analyzed to disclose novel genes and pathways involved in NFPA tumorigenesis. Raw microarray data were downloaded from Gene Expression Omnibus. Data pre-treatment and differential analysis were conducted using packages in R. Functional and pathway enrichment analyses were performed using package GOs-tats. A protein-protein interaction (PPI) network was constructed using server STRING and Cytoscape. Known genes involved in pituitary adenomas (PAs), were obtained from the Comparative Toxicogenomics Database. A total of 604 differentially expressed genes (DEGs) were identifed between NFPAs and controls, including 177 up- and 427 down-regulated genes. Jak-STAT and p53 signaling pathways were significantly enriched by DEGs. The PPI network of DEGs was constructed, containing 99 up- and 288 down-regulated known disease genes (e.g. EGFR and ESR1) as well as 16 up- and 17 down-regulated potential novel NFPAs-related genes (e.g. COL4A5, LHX3, MSN, and GHSR). Genes like COL4A5, LHX3, MSN, and GHSR and pathways such as p53 signaling and Jak-STAT signaling, might participate in NFPA development. Although further validations are required, these findings might provide guidance for future basic and therapy researches. PMID:28289583

  17. The time course of psychological stress as revealed by event-related potentials.

    Science.gov (United States)

    Yang, Juan; Qi, Mingming; Guan, Lili; Hou, Yan; Yang, Yu

    2012-11-14

    Psychological stress is common in everyday life and is believed to affect emotion, cognition and health. Previous brain imaging studies have been able to identify the brain regions involved in the stress response. However, our understanding of the temporal neurological response to psychological stress is limited. The present work aims to investigate the time course of psychological stress induced by a mental arithmetic task, utilizing event-related potentials (ERPs). The elicitation of stress was verified by self-reports of stress and increases in salivary cortisol levels. The subjective and physiological data showed that the stress-elicitation paradigm successfully induced a mild-to-moderate level of psychological stress. The electrophysiological data showed that the amplitude of occipital N1 was more negative in the control task than in the stress task, and the latency of frontal P2 was shorter in the stress task than in the control task. Our results provide electrophysiological evidence that psychological stress occurs primarily at the early stage of cognitive processing.

  18. Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells.

    Science.gov (United States)

    Singh, Jagdeep K; Simões, Bruno M; Howell, Sacha J; Farnie, Gillian; Clarke, Robert B

    2013-01-01

    Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are purported to be responsible for tumor initiation, maintenance, metastases, and disease recurrence. Interleukin-8 (IL-8) is upregulated in breast cancer compared with normal breast tissue and is associated with poor prognosis. IL-8 is reported to promote breast cancer progression by increasing cell invasion, angiogenesis, and metastases and is upregulated in HER2-positive cancers. Recently, we and others have established that IL-8 via its cognate receptors, CXCR1 and CXCR2, is also involved in regulating breast CSC activity. Our work demonstrates that in metastatic breast CSCs, CXCR1/2 signals via transactivation of HER2. Given the importance of HER2 in breast cancer and in regulating CSC activity, a pathway driving the activation of these receptors would have important biological and clinical consequences, especially in tumors that express high levels of IL-8 and other CXCR1/2-activating ligands. Here, we review the IL-8 signaling pathway and the role of HER2 in maintaining an IL-8 inflammatory loop and discuss the potential of combining CXCR1/2 inhibitors with other treatments such as HER2-targeted therapy as a novel approach to eliminate CSCs and improve patient survival.

  19. Source identification and distribution reveals the potential of the geochemical Antarctic sea ice proxy IPSO25

    Science.gov (United States)

    Belt, S. T.; Smik, L.; Brown, T. A.; Kim, J.-H.; Rowland, S. J.; Allen, C. S.; Gal, J.-K.; Shin, K.-H.; Lee, J. I.; Taylor, K. W. R.

    2016-01-01

    The presence of a di-unsaturated highly branched isoprenoid (HBI) lipid biomarker (diene II) in Southern Ocean sediments has previously been proposed as a proxy measure of palaeo Antarctic sea ice. Here we show that a source of diene II is the sympagic diatom Berkeleya adeliensis Medlin. Furthermore, the propensity for B. adeliensis to flourish in platelet ice is reflected by an offshore downward gradient in diene II concentration in >100 surface sediments from Antarctic coastal and near-coastal environments. Since platelet ice formation is strongly associated with super-cooled freshwater inflow, we further hypothesize that sedimentary diene II provides a potentially sensitive proxy indicator of landfast sea ice influenced by meltwater discharge from nearby glaciers and ice shelves, and re-examination of some previous diene II downcore records supports this hypothesis. The term IPSO25—Ice Proxy for the Southern Ocean with 25 carbon atoms—is proposed as a proxy name for diene II. PMID:27573030

  20. Cognitive impairment in generalized anxiety disorder revealed by event-related potential N270

    Directory of Open Access Journals (Sweden)

    Yang Y

    2015-06-01

    Full Text Available Yingxue Yang,1,2 Xiating Zhang,1,2 Yu Zhu,1,2 Yakang Dai,3 Ting Liu,3 Yuping Wang1,2 1Department of Neurology, Xuanwu Hospital, Capital Medical University, 2Beijing Key Laboratory of Neuromodulation, Beijing, People’s Republic of China; 3Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, People’s Republic of China Background: Cognitive function in anxiety disorders has been the subject of limited investigation, especially in generalized anxiety disorder (GAD. The purpose of this study was to investigate the cognitive function in subjects with GAD using mismatch-triggered negativity N270.Methods: Fifteen medication-free patients with a DSM-IV diagnosis of GAD, and 15 well-matched healthy controls performed a dual-feature delayed matching task while event-related potentials were recorded from their scalp.Results: The GAD group was characterized by the decreased N270 amplitude in the left hemisphere. The smaller N270 amplitude was associated with greater symptoms of anxiety and depression.Conclusion: Since N270 is thought to index cognitive function in different domains, including attention and memory, our results suggest that individuals with GAD have an impaired cognitive function, particularly in selective attention and working memory. These cognitive deficits may have clinical significance in subjects with GAD and should be considered in treatment planning. Keywords: generalized anxiety disorder, N270, cognitive function, selective attention, working memory

  1. Antifungal susceptibility profiles of 1698 yeast reference strains revealing potential emerging human pathogens.

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    Marie Desnos-Ollivier

    Full Text Available New molecular identification techniques and the increased number of patients with various immune defects or underlying conditions lead to the emergence and/or the description of novel species of human and animal fungal opportunistic pathogens. Antifungal susceptibility provides important information for ecological, epidemiological and therapeutic issues. The aim of this study was to assess the potential risk of the various species based on their antifungal drug resistance, keeping in mind the methodological limitations. Antifungal susceptibility profiles to the five classes of antifungal drugs (polyens, azoles, echinocandins, allylamines and antimetabolites were determined for 1698 yeast reference strains belonging to 992 species (634 Ascomycetes and 358 Basidiomycetes. Interestingly, geometric mean minimum inhibitory concentrations (MICs of all antifungal drugs tested were significantly higher for Basidiomycetes compared to Ascomycetes (p<0.001. Twenty four strains belonging to 23 species of which 19 were Basidiomycetes seem to be intrinsically "resistant" to all drugs. Comparison of the antifungal susceptibility profiles of the 4240 clinical isolates and the 315 reference strains belonging to 53 shared species showed similar results. Even in the absence of demonstrated in vitro/in vivo correlation, knowing the in vitro susceptibility to systemic antifungal agents and the putative intrinsic resistance of yeast species present in the environment is important because they could become opportunistic pathogens.

  2. Metagenomic analysis reveals potential biodegradation pathways of persistent pesticides in freshwater and marine sediments.

    Science.gov (United States)

    Fang, Hua; Cai, Lin; Yang, Ying; Ju, Feng; Li, Xiangdong; Yu, Yunlong; Zhang, Tong

    2014-02-01

    The abundance and diversity of biodegradation genes (BDGs) and potential degradation pathways of dichlorodiphenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), and atrazine (ATZ) in freshwater and marine sediments were investigated by metagenomic analysis using 6 datasets (16Gb in total). The datasets were derived using Illumina high-throughput sequencing and were based on BLAST against self-established databases of BDGs, DDT degradation genes (DDGs), HCH degradation genes (HDGs), and ATZ degradation genes (ADGs). The results showed that the abundance and diversity of BDGs, DDGs, HDGs, and ADGs varied with sample source and locations. The lip and mnp genes, which encode for peroxidase, and the carA gene, which encodes for laccase, were detected as the dominant genes for degradation of organic pollutants. The hdt, hdg, and atzB genes, which encode for hydratase, dehalogenase, and ethylaminohydrolase, were found to be the most abundant genes involved in DDT, HCH, and ATZ degradation, respectively. The identified 69 genera capable of degrading organic pollutants were mostly affiliated with Proteobacteria (49.3%) and Actinobacteria (21.7%). Four genera, including Plesiocystis, Anaerolinea, Jannaschia, and Mycobacterium, were the major biodegradation populations in all sediments. In this study, the nearly complete biodegradation pathways of DDT and ATZ were found, and the partial degradation pathway of HCH was detected in all sediments.

  3. Serum proteomic analysis reveals potential serum biomarkers for occupational medicamentosa-like dermatitis caused by trichloroethylene.

    Science.gov (United States)

    Huang, Peiwu; Ren, Xiaohu; Huang, Zhijun; Yang, Xifei; Hong, Wenxu; Zhang, Yanfang; Zhang, Hang; Liu, Wei; Huang, Haiyan; Huang, Xinfeng; Wu, Desheng; Yang, Linqing; Tang, Haiyan; Zhou, Li; Li, Xuan; Liu, Jianjun

    2014-08-17

    Trichloroethylene (TCE) is an industrial solvent with widespread occupational exposure and also a major environmental contaminant. Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease and it has become one major hazard in China. In this study, sera from 3 healthy controls and 3 OMLDT patients at different disease stages were used for a screening study by 2D-DIGE and MALDI-TOF-MS/MS. Eight proteins including transthyretin (TTR), retinol binding protein 4 (RBP4), haptoglobin, clusterin, serum amyloid A protein (SAA), apolipoprotein A-I, apolipoprotein C-III and apolipoprotein C-II were found to be significantly altered among the healthy, acute-stage, healing-stage and healed-stage groups. Specifically, the altered expression of TTR, RBP4 and haptoglobin were further validated by Western blot analysis and ELISA. Our data not only suggested that TTR, RBP4 and haptoglobin could serve as potential serum biomarkers of OMLDT, but also indicated that measurement of TTR, RBP4 and haptoglobin or their combination could help aid in the diagnosis, monitoring the progression and therapy of the disease.

  4. Multi-Analytical Approach Reveals Potential Microbial Indicators in Soil for Sugarcane Model Systems.

    Directory of Open Access Journals (Sweden)

    Acacio Aparecido Navarrete

    Full Text Available This study focused on the effects of organic and inorganic amendments and straw retention on the microbial biomass (MB and taxonomic groups of bacteria in sugarcane-cultivated soils in a greenhouse mesocosm experiment monitored for gas emissions and chemical factors. The experiment consisted of combinations of synthetic nitrogen (N, vinasse (V; a liquid waste from ethanol production, and sugarcane-straw blankets. Increases in CO2-C and N2O-N emissions were identified shortly after the addition of both N and V to the soils, thus increasing MB nitrogen (MB-N and decreasing MB carbon (MB-C in the N+V-amended soils and altering soil chemical factors that were correlated with the MB. Across 57 soil metagenomic datasets, Actinobacteria (31.5%, Planctomycetes (12.3%, Deltaproteobacteria (12.3%, Alphaproteobacteria (12.0% and Betaproteobacteria (11.1% were the most dominant bacterial groups during the experiment. Differences in relative abundance of metagenomic sequences were mainly revealed for Acidobacteria, Actinobacteria, Gammaproteobacteria and Verrucomicrobia with regard to N+V fertilization and straw retention. Differential abundances in bacterial groups were confirmed using 16S rRNA gene-targeted phylum-specific primers for real-time PCR analysis in all soil samples, whose results were in accordance with sequence data, except for Gammaproteobacteria. Actinobacteria were more responsive to straw retention with Rubrobacterales, Bifidobacteriales and Actinomycetales related to the chemical factors of N+V-amended soils. Acidobacteria subgroup 7 and Opitutae, a verrucomicrobial class, were related to the chemical factors of soils without straw retention as a surface blanket. Taken together, the results showed that MB-C and MB-N responded to changes in soil chemical factors and CO2-C and N2O-N emissions, especially for N+V-amended soils. The results also indicated that several taxonomic groups of bacteria, such as Acidobacteria, Actinobacteria and

  5. MicroRNA Profiling of CSF Reveals Potential Biomarkers to Detect Alzheimer`s Disease.

    Directory of Open Access Journals (Sweden)

    Johannes Denk

    Full Text Available The miRBase-21 database currently lists 1881 microRNA (miRNA precursors and 2585 unique mature human miRNAs. Since their discovery, miRNAs have proved to present a new level of epigenetic post-transcriptional control of protein synthesis. Initial results point to a possible involvement of miRNA in Alzheimer's disease (AD. We applied OpenArray technology to profile the expression of 1178 unique miRNAs in cerebrospinal fluid (CSF samples of AD patients (n = 22 and controls (n = 28. Using a Cq of 34 as cut-off, we identified positive signals for 441 miRNAs, while 729 miRNAs could not be detected, indicating that at least 37% of miRNAs are present in the brain. We found 74 miRNAs being down- and 74 miRNAs being up-regulated in AD using a 1.5 fold change threshold. By applying the new explorative "Measure of relevance" method, 6 reliable and 9 informative biomarkers were identified. Confirmatory MANCOVA revealed reliable miR-100, miR-146a and miR-1274a as differentially expressed in AD reaching Bonferroni corrected significance. MANCOVA also confirmed differential expression of informative miR-103, miR-375, miR-505#, miR-708, miR-4467, miR-219, miR-296, miR-766 and miR-3622b-3p. Discrimination analysis using a combination of miR-100, miR-103 and miR-375 was able to detect AD in CSF by positively classifying controls and AD cases with 96.4% and 95.5% accuracy, respectively. Referring to the Ingenuity database we could identify a set of AD associated genes that are targeted by these miRNAs. Highly predicted targets included genes involved in the regulation of tau and amyloid pathways in AD like MAPT, BACE1 and mTOR.

  6. Gene expression arrays reveal a rapid return to normal homeostasis in immunologically-challenged trophoblast-like JAR cells.

    Science.gov (United States)

    Jarvis, James N; Dozmorov, Igor; Jiang, Kaiyu; Chen, Yanmin; Frank, Mark Barton; Cadwell, Craig; Turner, Sean; Centola, Michael

    2004-04-01

    The immunologic adaptations of pregnancy have come under increasing scrutiny in the past 15 years. Existing experimental evidence clearly demonstrates that placental trophoblasts play an important role in regulating immunologic/inflammatory responses at the maternal-fetal interface. We used a well-developed gene expression array to examine in greater detail the physiologic response of trophoblast-like choriocarcinoma cells to a model immunologic 'challenge.' We co-cultured PHA-activated or resting peripheral blood mononuclear cells (PBMC) with the human choriocarcinoma cell line JAR for time periods ranging from 2 to 18 h. Messenger RNA expression in the JAR cells was then assessed using a 21,329-gene microarray and novel biostatistical analyses that we have previously published. Patterns of differential gene expression were assessed using a commercial pathway analysis software program. Differences in gene expression between JAR cells cultured with activated PBMC (experimental samples) and JAR cells cultured with resting PBMC (control samples) were seen only at the 2h time point. That is, multiple genes were transcribed in JAR cells in response to activated PBMC, but expression levels of the genes had all returned to baseline by 6h. Molecular modeling demonstrated that the differentially expressed genes were largely associated with cell growth and differentiation. This model was confirmed by noting a two-fold increase in CD10/neutral endopeptidase expression (a marker for cell differentiation) in JAR cells incubated with media from activated PBMC compared with JAR cells incubated with resting PBMC. These findings support the hypothesis that there is a delicate immunologic milieu at the maternal-fetal interface that must be maintained. Immunologic/inflammatory challenge at the maternal-fetal interface is compensated by cellular mechanisms that work to reduce inflammation and rapidly restore immunologic balance.

  7. Rare human papillomavirus 16 E6 variants reveal significant oncogenic potential

    Directory of Open Access Journals (Sweden)

    Tommasino Massimo

    2011-06-01

    Full Text Available Abstract The aim of this study was to determine whether low prevalence human papillomavirus (HPV 16 E6 variants differ from high prevalence types in their functional abilities. We evaluated functions relevant to carcinogenesis for the rarely-detected European variants R8Q, R10G and R48W as compared to the commonly detected L83V. Human immortalized keratinocytes (NIKS stably transduced with the E6 variants were used in most functional assays. Low and high prevalence E6 variants displayed similar abilities in abrogation of growth arrest and inhibition of p53 elevation induced by actinomycin D. Differences were detected in the abilities to dysregulate stratification and differentiation of NIKS in organotypic raft cultures, modulate detachment induced apoptosis (anoikis and hyperactivate Wnt signaling. No distinctive phenotype could be assigned to include all rare variants. Like L83V, raft cultures derived from variants R10G and R48W similarly induced hyperplasia and aberrantly expressed keratin 5 in the suprabasal compartment with significantly lower expression of keratin 10. Unlike L83V, both variants, and particularly R48W, induced increased levels of anoikis upon suspension in semisolid medium. R8Q induced a unique phenotype characterized by thin organotypic raft cultures, low expression of keratin 10, and high expression of keratins 5 and 14 throughout all raft layers. Interestingly, in a reporter based assay R8Q exhibited a higher ability to augment TCF/β-catenin transcription. The data suggests that differences in E6 variant prevalence in cervical carcinoma may not be related to the carcinogenic potential of the E6 protein.

  8. Neuropeptidomics of mouse hypothalamus after imipramine treatment reveal somatostatin as a potential mediator of antidepressant effects.

    Science.gov (United States)

    Nilsson, Anna; Stroth, Nikolas; Zhang, Xiaoqun; Qi, Hongshi; Fälth, Maria; Sköld, Karl; Hoyer, Daniel; Andrén, Per E; Svenningsson, Per

    2012-01-01

    Excessive activation of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with numerous diseases, including depression, and the tricyclic antidepressant imipramine has been shown to suppress activity of the HPA axis. Central hypothalamic control of the HPA axis is complex and involves a number of neuropeptides released from multiple hypothalamic subnuclei. The present study was therefore designed to determine the effects of imipramine administration on the mouse hypothalamus using a peptidomics approach. Among the factors found to be downregulated after acute (one day) or chronic (21 days) imipramine administration were peptides derived from secretogranin 1 (chromogranin B) as well as peptides derived from cerebellin precursors. In contrast, peptides SRIF-14 and SRIF-28 (1-11) derived from somatostatin (SRIF, somatotropin release inhibiting factor) were significantly upregulated by imipramine in the hypothalamus. Because diminished SRIF levels have long been known to occur in depression, a second part of the study investigated the roles of individual SRIF receptors in mediating potential antidepressant effects. SRA880, an antagonist of the somatostatin-1 autoreceptor (sst1) which positively modulates release of endogenous SRIF, was found to synergize with imipramine in causing antidepressant-like effects in the tail suspension test. Furthermore, chronic co-administration of SRA880 and imipramine synergistically increased BDNF mRNA expression in the cerebral cortex. Application of SRIF or L054264, an sst2 receptor agonist, but not L803807, an sst4 receptor agonist, increased phosphorylation of CaMKII and GluR1 in cerebrocortical slices. Our present experiments thus provide evidence for antidepressant-induced upregulation of SRIF in the brain, and strengthen the notion that augmented SRIF expression and signaling may counter depressive-like symptoms. This article is part of a Special Issue entitled 'Anxiety and Depression'.

  9. Environmental metabarcodes for insects: in silico PCR reveals potential for taxonomic bias.

    Science.gov (United States)

    Clarke, Laurence J; Soubrier, Julien; Weyrich, Laura S; Cooper, Alan

    2014-11-01

    Studies of insect assemblages are suited to the simultaneous DNA-based identification of multiple taxa known as metabarcoding. To obtain accurate estimates of diversity, metabarcoding markers ideally possess appropriate taxonomic coverage to avoid PCR-amplification bias, as well as sufficient sequence divergence to resolve species. We used in silico PCR to compare the taxonomic coverage and resolution of newly designed insect metabarcodes (targeting 16S) with that of existing markers [16S and cytochrome oxidase c subunit I (COI)] and then compared their efficiency in vitro. Existing metabarcoding primers amplified in silico mitochondrial genomes available, whereas new primers targeting 16S provided >90% coverage. Furthermore, metabarcodes targeting COI appeared to introduce taxonomic PCR-amplification bias, typically amplifying a greater percentage of Lepidoptera and Diptera species, while failing to amplify certain orders in silico. To test whether bias predicted in silico was observed in vitro, we created an artificial DNA blend containing equal amounts of DNA from 14 species, representing 11 insect orders and one arachnid. We PCR-amplified the blend using five primer sets, targeting either COI or 16S, with high-throughput amplicon sequencing yielding more than 6 million reads. In vitro results typically corresponded to in silico PCR predictions, with newly designed 16S primers detecting 11 insect taxa present, thus providing equivalent or better taxonomic coverage than COI metabarcodes. Our results demonstrate that in silico PCR is a useful tool for predicting taxonomic bias in mixed template PCR and that researchers should be wary of potential bias when selecting metabarcoding markers.

  10. Phase noise reveals early category-specific modulation of the event-related potentials.

    Science.gov (United States)

    Németh, Kornél; Kovács, Petra; Vakli, Pál; Kovács, Gyula; Zimmer, Márta

    2014-01-01

    Previous studies have found that the amplitude of the early event-related potential (ERP) components evoked by faces, such as N170 and P2, changes systematically as a function of noise added to the stimuli. This change has been linked to an increased perceptual processing demand and to enhanced difficulty in perceptual decision making about faces. However, to date it has not yet been tested whether noise manipulation affects the neural correlates of decisions about face and non-face stimuli similarly. To this end, we measured the ERPs for faces and cars at three different phase noise levels. Subjects performed the same two-alternative age-discrimination task on stimuli chosen from young-old morphing continua that were created from faces as well as cars and were calibrated to lead to similar performances at each noise-level. Adding phase noise to the stimuli reduced performance and enhanced response latency for the two categories to the same extent. Parallel to that, phase noise reduced the amplitude and prolonged the latency of the face-specific N170 component. The amplitude of the P1 showed category-specific noise dependence: it was enhanced over the right hemisphere for cars and over the left hemisphere for faces as a result of adding phase noise to the stimuli, but remained stable across noise levels for cars over the left and for faces over the right hemisphere. Moreover, noise modulation altered the category-selectivity of the N170, while the P2 ERP component, typically associated with task decision difficulty, was larger for the more noisy stimuli regardless of stimulus category. Our results suggest that the category-specificity of noise-induced modulations of ERP responses starts at around 100 ms post-stimulus.

  11. Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.

    Directory of Open Access Journals (Sweden)

    Aileen Marshall

    , demonstrated potential as a diagnostic HCC marker and should be evaluated in future studies.

  12. GREEN TECHNOLOGY FORESIGHT OF HIGH TECHNOLOGY: HYPE OR POTENTIALS - THE CHALLENGES FROM NANOTECHNOLOGY, BIOTECHNOLOGY AND ICT

    DEFF Research Database (Denmark)

    Jørgensen, Michael Søgaard

    2004-01-01

    The paper describes the theoretical and methodological approach in an ongoing Danish technology foresight project focusing on the environmental potentials and risks of nanotechnology, biotechnology, and information and communication technology (ICT). The paper gives a short overview of some...

  13. Spray-on Thin Film PV Solar Cells: Advances, Potentials and Challenges

    Directory of Open Access Journals (Sweden)

    Morteza Eslamian

    2014-01-01

    Full Text Available The capability to fabricate photovoltaic (PV solar cells on a large scale and at a competitive price is a milestone waiting to be achieved. Currently, such a fabrication method is lacking because the effective methods are either difficult to scale up or expensive due to the necessity for fabrication in a vacuum environment. Nevertheless, for a class of thin film solar cells, in which the solar cell materials can be processed in a solution, up scalable and vacuum-free fabrication techniques can be envisioned. In this context, all or some layers of polymer, dye-sensitized, quantum dot, and copper indium gallium selenide thin film solar cells illustrate some examples that may be processed in solution. The solution-processed materials may be transferred to the substrate by atomizing the solution and carrying the spray droplets to the substrate, a process that will form a thin film after evaporation of the solvent. Spray coating is performed at atmospheric pressure using low cost equipment with a roll-to-roll process capability, making it an attractive fabrication technique, provided that fairly uniform layers with high charge carrier separation and transport capability can be made. In this paper, the feasibility, the recent advances and challenges of fabricating spray-on thin film solar cells, the dynamics of spray and droplet impaction on the substrate, the photo-induced electron transfer in spray-on solar cells, the challenges on characterization and simulation, and the commercialization status of spray-on solar cells are discussed.

  14. Nanostructured ZnO - its challenging properties and potential for device applications

    Science.gov (United States)

    Dimova-Malinovska, D.

    2017-01-01

    Nanostructured ZnO possessing interesting structural and optical properties offers challenging opportunities for innovative applications. In this lecture the review of the optical and structural properties of ZnO nanostructured layers is presented. It is shown that they have a direct impact on the parameters of devices involving ZnO. An analysis of current trends in the photovoltaic (PV) field shows that improved light harvesting and efficiency of solar cells can be obtained by implementing nanostructured ZnO layers to process advanced solar cell structures. Because of amenability to doping, high chemical stability, sensitivity to different adsorbed gases, nontoxicity and low cost ZnO attracted much attention for application as gas sensors. The sensitivity of nano-grain ZnO gas elements is comparatively high because of the grain-size effect. Application of nanostructured ZnO for gas sensors and for increasing of light harvesting in solar cells is demonstrated.

  15. Cyber-Management of People with Chronic Disease: A Potential Solution to eHealth Challenges

    Science.gov (United States)

    Laakso, E-Liisa; Armstrong, Kylie; Usher, Wayne

    2012-01-01

    The evolving eHealth agenda presents a range of potential opportunities for the management and prevention of chronic disease. This paper identifies issues and barriers to the uptake of eHealth and describes a strategy ("Healthy Outcomes for Australians"[C]-HOFA) for creating a central knowledge filter and cyber space method for tracking health…

  16. Potentials and challenges of biogas from fish industry waste in the arctic

    DEFF Research Database (Denmark)

    Jensen, Pernille Erland; Heiske, Stefan

    2016-01-01

    The fish industry is a main industry in many Arctic locations. In most places by-products are disposed of at sea. Oxygen depletion and dead sea bottom is observed, as the organic material is biodegraded and methane produced; contributing to the global warming. In this study, the biogas potential...

  17. Challenging the claims on the potential of biochar to mitigate climate change

    NARCIS (Netherlands)

    Francischinelli Rittl, T.

    2015-01-01

    Summary In this PhD thesis I studied the influence of biochar discourses on the political practices in Brazil and the impact of biochar on soil organic carbon (SOC) stocks, thus contributing to the current debate on the potential of biochar to mitigate climate change. Biochar is the solid material o

  18. Textiles as Tangible Working Materials in Participatory Design Processes: Potentials and Challenges

    DEFF Research Database (Denmark)

    Heimdal, Elisabeth Jacobsen; Rosenqvist, Tanja Schultz

    2010-01-01

    Participatory design (PD) methods are currently of little use in the textile industry, even though the need for multiple stakeholder involvement in the industry is growing. In this paper, we argue that PD represents a potential for innovation in the textile industry, due to PD’s collaborative nat...

  19. Side Channels of the Impounded and Middle Mississippi River: Opportunities and Challenges to Maximize Restoration Potential

    Science.gov (United States)

    2016-07-01

    diverse plant and animal communities Restore hydrogeomorphic processes that create, maintain, and improve connectivity, bathymetric diversity...and Terrestrial Habitat” of Different Animal Groups* Resident Fish % change Migratory Fish % change Birds % change Largemouth bass -6 Blue catfish...food acquisition. • Restore reproductive potential – including provision of bare sediment for vegetation colonization. • Provide rearing and

  20. Population genetic patterns revealed by microsatellite data challenge the mitochondrial DNA based taxonomy of Astyanax in Mexico (Characidae, Teleostei).

    Science.gov (United States)

    Hausdorf, Bernhard; Wilkens, Horst; Strecker, Ulrike

    2011-07-01

    Astyanax has become an important model system for evolutionary studies of cave animals. We investigated correlations of population genetic patterns revealed by microsatellite data and phylogeographic patterns shown by mitochondrial DNA sequences in Mexican cave and surface fish of the genus Astyanax (Characidae, Teleostei) to improve the understanding of the colonization history of this neotropical fish in Central and North America and to assess a recent taxonomic classification. The distribution of nuclear genotypes is not congruent with that of the mitochondrial clades. Admixture analyses suggest there has been nuclear gene flow between populations defined by different mitochondrial clades. The microsatellite data indicate that there was mitochondrial capture of a cave population from adjacent populations. Furthermore, gene flow also occurred between populations belonging to different nuclear genotypic clusters. This indicates that neither the nuclear genotypic clusters nor the mitochondrial clades represent independent evolutionary units, although the mitochondrial divergences are high and in a range usually characteristic for different fish species. This conclusion is supported by the presence of morphologically intermediate forms. Our analyses show that the Trans-Mexican Volcanic Belt limited gene flow, but has been crossed by Astyanax several times. In Yucatán, where obvious geographic barriers are missing, the incongruence between the distribution of nuclear and mitochondrial markers reflects random colonization events caused by inundations or marine transgressions resulting in random phylogeographic breaks. Thus, conclusions about the phylogeographic history and even more about the delimitation of species should not be based on single genetic markers.

  1. Competition between inverse piezoelectric effect and deformation potential mechanism in undoped GaAs revealed by ultrafast acoustics

    Directory of Open Access Journals (Sweden)

    Pezeril T.

    2013-03-01

    Full Text Available By using the picosecond ultrasonics technique, piezoelectric effect in GaAs undoped sample at both faces (A[111] and B[-1-1-1] is experimentally studied. We demonstrate that piezoelectric generation of sound can dominate in GaAs material over the deformation potential mechanism even in the absence of static externally applied or built-in electric field in the semiconductor material. In that case, the Dember field, caused by the separation of photo-generated electrons and holes in the process of supersonic diffusion, is sufficient for the dominance of the piezoelectric mechanism during the optoacoustic excitation. The experimental results on the sample at both faces reveal that in one case (A face, the two mechanisms, piezoelectric effect and deformation potential, can compensate each other leading to a large decrease of the measured Brillouin oscillation magnitude.

  2. The potential application and challenge of powerful CRISPR/Cas9 system in cardiovascular research.

    Science.gov (United States)

    Li, Yangxin; Song, Yao-Hua; Liu, Bin; Yu, Xi-Yong

    2017-01-15

    CRISPR/Cas9 is a precision-guided munition found in bacteria to fight against invading viruses. This technology has enormous potential applications, including altering genes in both somatic and germ cells, as well as generating knockout animals. Compared to other gene editing techniques such as zinc finger nucleases and TALENS, CRISPR/Cas9 is much easier to use and highly efficient. Importantly, the multiplex capacity of this technology allows multiple genes to be edited simultaneously. CRISPR/Cas9 also has the potential to prevent and cure human diseases. In this review, we wish to highlight some key points regarding the future prospect of using CRISPR/Cas9 as a powerful tool for cardiovascular research, and as a novel therapeutic strategy to treat cardiovascular diseases.

  3. Bioprospecting microalgae as potential sources of "green energy"--challenges and perspectives (review).

    Science.gov (United States)

    Ratha, S K; Prasanna, R

    2012-01-01

    Microalgae and cyanobacteria are potential foods, feeds, sources of high-value bioactive molecules and biofuels, and find tremendous applications in bioremediation and agriculture. Although few efforts have been undertaken to index the microalgal germplasm available in terms of lipid content, information on suitability of strains for mass multiplication and advances in development of methods for extraction and generating biofuel are scarce. Our review summarizes the potential of microalgae, latest developments in the field and analyzes the "pitfalls" in oversimplification of their promise in the years to come. Microalgae represent "green gold mines" for generating energy; however, the path to success is long and winding and needs tremendous and concerted efforts from science and industry, besides political will and social acceptance for overcoming the limitations. The major advantages of second generation biofuels based on microalgal systems, include their higher photon conversion efficiency, growth all around the year, even in wastewaters, and production of environment friendly biodegradable biofuels.

  4. Massive MIMO and Millimeter Wave for 5G Wireless HetNet: Potentials and Challenges

    OpenAIRE

    Bogale, Tadilo Endeshaw; Le, Long Bao

    2015-01-01

    There have been active research activities worldwide in developing the next-generation 5G wireless network. The 5G network is expected to support significantly large amount of mobile data traffic and huge number of wireless connections, achieve better cost- and energy-efficiency as well as quality of service (QoS) in terms of communication delay, reliability and security. To this end, the 5G wireless network should exploit potential gains in different network dimensions including super dense ...

  5. Comparative genome analysis of Megasphaera sp. reveals niche specialization and its potential role in the human gut.

    Directory of Open Access Journals (Sweden)

    Sudarshan Anand Shetty

    Full Text Available With increasing number of novel bacteria being isolated from the human gut ecosystem, there is a greater need to study their role in the gut ecosystem and their effect on the host health. In the present study, we carried out in silico genome-wide analysis of two novel Megasphaera sp. isolates NM10 (DSM25563 and BL7 (DSM25562, isolated from feces of two healthy individuals and validated the key features by in vitro studies. The analysis revealed the general metabolic potential, adaptive features and the potential effects of these isolates on the host. The comparative genome analysis of the two human gut isolates NM10 and BL7 with ruminal isolate Megasphaera elsdenii (DSM20460 highlighted the differential adaptive features for their survival in human gut. The key findings include features like bile resistance, presence of various sensory and regulatory systems, stress response systems, membrane transporters and resistance to antibiotics. Comparison of the "glycobiome" based on the genomes of the ruminal isolate with the human gut isolates NM10 and BL revealed the presence of diverse and unique sets of Carbohydrate-Active enzymes (CAZymes amongst these isolates, with a higher collection of CAZymes in the human gut isolates. This could be attributed to the difference in host diet and thereby the environment, consequently suggesting host specific adaptation in these isolates. In silico analysis of metabolic potential predicted the ability of these isolates to produce important metabolites like short chain fatty acids (butyrate, acetate, formate, and caproate, vitamins and essential amino acids, which was further validated by in vitro experiments. The ability of these isolates to produce important metabolites advocates for a potential healthy influence on the host. Further in vivo studies including transcriptomic and proteomic analysis will be required for better understanding the role and impact of these Megasphaera sp. isolates NM10 and BL7 on the

  6. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions.

    Science.gov (United States)

    Roberts, Jason A; Abdul-Aziz, Mohd H; Lipman, Jeffrey; Mouton, Johan W; Vinks, Alexander A; Felton, Timothy W; Hope, William W; Farkas, Andras; Neely, Michael N; Schentag, Jerome J; Drusano, George; Frey, Otto R; Theuretzbacher, Ursula; Kuti, Joseph L

    2014-06-01

    Infections in critically ill patients are associated with persistently poor clinical outcomes. These patients have severely altered and variable antibiotic pharmacokinetics and are infected by less susceptible pathogens. Antibiotic dosing that does not account for these features is likely to result in suboptimum outcomes. In this Review, we explore the challenges related to patients and pathogens that contribute to inadequate antibiotic dosing and discuss how to implement a process for individualised antibiotic therapy that increases the accuracy of dosing and optimises care for critically ill patients. To improve antibiotic dosing, any physiological changes in patients that could alter antibiotic concentrations should first be established; such changes include altered fluid status, changes in serum albumin concentrations and renal and hepatic function, and microvascular failure. Second, antibiotic susceptibility of pathogens should be confirmed with microbiological techniques. Data for bacterial susceptibility could then be combined with measured data for antibiotic concentrations (when available) in clinical dosing software, which uses pharmacokinetic/pharmacodynamic derived models from critically ill patients to predict accurately the dosing needs for individual patients. Individualisation of dosing could optimise antibiotic exposure and maximise effectiveness.

  7. The potential, limitations, and challenges of divide and conquer quantum electronic structure calculations on energetic materials.

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, Jon R.; Magyar, Rudolph J.

    2012-02-01

    High explosives are an important class of energetic materials used in many weapons applications. Even with modern computers, the simulation of the dynamic chemical reactions and energy release is exceedingly challenging. While the scale of the detonation process may be macroscopic, the dynamic bond breaking responsible for the explosive release of energy is fundamentally quantum mechanical. Thus, any method that does not adequately describe bonding is destined to lack predictive capability on some level. Performing quantum mechanics calculations on systems with more than dozens of atoms is a gargantuan task, and severe approximation schemes must be employed in practical calculations. We have developed and tested a divide and conquer (DnC) scheme to obtain total energies, forces, and harmonic frequencies within semi-empirical quantum mechanics. The method is intended as an approximate but faster solution to the full problem and is possible due to the sparsity of the density matrix in many applications. The resulting total energy calculation scales linearly as the number of subsystems, and the method provides a path-forward to quantum mechanical simulations of millions of atoms.

  8. Community-based telemonitoring for hypertension management: practical challenges and potential solutions.

    Science.gov (United States)

    Hovey, Lauren; Kaylor, Mary Beth; Alwan, Majd; Resnick, Helaine E

    2011-10-01

    Older adults residing in rural areas often lack convenient, patient-centered, community-based approaches to facilitate receipt of routine care to manage common chronic conditions. Without adequate access to appropriate disease management resources, the risk of seniors' experiencing acute events related to these common conditions increases substantially. Further, poorly managed chronic conditions are costly and place seniors at increased risk of institutionalization and permanent loss of independence. Novel, telehealth-based approaches to management of common chronic conditions like hypertension may not only improve the health of older adults, but may also lead to substantial cost savings associated with acute care episodes and institutionalization. The aim of this report is to summarize practical considerations related to operations and logistics of a unique community-based telemonitoring pilot study targeting rural seniors who utilize community-based senior centers. This article reviews the technological challenges encountered during the study and proposes solutions relevant to future research and implementation of telehealth in community-based, congregate settings.

  9. An assessment of BWR (boiling water reactor) Mark-II containment challenges, failure modes, and potential improvements in performance

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, D.L.; Jones, K.R.; Dallman, R.J. (EG and G Idaho, Inc., Idaho Falls, ID (USA)); Wagner, K.C. (Science Applications International Corp., Albuquerque, NM (USA))

    1990-07-01

    This report assesses challenges to BWR Mark II containment integrity that could potentially arise from severe accidents. Also assessed are some potential improvements that could prevent core damage or containment failure, or could mitigate the consequences of such failure by reducing the release of fission products to the environment. These challenges and improvements are analyzed via a limited quantitative risk/benefit analysis of a generic BWR/4 reactor with Mark II containment. Point estimate frequencies of the dominant core damage sequences are obtained and simple containment event trees are constructed to evaluate the response of the containment to these severe accident sequences. The resulting containment release modes are then binned into source term release categories, which provide inputs to the consequence analysis. The output of the consequences analysis is used to construct an overall base case risk profile. Potential improvements and sensitivities are evaluated by modifying the event tree spilt fractions, thus generating a revised risk profile. Several important sensitivity cases are examined to evaluate the impact of phenomenological uncertainties on the final results. 75 refs., 25 figs., 65 tabs.

  10. Introducing Teacher Mentoring in Kosovo Schools – Potential and Challenges for Sustainability

    Directory of Open Access Journals (Sweden)

    Eda Vula

    2015-12-01

    Full Text Available This study examined the lessons learned from the introduction of a teacher mentoring culture within a teacher professional development program in selected pilot schools in Kosovo. Four mentor teachers and four mentee focus groups were involved in the open interviews, and their portfolios were examined. The important themes in terms of developing a school mentoring culture in a system that had lacked mentoring practices and is embarking on an ambitious curricular reform were identified. The study revealed that individual, collegial and institutional dimensions are critical in attempting to introduce the mentoring culture. The study concluded that mentoring is a mixed concept and is viewed as hierarchical but is, nevertheless, an important professional development tool for teachers who are facing the pressure of the reform. This formalized way, known as “Balkanization” culture, marks a critical step towards developing a collaborative school culture as the desired end point.

  11. POTENTIALLY GRAVE GASTRO-INTESTINAL TRACT PROBLEMS IN PREGNANCY - A CHALLENGE TO THE OBSTETRICIAN!

    Directory of Open Access Journals (Sweden)

    Chaitra

    2016-02-01

    Full Text Available CONTEXT Acute surgical pathology may be overlooked in pregnancy. Despite advances in medical technology, preoperative diagnosis of potentially grave pathologies of the gastrointestinal tract (GIT is often delayed due to overlap with symptoms of pregnancy non-specific elevation of some laboratory parameters due to pregnancy and a dilemma for obstetricians and surgeons in ordering radiological imaging modalities given the risk associated with fetal exposure to ionizing radiation and contrast. AIMS The aim of this study is to analyse the cases of gastrointestinal tract problems encountered in pregnancy so that increasing awareness can be created among obstetricians. This is important because early diagnosis and timely intervention can significantly improve maternal and fetal outcome in these cases. SETTINGS AND DESIGN There is a retrospective case study of potentially grave GIT problems encountered at Vanivilas hospital, Bangalore, a tertiary referral institute wherein the clinical presentation was confounded by pregnancy. MATERIALS AND METHODS All the included cases were analysed for age of the patient, pre-existing gastrointestinal tract disorders, gestational age at diagnosis, maternal and fetal outcome. RESULTS A total of 8 cases of GIT problems in pregnancy were studied. Though acute appendicitis is the most common cause of GIT emergency in pregnancy as quoted in literature 5, we did not encounter any case of acute appendicitis in pregnancy in the study period. Other conditions which were encountered were small bowel obstruction, stomach and bowel perforation and bleeding oesophageal varices. Whilst few of the conditions could be managed conservatively without harm to the pregnancy, others required a laparotomy and reparative procedures. Delay in diagnosis and intervention proved to be fatal in some of these women. CONCLUSIONS Knowledge about potentially grave gastrointestinal tract problems during pregnancy, high index of clinical suspicion

  12. Smart-watches: a potential challenger to the implantable loop recorder?

    Science.gov (United States)

    Carpenter, Alexander; Frontera, Antonio

    2016-06-01

    The newest generation of smart-watches offer heart rate monitoring technology via photoplethysmography, a technology shown to demonstrate impressive ability in diagnosing arrhythmias including atrial fibrillation. Combining such technology with the portability, connectivity and other location and activity tracking features smart-watches could represent a powerful new tool in extended non-invasive arrhythmia detection. The technology itself, including potential uses and limitations, is discussed. There is a need for further software development but crucially, further work into clarifying the diagnostic accuracy of such technology.

  13. POTENTIAL AND CHALLENGES OF ROMANIA’S RENEWABLE ENERGY MARKET TOWARDS EUROPA 2020 HORIZON

    Directory of Open Access Journals (Sweden)

    PÎRVU MARCEL

    2015-04-01

    Full Text Available This paper intends to offer a short analysis on the progress of Romania regarding renewable energy, by correlating the on-field situation with the National Renewable Energy Action Plan, in order to create an overview on how the objectives for Europa 2020 horizon are being followed. All the advantages, as well as natural potential, political environment, legal framework and other influential factors are being taken into consideration to launch a hypothesis on whether Romania will be able to meet the renewable energy targets set by 2009/28/CE Directive.

  14. Beliefs about weight gain among young adults: potential challenges to prevention.

    Science.gov (United States)

    Gokee LaRose, Jessica; Gorin, Amy A; Clarke, Megan M; Wing, Rena R

    2011-09-01

    This study assessed young adults' beliefs about weight gain with the goal of improving intervention efforts with this high-risk group. A total of 1,347 incoming freshman (45% male; 81% non-Hispanic white; 18.6 ± 1.7 years; BMI = 23.3 ± 2.3 kg/m2) at a large state university in the Northeast completed a survey designed to assess: (i) degree of concern about weight gain, (ii) level of interest in weight control programs, and (iii) the most acceptable setting for an intervention. Perceptions about freshman weight gain were consistent across gender, with men and women reporting that the average student gains 5.4 ± 1.9 kg and 5.6 ± 1.9 kg respectively. Men in general were less concerned about weight gain (P gain 6.2 ± 4.2 kg before becoming concerned compared to 3.1 ± 1.7 kg among women (P gaining weight than normal weight (NW) men (P gain less weight before becoming concerned (5.0 ± 3.0 kg vs. 6.7 ± 4.5 kg, P prevent weight gain (17% men vs. 40% women, P prevention program did not vary by weight status (P = 0.59). Both men and women were most likely to report a willingness to attend classes on a local college campus compared to other settings. Findings highlight the challenges of engaging young adults in weight gain prevention programs, particularly young men, and are discussed in terms of implications for improving recruitment efforts and intervention development with this population.

  15. Regenerative potential of the cartilaginous tissue in mesenchymal stem cells: update, limitations, and challenges.

    Science.gov (United States)

    Cruz, Ivana Beatrice Mânica da; Severo, Antônio Lourenço; Azzolin, Verônica Farina; Garcia, Luiz Filipe Machado; Kuhn, André; Lech, Osvandré

    2017-01-01

    Advances in the studies with adult mesenchymal stem cells (MSCs) have turned tissue regenerative therapy into a promising tool in many areas of medicine. In orthopedics, one of the main challenges has been the regeneration of cartilage tissue, mainly in diarthroses. In the induction of the MSCs, in addition to cytodifferentiation, the microenvironmental context of the tissue to be regenerated and an appropriate spatial arrangement are extremely important factors. Furthermore, it is known that MSC differentiation is fundamentally determined by mechanisms such as cell proliferation (mitosis), biochemical-molecular interactions, movement, cell adhesion, and apoptosis. Although the use of MSCs for cartilage regeneration remains at a research level, there are important questions to be resolved in order to make this therapy efficient and safe. It is known, for instance, that the expansion of chondrocytes in cultivation, needed to increase the number of cells, could end up producing fibrocartilage instead of hyaline cartilage. However, the latest results are promising. In 2014, the first stage I/II clinical trial to evaluate the efficacy and safety of the intra-articular injection of MSCs in femorotibial cartilage regeneration was published, indicating a decrease in injured areas. One issue to be explored is how many modifications in the articulate inflammatory environment could induce differentiation of MSCs already allocated in that region. Such issue arose from studies that suggested that the suppression of the inflammation may increase the efficiency of tissue regeneration. Considering the complexity of the events related to the chondrogenesis and cartilage repair, it can be concluded that the road ahead is still long, and that further studies are needed.

  16. Dual RNA-sequencing of Eucalyptus nitens during Phytophthora cinnamomi challenge reveals pathogen and host factors influencing compatibility

    Directory of Open Access Journals (Sweden)

    Febe Elizabeth Meyer

    2016-03-01

    Full Text Available Damage caused by Phytophthora cinnamomi Rands remains an important concern on forest tree species. The pathogen causes root and collar rot, stem cankers and dieback of various economically important Eucalyptus spp. In South Africa, susceptible cold tolerant Eucalyptus plantations have been affected by various Phytophthora spp. with P. cinnamomi considered one of the most virulent. The molecular basis of this compatible interaction is poorly understood. In this study, susceptible Eucalyptus nitens plants were stem inoculated with P. cinnamomi and tissue was harvested five days post inoculation. Dual RNA-sequencing, a technique which allows the concurrent detection of both pathogen and host transcripts during infection, was performed. Approximately 1% of the reads mapped to the draft genome of P. cinnamomi while 78% of the reads mapped to the Eucalyptus grandis genome. The highest expressed P. cinnamomi gene in planta was a putative crinkler effector (CRN1. Phylogenetic analysis indicated the high similarity of this P. cinnamomi CRN1 to that of Phytophthora infestans. Some CRN effectors are known to target host nuclei to suppress defense. In the host, over 1400 genes were significantly differentially expressed in comparison to mock inoculated trees, including suites of pathogenesis related (PR genes. In particular, a PR-9 peroxidase gene with a high similarity to a Carica papaya PR-9 ortholog previously shown to be suppressed upon infection by Phytophthora palmivora was down-regulated two-fold. This PR-9 gene may represent a cross-species effector target during P. cinnamomi infection. This study identified pathogenicity factors, potential manipulation targets and attempted host defense mechanisms activated by E. nitens that contributed to the susceptible outcome of the interaction.

  17. Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety.

    Science.gov (United States)

    Panda, R; Ariyarathna, H; Amnuaycheewa, P; Tetteh, A; Pramod, S N; Taylor, S L; Ballmer-Weber, B K; Goodman, R E

    2013-02-01

    Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15-fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop.

  18. Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges

    Science.gov (United States)

    Kim, Dana; Kim, Young-Sam; Shin, Dong Wun; Park, Chang-Shin

    2016-01-01

    No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

  19. Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges.

    Science.gov (United States)

    Kim, Dana; Kim, Young Sam; Shin, Dong Wun; Park, Chang Shin; Kang, Ju Hee

    2016-10-01

    No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

  20. Potential use and challenges of functional connectivity mapping in intractable epilepsy

    Directory of Open Access Journals (Sweden)

    Robert Todd Constable

    2013-05-01

    Full Text Available This review focuses on the use of resting-state functional magnetic resonance imaging data to assess functional connectivity in the human brain for surgical planning in intractable epilepsy. This approach has the potential to predict outcomes for a given surgical procedure based on the pre-surgical functional organization of the brain. Functional connectivity can also identify cortical regions that are organized differently in epilepsy patients either as a direct function of the disease or through indirect compensatory responses. Functional connectivity mapping can also potentially help identify epileptogenic tissue, whether this is a single focal location or a network of seizure-generating tissues and this information can assist in guiding the implantation of electrodes for invasive monitoring. This review covers the basics of connectivity analysis and discusses particular issues associated with analyzing such data. These issues include how to define nodes, as well as differences between connectivity analyses of individual nodes, groups of nodes, and whole-brain assessment at the voxel level. The need for arbitrary thresholds in some connectivity analyses is discussed and a solution to this problem is reviewed. Overall, functional connectivity analysis is becoming an important tool for assessing functional brain organization in surgical planning in epilepsy.

  1. Wastewater sludge - the challenges. What are the potentials of utilising the resources in sludge?

    Energy Technology Data Exchange (ETDEWEB)

    Kroiss, Helmut

    2003-07-01

    The actual best practice of urban water management has developed during the last 200 years and consists of: safe and reliable drinking water supply, sewerage to prevent hygienic problems and flooding in the settlements, mechanical -biological waste water treatment for receiving water protection. The hygienic and environmental goals of the urban water system have to be attained with a minimum of costs. Most of the drinking water supplied is used for the transport of pollution originating from human metabolism, washing and cleaning. Waste water contains all the substances which enter human metabolism as food, beverages, pharmaceuticals, a great variety of household chemicals and the substances discharged from trade and industry to the sewer system. Rain water is already contaminated by air pollution when it reaches the soil or other surfaces. Whatever material the rainwater gets into contact can be found in the waste water. As a consequence the composition of the waste water is a mirror of our civilisation and of human and urban metabolism. Waste water treatment results in two products which are closely related in their chemical composition: (1) treated waste water to be discharged to the receiving water, (2) wastewater sludge to be treated and disposed or (re)used without creating new (environmental) problems. All the compounds entering the waste water which are not completely degraded can be found in both products. The transfer coefficients between water and sludge differ widely and depend on physical and chemical equilibriums. The potentially hazardous compounds in the effluent and in the sludge belong to these compounds. Source control therefore is necessary for water protection and at the same time for low concentrations of potentially hazardous compounds in the sludge. It is also clear that improved biological treatment efficiency (longer sludge age) also results in lower loads of organic pollutants in the sludge, while physical-chemical treatment steps result

  2. Challenges and potential solutions for the connection of ESPAS, IUGONET and ISDC

    Science.gov (United States)

    Ritschel, B.; Borchert, F.; Kneitschel, G.; Neher, G.; Schildbach, S.; Iyemori, T.; Yatagai, A. I.; Koyama, Y.; Hori, T.; Hapgood, M. A.; Belehaki, A.; Galkin, I. A.; King, T. A.

    2013-12-01

    ESPAS and IUGONET are collaborative e-science infrastructure projects in the space weather and adjacent science domains. Whereas the ESPAS project - founded by the European Union (EU) - is bringing together more than 20 EU partner institutions, IUGONET is a Japanese only project based on the collaboration of 5 universities (7 organizations). ISDC is the data management system at GFZ German Research Centre for Geosciences for archiving and distribution of satellite and ground-based geodetic, geophysical and atmospheric data. Major objectives for the organization and realization of data management workflows and appropriate components are almost identical for the 3 systems. Centralized catalogs are filled via harvesting mechanism, and data search and provision is based on categorized metadata. Even though the data models are different, major entities and appropriate relationships are similar and used in the same way. The challenges in the connection of the systems are coming from the different technical realizations of the systems. The IUGONET system is based on DSPACE software using the SPASE data model. ESPAS is using ISO/OGC standards realized by D-NET system components. And for the development of a new ISDC system a semantic Web based approach using the ISDC ontology network consisting of merged domain and terminological ontologies is used. Proposals for the connection of the different systems have to take into account the operational status of the systems. The IUGONET system is up and running, the ESPAS system is in a realization phase, and the new ISDC system is still in a proof of concept phase. Interoperability can be realized step by step in different ways. A promising approach is the common development and use of a harmonized vocabulary for the annotation of data and context data. Standardized SKOS modeled terms derived from a combined thesauri (SPASE, GCMD, ...) can be used to connect identical or similar measurement data, and also data about used

  3. The Potential of RFID Technology in the Textile and Clothing Industry: Opportunities, Requirements and Challenges

    Science.gov (United States)

    Legnani, Elena; Cavalieri, Sergio; Pinto, Roberto; Dotti, Stefano

    In the current competitive environment, companies need to extensively exploit the use of advanced technologies in order to develop a sustainable advantage, enhance their operational efficiency and better serve customers. In this context, RFID technology has emerged as a valid support for the company progress and its value is becoming more and more apparent. In particular, the textile and clothing industry, characterised by short life-cycles , quick response production , fast distribution, erratic customer preferences and impulsive purchasing, is one of the sectors which can extensively benefit from the RFID technology. However, actual applications are still very limited, especially in the upstream side of the supply network. This chapter provides an insight into the main benefits and potentials of this technology and highlights the main issues which are currently inhibiting its large scale development in the textile and clothing industry. The experience of two industry-academia projects and the relative fallouts are reported.

  4. Transition metal dimers as potential molecular magnets: A challenge to computational chemistry

    CERN Document Server

    Fritsch, Daniel; Richter, Manuel; Eschrig, Helmut

    2008-01-01

    Dimers are the smallest chemical objects that show magnetic anisotropy. We focus on 3$d$ and 4$d$ transition metal dimers that have magnetic ground states in most cases. Some of these magnetic dimers have a considerable barrier against re-orientation of their magnetization, the so-called magnetic anisotropy energy, MAE. The height of this barrier is important for technological applications, as it determines, e.g., the stability of information stored in magnetic memory devices. It can be estimated by means of relativistic density functional calculations. Our approach is based on a full-potential local-orbital method (FPLO) in a four-component Dirac-Kohn-Sham implementation. Orbital polarization corrections to the local density approximation are employed. They are discussed in the broader context of orbital dependent density functionals. Ground state properties (spin multiplicity, bond length, harmonic vibrational frequency, spin- and orbital magnetic moment, and MAE) of the 3$d$ and 4$d$ transition metal dimer...

  5. The learning potentials and challenges when integrating Web 2.0 in a problem-based learning approach

    DEFF Research Database (Denmark)

    Buus, Lillian

    and “elements” in motion. The authors' assumption is built on the perspective that knowledge is constructed in social collaborative interactions between people. Furthermore, she claims that the ideology of Web 2.0 provides research opportunities to study phenomena also found in PBL and networked learning...... potentials, which show that this combination of Web 2.0, PBL and networked learning is able to develop and enhance students’ different skills and competences supporting the ideology within the two areas of pedagogy. Besides the learning potentials, she presents challenges or tensions, which can be seen...... as points of awareness in integrating Web 2.0-mediated learning activities and technology. These can be seen at different organisational levels. The research furthermore shows that there is a need to organise some kind of organisational support unit to scaffold and facilitate teachers’ design and implement...

  6. An overview of current practice in external beam radiation oncology with consideration to potential benefits and challenges for nanotechnology.

    Science.gov (United States)

    King, Raymond B; McMahon, Stephen J; Hyland, Wendy B; Jain, Suneil; Butterworth, Karl T; Prise, Kevin M; Hounsell, Alan R; McGarry, Conor K

    2017-01-01

    Over the past two decades, there has been a significant evolution in the technologies and techniques employed within the radiation oncology environment. Over the same period, extensive research into the use of nanotechnology in medicine has highlighted a range of potential benefits to its incorporation into clinical radiation oncology. This short communication describes key tools and techniques that have recently been introduced into specific stages of a patient's radiotherapy pathway, including diagnosis, external beam treatment and subsequent follow-up. At each pathway stage, consideration is given towards how nanotechnology may be combined with clinical developments to further enhance their benefit, with some potential opportunities for future research also highlighted. Prospective challenges that may influence the introduction of nanotechnology into clinical radiotherapy are also discussed, indicating the need for close collaboration between academic and clinical staff to realise the full clinical benefit of this exciting technology.

  7. From Amazonia to the Atlantic forest: molecular phylogeny of Phyzelaphryninae frogs reveals unexpected diversity and a striking biogeographic pattern emphasizing conservation challenges.

    Science.gov (United States)

    Fouquet, Antoine; Loebmann, Daniel; Castroviejo-Fisher, Santiago; Padial, José M; Orrico, Victor G D; Lyra, Mariana L; Roberto, Igor Joventino; Kok, Philippe J R; Haddad, Célio F B; Rodrigues, Miguel T

    2012-11-01

    Documenting the Neotropical amphibian diversity has become a major challenge facing the threat of global climate change and the pace of environmental alteration. Recent molecular phylogenetic studies have revealed that the actual number of species in South American tropical forests is largely underestimated, but also that many lineages are millions of years old. The genera Phyzelaphryne (1 sp.) and Adelophryne (6 spp.), which compose the subfamily Phyzelaphryninae, include poorly documented, secretive, and minute frogs with an unusual distribution pattern that encompasses the biotic disjunction between Amazonia and the Atlantic forest. We generated >5.8 kb sequence data from six markers for all seven nominal species of the subfamily as well as for newly discovered populations in order to (1) test the monophyly of Phyzelaphryninae, Adelophryne and Phyzelaphryne, (2) estimate species diversity within the subfamily, and (3) investigate their historical biogeography and diversification. Phylogenetic reconstruction confirmed the monophyly of each group and revealed deep subdivisions within Adelophryne and Phyzelaphryne, with three major clades in Adelophryne located in northern Amazonia, northern Atlantic forest and southern Atlantic forest. Our results suggest that the actual number of species in Phyzelaphryninae is, at least, twice the currently recognized species diversity, with almost every geographically isolated population representing an anciently divergent candidate species. Such results highlight the challenges for conservation, especially in the northern Atlantic forest where it is still degraded at a fast pace. Molecular dating revealed that Phyzelaphryninae originated in Amazonia and dispersed during early Miocene to the Atlantic forest. The two Atlantic forest clades of Adelophryne started to diversify some 7 Ma minimum, while the northern Amazonian Adelophryne diversified much earlier, some 13 Ma minimum. This striking biogeographic pattern coincides with

  8. Online professional development for inservice teachers in Information and Communication Technology: Potentials and challenges

    Directory of Open Access Journals (Sweden)

    George Zhou

    2008-03-01

    Full Text Available The purpose of this study was to evaluate an online professional development course for inservice teachers in the area of information and communication technology (ICT and concurrently explore the factors that influence online professional development. The study integrated quantitative and qualitative methods including survey, focus group and interview, and was conducted during the progress of the course and approximately nine months after the course was over. Data show that the online delivery of ICT professional development for inservice teachers was successful. However, a learning community was difficult to initiate in an online learning environment. Teacher participants experienced great challenges when applying what they learned from the course into their teaching. The study suggests that further online ICT professional development should incorporate face-to-face sessions and enrol more than one teacher from the same school. Professional development aiming at changes should be considered as an ongoing process and supported with school change. Résumé : L’objet de la présente étude consistait à évaluer un cours de perfectionnement professionnel en ligne pour les enseignants qualifiés dans le domaine des technologies de l’information et de la communication et à étudier les facteurs qui ont de l’influence sur le perfectionnement professionnel en ligne. L’étude a tenu compte de méthodes quantitatives et qualitatives, notamment un sondage, un groupe de discussion et une entrevue réalisée alors que le cours était donné et environ neuf mois après la fin du cours. Les données indiquent que la prestation en ligne du cours sur le perfectionnement professionnel sur les technologies de l’information et de la communication pour les enseignants qualifiés s’est avérée une réussite. Toutefois, il a été difficile d’initier une communauté d’apprentissage au milieu de l’apprentissage en ligne. Les enseignants

  9. The potential of geotourism to meet the challenges of geoconservation in Oman

    Science.gov (United States)

    Roepert, A.; Zacke, A.; Hoffmann, G.

    2012-04-01

    Geoconservation as well as the concept of geological heritage has been understood as a new challenge for geological research in the last decades. Traditionally, the approach to geology has been more often linked to the exploitation of resources rather than to preservation of sites of geological value. In many countries the protection of geological sites is connected to the protection of biodiversity. The Sultanate of Oman is situated in the north-eastern part of the Arabian Peninsula. During Late Cretaceous large parts of former Tethyan oceanic crust were obducted onto the Arabian plate to form one of the world's best exposed and best studied ophiolites (Searle and Cox, 1999). The Semail Ophiolite might be the best known example of Oman's geological heritage. However, the country offers far more geological features which are spectacular or unique. To name just a few, there are e.g. Neoproterocoic glacial sediments (Allen, 2007); surface piercing salt-domes (Al Siyabi and Newall, 2005); huge sand-deserts (Goudie et al., 1999); a mountain-range 3000 m high with spectacular canyons as Wadi Nakhr (Kusky et al., 2005); as well as outcropping Moho (Boudier and Nicolas, 1995). As the country is located in the arid to semiarid climatic zone, soil-development is very limited as is vegetation cover. Therefore the geology is easy accessible - a fact that attracts more and more geosciences students to study geology in the field, as well as tourists to enjoy the spectacular scenery. However, concerning the whole field of nature conservation, Oman just started facing the fact of increasing destruction of landscapes including endangering of biodiversity. The country's economic development mainly took place within the last 40 years. Large infrastructure projects are under construction to meet the needs of ongoing development of land and resources. As a consequence thereof geological heritage is in danger of being destroyed due to lack of awareness. The aim of this study is to

  10. Ice thickness estimations based on multi-temporal glacier inventories - potential and challenges

    Science.gov (United States)

    Helfricht, Kay; Huss, Matthias; Otto, Jan-Christoph

    2016-04-01

    The ongoing glacier retreat exposes a large number of surface depressions in the former glacier bed that can be filled with water or act as sediment traps. This has already been observed at various sites in Austria and in other mountain areas worldwide. The formation of glacial lakes can constitute an important environmental and socio-economic impact on high mountain systems including water resource management, sediment delivery, natural hazards, energy production and tourism. In general, information on ice thickness distribution is the basis for simulating future glacier change. We used the approach proposed by Huss and Farinotti (2012) to model the ice thickness distribution and potential locations of subglacial depressions. The study is part of the FUTURELAKE project that seeks to model the formation of new glacier lakes and their possible future evolution in the Austria Alps. The required data on glacier extent, surface elevation and slope were taken from the Austrian Glacier Inventories GI1 from 1969, GI2 from 1998 and GI3 from2006 (Fischer et al., 2015). The different glacier outlines and surface elevations from the inventories enable us to evaluate (i) the robustness of the modelled bedrock depressions with respect to different glacier settings, (ii) the power of the model to simulate recently formed glacial lakes, (iii) the similarities in calculated ice thickness distributions across the inventories and (iv) the feasibility of simulating observed changes in ice thickness and glacier volume. In general, the modelled localization of large potential depressions was relatively stable using the observed glacier settings. A number of examples show that recently formed glacial lakes could be detected by the model based on previous glacier extents. The locations of maximum ice depths within different elevation zones appeared to be sensitive to changes in glacier width. However, observed ice thickness changes and, thus, volume changes between the inventories could

  11. Potential Challenges Faced by the U.S. Chemicals Industry under a Carbon Policy

    Directory of Open Access Journals (Sweden)

    Andrea Bassi

    2009-09-01

    Full Text Available Chemicals have become the backbone of manufacturing within industrialized economies. Being energy-intensive materials to produce, this sector is threatened by policies aimed at combating and adapting to climate change. This study examines the worst-case scenario for the U.S. chemicals industry when a medium CO2 price policy is employed. After examining possible industry responses, the study goes on to identify and provide a preliminary evaluation of potential opportunities to mitigate these impacts. If climate regulations are applied only in the United States, and no action is taken to invest in advanced low- and no-carbon technologies to mitigate the impacts of rising energy costs, the examination shows that climate policies that put a price on carbon could have substantial impacts on the competiveness of the U.S. chemicals industry over the next two decades. In the long run, there exist technologies that are available to enable the chemicals sector to achieve sufficient efficiency gains to offset and manage the additional energy costs arising from a climate policy.

  12. Potential and challenges of interdisciplinary research on historical window glass, stained glass and reverse glass paintings

    Science.gov (United States)

    Trümpler, Stefan; Wolf, Sophie; Kessler, Cordula; Goll, Jürg

    The interdisciplinary study of ancient materials has become an increasingly common strategy, mainly because it has proved to be a highly rewarding approach to studying the age, provenance and production of archaeological objects. The results of such an approach sometimes also provide answers to questions relating not only to socio-cultural, economic or technological developments in a particular region or period (trade, innovation, production etc.), but also the conservation of the materials or artefacts in question. A number of analytical methods, ranging from microscopic to elementary analyses, have been successfully applied to determine the nature of materials and technologies used in the production, as well as to identify the provenance of ancient glass. As far as window glass and stained glass is concerned, the study of architectural context and art history - as well as the technological characteristics of materials - has proved to be most helpful in determining history, production and artistic importance of the objects under study. This paper discusses some of the multidisciplinary studies that the Vitrocentre Romont has conducted on early medieval window glass, stained glass and reverse glass paintings and illustrates the potential of a holistic approach in solving questions about materials, techniques, window design and conservation. It also addresses the limitations of the approach, which are often related to finding appropriate (i.e. non-destructive and possibly portable) methods for the analysis of sometimes extremely fragile stained glass windows.

  13. Technical Challenges in Current Primo Vascular System Research and Potential Solutions.

    Science.gov (United States)

    Kang, Kyung A; Maldonado, Claudio; Vodyanoy, Vitaly

    2016-12-01

    Since Bonghan Kim's discovery of the Bonghan system (BHS) in the 1960s, numerous reports have suggested that the system is fundamental for maintaining mammalian life. The BHS is a circulatory system independent of the blood or the lymphatic system, forms an extensive network throughout the entire mammalian body, has been reported to be the acupuncture meridian, stores distinct types of stem cells, and appears to have some roles in cancer metastasis. Despite Kim's first report having been published as early as 1962, research progress has been rather slow mainly because the system is very small and translucent, making it optically difficult to distinguish it from the hemoglobin-rich surrounding tissues. Unfortunately, Kim did not describe in detail the methods that he used for identifying and harvesting the system and the components of the system. In 2000, Kwang-Sup Soh reopened the BHS research, and since then, new and important scientific findings on the system have been reported, and many of Kim's results have been verified. In 2010, the BHS was renamed the primo vascular system. Nevertheless, good tools to properly deal with this system are still lacking. In this article, we address some of the technical difficulties involved in studying the primo vascular system and attempt to discuss potential ways to overcome those difficulties.

  14. Metabolic Engineering of Eukaryotic Microalgae: Potential and Challenges come with great diversity

    Directory of Open Access Journals (Sweden)

    Javier A Gimpel

    2015-12-01

    Full Text Available The great phylogenetic diversity of microalgae is corresponded by a wide arrange of interesting and useful metabolites. Nonetheless metabolic engineering in microalgae has been limited, since specific transformation tools must be developed for each species for either the nuclear or chloroplast genomes. Microalgae as production platforms for metabolites offer several advantages over plants and other microorganisms, like the ability of GMO containment and reduced costs in culture media, respectively. Currently, microalgae have proved particularly well suited for the commercial production of omega-3 fatty acids and carotenoids. Therefore most metabolic engineering strategies have been developed for these metabolites. Microalgal biofuels have also drawn great attention recently, resulting in efforts for improving the production of hydrogen and photosynthates, particularly triacylglycerides. Metabolic pathways of microalgae have also been manipulated in order to improve photosynthetic growth under specific conditions and for achieving trophic conversion. Although these pathways are not strictly related to secondary metabolites, the synthetic biology approaches could potentially be translated to this field and will also be discussed.

  15. Technical Challenges in Current Primo Vascular System Research and Potential Solutions

    Directory of Open Access Journals (Sweden)

    Kyung A. Kang

    2016-12-01

    Full Text Available Since Bonghan Kim's discovery of the Bonghan system (BHS in the 1960s, numerous reports have suggested that the system is fundamental for maintaining mammalian life. The BHS is a circulatory system independent of the blood or the lymphatic system, forms an extensive network throughout the entire mammalian body, has been reported to be the acupuncture meridian, stores distinct types of stem cells, and appears to have some roles in cancer metastasis. Despite Kim's first report having been published as early as 1962, research progress has been rather slow mainly because the system is very small and translucent, making it optically difficult to distinguish it from the hemoglobin-rich surrounding tissues. Unfortunately, Kim did not describe in detail the methods that he used for identifying and harvesting the system and the components of the system. In 2000, Kwang-Sup Soh reopened the BHS research, and since then, new and important scientific findings on the system have been reported, and many of Kim's results have been verified. In 2010, the BHS was renamed the primo vascular system. Nevertheless, good tools to properly deal with this system are still lacking. In this article, we address some of the technical difficulties involved in studying the primo vascular system and attempt to discuss potential ways to overcome those difficulties.

  16. In Metabolic Engineering of Eukaryotic Microalgae: Potential and Challenges Come with Great Diversity

    Science.gov (United States)

    Gimpel, Javier A.; Henríquez, Vitalia; Mayfield, Stephen P.

    2015-01-01

    The great phylogenetic diversity of microalgae is corresponded by a wide arrange of interesting and useful metabolites. Nonetheless metabolic engineering in microalgae has been limited, since specific transformation tools must be developed for each species for either the nuclear or chloroplast genomes. Microalgae as production platforms for metabolites offer several advantages over plants and other microorganisms, like the ability of GMO containment and reduced costs in culture media, respectively. Currently, microalgae have proved particularly well suited for the commercial production of omega-3 fatty acids and carotenoids. Therefore most metabolic engineering strategies have been developed for these metabolites. Microalgal biofuels have also drawn great attention recently, resulting in efforts for improving the production of hydrogen and photosynthates, particularly triacylglycerides. Metabolic pathways of microalgae have also been manipulated in order to improve photosynthetic growth under specific conditions and for achieving trophic conversion. Although these pathways are not strictly related to secondary metabolites, the synthetic biology approaches could potentially be translated to this field and will also be discussed. PMID:26696985

  17. O-GlcNAcomics--Revealing roles of O-GlcNAcylation in disease mechanisms and development of potential diagnostics.

    Science.gov (United States)

    Copeland, Ronald J; Han, Guanghui; Hart, Gerald W

    2013-10-01

    O-linked-β-N-acetylglucosamine (O-GlcNAc) is a dynamic PTM of the 3'-hydroxyl groups of serine or threonine residues of nuclear, cytoplasmic, and mitochondrial proteins. The cycling of this modification is regulated in response to nutrients, stress, and other extracellular stimuli by the catalytic activities of O-GlcNAc transferase and O-GlcNAcase. O-GlcNAc is functionally similar to phosphorylation and has been demonstrated to play critical roles in numerous biological processes, including cell signaling, transcription, and disease etiology. Since its discovery nearly 30 years ago, studies have demonstrated that the O-GlcNAc is highly abundant and widespread, like phosphorylation however, the development of methodologies to study O-GlcNAc at the site level has been challenging. Recently, a number of studies have overcome these challenges and describe new tagging, enrichment, and mass spectrometric-based approaches to study O-GlcNAc in terms of its site identification, stoichiometry, and dynamics on proteins. The development of these methods are key for elucidation of O-GlcNAc's functional crosstalk with phosphorylation and other PTMs, and will serve to provide the necessary information for the development of site-specific antibodies, which will aid in the determination of a particular protein's site-specific function. In this review, we describe these methods and summarize results obtained from them demonstrating the roles of O-GlcNAc in diabetes, cancer, Alzheimer's, and in learning and memory, while also describing how these new strategies have implicated O-GlcNAc as a potential diagnostic for the screening of patients for prediabetes.

  18. World Biofuels Production Potential Understanding the Challenges to Meeting the U.S. Renewable Fuel Standard

    Energy Technology Data Exchange (ETDEWEB)

    Sastri, B.; Lee, A.

    2008-09-15

    This study by the U.S. Department of Energy (DOE) estimates the worldwide potential to produce biofuels including biofuels for export. It was undertaken to improve our understanding of the potential for imported biofuels to satisfy the requirements of Title II of the 2007 Energy Independence and Security Act (EISA) in the coming decades. Many other countries biofuels production and policies are expanding as rapidly as ours. Therefore, we modeled a detailed and up-to-date representation of the amount of biofuel feedstocks that are being and can be grown, current and future biofuels production capacity, and other factors relevant to the economic competitiveness of worldwide biofuels production, use, and trade. The Oak Ridge National Laboratory (ORNL) identified and prepared feedstock data for countries that were likely to be significant exporters of biofuels to the U.S. The National Renewable Energy Laboratory (NREL) calculated conversion costs by conducting material flow analyses and technology assessments on biofuels technologies. Brookhaven National Laboratory (BNL) integrated the country specific feedstock estimates and conversion costs into the global Energy Technology Perspectives (ETP) MARKAL (MARKet ALlocation) model. The model uses least-cost optimization to project the future state of the global energy system in five year increments. World biofuels production was assessed over the 2010 to 2030 timeframe using scenarios covering a range U.S. policies (tax credits, tariffs, and regulations), as well as oil prices, feedstock availability, and a global CO{sub 2} price. All scenarios include the full implementation of existing U.S. and selected other countries biofuels policies (Table 4). For the U.S., the most important policy is the EISA Title II Renewable Fuel Standard (RFS). It progressively increases the required volumes of renewable fuel used in motor vehicles (Appendix B). The RFS requires 36 billion (B) gallons (gal) per year of renewable fuels by 2022

  19. Reproductive concerns of children and adolescents with cancer: challenges and potential solutions

    Directory of Open Access Journals (Sweden)

    Stern C

    2013-06-01

    Full Text Available Catharyn Stern,1 Rachel Conyers,2 Lisa Orme,2 Shlomi Barak,1,3 Franca Agresta,1 John Seymour2 1Melbourne IVF and Royal Women's Hospital, 2Peter MacCallum Cancer Centre, Melbourne, and University of Melbourne, 3Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia Abstract: The diagnosis of a potentially life-threatening cancer is one of the most traumatic events that can befall a young person and his or her family. However, fortunately, most young people will survive their cancer and its treatment and go on to lead a long and healthy life, with an appropriate expectation of being able to have their own genetic family. However, cancer treatment, including surgery, chemotherapy, and radiotherapy, can have temporary and permanent effects on fertility, including damage to the uterus and pituitary gland, and reduction, or obliteration, of gonadal function, with consequential loss of oocytes or spermatozoa, which may result in ovarian or testicular failure. As the gamete pool is nonrenewable, permanent gonadal failure precludes subsequent fertility with a patient's own genetic material. Awareness and acknowledgement of the likely future fertility implications of cancer treatment is an essential part of any discussion about proposed therapies. Options for girls and young women include freezing mature oocytes and ovarian tissue, as well as attempting to protect the ovaries from the gonadotoxic effects of treatment. Options for boys and young men include semen collection and storage as well as testicular biopsy with freezing of testicular tissue or spermatozoa retrieved from the tissue. Fertility options can now be offered with increasing optimism about success and the provision of a genuine opportunity for having a family. While the initiation of cancer treatment is sometimes truly urgent, the opportunity for a detailed discussion about implications for fertility is of paramount importance for patients and

  20. Stem cell engineering for treatment of heart diseases: potentials and challenges.

    Science.gov (United States)

    Li, Shengwen Calvin; Wang, Lang; Jiang, Hong; Acevedo, Julyana; Chang, Anthony Christopher; Loudon, William Gunter

    2009-03-01

    Heart disorders are a major health concern worldwide responsible for millions of deaths every year. Among the many disorders of the heart, myocardial infarction, which can lead to the development of congestive heart failure, arrhythmias, or even death, has the most severe social and economic ramifications. Lack of sufficient available donor hearts for heart transplantation, the only currently viable treatment for heart failure other than medical management options (ACE inhibition, beta blockade, use of AICDs, etc.) that improve the survival of patients with heart failure emphasises the need for alternative therapies. One promising alternative replaces cardiac muscle damaged by myocardial infarction with new contractile cardiomyocytes and vessels obtained through stem cell-based regeneration. We report on the state of the art of recovery of cardiac functions by using stem cell engineering. Current research focuses on (a) inducing stem cells into becoming cardiac cells before or after injection into a host, (b) growing replacement heart tissue in vitro, and (c) stimulating the proliferation of the post-mitotic cardiomyocytes in situ. The most promising treatment option for patients is the engineering of new heart tissue that can be implanted into damaged areas. Engineering of cardiac tissue currently employs the use of co-culture of stem cells with scaffold microenvironments engineered to improve tissue survival and enhance differentiation. Growth of heart tissue in vitro using scaffolds, soluble collagen, and cell sheets has unique advantages. To compensate for the loss of ventricular mass and contractility of the injured cardiomyocytes, different stem cell populations have been extensively studied as potential sources of new cells to ameliorate the injured myocardium and eventually restore cardiac function. Unresolved issues including insufficient cell generation survival, growth, and differentiation have led to mixed results in preclinical and clinical studies

  1. From regenerative dentistry to regenerative medicine: progress, challenges, and potential applications of oral stem cells

    Directory of Open Access Journals (Sweden)

    Xiao L

    2014-12-01

    Full Text Available Li Xiao,1 Masanori Nasu2 1Department of Pharmacology, 2Research Center, The Nippon Dental University, Tokyo, Japan Abstract: Adult mesenchymal stem cells (MSCs and epithelial stem cells play essential roles in tissue repair and self-healing. Oral MSCs and epithelial stem cells can be isolated from adult human oral tissues, for example, teeth, periodontal ligament, and gingiva. Cocultivated adult oral epithelial stem cells and MSCs could represent some developmental events, such as epithelial invagination and tubular structure formation, signifying their potentials for tissue regeneration. Oral epithelial stem cells have been used in regenerative medicine over 1 decade. They are able to form a stratified cell sheet under three-dimensional culture conditions. Both experimental and clinical data indicate that the cell sheets can not only safely and effectively reconstruct the damaged cornea in humans, but also repair esophageal ulcer in animal models. Oral MSCs include dental pulp stem cells (DPSCs, stem cells from exfoliated deciduous teeth (SHED, stem cells from apical papilla (SCAP, periodontal ligament stem cells (PDLSCs, and mesenchymal stem cells from gingiva (GMSCs. They are widely applied in both regenerative dentistry and medicine. DPSCs, SHED, and SCAP are able to form dentin–pulp complex when being transplanted into immunodeficient animals. They have been experimentally used for the regeneration of dental pulp, neuron, bone muscle and blood vessels in animal models and have shown promising results. PDLSCs and GMSCs are demonstrated to be ideal cell sources for repairing the damaged tissues of periodontal, muscle, and tendon. Despite the abovementioned applications of oral stem cells, only a few human clinical trials are now underway to use them for the treatment of certain diseases. Since clinical use is the end goal, their true regenerative power and safety need to be further examined.Keywords: oral mesenchymal stem cells, oral

  2. From regenerative dentistry to regenerative medicine: progress, challenges, and potential applications of oral stem cells.

    Science.gov (United States)

    Xiao, Li; Nasu, Masanori

    2014-01-01

    Adult mesenchymal stem cells (MSCs) and epithelial stem cells play essential roles in tissue repair and self-healing. Oral MSCs and epithelial stem cells can be isolated from adult human oral tissues, for example, teeth, periodontal ligament, and gingiva. Cocultivated adult oral epithelial stem cells and MSCs could represent some developmental events, such as epithelial invagination and tubular structure formation, signifying their potentials for tissue regeneration. Oral epithelial stem cells have been used in regenerative medicine over 1 decade. They are able to form a stratified cell sheet under three-dimensional culture conditions. Both experimental and clinical data indicate that the cell sheets can not only safely and effectively reconstruct the damaged cornea in humans, but also repair esophageal ulcer in animal models. Oral MSCs include dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), periodontal ligament stem cells (PDLSCs), and mesenchymal stem cells from gingiva (GMSCs). They are widely applied in both regenerative dentistry and medicine. DPSCs, SHED, and SCAP are able to form dentin-pulp complex when being transplanted into immunodeficient animals. They have been experimentally used for the regeneration of dental pulp, neuron, bone muscle and blood vessels in animal models and have shown promising results. PDLSCs and GMSCs are demonstrated to be ideal cell sources for repairing the damaged tissues of periodontal, muscle, and tendon. Despite the abovementioned applications of oral stem cells, only a few human clinical trials are now underway to use them for the treatment of certain diseases. Since clinical use is the end goal, their true regenerative power and safety need to be further examined.

  3. Environmental engineering of navigation infrastructure: a survey of existing practices, challenges, and potential opportunities.

    Science.gov (United States)

    Fredette, Thomas J; Foran, Christy M; Brasfield, Sandra M; Suedel, Burton C

    2012-01-01

    Navigation infrastructure such as channels, jetties, river training structures, and lock-and-dam facilities are primary components of a safe and efficient water transportation system. Planning for such infrastructure has until recently involved efforts to minimize impacts on the environment through a standardized environmental assessment process. More recently, consistent with environmental sustainability concepts, planners have begun to consider how such projects can also be constructed with environmental enhancements. This study examined the existing institutional conditions within the US Army Corps of Engineers and cooperating federal agencies relative to incorporating environmental enhancements into navigation infrastructure projects. The study sought to (1) investigate institutional attitudes towards the environmental enhancement of navigation infrastructure (EENI) concept, (2) identify potential impediments to implementation and solutions to such impediments, (3) identify existing navigation projects designed with the express intent of enhancing environmental benefit in addition to the primary project purpose, (4) identify innovative ideas for increasing environmental benefits for navigation projects, (5) identify needs for additional technical information or research, and (6) identify laws, regulations, and policies that both support and hinder such design features. The principal investigation tool was an Internet-based survey with 53 questions. The survey captured a wide range of perspectives on the EENI concept including ideas, concerns, research needs, and relevant laws and policies. Study recommendations included further promotion of the concept of EENI to planners and designers, documentation of existing projects, initiation of pilot studies on some of the innovative ideas provided through the survey, and development of national goals and interagency agreements to facilitate implementation.

  4. Perceptual suppression revealed by adaptive multi-scale entropy analysis of local field potential in monkey visual cortex.

    Science.gov (United States)

    Hu, Meng; Liang, Hualou

    2013-04-01

    Generalized flash suppression (GFS), in which a salient visual stimulus can be rendered invisible despite continuous retinal input, provides a rare opportunity to directly study the neural mechanism of visual perception. Previous work based on linear methods, such as spectral analysis, on local field potential (LFP) during GFS has shown that the LFP power at distinctive frequency bands are differentially modulated by perceptual suppression. Yet, the linear method alone may be insufficient for the full assessment of neural dynamic due to the fundamentally nonlinear nature of neural signals. In this study, we set forth to analyze the LFP data collected from multiple visual areas in V1, V2 and V4 of macaque monkeys while performing the GFS task using a nonlinear method - adaptive multi-scale entropy (AME) - to reveal the neural dynamic of perceptual suppression. In addition, we propose a new cross-entropy measure at multiple scales, namely adaptive multi-scale cross-entropy (AMCE), to assess the nonlinear functional connectivity between two cortical areas. We show that: (1) multi-scale entropy exhibits percept-related changes in all three areas, with higher entropy observed during perceptual suppression; (2) the magnitude of the perception-related entropy changes increases systematically over successive hierarchical stages (i.e. from lower areas V1 to V2, up to higher area V4); and (3) cross-entropy between any two cortical areas reveals higher degree of asynchrony or dissimilarity during perceptual suppression, indicating a decreased functional connectivity between cortical areas. These results, taken together, suggest that perceptual suppression is related to a reduced functional connectivity and increased uncertainty of neural responses, and the modulation of perceptual suppression is more effective at higher visual cortical areas. AME is demonstrated to be a useful technique in revealing the underlying dynamic of nonlinear/nonstationary neural signal.

  5. Bile acid-induced virulence gene expression of Vibrio parahaemolyticus reveals a novel therapeutic potential for bile acid sequestrants.

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Gotoh

    Full Text Available Vibrio parahaemolyticus, a bacterial pathogen, causes human gastroenteritis. A type III secretion system (T3SS2 encoded in pathogenicity island (Vp-PAI is the main contributor to enterotoxicity and expression of Vp-PAI encoded genes is regulated by two transcriptional regulators, VtrA and VtrB. However, a host-derived inducer for the Vp-PAI genes has not been identified. Here, we demonstrate that bile induces production of T3SS2-related proteins under osmotic conditions equivalent to those in the intestinal lumen. We also show that bile induces vtrA-mediated vtrB transcription. Transcriptome analysis of bile-responsive genes revealed that bile strongly induces expression of Vp-PAI genes in a vtrA-dependent manner. The inducing activity of bile was diminished by treatment with bile acid sequestrant cholestyramine. Finally, we demonstrate an in vivo protective effect of cholestyramine on enterotoxicity and show that similar protection is observed in infection with a different type of V. parahaemolyticus or with non-O1/non-O139 V. cholerae strains of vibrios carrying the same kind of T3SS. In summary, these results provide an insight into how bacteria, through the ingenious action of Vp-PAI genes, can take advantage of an otherwise hostile host environment. The results also reveal a new therapeutic potential for widely used bile acid sequestrants in enteric bacterial infections.

  6. Post-genomic analyses of fungal lignocellulosic biomass degradation reveal the unexpected potential of the plant pathogen Ustilago maydis

    Directory of Open Access Journals (Sweden)

    Couturier Marie

    2012-02-01

    Full Text Available Abstract Background Filamentous fungi are potent biomass degraders due to their ability to thrive in ligno(hemicellulose-rich environments. During the last decade, fungal genome sequencing initiatives have yielded abundant information on the genes that are putatively involved in lignocellulose degradation. At present, additional experimental studies are essential to provide insights into the fungal secreted enzymatic pools involved in lignocellulose degradation. Results In this study, we performed a wide analysis of 20 filamentous fungi for which genomic data are available to investigate their biomass-hydrolysis potential. A comparison of fungal genomes and secretomes using enzyme activity profiling revealed discrepancies in carbohydrate active enzymes (CAZymes sets dedicated to plant cell wall. Investigation of the contribution made by each secretome to the saccharification of wheat straw demonstrated that most of them individually supplemented the industrial Trichoderma reesei CL847 enzymatic cocktail. Unexpectedly, the most striking effect was obtained with the phytopathogen Ustilago maydis that improved the release of total sugars by 57% and of glucose by 22%. Proteomic analyses of the best-performing secretomes indicated a specific enzymatic mechanism of U. maydis that is likely to involve oxido-reductases and hemicellulases. Conclusion This study provides insight into the lignocellulose-degradation mechanisms by filamentous fungi and allows for the identification of a number of enzymes that are potentially useful to further improve the industrial lignocellulose bioconversion process.

  7. Suppression substractive hybridisation (SSH) and real time PCR reveal differential gene expression in the Pacific cupped oyster, Crassostrea gigas, challenged with Ostreid herpesvirus 1.

    Science.gov (United States)

    Renault, T; Faury, N; Barbosa-Solomieu, V; Moreau, K

    2011-07-01

    Virus-induced genes were identified using suppression subtractive hybridisation (SSH) from Pacific cupped oyster, Crassostrea gigas, haemocytes challenged by OsHV-1. A total of 304 clones from SSH forward library were sequenced. Among these sequences, some homologues corresponded to (i) immune related genes (macrophage express protein, IK cytokine, interferon-induced protein 44 or multicopper oxidase), (ii) apoptosis related genes (Bcl-2) and (iii) cell signalling and virus receptor genes (glypican). Molecular characterization and phylogenic analysis of 3 immune-related genes (macrophage expressed protein, multicopper oxidase and immunoglobulin domain cell adhesion molecule) were performed. Finally, quantitative PCR revealed significant changes in the expression of immune related genes (multicopper oxidase, macrophage expressed protein, myeloid differentiation factor 88 and interferon-induced protein 44) in oysters experimentally challenged with OsHV-1. These findings provide a first basis for studying the role of innate immunity in response to viruses in bivalves and identified genes may serve as markers of interest in breeding programs in order to obtain selected oysters presenting OsHV-1 resistance.

  8. [Primary healthcare: a multidimensional study on challenges and potential in the São Paulo Metropolitan Region (SP, Brazil)].

    Science.gov (United States)

    Heimann, Luiza Sterman; Ibanhes, Lauro Cesar; Boaretto, Roberta Cristina; Castro, Iracema Ester do Nascimento; Telesi Júnior, Emilio; Cortizo, Carlos Tato; Fausto, Márcia Cristina Rodrigues; do Nascimento, Vânia Barbosa; Kayano, Jorge

    2011-06-01

    This paper presents some results of a case study in the Metropolitan Region of São Paulo (SP, Brazil) as part of a multicentric study conducted in Argentina, Brazil, Paraguay and Uruguay. The aim is to evaluate Primary Health Care (PHC) as a strategy to achieve integrated and universal healthcare systems. The methodological approach was based on five analytical dimensions: stewardship capability; financing; provision; comprehensiveness and intersectoral approach. The techniques included literature review, document analysis and interviews with key informants: policy makers; managers, experts, users and professionals. The results were organized in response to the challenges and possibilities of PHC as a structural system according to the five dimensions. The following emerged from the interviews: different interpretations on the concept and role of PHC and a consensus as the gateway to the system; weaknesses in funding; challenges in health workforce administration and the need for new legal-institutional design for regional management. The potential aspects were: broader coverage/universality, PHC as the basis for the organization of the system; connection with the territory and understanding specific population needs.

  9. ModM DNA methyltransferase methylome analysis reveals a potential role for Moraxella catarrhalis phasevarions in otitis media.

    Science.gov (United States)

    Blakeway, Luke V; Power, Peter M; Jen, Freda E-C; Worboys, Sam R; Boitano, Matthew; Clark, Tyson A; Korlach, Jonas; Bakaletz, Lauren O; Jennings, Michael P; Peak, Ian R; Seib, Kate L

    2014-12-01

    Moraxella catarrhalis is a significant cause of otitis media and exacerbations of chronic obstructive pulmonary disease. Here, we characterize a phase-variable DNA methyltransferase (ModM), which contains 5'-CAAC-3' repeats in its open reading frame that mediate high-frequency mutation resulting in reversible on/off switching of ModM expression. Three modM alleles have been identified (modM1-3), with modM2 being the most commonly found allele. Using single-molecule, real-time (SMRT) genome sequencing and methylome analysis, we have determined that the ModM2 methylation target is 5'-GAR(m6)AC-3', and 100% of these sites are methylated in the genome of the M. catarrhalis 25239 ModM2 on strain. Proteomic analysis of ModM2 on and off variants revealed that ModM2 regulates expression of multiple genes that have potential roles in colonization, infection, and protection against host defenses. Investigation of the distribution of modM alleles in a panel of M. catarrhalis strains, isolated from the nasopharynx of healthy children or middle ear effusions from patients with otitis media, revealed a statistically significant association of modM3 with otitis media isolates. The modulation of gene expression via the ModM phase-variable regulon (phasevarion), and the significant association of the modM3 allele with otitis media, suggests a key role for ModM phasevarions in the pathogenesis of this organism.

  10. The complete genome and proteome of Laribacter hongkongensis reveal potential mechanisms for adaptations to different temperatures and habitats.

    Directory of Open Access Journals (Sweden)

    Patrick C Y Woo

    2009-03-01

    Full Text Available Laribacter hongkongensis is a newly discovered Gram-negative bacillus of the Neisseriaceae family associated with freshwater fish-borne gastroenteritis and traveler's diarrhea. The complete genome sequence of L. hongkongensis HLHK9, recovered from an immunocompetent patient with severe gastroenteritis, consists of a 3,169-kb chromosome with G+C content of 62.35%. Genome analysis reveals different mechanisms potentially important for its adaptation to diverse habitats of human and freshwater fish intestines and freshwater environments. The gene contents support its phenotypic properties and suggest that amino acids and fatty acids can be used as carbon sources. The extensive variety of transporters, including multidrug efflux and heavy metal transporters as well as genes involved in chemotaxis, may enable L. hongkongensis to survive in different environmental niches. Genes encoding urease, bile salts efflux pump, adhesin, catalase, superoxide dismutase, and other putative virulence factors-such as hemolysins, RTX toxins, patatin-like proteins, phospholipase A1, and collagenases-are present. Proteomes of L. hongkongensis HLHK9 cultured at 37 degrees C (human body temperature and 20 degrees C (freshwater habitat temperature showed differential gene expression, including two homologous copies of argB, argB-20, and argB-37, which encode two isoenzymes of N-acetyl-L-glutamate kinase (NAGK-NAGK-20 and NAGK-37-in the arginine biosynthesis pathway. NAGK-20 showed higher expression at 20 degrees C, whereas NAGK-37 showed higher expression at 37 degrees C. NAGK-20 also had a lower optimal temperature for enzymatic activities and was inhibited by arginine probably as negative-feedback control. Similar duplicated copies of argB are also observed in bacteria from hot springs such as Thermus thermophilus, Deinococcus geothermalis, Deinococcus radiodurans, and Roseiflexus castenholzii, suggesting that similar mechanisms for temperature adaptation may be

  11. Comparative genomics of four closely related Clostridium perfringens bacteriophages reveals variable evolution among core genes with therapeutic potential

    Directory of Open Access Journals (Sweden)

    Siragusa Gregory R

    2011-06-01

    Full Text Available Abstract Background Because biotechnological uses of bacteriophage gene products as alternatives to conventional antibiotics will require a thorough understanding of their genomic context, we sequenced and analyzed the genomes of four closely related phages isolated from Clostridium perfringens, an important agricultural and human pathogen. Results Phage whole-genome tetra-nucleotide signatures and proteomic tree topologies correlated closely with host phylogeny. Comparisons of our phage genomes to 26 others revealed three shared COGs; of particular interest within this core genome was an endolysin (PF01520, an N-acetylmuramoyl-L-alanine amidase and a holin (PF04531. Comparative analyses of the evolutionary history and genomic context of these common phage proteins revealed two important results: 1 strongly significant host-specific sequence variation within the endolysin, and 2 a protein domain architecture apparently unique to our phage genomes in which the endolysin is located upstream of its associated holin. Endolysin sequences from our phages were one of two very distinct genotypes distinguished by variability within the putative enzymatically-active domain. The shared or core genome was comprised of genes with multiple sequence types belonging to five pfam families, and genes belonging to 12 pfam families, including the holin genes, which were nearly identical. Conclusions Significant genomic diversity exists even among closely-related bacteriophages. Holins and endolysins represent conserved functions across divergent phage genomes and, as we demonstrate here, endolysins can have significant variability and host-specificity even among closely-related genomes. Endolysins in our phage genomes may be subject to different selective pressures than the rest of the genome. These findings may have important implications for potential biotechnological applications of phage gene products.

  12. Heterogeneity in the developmental potential of motor neuron progenitors revealed by clonal analysis of single cells in vitro

    Directory of Open Access Journals (Sweden)

    Schieren Ira

    2009-01-01

    Full Text Available Abstract Background The differentiation of neural progenitors into distinct classes within the central nervous system occurs over an extended period during which cells become progressively restricted in their fates. In the developing spinal cord, Sonic Hedgehog (Shh controls neural fates in a concentration-dependent manner by establishing discrete ventral progenitor domains characterized by specific combinations of transcription factors. It is unclear whether motor neuron progenitors can maintain their identities when expanded in vitro and whether their developmental potentials are restricted when exposed to defined extracellular signals. Results We have generated mice expressing the enhanced green fluorescent protein under the control of the Nkx6.1 promoter, enabling fluorescence-activated cell sorting (FACS, purification and culture of individual spinal progenitors at clonal density, and analysis of their progeny. We demonstrate that cells isolated after progenitor domains are established are heterogeneous with respect to maintaining their identity after in vitro expansion. Most Nkx6.1+ progenitors lose their ventral identity following several divisions in culture, whereas a small subset is able to maintain its identity. Thus, subtype-restricted progenitors from the Nkx6.1+ region are present in the ventral spinal cord, although at a lower frequency than expected. Clones that maintain a motor neuron identity assume a transcriptional profile characteristic of thoracic motor neurons, despite some having been isolated from non-thoracic regions initially. Exposure of progenitors to Bone Morphogenetic Protein-4 induces some dorsal cell type characteristics in their progeny, revealing that lineage-restricted progenitor subtypes are not fully committed to their fates. Conclusion These findings support a model whereby continuous Shh signaling is required to maintain the identity of ventral progenitors isolated from the spinal cord, including motor

  13. Field transcriptome revealed critical developmental and physiological transitions involved in the expression of growth potential in japonica rice

    Directory of Open Access Journals (Sweden)

    Kamatsuki Kaori

    2011-01-01

    Full Text Available Abstract Background Plant growth depends on synergistic interactions between internal and external signals, and yield potential of crops is a manifestation of how these complex factors interact, particularly at critical stages of development. As an initial step towards developing a systems-level understanding of the biological processes underlying the expression of overall agronomic potential in cereal crops, a high-resolution transcriptome analysis of rice was conducted throughout life cycle of rice grown under natural field conditions. Results A wide range of gene expression profiles based on 48 organs and tissues at various developmental stages identified 731 organ/tissue specific genes as well as 215 growth stage-specific expressed genes universally in leaf blade, leaf sheath, and root. Continuous transcriptome profiling of leaf from transplanting until harvesting further elucidated the growth-stage specificity of gene expression and uncovered two major drastic changes in the leaf transcriptional program. The first major change occurred before the panicle differentiation, accompanied by the expression of RFT1, a putative florigen gene in long day conditions, and the downregulation of the precursors of two microRNAs. This transcriptome change was also associated with physiological alterations including phosphate-homeostasis state as evident from the behavior of several key regulators such as miR399. The second major transcriptome change occurred just after flowering, and based on analysis of sterile mutant lines, we further revealed that the formation of strong sink, i.e., a developing grain, is not the major cause but is rather a promoter of this change. Conclusions Our study provides not only the genetic basis for functional genomics in rice but also new insight into understanding the critical physiological processes involved in flowering and seed development, that could lead to novel strategies for optimizing crop productivity.

  14. Metabolomics approach reveals metabolic disorders and potential biomarkers associated with the developmental toxicity of tetrabromobisphenol A and tetrachlorobisphenol A

    Science.gov (United States)

    Ye, Guozhu; Chen, Yajie; Wang, Hong-Ou; Ye, Ting; Lin, Yi; Huang, Qiansheng; Chi, Yulang; Dong, Sijun

    2016-10-01

    Tetrabromobisphenol A and tetrachlorobisphenol A are halogenated bisphenol A (H-BPA), and has raised concerns about their adverse effects on the development of fetuses and infants, however, the molecular mechanisms are unclear, and related metabolomics studies are limited. Accordingly, a metabolomics study based on gas chromatography-mass spectrometry was employed to elucidate the molecular developmental toxicology of H-BPA using the marine medaka (Oryzias melastigmas) embryo model. Here, we revealed decreased synthesis of nucleosides, amino acids and lipids, and disruptions in the TCA (tricarboxylic acid) cycle, glycolysis and lipid metabolism, thus inhibiting the developmental processes of embryos exposed to H-BPA. Unexpectedly, we observed enhanced neural activity accompanied by lactate accumulation and accelerated heart rates due to an increase in dopamine pathway and a decrease in inhibitory neurotransmitters following H-BPA exposure. Notably, disorders of the neural system, and disruptions in glycolysis, the TCA cycle, nucleoside metabolism, lipid metabolism, glutamate and aspartate metabolism induced by H-BPA exposure were heritable. Furthermore, lactate and dopa were identified as potential biomarkers of the developmental toxicity of H-BPA and related genetic effects. This study has demonstrated that the metabolomics approach is a useful tool for obtaining comprehensive and novel insights into the molecular developmental toxicity of environmental pollutants.

  15. Phonological abilities in literacy-impaired children: Brain potentials reveal deficient phoneme discrimination, but intact prosodic processing

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    Claudia Männel

    2017-02-01

    Full Text Available Intact phonological processing is crucial for successful literacy acquisition. While individuals with difficulties in reading and spelling (i.e., developmental dyslexia are known to experience deficient phoneme discrimination (i.e., segmental phonology, findings concerning their prosodic processing (i.e., suprasegmental phonology are controversial. Because there are no behavior-independent studies on the underlying neural correlates of prosodic processing in dyslexia, these controversial findings might be explained by different task demands. To provide an objective behavior-independent picture of segmental and suprasegmental phonological processing in impaired literacy acquisition, we investigated event-related brain potentials during passive listening in typically and poor-spelling German school children. For segmental phonology, we analyzed the Mismatch Negativity (MMN during vowel length discrimination, capturing automatic auditory deviancy detection in repetitive contexts. For suprasegmental phonology, we analyzed the Closure Positive Shift (CPS that automatically occurs in response to prosodic boundaries. Our results revealed spelling group differences for the MMN, but not for the CPS, indicating deficient segmental, but intact suprasegmental phonological processing in poor spellers. The present findings point towards a differential role of segmental and suprasegmental phonology in literacy disorders and call for interventions that invigorate impaired literacy by utilizing intact prosody in addition to training deficient phonemic awareness.

  16. Sex-specific automatic responses to infant cries: TMS reveals greater excitability in females than males in motor evoked potentials

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    Irene eMessina

    2016-01-01

    Full Text Available Neuroimaging reveals that infant cries activate parts of the premotor cortical system. To validate this effect in a more direct way, we used event-related transcranial magnetic stimulation (TMS. Here, we investigated the presence and the time course of modulation of motor cortex excitability in young adults who listened to infant cries. Specifically, we recorded motor evoked potentials (MEPs from the biceps brachii (BB and interosseus dorsalis primus (ID1 muscles as produced by TMS delivered from 0 to 250 ms from sound onset in six steps of 50 ms in 10 females and 10 males. We observed an excitatory modulation of MEPs at 100 ms from the onset of the infant cry specific to females and to the ID1 muscle. We regard this modulation as a response to natural cry sounds because it was delayed, attenuated to stimuli increasingly different from natural cry, and was absent in a separate group of females who listened to non-cry stimuli physically matched to natural infant cries. Furthermore, the 100-ms latency of this modulation is not compatible with a voluntary reaction to the stimulus but suggests an automatic, bottom-up audiomotor association. The brains of adult females appear to be tuned to respond to infant cries with automatic motor excitation. This effect may reflect the greater and longstanding burden on females in caregiving infants.

  17. Comparative Analysis of JmjC Domain-containing Proteins Reveals the Potential Histone Demethylases in Arabidopsis and Rice

    Institute of Scientific and Technical Information of China (English)

    Falong Lu; Guanglin Li; Xia Cui; Chunyan Liu; Xiu-Jie Wang; Xiaofeng Cao

    2008-01-01

    Histone methylation homeostasis is achieved by controlling the balance between methylation and demethylation to maintain chromatin function and developmental regulation. In animals, a conserved Jumonji C (JmjC) domain was found In a large group of histone demethylases. However, it is still unclear whether plants also contain the JmjC domaincontaining active histone demethylases. Here we performed genome-wide screen and phylogenetic analysis of JmjC domaincontaining proteins in the dicot plant, Arabidopsis, and monocot plant rice, and found 21 and 20 JmjC domain-containing, respectively. We also examined the expression of JmjC domain-containing proteins and compared them to human JmjC counterparts for potential enzymatic activity. The spatial expression patterns of the Arabidopsis JmjC domaincontaining genes revealed that they are all actively transcribed genes. These active plant JmjC domain-containing genes could possibly function in epigenetic regulation to antagonize the activity of the large number of putative SET domaincontaining histone methyltransferase activity to dynamically regulate histone methylation homeostasis.

  18. Diminished social reward anticipation in the broad autism phenotype as revealed by event-related brain potentials.

    Science.gov (United States)

    Cox, Anthony; Kohls, Gregor; Naples, Adam J; Mukerji, Cora E; Coffman, Marika C; Rutherford, Helena J V; Mayes, Linda C; McPartland, James C

    2015-10-01

    Diminished responsivity to reward incentives is a key contributor to the social-communication problems seen in autism spectrum disorders (ASDs). Social motivation theories suggest that individuals with ASD do not experience social interactions as rewarding, leading to negative consequences for the development of brain circuitry subserving social information. In this study, we examined neural responses to social and non-social reward anticipation in 35 typically developing young adults, examining modulation of reward sensitivity by level of autistic traits. Using an Event-related potential incentive-delay task incorporating novel, more ecologically valid forms of reward, higher expression of autistic traits was associated with an attenuated P3 response to the anticipation of social (simulated real-time video feedback from an observer), but not non-social (candy), rewards. Exploratory analyses revealed that this was unrelated to mentalizing ability. The P3 component reflects motivated attention to reward signals, suggesting attenuated motivation allocation specific to social incentives. The study extends prior findings of atypical reward anticipation in ASD, demonstrating that attenuated social reward responsiveness extends to autistic traits in the range of typical functioning. Results support the development of innovative paradigms for investigating social and non-social reward responsiveness. Insight into vulnerabilities in reward processing is critical for understanding social function in ASD.

  19. Deep sequencing of Lotus corniculatus L. reveals key enzymes and potential transcription factors related to the flavonoid biosynthesis pathway.

    Science.gov (United States)

    Wang, Ying; Hua, Wenping; Wang, Jian; Hannoufa, Abdelali; Xu, Ziqin; Wang, Zhezhi

    2013-04-01

    Lotus corniculatus L. is used worldwide as a forage crop due to its abundance of secondary metabolites and its ability to grow in severe environments. Although the entire genome of L. corniculatus var. japonicus R. is being sequenced, the differences in morphology and production of secondary metabolites between these two related species have led us to investigate this variability at the genetic level, in particular the differences in flavonoid biosynthesis. Our goal is to use the resulting information to develop more valuable forage crops and medicinal materials. Here, we conducted Illumina/Solexa sequencing to profile the transcriptome of L. corniculatus. We produced 26,492,952 short reads that corresponded to 2.38 gigabytes of total nucleotides. These reads were then assembled into 45,698 unigenes, of which a large number associated with secondary metabolism were annotated. In addition, we identified 2,998 unigenes based on homology with L. japonicus transcription factors (TFs) and grouped them into 55 families. Meanwhile, a comparison of four tag-based digital gene expression libraries, built from the flowers, pods, leaves, and roots, revealed distinct patterns of spatial expression of candidate unigenes in flavonoid biosynthesis. Based on these results, we identified many key enzymes from L. corniculatus which were different from reference genes of L. japonicus, and five TFs that are potential enhancers in flavonoid biosynthesis. Our results provide initial genetics resources that will be valuable in efforts to manipulate the flavonoid metabolic pathway in plants.

  20. Assessment of the Bacteriocinogenic Potential of Marine Bacteria Reveals Lichenicidin Production by Seaweed-Derived Bacillus spp.

    Directory of Open Access Journals (Sweden)

    Gillian E. Gardiner

    2012-10-01

    Full Text Available The objectives of this study were (1 to assess the bacteriocinogenic potential of bacteria derived mainly from seaweed, but also sand and seawater, (2 to identify at least some of the bacteriocins produced, if any and (3 to determine if they are unique to the marine environment and/or novel. Fifteen Bacillus licheniformis or pumilus isolates with antimicrobial activity against at least one of the indicator bacteria used were recovered. Some, at least, of the antimicrobials produced were bacteriocins, as they were proteinaceous and the producers displayed immunity. Screening with PCR primers for known Bacillus bacteriocins revealed that three seaweed-derived Bacillus licheniformis harbored the bli04127 gene which encodes one of the peptides of the two-peptide lantibiotic lichenicidin. Production of both lichenicidin peptides was then confirmed by mass spectrometry. This is the first definitive proof of bacteriocin production by seaweed-derived bacteria. The authors acknowledge that the bacteriocin produced has previously been discovered and is not unique to the marine environment. However, the other marine isolates likely produce novel bacteriocins, as none harboured genes for known Bacillus bacteriocins.

  1. In silico serine β-lactamases analysis reveals a huge potential resistome in environmental and pathogenic species

    Science.gov (United States)

    Brandt, Christian; Braun, Sascha D.; Stein, Claudia; Slickers, Peter; Ehricht, Ralf; Pletz, Mathias W.; Makarewicz, Oliwia

    2017-01-01

    The secretion of antimicrobial compounds is an ancient mechanism with clear survival benefits for microbes competing with other microorganisms. Consequently, mechanisms that confer resistance are also ancient and may represent an underestimated reservoir in environmental bacteria. In this context, β-lactamases (BLs) are of great interest due to their long-term presence and diversification in the hospital environment, leading to the emergence of Gram-negative pathogens that are resistant to cephalosporins (extended spectrum BLs = ESBLs) and carbapenems (carbapenemases). In the current study, protein sequence databases were used to analyze BLs, and the results revealed a substantial number of unknown and functionally uncharacterized BLs in a multitude of environmental and pathogenic species. Together, these BLs represent an uncharacterized reservoir of potentially transferable resistance genes. Considering all available data, in silico approaches appear to more adequately reflect a given resistome than analyses of limited datasets. This approach leads to a more precise definition of BL clades and conserved motifs. Moreover, it may support the prediction of new resistance determinants and improve the tailored development of robust molecular diagnostics. PMID:28233789

  2. Revealing the challenges of low template DNA analysis with the prototype Ion AmpliSeq™ Identity panel v2.3 on the PGM™ Sequencer.

    Science.gov (United States)

    Elena, Salata; Alessandro, Agostino; Ignazio, Ciuna; Sharon, Wootton; Luigi, Ripani; Andrea, Berti

    2016-05-01

    Forensic scientists frequently have to deal with the analysis of challenging sources of DNA such as degraded and low template DNA (LtDNA). The capacity to genotype difficult biological traces has been facilitated by emerging technologies. Massive parallel sequencing (MPS) on microchip among other technologies promises high sensitivity and discrimination power. In this study we evaluated the combined use of the Quantifiler(®) Trio DNA Quantification Kit with the prototype Ion AmpliSeq™ Identity panel v2.3 and PGM™ platform in LtDNA samples. Coverage, allele balance, allele drop-out/in, consistency and variance were assessed. Overall, the results showed a great level of performance and consistency in terms of genotyping capability even under the most challenging conditions, making it possible to obtain consistent SNP profiles with 31 pg of DNA and partial informative profiles with as little as 5 pg or with severely degraded DNA. In addition, we demonstrated that the stochastic effects observed in some samples are due to the amplification of the library rather than sequencing. Based on our data, we proposed general recommendations for the analysis of casework samples starting from the use of quantification data, which proved to be critical in deciding whether to process the samples via STR (short tandem repeat) analysis or SNP MPS. In our experience, the use of the prototype Ion AmpliSeq™ Identity panel v2.3 has revealed a new applicable solution for processing LtDNAs. This approach provides users with an additional tool for analysis of traces that either would not give informative results with conventional STR-based techniques.

  3. Hepatoprotective potential of antioxidant potent fraction from Urtica dioica Linn. (whole plant in CCl4 challenged rats

    Directory of Open Access Journals (Sweden)

    Bhuwan Chandra Joshi

    2015-01-01

    Full Text Available The aim of the present study was to isolate hepatoprotective component from Urtica dioica Linn. (whole plant against CCl4-induced hepatotoxicity in-vitro (HepG2 cells and in-vivo (rats model. Antioxidant activity of hydro alcoholic extract and its fractions petroleum ether fraction (PEF, ethyl acetate fraction (EAF, n-butanol fraction (NBF and aqueous fraction (AF were determined by DPPH and NO radicals scavenging assay. Fractions were subjected to in-vitro HepG2 cell line study. Further, the most potent fraction (EAF was subjected to in-vivo hepatoprotective potential against CCl4 challenged rats. The in-vivo hepatoprotective active fraction was chromatographed on silica column to isolate the bioactive constituent(s. Structure elucidation was done by using various spectrophotometric techniques like UV, IR, 1H NMR, 13C NMR and MS spectroscopy. Ethyl acetate fraction (EAF of hydro-alcoholic extract of U. dioica possessed the potent antioxidant activity viz. DPPH (IC50 78.99 ± 0.17 μg/ml and NO (IC50101.39 ± 0.30 μg/ml. The in-vitro HepG2 cell line study showed that the EAF prevented the cell damage. The EAF significantly attenuated the increased liver enzymes activities in serum and oxidative parameters in tissue of CCl4-induced rats, suggesting hepatoprotective and anti-oxidant action respectively. Column chromatography of most potent antioxidant fraction (EAF lead to the isolation of 4-hydroxy-3-methoxy cinnamic acid (ferulic acid which is responsible for its hepatoprotective potential. Hence, the present study suggests that EAF of hydro-alcoholic extract has significant antioxidant and hepatoprotective potential on CCl4 induced hepatotoxicity in-vitro and in-vivo.

  4. The therapeutic potential, challenges and future clinical directions of stem cells from the Wharton's jelly of the human umbilical cord.

    Science.gov (United States)

    Bongso, Ariff; Fong, Chui-Yee

    2013-04-01

    Mesenchymal stem cells (MSCs) from bone marrow, adult organs and fetuses face the disadvantages of invasive isolation, limited cell numbers and ethical constraints while embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) face the clinical hurdles of potential immunorejection and tumorigenesis respectively. These challenges have prompted interest in the study and evaluation of stem cells from birth-associated tissues. The umbilical cord (UC) has been the most popular. Hematopoietic stem cells (HSCs) harvested from cord blood have been successfully used for the treatment of hematopoietic diseases. Stem cell populations have also been reported in other compartments of the UC viz., amnion, subamnion, perivascular region, Wharton's jelly, umbilical blood vessel adventia and endothelium. Differences in stemness characteristics between compartments have been reported and hence derivation protocols using whole UC pieces containing all compartments yield mixed stem cell populations with varied characteristics. Stem cells derived directly from the uncontaminated Wharton's jelly (hWJSCs) appear to offer the best clinical utility because of their unique beneficial properties. They are non-controversial, can be harvested painlessly in abundance, proliferative, possess stemness properties that last several passages in vitro, multipotent, hypoimmunogenic and do not induce tumorigenesis even though they have some ESC markers. hWJSCs and its extracts (conditioned medium and lysate) also possess anti-cancer properties and support HSC expansion ex vivo. They are thus attractive autologous or allogeneic agents for the treatment of malignant and non-malignant hematopoietic and non-hematopoietic diseases. This review critically evaluates their therapeutic value, the challenges and future directions for their clinical application.

  5. LncRNAs expression in preeclampsia placenta reveals the potential role of LncRNAs contributing to preeclampsia pathogenesis.

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    Xiaoju He

    Full Text Available BACKGROUND: Long non-coding RNAs (lncRNAs are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of diseases. In this study, we aimed to investigate the lncRNA profiles in preeclampsia. Preeclampsia has been observed in patients with molar pregnancy where a fetus is absent, which demonstrate that the placenta is sufficient to cause this condition. Thus, we analyzed the lncRNA profiles in preeclampsia placentas. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we described the lncRNA profiles in six preeclampsia placentas (T and five normal pregnancy placentas (N using microarray. With abundant and varied probes accounting for 33,045 LncRNAs in our microarray, 28,443 lncRNAs that were expressed at a specific level were detected. From the data, we found 738 lncRNAs that were differentially expressed (≥ 1.5-fold-change among preeclampsia placentas compared with controls. Coding-non-coding gene co-expression networks (CNC network were constructed based on the correlation analysis between the differentially expressed lncRNAs and mRNAs. According to the CNC network and GO analysis of differentially expressed lncRNAs/mRNAs, we selected three lncRNAs to analyze the relationship between lncRNAs and preeclampsia. LOC391533, LOC284100, and CEACAMP8 were evaluated using qPCR in 40 preeclampsia placentas and 40 controls. These results revealed that three lncRNAs were aberrantly expressed in preeclampsia placentas compared with controls. CONCLUSIONS/SIGNIFICANCE: Our study is the first study to determine the genome-wide lncRNAs expression patterns in preeclampsia placenta using microarray. These results revealed that clusters of lncRNAs were aberrantly expressed in preeclampsia placenta compared with controls, which indicated that lncRNAs differentially expressed in preeclampsia placenta might play a partial or key role in preeclampsia development. Misregulation of LOC391533, LOC

  6. Development of computational fluid dynamics--habitat suitability (CFD-HSI) models to identify potential passage--Challenge zones for migratory fishes in the Penobscot River

    Science.gov (United States)

    Haro, Alexander J.; Dudley, Robert W.; Chelminski, Michael

    2012-01-01

    A two-dimensional computational fluid dynamics-habitat suitability (CFD–HSI) model was developed to identify potential zones of shallow depth and high water velocity that may present passage challenges for five anadromous fish species in the Penobscot River, Maine, upstream from two existing dams and as a result of the proposed future removal of the dams. Potential depth-challenge zones were predicted for larger species at the lowest flow modeled in the dam-removal scenario. Increasing flows under both scenarios increased the number and size of potential velocity-challenge zones, especially for smaller species. This application of the two-dimensional CFD–HSI model demonstrated its capabilities to estimate the potential effects of flow and hydraulic alteration on the passage of migratory fish.

  7. A review: Potential and challenges of biologically activated carbon to remove natural organic matter in drinking water purification process.

    Science.gov (United States)

    Korotta-Gamage, Shashika Madushi; Sathasivan, Arumugam

    2017-01-01

    The use of biologically activated carbon (BAC) in drinking water purification is reviewed. In the past BAC is seen mostly as a polishing treatment. However, BAC has the potential to provide solution to recent challenges faced by water utilities arising from change in natural organic matter (NOM) composition in drinking water sources - increased NOM concentration with a larger fraction of hydrophilic compounds and ever increasing trace level organic pollutants. Hydrophilic NOM is not removed by traditional coagulation process and causes bacterial regrowth and increases disinfection by-products (DBPs) formation during disinfection. BAC can offer many advantages by removing hydrophilic fraction and many toxic and endocrine compounds which are not otherwise removed. BAC can also aid the other downstream processes if used as a pre-treatment. Major drawback of BAC was longer empty bed contact time (EBCT) required for an effective NOM removal. This critical review analyses the strategies that have been adopted to enhance the biological activity of the carbon by operational means and summarises the surface modification methods. To maximize the benefit of the BAC, a rethink of current treatment plant configuration is proposed. If the process can be expedited and adopted appropriately, BAC can solve many of the current problems.

  8. microRNAs with different functions and roles in disease development and as potential biomarkers of diabetes: progress and challenges.

    Science.gov (United States)

    Seyhan, Attila A

    2015-05-01

    Biomarkers provide information on early detection of diseases, in determining individuals at risk of developing complications or subtyping individuals for disease phenotypes. In addition, biomarkers may lead to better treatment strategies, personalized therapy, and improved outcome. A major gap in the field of biomarker development is that we have not identified appropriate (minimally invasive, life-style independent and informative) biomarkers for the underlying disease process(es) that can be measured in readily accessible samples (e.g. serum, plasma, blood, urine). miRNAs function as regulators in wide ranging cellular and physiological functions and also participate in many physiopathological processes and thus have been linked to many diseases including diabetes, metabolic and cardiovascular diseases, cancer, neurodegenerative diseases, and autoimmunity. Many miRNAs have been shown to have predictive value as potential biomarkers in a variety of diseases including diabetes, which are detectable in some instances many years before the manifestation of disease. Although some technical challenges still remain, due to their availability in the circulation, relative stability, and ease of detection; miRNAs have emerged as a promising new class of biomarkers to provide information on early detection of disease, monitoring disease progression, in determining individual's risk of developing complications or subtyping individuals for disease phenotypes, and to monitor response to therapeutic interventions. As a final note, most of the miRNAs reported in the literature have not yet been validated in sufficiently powered and longitudinal studies for specificity for that particular disease.

  9. Alkali Metal Rankine Cycle Boiler Technology Challenges and Some Potential Solutions for Space Nuclear Power and Propulsion Applications

    Science.gov (United States)

    Stone, James R.

    1994-01-01

    Alkali metal boilers are of interest for application to future space Rankine cycle power conversion systems. Significant progress on such boilers was accomplished in the 1960's and early 1970's, but development was not continued to operational systems since NASA's plans for future space missions were drastically curtailed in the early 1970's. In particular, piloted Mars missions were indefinitely deferred. With the announcement of the Space Exploration Initiative (SEI) in July 1989 by President Bush, interest was rekindled in challenging space missions and, consequently in space nuclear power and propulsion. Nuclear electric propulsion (NEP) and nuclear thermal propulsion (NTP) were proposed for interplanetary space vehicles, particularly for Mars missions. The potassium Rankine power conversion cycle became of interest to provide electric power for NEP vehicles and for 'dual-mode' NTP vehicles, where the same reactor could be used directly for propulsion and (with an additional coolant loop) for power. Although the boiler is not a major contributor to system mass, it is of critical importance because of its interaction with the rest of the power conversion system; it can cause problems for other components such as excess liquid droplets entering the turbine, thereby reducing its life, or more critically, it can drive instabilities-some severe enough to cause system failure. Funding for the SEI and its associated technology program from 1990 to 1993 was not sufficient to support significant new work on Rankine cycle boilers for space applications. In Fiscal Year 1994, funding for these challenging missions and technologies has again been curtailed, and planning for the future is very uncertain. The purpose of this paper is to review the technologies developed in the 1960's and 1970's in the light of the recent SEI applications. In this way, future Rankine cycle boiler programs may be conducted most efficiently. This report is aimed at evaluating alkali metal boiler

  10. Systems Perturbation Analysis of a Large-Scale Signal Transduction Model Reveals Potentially Influential Candidates for Cancer Therapeutics

    Science.gov (United States)

    Puniya, Bhanwar Lal; Allen, Laura; Hochfelder, Colleen; Majumder, Mahbubul; Helikar, Tomáš

    2016-01-01

    Dysregulation in signal transduction pathways can lead to a variety of complex disorders, including cancer. Computational approaches such as network analysis are important tools to understand system dynamics as well as to identify critical components that could be further explored as therapeutic targets. Here, we performed perturbation analysis of a large-scale signal transduction model in extracellular environments that stimulate cell death, growth, motility, and quiescence. Each of the model’s components was perturbed under both loss-of-function and gain-of-function mutations. Using 1,300 simulations under both types of perturbations across various extracellular conditions, we identified the most and least influential components based on the magnitude of their influence on the rest of the system. Based on the premise that the most influential components might serve as better drug targets, we characterized them for biological functions, housekeeping genes, essential genes, and druggable proteins. The most influential components under all environmental conditions were enriched with several biological processes. The inositol pathway was found as most influential under inactivating perturbations, whereas the kinase and small lung cancer pathways were identified as the most influential under activating perturbations. The most influential components were enriched with essential genes and druggable proteins. Moreover, known cancer drug targets were also classified in influential components based on the affected components in the network. Additionally, the systemic perturbation analysis of the model revealed a network motif of most influential components which affect each other. Furthermore, our analysis predicted novel combinations of cancer drug targets with various effects on other most influential components. We found that the combinatorial perturbation consisting of PI3K inactivation and overactivation of IP3R1 can lead to increased activity levels of apoptosis

  11. Challenges and potentials in using alternative landscape futures during climate change: A literature review and survey study

    Directory of Open Access Journals (Sweden)

    Amin Rastandeh

    2015-12-01

    Full Text Available This study focuses on the feasibility of applying alternative futures and scenario analysis in landscape planning during climate change to provide a wider perspective and deeper understanding of this approach for better use and more effective application in the future. The study consists of a literature review and an analysis of recent applied projects carried out worldwide. In addition, an electronic survey was conducted from March to September 2014 to examine viewpoints on the use and application of this approach with reference to climate-change impacts. The survey participants were a group of highly experienced researchers from eighteen countries involved in at least one applied project since 2000 relating to this topic. After analysis of more than forty applied projects, the survey results were incorporated into the analysis to create a comprehensive picture regarding the potentials and limitations of alternative futures and scenario analysis in landscape planning with particular attention to climate change. The findings show that this method is one of the most effective decision-making approaches for adopting landscape policies where landscapes change rapidly under the pressure of urbanisation and climate change. Nevertheless, there is a gap between the advances offered by the approach in various dimensions and the complexity of patterns, uncertainties and upheavals in landscapes due to climate-change impacts in the urbanising world. The research indicates that the approach opens up a great opportunity for decision-makers to expand their perspective and adopt appropriate landscape policies before reaching a point of no return from the sustainability point of view. Meanwhile, there are challenges and barriers in the application of alternative futures and scenario analysis for envisioning the landscapes influenced by climate change and urbanisation that should be pushed back. Although informative, this research raises new questions about this

  12. Effect of endophytic Bacillus cereus ERBP inoculation into non-native host: Potentials and challenges for airborne formaldehyde removal.

    Science.gov (United States)

    Khaksar, Gholamreza; Treesubsuntorn, Chairat; Thiravetyan, Paitip

    2016-10-01

    Phytoremediation could be a cost-effective, environmentally friendly approach for the treatment of indoor air. However, some drawbacks still dispute the expediency of phytotechnology. Our objectives were to investigate the competency of plant growth-promoting (PGP) endophytic Bacillus cereus ERBP (endophyte root blue pea), isolated from the root of Clitoria ternatea, to colonize and stabilize within Zamioculcas zamiifolia and Euphorbia milii as non-native hosts without causing any disease or stress symptoms. Moreover, the impact of B. cereus ERBP on the natural shoot endophytic community and for the airborne formaldehyde removal capability of non-native hosts was assessed. Non-native Z. zamiifolia was effectively inoculated with B. cereus ERBP through soil as the most efficient method of endophyte inoculation. Denaturing gradient gel electrophoresis profiling of the shoot endophytic community verified the colonization and stability of B. cereus ERBP within its non-native host during a 20-d fumigation period without interfering with the natural shoot endophytic diversity of Z. zamiifolia. B. cereus ERBP conferred full protection to its non-native host against formaldehyde phytotoxicity and enhanced airborne formaldehyde removal of Z. zamiifolia whereas non-inoculated plants suffered from formaldehyde phytotoxicity because their natural shoot endophytic community was detrimentally affected by formaldehyde. In contrast, B. cereus ERBP inoculation into non-native E. milii deteriorated airborne formaldehyde removal of the non-native host (compared to a non-inoculated one) as B. cereus ERBP interfered with natural shoot endophytic community of E. milii, which caused stress symptoms and stimulated ethylene biosynthesis. Non-native host inoculation with PGP B. cereus ERBP could bear potentials and challenges for airborne formaldehyde removal.

  13. Unexpected tolerance of glycosylation by UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferase revealed by electron capture dissociation mass spectrometry: carbohydrate as potential protective groups.

    Science.gov (United States)

    Yoshimura, Yayoi; Matsushita, Takahiko; Fujitani, Naoki; Takegawa, Yasuhiro; Fujihira, Haruhiko; Naruchi, Kentarou; Gao, Xiao-Dong; Manri, Naomi; Sakamoto, Takeshi; Kato, Kentaro; Hinou, Hiroshi; Nishimura, Shin-Ichiro

    2010-07-20

    UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (ppGalNAcTs, EC 2.4.1.41), a family of key enzymes that initiate posttranslational modification with O-glycans in mucin synthesis by introduction of alpha-GalNAc residues, are structurally composed of a catalytic domain and a lectin domain. It has been known that multiple Ser/Thr residues are assigned in common mucin glycoproteins as potential O-glycosylation sites and more than 20 distinct isoforms of this enzyme family contribute to produce densely O-glycosylated mucin glycoproteins. However, it seems that the functional role of the lectin domain of ppGalNAcTs remains unclear. We considered that electron capture dissociation mass spectrometry (ECD-MS), a promising method for highly selective fragmentation at peptide linkages of glycopeptides to generate unique c and z series of ions, should allow for precise structural characterization to uncover the mechanism in O-glycosylation of mucin peptides by ppGalNAcTs. In the present study, it was demonstrated that a system composed of an electrospray source, a linear RFQ ion trap that isolates precursor ions, the ECD device, and a TOF mass spectrometer is a nice tool to identify the preferential O-glycosylation sites without any decomposition of the carbohydrate moiety. It should be noted that electrons used for ECD are accelerated within a range from 1.75 to 9.75 eV depending on the structures of glycopeptides of interest. We revealed for the first time that additional installation of a alpha-GalNAc residue at potential glycosylation sites by ppGalNAcT2 proceeds smoothly in various unnatural glycopeptides having alpha-Man, alpha-Fuc, and beta-Gal residues as well as alpha-GalNAc residues. The results may suggest that ppGalNAcT2 did not differentiate totally presubstituted sugar residues in terms of configuration of functional groups, d-, l-configuration, and even alpha-, beta-stereochemistry at an anomeric carbon atom when relatively short synthetic

  14. Comparative genomic analysis ofLactobacillus plantarum ZJ316 reveals its genetic adaptation and potential probiotic profiles

    Institute of Scientific and Technical Information of China (English)

    Ping LI; Xuan LI; Qing GU; Xiu-yu LOU; Xiao-mei ZHANG; Da-feng SONG; Chen ZHANG

    2016-01-01

    题目:比较基因组学揭示植物乳杆菌ZJ316的生境适应性及潜在益生特性目的:前期研究发现植物乳杆菌ZJ316能显著抑制病原菌,促进仔猪生长,提高猪肉质量等,本研究拟在ZJ316全基因组测序的基础上,运用比较基因组学手段揭示与其生境适应性及益生特性相关基因。创新点:首次从基因水平上分析与植物乳杆菌ZJ316的生境适应性、抑菌活性及益生特性等相关的基因,为进一步揭示其生理功能打下基础。方法:运用BLASTN、Mauve和MUMmer等将植物乳杆菌ZJ316全基因组序列与已测序的8个植物乳杆菌全基因组序列进行比对及分析;用CRISPRFinder寻找CRISPR重复序列。结论:植物乳杆菌ZJ316包含碳水化合物的运输和代谢、蛋白水解酶系统和氨基酸的生物合成等相关基因,具有CRISPR、应激反应、耐胆盐、粘附宿主肠壁、胞外多糖、生物合成和细菌素生物合成等相关基因。这些基因的功能是其作为益生菌的重要特征和基础。%Objective: In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as an-timicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentialy related to its genetic adaptation and probiotic profiles based on comparative genomic analysis. Methods: The genome sequence ofL. plantarumZJ316 was compared with those of eightL. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palin-dromic repeats (CRISPRs). Results: We identified genes that encode proteins related to genetic adaptation and pro-biotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid bio-synthesis, CRISPR adaptive

  15. Resistance to re-challenge in the Brown Norway rat model of vasculitis is not always complete and may reveal separate effector and regulatory populations

    Science.gov (United States)

    Vinen, C S; Turner, D R; Oliveira, D B G

    2004-01-01

    Administration of mercuric chloride to Brown Norway rats results in T helper type 2 (Th2)- dominated autoimmunity characterized by high immunoglobulin E (IgE) concentrations, the production of multiple IgG autoantibodies, including those to glomerular basement membrane (GBM), arthritis and caecal vasculitis. After 14 days animals immunoregulate and auto-immunity resolves even if mercuric chloride injections are continued. In a third phase, if animals are re-challenged with mercuric chloride 6 weeks later, they show only attenuated autoimmunity with lower anti-GBM antibody concentrations and arthritis scores. Resistance to the induction of anti-GBM antibodies can also be achieved following an initial challenge with low-dose (one-tenth standard dose) mercuric chloride. We have now studied this resistant phase in more detail. We have shown, first, that following an initial full-dose mercuric chloride challenge, resistance also affects susceptibility to caecal vasculitis. Second, following an initial full-dose mercuric chloride challenge, the IgE response upon re-challenge is initially accelerated but subsequently enters a resistant phase and third, following an initial challenge with low-dose mercuric chloride, resistance is also seen to the induction of caecal vasculitis but is not seen in IgE serology (where results suggest competing effector and regulatory cell populations). Studying such regulatory phases in animal models of autoimmunity may be of benefit in the future in designing new therapies for human vasculitis. PMID:15379988

  16. Targeted capture sequencing in whitebark pine reveals range-wide demographic and adaptive patterns despite challenges of a large, repetitive genome

    Directory of Open Access Journals (Sweden)

    John eSyring

    2016-04-01

    Full Text Available Whitebark pine (Pinus albicaulis inhabits an expansive range in western North America, and it is a keystone species of subalpine environments. Whitebark is susceptible to multiple threats – climate change, white pine blister rust, mountain pine beetle, and fire exclusion – and it is suffering significant mortality range-wide, prompting the tree to be listed as ‘globally endangered’ by the International Union for Conservation of Nature (IUCN and ‘endangered’ by the Canadian government. Conservation collections (in situ and ex situ are being initiated to preserve the genetic legacy of the species. Reliable, transferrable, and highly variable genetic markers are essential for quantifying the genetic profiles of seed collections relative to natural stands, and ensuring the completeness of conservation collections. We evaluated the use of hybridization-based target capture to enrich specific genomic regions from the 30+ GB genome of whitebark pine, and to evaluate genetic variation across loci, trees, and geography. Probes were designed to capture 7,849 distinct genes, and screening was performed on 48 trees. Despite the inclusion of repetitive elements in the probe pool, the resulting dataset provided information on 4,452 genes and 32% of targeted positions (528,873 bp, and we were able to identify 12,390 segregating sites from 47 trees. Variations reveal strong geographic trends in heterozygosity and allelic richness, with trees from the southern Cascade and Sierra Range showing the greatest distinctiveness and differentiation. Our results show that even under non-optimal conditions (low enrichment efficiency; inclusion of repetitive elements in baits, targeted enrichment produces high quality, codominant genotypes from large genomes. The resulting data can be readily integrated into management and gene conservation activities for whitebark pine, and have the potential to be applied to other members of 5-needle pine group (Pinus subsect

  17. Crystal structure of human importin-α1 (Rch1, revealing a potential autoinhibition mode involving homodimerization.

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    Hideyuki Miyatake

    Full Text Available In this study, we determined the crystal structure of N-terminal importin-β-binding domain (IBB-truncated human importin-α1 (ΔIBB-h-importin-α1 at 2.63 Å resolution. The crystal structure of ΔIBB-h-importin-α1 reveals a novel closed homodimer. The homodimer exists in an autoinhibited state in which both the major and minor nuclear localization signal (NLS binding sites are completely buried in the homodimerization interface, an arrangement that restricts NLS binding. Analytical ultracentrifugation studies revealed that ΔIBB-h-importin-α1 is in equilibrium between monomers and dimers and that NLS peptides shifted the equilibrium toward the monomer side. This finding suggests that the NLS binding sites are also involved in the dimer interface in solution. These results show that when the IBB domain dissociates from the internal NLS binding sites, e.g., by binding to importin-β, homodimerization possibly occurs as an autoinhibition state.

  18. High-Bandwidth Atomic Force Microscopy Reveals A Mechanical spike Accompanying the Action Potential in mammalian Nerve Terminals

    Science.gov (United States)

    Salzberg, Brian M.

    2008-03-01

    Information transfer from neuron to neuron within nervous systems occurs when the action potential arrives at a nerve terminal and initiates the release of a chemical messenger (neurotransmitter). In the mammalian neurohypophysis (posterior pituitary), large and rapid changes in light scattering accompany secretion of transmitter-like neuropeptides. In the mouse, these intrinsic optical signals are intimately related to the arrival of the action potential (E-wave) and the release of arginine vasopressin and oxytocin (S-wave). We have used a high bandwidth (20 kHz) atomic force microscope (AFM) to demonstrate that these light scattering signals are associated with changes in nerve terminal volume, detected as nanometer-scale movements of a cantilever positioned on top of the neurohypophysis. The most rapid mechanical response, the ``spike'', has duration comparable to that of the action potential (˜2 ms) and probably reflects an increase in terminal volume due to H2O movement associated with Na^+-influx. Elementary calculations suggest that two H2O molecules accompanying each Na^+-ion could account for the ˜0.5-1.0 å increase in the diameter of each terminal during the action potential. Distinguishable from the mechanical ``spike'', a slower mechanical event, the ``dip'', represents a decrease in nerve terminal volume, depends upon Ca^2+-entry, as well as on intra-terminal Ca^2+-transients, and appears to monitor events associated with secretion. A simple hypothesis is that this ``dip'' reflects the extrusion of the dense core granule that comprises the secretory products. These dynamic high bandwidth AFM recordings are the first to monitor mechanical events in nervous systems and may provide novel insights into the mechanism(s) by which excitation is coupled to secretion at nerve terminals.

  19. DNA methylome profiling of maternal peripheral blood and placentas reveal potential fetal DNA markers for non-invasive prenatal testing.

    Science.gov (United States)

    Xiang, Yuqian; Zhang, Junyu; Li, Qiaoli; Zhou, Xinyao; Wang, Teng; Xu, Mingqing; Xia, Shihui; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi

    2014-09-01

    Utilizing epigenetic (DNA methylation) differences to differentiate between maternal peripheral blood (PBL) and fetal (placental) DNA has been a promising strategy for non-invasive prenatal testing (NIPT). However, the differentially methylated regions (DMRs) have yet to be fully ascertained. In the present study, we performed genome-wide comparative methylome analysis between maternal PBL and placental DNA from pregnancies of first trimester by methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) and Infinium HumanMethylation450 BeadChip assays. A total of 36 931 DMRs and 45 804 differentially methylated sites (DMSs) covering the whole genome, exclusive of the Y chromosome, were identified via MeDIP-Seq and Infinium 450k array, respectively, of which 3759 sites in 2188 regions were confirmed by both methods. Not only did we find the previously reported potential fetal DNA markers in our identified DMRs/DMSs but also we verified fully the identified DMRs/DMSs in the validation round by MassARRAY EpiTYPER. The screened potential fetal DNA markers may be used for NIPT on aneuploidies and other chromosomal diseases, such as cri du chat syndrome and velo-cardio-facial syndrome. In addition, these potential markers may have application in the early diagnosis of placental dysfunction, such as pre-eclampsia.

  20. Reviewing the Nutrition and Health Claims Regulation (EC) No. 1924/2006: What do we know about its challenges and potential impact on innovation?

    Science.gov (United States)

    Bröring, Stefanie; Khedkar, Sukhada; Ciliberti, Stefano

    2017-02-01

    Health claims potentially represent an opportunity for firms to engage in product differentiation and thereby induce investment into R&D and innovation in the food sector. The Nutrition and Health Claims Regulation (EC) No. 1924/2006 (NHCR) aims at protecting and promoting innovation as one of its objectives. However, existing studies indicate that this regulation may create several challenges for innovation in the food sector. To this end, we review the challenges related to the NHCR (Article 13.1) and its impact on innovation. Extant literature suggests that companies face challenges related to changing list of ingredients, missing transparency, wording of claims, limited financial resources, limited R&D resources, switching product categories and abandoning the functional foods sector. Moreover, current studies imply that so far the NHCR (in specific Article 13.1) does not seem to encourage innovation in the EU food sector.

  1. Poly(ADP-ribose) polymerase inhibition reveals a potential mechanism to promote neuroprotection and treat neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    Prashanth Komirishetty; Aparna Areti; Ranadeep Gogoi; Ramakrishna Sistla; Ashutosh Kumar

    2016-01-01

    Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially per-oxynitrite atfer the nerve injury. hTey provoke oxidative DNA damage and consequent over-activation of the poly(ADP-ribose) polymerase (PARP) upregulates pro-inlfammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neu-ronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown beneifts in treating experimental neuropathy. hTis article reviews the in-volvement of PARP over-activation in trauma induced neuropathy and therapeutic signiifcance of PARP inhibitors in the experimental neuropathy and neuropathic pain.

  2. Poly(ADP-ribose polymerase inhibition reveals a potential mechanism to promote neuroprotection and treat neuropathic pain

    Directory of Open Access Journals (Sweden)

    Prashanth Komirishetty

    2016-01-01

    Full Text Available Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially peroxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly(ADP-ribose polymerase (PARP upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neuronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the involvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.

  3. Poly(ADP-ribose) polymerase inhibition reveals a potential mechanism to promote neuroprotection and treat neuropathic pain.

    Science.gov (United States)

    Komirishetty, Prashanth; Areti, Aparna; Gogoi, Ranadeep; Sistla, Ramakrishna; Kumar, Ashutosh

    2016-10-01

    Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially peroxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly(ADP-ribose) polymerase (PARP) upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neuronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the involvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.

  4. The functional potential of high Arctic permafrost revealed by metagenomic sequencing, qPCR and microarray analyses.

    Science.gov (United States)

    Yergeau, Etienne; Hogues, Hervé; Whyte, Lyle G; Greer, Charles W

    2010-09-01

    The fate of the carbon stocked in permafrost following global warming and permafrost thaw is of major concern in view of the potential for increased CH(4) and CO(2) emissions from these soils. Complex carbon compound degradation and greenhouse gas emissions are due to soil microbial communities, but no comprehensive study has yet addressed their composition and functional potential in permafrost. Here, a 2-m deep permafrost sample and its overlying active layer soil were subjected to metagenomic sequencing, quantitative PCR (qPCR) and microarray analyses. The active layer soil and the 2-m permafrost microbial community structures were very similar, with Actinobacteria being the dominant phylum. The two samples also possessed a highly similar spectrum of functional genes, especially when compared with other already published metagenomes. Key genes related to methane generation, methane oxidation and organic matter degradation were highly diverse for both samples in the metagenomic libraries and some (for example, pmoA) showed relatively high abundance in qPCR assays. Genes related to nitrogen fixation and ammonia oxidation, which could have important roles following climatic change in these nitrogen-limited environments, showed low diversity but high abundance. The 2-m permafrost showed lower abundance and diversity for all the assessed genes and taxa. Experimental biases were also evaluated using qPCR and showed that the whole-community genome amplification technique used caused representational biases in the metagenomic libraries by increasing the abundance of Bacteroidetes and decreasing the abundance of Actinobacteria. This study describes for the first time the detailed functional potential of permafrost-affected soils.

  5. Functional genes reveal the intrinsic PAH biodegradation potential in creosote-contaminated groundwater following in situ biostimulation.

    Science.gov (United States)

    Nyyssönen, Mari; Kapanen, Anu; Piskonen, Reetta; Lukkari, Tuomas; Itävaara, Merja

    2009-08-01

    A small-scale functional gene array containing 15 functional gene probes targeting aliphatic and aromatic hydrocarbon biodegradation pathways was used to investigate the effect of a pilot-scale air sparging and nutrient infiltration treatment on hydrocarbon biodegradation in creosote-contaminated groundwater. Genes involved in the different phases of polycyclic aromatic hydrocarbon (PAH) biodegradation were detected with the functional gene array in the contaminant plume, thus indicating the presence of intrinsic biodegradation potential. However, the low aerobic fluorescein diacetate hydrolysis, the polymerase chain reaction (PCR) amplification of 16S rRNA genes closely similar to sulphate-reducing and denitrifying bacteria and the negligible decrease in contaminant concentrations showed that aerobic PAH biodegradation was limited in the anoxic groundwater. Increased abundance of PAH biodegradation genes was detected by functional gene array in the monitoring well located at the rear end of the biostimulated area, which indicated that air sparging and nutrient infiltration enhanced the intrinsic, aerobic PAH biodegradation. Furthermore, ten times higher naphthalene dioxygenase gene copy numbers were detected by real-time PCR in the biostimulated area, which was in good agreement with the functional gene array data. As a result, functional gene array analysis was demonstrated to provide a potential tool for evaluating the efficiency of the bioremediation treatment for enhancing hydrocarbon biodegradation in field-scale applications.

  6. Comparative analyses reveal potential uses of Brachypodium distachyon as a model for cold stress responses in temperate grasses

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    Li Chuan

    2012-05-01

    Full Text Available Abstract Background Little is known about the potential of Brachypodium distachyon as a model for low temperature stress responses in Pooideae. The ice recrystallization inhibition protein (IRIP genes, fructosyltransferase (FST genes, and many C-repeat binding factor (CBF genes are Pooideae specific and important in low temperature responses. Here we used comparative analyses to study conservation and evolution of these gene families in B. distachyon to better understand its potential as a model species for agriculturally important temperate grasses. Results Brachypodium distachyon contains cold responsive IRIP genes which have evolved through Brachypodium specific gene family expansions. A large cold responsive CBF3 subfamily was identified in B. distachyon, while CBF4 homologs are absent from the genome. No B. distachyon FST gene homologs encode typical core Pooideae FST-motifs and low temperature induced fructan accumulation was dramatically different in B. distachyon compared to core Pooideae species. Conclusions We conclude that B. distachyon can serve as an interesting model for specific molecular mechanisms involved in low temperature responses in core Pooideae species. However, the evolutionary history of key genes involved in low temperature responses has been different in Brachypodium and core Pooideae species. These differences limit the use of B. distachyon as a model for holistic studies relevant for agricultural core Pooideae species.

  7. Inverted U-Shaped Curvilinear Relationship between Challenge and One's Intrinsic Motivation: Evidence from Event-Related Potentials.

    Science.gov (United States)

    Ma, Qingguo; Pei, Guanxiong; Meng, Liang

    2017-01-01

    The balance between task demand and one's competence is critical for the maintenance of intrinsic motivation. According to Flow theory and Self-determination theory, optimal challenge gives rise to the maximum intrinsic motivation, and an inverted U-shaped curvilinear relationship between perceived challenge and one's intrinsic motivation is suggested. In order to provide direct experimental evidences for predictions of these theories, in this study, we employed the two-player StopWatch game that we previously designed, which made references to the game format of a badminton tournament. According to our manipulation, a male participant was defeated by the same-sex player paired with him (played by a well-trained confederate of the experimenter) in two matches, one with a wide margin (the complete defeat condition) and another with a narrow one (the near miss condition). Participants performed better and reported to enjoy the near miss match to a greater extent. Besides, an enlarged Stimulus-preceding negativity was elicited when participants were actively anticipating outcomes in the near miss condition, suggesting greater anticipatory attention toward the outcome and an enhanced intrinsic motivation to win. Thus, converging electrophysiological evidences from this study and our former study confirmed the inverted U-shaped curvilinear relationship between perceived challenge and one's intrinsic motivation.

  8. Virtual and In Vitro Screens Reveal a Potential Pharmacophore that Avoids the Fibrillization of Aβ1–42

    Science.gov (United States)

    Hernández-Rodríguez, Maricarmen; Correa-Basurto, José; Nicolás-Vázquez, María Inés; Miranda-Ruvalcaba, René; Benítez-Cardoza, Claudia Guadalupe; Reséndiz-Albor, Aldo Arturo; Méndez-Méndez, Juan Vicente; Rosales-Hernández, Martha C.

    2015-01-01

    Among the multiple factors that induce Alzheimer’s disease, aggregation of the amyloid β peptide (Aβ) is considered the most important due to the ability of the 42-amino acid Aβ peptides (Aβ1–42) to form oligomers and fibrils, which constitute Aβ pathological aggregates. For this reason, the development of inhibitors of Aβ1–42 pathological aggregation represents a field of research interest. Several Aβ1–42 fibrillization inhibitors possess tertiary amine and aromatic moieties. In the present study, we selected 26 compounds containing tertiary amine and aromatic moieties with or without substituents and performed theoretical studies that allowed us to select four compounds according to their free energy values for Aβ1–42 in α-helix (Aβ-α), random coil (Aβ-RC) and β-sheet (Aβ-β) conformations. Docking studies revealed that compound 5 had a higher affinity for Aβ-α and Aβ-RC than the other compounds. In vitro, this compound was able to abolish Thioflavin T fluorescence and favored an RC conformation of Aβ1–42 in circular dichroism studies, resulting in the formation of amorphous aggregates as shown by atomic force microscopy. The results obtained from quantum studies allowed us to identify a possible pharmacophore that can be used to design Aβ1–42 aggregation inhibitors. In conclusion, compounds with higher affinity for Aβ-α and Aβ-RC prevented the formation of oligomeric species. PMID:26172152

  9. Gorilla gorilla gorilla gut: a potential reservoir of pathogenic bacteria as revealed using culturomics and molecular tools.

    Science.gov (United States)

    Bittar, Fadi; Keita, Mamadou B; Lagier, Jean-Christophe; Peeters, Martine; Delaporte, Eric; Raoult, Didier

    2014-11-24

    Wild apes are considered to be the most serious reservoir and source of zoonoses. However, little data are available about the gut microbiota and pathogenic bacteria in gorillas. For this propose, a total of 48 fecal samples obtained from 21 Gorilla gorilla gorilla individuals (as revealed via microsatellite analysis) were screened for human bacterial pathogens using culturomics and molecular techniques. By applying culturomics to one index gorilla and using specific media supplemented by plants, we tested 12,800 colonies and identified 147 different bacterial species, including 5 new species. Many opportunistic pathogens were isolated, including 8 frequently associated with human diseases; Mycobacterium bolletii, Proteus mirabilis, Acinetobacter baumannii, Klebsiella pneumoniae, Serratia marcescens, Escherichia coli, Staphylococcus aureus and Clostridium botulinum. The genus Treponema accounted for 27.4% of the total reads identified at the genus level via 454 pyrosequencing. Using specific real-time PCR on 48 gorilla fecal samples, in addition to classical human pathogens, we also observed the fastidious bacteria Bartonella spp. Borrelia spp., Coxiella burnetii and Tropheryma whipplei in the gorilla population. We estimated that the prevalence of these pathogens vary between 4.76% and 85.7%. Therefore, gorillas share many bacterial pathogens with humans suggesting that they could be a reservoir for their emergence.

  10. Virtual and In Vitro Screens Reveal a Potential Pharmacophore that Avoids the Fibrillization of Aβ1-42.

    Directory of Open Access Journals (Sweden)

    Maricarmen Hernández-Rodríguez

    Full Text Available Among the multiple factors that induce Alzheimer's disease, aggregation of the amyloid β peptide (Aβ is considered the most important due to the ability of the 42-amino acid Aβ peptides (Aβ1-42 to form oligomers and fibrils, which constitute Aβ pathological aggregates. For this reason, the development of inhibitors of Aβ1-42 pathological aggregation represents a field of research interest. Several Aβ1-42 fibrillization inhibitors possess tertiary amine and aromatic moieties. In the present study, we selected 26 compounds containing tertiary amine and aromatic moieties with or without substituents and performed theoretical studies that allowed us to select four compounds according to their free energy values for Aβ1-42 in α-helix (Aβ-α, random coil (Aβ-RC and β-sheet (Aβ-β conformations. Docking studies revealed that compound 5 had a higher affinity for Aβ-α and Aβ-RC than the other compounds. In vitro, this compound was able to abolish Thioflavin T fluorescence and favored an RC conformation of Aβ1-42 in circular dichroism studies, resulting in the formation of amorphous aggregates as shown by atomic force microscopy. The results obtained from quantum studies allowed us to identify a possible pharmacophore that can be used to design Aβ1-42 aggregation inhibitors. In conclusion, compounds with higher affinity for Aβ-α and Aβ-RC prevented the formation of oligomeric species.

  11. Barcoding Turkish Culex mosquitoes to facilitate arbovirus vector incrimination studies reveals hidden diversity and new potential vectors.

    Science.gov (United States)

    Gunay, Filiz; Alten, Bulent; Simsek, Fatih; Aldemir, Adnan; Linton, Yvonne-Marie

    2015-03-01

    As a precursor to planned arboviral vector incrimination studies, an integrated systematics approach was adopted using morphology and DNA barcoding to examine the Culex fauna present in Turkey. The mitochondrial COI gene (658bp) were sequenced from 185 specimens collected across 11 Turkish provinces, as well as from colony material. Although by morphology only 9 species were recognised, DNA barcoding recovered 13 distinct species including: Cx. (Barraudius) modestus, Cx. (Culex) laticinctus, Cx. (Cux.) mimeticus, Cx. (Cux.) perexiguus, Cx. (Cux.) pipiens, Cx. (Cux.) pipiens form molestus, Cx. (Cux.) quinquefasciatus, Cx. (Cux.) theileri, Cx. (Cux.) torrentium, Cx. (Cux.) tritaeniorhynchus and Cx. (Maillotia) hortensis. The taxon formerly identified as Cx. (Neoculex) territans was shown to comprise two distinct species, neither of which correspond to Cx. territans s.s. These include Cx. (Neo.) impudicus and another uncertain species, which may be Cx. (Neo.) europaeus or Cx. (Neo.) martinii (herein=Cx. (Neo.) sp. 1). Detailed examination of the Pipiens Group revealed Cx. pipiens, Cx. pipiens f. molestus and the widespread presence of the highly efficient West Nile virus vector Cx. quinquefasciatus for the first time. Four new country records are reported, increasing the Culex of Turkey to 15 recognised species and Cx. pipiens f. molestus. A new taxonomic checklist is provided, annotated with respective vector competencies for transmission of arboviruses.

  12. Comparative exoprotein profiling of different Staphylococcus epidermidis strains reveals potential link between nonclassical protein export and virulence.

    Science.gov (United States)

    Siljamäki, Pia; Varmanen, Pekka; Kankainen, Matti; Sukura, Antti; Savijoki, Kirsi; Nyman, Tuula A

    2014-07-03

    Staphylococcus epidermidis (SE) includes commensal and pathogenic strains capable of infecting humans and animals. This study reports global exoproteome profiling of bovine mastitis strain PM221 and two human strains, commensal-type ATCC12228 and sepsis-associated RP62A. We identified 451, 395, and 518 proteins from culture supernatants of PM221, ATCC12228, and RP62A, respectively. Comparison of the identified exoproteomes revealed several strain-specific differences related to secreted antigens and adhesins, higher virulence capability for RP62A, and similarities between the PM221 and RP62A exoproteomes. The majority of the identified proteins (∼80%) were predicted to be cytoplasmic, including proteins known to be associated in membrane vesicles (MVs) in Staphylococcus aureus and immunogenic/adhesive moonlighting proteins. Enrichment of MV fractions from culture supernatants and analysis of their protein composition indicated that this nonclassical protein secretion pathway was being exploited under the conditions used and that there are strain-specific differences in nonclassical protein export. In addition, several predicted cell-surface proteins were identified in the culture media. In summary, the present study is the first in-depth exoproteome analysis of SE highlighting strain-specific factors able to contribute to virulence and adaptation.

  13. Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer.

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    Dogus Murat Altintas

    Full Text Available BACKGROUND: Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa among androgen-regulated genes (ARG and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely give rise to cancer. METHODS: ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1. RESULTS AND DISCUSSION: By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91 and DLX1 (0.94. CONCLUSIONS: We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could

  14. Proteomics Reveals that Proteins Expressed During the Early Stage of Bacillus anthracis Infection Are Potential Targets for the Development of Vaccines and Drugs

    Institute of Scientific and Technical Information of China (English)

    Chun-Ming Huang; Craig A. Elmets; De-chu C. Tang; Fuming Li; Nabiha Yusuf

    2004-01-01

    In this review, we advance a new concept in developing vaccines and/or drugs to target specific proteins expressed during the early stage of Bacillus anthracis (an thrax) infection and address existing challenges to this concept. Three proteins (immune inhibitor A, GPR-like spore protease, and alanine racemase) initially identified by proteomics in our laboratory were found to have differential expres sions during anthrax spore germination and early outgrowth. Other studies of different bacillus strains indicate that these three proteins are involved in either germination or cytotoxicity of spores, suggesting that they may serve as potential targets for the design of anti-anthrax vaccines and drugs.

  15. Proteome profiling of neuroblastoma-derived exosomes reveal the expression of proteins potentially involved in tumor progression.

    Directory of Open Access Journals (Sweden)

    Danilo Marimpietri

    Full Text Available Neuroblastoma (NB is the most common extracranial solid tumor in childhood, with grim prognosis in a half of patients. Exosomes are nanometer-sized membrane vesicles derived from the multivesicular bodies (MVBs of the endocytic pathway and released by normal and neoplastic cells. Tumor-derived exosomes have been shown in different model systems to carry molecules that promote cancer growth and dissemination. In this respect, we have here performed the first characterization and proteomic analysis of exosomes isolated from human NB cell lines by filtration and ultracentrifugation. Electron microscopy demonstrated that NB-derived exosomes exhibited the characteristic cup-shaped morphology. Dynamic light scattering studies showed a bell-shaped curve and a polydispersity factor consistent with those of exosomes. Zeta potential values suggested a good nanoparticle stability. We performed proteomic analysis of NB-derived exosomes by two dimension liquid chromatography separation and mass spectrometry analyses using the multidimensional protein identification technology strategy. We found that the large majority of the proteins identified in NB derived exosomes are present in Exocarta database including tetraspanins, fibronectin, heat shock proteins, MVB proteins, cytoskeleton-related proteins, prominin-1 (CD133, basigin (CD147 and B7-H3 (CD276. Expression of the CD9, CD63 and CD81 tetraspanins, fibronectin, CD133, CD147 and CD276 was validated by flow cytometry. Noteworthy, flow cytometric analysis showed that NB-derived exosomes expressed the GD2 disialoganglioside, the most specific marker of NB. In conclusion, this study shows that NB-derived exosomes express a discrete set of molecules involved in defense response, cell differentiation, cell proliferation and regulation of other important biological process. Thus, NB-derived exosomes may play an important role in the modulation of tumor microenvironment and represent potential tumor biomarkers.

  16. Proteomics analysis of human obesity reveals the epigenetic factor HDAC4 as a potential target for obesity.

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    Mohamed Abu-Farha

    Full Text Available Sedentary lifestyle and excessive energy intake are prominent contributors to obesity; a major risk factors for the development of insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidating the molecular mechanisms underlying these chronic conditions is of relevant importance as it might lead to the identification of novel anti-obesity targets. The purpose of the current study is to investigate differentially expressed proteins between lean and obese subjects through a shot-gun quantitative proteomics approach using peripheral blood mononuclear cells (PBMCs extracts as well as potential modulation of those proteins by physical exercise. Using this approach, a total of 47 proteins showed at least 1.5 fold change between lean and obese subjects. In obese, the proteomic profiling before and after 3 months of physical exercise showed differential expression of 38 proteins. Thrombospondin 1 (TSP1 was among the proteins that were upregulated in obese subjects and then decreased by physical exercise. Conversely, the histone deacetylase 4 (HDAC4 was downregulated in obese subjects and then induced by physical exercise. The proteomic data was further validated by qRT-PCR, Western blot and immunohistochemistry in both PBMCs and adipose tissue. We also showed that HDAC4 levels correlated positively with maximum oxygen consumption (VO2 Max but negatively with body mass index, percent body fat, and the inflammatory chemokine RANTES. In functional assays, our data indicated that ectopic expression of HDAC4 significantly impaired TNF-α-dependent activation of NF-κB, establishing thus a link between HDAC4 and regulation of the immune system. Together, the expression pattern of HDAC4 in obese subjects before and after physical exercise, its correlation with various physical, clinical and metabolic parameters along with its inhibitory effect on NF-κB are suggestive of a protective role of HDAC4 against obesity. HDAC4 could therefore represent

  17. Interspecific proteomic comparisons reveal ash phloem genes potentially involved in constitutive resistance to the emerald ash borer.

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    Justin G A Whitehill

    Full Text Available The emerald ash borer (Agrilus planipennis is an invasive wood-boring beetle that has killed millions of ash trees since its accidental introduction to North America. All North American ash species (Fraxinus spp. that emerald ash borer has encountered so far are susceptible, while an Asian species, Manchurian ash (F. mandshurica, which shares an evolutionary history with emerald ash borer, is resistant. Phylogenetic evidence places North American black ash (F. nigra and Manchurian ash in the same clade and section, yet black ash is highly susceptible to the emerald ash borer. This contrast provides an opportunity to compare the genetic traits of the two species and identify those with a potential role in defense/resistance. We used Difference Gel Electrophoresis (DIGE to compare the phloem proteomes of resistant Manchurian to susceptible black, green, and white ash. Differentially expressed proteins associated with the resistant Manchurian ash when compared to the susceptible ash species were identified using nano-LC-MS/MS and putative identities assigned. Proteomic differences were strongly associated with the phylogenetic relationships among the four species. Proteins identified in Manchurian ash potentially associated with its resistance to emerald ash borer include a PR-10 protein, an aspartic protease, a phenylcoumaran benzylic ether reductase (PCBER, and a thylakoid-bound ascorbate peroxidase. Discovery of resistance-related proteins in Asian species will inform approaches in which resistance genes can be introgressed into North American ash species. The generation of resistant North American ash genotypes can be used in forest ecosystem restoration and urban plantings following the wake of the emerald ash borer invasion.

  18. Interspecific proteomic comparisons reveal ash phloem genes potentially involved in constitutive resistance to the emerald ash borer.

    Science.gov (United States)

    Whitehill, Justin G A; Popova-Butler, Alexandra; Green-Church, Kari B; Koch, Jennifer L; Herms, Daniel A; Bonello, Pierluigi

    2011-01-01

    The emerald ash borer (Agrilus planipennis) is an invasive wood-boring beetle that has killed millions of ash trees since its accidental introduction to North America. All North American ash species (Fraxinus spp.) that emerald ash borer has encountered so far are susceptible, while an Asian species, Manchurian ash (F. mandshurica), which shares an evolutionary history with emerald ash borer, is resistant. Phylogenetic evidence places North American black ash (F. nigra) and Manchurian ash in the same clade and section, yet black ash is highly susceptible to the emerald ash borer. This contrast provides an opportunity to compare the genetic traits of the two species and identify those with a potential role in defense/resistance. We used Difference Gel Electrophoresis (DIGE) to compare the phloem proteomes of resistant Manchurian to susceptible black, green, and white ash. Differentially expressed proteins associated with the resistant Manchurian ash when compared to the susceptible ash species were identified using nano-LC-MS/MS and putative identities assigned. Proteomic differences were strongly associated with the phylogenetic relationships among the four species. Proteins identified in Manchurian ash potentially associated with its resistance to emerald ash borer include a PR-10 protein, an aspartic protease, a phenylcoumaran benzylic ether reductase (PCBER), and a thylakoid-bound ascorbate peroxidase. Discovery of resistance-related proteins in Asian species will inform approaches in which resistance genes can be introgressed into North American ash species. The generation of resistant North American ash genotypes can be used in forest ecosystem restoration and urban plantings following the wake of the emerald ash borer invasion.

  19. Putatively novel serotypes and the potential for reduced vaccine effectiveness: capsular locus diversity revealed among 5405 pneumococcal genomes

    Science.gov (United States)

    van Tonder, Andries J.; Bray, James E.; Quirk, Sigríður J.; Haraldsson, Gunnsteinn; Jolley, Keith A.; Maiden, Martin C. J.; Hoffmann, Steen; Bentley, Stephen D.; Haraldsson, Ásgeir; Erlendsdóttir, Helga; Kristinsson, Karl G.; Brueggemann, Angela B.

    2017-01-01

    The pneumococcus is a leading global pathogen and a key virulence factor possessed by the majority of pneumococci is an antigenic polysaccharide capsule (‘serotype’), which is encoded by the capsular (cps) locus. Approximately 100 different serotypes are known, but the extent of sequence diversity within the cps loci of individual serotypes is not well understood. Investigating serotype-specific sequence variation is crucial to the design of sequence-based serotyping methodology, understanding pneumococcal conjugate vaccine (PCV) effectiveness and the design of future PCVs. The availability of large genome datasets makes it possible to assess population-level variation among pneumococcal serotypes and in this study 5405 pneumococcal genomes were used to investigate cps locus diversity among 49 different serotypes. Pneumococci had been recovered between 1916 and 2014 from people of all ages living in 51 countries. Serotypes were deduced bioinformatically, cps locus sequences were extracted and variation was assessed within the cps locus, in the context of pneumococcal genetic lineages. Overall, cps locus sequence diversity varied markedly: low to moderate diversity was revealed among serogroups/types 1, 3, 7, 9, 11 and 22; whereas serogroups/types 6, 19, 23, 14, 15, 18, 33 and 35 displayed high diversity. Putative novel and/or hybrid cps loci were identified among all serogroups/types apart from 1, 3 and 9. This study demonstrated that cps locus sequence diversity varied widely between serogroups/types. Investigation of the biochemical structure of the polysaccharide capsule of major variants, particularly PCV-related serotypes and those that appear to be novel or hybrids, is warranted. PMID:28133541

  20. Genomic analysis reveals a potential role for cell cycle perturbation in HCV-mediated apoptosis of cultured hepatocytes.

    Directory of Open Access Journals (Sweden)

    Kathie-Anne Walters

    2009-01-01

    Full Text Available The mechanisms of liver injury associated with chronic HCV infection, as well as the individual roles of both viral and host factors, are not clearly defined. However, it is becoming increasingly clear that direct cytopathic effects, in addition to immune-mediated processes, play an important role in liver injury. Gene expression profiling during multiple time-points of acute HCV infection of cultured Huh-7.5 cells was performed to gain insight into the cellular mechanism of HCV-associated cytopathic effect. Maximal induction of cell-death-related genes and appearance of activated caspase-3 in HCV-infected cells coincided with peak viral replication, suggesting a link between viral load and apoptosis. Gene ontology analysis revealed that many of the cell-death genes function to induce apoptosis in response to cell cycle arrest. Labeling of dividing cells in culture followed by flow cytometry also demonstrated the presence of significantly fewer cells in S-phase in HCV-infected relative to mock cultures, suggesting HCV infection is associated with delayed cell cycle progression. Regulation of numerous genes involved in anti-oxidative stress response and TGF-beta1 signaling suggest these as possible causes of delayed cell cycle progression. Significantly, a subset of cell-death genes regulated during in vitro HCV infection was similarly regulated specifically in liver tissue from a cohort of HCV-infected liver transplant patients with rapidly progressive fibrosis. Collectively, these data suggest that HCV mediates direct cytopathic effects through deregulation of the cell cycle and that this process may contribute to liver disease progression. This in vitro system could be utilized to further define the cellular mechanism of this perturbation.

  1. Revealing polychaetes invasion patterns: Identification, reproduction and potential risks of the Korean ragworm, Perinereis linea (Treadwell), in the Western Mediterranean

    Science.gov (United States)

    Arias, Andrés; Richter, Alexandra; Anadón, Nuria; Glasby, Christopher J.

    2013-10-01

    An established population of the polychaetous annelid Perinereis linea (Treadwell) is reported for the first time outside its native distribution range (NW Pacific). This exotic worm has reached the Western Mediterranean (Mar Menor lagoon) via importing live fishing-bait as it is commonly used by anglers in Mar Menor lagoon, an area largely used for recreational fishing. To avoid confusion with other related species, and because the scientific name has been in synonymy for many years, P. linea is redescribed and illustrated. We focus on the reproductive biology and ecology of P. linea to help to understand its introduction, naturalization and spread along this coastal lagoon. Comparison between the Mediterranean population with a native population from South Korea revealed that the species exhibits a great reproductive plasticity and adaptability, which depends on the environmental conditions. Perinereis linea can reproduce after acquiring the epitokous form or prior to complete epitokal modification. In the Mar Menor lagoon population females release eggs asynchronically without completing epitokal modifications. However, under particular laboratory conditions females produce eggs synchronically and release them after complete epitokal transformations. Fertilization can occur internally in the female coelom, and females release zygotes and larvae through openings in their body walls; they are then incubated in gelatinous masses attached to the female parapodia. The sperm morphology is of the ent-aquasperm type. The eggs and larvae are attacked by symbiotic ciliate protozoa that feed on their yolk reserves. These foreign ciliates may act as carriers of disease in native beachworms and constitute an important risk for the ecosystem health. Finally, we provide recommendations on the prevention of the adverse effects that this exotic ragworm can cause in receiving ecosystems.

  2. Involvement of potential pathways in malignant transformation from Oral Leukoplakia to Oral Squamous Cell Carcinoma revealed by proteomic analysis

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    Li Jing

    2009-08-01

    Full Text Available Abstract Background Oral squamous cell carcinoma (OSCC is one of the most common forms of cancer associated with the presence of precancerous oral leukoplakia. Given the poor prognosis associated with oral leukoplakia, and the difficulties in distinguishing it from cancer lesions, there is an urgent need to elucidate the molecular determinants and critical signal pathways underlying the malignant transformation of precancerous to cancerous tissue, and thus to identify novel diagnostic and therapeutic target. Results We have utilized two dimensional electrophoresis (2-DE followed by ESI-Q-TOF-LC-MS/MS to identify proteins differentially expressed in six pairs of oral leukoplakia tissues with dysplasia and oral squamous cancer tissues, each pair was collected from a single patient. Approximately 85 differentially and constantly expressed proteins (> two-fold change, P Conclusion Varying levels of differentially expressed proteins were possibly involved in the malignant transformation of oral leukoplakia. Their expression levels, bioprocess, and interaction networks were analyzed using a bioinformatics approach. This study shows that the three homologs of PA28 may play an important role in malignant transformation and is an example of a systematic biology study, in which functional proteomics were constructed to help to elucidate mechanistic aspects and potential involvement of proteins. Our results provide new insights into the pathogenesis of oral cancer. These differentially expressed proteins may have utility as useful candidate markers of OSCC.

  3. Event-related brain potentials reveal the time-course of language change detection in early bilinguals.

    Science.gov (United States)

    Kuipers, Jan-Rouke; Thierry, Guillaume

    2010-05-01

    Using event-related brain potentials, we investigated the temporal course of language change detection in proficient bilinguals as compared to matched controls. Welsh-English bilingual participants and English controls were presented with a variant of the oddball paradigm involving picture-word pairs. The language of the spoken word was manipulated such that English was the frequent stimulus (75%) and Welsh the infrequent stimulus (25%). We also manipulated semantic relatedness between pictures and words, such that only half of the pictures were followed by a word that corresponded with the identity of the picture. The P2 wave was significantly modulated by language in the bilingual group only, suggesting that this group detected a language change as early as 200 ms after word onset. Monolinguals also reliably detected the language change, but at a later stage of semantic integration (N400 range), since Welsh words were perceived as meaningless. The early detection of a language change in bilinguals triggered stimulus re-evaluation mechanisms reflected by a significant P600 modulation by Welsh words. Furthermore, compared to English unrelated words, English words matching the picture identity elicited significantly greater P2 amplitudes in the bilingual group only, suggesting that proficient bilinguals validate an incoming word against their expectation based on the context. Overall, highly proficient bilinguals appear to detect language changes very early on during speech perception and to consciously monitor language changes when they occur.

  4. The genetic potential for key biogeochemical processes in Arctic frost flowers and young sea ice revealed by metagenomic analysis.

    Science.gov (United States)

    Bowman, Jeff S; Berthiaume, Chris T; Armbrust, E Virginia; Deming, Jody W

    2014-08-01

    Newly formed sea ice is a vast and biogeochemically active environment. Recently, we reported an unusual microbial community dominated by members of the Rhizobiales in frost flowers at the surface of Arctic young sea ice based on the presence of 16S gene sequences related to these strains. Here, we use metagenomic analysis of two samples, from a field of frost flowers and the underlying young sea ice, to explore the metabolic potential of this surface ice community. The analysis links genes for key biogeochemical processes to the Rhizobiales, including dimethylsulfide uptake, betaine glycine turnover, and halocarbon production. Nodulation and nitrogen fixation genes characteristic of terrestrial root-nodulating Rhizobiales were generally lacking from these metagenomes. Non-Rhizobiales clades at the ice surface had genes that would enable additional biogeochemical processes, including mercury reduction and dimethylsulfoniopropionate catabolism. Although the ultimate source of the observed microbial community is not known, considerations of the possible role of eolian deposition or transport with particles entrained during ice formation favor a suspended particle source for this microbial community.

  5. Metagenome reveals potential microbial degradation of hydrocarbon coupled with sulfate reduction in an oil-immersed chimney from Guaymas Basin

    Directory of Open Access Journals (Sweden)

    Ying eHe

    2013-06-01

    Full Text Available Deep-sea hydrothermal vent chimneys contain a high diversity of microorganisms, yet the metabolic activity and the ecological functions of the microbial communities remain largely unexplored. In this study, a metagenomic approach was applied to characterize the metabolic potential in a Guaymas hydrothermal vent chimney and to conduct comparative genomic analysis among a variety of environments with sequenced metagenomes. Complete clustering of functional gene categories with a comparative metagenomic approach showed that this Guaymas chimney metagenome was clustered most closely with a chimney metagenome from Juan de Fuca. All chimney samples were enriched with genes involved in recombination and repair, chemotaxis and flagellar assembly, highlighting their roles in coping with the fluctuating extreme deep-sea environments. A high proportion of transposases was observed in all the metagenomes from deep-sea chimneys, supporting the previous hypothesis that horizontal gene transfer may be common in the deep-sea vent chimney biosphere. In the Guaymas chimney metagenome, thermophilic sulfate reducing microorganisms including bacteria and archaea were found predominant, and genes coding for the degradation of refractory organic compounds such as cellulose, lipid, pullullan, as well as a few hydrocarbons including toluene, ethylbenzene and o-xylene were identified. Therefore, this oil-immersed chimney supported a thermophilic microbial community capable of oxidizing a range of hydrocarbons that served as electron donors for sulphate reduction under anaerobic conditions.

  6. Crystal structure of the papain-like protease of MERS coronavirus reveals unusual, potentially druggable active-site features.

    Science.gov (United States)

    Lei, Jian; Mesters, Jeroen R; Drosten, Christian; Anemüller, Stefan; Ma, Qingjun; Hilgenfeld, Rolf

    2014-09-01

    The Middle-East Respiratory Syndrome coronavirus (MERS-CoV) causes severe acute pneumonia and renal failure. The MERS-CoV papain-like protease (PL(pro)) is a potential target for the development of antiviral drugs. To facilitate these efforts, we determined the three-dimensional structure of the enzyme by X-ray crystallography. The molecule consists of a ubiquitin-like domain and a catalytic core domain. The catalytic domain displays an extended right-hand fold with a zinc ribbon and embraces a solvent-exposed substrate-binding region. The overall structure of the MERS-CoV PL(pro) is similar to that of the corresponding SARS-CoV enzyme, but the architecture of the oxyanion hole and of the S3 as well as the S5 specificity sites differ from the latter. These differences are the likely reason for reduced in vitro peptide hydrolysis and deubiquitinating activities of the MERS-CoV PL(pro), compared to the homologous enzyme from the SARS coronavirus. Introduction of a side-chain capable of oxyanion stabilization through the Leu106Trp mutation greatly enhances the in vitro catalytic activity of the MERS-CoV PL(pro). The unique features observed in the crystal structure of the MERS-CoV PL(pro) should allow the design of antivirals that would not interfere with host ubiquitin-specific proteases.

  7. Megathrust Earthquake Potential of the Manila Subduction Systems Revealed by the Radial Component of Seismic Moment Tensors Mrr

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    Jing-Yi Lin

    2015-01-01

    Full Text Available We undertook an investigation of the seismic behavior of large earthquake and estimated the crustal deformation state in the northern Philippine area in terms of the radial component of seismic moment tensors (Mrr distribution. Based upon these two analyses, the seismic potential of the Manila Trench has been assessed. Regarding the seismic characteristics of large earthquakes, results show that both the overriding and the subducting plates are under compressive stress before the main large events but are characterized by an extensional regime after mainshocks. In the northern Manila Trench area, the broad zone of extensional seismic activity along the trench and its neighboring areas shows a stress environment distinct from that of the interseismic environment of large earthquakes, suggesting that the plates are in a relaxed state instead of accumulating tectonic stress. Thus, the coupling between the two plates could be weak. Along the central Manila Trench, even though only few extensional earthquakes occurred near the trench, numerous negative Mrr events in the overriding plate indicate that the crust is affected by a dilatational regime and also suggests a relatively low coupling environment. In the southern Manila Trench, with the exception of a few extensional events that occurred locally in the Central Valley Basin, most earthquakes show compressive mechanisms. We suggest that a relatively high plate coupling exists along this portion of the trench and results in stress accumulation not only along the plate interface but also in its vicinity, within the subducting and overriding plates.

  8. A genome-wide CNV analysis of schizophrenia reveals a potential role for a multiple-hit model.

    Science.gov (United States)

    Rudd, Danielle S; Axelsen, Michael; Epping, Eric A; Andreasen, Nancy C; Wassink, Thomas H

    2014-12-01

    Schizophrenia is a chronic and severe psychiatric disorder that is highly heritable. While both common and rare genetic variants contribute to disease risk, many questions still remain about disease etiology. We performed a genome-wide analysis of copy number variants (CNVs) in 166 schizophrenia subjects and 52 psychiatrically healthy controls. First, overall CNV characteristics were compared between cases and controls. The only statistically significant finding was that deletions comprised a greater proportion of CNVs in cases. High interest CNVs were then identified as conservative using the following filtering criteria: (i) known deleterious CNVs; (ii) CNVs > 1 Mb that were novel (not found in a database of control individuals); and (iii) CNVs 1 Mb) or with multiple conservative CNVs. Two case individuals with the highest burden of conservative CNVs also share a recurrent 15q11.2 BP1-2 deletion, indicating a role for a potential multiple-hit CNV model for schizophrenia. In total, we report three 15q11.2 BP1-2 deletion individuals with schizophrenia, adding to a growing body of evidence that this CNV is involved in disease etiology.

  9. Redox potential of the terminal quinone electron acceptor QB in photosystem II reveals the mechanism of electron transfer regulation.

    Science.gov (United States)

    Kato, Yuki; Nagao, Ryo; Noguchi, Takumi

    2016-01-19

    Photosystem II (PSII) extracts electrons from water at a Mn4CaO5 cluster using light energy and then transfers them to two plastoquinones, the primary quinone electron acceptor QA and the secondary quinone electron acceptor QB. This forward electron transfer is an essential process in light energy conversion. Meanwhile, backward electron transfer is also significant in photoprotection of PSII proteins. Modulation of the redox potential (Em) gap of QA and QB mainly regulates the forward and backward electron transfers in PSII. However, the full scheme of electron transfer regulation remains unresolved due to the unknown Em value of QB. Here, for the first time (to our knowledge), the Em value of QB reduction was measured directly using spectroelectrochemistry in combination with light-induced Fourier transform infrared difference spectroscopy. The Em(QB (-)/QB) was determined to be approximately +90 mV and was virtually unaffected by depletion of the Mn4CaO5 cluster. This insensitivity of Em(QB (-)/QB), in combination with the known large upshift of Em(QA (-)/QA), explains the mechanism of PSII photoprotection with an impaired Mn4CaO5 cluster, in which a large decrease in the Em gap between QA and QB promotes rapid charge recombination via QA (-).

  10. Redox potential of the terminal quinone electron acceptor QB in photosystem II reveals the mechanism of electron transfer regulation

    Science.gov (United States)

    Kato, Yuki; Nagao, Ryo; Noguchi, Takumi

    2016-01-01

    Photosystem II (PSII) extracts electrons from water at a Mn4CaO5 cluster using light energy and then transfers them to two plastoquinones, the primary quinone electron acceptor QA and the secondary quinone electron acceptor QB. This forward electron transfer is an essential process in light energy conversion. Meanwhile, backward electron transfer is also significant in photoprotection of PSII proteins. Modulation of the redox potential (Em) gap of QA and QB mainly regulates the forward and backward electron transfers in PSII. However, the full scheme of electron transfer regulation remains unresolved due to the unknown Em value of QB. Here, for the first time (to our knowledge), the Em value of QB reduction was measured directly using spectroelectrochemistry in combination with light-induced Fourier transform infrared difference spectroscopy. The Em(QB−/QB) was determined to be approximately +90 mV and was virtually unaffected by depletion of the Mn4CaO5 cluster. This insensitivity of Em(QB−/QB), in combination with the known large upshift of Em(QA−/QA), explains the mechanism of PSII photoprotection with an impaired Mn4CaO5 cluster, in which a large decrease in the Em gap between QA and QB promotes rapid charge recombination via QA−. PMID:26715751

  11. Integrative analysis reveals clinical phenotypes and oncogenic potentials of long non-coding RNAs across 15 cancer types

    Science.gov (United States)

    Piccolo, Stephen R.; Zhang, Xiao-Qin; Li, Jun-Hao; Zhou, Hui; Yang, Jian-Hua; Qu, Liang-Hu

    2016-01-01

    Long non-coding RNAs (lncRNAs) have been shown to contribute to tumorigenesis. However, surprisingly little is known about the comprehensive clinical and genomic characterization of lncRNAs across human cancer. In this study, we conducted comprehensive analyses for the expression profile, clinical outcomes, somatic copy number alterations (SCNAs) profile of lncRNAs in ~7000 clinical samples from 15 different cancer types. We identified significantly differentially expressed lncRNAs between tumor and normal tissues from each cancer. Notably, we characterized 47 lncRNAs which were extensively dysregulated in at least 10 cancer types, suggesting a conserved function in cancer development. We also analyzed the associations between lncRNA expressions and patient survival, and identified sets of lncRNAs that possessed significant prognostic values in specific cancer types. Our combined analysis of SCNA data and expression data uncovered 116 dysregulated lncRNAs are strikingly genomic altered across 15 cancer types, indicating their oncogenic potentials. Our study may lay the groundwork for future functional studies of lncRNAs and help facilitate the discovery of novel clinical biomarkers. PMID:27147563

  12. Proteomic Analysis of Excretory-Secretory Products of Mesocestoides corti Metacestodes Reveals Potential Suppressors of Dendritic Cell Functions

    Science.gov (United States)

    Vendelova, Emilia; Camargo de Lima, Jeferson; Lorenzatto, Karina Rodrigues; Monteiro, Karina Mariante; Mueller, Thomas; Veepaschit, Jyotishman; Grimm, Clemens; Brehm, Klaus; Hrčková, Gabriela; Lutz, Manfred B.; Ferreira, Henrique B.

    2016-01-01

    Accumulating evidences have assigned a central role to parasite-derived proteins in immunomodulation. Here, we report on the proteomic identification and characterization of immunomodulatory excretory-secretory (ES) products from the metacestode larva (tetrathyridium) of the tapeworm Mesocestoides corti (syn. M. vogae). We demonstrate that ES products but not larval homogenates inhibit the stimuli-driven release of the pro-inflammatory, Th1-inducing cytokine IL-12p70 by murine bone marrow-derived dendritic cells (BMDCs). Within the ES fraction, we biochemically narrowed down the immunosuppressive activity to glycoproteins since active components were lipid-free, but sensitive to heat- and carbohydrate-treatment. Finally, using bioassay-guided chromatographic analyses assisted by comparative proteomics of active and inactive fractions of the ES products, we defined a comprehensive list of candidate proteins released by M. corti tetrathyridia as potential suppressors of DC functions. Our study provides a comprehensive library of somatic and ES products and highlight some candidate parasite factors that might drive the subversion of DC functions to facilitate the persistence of M. corti tetrathyridia in their hosts. PMID:27736880

  13. Next-Generation Sequencing of Genomic DNA Fragments Bound to a Transcription Factor in Vitro Reveals Its Regulatory Potential

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    Yukio Kurihara

    2014-12-01

    Full Text Available Several transcription factors (TFs coordinate to regulate expression of specific genes at the transcriptional level. In Arabidopsis thaliana it is estimated that approximately 10% of all genes encode TFs or TF-like proteins. It is important to identify target genes that are directly regulated by TFs in order to understand the complete picture of a plant’s transcriptome profile. Here, we investigate the role of the LONG HYPOCOTYL5 (HY5 transcription factor that acts as a regulator of photomorphogenesis. We used an in vitro genomic DNA binding assay coupled with immunoprecipitation and next-generation sequencing (gDB-seq instead of the in vivo chromatin immunoprecipitation (ChIP-based methods. The results demonstrate that the HY5-binding motif predicted here was similar to the motif reported previously and that in vitro HY5-binding loci largely overlapped with the HY5-targeted candidate genes identified in previous ChIP-chip analysis. By combining these results with microarray analysis, we identified hundreds of HY5-binding genes that were differentially expressed in hy5. We also observed delayed induction of some transcripts of HY5-binding genes in hy5 mutants in response to blue-light exposure after dark treatment. Thus, an in vitro gDNA-binding assay coupled with sequencing is a convenient and powerful method to bridge the gap between identifying TF binding potential and establishing function.

  14. Suppression substractive hybridisation (SSH) and real time PCR reveal differential gene expression in the Pacific cupped oyster, Crassostrea gigas, challenged with Ostreid herpesvirus 1

    OpenAIRE

    2011-01-01

    Virus-induced genes were identified using suppression subtractive hybridisation (SSH) from Pacific cupped oyster, Crassostrea gigas, haemocytes challenged by OsHV-1. A total of 304 clones from SSH forward library were sequenced. Among these sequences, some homologues corresponded to (i) immune related genes (macrophage express protein, IK cytokine, interferon-induced protein 44 or multicopper oxidase), (ii) apoptosis related genes (Bcl-2) and (iii) cell signalling and virus receptor genes (gl...

  15. Early infection dynamics after experimental challenge with Mycobacterium avium subspecies paratuberculosis in calves reveal limited calf-to-calf transmission and no impact of Hsp70 vaccination.

    Science.gov (United States)

    Santema, Wiebren J; Poot, Jacqueline; Segers, Ruud P A M; Van den Hoff, Daniëlle J P; Rutten, Victor P M G; Koets, Ad P

    2012-11-19

    Efficient control of bovine paratuberculosis is hampered by lack of a vaccine. The purpose of this study was to evaluate efficacy of a candidate vaccine, consisting of recombinant Mycobacterium avium subspecies paratuberculosis (MAP) Hsp70 with DDA adjuvant, in calves experimentally infected with MAP. Four groups of 14 animals each were used. Animals in group 1 and 2 were all vaccinated with Hsp70/DDA at day 0, 84, 168 and 357, and those in group 3 and 4 were non-vaccinated controls. In each group half (n=7) of the animals were challenged and the remaining half served as contacts. Blood and fecal samples were collected at three week intervals until day 588, and subsequently all animals were subjected to necropsy. The primary outcomes assessed were fecal culture (FC) of MAP, tissue colonization of MAP, and transmission of infection to contact animals. The kinetics of MAP shedding in feces of challenged animals showed a peak around 130 days post-challenge, irrespective of vaccination status. At necropsy no differences in the level of tissue colonization between vaccinated animals and controls were observed in the challenged groups. Only one contact animal (non-vaccinated) was positive at necropsy, indicating limited to no transmission within groups. These findings indicate that Hsp70/DDA vaccination does not influence early infection dynamics after experimental infection. However, early shedding of MAP in calves did not result in efficient transmission of infection to contact animals. The latter implies that introduction of an infected calf in a cohort of susceptibles has limited consequences for spread of infection.

  16. Part-load performance characterization and energy savings potential of the RTU challenge unit: Carrier weather expert

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Weimin [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Katipamula, Srinivas [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Taasevigen, Danny J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-09-29

    This report documents the development of part-load performance curves and there use with the EnergyPlus simulation tool to estimate the potential savings from the use of WeatherExpert units compared to other standard options.

  17. Differences in potential for amino acid change after mutation reveals distinct strategies for kappa and lambda light-chain variation.

    Science.gov (United States)

    Hershberg, Uri; Shlomchik, Mark J

    2006-10-24

    B cells generate varied yet functional clones under high rates of mutation of their V genes. It has been proposed that as a result of the opposing demands of diversification and preservation of integrity, the V genes of heavy and light chains have evolved to overexpress codons prone to amino acid change in their complementarity determining regions (CDR) compared with the framework (FW) regions. We have analyzed the germ-line V genes of heavy and light chains (both kappa and lambda), comparing codons of CDR and FW of the germ-line V regions both to each other and to control regions. We found that in both germ-line heavy chains and lambda chains, CDR codons are prone to replacement mutations, whereas in the FW, the opposite is true. Furthermore, the difference between CDR and FW in heavy chains and lambda chains is based on codons that are prone to nonconservative changes of amino acid. In contrast, in germ-line kappa chains, the codons in both CDR and FW are more prone to replacement mutations. We also demonstrated that negative selection during immune responses is more sensitive to nonconservative amino acid substitutions than overall amino acid change, demonstrating the applicability of our analysis to real-time process of selection in the immune system. The differences in germ-line kappa and lambda light chains' potential reaction to mutation suggests that via these two differently evolved light-chain types, the B cell repertoire encompasses two different strategies to balance diversity and stability in an immune response.

  18. Different frontal involvement in ALS and PLS revealed by Stroop event-related potentials and reaction times

    Directory of Open Access Journals (Sweden)

    Ninfa eAmato

    2013-12-01

    Full Text Available BACKGROUND: A growing body of evidence suggests a link between cognitive and pathological changes in amyotrophic lateral sclerosis (ALS and in frontotemporal lobar dementia (FTLD. Cognitive deficits have been investigated much less extensively in primary lateral sclerosis (PLS than in ALS. OBJECTIVE: to investigate bioelectrical activity to Stroop test, assessing frontal function, in ALS, PLS and control groups. METHODS: 32 non-demented ALS patients, 10 non-demented PLS patients and 27 healthy subjects were included. Twenty-nine electroencephalography (EEG channels with binaural reference were recorded during covert Stroop task performance, involving mental discrimination of the stimuli and not vocal or motor response. Group effects on event related potentials (ERPs latency were analyzed using statistical multivariate analysis. Topographic analysis was performed using low resolution brain electromagnetic tomography (LORETA. RESULTS: ALS patients committed more errors in the execution of the task but they were not slower, whereas PLS patients did not show reduced accuracy, despite a slowing of reaction times (RTs. The main ERP components were delayed in ALS, but not in PLS, compared with controls. Moreover, RTs speed but not ERP latency correlated with clinical scores. ALS had decreased frontotemporal activity in the P2, P3 and N4 time windows compared to controls. CONCLUSION: These findings suggest a different pattern of psychophysiological involvement in ALS compared with PLS. The former is increasingly recognized to be a multisystems disorder, with a spectrum of executive and behavioural impairments reflecting frontotemporal dysfunction. The latter seems to mainly involve the motor system, with largely spared cognitive functions. Moreover, our results suggest that the covert version of the Stroop task used in the present study, may be useful to assess cognitive state in the very advanced stage of the disease, when other cognitive tasks are not

  19. Integrated gene co-expression network analysis in the growth phase of Mycobacterium tuberculosis reveals new potential drug targets.

    Science.gov (United States)

    Puniya, Bhanwar Lal; Kulshreshtha, Deepika; Verma, Srikant Prasad; Kumar, Sanjiv; Ramachandran, Srinivasan

    2013-11-01

    We have carried out weighted gene co-expression network analysis of Mycobacterium tuberculosis to gain insights into gene expression architecture during log phase growth. The differentially expressed genes between at least one pair of 11 different M. tuberculosis strains as source of biological variability were used for co-expression network analysis. This data included genes with highest coefficient of variation in expression. Five distinct modules were identified using topological overlap based clustering. All the modules together showed significant enrichment in biological processes: fatty acid biosynthesis, cell membrane, intracellular membrane bound organelle, DNA replication, Quinone biosynthesis, cell shape and peptidoglycan biosynthesis, ribosome and structural constituents of ribosome and transposition. We then extracted the co-expressed connections which were supported either by transcriptional regulatory network or STRING database or high edge weight of topological overlap. The genes trpC, nadC, pitA, Rv3404c, atpA, pknA, Rv0996, purB, Rv2106 and Rv0796 emerged as top hub genes. After overlaying this network on the iNJ661 metabolic network, the reactions catalyzed by 15 highly connected metabolic genes were knocked down in silico and evaluated by Flux Balance Analysis. The results showed that in 12 out of 15 cases, in 11 more than 50% of reactions catalyzed by genes connected through co-expressed connections also had altered fluxes. The modules 'Turquoise', 'Blue' and 'Red' also showed enrichment in essential genes. We could map 152 of the previously known or proposed drug targets in these modules and identified 15 new potential drug targets based on their high degree of co-expressed connections and strong correlation with module eigengenes.

  20. Suppression subtractive hybridization profiles of radial growth phase and metastatic melanoma cell lines reveal novel potential targets

    Directory of Open Access Journals (Sweden)

    Espreafico Enilza M

    2008-01-01

    available expression study databases allowed us to point to a great potential of involvement in tumor progression for several of the genes identified here. A few sequences obtained here may also contribute to extend annotated mRNAs or to the identification of novel transcripts.

  1. Proteomic Analysis of Fetal Ovary Reveals That Ovarian Developmental Potential Is Greater in Meishan Pigs than in Yorkshire Pigs.

    Directory of Open Access Journals (Sweden)

    Mengmeng Xu

    responsible for the low reproductive efficiency reported in other obese breeds. The ovarian developmental potential was found to be greater in Meishan pigs than in Yorkshire pigs.

  2. Proteomic Analysis of Fetal Ovary Reveals That Ovarian Developmental Potential Is Greater in Meishan Pigs than in Yorkshire Pigs.

    Science.gov (United States)

    Xu, Mengmeng; Che, Long; Wang, Dingyue; Yang, Zhenguo; Zhang, Pan; Lin, Yan; Fang, Zhengfeng; Che, Lianqiang; Li, Jian; Chen, Daiwen; Wu, De; Xu, Shengyu

    2015-01-01

    the low reproductive efficiency reported in other obese breeds. The ovarian developmental potential was found to be greater in Meishan pigs than in Yorkshire pigs.

  3. Secretome Prediction of Two M. tuberculosis Clinical Isolates Reveals Their High Antigenic Density and Potential Drug Targets

    Science.gov (United States)

    Cornejo-Granados, Fernanda; Zatarain-Barrón, Zyanya L.; Cantu-Robles, Vito A.; Mendoza-Vargas, Alfredo; Molina-Romero, Camilo; Sánchez, Filiberto; Del Pozo-Yauner, Luis; Hernández-Pando, Rogelio; Ochoa-Leyva, Adrián

    2017-01-01

    druggability analysis of the secretomes, we found potential drug targets such as cytochrome P450, thiol peroxidase, the Ag85C, and Ribonucleoside Reductase in the secreted proteins that could be used as drug targets for novel treatments against Tuberculosis. PMID:28223967

  4. Potential seasonal ecological challenge of heat strain among Australian Aboriginal people practicing traditional subsistence methods: a computer simulation.

    Science.gov (United States)

    Ulijaszek, S J

    2001-11-01

    It has been largely accepted that Australian Aboriginal people practicing hunting and gathering traditionally underused their objective economic possibilities by working short hours relative to nonhunter-gatherer populations. However, the possibility that their subsistence quest might have been limited by potential heat strain has not been considered for Australian hunter-gatherers. In this article the influence of work and heat load on the potential for heat strain among adult male Australian Aboriginal people is modelled. The possibility that the short working day of Arnhem Land adults reported in the literature might reflect ecologically limited work scheduling by way of potential heat strain is examined. Three climatic regions of the North of Western Australia and the Northern Territory were identified, using data available from the Australian Bureau of Meteorology. Data from the months of January, April, July, and October were used with the United States Army Heat Strain Model, along with assumptions with respect to work load and time scheduling. Predictive modelling indicates that a late start to the working day could carry considerable risks of potential heat strain during the summer, when humidity and maximum daily temperature are highest for all three climatic regions, but especially in the tropical coastal region. While extended work times may have been needed to acquire adequate food under traditional conditions, work output could have been limited by potential heat strain under some conditions likely to have prevailed.

  5. Critical roles of microRNAs in the pathogenesis of systemic sclerosis: New advances, challenges and potential directions.

    Science.gov (United States)

    Miao, Cheng-Gui; Xiong, You-Yi; Yu, Hao; Zhang, Xiao-Lin; Qin, Mei-Song; Song, Tong-Wen; Du, Chuan-Lai

    2015-09-01

    Systemic sclerosis (SSc) is an autoimmune disease characterized by immune disorders, vascular obliteration, excessive extracellular matrix deposition, skin fibrosis, and further pathological change of internal organs. To date, the exact etiology of this complicated disease remains unknown. Over the past few years, the roles of epigenetic modifications caused by environmental factors have been intensively studied in relation to the disease pathogenesis, and important advances have been made. This review focuses on the new advances of microRNAs (miRNAs) in the field of SSc research, including the upstream regulatory factors of miRNAs, the downstream targets, and the feedback mechanisms between miRNAs and their targets. We also discussed the correlation of miRNAs and DNA methylation, the miRNAs and the gene polymorphism. Overall, the findings presented in this review illustrated how miRNAs play important roles in the pathogenesis of SSc. However, several unanswered questions continue to impede our understanding of this complex disease. Future research should focus on the identification of new biomarkers for early diagnosis and prognosis, which will help us improve the clinical treatment of patients with SSc. In addition, we discussed the challenges of miRNA study in SSc in the future. Since the miRNA injection may be a promising therapeutic approach for SSc treatment, one of the challenges in the future is to evaluate the therapeutic effects of miRNA and anti-miRNAs using SSc model animals. In light of the fact that one miRNA can target many mRNAs, and one mRNA is targeted by many miRNAs, the effect of miRNA changes on other gene expression should be investigated to evaluate the treatment safety of miRNA injection in vivo.

  6. Potential relationship between phenotypic and molecular characteristics in revealing livestock-associated Staphylococcus aureus in Chinese humans without occupational livestock contact

    Directory of Open Access Journals (Sweden)

    Yanping Fan

    2016-09-01

    Full Text Available While some studies have defined Staphylococcus aureus based on its clonal complex and resistance pattern, few have explored the relations between the genetic lineages and antibiotic resistance patterns and immune evasion cluster (IEC genes. Our aim was to investigate the potential relationship between phenotypic and molecular characteristics so as to reveal livestock-associated S. aureus in humans. The study participants were interviewed, and they provided two nasal swabs for S. aureus analysis. All S. aureus and methicillin-resistant S. aureus (MRSA were tested for antibiotic susceptibility, multilocus sequence type and IEC genes. Of the 1162 participants, 9.3% carried S. aureus, including MRSA (1.4% and multidrug-resistant S. aureus (MDRSA, 2.8%. The predominant multidrug-resistant pattern among MDRSA isolates was nonsusceptibility to erythromycin, clindamycin and tetracycline. The most common S. aureus genotypes were ST7, ST6, ST188 and ST59, and the predominant MRSA genotype was ST7. Notably, the livestock-associated S. aureus isolates (IEC-negative CC9, IEC-negative tetracycline-resistant CC398, and IEC-negative tetracycline-resistant CC5 were found in people with no occupational livestock contact. These findings reveal a potential relationship between S. aureus CCs and IEC genes and antibiotic resistance patterns in defining livestock-associated S. aureus in humans and support growing concern about the potential livestock-to-human transmission of livestock-associated S. aureus by non-occupational livestock contact.

  7. The High Luminosity Challenge: potential and limitations of High Intensity High Brightness in the LHC and its injectors

    CERN Document Server

    De Maria, R; Banfi, D; Barranco, J; Bartosik, H; Benedetto, E; Bruce, R; Brüning, O; Calaga, R; Cerutti, F; Damerau, H; Esposito, L; Fartoukh, S; Fitterer, M; Garoby, R; Gilardoni, S; Giovannozzi, M; Goddard, B; Gorini, B; Hanke, K; Iadarola, G; Lamont, M; Meddahi, M; Métral, E; Mikulec, B; Mounet, N; Papaphilippou, Y; Pieloni, T; Redaelli, S; Rossi, L; Rumolo, G; Shaposhnikova, E; Sterbini, G; Todesco, E; Tomás, R; Zimmermann, F; Valishev, A

    2014-01-01

    High-intensity and high-brightness beams are key ingredients to maximize the LHC integrated luminosity and to exploit its full potential. This contribution describes the optimization of beam and machine parameters to maximize the integrated luminosity as seen by the LHC experiments, by taking into account the expected intensity and brightness reach of LHC itself and its injector chain as well as the capabilities of the detectors for next run and foreseen upgrade scenarios.

  8. Determination of genetic toxicity and potential carcinogenicity in vitro--challenges post the Seventh Amendment to the European Cosmetics Directive.

    Science.gov (United States)

    Tweats, D J; Scott, A D; Westmoreland, C; Carmichael, P L

    2007-01-01

    Genetic toxicology and its role in the detection of carcinogens is currently undergoing a period of reappraisal. There is an increasing interest in developing alternatives to animal testing and the three R's of reduction, refinement and replacement are the basis for EU and national animal protection laws the Seventh Amendment to the EU Cosmetics Directive will ban the marketing of cosmetic/personal care products that contain ingredients that have been tested in animal models. Thus in vivo tests such as the bone marrow micronucleus test, which has a key role in current testing strategies for genotoxicity, will not be available for this class of products. The attrition rate for new, valuable and safe chemicals tested in an in vitro-only testing battery, using the in vitro tests currently established for genotoxicity screening, will greatly increase once this legislation is in place. In addition there has been an explosion of knowledge concerning the cellular and molecular events leading to carcinogenesis. This knowledge has not yet been fully factored into screening chemicals for properties that are not directly linked to mutation induction. Thus there is a pressing need for new, more accurate approaches to determine genotoxicity and carcinogenicity. However, a considerable challenge is presented for these new approaches to be universally accepted and new tests sufficiently validated by March 2009 when the animal testing and marketing bans associated with the Seventh Amendment are due to come into force. This commentary brings together ideas and approaches from several international workshops and meetings to consider these issues.

  9. Renewable energy-driven desalination technologies: A comprehensive review on challenges and potential applications of integrated systems

    KAUST Repository

    Ghaffour, Noreddine

    2015-01-01

    Despite the tremendous improvements in conventional desalination technologies, its wide use is still limited due primarily to high energy requirements which are currently met with expensive fossil fuels. The use of alternative energy sources is essential to meet the growing demand for water desalination. In the last few decades a lot of effort has being directed in the use of different renewable energy (RE) sources to run desalination processes. However, the expansion of these efforts towards larger scale plants is hampered by several techno-economic challenges. Several medium-scale RE-driven desalination plants have been installed worldwide. Nevertheless, most of these plants are connected to the electrical grid to assure a continuous energy supply for stable operation. Furthermore, RE is mostly used to produce electric power which can be used to run desalination systems. This review paper focuses on an integrated approach in using RE-driven with an emphasis on solar and geothermal desalination technologies. Innovative and sustainable desalination processes which are suitable for integrated RE systems are presented. An assessment of the benefits of these technologies and their limitations are also discussed.

  10. Identification of a gene expression core signature for Duchenne Muscular Dystrophy (DMD) via integrative analysis reveals novel potential compounds for treatment

    KAUST Repository

    Ichim-Moreno, Norú

    2010-05-01

    Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy and one of the most prevalent genetic disorders of childhood. DMD is characterized by rapid progression of muscle degeneration, and ultimately death. Currently, glucocorticoids are the only available treatment for DMD, but they have been shown to result in serious side effects. The purpose of this research was to define a core signature of gene expression related to DMD via integrative analysis of mouse and human datasets. This core signature was subsequently used to screen for novel potential compounds that antagonistically affect the expression of signature genes. With this approach we were able to identify compounds that are 1) already used to treat DMD, 2) currently under investigation for treatment, and 3) so far unknown but promising candidates. Our study highlights the potential of meta-analyses through the combination of datasets to unravel previously unrecognized associations and reveal new relationships. © IEEE.

  11. Food waste collection and recycling for value-added products: potential applications and challenges in Hong Kong.

    Science.gov (United States)

    Lo, Irene M C; Woon, Kok Sin

    2016-04-01

    About 3600 tonnes food waste are discarded in the landfills in Hong Kong daily. It is expected that the three strategic landfills in Hong Kong will be exhausted by 2020. In consideration of the food waste management environment and community needs in Hong Kong, as well as with reference to the food waste management systems in cities such as Linköping in Sweden and Oslo in Norway, a framework of food waste separation, collection, and recycling for food waste valorization is proposed in this paper. Food waste can be packed in an optic bag (i.e., a bag in green color), while the residual municipal solid waste (MSW) can be packed in a common plastic bag. All the wastes are then sent to the refuse transfer stations, in which food waste is separated from the residual MSW using an optic sensor. On the one hand, the sorted food waste can be converted into valuable materials (e.g., compost, swine feed, fish feed). On the other hand, the sorted food waste can be sent to the proposed Organic Waste Treatment Facilities and sewage treatment works for producing biogas. The biogas can be recovered to produce electricity and city gas (i.e., heating fuel for cooking purpose). Due to the challenges faced by the value-added products in Hong Kong, the biogas is recommended to be upgraded as a biogas fuel for vehicle use. Hopefully, the proposed framework will provide a simple and effective approach to food waste separation at source and promote sustainable use of waste to resource in Hong Kong.

  12. Quantitative profiling of the shedding rate of the three Marek's disease virus (MDV) serotypes reveals that challenge with virulent MDV markedly increases shedding of vaccinal viruses.

    Science.gov (United States)

    Islam, Aminul; Walkden-Brown, Stephen W

    2007-08-01

    The shedding profile of Marek's disease virus serotype 1 (MDV1, virulent), serotype 2 (MDV2, vaccinal) and herpesvirus of turkeys (HVT, vaccinal) in commercial broiler chickens was determined by measuring the daily rate of production of feather dander from chickens housed in isolators and by quantifying the viral load of each of these serotypes in the dander using quantitative real-time PCR (qPCR). MDV1 and HVT viruses were detectable in dander filtered from isolator exhaust air from day 7 and MDV2 from day 12 after infection and thereafter until the end of the experiment at 61 days of age of the chickens. There was no difference in shedding rate among the three MDV1 isolates. Daily shedding of MDV1 increased sharply between days 7 and 28 and stabilized thereafter at about 10(9) virus copies per chicken per day, irrespective of vaccination status. Challenge with the three different MDV1 isolates markedly increased shedding of the vaccinal viruses HVT and MDV2 in dander by 38- and 75-fold, respectively. These results demonstrate the utility of qPCR for the differentiation and quantification of different MDV serotypes in feather dander and have significant implications for the routine monitoring of Marek's disease using qPCR assays of dust, for epidemiological modelling of the behaviour and spread of MDVs in chicken populations and for studies into the evolution of virulence in MDV1 in the face of blanket vaccination with imperfect vaccines that ameliorate disease but do not prevent infection and replication of virulent virus.

  13. Immunization with a synthetic robustoxin derivative lacking disulphide bridges protects against a potentially lethal challenge with funnel-web spider (Atrax robustus) venom

    Indian Academy of Sciences (India)

    Alfio Comis; Margaret Tyler; Ewan Mylecharane; Ian Spence; Merlin Howden

    2009-03-01

    The venom of male Atrax robustus spiders is potentially lethal to primates. These spiders have been responsible for a number of human deaths. Robustoxin is the lethal toxin in the venom. It is a highly cross-linked polypeptide that has 42 amino acid residues and four disulphide bridges. If these bridges are broken, the resulting polypeptide is nontoxic. Robustoxin was chemically synthesized with all of its eight cysteine residues protected with acetamidomethyl groups in order to avoid formation of disulphide bridges. The resulting derivative was co-polymerized with keyhole limpet haemocyanin. Two Macaca fascicularis monkeys were immunized with this conjugate. The monkeys were challenged, under anaesthesia, with a potentially lethal dose of male A. robustus crude venom. Both monkeys showed some minor symptoms of intoxication but recovered fully with no adverse after-effects. Immunization with the same immunogen, in the absence of keyhole limpet haemocyanin, did not protect a third monkey. The N-terminal 23 amino acid peptide derived from the sequence of robustoxin was synthesized and conjugated with ovalbumin. A fourth monkey was immunized with this conjugate. However, it was not protected against challenge. The implications of these results for the preparation of synthetic peptide vaccines are discussed.

  14. Immunization with a synthetic robustoxin derivative lacking disulphide bridges protects against a potentially lethal challenge with funnel-web spider (Atrax robustus) venom.

    Science.gov (United States)

    Comis, Alfio; Tyler, Margaret; Mylecharane, Ewan; Spence, Ian; Howden, Merlin

    2009-03-01

    The venom of male Atrax robustus spiders is potentially lethal to primates. These spiders have been responsible for a number of human deaths. Robustoxin is the lethal toxin in the venom. It is a highly cross-linked polypeptide that has 42 amino acid residues and four disulphide bridges. If these bridges are broken, the resulting polypeptide is non-toxic. Robustoxin was chemically synthesized with all of its eight cysteine residues protected with acetamidomethyl groups in order to avoid formation of disulphide bridges. The resulting derivative was co-polymerized with keyhole limpet haemocyanin. Two Macaca fascicularis monkeys were immunized with this conjugate. The monkeys were challenged,under anaesthesia,with a potentially lethal dose of male A.robustus crude venom. Both monkeys showed some minor symptoms of intoxication but recovered fully with no adverse after-effects. Immunization with the same immunogen, in the absence of keyhole limpet haemocyanin, did not protect a third monkey. The N-terminal 23 amino acid peptide derived from the sequence of robustoxin was synthesized and conjugated with ovalbumin. A fourth monkey was immunized with this conjugate. However,it was not protected against challenge.The implications of these results for the preparation of synthetic peptide vaccines are discussed.

  15. IMMUNOSTIMULATORY POTENTIAL OF DIETARY AMLA (PHYLLANTHUS EMBLICA IN GROWTH AND HAEMATOLOGY OF TILAPIA MOSSAMBICUS CHALLENGED WITH PSEUDOMONAS AERUGINOSA

    Directory of Open Access Journals (Sweden)

    A.Sivagurunathan

    2012-07-01

    Full Text Available The present study was carried out to evaluate the immunostimulant potential of Amla (Phyllanthus emblica. Formulated diets with different concentrations of ethanolic extract of P.emblica (D1=0%, D2=1% and D3=2% were fed to T.mossambicus for 40 days, the Specific Growth Rate (SGR, Feed Conversion Ratio (FCR were calculated and significant increase was observed in SGR & FCR. The experimental fishes were infected with Pseudomonas aeruginosa and after 5 days the haematological parameters like Total Erythrocyte count (TEC, Haemoglobin (Hb, Total leucocyte count (TLC, Differential leucocyte count (DLC, serum total protein, serum albumin and globulin levels were analyzed. The TEC, Hb, TLC, Lymphocytes, Neutrophils and monocyte counts increased significantly in D3 diet fed fishes. Highly significant increase was observed in serum total protein and albumin levels in fishes fed with D2 diet and increase in Globulin levels were insignificant. Basophil and Eosinophil counts decreased significantly. Thus P.emblica in fish feed preparations may be included as growth promoter and immunostimulator.

  16. “The Soft Power” of Small Countries: Kosovo Challenges and Potentials based on the Experience of Switzerland and Slovenia

    Directory of Open Access Journals (Sweden)

    MA. Gjenis Haxhimehmeti

    2015-12-01

    Full Text Available In the period of globalization when a big number of actors are involved in international relations, there is a need for smaller countries to be focused in a specific field in order to be successful in their foreign politics. The soft power with its increased importance is attracting academic circuits and those directly involved in foreign politics of different countries. The aim of this paper is to raise awareness among compilers and executers of foreign politics in Kosovo on the capacities that Kosovo has to achieve a success in foreign politics by the soft power. The goal can be achieved by the use of many scientific methods like: analytical – interpretive method, hermeneutic one, comparative method all of them having a holist approach to the topic. To have a better and more understandable output the study is focused in concrete examples of Switzerland and Slovenia as a potential topic to be elaborated due to the fact that in the past the states of Western Balkan didn’t pay that much attention the use of soft power in foreign politics. Instead they used the forms of classical diplomacy that resulted with not that good image of the region. Achievements of Switzerland and Slovenia by using an efficient soft power, could be a good example for Kosovo. In this case, being a crucial need, Kosovo can benefit by applying the soft power in the foreign policy.

  17. The challenges of big data.

    Science.gov (United States)

    Mardis, Elaine R

    2016-05-01

    The largely untapped potential of big data analytics is a feeding frenzy that has been fueled by the production of many next-generation-sequencing-based data sets that are seeking to answer long-held questions about the biology of human diseases. Although these approaches are likely to be a powerful means of revealing new biological insights, there are a number of substantial challenges that currently hamper efforts to harness the power of big data. This Editorial outlines several such challenges as a means of illustrating that the path to big data revelations is paved with perils that the scientific community must overcome to pursue this important quest.

  18. The challenges of big data

    Science.gov (United States)

    2016-01-01

    ABSTRACT The largely untapped potential of big data analytics is a feeding frenzy that has been fueled by the production of many next-generation-sequencing-based data sets that are seeking to answer long-held questions about the biology of human diseases. Although these approaches are likely to be a powerful means of revealing new biological insights, there are a number of substantial challenges that currently hamper efforts to harness the power of big data. This Editorial outlines several such challenges as a means of illustrating that the path to big data revelations is paved with perils that the scientific community must overcome to pursue this important quest. PMID:27147249

  19. The Use of Islamic Real Estate Investment Trust (I-REITs as a Contemporary Instrument in Developing Waqf Assets: Potential Structure, Issues and Challenges

    Directory of Open Access Journals (Sweden)

    Aznan Hasan

    2017-01-01

    Full Text Available The primary objective of this paper is to explore the potential of Islamic Real Estate Investment Trusts (I-REITs as an effective instrument for financing waqf development activities. This study employs legal research methodology, (the data used were largely library-based and documentary in nature, in which opinions of jurists, classical and contemporary are analysed in discussing the potential of I-REITs as a mechanism to develop waqf assets. Besides, several resolutions issued by relevant market authorities are referred to in this study. The study concludes that despite several challenges, with proper implementation, I-REITs may be adopted by a waqf institution as a mechanism to finance the development of their waqf assets. The novelty of this paper lies in the proposed structure of I-REITs, which can be a useful reference for the policy-makers and REITs issuers in establishing an enabling environment within which waqf I-REITs can potentially operate. Therefore, this study hopes to shed some light on the potential of waqf I-REIT to become an asset class to provide diversity for the public to give waqf.

  20. cDNA-AFLP analysis reveals differential gene expression in compatible interaction of wheat challenged with Puccinia striiformis f. sp. tritici

    Directory of Open Access Journals (Sweden)

    Huang Lili

    2009-06-01

    Full Text Available Abstract Background Puccinia striiformis f. sp. tritici is a fungal pathogen causing stripe rust, one of the most important wheat diseases worldwide. The fungus is strictly biotrophic and thus, completely dependent on living host cells for its reproduction, which makes it difficult to study genes of the pathogen. In spite of its economic importance, little is known about the molecular basis of compatible interaction between the pathogen and wheat host. In this study, we identified wheat and P. striiformis genes associated with the infection process by conducting a large-scale transcriptomic analysis using cDNA-AFLP. Results Of the total 54,912 transcript derived fragments (TDFs obtained using cDNA-AFLP with 64 primer pairs, 2,306 (4.2% displayed altered expression patterns after inoculation, of which 966 showed up-regulated and 1,340 down-regulated. 186 TDFs produced reliable sequences after sequencing of 208 TDFs selected, of which 74 (40% had known functions through BLAST searching the GenBank database. Majority of the latter group had predicted gene products involved in energy (13%, signal transduction (5.4%, disease/defence (5.9% and metabolism (5% of the sequenced TDFs. BLAST searching of the wheat stem rust fungus genome database identified 18 TDFs possibly from the stripe rust pathogen, of which 9 were validated of the pathogen origin using PCR-based assays followed by sequencing confirmation. Of the 186 reliable TDFs, 29 homologous to genes known to play a role in disease/defense, signal transduction or uncharacterized genes were further selected for validation of cDNA-AFLP expression patterns using qRT-PCR analyses. Results confirmed the altered expression patterns of 28 (96.5% genes revealed by the cDNA-AFLP technique. Conclusion The results show that cDNA-AFLP is a reliable technique for studying expression patterns of genes involved in the wheat-stripe rust interactions. Genes involved in compatible interactions between wheat and the

  1. Intramolecular telomeric G-quadruplexes dramatically inhibit DNA synthesis by replicative and translesion polymerases, revealing their potential to lead to genetic change.

    Directory of Open Access Journals (Sweden)

    Deanna N Edwards

    Full Text Available Recent research indicates that hundreds of thousands of G-rich sequences within the human genome have the potential to form secondary structures known as G-quadruplexes. Telomeric regions, consisting of long arrays of TTAGGG/AATCCC repeats, are among the most likely areas in which these structures might form. Since G-quadruplexes assemble from certain G-rich single-stranded sequences, they might arise when duplex DNA is unwound such as during replication. Coincidentally, these bulky structures when present in the DNA template might also hinder the action of DNA polymerases. In this study, single-stranded telomeric templates with the potential to form G-quadruplexes were examined for their effects on a variety of replicative and translesion DNA polymerases from humans and lower organisms. Our results demonstrate that single-stranded templates containing four telomeric GGG runs fold into intramolecular G-quadruplex structures. These intramolecular G quadruplexes are somewhat dynamic in nature and stabilized by increasing KCl concentrations and decreasing temperatures. Furthermore, the presence of these intramolecular G-quadruplexes in the template dramatically inhibits DNA synthesis by various DNA polymerases, including the human polymerase δ employed during lagging strand replication of G-rich telomeric strands and several human translesion DNA polymerases potentially recruited to sites of replication blockage. Notably, misincorporation of nucleotides is observed when certain translesion polymerases are employed on substrates containing intramolecular G-quadruplexes, as is extension of the resulting mismatched base pairs upon dynamic unfolding of this secondary structure. These findings reveal the potential for blockage of DNA replication and genetic changes related to sequences capable of forming intramolecular G-quadruplexes.

  2. Whole-exome sequencing reveals potential molecular predictors of relapse after discontinuation of the targeted therapy in chronic myeloid leukemia patients.

    Science.gov (United States)

    Smirnikhina, Svetlana A; Lavrov, Alexander V; Chelysheva, Ekaterina Yu; Adilgereeva, Elmira P; Shukhov, Oleg A; Turkina, Anna; Kutsev, Sergey I

    2016-07-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disease well treated by tyrosine kinase inhibitors (TKIs). The aim was to identify genes with a predictive value for relapse-free survival after TKI cessation in CML patients. We performed whole-exome sequencing of DNA from six CML patients in long-lasting deep molecular remission. Patients were divided into two groups with relapse (n = 3) and without relapse (n = 3) after TKI discontinuation. We found variants in genes CYP1B1, ALPK2, and IRF1 in group of patients with relapse and one variant in gene PARP9 in group of patients without relapse. We verified prognostic value of the found markers in a small group of patients with TKI discontinuation and demonstrated their high sensitivity (77%), specificity (86%), positive (85%), and negative (79%) predictive values. Thus we revealed genetic variants, which are potential markers of outcome prediction in CML patients after TKI discontinuation.

  3. iTRAQ-based quantitative proteomic analysis reveals potential factors associated with the enhancement of phenazine-1-carboxamide production in Pseudomonas chlororaphis P3.

    Science.gov (United States)

    Jin, Xue-Jie; Peng, Hua-Song; Hu, Hong-Bo; Huang, Xian-Qing; Wang, Wei; Zhang, Xue-Hong

    2016-06-07

    Phenazine-1-carboxamide (PCN), a phenazine derivative, is strongly antagonistic to fungal phytopathogens. Pseudomonas chlororaphis HT66 is a PCN-producing, non-pathogenic biocontrol strain, and we obtained the mutant P. chlororaphis P3, which produces 4.7 times more PCN than the wild-type HT66 strain. To reveal the cause of PCN production enhancement in P3 and find potential factors related to PCN biosynthesis, an iTRAQ-based quantitative proteomic analysis was used to study the expression changes between the two strains. Of the 452 differentially expressed proteins, most were functionally mapped into PCN biosynthesis pathway or other related metabolisms. The upregulation of proteins, including PhzA/B, PhzD, PhzF, PhzG, and PhzH, involved in PCN biosynthesis was in agreement with the efficient production of PCN in P3. A number of proteins that function primarily in energy production, amino acid metabolism, and secondary metabolism played important roles in PCN biosynthesis. Notably, proteins involved in the uptake and conversion of phosphate, inorganic nitrogen sources, and iron improved the PCN production. Furthermore, the type VI secretion system may participate in the secretion or/and indirect biosynthetic regulation of PCN in P. chlororaphis. This study provides valuable clues to better understand the biosynthesis, excretion and regulation of PCN in Pseudomonas and also provides potential gene targets for further engineering high-yield strains.

  4. Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin Dynamics.

    Science.gov (United States)

    Nicolai, Serena; Filippi, Silvia; Caputo, Manuela; Cipak, Lubos; Gregan, Juraj; Ammerer, Gustav; Frontini, Mattia; Willems, Daniela; Prantera, Giorgio; Balajee, Adayabalam S; Proietti-De-Santis, Luca

    2015-01-01

    The CSB protein, a member of the SWI/SNF ATP dependent chromatin remodeling family of proteins, plays a role in a sub-pathway of nucleotide excision repair (NER) known as transcription coupled repair (TCR). CSB is frequently mutated in Cockayne syndrome group B, a segmental progeroid human autosomal recessive disease characterized by growth failure and degeneration of multiple organs. Though initially classified as a DNA repair protein, recent studies have demonstrated that the loss of CSB results in pleiotropic effects. Identification of novel proteins belonging to the CSB interactome may be useful not only for predicting the molecular basis for diverse pathological symptoms of CS-B patients but also for unraveling the functions of CSB in addition to its authentic role in DNA repair. In this study, we performed tandem affinity purification (TAP) technology coupled with mass spectrometry and co-immunoprecipitation studies to identify and characterize the proteins that potentially interact with CSB-TAP. Our approach revealed 33 proteins that were not previously known to interact with CSB. These newly identified proteins indicate potential roles for CSB in RNA metabolism involving repression and activation of transcription process and in the maintenance of chromatin dynamics and integrity.

  5. Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group B (CSB Reveals Potential Roles for CSB in RNA Metabolism and Chromatin Dynamics.

    Directory of Open Access Journals (Sweden)

    Serena Nicolai

    Full Text Available The CSB protein, a member of the SWI/SNF ATP dependent chromatin remodeling family of proteins, plays a role in a sub-pathway of nucleotide excision repair (NER known as transcription coupled repair (TCR. CSB is frequently mutated in Cockayne syndrome group B, a segmental progeroid human autosomal recessive disease characterized by growth failure and degeneration of multiple organs. Though initially classified as a DNA repair protein, recent studies have demonstrated that the loss of CSB results in pleiotropic effects. Identification of novel proteins belonging to the CSB interactome may be useful not only for predicting the molecular basis for diverse pathological symptoms of CS-B patients but also for unraveling the functions of CSB in addition to its authentic role in DNA repair. In this study, we performed tandem affinity purification (TAP technology coupled with mass spectrometry and co-immunoprecipitation studies to identify and characterize the proteins that potentially interact with CSB-TAP. Our approach revealed 33 proteins that were not previously known to interact with CSB. These newly identified proteins indicate potential roles for CSB in RNA metabolism involving repression and activation of transcription process and in the maintenance of chromatin dynamics and integrity.

  6. Parasite-based screening and proteome profiling reveal orlistat, an FDA-approved drug, as a potential anti Trypanosoma brucei agent.

    Science.gov (United States)

    Yang, Peng-Yu; Wang, Min; Liu, Kai; Ngai, Mun Hong; Sheriff, Omar; Lear, Martin J; Sze, Siu Kwan; He, Cynthia Y; Yao, Shao Q

    2012-07-02

    Trypanosoma brucei is a parasite that causes African sleeping sickness in humans and nagana in livestock and is transmitted by the tsetse fly. There is an urgent need for the development of new drugs against African trypanosomiasis due to the lack of vaccines and effective drugs. Orlistat (also called tetrahydrolipstatin or THL) is an FDA-approved antiobesity drug targeting primarily the pancreatic and gastric lipases within the gastrointestinal tract. It shows potential activities against tumors, mycobacteria, and parasites. Herein, we report the synthesis and evaluation of an expanded set of orlistat-like compounds, some of which showed highly potent trypanocidal activities in both the bloodstream form (BSF) and the procyclic form (PCF) of T. brucei. Subsequent in situ parasite-based proteome profiling was carried out to elucidate potential cellular targets of the drug in both forms. Some newly identified targets were further validated by the labeling of recombinantly expressed enzymes in Escherichia coli lysates. Bioimaging experiments with a selected compound were carried out to study the cellular uptake of the drug in T. brucei. Results indicated that orlistat is much more efficiently taken up by the BSF than the PCF of T. brucei and has clear effects on the morphology of mitochondria, glycosomes, and the endoplasmic reticulum in both BSF and PCF cells. These results support specific effects of orlistat on these organelles and correlate well with our in situ proteome profiling. Given the economic challenges of de novo drug development for neglected diseases, we hope that our findings will stimulate further research towards the conversion of orlistat-like compounds into new trypanocidal drugs.

  7. Revealing Cultural Ecosystem Services through Instagram Images: The Potential of Social Media Volunteered Geographic Information for Urban Green Infrastructure Planning and Governance

    Directory of Open Access Journals (Sweden)

    Paulina Guerrero

    2016-06-01

    Full Text Available With the prevalence of smartphones, new ways of engaging citizens and stakeholders in urban planning and governance are emerging. The technologies in smartphones allow citizens to act as sensors of their environment, producing and sharing rich spatial data useful for new types of collaborative governance set-ups. Data derived from Volunteered Geographic Information (VGI can support accessible, transparent, democratic, inclusive, and locally-based governance situations of interest to planners, citizens, politicians, and scientists. However, there are still uncertainties about how to actually conduct this in practice. This study explores how social media VGI can be used to document spatial tendencies regarding citizens’ uses and perceptions of urban nature with relevance for urban green space governance. Via the hashtag #sharingcph, created by the City of Copenhagen in 2014, VGI data consisting of geo-referenced images were collected from Instagram, categorised according to their content and analysed according to their spatial distribution patterns. The results show specific spatial distributions of the images and main hotspots. Many possibilities and much potential of using VGI for generating, sharing, visualising and communicating knowledge about citizens’ spatial uses and preferences exist, but as a tool to support scientific and democratic interaction, VGI data is challenged by practical, technical and ethical concerns. More research is needed in order to better understand the usefulness and application of this rich data source to governance.

  8. High-resolution GPS tracking reveals habitat selection and the potential for long-distance seed dispersal by Madagascan flying foxes Pteropus rufus

    Directory of Open Access Journals (Sweden)

    Ryszard Oleksy

    2015-01-01

    Full Text Available Long-distance seed dispersal can be important for the regeneration of forested habitats, especially in regions where deforestation has been severe. Old World fruit bats (Pteropodidae have considerable potential for long-distance seed dispersal. We studied the movement patterns and feeding behaviour of the endemic Madagascan flying fox Pteropus rufus, in Berenty Reserve, southeast Madagascar. Between July and September 2012 (the dry season nine males and six females were tagged with customised GPS loggers which recorded fixes every 2.5 min between 18.00 and 06.00 h. The combined home range of all of the tagged bats during 86 nights exceeded 58,000 ha. Females had larger home ranges and core foraging areas and foraged over longer distances (average 28.1 km; median 26.7 km than males (average 15.4 km; median 9.5 km. Because the study was conducted during the gestation period, the increased energy requirements of females may explain their greater mean foraging area. Compositional analysis revealed that bats show strong preferences for overgrown sisal (Agave sisalana plantations (a mix of shrub, trees and sisal plants and remnant riverside forest patches. Sisal nectar and pollen were abundant food sources during the tracking period and this probably contributed to the selective use of overgrown sisal plantations. The bats also ate large quantities of figs (Ficus grevei during the study, and dispersed seeds of this important pioneer species. The bats flew at an average speed of 9.13 m/s, perhaps to optimise gliding performance. The study confirms that P. rufus has the potential to be a long-distance seed disperser, and is able to fly over a large area, often crossing cleared parts of its habitat. It potentially plays an important role in the regeneration of threatened forest habitats in this biodiversity hotspot.

  9. Ubiquitous Computing: Potentials and Challenges

    OpenAIRE

    Sen, Jaydip

    2010-01-01

    The world is witnessing the birth of a revolutionary computing paradigm that promises to have a profound effect on the way we interact with computers, devices, physical spaces, and other people. This new technology, called ubiquitous computing, envisions a world where embedded processors, computers, sensors, and digital communications are inexpensive commodities that are available everywhere. This paper presents a comprehensive discussion on the central trends in ubiquitous computing consider...

  10. Potential and Challenge of Ankylography

    CERN Document Server

    Miao, Jianwei; Mao, Yu; Martin, Leigh S; Kapteyn, Henry C

    2011-01-01

    The concept of ankylography, which under certain circumstances enables 3D structure determination from a single view[1], had ignited a lively debate even before its publication[2,3]. Since then, a number of readers requested the ankylographic reconstruction codes from us. To facilitate a better understanding of ankylography, we posted the source codes of the ankylographic reconstruction on a public website and encouraged interested readers to download the codes and test the method[4]. Those who have tested our codes confirm that the principle of ankylography works. Furthermore, our mathematical analysis and numerical simulations suggest that, for a continuous object with array size of 14x14x14 voxels, its 3D structure can usually be reconstructed from the diffraction intensities sampled on a spherical shell of 1 voxel thick[4]. In some cases where the object does not have very dense structure, ankylography can be applied to reconstruct its 3D image with array size of 25x25x25 voxels[4]. What remains to be elu...

  11. Ubiquitous Computing: Potentials and Challenges

    CERN Document Server

    Sen, Jaydip

    2010-01-01

    The world is witnessing the birth of a revolutionary computing paradigm that promises to have a profound effect on the way we interact with computers, devices, physical spaces, and other people. This new technology, called ubiquitous computing, envisions a world where embedded processors, computers, sensors, and digital communications are inexpensive commodities that are available everywhere. Ubiquitous computing will surround users with a comfortable and convenient information environment that merges physical and computational infrastructures into an integrated habitat. This habitat will feature a proliferation of hundreds or thousands of computing devices and sensors that will provide new functionality, offer specialized services, and boost productivity and interaction. This paper presents a comprehensive discussion on the central trends in ubiquitous computing considering them form technical, social and economic perspectives. It clearly identifies different application areas and sectors that will benefit f...

  12. Working Pupils: Challenges and Potential

    Science.gov (United States)

    Howieson, C.; McKechnie, J.; Semple, S.

    2012-01-01

    Successive governments, agencies and employer organisations have stressed the need for school leavers to be better prepared for working life, in particular, to achieve what are frequently termed employability skills; schools are expected to contribute to this policy agenda. Some academic commentators, however, criticise the concept of…

  13. Crystal structure of the adenosine A 2A receptor bound to an antagonist reveals a potential allosteric pocket

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Bingfa; Bachhawat, Priti; Chu, Matthew Ling-Hon; Wood, Martyn; Ceska, Tom; Sands, Zara A.; Mercier, Joel; Lebon, Florence; Kobilka, Tong Sun; Kobilka, Brian K.

    2017-02-06

    The adenosine A2A receptor (A2AR) has long been implicated in cardiovascular disorders. As more selective A2AR ligands are being identified, its roles in other disorders, such as Parkinson’s disease, are starting to emerge, and A2AR antagonists are important drug candidates for nondopaminergic anti-Parkinson treatment. Here we report the crystal structure of A2A receptor bound to compound 1 (Cmpd-1), a novel A2AR/N-methyl D-aspartate receptor subtype 2B (NR2B) dual antagonist and potential anti-Parkinson candidate compound, at 3.5 Å resolution. The A2A receptor with a cytochrome b562-RIL (BRIL) fusion (A2AR–BRIL) in the intracellular loop 3 (ICL3) was crystallized in detergent micelles using vapor-phase diffusion. Whereas A2AR–BRIL bound to the antagonist ZM241385 has previously been crystallized in lipidic cubic phase (LCP), structural differences in the Cmpd-1–bound A2AR–BRIL prevented formation of the lattice observed with the ZM241385–bound receptor. The crystals grew with a type II crystal lattice in contrast to the typical type I packing seen from membrane protein structures crystallized in LCP. Cmpd-1 binds in a position that overlaps with the native ligand adenosine, but its methoxyphenyl group extends to an exosite not previously observed in other A2AR structures. Structural analysis revealed that Cmpd-1 binding results in the unique conformations of two tyrosine residues, Tyr91.35 and Tyr2717.36, which are critical for the formation of the exosite. The structure reveals insights into antagonist binding that are not observed in other A2AR structures, highlighting flexibility in the binding pocket that may facilitate the development of A2AR-selective compounds for the treatment of Parkinson’s disease.

  14. The Crystal Structure of the Ivy delta4-16:0-ACP Desaturase Reveals Structural Details of the Oxidized Active Site and Potential Determinants of Regioselectivity

    Energy Technology Data Exchange (ETDEWEB)

    Guy,J.; Whittle, E.; Kumaran, D.; Lindqvist, Y.; Shanklin, J.

    2007-01-01

    The multifunctional acyl-acyl carrier protein (ACP) desaturase from Hedera helix (English ivy) catalyzes the {Delta}{sup 4} desaturation of 16:0-ACP and the{Delta}{sup 9} desaturation of 18:0-ACP and further desaturates{Delta}{sup 9}-16:1 or {Delta}{sup 9}-18:1 to the corresponding {Delta}{sup 4,9} dienes. The crystal structure of the enzyme has been solved to 1.95{angstrom} resolution, and both the iron-iron distance of 3.2{angstrom} and the presence of a {mu}-oxo bridge reveal this to be the only reported structure of a desaturase in the oxidized FeIII-FeIII form. Significant differences are seen between the oxidized active site and the reduced active site of the Ricinus communis (castor) desaturase; His{sup 227} coordination to Fe2 is lost, and the side chain of Glu{sup 224}, which bridges the two iron ions in the reduced structure, does not interact with either iron. Although carboxylate shifts have been observed on oxidation of other diiron proteins, this is the first example of the residue moving beyond the coordination range of both iron ions. Comparison of the ivy and castor structures reveal surface amino acids close to the annulus of the substrate-binding cavity and others lining the lower portion of the cavity that are potential determinants of their distinct substrate specificities. We propose a hypothesis that differences in side chain packing explains the apparent paradox that several residues lining the lower portion of the cavity in the ivy desaturase are bulkier than their equivalents in the castor enzyme despite the necessity for the ivy enzyme to accommodate three more carbons beyond the diiron site.

  15. IL-2 immunotherapy reveals potential for innate beta cell regeneration in the non-obese diabetic mouse model of autoimmune diabetes.

    Directory of Open Access Journals (Sweden)

    Yaiza Diaz-de-Durana

    Full Text Available Type-1 diabetes (T1D is an autoimmune disease targeting insulin-producing beta cells, resulting in dependence on exogenous insulin. To date, significant efforts have been invested to develop immune-modulatory therapies for T1D treatment. Previously, IL-2 immunotherapy was demonstrated to prevent and reverse T1D at onset in the non-obese diabetic (NOD mouse model, revealing potential as a therapy in early disease stage in humans. In the NOD model, IL-2 deficiency contributes to a loss of regulatory T cell function. This deficiency can be augmented with IL-2 or antibody bound to IL-2 (Ab/IL-2 therapy, resulting in regulatory T cell expansion and potentiation. However, an understanding of the mechanism by which reconstituted regulatory T cell function allows for reversal of diabetes after onset is not clearly understood. Here, we describe that Ab/IL-2 immunotherapy treatment, given at the time of diabetes onset in NOD mice, not only correlated with reversal of diabetes and expansion of Treg cells, but also demonstrated the ability to significantly increase beta cell proliferation. Proliferation appeared specific to Ab/IL-2 immunotherapy, as anti-CD3 therapy did not have a similar effect. Furthermore, to assess the effect of Ab/IL-2 immunotherapy well after the development of diabetes, we tested the effect of delaying treatment for 4 weeks after diabetes onset, when beta cells were virtually absent. At this late stage after diabetes onset, Ab/IL-2 treatment was not sufficient to reverse hyperglycemia. However, it did promote survival in the absence of exogenous insulin. Proliferation of beta cells could not account for this improvement as few beta cells remained. Rather, abnormal insulin and glucagon dual-expressing cells were the only insulin-expressing cells observed in islets from mice with established disease. Thus, these data suggest that in diabetic NOD mice, beta cells have an innate capacity for regeneration both early and late in disease

  16. High-Throughput Sequencing Reveals H2O2 Stress-Associated MicroRNAs and a Potential Regulatory Network in Brachypodium distachyon Seedlings

    Science.gov (United States)

    Lv, Dong-Wen; Zhen, Shoumin; Zhu, Geng-Rui; Bian, Yan-Wei; Chen, Guan-Xing; Han, Cai-Xia; Yu, Zi-Tong; Yan, Yue-Ming

    2016-01-01

    Oxidative stress in plants can be triggered by many environmental stress factors, such as drought and salinity. Brachypodium distachyon is a model organism for the study of biofuel plants and crops, such as wheat. Although recent studies have found many oxidative stress response-related proteins, the mechanism of microRNA (miRNA)-mediated oxidative stress response is still unclear. Using next generation high-throughput sequencing technology, the small RNAs were sequenced from the model plant B. distachyon 21 (Bd21) under H2O2 stress and normal growth conditions. In total, 144 known B. distachyon miRNAs and 221 potential new miRNAs were identified. Further analysis of potential new miRNAs suggested that 36 could be clustered into known miRNA families, while the remaining 185 were identified as B. distachyon-specific new miRNAs. Differential analysis of miRNAs from the normal and H2O2 stress libraries identified 31 known and 30 new H2O2 stress responsive miRNAs. The expression patterns of seven representative miRNAs were verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis, which produced results consistent with those of the deep sequencing method. Moreover, we also performed RT-qPCR analysis to verify the expression levels of 13 target genes and the cleavage site of 5 target genes by known or novel miRNAs were validated experimentally by 5′ RACE. Additionally, a miRNA-mediated gene regulatory network for H2O2 stress response was constructed. Our study identifies a set of H2O2-responsive miRNAs and their target genes and reveals the mechanism of oxidative stress response and defense at the post-transcriptional regulatory level.

  17. Potentiation of the bioavailability of blueberry phenolic compounds by co-ingested grape phenolic compounds in mice, revealed by targeted metabolomic profiling in plasma and feces.

    Science.gov (United States)

    Dudonné, Stéphanie; Dal-Pan, Alexandre; Dubé, Pascal; Varin, Thibault V; Calon, Frédéric; Desjardins, Yves

    2016-08-10

    The low bioavailability of dietary phenolic compounds, resulting from poor absorption and high rates of metabolism and excretion, is a concern as it can limit their potential beneficial effects on health. Targeted metabolomic profiling in plasma and feces of mice supplemented for 15 days with a blueberry extract, a grape extract or their combination revealed significantly increased plasma concentrations (3-5 fold) of blueberry phenolic metabolites in the presence of a co-ingested grape extract, associated with an equivalent decrease in their appearance in feces. Additionally, the repeated daily administration of the blueberry-grape combination significantly increased plasma phenolic concentrations (2-3-fold) compared to animals receiving only a single acute dose, with no such increase being observed with individual extracts. These findings highlight a positive interaction between blueberry and grape constituents, in which the grape extract enhanced the absorption of blueberry phenolic compounds. This study provides for the first time in vivo evidence of such an interaction occurring between co-ingested phenolic compounds from fruit extracts leading to their improved bioavailability.

  18. The oscillatory activities and its synchronization in auditory-visual integration as revealed by event-related potentials to bimodal stimuli

    Science.gov (United States)

    Guo, Jia; Xu, Peng; Yao, Li; Shu, Hua; Zhao, Xiaojie

    2012-03-01

    Neural mechanism of auditory-visual speech integration is always a hot study of multi-modal perception. The articulation conveys speech information that helps detect and disambiguate the auditory speech. As important characteristic of EEG, oscillations and its synchronization have been applied to cognition research more and more. This study analyzed the EEG data acquired by unimodal and bimodal stimuli using time frequency and phase synchrony approach, investigated the oscillatory activities and its synchrony modes behind evoked potential during auditory-visual integration, in order to reveal the inherent neural integration mechanism under these modes. It was found that beta activity and its synchronization differences had relationship with gesture N1-P2, which happened in the earlier stage of speech coding to pronouncing action. Alpha oscillation and its synchronization related with auditory N1-P2 might be mainly responsible for auditory speech process caused by anticipation from gesture to sound feature. The visual gesture changing enhanced the interaction of auditory brain regions. These results provided explanations to the power and connectivity change of event-evoked oscillatory activities which matched ERPs during auditory-visual speech integration.

  19. Garlic, from Remedy to Stimulant: Evaluation of Antifungal Potential Reveals Diversity in Phytoalexin Allicin Content among Garlic Cultivars; Allicin Containing Aqueous Garlic Extracts Trigger Antioxidants in Cucumber

    Science.gov (United States)

    Hayat, Sikandar; Cheng, Zhihui; Ahmad, Husain; Ali, Muhammad; Chen, Xuejin; Wang, Mengyi

    2016-01-01

    Garlic has the charisma of a potent remedy and holds its repute of a therapeutic panacea since the dawn of civilization. An integrated approach was adopted to evaluate the genetic diversity among Chinese garlic cultivars for their antifungal potency as well as allicin content distribution and, furthermore; a bioassay was performed to study the bio-stimulation mechanism of aqueous garlic extracts (AGE) in the growth and physiology of cucumber (Cucumis sativus). Initially, 28 garlic cultivars were evaluated against four kinds of phytopathogenic fungi; Fusarium oxysporum, Botrytis cinerea, Verticillium dahliae and Phytophthora capsici, respectively. A capricious antifungal potential among the selected garlic cultivars was observed. HPLC fingerprinting and quantification confirmed diversity in allicin abundance among the selected cultivars. Cultivar G025, G064, and G074 had the highest allicin content of 3.98, 3.7, and 3.66 mg g-1, respectively, whereas G110 was found to have lowest allicin content of 0.66 mg g-1. Cluster analysis revealed three groups on the basis of antifungal activity and allicin content among the garlic cultivars. Cultivar G025, G2011-4, and G110 were further evaluated to authenticate the findings through different solvents and shelf life duration and G025 had the strongest antifungal activity in all conditions. minimum inhibitory concentration and minimum fungicidal concentration of Allicin aqueous standard (AAS) and AGE showed significant role of allicin as primary antifungal substance of AGE. Leaf disk bioassay against P. capsici and V. dahliae to comparatively study direct action of AGE and AAS during infection process employing eggplant and pepper leaves showed a significant reduction in infection percentage. To study the bioactivity of AGE, a bioassay was performed using cucumber seedlings and results revealed that AGE is biologically active inside cucumber seedlings and alters the defense mechanism of the plant probably activating reactive

  20. Garlic, from Remedy to Stimulant:Evaluation of Antifungal Potential Reveals Diversity in Phytoalexin Allicin Content among Garlic Cultivars; Allicin Containing Aqueous Garlic Extracts Trigger Antioxidants in Cucumber

    Directory of Open Access Journals (Sweden)

    Sikandar Hayat

    2016-08-01

    Full Text Available Garlic has the charisma of a potent remedy and holds its repute of a therapeutic panacea since the dawn of civilization. An integrated approach was adopted to evaluate the genetic diversity among Chinese garlic cultivars for their antifungal potency as well as allicin content distribution and, furthermore; a bioassay was performed to study the bio-stimulation mechanism of aqueous garlic extracts (AGE in the growth and physiology of cucumber (Cucumis sativus. Initially, 28 garlic cultivars were evaluated against four kinds of phytopathogenic fungi; Fusarium oxysporum, Botrytis cinerea, Verticillium dahliae and Phytopthora capsici, respectively. A capricious antifungal potential among the selected garlic cultivars was observed. HPLC fingerprinting and quantification confirmed diversity in allicin abundance among the selected cultivars. Cultivar G025, G064 and G074 had the highest allicin content of 3.98, 3.7 and 3.66 mg g-1 respectively, whereas G110 was found to have lowest allicin content of 0.66 mg g-1. Cluster analysis revealed three groups on the basis of antifungal activity and allicin content among the garlic cultivars. Cultivar G025, G2011-4 and G110 were further evaluated to authenticate the findings through different solvents and shelf life duration and G025 had the strongest antifungal activity in all conditions. Leaf disc bioassay against Phytophthora capsici and Verticillium dahliae to comparatively study direct action of AGE and Allicin aqueous standard (AAS during infection process employing eggplant and pepper leaves showed a significant reduction in infection percentage. To study the bioactivity of AGE, a bioassay was performed using cucumber seedlings and results revealed that AGE is biologically active inside cucumber seedlings and alters the defense mechanism of the plant probably activating ROS at mild concentrations. However, at higher concentrations, it might cause lipid peroxidation and membrane damage which temper the

  1. Immunohistochemical determination of HER-2/neu overexpression in malignant melanoma reveals no prognostic value, while c-Kit (CD117 overexpression exhibits potential therapeutic implications

    Directory of Open Access Journals (Sweden)

    Potti Anil

    2003-01-01

    Full Text Available Abstract Background HER-2/neu and c-kit (CD117 onco-protein are increasingly being recognized as targets for therapy in solid tumors, but data on their role in malignant melanoma is currently limited. We studied the prevalence of overexpression of HER-2/neu and c-Kit in 202 patients with malignant melanoma to evaluate a possible prognostic value of these molecular targets in malignant melanoma. Methods Overexpression of HER-2/neu and c-Kit was evaluated using immunohistochemical assays in 202 archival tissue specimens. Results Between 1991 and 2001, 202 subjects (109 males; 54% and 93 females; 46% with malignant melanoma were studied with a mean age of 57 years (age range: 15–101 years. The most common histologic type was amelanotic melanoma (n = 62; 30.7% followed by superficial spreading melanoma (n = 54; 26.7%. The depth of penetration of melanoma (Breslow thickness, pT Stage ranged from 0.4 mm (stage pT1 to 8.0 mm (stage pT4A. Mean thickness was 2.6 mm (stage pT3A. The ECOG performance scores ranged from 0 to 3. Only 2 patients (0.9% revealed HER-2/neu overexpression, whereas 46 (22.8% revealed c-Kit overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit positive and negative groups (p = 0.36. Interestingly, not only was c-Kit more likely to be overexpressed in the superficial spreading type, a preliminary association between the presence or absence of c-Kit overexpression and the existence of another second primary tumor was also observed. Conclusions The results of our large study indicate that the HER-2/neu onco-protein neither has a role in melanogenesis nor is a potential target for clinical trials with monoclonal antibody therapy. This indicates there is no role for its testing in patients with malignant melanoma. Although c-Kit, expressed preferentially in the superficial spreading type, may not have prognostic value, it does have significant therapeutic implications as a

  2. Long Non-coding RNAs Expression Profile in HepG2 Cells Reveals the Potential Role of Long Non-coding RNAs in the Cholesterol Metabolism

    Directory of Open Access Journals (Sweden)

    Gang Liu

    2015-01-01

    Full Text Available Background: Green tea has been shown to improve cholesterol metabolism in animal studies, but the molecular mechanisms underlying this function have not been fully understood. Long non-coding RNAs (lncRNAs have recently emerged as a major class of regulatory molecules involved in a broad range of biological processes and complex diseases. Our aim was to identify important lncRNAs that might play an important role in contributing to the benefits of epigallocatechin-3-gallate (EGCG on cholesterol metabolism. Methods: Microarrays was used to reveal the lncRNA and mRNA profiles in green tea polyphenol(--epigallocatechin gallate in cultured human liver (HepG2 hepatocytes treated with EGCG and bioinformatic analyses of the predicted target genes were performed to identify lncRNA-mRNA targeting relationships. RNA interference was used to investigate the role of lncRNAs in cholesterol metabolism. Results: The expression levels of 15 genes related to cholesterol metabolism and 285 lncRNAs were changed by EGCG treatment. Bioinformatic analysis found five matched lncRNA-mRNA pairs for five differentially expressed lncRNAs and four differentially expressed mRNA. In particular, the lncRNA AT102202 and its potential targets mRNA-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR were identified. Using a real-time polymerase chain reaction technique, we confirmed that EGCG down-regulated mRNA expression level of the HMGCR and up-regulated expression of AT102202. After AT102202 knockdown in HepG2, we observed that the level of HMGCR expression was significantly increased relative to the scrambled small interfering RNA control (P < 0.05. Conclusions: Our results indicated that EGCG improved cholesterol metabolism and meanwhile changed the lncRNAs expression profile in HepG2 cells. LncRNAs may play an important role in the cholesterol metabolism.

  3. Complete genome-wide screening and subtractive genomic approach revealed new virulence factors, potential drug targets against bio-war pathogen Brucella melitensis 16M.

    Science.gov (United States)

    Pradeepkiran, Jangampalli Adi; Sainath, Sri Bhashyam; Kumar, Konidala Kranthi; Bhaskar, Matcha

    2015-01-01

    Brucella melitensis 16M is a Gram-negative coccobacillus that infects both animals and humans. It causes a disease known as brucellosis, which is characterized by acute febrile illness in humans and causes abortions in livestock. To prevent and control brucellosis, identification of putative drug targets is crucial. The present study aimed to identify drug targets in B. melitensis 16M by using a subtractive genomic approach. We used available database repositories (Database of Essential Genes, Kyoto Encyclopedia of Genes and Genomes Automatic Annotation Server, and Kyoto Encyclopedia of Genes and Genomes) to identify putative genes that are nonhomologous to humans and essential for pathogen B. melitensis 16M. The results revealed that among 3 Mb genome size of pathogen, 53 putative characterized and 13 uncharacterized hypothetical genes were identified; further, from Basic Local Alignment Search Tool protein analysis, one hypothetical protein showed a close resemblance (50%) to Silicibacter pomeroyi DUF1285 family protein (2RE3). A further homology model of the target was constructed using MODELLER 9.12 and optimized through variable target function method by molecular dynamics optimization with simulating annealing. The stereochemical quality of the restrained model was evaluated by PROCHECK, VERIFY-3D, ERRAT, and WHATIF servers. Furthermore, structure-based virtual screening was carried out against the predicted active site of the respective protein using the glycerol structural analogs from the PubChem database. We identified five best inhibitors with strong affinities, stable interactions, and also with reliable drug-like properties. Hence, these leads might be used as the most effective inhibitors of modeled protein. The outcome of the present work of virtual screening of putative gene targets might facilitate design of potential drugs for better treatment against brucellosis.

  4. Yeast population dynamics reveal a potential 'collaboration' between Metschnikowia pulcherrima and Saccharomyces uvarum for the production of reduced alcohol wines during Shiraz fermentation.

    Science.gov (United States)

    Contreras, A; Curtin, C; Varela, C

    2015-02-01

    The wine sector is actively seeking strategies and technologies that facilitate the production of wines with lower alcohol content. One of the simplest approaches to achieve this aim would be the use of wine yeast strains which are less efficient at transforming grape sugars into ethanol; however, commercial wine yeasts have very similar ethanol yields. We recently demonstrated that Metschnikowia pulcherrima AWRI1149 was able to produce wine with reduced alcohol concentration when used in sequential inoculation with a wine strain of Saccharomyces cerevisiae. Here, different inoculation regimes were explored to study the effect of yeast population dynamics and potential yeast interactions on the metabolism of M. pulcherrima AWRI1149 during fermentation of non-sterile Shiraz must. Of all inoculation regimes tested, only ferments inoculated with M. pulcherrima AWRI1149 showed reduced ethanol concentration. Population dynamics revealed the presence of several indigenous yeast species and one of these, Saccharomyces uvarum (AWRI 2846), was able to produce wine with reduced ethanol concentration in sterile conditions. Both strains however, were inhibited when a combination of three non-Saccharomyces strains, Hanseniaspora uvarum AWRI863, Pichia kluyveri AWRI1896 and Torulaspora delbrueckii AWRI2845 were inoculated into must, indicating that the microbial community composition might impact on the growth of M. pulcherrima AWRI1149 and S. uvarum AWRI 2846. Our results indicate that mixed cultures of M. pulcherrima AWRI1149 and S. uvarum AWRI2846 enable an additional reduction of wine ethanol concentration compared to the same must fermented with either strain alone. This work thus provides a foundation to develop inoculation regimes for the successful application of non-cerevisiae yeast to the production of wines with reduced alcohol.

  5. Proteomic analysis in type 2 diabetes patients before and after a very low calorie diet reveals potential disease state and intervention specific biomarkers.

    Directory of Open Access Journals (Sweden)

    Maria A Sleddering

    Full Text Available Very low calorie diets (VLCD with and without exercise programs lead to major metabolic improvements in obese type 2 diabetes patients. The mechanisms underlying these improvements have so far not been elucidated fully. To further investigate the mechanisms of a VLCD with or without exercise and to uncover possible biomarkers associated with these interventions, blood samples were collected from 27 obese type 2 diabetes patients before and after a 16-week VLCD (Modifast ∼ 450 kcal/day. Thirteen of these patients followed an exercise program in addition to the VCLD. Plasma was obtained from 27 lean and 27 obese controls as well. Proteomic analysis was performed using mass spectrometry (MS and targeted multiple reaction monitoring (MRM and a large scale isobaric tags for relative and absolute quantitation (iTRAQ approach. After the 16-week VLCD, there was a significant decrease in body weight and HbA1c in all patients, without differences between the two intervention groups. Targeted MRM analysis revealed differences in several proteins, which could be divided in diabetes-associated (fibrinogen, transthyretin, obesity-associated (complement C3, and diet-associated markers (apolipoproteins, especially apolipoprotein A-IV. To further investigate the effects of exercise, large scale iTRAQ analysis was performed. However, no proteins were found showing an exercise effect. Thus, in this study, specific proteins were found to be differentially expressed in type 2 diabetes patients versus controls and before and after a VLCD. These proteins are potential disease state and intervention specific biomarkers.Controlled-Trials.com ISRCTN76920690.

  6. Revealing mechanisms of selective, concentration-dependent potentials of 4-hydroxy-2-nonenal to induce apoptosis in cancer cells through inactivation of membrane-associated catalase.

    Science.gov (United States)

    Bauer, Georg; Zarkovic, Neven

    2015-04-01

    Tumor cells generate extracellular superoxide anions and are protected against superoxide anion-mediated intercellular apoptosis-inducing signaling by the expression of membrane-associated catalase. 4-Hydroxy-2-nonenal (4-HNE), a versatile second messenger generated during lipid peroxidation, has been shown to induce apoptosis selectively in malignant cells. The findings described in this paper reveal the strong, concentration-dependent potential of 4-HNE to specifically inactivate extracellular catalase of tumor cells both indirectly and directly and to consequently trigger apoptosis in malignant cells through superoxide anion-mediated intercellular apoptosis-inducing signaling. Namely, 4-HNE caused apoptosis selectively in NOX1-expressing tumor cells through inactivation of their membrane-associated catalase, thus reactivating subsequent intercellular signaling through the NO/peroxynitrite and HOCl pathways, followed by the mitochondrial pathway of apoptosis. Concentrations of 4-HNE of 1.2 µM and higher directly inactivated membrane-associated catalase of tumor cells, whereas at lower concentrations, 4-HNE triggered a complex amplificatory pathway based on initial singlet oxygen formation through H2O2 and peroxynitrite interaction. Singlet-oxygen-dependent activation of the FAS receptor and caspase-8 increased superoxide anion generation by NOX1 and amplification of singlet oxygen generation, which allowed singlet-oxygen-dependent inactivation of catalase. 4-HNE and singlet oxygen cooperate in complex autoamplificatory loops during this process. The finding of these novel anticancer pathways may be useful for understanding the role of 4-HNE in the control of malignant cells and for the optimization of ROS-dependent therapeutic approaches including antioxidant treatments.

  7. Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay.

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    Kaoru Miyazaki

    Full Text Available BACKGROUND: Endometrial stem/progenitor cells contribute to the cyclical regeneration of human endometrium throughout a woman's reproductive life. Although the candidate cell populations have been extensively studied, no consensus exists regarding which endometrial population represents the stem/progenitor cell fraction in terms of in vivo stem cell activity. We have previously reported that human endometrial side population cells (ESP, but not endometrial main population cells (EMP, exhibit stem cell-like properties, including in vivo reconstitution of endometrium-like tissues when xenotransplanted into immunodeficient mice. The reconstitution efficiency, however, was low presumably because ESP cells alone could not provide a sufficient microenvironment (niche to support their stem cell activity. The objective of this study was to establish a novel in vivo endometrial stem cell assay employing cell tracking and tissue reconstitution systems and to examine the stem cell properties of ESP through use of this assay. METHODOLOGY/PRINCIPAL FINDINGS: ESP and EMP cells isolated from whole endometrial cells were infected with lentivirus to express tandem Tomato (TdTom, a red fluorescent protein. They were mixed with unlabeled whole endometrial cells and then transplanted under the kidney capsule of ovariectomized immunodeficient mice. These mice were treated with estradiol and progesterone for eight weeks and nephrectomized. All of the grafts reconstituted endometrium-like tissues under the kidney capsules. Immunofluorescence revealed that TdTom-positive cells were significantly more abundant in the glandular, stromal, and endothelial cells of the reconstituted endometrium in mice transplanted with TdTom-labeled ESP cells than those with TdTom-labeled EMP cells. CONCLUSIONS/SIGNIFICANCE: We have established a novel in vivo endometrial stem cell assay in which multi-potential differentiation can be identified through cell tracking during in vivo

  8. The potential of Tillandsia dune ecosystems for revealing past and present variations in advective fog along the coastal Atacama Desert, northern Chile

    Science.gov (United States)

    Latorre Hidalgo, C.; García, J. L.; Gonzalez, A. L.; Marquet, P. A.

    2015-12-01

    The coastal Atacama Desert is home to a complex geo-ecosystem supported by fog with multiple atmospheric and oceanic drivers. Fog collectors in place for the last 17 years reveal that monthly fog intensity and amount are significantly linked to the El Niño-Southern Oscillation (ENSO 1+2) with cold (warm) anomalies correlated to increased (decreased) fog (R2 = 0.41). Rainfall, however, can occur during extreme positive ENSO anomalies. Tillandsia landbeckii is an epiarenitic plant common to the coastal Atacama where fog is intercepted by the coastal escarpment between 950-1250 m.a.s.l. These plants possess multiple adaptations to survive exclusively on fog, including the construction of "dune" ecosystems known as "tillandsiales". Buried T. landbeckii layers in such dunes contain a record of past variations of fog over time (dunes can top 3 m in height) and alternating plant and sand layers are readily visible in dune stratigraphy. Stable N isotopes on modern plants and fog indicate that these plants reflect δ15N values of total N dissolved in fog. We measured δ15N values from buried T. landbeckii layers from five different tillandsiales found across c. 50 km the coastal escarpment. The isotope values in these buried plants indicate a prominent c. 8.0 ‰ shift towards more negative δ15N values on average over the last 3,200 years. Based on differences in δ15N between modern and more extensive "paleo" tillandsiales at one of our lowest elevation study sites, we interpret this shift as an increase in available moisture due to increased fog input during the late Holocene. Increased variability in ENSO as well as increased upwelling and southerly winds along the coastal Atacama would explain in part this increase. Clearly, the Atacama tillandsiales have considerable potential for monitoring past and present change of these large-scale ocean-atmosphere systems.

  9. RNA-seq-based metatranscriptomic and microscopic investigation reveals novel metalloproteases of Neobodo sp. as potential virulence factors for soft tunic syndrome in Halocynthia roretzi.

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    Ho Bin Jang

    Full Text Available Bodonids and trypanosomatids are derived from a common ancestor with the bodonids being a more primitive lineage. The Neobodonida, one of the three clades of bodonids, can be free-living, commensal or parasitic. Despite the ecological and evolutionary significance of these organisms, however, many of their biological and pathological features are currently unknown. Here, we employed metatranscriptomics using RNA-seq technology combined with field-emission microscopy to reveal the virulence factors of a recently described genus of Neobodonida that is considered to be responsible for ascidian soft tunic syndrome (AsSTS, but whose pathogenesis is unclear. Our microscopic observation of infected tunic tissues suggested putative virulence factors, enabling us to extract novel candidate transcripts; these included cysteine proteases of the families C1 and C2, serine proteases of S51 and S9 families, and metalloproteases grouped into families M1, M3, M8, M14, M16, M17, M24, M41, and M49. Protease activity/inhibition assays and the estimation of expression levels within gene clusters allowed us to identify metalloprotease-like enzymes as potential virulence attributes for AsSTS. Furthermore, a multimarker-based phylogenetic analysis using 1,184 concatenated amino acid sequences clarified the order Neobodo sp. In sum, we herein used metatranscriptomics to elucidate the in situ expression profiles of uncharacterized putative transcripts of Neobodo sp., combined these results with microscopic observation to select candidate genes relevant to pathogenesis, and used empirical screening to define important virulence factors.

  10. Complete genome-wide screening and subtractive genomic approach revealed new virulence factors, potential drug targets against bio-war pathogen Brucella melitensis 16M

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    Pradeepkiran JA

    2015-03-01

    Full Text Available Jangampalli Adi Pradeepkiran,1* Sri Bhashyam Sainath,2,3* Konidala Kranthi Kumar,1 Matcha Bhaskar1 1Division of Animal Biotechnology, Department of Zoology, Sri Venkateswara University, Tirupati, India; 2CIMAR/CIIMAR, Centro Interdisciplinar de Investigação Marinha e Ambiental, Universidade do Porto, Rua dos Bragas, Porto, Portugal, 3Department of Biotechnology, Vikrama Simhapuri University, Nellore, Andhra Pradesh, India *These authors contributed equally to this work Abstract: Brucella melitensis 16M is a Gram-negative coccobacillus that infects both animals and humans. It causes a disease known as brucellosis, which is characterized by acute febrile illness in humans and causes abortions in livestock. To prevent and control brucellosis, identification of putative drug targets is crucial. The present study aimed to identify drug targets in B. melitensis 16M by using a subtractive genomic approach. We used available database repositories (Database of Essential Genes, Kyoto Encyclopedia of Genes and Genomes Automatic Annotation Server, and Kyoto Encyclopedia of Genes and Genomes to identify putative genes that are nonhomologous to humans and essential for pathogen B. melitensis 16M. The results revealed that among 3 Mb genome size of pathogen, 53 putative characterized and 13 uncharacterized hypothetical genes were identified; further, from Basic Local Alignment Search Tool protein analysis, one hypothetical protein showed a close resemblance (50% to Silicibacter pomeroyi DUF1285 family protein (2RE3. A further homology model of the target was constructed using MODELLER 9.12 and optimized through variable target function method by molecular dynamics optimization with simulating annealing. The stereochemical quality of the restrained model was evaluated by PROCHECK, VERIFY-3D, ERRAT, and WHATIF servers. Furthermore, structure-based virtual screening was carried out against the predicted active site of the respective protein using the

  11. DNA microarray data integration by ortholog gene analysis reveals potential molecular mechanisms of estrogen-dependent growth of human uterine fibroids

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    Shou Jianyong

    2007-04-01

    acid (RA synthesis and mobilization by regulating expression of CRABP2 and ALDH1A1. RA has been shown to play a significant role in the development of uterine fibroids in an animal model. Conclusion Integrated analysis of multiple array datasets revealed twelve human and rat ortholog genes that were differentially expressed in human uterine fibroids and transcriptionally responsive to estrogen in the rat uterus. Functional and pathway analysis of these genes suggest multiple potential molecular mechanisms for the poorly understood estrogen-dependent growth of uterine fibroids. Fully understanding the exact molecular interactions among these gene products requires further study to validate their roles in uterine fibroids. This work provides new avenues of study which could influence the future direction of therapeutic intervention for the disease.

  12. Long Non-coding RNAs Expression Profile in HepG2 Cells Reveals the Potential Role of Long Non-coding RNAs in the Cholesterol Metabolism

    Institute of Scientific and Technical Information of China (English)

    Gang Liu; Xinxin Zheng; Yanlu Xu; Jie Lu; Jingzhou Chen; Xiaohong Huang

    2015-01-01

    Background:Green tea has been shown to improve cholesterol metabolism in animal studies,but the molecular mechanisms underlying this function have not been fully understood.Long non-coding RNAs (lncRNAs) have recently emerged as a major class of regulatory molecules involved in a broad range of biological processes and complex diseases.Our aim was to identify important lncRNAs that might play an important role in contributing to the benefits of epigallocatechin-3-gallate (EGCG) on cholesterol metabolism.Methods:Microarrays was used to reveal the lncRNA and mRNA profiles in green tea polyphenol(-)-epigallocatechin gallate in cultured human liver (HepG2) hepatocytes treated with EGCG and bioinformatic analyses of the predicted target genes were performed to identify lncRNA-mRNA targeting relationships.RNA interference was used to investigate the role of lncRNAs in cholesterol metabolism.Results:The expression levels of 15 genes related to cholesterol metabolism and 285 lncRNAs were changed by EGCG treatment.Bioinformatic analysis found five matched lncRNA-mRNA pairs for five differentially expressed lncRNAs and four differentially expressed mRNA.In particular,the lncRNA4 T102202 and its potential targets mRNA-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) were identified.Using a real-time polymerase chain reaction technique,we confirmed that EGCG down-regulated mRNA expression level of the HMGCR and up-regulated expression ofAT102202.After AT102202 knockdown in HepG2,we observed that the level of HMGCR expression was significantly increased relative to the scrambled small interfering RNA control (P < 0.05).Conclusions:Our results indicated that EGCG improved cholesterol metabolism and meanwhile changed the lncRNAs expression profile in HepG2 cells.LncRNAs may play an important role in the cholesterol metabolism.

  13. Predictive validity of a MK-801-induced cognitive impairment model in mice: implications on the potential limitations and challenges of modeling cognitive impairment associated with schizophrenia preclinically.

    Science.gov (United States)

    Brown, Jordan W; Rueter, Lynne E; Zhang, Min

    2014-03-03

    Cognitive impairment associated with schizophrenia (CIAS) is a major and disabling symptom domain of the disease that is generally unresponsive to current pharmacotherapies. Critically important to the discovery of novel therapeutics for CIAS is the utilization of preclinical models with robust predictive validity. We investigated the predictive validity of MK-801-induced memory impairments in mouse inhibitory avoidance (MK-IA) as a preclinical model for CIAS by investigating compounds that have been tested in humans, including antipsychotics, sodium channel blocker mood stabilizers, and putative cognitive enhancers. The atypical antipsychotic clozapine, as well as risperidone and olanzapine (see Brown et al., 2013), had no effect on MK-801-induced memory impairments. For sodium channel blockers, carbamazepine significantly attenuated memory impairments induced by MK-801, whereas lamotrigine had no effect. Nicotine, donepezil, modafinil, and xanomeline all significantly attenuated MK-801-induced memory impairments, but the magnitude of effects and the dose-responses observed varied across compounds. Clinically, only acute administration of nicotine has demonstrated consistent positive effects on CIAS, while inconsistent results have been reported for lamotrigine, donepezil, and modafinil; atypical antipsychotics produce only moderate improvements at best. A positive clinical signal has been observed with xanomeline, but only in a small pilot trial. The results presented here suggest that the MK-IA model lacks robust predictive validity for CIAS as the model is likely permissive and may indicate false positive signals for compounds and mechanisms that lack clear clinical efficacy for CIAS. Our findings also highlight the potential limitations and challenges of using NMDA receptor antagonists in rodents to model CIAS.

  14. Claude Bernard Distinguished Lecture. Becoming a truly helpful teacher: considerably more challenging, and potentially more fun, than merely doing business as usual.

    Science.gov (United States)

    Jason, Hilliard

    2007-12-01

    Few medical faculty members are adequately prepared for their instructional responsibilities. Our educational traditions were established before we had research-based understandings of the teaching-learning process and before brain research began informing our understandings of how humans achieve lasting learning. Yet, there are several advantages you may have. If your expertise is at one of the frontiers of human biology, your teaching can be inherently fascinating to aspiring health professionals. If your work has implications for human health, you have another potential basis for engaging future clinicians. And, thanks to Claude Bernard's influence, you likely are "process oriented," a necessary mindset for being an effective teacher. There are also challenges you may face. Your medical students will mostly become clinicians. Unless you can help them see connections between your offerings and their future work, you may not capture and sustain their interest. To be effective, teachers, like clinicians, need to be interactive, make on-the-spot decisions, and be "emotional literate." If you aren't comfortable with these demands, you may have work to do toward becoming a truly helpful teacher. Program changes may be needed. Might your program need to change 1) from being adversarial and controlling to being supportive and trust based or 2) from mainly dispensing information to mainly asking and inviting questions? In conclusion, making changes toward becoming a truly helpful teacher can bring benefits to your students while increasing your sense of satisfaction and fulfillment as a teacher. If you choose to change, be gentle with yourself, as you should be when expecting your students to make important changes.

  15. 发展教育大数据:内涵、价值和挑战%The Definition, Potential Value and Challenges of Big Data in Education

    Institute of Scientific and Technical Information of China (English)

    杨现民; 唐斯斯; 李冀红

    2016-01-01

    The education development and reform in China faces unprecedented actual challenges. The integration of big data and education has become an irresistible trend in this new era. Big Data in Education (BDE) is a large data set used for educational development with huge potential value in which all data are produced in educational activities, or collected according to educational needs. In a global context, BDE should be viewed as a new kind of strategic asset to promote education innovation, a scientific power to promote comprehensive educational reform, and the foundation of smart education. The ultimate value of BDE is reflected in its deep integration with educational businesses and in the promotion of intelligent education reform, including making educational management scientific, driving instructional reform, achieving truly individualized learning, promoting the reconstruction of educational evaluation system, driving the transformation of scientific research paradigm, and making educational services more human-oriented. However, since our educational system is peculiar and complex, the development of our national BDE still faces numerous challenges, such as the application, the data security, the data governance and operation. Therefore, only by facing these problems clearly, as well as conducting deep research, can we promote the sustainable and healthy development of BDE.%我国教育领域的发展与改革正面临前所未有的挑战,大数据与教育的结合成为时代发展的必然要求.教育大数据是指整个教育活动过程中所产生的以及根据教育需要采集到的,一切用于教育发展并可创造巨大潜在价值的数据集合.在当前国际形势下,教育大数据从战略高度应定位为推动教育变革的新型战略资产、推进教育领域综合改革的科学力量以及发展智慧教育的基石.教育大数据的最终价值应体现在与教育主流业务的深度融合以及持续推动教育系统的

  16. Targeted sequencing reveals TP53 as a potential diagnostic biomarker in the post-treatment surveillance of head and neck cancer

    NARCIS (Netherlands)

    van Ginkel, Joost H.; de Leng, Wendy W J; de Bree, Remco; van Es, Robert J J; Willems, Stefan M.

    2016-01-01

    Head and neck squamous cell carcinomas (HNSCC) form a large heterogeneous group of tumors and have a relatively poor outcome in advanced cases. Revealing the underlying genetic mutations in HNSCC facilitates the development of diagnostic biomarkers, which might lead to improved diagnosis and post tr

  17. Genome-wide association analysis of bacterial cold water disease resistance in rainbow trout reveals the potential of a hybrid approach between genomic selection and marker assisted selection

    Science.gov (United States)

    Genomic selection (GS) simultaneously incorporates dense SNP marker genotypes with phenotypic data from related animals to predict animal-specific genomic breeding value (GEBV), which circumvents the need to measure the disease phenotype in potential breeders. Marker assisted selection (MAS) involv...

  18. High-throughput Screening of ToxCast™ Phase I Chemicals in a Mouse Embryonic Stem Cell (mESC) Assay Reveals Disruption of Potential Toxicity Pathways

    Science.gov (United States)

    Little information is available regarding the potential for many commercial chemicals to induce developmental toxicity. The mESC Adherent Cell Differentiation and Cytoxicity (ACDC) assay is a high-throughput screen used to close this data gap. Thus, ToxCast™ Phase I chemicals wer...

  19. The Memory That's Right and the Memory That's Left: Event-Related Potentials Reveal Hemispheric Asymmetries in the Encoding and Retention of Verbal Information

    Science.gov (United States)

    Evans, Karen M.; Federmeier, Kara D.

    2007-01-01

    We examined the nature and timecourse of hemispheric asymmetries in verbal memory by recording event-related potentials (ERPs) in a continuous recognition task. Participants made overt recognition judgments to test words presented in central vision that were either novel (new words) or had been previously presented in the left or right visual…

  20. In silico and experimental methods revealed highly diverse bacteria with quorum sensing and aromatics biodegradation systems--a potential broad application on bioremediation.

    Science.gov (United States)

    Huang, Yili; Zeng, Yanhua; Yu, Zhiliang; Zhang, Jing; Feng, Hao; Lin, Xiuchun

    2013-11-01

    Phylogenetic overlaps between aromatics-degrading bacteria and acyl-homoserine-lactone (AHL) or autoinducer (AI) based quorum-sensing (QS) bacteria were evident in literatures; however, the diversity of bacteria with both activities had never been finely described. In-silico searching in NCBI genome database revealed that more than 11% of investigated population harbored both aromatic ring-hydroxylating-dioxygenase (RHD) gene and AHL/AI-synthetase gene. These bacteria were distributed in 10 orders, 15 families, 42 genus and 78 species. Horizontal transfers of both genes were common among them. Using enrichment and culture dependent method, 6 Sphingomonadales and 4 Rhizobiales with phenanthrene- or pyrene-degrading ability and AHL-production were isolated from marine, wetland and soil samples. Thin-layer-chromatography and gas-chromatography-mass-spectrum revealed that these Sphingomonads produced various AHL molecules. This is the first report of highly diverse bacteria that harbored both aromatics-degrading and QS systems. QS regulation may have broad impacts on aromatics biodegradation, and would be a new angle for developing bioremediation technology.

  1. Dynamic energy budget modeling reveals the potential of future growth and calcification for the coccolithophore Emiliania huxleyi in an acidified ocean.

    Science.gov (United States)

    Muller, Erik B; Nisbet, Roger M

    2014-06-01

    Ocean acidification is likely to impact the calcification potential of marine organisms. In part due to the covarying nature of the ocean carbonate system components, including pH and CO2 and CO3(2-) levels, it remains largely unclear how each of these components may affect calcification rates quantitatively. We develop a process-based bioenergetic model that explains how several components of the ocean carbonate system collectively affect growth and calcification rates in Emiliania huxleyi, which plays a major role in marine primary production and biogeochemical carbon cycling. The model predicts that under the IPCC A2 emission scenario, its growth and calcification potential will have decreased by the end of the century, although those reductions are relatively modest. We anticipate that our model will be relevant for many other marine calcifying organisms, and that it can be used to improve our understanding of the impact of climate change on marine systems.

  2. Antioxidant assays - consistent findings from FRAP and ORAC reveal a negative impact of organic cultivation on antioxidant potential in spinach but not watercress or rocket leaves.

    Science.gov (United States)

    Payne, Adrienne C; Mazzer, Alice; Clarkson, Graham J J; Taylor, Gail

    2013-11-01

    Watercress (Rorippa nasturtium-aquaticum), wild rocket (Diplotaxis tenuifolia), and spinach (Spinacia oleracea) are commercial crops reported to have high concentrations of antioxidants, possibly contributing to disease prevention following human consumption. Following analysis of supermarket-purchased salad leaves, we report the antioxidant content potential of these species using two comparable techniques assessing the consistency between the assays - by the ferric reducing antioxidant power (FRAP) assay and the oxygen radical absorbance capacity (ORAC) assay. The leaves were harvested from both conventionally and organically managed crops, to investigate whether organic agriculture results in improved crop quality. Watercress had the highest FRAP and ability to scavenge free radicals, followed by spinach and rocket. For watercress and rocket, there was no significant effect of organic agriculture on FRAP and ORAC, but for spinach, the antioxidant potential was reduced and this was significant at the 5% level of probability for FRAP but not ORAC, although the trend was clear in both tests. We conclude that there is variation in salad crop antioxidant potential and that FRAP and ORAC are useful techniques for measuring antioxidants in these salad crops with similar ranking for each salad crop studied.

  3. Computational modeling of protein mutant stability: analysis and optimization of statistical potentials and structural features reveal insights into prediction model development

    Directory of Open Access Journals (Sweden)

    Abhinandan Madenhalli

    2007-08-01

    Full Text Available Abstract Background Understanding and predicting protein stability upon point mutations has wide-spread importance in molecular biology. Several prediction models have been developed in the past with various algorithms. Statistical potentials are one of the widely used algorithms for the prediction of changes in stability upon point mutations. Although the methods provide flexibility and the capability to develop an accurate and reliable prediction model, it can be achieved only by the right selection of the structural factors and optimization of their parameters for the statistical potentials. In this work, we have selected five atom classification systems and compared their efficiency for the development of amino acid atom potentials. Additionally, torsion angle potentials have been optimized to include the orientation of amino acids in such a way that altered backbone conformation in different secondary structural regions can be included for the prediction model. This study also elaborates the importance of classifying the mutations according to their solvent accessibility and secondary structure specificity. The prediction efficiency has been calculated individually for the mutations in different secondary structural regions and compared. Results Results show that, in addition to using an advanced atom description, stepwise regression and selection of atoms are necessary to avoid the redundancy in atom distribution and improve the reliability of the prediction model validation. Comparing to other atom classification models, Melo-Feytmans model shows better prediction efficiency by giving a high correlation of 0.85 between experimental and theoretical ΔΔG with 84.06% of the mutations correctly predicted out of 1538 mutations. The theoretical ΔΔG values for the mutations in partially buried β-strands generated by the structural training dataset from PISCES gave a correlation of 0.84 without performing the Gaussian apodization of the

  4. Crystal Structures of GII.10 and GII.12 Norovirus Protruding Domains in Complex with Histo-Blood Group Antigens Reveal Details for a Potential Site of Vulnerability

    Energy Technology Data Exchange (ETDEWEB)

    Hansman, Grant S.; Biertümpfel, Christian; Georgiev, Ivelin; McLellan, Jason S.; Chen, Lei; Zhou, Tongqing; Katayama, Kazuhiko; Kwong, Peter D. (NIH); (NIID-Japan)

    2011-10-10

    Noroviruses are the dominant cause of outbreaks of gastroenteritis worldwide, and interactions with human histo-blood group antigens (HBGAs) are thought to play a critical role in their entry mechanism. Structures of noroviruses from genogroups GI and GII in complex with HBGAs, however, reveal different modes of interaction. To gain insight into norovirus recognition of HBGAs, we determined crystal structures of norovirus protruding domains from two rarely detected GII genotypes, GII.10 and GII.12, alone and in complex with a panel of HBGAs, and analyzed structure-function implications related to conservation of the HBGA binding pocket. The GII.10- and GII.12-apo structures as well as the previously solved GII.4-apo structure resembled each other more closely than the GI.1-derived structure, and all three GII structures showed similar modes of HBGA recognition. The primary GII norovirus-HBGA interaction involved six hydrogen bonds between a terminal {alpha}fucose1-2 of the HBGAs and a dimeric capsid interface, which was composed of elements from two protruding subdomains. Norovirus interactions with other saccharide units of the HBGAs were variable and involved fewer hydrogen bonds. Sequence analysis revealed a site of GII norovirus sequence conservation to reside under the critical {alpha}fucose1-2 and to be one of the few patches of conserved residues on the outer virion-capsid surface. The site was smaller than that involved in full HBGA recognition, a consequence of variable recognition of peripheral saccharides. Despite this evasion tactic, the HBGA site of viral vulnerability may provide a viable target for small molecule- and antibody-mediated neutralization of GII norovirus.

  5. Proteomic profiling of Pseudomonas aeruginosa AES-1R, PAO1 and PA14 reveals potential virulence determinants associated with a transmissible cystic fibrosis-associated strain

    Directory of Open Access Journals (Sweden)

    Hare Nathan J

    2012-01-01

    Full Text Available Abstract Background Pseudomonas aeruginosa is an opportunistic pathogen that is the major cause of morbidity and mortality in patients with cystic fibrosis (CF. While most CF patients are thought to acquire P. aeruginosa from the environment, person-person transmissible strains have been identified in CF clinics worldwide. The molecular basis for transmissibility and colonization of the CF lung remains poorly understood. Results A dual proteomics approach consisting of gel-based and gel-free comparisons were undertaken to analyse protein profiles in a transmissible, early (acute isolate of the Australian epidemic strain 1 (AES-1R, the virulent burns/wound isolate PA14, and the poorly virulent, laboratory-associated strain PAO1. Over 1700 P. aeruginosa proteins were confidently identified. AES-1R protein profiles revealed elevated abundance of proteins associated with virulence and siderophore biosynthesis and acquisition, antibiotic resistance and lipopolysaccharide and fatty acid biosynthesis. The most abundant protein in AES-1R was confirmed as a previously hypothetical protein with sequence similarity to carbohydrate-binding proteins and database search revealed this gene is only found in the CF-associated strain PA2192. The link with CF infection may suggest that transmissible strains have acquired an ability to rapidly interact with host mucosal glycoproteins. Conclusions Our data suggest that AES-1R expresses higher levels of proteins, such as those involved in antibiotic resistance, iron acquisition and virulence that may provide a competitive advantage during early infection in the CF lung. Identification of novel proteins associated with transmissibility and acute infection may aid in deciphering new strategies for intervention to limit P. aeruginosa infections in CF patients.

  6. A novel HMM-based method for detecting enriched transcription factor binding sites reveals RUNX3 as a potential target in pancreatic cancer biology.

    Directory of Open Access Journals (Sweden)

    Liron Levkovitz

    Full Text Available BACKGROUND: Pancreatic adenocarcinoma (PAC is one of the most intractable malignancies. In order to search for potential new therapeutic targets, we relied on computational methods aimed at identifying transcription factor binding sites (TFBSs over-represented in the promoter regions of genes differentially expressed in PAC. Though many computational methods have been implemented to accomplish this, none has gained overall acceptance or produced proven novel targets in PAC. To this end we have developed DEMON, a novel method for motif detection. METHODOLOGY: DEMON relies on a hidden Markov model to score the appearance of sequence motifs, taking into account all potential sites in a promoter of potentially varying binding affinities. We demonstrate DEMON's accuracy on simulated and real data sets. Applying DEMON to PAC-related data sets identifies the RUNX family as highly enriched in PAC-related genes. Using a novel experimental paradigm to distinguish between normal and PAC cells, we find that RUNX3 mRNA (but not RUNX1 or RUNX2 mRNAs exhibits time-dependent increases in normal but not in PAC cells. These increases are accompanied by changes in mRNA levels of putative RUNX gene targets. CONCLUSIONS: The integrated application of DEMON and a novel differentiation system led to the identification of a single family member, RUNX3, which together with four of its putative targets showed a robust response to a differentiation stimulus in healthy cells, whereas this regulatory mechanism was absent in PAC cells, emphasizing RUNX3 as a promising target for further studies.

  7. Health access livelihood framework reveals potential barriers in the control of schistosomiasis in the Dongting Lake area of Hunan Province, China.

    Directory of Open Access Journals (Sweden)

    Julie Balen

    Full Text Available BACKGROUND: Access to health care is a major requirement in improving health and fostering socioeconomic development. In the People's Republic of China (P.R. China, considerable changes have occurred in the social, economic, and health systems with a shift from a centrally planned to a socialist market economy. This brought about great benefits and new challenges, particularly for vertical disease control programs, including schistosomiasis. We explored systemic barriers in access to equitable and effective control of schistosomiasis. METHODOLOGY: Between August 2002 and February 2003, 66 interviews with staff from anti-schistosomiasis control stations and six focus group discussions with health personnel were conducted in the Dongting Lake area, Hunan Province. Additionally, 79 patients with advanced schistosomiasis japonica were interviewed. The health access livelihood framework was utilized to examine availability, accessibility, affordability, adequacy, and acceptability of schistosomiasis-related health care. PRINCIPAL FINDINGS: We found sufficient availability of infrastructure and human resources at most control stations. Many patients with advanced schistosomiasis resided in non-endemic or moderately endemic areas, however, with poor accessibility to disease-specific knowledge and specialized health services. Moreover, none of the patients interviewed had any form of health insurance, resulting in high out-of-pocket expenditure or unaffordable care. Reports on the adequacy and acceptability of care were mixed. CONCLUSIONS/SIGNIFICANCE: There is a need to strengthen health awareness and schistosomiasis surveillance in post-transmission control settings, as well as to reduce diagnostic and treatment costs. Further studies are needed to gain a multi-layered, in-depth understanding of remaining barriers, so that the ultimate goal of schistosomiasis elimination in P.R. China can be reached.

  8. Challenges of serious games

    Directory of Open Access Journals (Sweden)

    B. Fernández-Manjón

    2015-11-01

    Full Text Available Although educational games have revealed to be a very effective focus in diverse situations, their use in education is still very limited. In this paper we analyse the main challenges concerning educational games that, from our perspective, have to be approached so that the use of this kind of games can be widespread. These challenges are classified in three main dimensions: socio-cultural, educational and technological. Once the challenges are identified, some possible measures are suggested to address or reduce these problems so that the use of educational games may be widespread.

  9. Of monkeys and men: immunomic profiling of sera from humans and non-human primates resistant to schistosomiasis reveals novel potential vaccine candidates.

    Science.gov (United States)

    Pearson, Mark S; Becker, Luke; Driguez, Patrick; Young, Neil D; Gaze, Soraya; Mendes, Tiago; Li, Xiao-Hong; Doolan, Denise L; Midzi, Nicholas; Mduluza, Takafira; McManus, Donald P; Wilson, R Alan; Bethony, Jeffrey M; Nausch, Norman; Mutapi, Francisca; Felgner, Philip L; Loukas, Alex

    2015-01-01

    Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione-S-transferases, and glucose transporters (SGTP1), as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to S. japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognized by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens.

  10. Of monkeys and men: immunomic profiling of sera from humans and non-human primates resistant to schistosomiasis reveals novel potential vaccine candidates

    Directory of Open Access Journals (Sweden)

    Mark ePearson

    2015-05-01

    Full Text Available Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80, tetraspanins, glutathione-S-transferases and glucose transporters (SGTP1, as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to Schistosoma japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognised by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens.

  11. IMAC fractionation in combination with LC-MS reveals H2B and NIF-1 peptides as potential bladder cancer biomarkers.

    Science.gov (United States)

    Frantzi, Maria; Zoidakis, Jerome; Papadopoulos, Theofilos; Zürbig, Petra; Katafigiotis, Ioannis; Stravodimos, Konstantinos; Lazaris, Andreas; Giannopoulou, Ioanna; Ploumidis, Achilles; Mischak, Harald; Mullen, William; Vlahou, Antonia

    2013-09-06

    Improvement in bladder cancer (BC) management requires more effective diagnosis and prognosis of disease recurrence and progression. Urinary biomarkers attract special interest because of the noninvasive means of urine collection. Proteomic analysis of urine entails the adoption of a fractionation methodology to reduce sample complexity. In this study, we applied immobilized metal affinity chromatography in combination with high-resolution LC-MS/MS for the discovery of native urinary peptides potentially associated with BC aggressiveness. This approach was employed toward urine samples from patients with invasive BC, noninvasive BC, and benign urogenital diseases. A total of 1845 peptides were identified, corresponding to a total of 638 precursor proteins. Specific enrichment for proteins involved in nucleosome assembly and for zinc-finger transcription factors was observed. The differential expression of two candidate biomarkers, histone H2B and NIF-1 (zinc finger 335) in BC, was verified in independent sets of urine samples by ELISA and by immunohistochemical analysis of BC tissue. The results collectively support changes in the expression of both of these proteins with tumor progression, suggesting their potential role as markers for discriminating BC stages. In addition, the data indicate a possible involvement of NIF-1 in BC progression, likely as a suppressor and through interactions with Sox9 and HoxA1.

  12. A novel role for peptidylarginine deiminases in microvesicle release reveals therapeutic potential of PAD inhibition in sensitizing prostate cancer cells to chemotherapy

    Directory of Open Access Journals (Sweden)

    Sharad Kholia

    2015-06-01

    Full Text Available Introduction: Protein deimination, defined as the post-translational conversion of protein-bound arginine to citrulline, is carried out by a family of 5 calcium-dependent enzymes, the peptidylarginine deiminases (PADs and has been linked to various cancers. Cellular microvesicle (MV release, which is involved in cancer progression, and deimination have not been associated before. We hypothesize that elevated PAD expression, observed in cancers, causes increased MV release in cancer cells and contributes to cancer progression. Background: We have previously reported that inhibition of MV release sensitizes cancer cells to chemotherapeutic drugs. PAD2 and PAD4, the isozymes expressed in patients with malignant tumours, can be inhibited with the pan-PAD-inhibitor chloramidine (Cl-am. We sought to investigate whether Cl-am can inhibit MV release and whether this pathway could be utilized to further increase the sensitivity of cancer cells to drug-directed treatment. Methods: Prostate cancer cells (PC3 were induced to release high levels of MVs upon BzATP stimulation of P2X7 receptors. Western blotting with the pan-protein deimination antibody F95 was used to detect a range of deiminated proteins in cells stimulated to microvesiculate. Changes in deiminated proteins during microvesiculation were revealed by immunoprecipitation and immunoblotting, and mass spectrometry identified deiminated target proteins with putative roles in microvesiculation. Conclusion: We report for the first time a novel function of PADs in the biogenesis of MVs in cancer cells. Our results reveal that during the stimulation of prostate cancer cells (PC3 to microvesiculate, PAD2 and PAD4 expression levels and the deimination of cytoskeletal actin are increased. Pharmacological inhibition of PAD enzyme activity using Cl-am significantly reduced MV release and abrogated the deimination of cytoskeletal actin. We demonstrated that combined Cl-am and methotrexate (MTX treatment of

  13. Intra-Section Analysis of Human Coronary Arteries Reveals a Potential Role for Micro-Calcifications in Macrophage Recruitment in the Early Stage of Atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Martijn L L Chatrou

    in combination with calcification, suggesting a pro-inflammatory effect of micro-calcifications. In vitro, invasion assays revealed chemoattractant properties of cell-culture medium of calcifying vascular smooth muscle cells towards THP-1 cells, which implies pro-inflammatory effect of calcium deposits. Additionally, calcifying hVSMCs revealed a pro-inflammatory profile as compared to non-calcifying hVSMCs.Our data indicate that calcification of VSMCs is one of the earliest events in the genesis of atherosclerosis, which strongly correlates with ucMGP staining. Our findings suggest that loss of calcification inhibitors and/or failure of inhibitory capacity is causative for the early precipitation of calcium, with concomitant increased inflammation followed by osteochondrogenic transdifferentiation of VSMCs.

  14. Probabilistic Evaluation of Ecological and Economic Objectives of River Basin Management Reveals a Potential Flaw in the Goal Setting of the EU Water Framework Directive.

    Science.gov (United States)

    Hjerppe, Turo; Taskinen, Antti; Kotamäki, Niina; Malve, Olli; Kettunen, Juhani

    2017-04-01

    The biological status of European lakes has not improved as expected despite up-to-date legislation and ecological standards. As a result, the realism of objectives and the attainment of related ecological standards are under doubt. This paper gets to the bottom of a river basin management plan of a eutrophic lake in Finland and presents the ecological and economic impacts of environmental and societal drivers and planned management measures. For these purposes, we performed a Monte Carlo simulation of a diffuse nutrient load, lake water quality and cost-benefit models. Simulations were integrated into a Bayesian influence diagram that revealed the basic uncertainties. It turned out that the attainment of good ecological status as qualified in the Water Framework Directive of the European Union is unlikely within given socio-economic constraints. Therefore, management objectives and ecological and economic standards need to be reassessed and reset to provide a realistic goal setting for management. More effort should be put into the evaluation of the total monetary benefits and on the monitoring of lake phosphorus balances to reduce the uncertainties, and the resulting margin of safety and costs and risks of planned management measures.

  15. Human 45,X fibroblast transcriptome reveals distinct differentially expressed genes including long noncoding RNAs potentially associated with the pathophysiology of Turner syndrome.

    Directory of Open Access Journals (Sweden)

    Shriram N Rajpathak

    Full Text Available Turner syndrome is a chromosomal abnormality characterized by the absence of whole or part of the X chromosome in females. This X aneuploidy condition is associated with a diverse set of clinical phenotypes such as gonadal dysfunction, short stature, osteoporosis and Type II diabetes mellitus, among others. These phenotypes differ in their severity and penetrance among the affected individuals. Haploinsufficiency for a few X linked genes has been associated with some of these disease phenotypes. RNA sequencing can provide valuable insights to understand molecular mechanism of disease process. In the current study, we have analysed the transcriptome profiles of human untransformed 45,X and 46,XX fibroblast cells and identified differential expression of genes in these two karyotypes. Functional analysis revealed that these differentially expressing genes are associated with bone differentiation, glucose metabolism and gonadal development pathways. We also report differential expression of lincRNAs in X monosomic cells. Our observations provide a basis for evaluation of cellular and molecular mechanism(s in the establishment of Turner syndrome phenotypes.

  16. ‘Get in Early’; Biofilm and Wax Moth (Galleria mellonella) Models Reveal New Insights into the Therapeutic Potential of Clostridium difficile Bacteriophages

    Science.gov (United States)

    Nale, Janet Y.; Chutia, Mahananda; Carr, Philippa; Hickenbotham, Peter T.; Clokie, Martha R. J.

    2016-01-01

    Clostridium difficile infection (CDI) is a global health threat associated with high rates of morbidity and mortality. Conventional antibiotic CDI therapy can result in treatment failure and recurrent infection. C. difficile produces biofilms which contribute to its virulence and impair antimicrobial activity. Some bacteriophages (phages) can penetrate biofilms and thus could be developed to either replace or supplement antibiotics. Here, we determined the impact of a previously optimized 4-phage cocktail on C. difficile ribotype 014/020 biofilms, and additionally as adjunct to vancomycin treatment in Galleria mellonella larva CDI model. The phages were applied before or after biofilm establishment in vitro, and the impact was analyzed according to turbidity, viability counts and topography as observed using scanning electron and confocal microscopy. The infectivity profiles and efficacies of orally administered phages and/or vancomycin were ascertained by monitoring colonization levels and larval survival rates. Phages prevented biofilm formation, and penetrated established biofilms. A single phage application reduced colonization causing extended longevity in the remedial treatment and prevented disease in the prophylaxis group. Multiple phage doses significantly improved the larval remedial regimen, and this treatment is comparable to vancomycin and the combined treatments. Taken together, our data suggest that the phages significantly reduce C. difficile biofilms, and prevent colonization in the G. mellonella model when used alone or in combination with vancomycin. The phages appear to be highly promising therapeutics in the targeted eradication of CDI and the use of these models has revealed that prophylactic use could be a propitious therapeutic option. PMID:27630633

  17. 'Get in Early'; Biofilm and Wax Moth (Galleria mellonella) Models Reveal New Insights into the Therapeutic Potential of Clostridium difficile Bacteriophages.

    Science.gov (United States)

    Nale, Janet Y; Chutia, Mahananda; Carr, Philippa; Hickenbotham, Peter T; Clokie, Martha R J

    2016-01-01

    Clostridium difficile infection (CDI) is a global health threat associated with high rates of morbidity and mortality. Conventional antibiotic CDI therapy can result in treatment failure and recurrent infection. C. difficile produces biofilms which contribute to its virulence and impair antimicrobial activity. Some bacteriophages (phages) can penetrate biofilms and thus could be developed to either replace or supplement antibiotics. Here, we determined the impact of a previously optimized 4-phage cocktail on C. difficile ribotype 014/020 biofilms, and additionally as adjunct to vancomycin treatment in Galleria mellonella larva CDI model. The phages were applied before or after biofilm establishment in vitro, and the impact was analyzed according to turbidity, viability counts and topography as observed using scanning electron and confocal microscopy. The infectivity profiles and efficacies of orally administered phages and/or vancomycin were ascertained by monitoring colonization levels and larval survival rates. Phages prevented biofilm formation, and penetrated established biofilms. A single phage application reduced colonization causing extended longevity in the remedial treatment and prevented disease in the prophylaxis group. Multiple phage doses significantly improved the larval remedial regimen, and this treatment is comparable to vancomycin and the combined treatments. Taken together, our data suggest that the phages significantly reduce C. difficile biofilms, and prevent colonization in the G. mellonella model when used alone or in combination with vancomycin. The phages appear to be highly promising therapeutics in the targeted eradication of CDI and the use of these models has revealed that prophylactic use could be a propitious therapeutic option.

  18. Targeted sequencing reveals TP53 as a potential diagnostic biomarker in the post-treatment surveillance of head and neck cancer.

    Science.gov (United States)

    van Ginkel, Joost H; de Leng, Wendy W J; de Bree, Remco; van Es, Robert J J; Willems, Stefan M

    2016-09-20

    Head and neck squamous cell carcinomas (HNSCC) form a large heterogeneous group of tumors and have a relatively poor outcome in advanced cases. Revealing the underlying genetic mutations in HNSCC facilitates the development of diagnostic biomarkers, which might lead to improved diagnosis and post treatment surveillance. We retrospectively analyzed mutational hotspots using targeted next-generation sequencing (NGS) of 239 HNSCC tumor samples in order to examine the mutational profile of HNSCC. Furthermore, we assessed prevalence, co-occurrence, and synonymy of gene mutations in (matched) tumor samples. TP53 was found mutated the most frequent with mutation rates of up to 83% in all tumors, compared to mutation rates of between 0 and 21% of CDKN2A, PIK3CA, HRAS, CDK4, FBXW7 and RB1. Mutational co-occurrence predominantly existed between TP53 and PIK3CA, TP53 and CDKN2A, and HRAS and PIK3CA. Mutational synonymy between primary tumor and associated metastasis and recurrence was present in respectively 88% and 89%. TP53 mutations were concordantly mutated in 95% of metastases and in 91% of recurrences. This indicates TP53 mutations to be highly prevalent and concordant in primary tumors and associated locoregional metastases and recurrences. In turn, this provides ground for further investigating the use of TP53 mutations as diagnostic biomarkers in HNSCC patients.

  19. Human 45,X Fibroblast Transcriptome Reveals Distinct Differentially Expressed Genes Including Long Noncoding RNAs Potentially Associated with the Pathophysiology of Turner Syndrome

    Science.gov (United States)

    Patowary, Ashok; Scaria, Vinod; Sivasubbu, Sridhar; Deobagkar, Deepti D.

    2014-01-01

    Turner syndrome is a chromosomal abnormality characterized by the absence of whole or part of the X chromosome in females. This X aneuploidy condition is associated with a diverse set of clinical phenotypes such as gonadal dysfunction, short stature, osteoporosis and Type II diabetes mellitus, among others. These phenotypes differ in their severity and penetrance among the affected individuals. Haploinsufficiency for a few X linked genes has been associated with some of these disease phenotypes. RNA sequencing can provide valuable insights to understand molecular mechanism of disease process. In the current study, we have analysed the transcriptome profiles of human untransformed 45,X and 46,XX fibroblast cells and identified differential expression of genes in these two karyotypes. Functional analysis revealed that these differentially expressing genes are associated with bone differentiation, glucose metabolism and gonadal development pathways. We also report differential expression of lincRNAs in X monosomic cells. Our observations provide a basis for evaluation of cellular and molecular mechanism(s) in the establishment of Turner syndrome phenotypes. PMID:24932682

  20. Human 45,X fibroblast transcriptome reveals distinct differentially expressed genes including long noncoding RNAs potentially associated with the pathophysiology of Turner syndrome.

    Science.gov (United States)

    Rajpathak, Shriram N; Vellarikkal, Shamsudheen Karuthedath; Patowary, Ashok; Scaria, Vinod; Sivasubbu, Sridhar; Deobagkar, Deepti D

    2014-01-01

    Turner syndrome is a chromosomal abnormality characterized by the absence of whole or part of the X chromosome in females. This X aneuploidy condition is associated with a diverse set of clinical phenotypes such as gonadal dysfunction, short stature, osteoporosis and Type II diabetes mellitus, among others. These phenotypes differ in their severity and penetrance among the affected individuals. Haploinsufficiency for a few X linked genes has been associated with some of these disease phenotypes. RNA sequencing can provide valuable insights to understand molecular mechanism of disease process. In the current study, we have analysed the transcriptome profiles of human untransformed 45,X and 46,XX fibroblast cells and identified differential expression of genes in these two karyotypes. Functional analysis revealed that these differentially expressing genes are associated with bone differentiation, glucose metabolism and gonadal development pathways. We also report differential expression of lincRNAs in X monosomic cells. Our observations provide a basis for evaluation of cellular and molecular mechanism(s) in the establishment of Turner syndrome phenotypes.

  1. Probabilistic Evaluation of Ecological and Economic Objectives of River Basin Management Reveals a Potential Flaw in the Goal Setting of the EU Water Framework Directive

    Science.gov (United States)

    Hjerppe, Turo; Taskinen, Antti; Kotamäki, Niina; Malve, Olli; Kettunen, Juhani

    2017-04-01

    The biological status of European lakes has not improved as expected despite up-to-date legislation and ecological standards. As a result, the realism of objectives and the attainment of related ecological standards are under doubt. This paper gets to the bottom of a river basin management plan of a eutrophic lake in Finland and presents the ecological and economic impacts of environmental and societal drivers and planned management measures. For these purposes, we performed a Monte Carlo simulation of a diffuse nutrient load, lake water quality and cost-benefit models. Simulations were integrated into a Bayesian influence diagram that revealed the basic uncertainties. It turned out that the attainment of good ecological status as qualified in the Water Framework Directive of the European Union is unlikely within given socio-economic constraints. Therefore, management objectives and ecological and economic standards need to be reassessed and reset to provide a realistic goal setting for management. More effort should be put into the evaluation of the total monetary benefits and on the monitoring of lake phosphorus balances to reduce the uncertainties, and the resulting margin of safety and costs and risks of planned management measures.

  2. Lattice dynamical analogies and differences between SrTiO3 and EuTiO3 revealed by phonon-dispersion relations and double-well potentials

    Science.gov (United States)

    Bettis, Jerry L.; Whangbo, Myung-Hwan; Köhler, Jürgen; Bussmann-Holder, Annette; Bishop, A. R.

    2011-11-01

    A comparative analysis of the structural phase transitions of EuTiO3 and SrTiO3 (at TS = 282 and 105 K, respectively) is made on the basis of phonon-dispersion and density functional calculations. The phase transition of EuTiO3 is predicted to arise from the softening of a transverse acoustic zone boundary mode caused by the rotations of the TiO6 octahedra, as also found for the phase transition of SrTiO3. Although the temperature dependence of the soft mode is similar in both compounds, their elastic properties differ drastically because of a large difference in the double-well potentials associated with the soft zone boundary acoustic mode.

  3. Mapping the genome of Plasmodium falciparum on the drug-like chemical space reveals novel anti-malarial targets and potential drug leads

    DEFF Research Database (Denmark)

    Jensen, Kasper; Plichta, Damian Rafal; Panagiotou, Gianni;

    2012-01-01

    The parasite Plasmodium falciparum is the main agent responsible for malaria. In this study, we exploited a recently published chemical library from GlaxoSmithKline (GSK) that had previously been confirmed to inhibit parasite growth of the wild type (3D7) and the multi-drug resistance (D2d) strains......, in order to uncover the weak links in the proteome of the parasite. We predicted 293 proteins of P. falciparum, including the six out of the seven verified targets for P. falciparum malaria treatment, as targets of 4645 GSK active compounds. Furthermore, we prioritized druggable targets, based on a number...... on integration of available chemical-protein and protein-protein interaction data. Our work suggests that a large number of the P. falciparum proteome is potentially druggable and could therefore serve as novel drug targets in the fight against malaria. At the same time, prioritized compounds from the GSK...

  4. Event-related potentials reveal task-dependence and inter-individual differences in negation processing during silent listening and explicit truth-value evaluation.

    Science.gov (United States)

    Herbert, C; Kissler, J

    2014-09-26

    In sentences such as dogs cannot fly/bark, evaluation of the truth-value of the sentence is assumed to appear after the negation has been integrated into the sentence structure. Moreover negation processing and truth-value processing are considered effortful processes, whereas processing of the semantic relatedness of the words within sentences is thought to occur automatically. In the present study, modulation of event-related brain potentials (N400 and late positive potential, LPP) was investigated during an implicit task (silent listening) and active truth-value evaluation to test these theoretical assumptions and determine if truth-value evaluation will be modulated by the way participants processed the negated information implicitly prior to truth-value verification. Participants first listened to negated sentences and then evaluated these sentences for their truth-value in an active evaluation task. During passive listening, the LPP was generally more pronounced for targets in false negative (FN) than true negative (TN) sentences, indicating enhanced attention allocation to semantically-related but false targets. N400 modulation by truth-value (FN>TN) was observed in 11 out of 24 participants. However, during active evaluation, processing of semantically-unrelated but true targets (TN) elicited larger N400 and LPP amplitudes as well as a pronounced frontal negativity. This pattern was particularly prominent in those 11 individuals, whose N400 modulation during silent listening indicated that they were more sensitive to violations of the truth-value than to semantic priming effects. The results provide evidence for implicit truth-value processing during silent listening of negated sentences and for task dependence related to inter-individual differences in implicit negation processing.

  5. Molecular Targeted Enhanced Ultrasound Imaging of Flk1 Reveals Diagnosis and Prognosis Potential in a Genetically Engineered Mouse Prostate Cancer Model

    Directory of Open Access Journals (Sweden)

    Jim W. Xuan

    2009-07-01

    Full Text Available Molecular imaging techniques used to detect the initiation of disease have the potential to provide the best opportunity for early treatment and cure. This report aimed at testing the possibility that Flk1+ (vascular endothelial growth factor receptor 2, a crucial angiogenesis factor of most tumor cells, could be a molecular targeted imaging marker for the diagnosis and prognosis of cancer. We performed Flk1-targeted microbubble-enhanced ultrasound (US imaging of prostate cancer in a genetically engineered mouse model with normal-appearing intact US (negative prostates and with three different tumor sizes (small, medium, and large. Higher levels of Flk1+ molecular signals were identified in the intact US (negative prostate group by US-targeted imaging and immunohistochemical analysis. The increase in Flk1+ expression occurred prior to the angiogenesis switch-on phase and vascularity peak. After this peak accumulation stage of Flk1+ molecules, lower and stabilized levels of Flk1+ signals were maintained together with tumor growth from small, to medium, to large size. In a longitudinal observation in a subset (n = 5 of mice with established tumors, elevated Flk1+ signals were observed in tissues surrounding the prostate cancer, for example, the ipsilateral boundary zones between two developing tumor lobes, new tumor blood vessel recruits, the urethra border, and the pelvic node basin. The potential of Flk1-targeted US imaging as a predictive imaging tool was confirmed by correlation studies of three-dimensional US B-mode imaging, gross pathology, and histology analyses. The results of the application in a genetically engineered mouse model with prostate cancer of molecular Flk1-targeted US imaging support the contention that Flk1 can be used as a molecular imaging marker for small tumors undetectable by microimaging and as a molecular diagnostic and prognosis marker for tumor metastasis and progression.

  6. The curse of the prey: Sarcoptes mite molecular analysis reveals potential prey-to-predator parasitic infestation in wild animals from Masai Mara, Kenya

    Directory of Open Access Journals (Sweden)

    Soriguer Ramón C

    2011-10-01

    Full Text Available Abstract Background Recently, there have been attempts to understand the molecular epidemiology of Sarcoptes scabiei, to evaluate the gene flow between isolates of S. scabiei from different hosts and geographic regions. However, to our knowledge, a molecular study has not been carried out to assess the molecular diversity and gene flow of Sarcoptes mite in a predator/prey ecosystem. Results Our study revealed an absence of gene flow between the two herbivore (Thomson's gazelle and wildebeest- and between the two carnivore (lion and cheetah-derived Sarcoptes populations from Masai Mara (Kenya, which is in discrepancy with the host-taxon law described for wild animals in Europe. Lion- and wildebeest-derived Sarcoptes mite populations were similar yet different from the Thomson's gazelle-derived Sarcoptes population. This could be attributed to Sarcoptes cross-infestation from wildebeest ("favourite prey" of the lion, but not from Thomson's gazelle. The cheetah-derived Sarcoptes population had different subpopulations: one is cheetah-private, one similar to the wildebeest- and lion-derived Sarcoptes populations, and another similar to the Thomson's gazelle-derived Sarcoptes mite population, where both wildebeest and Thomson's gazelle are "favourite preys" for the cheetah. Conclusions In a predator/prey ecosystem, like Masai Mara in Kenya, it seems that Sarcoptes infestation in wild animals is prey-to-predator-wise, depending on the predator's "favourite prey". More studies on the lion and cheetah diet and behaviour could be of great help to clarify the addressed hypotheses. This study could have further ramification in the epidemiological studies and the monitoring protocols of the neglected Sarcoptes mite in predator/prey ecosystems.

  7. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations

    Directory of Open Access Journals (Sweden)

    Rajani Rai

    2015-11-01

    Full Text Available Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR and Classification and Regression Tree Analysis (CRT to investigate the gene–gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634; FAS (rs2234767; FASL (rs763110; DCC (rs2229080, rs4078288, rs7504990, rs714; PSCA (rs2294008, rs2978974; ADRA2A (rs1801253; ADRB1 (rs1800544; ADRB3 (rs4994; CYP17 (rs2486758 involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634, DCC (rs714, rs2229080, rs4078288 and ADRB3 (rs4994 polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994 to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10 or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10. Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility.

  8. Remote video bioassays reveal the potential feeding impact of the rabbitfish Siganus canaliculatus (f: Siganidae) on an inner-shelf reef of the Great Barrier Reef

    Science.gov (United States)

    Fox, R. J.; Bellwood, D. R.

    2008-09-01

    Herbivores are widely acknowledged as key elements maintaining the health and resilience of terrestrial and aquatic ecosystems. Understanding and quantifying the impact of herbivores in ecosystems are fundamental to our ability to manage these systems. The traditional method of quantifying the impact of herbivorous fishes on coral reefs has been to use transplanted pieces of seagrass or algae as “bioassays”. However, these experiments leave a key question unanswered, namely: Which species are responsible for the impact being quantified? This study revisits the use of bioassays and tested the assumption that the visual abundance of species reflects their role in the removal of assay material. Using remote video cameras to film removal of assay material on an inner-shelf reef of the Great Barrier Reef, the species responsible for assay-based herbivory were identified. The video footage revealed that Siganus canaliculatus, a species not previously recorded at the study site, was primarily responsible for removal of macroalgal biomass. The average percentage decrease in thallus length of whole plants of Sargassum at the reef crest was 54 ± 8.9% (mean ± SE), and 50.4 ± 9.8% for individually presented Sargassum strands (for a 4.5-h deployment). Of the 14,656 bites taken from Sargassum plants and strands across all reef zones, nearly half (6,784 bites or 46%) were taken by S. canaliculatus, with the majority of the remainder attributable to Siganus doliatus. However, multiple regression analysis demonstrated that only the bites of S. canaliculatus were removing macroalgal biomass. The results indicate that, even with detailed observations, the species of herbivore that may be responsible for maintaining benthic community structure can go unnoticed. Some of our fundamental ideas of the relative importance of individual species in ecosystem processes may be in need of re-evaluation.

  9. ‘Get in early’; biofilm and wax moth (Galleria mellonella models reveal new insights into the therapeutic potential of Clostridium difficile bacteriophages

    Directory of Open Access Journals (Sweden)

    Janet Yakubu Nale

    2016-08-01

    Full Text Available Clostridium difficile infection (CDI is a global health threat associated with high rates of morbidity and mortality. Conventional antibiotic CDI therapy can result in treatment failure and recurrent infection. C. difficile produces biofilms which contribute to its virulence and impair antimicrobial activity. Some bacteriophages (phages can penetrate biofilms and thus could be developed to either replace or supplement antibiotics. Here, we determined the impact of a previously optimized 4-phage cocktail on C. difficile ribotype 014/020 biofilms, and additionally as adjunct to vancomycin treatment in Galleria mellonella larva CDI model. The phages were applied before or after biofilm establishment in vitro, and the impact was analyzed according to turbidity, viability counts and topography as observed using scanning electron and confocal microscopy. The infectivity profiles and efficacies of orally administered phages and/or vancomycin were ascertained by monitoring colonization levels and larval survival rates. Phages prevented biofilm formation, and penetrated established biofilms. A single phage application reduced colonization causing extended longevity in the remedial treatment and prevented disease in the prophylaxis group. Multiple phage doses significantly improved the larval remedial regimen, and this treatment is comparable to vancomycin and the combined treatments. Taken together, our data suggest that the phages significantly reduce C. difficile biofilms, and prevent colonization in the G. mellonella model when used alone or in combination with vancomycin. The phages appear to be highly promising therapeutics in the targeted eradication of CDI and the use of these models has revealed that prophylactic use could be a propitious therapeutic option.

  10. Development of therapeutic antibodies to G protein-coupled receptors and ion channels: Opportunities, challenges and their therapeutic potential in respiratory diseases.

    Science.gov (United States)

    Douthwaite, Julie A; Finch, Donna K; Mustelin, Tomas; Wilkinson, Trevor C I

    2017-01-01

    The development of recombinant antibody therapeutics continues to be a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Therapeutic drug targets such as soluble cytokines, growth factors and single transmembrane spanning receptors have been successfully targeted by recombinant monoclonal antibodies and the development of new product candidates continues. Despite this growth, however, certain classes of important disease targets have remained intractable to therapeutic antibodies due to the complexity of the target molecules. These complex target molecules include G protein-coupled receptors and ion channels which represent a large target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these important regulators of cell function. Given this opportunity, a significant effort has been applied to address the challenges of targeting these complex molecules and a number of targets are linked to the pathophysiology of respiratory diseases. In this review, we provide a summary of the importance of GPCRs and ion channels involved in respiratory disease and discuss advantages offered by antibodies as therapeutics at these targets. We highlight some recent GPCRs and ion channels linked to respiratory disease mechanisms and describe in detail recent progress made in the strategies for discovery of functional antibodies against challenging membrane protein targets such as GPCRs and ion channels.

  11. Efficacy of soluble recombinant FliC protein from Salmonella enterica serovar enteritidis as a potential vaccine candidate against homologous challenge in chickens.

    Science.gov (United States)

    Okamura, Masashi; Matsumoto, Wakako; Seike, Fumio; Tanaka, Yuuya; Teratani, Chie; Tozuka, Maki; Kashimoto, Takashige; Takehara, Kazuaki; Nakamura, Masayuki; Yoshikawa, Yasuhiro

    2012-06-01

    FliC, the flagellin antigen of Salmonella Enteritidis, was tested as a vaccine candidate for protective effect against a homologous challenge in chickens. After immunization with recombinant FliC (rFliC) or administration of phosphate-buffered saline (PBS) at 56 days old, the chickens were challenged with 10(9) colony-forming units of Salmonella Enteritidis at 76 days old. The vaccinated birds showed significantly decreased bacterial counts in the liver and cecal contents compared to those administered PBS at 7 days postchallenge, but the protection was partial. The replication experiment also showed a similar result. In both experiments, vaccination induced an increased level of serum anti-rFliC IgG, which was also reactive to the native flagella. The intestinal IgA level was slightly higher in the vaccinated birds than in the control. However, neither the proliferative response nor interferon-gamma secretion of splenic cells upon stimulation with rFliC was induced. Therefore, the effect of rFliC as a vaccine is limited, and further improvement is needed.

  12. The spatial epidemiology of trauma: the potential of geographic information science to organize data and reveal patterns of injury and services.

    Science.gov (United States)

    Schuurman, Nadine; Hameed, S Morad; Fiedler, Robert; Bell, Nathaniel; Simons, Richard K

    2008-10-01

    Despite important advances in the prevention and treatment of trauma, preventable injuries continue to impact the lives of millions of people. Motor vehicle collisions and violence claim close to 3 million lives each year worldwide. Public health agencies have promoted the need for systematic and ongoing surveillance as a foundation for successful injury control. Surveillance has been used to quantify the incidence of injury for the prioritization of further research, monitor trends over time, identify new injury patterns, and plan and evaluate prevention and intervention efforts. Advances in capability to handle spatial data and substantial increases in computing power have positioned geographic information science (GIS) as a potentially important tool for health surveillance and the spatial organization of health care, and for informing prevention and acute care interventions. Two themes emerge in the trauma literature with respect to GIS theory and techniques: identifying determinants associated with the risk of trauma to guide injury prevention efforts and evaluating the spatial organization and accessibility of acute trauma care systems. We review the current literature on trauma and GIS research and provide examples of the importance of accounting for spatial scale when using spatial analysis for surveillance. The examples illustrate the effect of scale on incident analysis, the geographic variation of major injury across British Columbia's health service delivery areas (HSDAs) and the rates of variation of injury within individual HSDAs.

  13. The synthesis and characterisation of MDMA derived from a catalytic oxidation of material isolated from black pepper reveals potential route specific impurities.

    Science.gov (United States)

    Plummer, Christopher M; Breadon, Thomas W; Pearson, James R; Jones, Oliver A H

    2016-05-01

    This work examines the chemical synthesis of 3,4-methylenedioxy-N-methylamphetamine (MDMA) from piperonal prepared via a catalytic ruthenium tetroxide oxidation of piperine extracted from black pepper. A variety of oxidation conditions were experimented with including different solvent systems and co-oxidants. A sample of prepared piperonal was successfully converted into MDMA via 3,4-methylenedioxyphenyl-2-nitropropene (MDP2NP) and 3,4-methylenedioxyphenyl-2-propanone (MDP2P) and the impurities within each product characterised by GC-MS to give a contaminant profile of the synthetic pathway. Interestingly, it was discovered that a chlorinated analogue of piperonal (6-chloropiperonal) was created during the oxidation process by an as yet unknown mechanism. This impurity reacted alongside piperonal to give chlorinated analogues of each precursor, ultimately yielding 2-chloro-4,5-methylenedioxymethamphetamine (6-Cl-MDMA) as an impurity within the MDMA sample. The methodology developed is a simple way to synthesise a substantial amount of precursor material with easy to obtain reagents. The results also show that chlorinated MDMA analogues, previously thought to be deliberately included adulterants, may in fact be route specific impurities with potential application in determining the origin and synthesis method of seized illicit drugs.

  14. Activation and application of an obligatory phonotactic constraint in German during automatic speech processing is revealed by human event-related potentials.

    Science.gov (United States)

    Steinberg, Johanna; Truckenbrodt, Hubert; Jacobsen, Thomas

    2010-07-01

    In auditory speech processing, implicit linguistic knowledge is activated and applied on phonetic and segment-related phonological processing level even if the perceived sound sequence is outside the focus of attention. In this study, the effects of language-specific phonotactic restrictions on pre-attentive auditory speech processing were investigated, using the Mismatch Negativity component of the human event-related brain potential. In German grammar, the distribution of the velar and the palatal dorsal fricative is limited by an obligatory phonotactic constraint, Dorsal Fricative Assimilation, which demands that a vowel and a following dorsal fricative must have the same specifications for articulatory backness. For passive oddball stimulation, we used three phonotactically correct VC syllables and one incorrect VC syllable, composed of the vowels [epsilon] and [open o] and the fricatives [ç] and []. Stimuli were contrasted pairwise in experimental oddball blocks in a way that they differed in regard to their respective vowel but shared the fricative. Additionally to the usual Mismatch Negativity which is attributable to the change of the initial vowel and which was elicited by all deviants, we observed a second negative deflection in the deviant ERP elicited by the phonotactically ill-formed syllable only. This negativity cannot be attributed to any acoustical or phonemic difference between standard and deviant, it rather reflects the effect of a phonotactic evaluation process after both sounds of the syllable were identified. Our finding suggests that implicit phonotactic knowledge is activated and applied even outside the focus of the participants' attention.

  15. High Genetic Diversity of Newcastle Disease Virus in Wild and Domestic Birds in Northeastern China from 2013 to 2015 Reveals Potential Epidemic Trends.

    Science.gov (United States)

    Zhang, Pingze; Xie, Guangyao; Liu, Xinxin; Ai, Lili; Chen, Yanyu; Meng, Xin; Bi, Yuhai; Chen, Jianjun; Sun, Yuzhang; Stoeger, Tobias; Ding, Zhuang; Yin, Renfu

    2015-12-28

    Newcastle disease (ND), caused by the virulent Newcastle disease virus (NDV), is one of the most important viral diseases of birds globally, but little is currently known regarding enzootic trends of NDV in northeastern China, especially for class I viruses. Thus, we performed a surveillance study for NDV in northeastern China from 2013 to 2015. A total 755 samples from wild and domestic birds in wetlands and live bird markets (LBMs) were collected, and 10 isolates of NDV were identified. Genetic and phylogenetic analyses showed that five isolates from LBMs belong to class I subgenotype 1b, two (one from wild birds and one from LBMs) belong to the vaccine-like class II genotype II, and three (all from wild birds) belong to class II subgenotype Ib. Interestingly, the five class I isolates had epidemiological connections with viruses from southern, eastern, and southeastern China. Our findings, together with recent prevalence trends of class I and virulent class II NDV in China, suggest possible virus transmission between wild and domestic birds and the potential for an NDV epidemic in the future.

  16. The phenome analysis of mutant alleles in Leucine-Rich Repeat Receptor-Like Kinase genes in rice reveals new potential targets for stress tolerant cereals.

    Science.gov (United States)

    Dievart, Anne; Perin, Christophe; Hirsch, Judith; Bettembourg, Mathilde; Lanau, Nadège; Artus, Florence; Bureau, Charlotte; Noel, Nicolas; Droc, Gaétan; Peyramard, Matthieu; Pereira, Serge; Courtois, Brigitte; Morel, Jean-Benoit; Guiderdoni, Emmanuel

    2016-01-01

    Plants are constantly exposed to a variety of biotic and abiotic stresses that reduce their fitness and performance. At the molecular level, the perception of extracellular stimuli and the subsequent activation of defense responses require a complex interplay of signaling cascades, in which protein phosphorylation plays a central role. Several studies have shown that some members of the Leucine-Rich Repeat Receptor-Like Kinase (LRR-RLK) family are involved in stress and developmental pathways. We report here a systematic analysis of the role of the members of this gene family by mutant phenotyping in the monocotyledon model plant rice, Oryza sativa. We have then targeted 176 of the ∼320 LRR-RLK genes (55.7%) and genotyped 288 mutant lines. Position of the insertion was confirmed in 128 lines corresponding to 100 LRR-RLK genes (31.6% of the entire family). All mutant lines harboring homozygous insertions have been screened for phenotypes under normal conditions and under various abiotic stresses. Mutant plants have been observed at several stages of growth, from seedlings in Petri dishes to flowering and grain filling under greenhouse conditions. Our results show that 37 of the LRR-RLK rice genes are potential targets for improvement especially in the generation of abiotic stress tolerant cereals.

  17. Evaluation of current and new biomarkers in severe preeclampsia: a microarray approach reveals the VSIG4 gene as a potential blood biomarker.

    Science.gov (United States)

    Textoris, Julien; Ivorra, Delphine; Ben Amara, Amira; Sabatier, Florence; Ménard, Jean-Pierre; Heckenroth, Hélène; Bretelle, Florence; Mege, Jean-Louis

    2013-01-01

    Preeclampsia is a placental disease characterized by hypertension and proteinuria in pregnant women, and it is associated with a high maternal and neonatal morbidity. However, circulating biomarkers that are able to predict the prognosis of preeclampsia are lacking. Thirty-eight women were included in the current study. They consisted of 19 patients with preeclampsia (13 with severe preeclampsia and 6 with non-severe preeclampsia) and 19 gestational age-matched women with normal pregnancies as controls. We measured circulating factors that are associated with the coagulation pathway (including fibrinogen, fibronectin, factor VIII, antithrombin, protein S and protein C), endothelial activation (such as soluble endoglin and CD146), and the release of total and platelet-derived microparticles. These markers enabled us to discriminate the preeclampsia condition from a normal pregnancy but were not sufficient to distinguish severe from non-severe preeclampsia. We then used a microarray to study the transcriptional signature of blood samples. Preeclampsia patients exhibited a specific transcriptional program distinct from that of the control group of women. Interestingly, we also identified a severity-related transcriptional signature. Functional annotation of the upmodulated signature in severe preeclampsia highlighted two main functions related to "ribosome" and "complement". Finally, we identified 8 genes that were specifically upmodulated in severe preeclampsia compared with non-severe preeclampsia and the normotensive controls. Among these genes, we identified VSIG4 as a potential diagnostic marker of severe preeclampsia. The determination of this gene may improve the prognostic assessment of severe preeclampsia.

  18. Evaluation of current and new biomarkers in severe preeclampsia: a microarray approach reveals the VSIG4 gene as a potential blood biomarker.

    Directory of Open Access Journals (Sweden)

    Julien Textoris

    Full Text Available Preeclampsia is a placental disease characterized by hypertension and proteinuria in pregnant women, and it is associated with a high maternal and neonatal morbidity. However, circulating biomarkers that are able to predict the prognosis of preeclampsia are lacking. Thirty-eight women were included in the current study. They consisted of 19 patients with preeclampsia (13 with severe preeclampsia and 6 with non-severe preeclampsia and 19 gestational age-matched women with normal pregnancies as controls. We measured circulating factors that are associated with the coagulation pathway (including fibrinogen, fibronectin, factor VIII, antithrombin, protein S and protein C, endothelial activation (such as soluble endoglin and CD146, and the release of total and platelet-derived microparticles. These markers enabled us to discriminate the preeclampsia condition from a normal pregnancy but were not sufficient to distinguish severe from non-severe preeclampsia. We then used a microarray to study the transcriptional signature of blood samples. Preeclampsia patients exhibited a specific transcriptional program distinct from that of the control group of women. Interestingly, we also identified a severity-related transcriptional signature. Functional annotation of the upmodulated signature in severe preeclampsia highlighted two main functions related to "ribosome" and "complement". Finally, we identified 8 genes that were specifically upmodulated in severe preeclampsia compared with non-severe preeclampsia and the normotensive controls. Among these genes, we identified VSIG4 as a potential diagnostic marker of severe preeclampsia. The determination of this gene may improve the prognostic assessment of severe preeclampsia.

  19. Spatially resolved physical conditions of molecular gas and potential star formation tracers in M83, revealed by the Herschel SPIRE FTS

    CERN Document Server

    Wu, Ronin; Galliano, Frédéric; Wilson, Christine D; Kamenetzky, Julia; Lee, Min-Young; Schirm, Maximilien; Hony, Sacha; Lebouteiller, Vianney; Spinoglio, Luigi; Cormier, Diane; Glenn, Jason; Maloney, Philip R; Pereira-Santaella, Miguel; Rémy-Ruyer, Aurélie; Baes, Martin; Boselli, Alexandro; Bournaud, Frédéric; De Looze, Ilse; Hughes, Thomas M; Panuzzo, Pasquale; Rangwala, Naseem

    2014-01-01

    Since the launch of the Herschel Space Observatory, our understanding about the photo-dissociation regions (PDR) has taken a step forward. In the bandwidth of the Fourier Transform Spectrometer (FTS) of the Spectral and Photometric Imaging REceiver (SPIRE) on board Herschel, ten CO rotational transitions, including J=4-3 to J=13-12, and three fine structure lines, including [CI] 609, [CI] 370, and [NII] 250 micron, are covered. In this paper, I present our findings from the FTS observations at the nuclear region of M83, based on the spatially resolved physical parameters derived from the CO spectral line energy distribution (SLED) map and the comparisons with the dust properties and star-formation tracers. I will discuss (1) the potential of using [NII] 250 and [CI] 370 micron as star-formation tracers; (2) the reliability of tracing molecular gas with CO; (3) the excitation mechanisms of warm CO; (4) the possibility of studying stellar feedback by tracing the thermal pressure of molecular gas in the nuclear ...

  20. Combined morphological and molecular data unveils relationships of Pseudobranchiomma (Sabellidae, Annelida and reveals higher diversity of this intriguing group of fan worms in Australia, including potentially introduced species

    Directory of Open Access Journals (Sweden)

    Maria Capa

    2016-10-01

    Full Text Available Pseudobranchiomma (Sabellidae, Annelida is a small and heterogeneous group of fan worms found in shallow marine environments and is generally associated with hard substrates. The delineation and composition of this genus is problematic since it has been defined only by plesiomorphic characters that are widely distributed among other sabellids. In this study we have combined morphological and molecular (mitochondrial and nuclear DNA sequences data to evaluate species diversity in Australia and assess the phylogenetic relationships of these and other related sabellids. Unlike morphological data alone, molecular data and combined datasets suggest monophyly of Pseudobranchiomma. In this study, a new species of Pseudobranchiomma is described and three others are considered as potential unintentional introductions to Australian waters, one of them reported for the first time for the continent. Pseudobranchiomma pallida sp. n. bears 4–6 serrations along the radiolar flanges, lacks radiolar eyes and has uncini with three transverse rows of teeth over the main fang. In the new species the colour pattern as well is characteristic and species specific.

  1. First study on gene expression of cement proteins and potential adhesion-related genes of a membranous-based barnacle as revealed from Next-Generation Sequencing technology

    KAUST Repository

    Lin, Hsiu Chin

    2013-12-12

    This is the first study applying Next-Generation Sequencing (NGS) technology to survey the kinds, expression location, and pattern of adhesion-related genes in a membranous-based barnacle. A total of 77,528,326 and 59,244,468 raw sequence reads of total RNA were generated from the prosoma and the basis of Tetraclita japonica formosana, respectively. In addition, 55,441 and 67,774 genes were further assembled and analyzed. The combined sequence data from both body parts generates a total of 79,833 genes of which 47.7% were shared. Homologues of barnacle cement proteins - CP-19K, -52K, and -100K - were found and all were dominantly expressed at the basis where the cement gland complex is located. This is the main area where transcripts of cement proteins and other potential adhesion-related genes were detected. The absence of another common barnacle cement protein, CP-20K, in the adult transcriptome suggested a possible life-stage restricted gene function and/or a different mechanism in adhesion between membranous-based and calcareous-based barnacles. © 2013 © 2013 Taylor & Francis.

  2. An Immunocompetent Mouse Model for MLL/AF9 Leukemia Reveals the Potential of Spontaneous Cytotoxic T-Cell Response to an Antigen Expressed in Leukemia Cells.

    Directory of Open Access Journals (Sweden)

    Kana Hasegawa

    Full Text Available Leukemia differs substantially with respect to stromal milieu from tumors that progress locally as solid masses, and the physiological importance of immunosurveillance in leukemia remains unclear. However, currently available mouse leukemia models have critical limitations in the context of analyzing immunological regulation of leukemia development. In this study, we transferred mouse MLL/AF9 leukemia-initiating cells into immunocompetent recipient mice without any pre-conditioning such as irradiation, and then analyzed the spontaneous T cell response to an immunogenic antigen expressed in leukemia cells. When the minimum numbers of leukemia-initiating cells for engraftment were transferred, leukemia cells were eradicated by the adaptive immune response in most, if not all, wild-type mice, but not in Rag2-/- recipient mice, which lack adaptive immunity. By contrast, mice transplanted with larger numbers of leukemia cells always developed leukemia. In mice with advanced leukemia, antigen-specific CTLs were also expanded, but were unresponsive to antigen stimulation and expressed high levels of PD-1 and LAG-3. These results provide the first clear demonstration that the spontaneous CTL response to a tumor-cell antigen has the potential to eradicate leukemia, whereas antigen-specific CTLs are exhausted in animals with advanced leukemia. This immunocompetent mouse leukemia model provides a useful platform for developing effective immunotherapies against leukemia.

  3. Analysis of Large Seeds from Three Different Medicago truncatula Ecotypes Reveals a Potential Role of Hormonal Balance in Final Size Determination of Legume Grains

    Directory of Open Access Journals (Sweden)

    Kaustav Bandyopadhyay

    2016-09-01

    Full Text Available Legume seeds are important as protein and oil source for human diet. Understanding how their final seed size is determined is crucial to improve crop yield. In this study, we analyzed seed development of three accessions of the model legume, Medicago truncatula, displaying contrasted seed size. By comparing two large seed accessions to the reference accession A17, we described mechanisms associated with large seed size determination and potential factors modulating the final seed size. We observed that early events during embryogenesis had a major impact on final seed size and a delayed heart stage embryo development resulted to large seeds. We also observed that the difference in seed growth rate was mainly due to a difference in embryo cell number, implicating a role of cell division rate. Large seed accessions could be explained by an extended period of cell division due to a longer embryogenesis phase. According to our observations and recent reports, we observed that auxin (IAA and abscisic acid (ABA ratio could be a key determinant of cell division regulation at the end of embryogenesis. Overall, our study highlights that timing of events occurring during early seed development play decisive role for final seed size determination.

  4. Single-cell analysis reveals IGF-1 potentiation of inhibition of the TGF-β/Smad pathway of fibrosis in human keratocytes in vitro

    Science.gov (United States)

    Sarenac, Tomislav; Trapecar, Martin; Gradisnik, Lidija; Rupnik, Marjan Slak; Pahor, Dusica

    2016-01-01

    Corneal wound healing is often affected by TGF-β–mediated fibrosis and scar formation. Guided fibrosis with IGF-1 and antifibrotic substances might maintain corneal transparency. Primary human corneal keratocytes under serum-free conditions were used as a model of corneal stromal wounding, with markers of corneal fibrosis and opacity studied under TGF-β2 stimulation. Single-cell imaging flow cytometry was used to determine nuclearization of Smad3, and intracellular fluorescence intensity of Smad7 and the corneal crystallin aldehyde dehydrogenase 3A1. Extracellular matrix proteoglycans keratocan and biglycan were quantified using ELISAs. On the TGF-β2 background, the keratocytes were treated with IGF-1, and suberoylanilidehydroxamic acid (SAHA) or halofuginone ± IGF-1. IGF-1 alone decreased Smad3 nuclearization and increased aldehyde dehydrogenase 3A1 expression, with favorable extracellular matrix proteoglycan composition. SAHA induced higher Smad7 levels and inhibited translocation of Smad3 to the nucleus, also when combined with IGF-1. Immunofluorescence showed that myofibroblast transdifferentiation is attenuated and appearance of fibroblasts is favored by IGF-1 alone and in combination with the antifibrotic substances. The TGF-β/Smad pathway of fibrosis and opacity was inhibited by IGF-1, and further with SAHA in particular, and with halofuginone. IGF-1 is thus a valid aid to antifibrotic treatment, with potential for effective and transparent corneal wound healing. PMID:27687492

  5. Temporal Variation in Honey Production by the Stingless Bee Melipona subnitida (Hymenoptera: Apidae): Long-Term Management Reveals its Potential as a Commercial Species in Northeastern Brazil.

    Science.gov (United States)

    Koffler, Sheina; Menezes, Cristiano; Menezes, Paulo Roberto; Kleinert, Astrid de Matos Peixoto; Imperatriz-Fonseca, Vera Lucia; Pope, Nathaniel; Jaffé, Rodolfo

    2015-06-01

    Even though stingless beekeeping has a great potential as a sustainable development tool, the activity remains essentially informal, technical knowledge is scarce, and management practices lack the sophistication and standardization found in apiculture. Here, we contributed to the further development of stingless beekeeping by investigating the long-term impact of management and climate on honey production and colony survival in the stingless bee Melipona subnitida Ducke (1910). We analyzed a 10-yr record of 155 M. subnitida colonies kept by a commercial honey producer of northeastern Brazil. This constitutes the longest and most accurate record available for a stingless bee. We modeled honey production in relation to time (years), age, management practices (colony division and food supplementation), and climatic factors (temperature and precipitation), and used a model selection approach to identify which factors best explained honey production. We also modeled colony mortality in relation to climatic factors. Although the amount of honey produced by each colony decreased over time, we found that the probability of producing honey increased over the years. Colony divisions decreased honey production, but did not affect honey presence, while supplementary feeding positively affected honey production. In warmer years, the probability of producing honey decreased and the amount of honey produced was lower. In years with lower precipitation, fewer colonies produced honey. In contrast, colony mortality was not affected by climatic factors, and some colonies lived up to nine years, enduring extreme climatic conditions. Our findings provide useful guidelines to improve management and honey production in stingless bees.

  6. Cost-of-illness analysis reveals potential healthcare savings with reductions in type 2 diabetes and cardiovascular disease following recommended intakes of dietary fibre in Canada

    Directory of Open Access Journals (Sweden)

    Mohammad eAbdullah

    2015-08-01

    Full Text Available Background: Consumption of fibre-rich diets is associated with favourable impacts on type 2 diabetes (T2D and cardiovascular disease (CVD, two of the most costly ailments worldwide, however the economic value of altered fibre intakes remains poorly understood. Methods: A cost-of-illness analysis was conducted to identify the percentage of adults expected to consume fibre-rich diets in Canada, estimate fibre intakes in relation to T2D and CVD reductions, and assess the potential annual savings in healthcare costs with reductions in rates of these two epidemics. Results: Non-trivial healthcare and related savings of CAD$35.9-$718.8 million in T2D costs and CAD$64.8-$1,295.7 million in CVD costs were calculated under a scenario where cereal fibre was used to increase current intakes of dietary fibre to the recommended levels of 38 g per day for men and 25 g per day for women. Each 1 g per day increase in fibre consumption resulted in annual CAD$2.6-$51.1 and $4.6-$92.1 million savings for T2D and CVD, respectively. Conclusions: Strategies to increase consumers’ knowledge of the recommended dietary fibre intakes, as part of healthy diet, and to facilitate stakeholder synergy are warranted to enable better management of costs associated with T2D and CVD in Canada.

  7. Analysis of Large Seeds from Three Different Medicago truncatula Ecotypes Reveals a Potential Role of Hormonal Balance in Final Size Determination of Legume Grains

    Science.gov (United States)

    Bandyopadhyay, Kaustav; Uluçay, Orhan; Şakiroğlu, Muhammet; Udvardi, Michael K.; Verdier, Jerome

    2016-01-01

    Legume seeds are important as protein and oil source for human diet. Understanding how their final seed size is determined is crucial to improve crop yield. In this study, we analyzed seed development of three accessions of the model legume, Medicago truncatula, displaying contrasted seed size. By comparing two large seed accessions to the reference accession A17, we described mechanisms associated with large seed size determination and potential factors modulating the final seed size. We observed that early events during embryogenesis had a major impact on final seed size and a delayed heart stage embryo development resulted to large seeds. We also observed that the difference in seed growth rate was mainly due to a difference in embryo cell number, implicating a role of cell division rate. Large seed accessions could be explained by an extended period of cell division due to a longer embryogenesis phase. According to our observations and recent reports, we observed that auxin (IAA) and abscisic acid (ABA) ratio could be a key determinant of cell division regulation at the end of embryogenesis. Overall, our study highlights that timing of events occurring during early seed development play decisive role for final seed size determination. PMID:27618017

  8. MicroRNA profiling analysis throughout tomato fruit development and ripening reveals potential regulatory role of RIN on microRNAs accumulation.

    Science.gov (United States)

    Gao, Chao; Ju, Zheng; Cao, Dongyan; Zhai, Baiqiang; Qin, Guozheng; Zhu, Hongliang; Fu, Daqi; Luo, Yunbo; Zhu, Benzhong

    2015-04-01

    The development and ripening of tomato fruit are complex processes involving many gene regulatory pathways at the transcriptional and post-transcriptional level. Ripening inhibitor (RIN) is a vital transcription factor, which targets numerous ripening-related genes at the transcriptional level during tomato fruit ripening. MicroRNAs (miRNAs) are a class of short noncoding RNAs that play important roles in post-transcriptional gene regulation. To elucidate the potential regulatory relationship between rin and miRNAs during fruit development and ripening, we identified known miRNAs and profiled their expression in wild-type tomato and rin mutant using a deep sequencing approach combined with quantitative RT-PCR. A total of 33 known miRNA families were identified, of which 14 miRNA families were differently accumulated. Subsequent promoter analysis showed that possible RIN-binding motifs (CArG-box) tended to occur frequently in the promoter regions of partial differently expressed miRNAs. In addition, ethylene may participate in the regulation of miRNAs accumulation during tomato fruit ripening. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay confirmed the direct binding of RIN to the promoter of MIR172a. Collectively, these results showed a close correlation between miRNA expression and RIN as well as ethylene, which further elucidated the regulatory roles of miRNAs during fruit development and ripening and enriched the regulatory network of RIN in tomato fruit.

  9. Pyrosequencing of 16S rRNA genes in fecal samples reveals high diversity of hindgut microflora in horses and potential links to chronic laminitis

    Directory of Open Access Journals (Sweden)

    Steelman Samantha M

    2012-11-01

    Full Text Available Abstract Background The nutrition and health of horses is closely tied to their gastrointestinal microflora. Gut bacteria break down plant structural carbohydrates and produce volatile fatty acids, which are a major source of energy for horses. Bacterial communities are also essential for maintaining gut homeostasis and have been hypothesized to contribute to various diseases including laminitis. We performed pyrosequencing of 16S rRNA bacterial genes isolated from fecal material to characterize hindgut bacterial communities in healthy horses and those with chronic laminitis. Results Fecal samples were collected from 10 normal horses and 8 horses with chronic laminitis. Genomic DNA was extracted and the V4-V5 segment of the 16S rRNA gene was PCR amplified and sequenced on the 454 platform generating a mean of 2,425 reads per sample after quality trimming. The bacterial communities were dominated by Firmicutes (69.21% control, 56.72% laminitis and Verrucomicrobia (18.13% control, 27.63% laminitis, followed by Bacteroidetes, Proteobacteria, and Spirochaetes. We observed more OTUs per individual in the laminitis group than the control group (419.6 and 355.2, respectively, P = 0.019 along with a difference in the abundance of two unassigned Clostridiales genera (P = 0.03 and P = 0.01. The most abundant bacteria were Streptococcus spp., Clostridium spp., and Treponema spp.; along with unassigned genera from Subdivision 5 of Verrucomicrobia, Ruminococcaceae, and Clostridiaceae, which together constituted ~ 80% of all OTUs. There was a high level of individual variation across all taxonomic ranks. Conclusions Our exploration of the equine fecal microflora revealed higher bacterial diversity in horses with chronic laminitis and identification of two Clostridiales genera that differed in abundance from control horses. There was large individual variation in bacterial communities that was not explained in our study. The core hindgut microflora was

  10. Ambiguity Revealed

    OpenAIRE

    Subir Bose; Matthew Polisson; Ludovic Renou

    2012-01-01

    We derive necessary and suffcient conditions for data sets composed of state-contingent prices and consumption to be consistent with two prominent models of decision making under ambiguity: variational preferences and smooth ambiguity. The revealed preference conditions for the maxmin expected utility and subjective expected utility models are characterized as special cases.

  11. Ambiguity revealed

    OpenAIRE

    Bayer, Ralph-C; Bose, Subir; Polisson, Matthew; Renou, Ludovic

    2013-01-01

    We derive necessary and sufficient conditions for data sets composed of state-contingent prices and consumption to be consistent with two prominent models of decision making under uncertainty: variational preferences and smooth ambiguity. The revealed preference conditions for subjective expected utility, maxmin expected utility, and multiplier preferences are characterised as special cases. We implement our tests on data from a portfolio choice experiment.

  12. Characterization of Missouri surface waters near point sources of pollution reveals potential novel atmospheric route of exposure for bisphenol A and wastewater hormonal activity pattern

    Science.gov (United States)

    Kassotis, Christopher D.; Alvarez, David A.; Taylor, Julia A.; vom Saal, Frederick S.; Nagel, Susan C.; Tillitt, Donald E.

    2015-01-01

    Surface water contamination by chemical pollutants increasingly threatens water quality around the world. Among the many contaminants found in surface water, there is growing concern regarding endocrine disrupting chemicals, based on their ability to interfere with some aspect of hormone action in exposed organisms, including humans. This study assessed water quality at several sites across Missouri (near wastewater treatment plants and airborne release sites of bisphenol A) based on hormone receptor activation potencies and chemical concentrationspresent in the surface water. We hypothesized that bisphenol A and ethinylestradiol would be greater in water near permitted airborne release sites and wastewater treatment plant inputs, respectively, and that these two compounds would be responsible for the majority of activities in receptor-based assays conducted with water collected near these sites. Concentrations of bisphenol A and ethinylestradiol were compared to observed receptor activities using authentic standards to assess contribution to total activities, and quantitation of a comprehensive set of wastewater compounds was performed to better characterize each site. Bisphenol A concentrations were found to be elevated in surface water near permitted airborne release sites, raising questions that airborne releases of BPA may influence nearby surface water contamination and may represent a previously underestimated source to the environment and potential for human exposure. Estrogen and androgen receptor activities of surface water samples were predictive of wastewater input, although the lower sensitivity of the ethinylestradiol ELISA relative to the very high sensitivity of the bioassay approaches did not allow a direct comparison. Wastewater-influenced sites also had elevated anti-estrogenic and anti-androgenic equivalence, while sites without wastewater discharges exhibited no antagonist activities.

  13. Connexin 43 mimetic peptide Gap27 reveals potential differences in the role of Cx43 in wound repair between diabetic and non-diabetic cells.

    Science.gov (United States)

    Pollok, Simone; Pfeiffer, Ann-Catherine; Lobmann, Ralf; Wright, Catherine S; Moll, Ingrid; Martin, Patricia E M; Brandner, Johanna M

    2011-04-01

    During early wound healing (WH) events Connexin 43 (Cx43) is down-regulated at wound margins. In chronic wound margins, including diabetic wounds, Cx43 expression is enhanced suggesting that down-regulation is important for WH. We previously reported that the Cx43 mimetic peptide Gap27 blocks Cx43 mediated intercellular communication and promotes skin cell migration of infant cells in vitro. In the present work we further investigated the molecular mechanism of Gap27 action and its therapeutic potential to improve WH in skin tissue and diabetic and non-diabetic cells. Ex vivo skin, organotypic models and human keratinocytes/fibroblasts of young and old donors and of diabetic and non-diabetic origin were used to assess the impact of Gap27 on cell migration, proliferation, Cx43 expression, localization, phosphorylation and hemichannel function. Exposure of ex vivo WH models to Gap27 decreased dye spread, accelerated WH and elevated cell proliferation. In non-diabetic cell cultures Gap27 decreased dye uptake through Cx hemichannels and after scratch wounding cells showed enhanced migration and proliferation. Cells of diabetic origin were less susceptible to Gap27 during early passages. In late passages these cells showed responses comparable to non-diabetic cells. The cause of the discrepancy between diabetic and non-diabetic cells correlated with decreased Cx hemichannel activity in diabetic cells but excluded differences in Cx43 expression, localization and Ser368-phosphorylation. These data emphasize the importance of Cx43 in WH and support the concept that Gap27 could be a beneficial therapeutic to accelerate normal WH. However, its use in diabetic WH may be restricted and our results highlight differences in the role of Cx43 in skin cells of different origin.

  14. Potentiation of motor sub-networks for motor control but not working memory: Interaction of dACC and SMA revealed by resting-state directed functional connectivity

    Science.gov (United States)

    Diwadkar, Vaibhav A.; Asemi, Avisa; Burgess, Ashley; Chowdury, Asadur; Bressler, Steven L.

    2017-01-01

    The dorsal Anterior Cingulate Cortex (dACC) and the Supplementary Motor Area (SMA) are known to interact during motor coordination behavior. We previously discovered that the directional influences underlying this interaction in a visuo-motor coordination task are asymmetric, with the dACC→SMA influence being significantly greater than that in the reverse direction. To assess the specificity of this effect, here we undertook an analysis of the interaction between dACC and SMA in two distinct contexts. In addition to the motor coordination task, we also assessed these effects during a (n-back) working memory task. We applied directed functional connectivity analysis to these two task paradigms, and also to the rest condition of each paradigm, in which rest blocks were interspersed with task blocks. We report here that the previously known asymmetric interaction between dACC and SMA, with dACC→SMA dominating, was significantly larger in the motor coordination task than the memory task. Moreover the asymmetry between dACC and SMA was reversed during the rest condition of the motor coordination task, but not of the working memory task. In sum, the dACC→SMA influence was significantly greater in the motor task than the memory task condition, and the SMA→dACC influence was significantly greater in the motor rest than the memory rest condition. We interpret these results as suggesting that the potentiation of motor sub-networks during the motor rest condition supports the motor control of SMA by dACC during the active motor task condition. PMID:28278267

  15. Characterization of Missouri surface waters near point sources of pollution reveals potential novel atmospheric route of exposure for bisphenol A and wastewater hormonal activity pattern.

    Science.gov (United States)

    Kassotis, Christopher D; Alvarez, David A; Taylor, Julia A; vom Saal, Frederick S; Nagel, Susan C; Tillitt, Donald E

    2015-08-15

    Surface water contamination by chemical pollutants increasingly threatens water quality around the world. Among the many contaminants found in surface water, there is growing concern regarding endocrine disrupting chemicals, based on their ability to interfere with some aspect of hormone action in exposed organisms, including humans. This study assessed water quality at several sites across Missouri (near wastewater treatment plants and airborne release sites of bisphenol A) based on hormone receptor activation potencies and chemical concentrations present in the surface water. We hypothesized that bisphenol A and ethinylestradiol would be greater in water near permitted airborne release sites and wastewater treatment plant inputs, respectively, and that these two compounds would be responsible for the majority of activities in receptor-based assays conducted with water collected near these sites. Concentrations of bisphenol A and ethinylestradiol were compared to observed receptor activities using authentic standards to assess contribution to total activities, and quantitation of a comprehensive set of wastewater compounds was performed to better characterize each site. Bisphenol A concentrations were found to be elevated in surface water near permitted airborne release sites, raising questions that airborne releases of BPA may influence nearby surface water contamination and may represent a previously underestimated source to the environment and potential for human exposure. Estrogen and androgen receptor activities of surface water samples were predictive of wastewater input, although the lower sensitivity of the ethinylestradiol ELISA relative to the very high sensitivity of the bioassay approaches did not allow a direct comparison. Wastewater-influenced sites also had elevated anti-estrogenic and anti-androgenic equivalence, while sites without wastewater discharges exhibited no antagonist activities.

  16. STOP-EVENT-RELATED POTENTIALS FROM INTRACRANIAL ELECTRODES REVEAL A KEY ROLE OF PREMOTOR AND MOTOR CORTICES IN STOPPING ONGOING MOVEMENTS

    Directory of Open Access Journals (Sweden)

    Maurizio eMattia

    2012-06-01

    Full Text Available In humans, the ability to withhold manual motor responses seems to rely on a right-lateralized frontal–basal ganglia–thalamic network, including the pre-supplementary motor area and the inferior frontal gyrus. These areas should drive subthalamic nuclei to implement movement inhibition via the hyperdirect pathway. The output of this network is expected to influence those cortical areas underlying limb movement preparation and initiation, i.e. premotor (PMA and primary motor (M1 cortices. Electroencephalographic (EEG studies have shown an enhancement of the N200/P300 complex in the event-related potentials (ERPs when a planned reaching movement is successfully stopped after the presentation of an infrequent stop-signal. PMA and M1 have been suggested as possible neural sources of this ERP complex but, due to the limited spatial resolution of scalp EEG, it is not yet clear which cortical areas contribute to its generation. To elucidate the role of motor cortices, we recorded epicortical ERPs from the lateral surface of the fronto-temporal lobes of five pharmacoresistant epileptic patients performing a reaching version of the countermanding task while undergoing presurgical monitoring. We consistently found a stereotyped ERP complex on a single-trial level when a movement was successfully cancelled. These ERPs were selectively expressed in M1, PMA and Brodmann's area (BA 9 and their onsets preceded the end of the stop process, suggesting a causal involvement in this executive function. Such ERPs also occurred in unsuccessful-stop trials, that is, when subjects moved despite the occurrence of a stop-signal, mostly when they had long reaction times. These findings support the hypothesis that motor cortices are the final target of the inhibitory command elaborated by the frontal–basal ganglia–thalamic network.

  17. Regulatory challenges

    Energy Technology Data Exchange (ETDEWEB)

    Austvik, Ole Gunnar

    2003-07-01

    The problem for policy makers wanting to liberalize natural gas markets is that its concentrated structure may also be the socially most efficient one. Because of scale economies, more firms operating in the market may incur higher transportation costs unless the market grows sufficiently in each geographic segment. This argument goes for product extension through vertical (or horizontal) integration and the exploitation of economies of scope as well. Thus, the challenge for governments is to intervene in a way that preserves a market structure that has the potential to minimize cost, and at the same lime change its behavior in order to avoid possible lax cost control and exploitation of market power. The existence of scope advantages indicates that liberalization of the market should open for the possibility to bundle services in competition with provision of unbundled services. If operations are unbundled and there exist economies of scope, the gain from increased competition should be weighed against the losses of less efficient operations of each firm. Thus, with the growth in the European market, gradually more arguments support the idea of unbundling. The significant scale economy in trunk pipelines, sunk investments and capital immobility, possible economies of scope in vertical integration and companies' bundling of services influences vertical and horizontal ownership relations and contractual terms in the European gas market. In specific segments of the markets, these relationships may promote efficient investments and pricing without public interference, but the strong concentration of market power indicates that this is rather the exception than the rule. In order to design an efficient and welfare maximizing way of regulating the market one needs a closer identification of the actual goal of the regulation. Microeconomic theory is often used for this purpose. The author discusses the alternatives of laissez-faire, nationalization or regulation for

  18. Differential responses of dinitrogen fixation, diazotrophic cyanobacteria and ammonia oxidation reveal a potential warming-induced imbalance of the N-cycle in biological soil crusts

    Science.gov (United States)

    Zhou, Xiaobing; Smith, Hilda J.; Giraldo Silva, Ana; Belnap, Jayne; Garcia-Pichel, Ferran

    2017-01-01

    N2 fixation and ammonia oxidation (AO) are the two most important processes in the nitrogen (N) cycle of biological soil crusts (BSCs). We studied the short-term response of acetylene reduction assay (ARA) rates, an indicator of potential N2 fixation, and AO rates to temperature (T, -5°C to 35°C) in BSC of different successional stages along the BSC ecological succession and geographic origin (hot Chihuahuan and cooler Great Basin deserts). ARA in all BSCs increased with T until saturation occurred between 15 and 20°C, and declined at 30–35°C. Culture studies using cyanobacteria isolated from these crusts indicated that the saturating effect was traceable to their inability to grow well diazotrophically within the high temperature range. Below saturation, temperature response was exponential, with Q10 significantly different in the two areas (~ 5 for Great Basin BSCs; 2–3 for Chihuahuan BSCs), but similar between the two successional stages. However, in contrast to ARA, AO showed a steady increase to 30–35°C in Great Basin, and Chihuhuan BSCs showed no inhibition at any tested temperature. The T response of AO also differed significantly between Great Basin (Q10 of 4.5–4.8) and Chihuahuan (Q10 of 2.4–2.6) BSCs, but not between successional stages. Response of ARA rates to T did not differ from that of AO in either desert. Thus, while both processes scaled to T in unison until 20°C, they separated to an increasing degree at higher temperature. As future warming is likely to occur in the regions where BSCs are often the dominant living cover, this predicted decoupling is expected to result in higher proportion of nitrates in soil relative to ammonium. As nitrate is more easily lost as leachate or to be reduced to gaseous forms, this could mean a depletion of soil N over large landscapes globally.

  19. Challenges of predicting the potential distribution of a slow-spreading invader: a habitat suitability map for an invasive riparian tree

    Science.gov (United States)

    Jarnevich, Catherine S.; Reynolds, Lindsay V.

    2011-01-01

    Understanding the potential spread of invasive species is essential for land managers to prevent their establishment and restore impacted habitat. Habitat suitability modeling provides a tool for researchers and managers to understand the potential extent of invasive species spread. Our goal was to use habitat suitability modeling to map potential habitat of the riparian plant invader, Russian olive (Elaeagnus angustifolia). Russian olive has invaded riparian habitat across North America and is continuing to expand its range. We compiled 11 disparate datasets for Russian olive presence locations (n = 1,051 points and 139 polygons) in the western US and used Maximum entropy (Maxent) modeling to develop two habitat suitability maps for Russian olive in the western United States: one with coarse-scale water data and one with fine-scale water data. Our models were able to accurately predict current suitable Russian olive habitat (Coarse model: training AUC = 0.938, test AUC = 0.907; Fine model: training AUC = 0.923, test AUC = 0.885). Distance to water was the most important predictor for Russian olive presence in our coarse-scale water model, but it was only the fifth most important variable in the fine-scale model, suggesting that when water bodies are considered on a fine scale, Russian olive does not necessarily rely on water. Our model predicted that Russian olive has suitable habitat further west from its current distribution, expanding into the west coast and central North America. Our methodology proves useful for identifying potential future areas of invasion. Model results may be influenced by locations of cultivated individuals and sampling bias. Further study is needed to examine the potential for Russian olive to invade beyond its current range. Habitat suitability modeling provides an essential tool for enhancing our understanding of invasive species spread.

  20. Developing Walvis Bay Port into a logistics gateway for southern Africa: Issues, challenges and the potential implications for Namibia’s future

    Directory of Open Access Journals (Sweden)

    Christopher J. Savage

    2014-03-01

    Full Text Available Many developing countries wish to become the ‘gateway’ to a region or part of a continent.One strategy involves encouraging logistics cluster development. These hubs support global supply chains and may enable the economic growth of the host country through the resulting trade, as well as providing direct and indirect employment opportunities during the build and subsequent operation of the hub. Namibia intends to develop the Port of Walvis Bay to be come the preferred gateway to southern Africa and the Southern African Development Community region. This article builds on research on Caribbean cluster potential and Namibian logistics to identify the potential benefits and impact on development, as well as the drawbacks and risks of such a strategy.

  1. Predicting the ethanol potential of wheat straw using near-infrared spectroscopy and chemometrics: The challenge of inherently intercorrelated response functions

    Energy Technology Data Exchange (ETDEWEB)

    Rinnan, Åsmund; Bruun, Sander; Lindedam, Jane; Decker, Stephen R.; Turner, Geoffrey B.; Felby, Claus; Engelsen, Søren Balling

    2017-04-01

    The combination of NIR spectroscopy and chemometrics is a powerful correlation method for predicting the chemical constituents in biological matrices, such as the glucose and xylose content of straw. However, difficulties arise when it comes to predicting enzymatic glucose and xylose release potential, which is matrix dependent. Further complications are caused by xylose and glucose release potential being highly intercorrelated. This study emphasizes the importance of understanding the causal relationship between the model and the constituent of interest. It investigates the possibility of using near-infrared spectroscopy to evaluate the ethanol potential of wheat straw by analyzing more than 1000 samples from different wheat varieties and growth conditions. During the calibration model development, the prime emphasis was to investigate the correlation structure between the two major quality traits for saccharification of wheat straw: glucose and xylose release. The large sample set enabled a versatile and robust calibration model to be developed, showing that the prediction model for xylose release is based on a causal relationship with the NIR spectral data. In contrast, the prediction of glucose release was found to be highly dependent on the intercorrelation with xylose release. If this correlation is broken, the model performance breaks down. A simple method was devised for avoiding this breakdown and can be applied to any large dataset for investigating the causality or lack of causality of a prediction model.

  2. Background parenchymal enhancement at breast MR imaging: normal patterns, diagnostic challenges, and potential for false-positive and false-negative interpretation.

    Science.gov (United States)

    Giess, Catherine S; Yeh, Eren D; Raza, Sughra; Birdwell, Robyn L

    2014-01-01

    At magnetic resonance (MR) imaging, both normal and abnormal breast tissue enhances after contrast material administration. The morphology and temporal degree of enhancement of pathologic breast tissue relative to normal breast tissue form the basis of MR imaging's diagnostic accuracy in the detection and diagnosis of breast disease. Normal parenchymal enhancement at breast MR imaging is termed background parenchymal enhancement (BPE). BPE may vary in degree and distribution in different patients as well as in the same patient over time. Typically BPE is minimal or mild in overall degree, with a bilateral, symmetric, diffuse distribution and slow early and persistent delayed kinetic features. However, BPE may sometimes be moderate or marked in degree, with an asymmetric or nondiffuse distribution and rapid early and plateau or washout delayed kinetic features. These patterns cause diagnostic difficulty because these features can be seen with malignancy. This article reviews typical and atypical patterns of BPE seen at breast MR imaging. The anatomic and physiologic influences on BPE in women undergoing diagnostic and screening breast MR imaging are reviewed. The potential for false-positive and false-negative interpretations due to BPE are discussed. Radiologists can improve their interpretive accuracy by increasing their understanding of various BPE patterns, influences on BPE, and the potential effects of BPE on MR imaging interpretation.

  3. Banking of pluripotent adult stem cells as an unlimited source for red blood cell production: potential applications for alloimmunized patients and rare blood challenges.

    Science.gov (United States)

    Peyrard, Thierry; Bardiaux, Laurent; Krause, Claire; Kobari, Ladan; Lapillonne, Hélène; Andreu, Georges; Douay, Luc

    2011-07-01

    The transfusion of red blood cells (RBCs) is now considered a well-settled and essential therapy. However, some difficulties and constraints still occur, such as long-term blood product shortage, blood donor population aging, known and yet unknown transfusion-transmitted infectious agents, growing cost of the transfusion supply chain management, and the inescapable blood group polymorphism barrier. Red blood cells can be now cultured in vitro from human hematopoietic, human embryonic, or human-induced pluripotent stem cells (hiPSCs). The highly promising hiPSC technology represents a potentially unlimited source of RBCs and opens the door to the revolutionary development of a new generation of allogeneic transfusion products. Assuming that in vitro large-scale cultured RBC production efficiently operates in the near future, we draw here some futuristic but realistic scenarios regarding potential applications for alloimmunized patients and those with a rare blood group. We retrospectively studied a cohort of 16,486 consecutive alloimmunized patients (10-year period), showing 1 to 7 alloantibodies with 361 different antibody combinations. We showed that only 3 hiPSC clones would be sufficient to match more than 99% of the 16,486 patients in need of RBC transfusions. The study of the French National Registry of People with a Rare Blood Phenotype/Genotype (10-year period) shows that 15 hiPSC clones would cover 100% of the needs in patients of white ancestry. In addition, one single hiPSC clone would meet 73% of the needs in alloimmunized patients with sickle cell disease for whom rare cryopreserved RBC units were required. As a result, we consider that a very limited number of RBC clones would be able to not only provide for the need for most alloimmunized patients and those with a rare blood group but also efficiently allow for a policy for alloimmunization prevention in multiply transfused patients.

  4. Pressurized HxCyOz Cells at ca. 250 °C: Potential and Challenges

    DEFF Research Database (Denmark)

    Mogensen, Mogens Bjerg; Chatzichristodoulou, Christodoulos; Allebrod, Frank

    2013-01-01

    rate limiting processes are strongly thermal activated. Also, increased pressure may increase the electrode reaction rates. High pressure means increase energy density in gaseous products. Furthermore, as hydrocarbons, alcohols or ethers - in common denoted HxCyOz - are very convenient fuels, we have...... focus on cells that may have a potential of forming or using HxCyOz in electrolysis or fuel cell mode, respectively. Examples of HxCyOz are hydrogen with (x,y,z) = (2,0,0), carbon monoxide with (x,y,z) = (0,1,1), methane with (x,y,z) = (4,1,0), gasoline with approximately (x,y,z) = (18,8,0), methanol...... with (x,y,z) = (4,1,1), and dimethyl ether (DME) with (x,y,z) = (6,2,1). The temperature about 200 – 300 °C is of particular interest because if the direct electrochemical reduction products from electrolysis of H2O and CO2 mixtures are H2 and CO (syngas) then this temperature together with increased...

  5. Reassessing the discovery potential of the $B \\to K^{*} \\ell^+\\ell^-$ decays in the large-recoil region: SM challenges and BSM opportunities

    CERN Document Server

    Jäger, Sebastian

    2014-01-01

    We critically examine the potential to disentangle Standard Model (SM) and New Physics (NP) in $B \\to K^* \\mu^+\\mu^-$ and $B\\to K^* e^+ e^-$ decays, focusing on $(i)$ the LHCb anomaly, $(ii)$ the search for right-handed currents, and $(iii)$ lepton-universality violation. Restricting ourselves to the large-recoil region, we advocate a parameterisation of the hadronic matrix elements that separates model-independent information about nonperturbative QCD from the results of model calculations. We clarify how to estimate corrections to the heavy-quark limit that would generate a right-handed (virtual) photon in the $b\\to s\\gamma$ contribution to the decay. We then apply this approach to the discussion of various sets of observables of increasing theoretical cleanness. First, we show that angular observables in the optimized $P_i^{(\\prime)}$ basis are, in general, not robust against the long-distance QCD effects. While a fit to data shows a preference towards new-physics contributions in semileptonic operators, t...

  6. Revealing Rembrandt

    Directory of Open Access Journals (Sweden)

    Andrew J Parker

    2014-04-01

    Full Text Available The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI. Our results emphasised the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt’s portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings.

  7. Challenged Pragmatism

    DEFF Research Database (Denmark)

    Christoffersen, Lisbet; Vinding, Niels Valdemar

    2013-01-01

    of religious faith have made religious claims and thereby challenged a secular understanding of the Danish labour market. This raises the question of the extent to which the religion of the individual can be accepted in the general public sphere. At the same time, religious ethos organisations have argued...

  8. Improved Culture Medium (TiKa) for Mycobacterium avium Subspecies Paratuberculosis (MAP) Matches qPCR Sensitivity and Reveals Significant Proportions of Non-viable MAP in Lymphoid Tissue of Vaccinated MAP Challenged Animals

    DEFF Research Database (Denmark)

    Bull, Tim J.; Munshil, Tulika; Melvang, Heidi Mikkelsen

    2017-01-01

    in recoverability and an improved sensitivity of up to three logs when compared with conventional culture. Using TiKa culture, MAP clumping was minimal and produced visible colonies in half the time required by standard culture methods. Parallel quantitative evaluation of the TiKa culture approach and qPCR on MAP...... loads in tissue and gut mucosal samples from a MAP vaccine-challenge study, showed good correlations between colony counts (cfu) and qPCR derived genome equivalents (Geq) over a large range of loads with a 30% greater sensitivity for TiKa culture approach at low loads (two logs). Furthermore......Ka culture equates well with qPCR and provides important evidence that accuracy in estimating viable MAP load using DNA tests alone may vary significantly between samples of mucosal and lymphatic origin....

  9. Mobility Challenges

    DEFF Research Database (Denmark)

    Jensen, Ole B.; Lassen, Claus

    2011-01-01

    This article takes point of departure in the challenges to understand the importance of contemporary mobility. The approach advocated is a cross-disciplinary one drawing on sociology, geography, urban planning and design, and cultural studies. As such the perspective is to be seen as a part of th...... mobilities. In particular the article discusses 1) the physical city, its infrastructures and technological hardware/software, 2) policies and planning strategies for urban mobility and 3) the lived everyday life in the city and the region.......This article takes point of departure in the challenges to understand the importance of contemporary mobility. The approach advocated is a cross-disciplinary one drawing on sociology, geography, urban planning and design, and cultural studies. As such the perspective is to be seen as a part...... of the so-called ‘mobility turn’ within social science. The perspective is illustrative for the research efforts at the Centre for Mobility and Urban Studies (C-MUS), Aalborg University. The article presents the contours of a theoretical perspective meeting the challenges to research into contemporary urban...

  10. Liver Transplantation: Past Accomplishments and Future Challenges

    Directory of Open Access Journals (Sweden)

    William J Wall

    1999-01-01

    Full Text Available Liver transplantation has evolved from a rare and risky operation of questionable therapeutic value to the preferred treatment for an extensive list of end-stage liver diseases. Superior immunosuppression (cyclosporine, and improvements in surgery and anesthesia brought liver grafting to its current level of success. Nearly 60,000 liver transplants have been performed, and survival rates are very good; however liver grafting faces serious immediate and long term challenges, mainly due to the widening gap between donor supply and recipient demand. Increasing numbers of sick candidates, recurrent disease (especially hepatitis C and recidivism rates after transplantation for alcoholic cirrhosis will force increasingly difficult decisions on candidate selection and priority listing of potential recipients. Although xenotransplantation may be the ultimate solution, it has its own specific set of biological and societal challenges - the full extent of which should be revealed in the next several years.

  11. Improved Culture Medium (TiKa) for Mycobacterium avium Subspecies Paratuberculosis (MAP) Matches qPCR Sensitivity and Reveals Significant Proportions of Non-viable MAP in Lymphoid Tissue of Vaccinated MAP Challenged Animals.

    Science.gov (United States)

    Bull, Tim J; Munshi, Tulika; Mikkelsen, Heidi; Hartmann, Sofie B; Sørensen, Maria R; Garcia, Joanna S; Lopez-Perez, Paula M; Hofmann, Sven; Hilpert, Kai; Jungersen, Gregers

    2016-01-01

    The quantitative detection of viable pathogen load is an important tool in determining the degree of infection in animals and contamination of foodstuffs. Current conventional culture methods are limited in their ability to determine these levels in Mycobacterium avium subspecies paratuberculosis (MAP) due to slow growth, clumping and low recoverability issues. The principle goal of this study was to evaluate a novel culturing process (TiKa) with unique ability to stimulate MAP growth from low sample loads and dilutions. We demonstrate it was able to stimulate a mean 29-fold increase in recoverability and an improved sensitivity of up to three logs when compared with conventional culture. Using TiKa culture, MAP clumping was minimal and produced visible colonies in half the time required by standard culture methods. Parallel quantitative evaluation of the TiKa culture approach and qPCR on MAP loads in tissue and gut mucosal samples from a MAP vaccine-challenge study, showed good correlations between colony counts (cfu) and qPCR derived genome equivalents (Geq) over a large range of loads with a 30% greater sensitivity for TiKa culture approach at low loads (two logs). Furthermore, the relative fold changes in Geq and cfu from the TiKa culture approach suggests that non-mucosal tissue loads from MAP infected animals contained a reduced proportion of non-viable MAP (mean 19-fold) which was reduced significantly further (mean 190-fold) in vaccinated "reactor" calves. This study shows TiKa culture equates well with qPCR and provides important evidence that accuracy in estimating viable MAP load using DNA tests alone may vary significantly between samples of mucosal and lymphatic origin.

  12. Port State Jurisdiction: Challenges and Potential

    NARCIS (Netherlands)

    Ryngaert, C.M.J.; Ringbom, H.

    2016-01-01

    Confronted with the failures of flag states to adequately regulate their vessels, and/or to enforce applicable law, port states may assume a subsidiary regulatory and enforcement role. Exercising port state jurisdiction (PSJ) over foreign-flagged vessels, these port states may give effect to general

  13. Challenging Identities

    DEFF Research Database (Denmark)

    Keydar, Ceglar; Marin, Manuela; Janik, Allan;

    , cultural, and political practices. Notions of national identity and national politics are challenged by European integration, as well as by increasing demographic heterogeneity due to migration, and migrants experience conflicts of identification stemming from clashes between cultural heritage...... and the cultures of the new habitat. European horizons—frames of mind, historical memories, and expectations at the level of groups or communities, at the national level, and at the general European level—are at odds. Analyzing a series of issues in European countries from Turkey to Spain and from Scandinavia...

  14. Gene network and pathway analysis of bovine mammary tissue challenged with Streptococcus uberis reveals induction of cell profileration and inhibition of PPARγ signaling as potential mechanism for the negative relationships between immune response and lipid metabolism

    DEFF Research Database (Denmark)

    Moyes, Kasey M; Drackley, James K; Morin, Dawn E

    2009-01-01

    with immune system function (e.g., CD14, IL8, IL1B, and TLR2) and negative relationships with genes involved with lipid metabolism (e.g., GPAM, SCD, FABP4, CD36, and LPL) and antioxidant activity (SOD1). Conclusion Results provided novel information into the early signaling and metabolic pathways in mammary...... of lipid synthesis, stress-activated kinase signaling cascades, and PPAR signaling (most likely PPARγ). This latter effect may provide a mechanistic explanation for the inverse relationship between immune response and milk fat synthesis.......Background Information generated via microarrays might uncover interactions between the mammary gland and Streptococcus uberis (S. uberis) that could help identify control measures for the prevention and spread of S. uberis mastitis, as well as improve overall animal health and welfare...

  15. Data Challenges

    CERN Multimedia

    McCubbin, N A

    Some two years ago we planned a series of Data Challenges starting at the end of 2001. At the time, that seemed to be comfortingly far in the future... Well, as the saying goes, doesn't time fly when you are having fun! ATLAS Computing is now deep in the throes of getting the first Data Challenge (DC0) up and running. One of the main aims of DC0 is to have a software 'release' in which we can generate full physics events, track all particles through the detector, simulate the detector response, reconstruct the event, and study it, with appropriate data storage en route. As all software is "always 95% ready" (!), we have been able to do most of this, more or less, for some time. But DC0 forces us to have everything working, together, at the same time: a reality check. DC0 should finish early next year, and it will be followed almost immediately afterwards by DC1 (DC0 was foreseen as the 'check' for DC1). DC1 will last into the middle of 2002, and has two major goals. The first is generation, simulation, and r...

  16. SPS Challenges

    CERN Document Server

    Chapochnikova, Elena

    2008-01-01

    In future the SPS should be able to transfer to the LHC the beam produced by a completely new pre-injector chain and required by the LHC for different upgrade scenarios. The issues related to this extremely challenging task are presented together with some possible ways of overcoming the problems that arise. Besides an increase in injection energy provided by PS2, these measures can include both an SPS vacuum chamber upgrade against the e-cloud and operation with larger longitudinal emittance for beam stability. As a result the power plant of the SPS RF system must be doubled. The SPS upgrade will also need the improvement or replacement of many other machine elements.

  17. The Pharmacology of TUG-891, a Potent and Selective Agonist of the Free Fatty Acid Receptor 4 (FFA4/GPR120), Demonstrates Both Potential Opportunity and Possible Challenges to Therapeutic Agonism

    Science.gov (United States)

    Hudson, Brian D.; Shimpukade, Bharat; Mackenzie, Amanda E.; Butcher, Adrian J.; Pediani, John D.; Christiansen, Elisabeth; Heathcote, Helen; Tobin, Andrew B.; Ulven, Trond

    2013-01-01

    TUG-891 [3-(4-((4-fluoro-4′-methyl-[1,1′-biphenyl]-2-yl)methoxy)phenyl)propanoic acid] was recently described as a potent and selective agonist for the long chain free fatty acid (LCFA) receptor 4 (FFA4; previously G protein–coupled receptor 120, or GPR120). Herein, we have used TUG-891 to further define the function of FFA4 and used this compound in proof of principle studies to indicate the therapeutic potential of this receptor. TUG-891 displayed similar signaling properties to the LCFA α-linolenic acid at human FFA4 across various assay end points, including stimulation of Ca2+ mobilization, β-arrestin-1 and β-arrestin-2 recruitment, and extracellular signal-regulated kinase phosphorylation. Activation of human FFA4 by TUG-891 also resulted in rapid phosphorylation and internalization of the receptor. While these latter events were associated with desensitization of the FFA4 signaling response, removal of TUG-891 allowed both rapid recycling of FFA4 back to the cell surface and resensitization of the FFA4 Ca2+ signaling response. TUG-891 was also a potent agonist of mouse FFA4, but it showed only limited selectivity over mouse FFA1, complicating its use in vivo in this species. Pharmacologic dissection of responses to TUG-891 in model murine cell systems indicated that activation of FFA4 was able to mimic many potentially beneficial therapeutic properties previously reported for LCFAs, including stimulating glucagon-like peptide-1 secretion from enteroendocrine cells, enhancing glucose uptake in 3T3-L1 adipocytes, and inhibiting release of proinflammatory mediators from RAW264.7 macrophages, which suggests promise for FFA4 as a therapeutic target for type 2 diabetes and obesity. Together, these results demonstrate both potential but also significant challenges that still need to be overcome to therapeutically target FFA4. PMID:23979972

  18. Imaging polarimetry for the characterisation of exoplanets and protoplanetary discs : scientific and technical challenges

    NARCIS (Netherlands)

    Juan Ovelar, Maria de

    2013-01-01

    The study of exoplanets and the protoplanetary discs in which they form is a very challenging task. In this thesis we present several studies in which we investigate the potential of imaging polarimetry at visible and near-infrared wavelengths to reveal the characteristics of these objects and overc

  19. Scrapheap Challenge

    CERN Document Server

    2004-01-01

    Three British guys at CERN recently took a break from work to try their hand at Scrapheap Challenge. Shown on Channel 4 in the UK, it is a show where two teams must construct a machine for a specific task using only the junk they can scavenge from the scrap yard around them. And they have just 10 hours to build their contraption before it is put to the test. The first round, aired 19 September, pitted a team of three women, from the British Army's Royal Electrical and Mechanical Engineers, against the CERN guys - the Up 'n Atoms: Ali Day, David McFarlane and James Ridewood. Each team, with the help of an appointed expert, had the task of making a giant, 3-metre self-propelled "bowling ball", to roll down a 50 metre bowling alley at skittles 4 metres high. The Up 'n Atoms' contraption featured a small car with a huge wheel on its back. Once up to speed, slamming on the brakes caused the wheel to roll over and take the car with it. On their very last run they managed to take out seven pins. Luckily, though, ...

  20. Potential and Challenges of Low-Cost and High-Tech Crowd-sensing Approaches in Hydrometeorology for Better Water Resources Management - Insights and Learnings from the Global iMoMo Initiative

    Science.gov (United States)

    Siegfried, Tobias

    2016-04-01

    In developing and transition countries and despite significant global investments in hydrometeorology, data on water remain scarce/fragmented. One key reason is that traditional sensing in hydrology, hydro- and agro-meteorology does not scale because of high investment costs and difficult maintenance of traditional technology, esp. in remote and/or poor regions. Even where there are data, these are often difficult to access and interpret for local stakeholders due outdated data transmission and the lack of access to modern tools for data management/analysis/synthesis and exchange. In recent years, there have been substantial technology developments in environmental sensing and mobile communication technology that enable the application and deployment of affordable and scalable high-tech solutions for better water monitoring at different scales (local to transboundary levels). The WMO is acknowledging and promoting the potential for application of these technologies. One key aspect is to anchor these technologies in local communities that perform crowd-sensing tasks on a regular basis. The merits as well as challenges (including introduction of human factor, less accuracy as compared to traditional sensing, intermittency of data, …) of such approaches will be discussed in the context of the WMO-led Global iMoMo Initiative and its numerous activities on the ground in Eastern and Southern Africa as well as in Central Asia.

  1. Challenges and Advances in Nanotoxicology

    Directory of Open Access Journals (Sweden)

    Robert L. Tanguay

    2014-08-01

    Full Text Available This Special Issue of Nanomaterials examines the potential for engineered nanomaterials to negatively impact biological systems and highlights some advances in evaluating key areas of their hazard potential. Nanomaterial science is evolving rapidly with the generation of more complex nanostructures with exciting potential applications. Keeping modern toxicology abreast of this innovation to the point that it guides a safer nanotechnology presents an equally exciting and eminently worthwhile challenge. [...

  2. Health Care Challenges in Iran

    Directory of Open Access Journals (Sweden)

    M Davari

    2005-10-01

    Full Text Available All health systems across the world have faced new challenges, which is primarily referable to increasing the cost of health care services as well as growing demands for new and expensive health technologies. The aim of this study is to analyse the main challenges facing the Iranian health system. A review of available governmental and relevant publications about Iranian health care system was undertaken to assess the direction of future healthcare policy. Electronic news agencies, newspapers, and parliament’s electronic news also reviewed to realise policy-makers points of view about the health system. Healthcare services in Iran have had a great success in primary healthcare services in last 25 years, which is mainly attributable to National Health Networks policy. Between 1979 and 2003, average life expectancy at birth increased from 57 to 70 and infant mortality rate fell from 104 to 26 per thousand live births. Active vaccination system, very good distribution and coverage, free end point services, family planning, maternal teaching, and primary referral system are of strong advantages of health networks in Iran. However, the healthcare system is now subject to a range of new pressures that must be addressed. Many of these pressures are common to all health services (rising consumer demands and expectations for expensive new technologies, changing disease patterns, and resources shortage, but some are largely specific to Iran. Financial fairness contribution of the population to health system, responsiveness of health system, overusing new technologies, inadequate integration of health services, and inequitable distribution of the resources are of the main challenges of health system in Iran. In addition, considering demographic changes of the Iranian population in recent decades, which made Iranian population young, potential pressures due to an aging population will reveal in coming years. Many of these pressures relate to policies and

  3. Nanotechnology: Opportunities and Challenges

    Science.gov (United States)

    Meyyappan, Meyya

    2003-01-01

    Nanotechnology seeks to exploit novel physical, chemical, biological, mechanical, electrical, and other properties, which arise primarily due to the nanoscale nature of certain materials. A key example is carbon nanotubes (CNTs) which exhibit unique electrical and extraordinary mechanical properties and offer remarkable potential for revolutionary applications in electronics devices, computing, and data storage technology, sensors, composites, nanoelectromechanical systems (NEMS), and as tip in scanning probe microscopy (SPM) for imaging and nanolithography. Thus the CNT synthesis, characterization, and applications touch upon all disciplines of science and engineering. This presentation will provide an overview and progress report on this and other major research candidates in Nanotechnology and address opportunities and challenges ahead.

  4. Energy Challenges for ICT

    DEFF Research Database (Denmark)

    Fagas, Giorgos; Gallagher, John Patrick; Gammaitoni, Luca

    2017-01-01

    The energy consumption from the expanding use of information and communications technology (ICT) is unsustainable with present drivers, and it will impact heavily on the future climate change. However, ICT devices have the potential to contribute significantly to the reduction of CO2 emission...... the energy sustainability of ICT and capture the full potential of ICT in resource efficiency, a multidisciplinary ICT-energy community needs to be brought together covering devices, microarchitectures, ultra large-scale integration (ULSI), high-performance computing (HPC), energy harvesting, energy storage......, system design, embedded systems, efficient electronics, static analysis, and computation. In this chapter, we introduce challenges and opportunities in this emerging field and a common framework to strive towards energy-sustainable ICT....

  5. Challenges in plastics recycling

    DEFF Research Database (Denmark)

    Pivnenko, Kostyantyn; Jakobsen, L. G.; Eriksen, Marie Kampmann

    2015-01-01

    Recycling of waste plastics still remains a challenging area in the waste management sector. The current and potential goals proposed on EU or regional levels are difficult to achieve, and even to partially fullfil them the improvements in collection and sorting should be considerable. A study...... was undertaken to investigate the factors affecting quality in plastics recycling. The preliminary results showed factors primarily influencing quality of plastics recycling to be polymer cross contamination, presence of additives, non-polymer impurities, and polymer degradation. Deprivation of plastics quality......, with respect to recycling, has been shown to happen throughout the plastics value chain, but steps where improvements may happen have been preliminary identified. Example of Cr in plastic samples analysed showed potential spreading and accumulation of chemicals ending up in the waste plastics. In order...

  6. Social media and physicians: Exploring the benefits and challenges.

    Science.gov (United States)

    Panahi, Sirous; Watson, Jason; Partridge, Helen

    2016-06-01

    Healthcare professionals' use of social media platforms, such as blogs, wikis, and social networking web sites has grown considerably in recent years. However, few studies have explored the perspectives and experiences of physicians in adopting social media in healthcare. This article aims to identify the potential benefits and challenges of adopting social media by physicians and demonstrates this by presenting findings from a survey conducted with physicians. A qualitative survey design was employed to achieve the research goal. Semi-structured interviews were conducted with 24 physicians from around the world who were active users of social media. The data were analyzed using the thematic analysis approach. The study revealed six main reasons and six major challenges for physicians adopting social media. The main reasons to join social media were as follows: staying connected with colleagues, reaching out and networking with the wider community, sharing knowledge, engaging in continued medical education, benchmarking, and branding. The main challenges of adopting social media by physicians were also as follows: maintaining confidentiality, lack of active participation, finding time, lack of trust, workplace acceptance and support, and information anarchy. By revealing the main benefits as well as the challenges of adopting social media by physicians, the study provides an opportunity for healthcare professionals to better understand the scope and impact of social media in healthcare, and assists them to adopt and harness social media effectively, and maximize the benefits for the specific needs of the clinical community.

  7. Revealing the programming process

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Caspersen, Michael Edelgaard

    2005-01-01

    One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because the textb......One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because...... the textbook medium is static and therefore ill-suited to expose the process of programming. We have found that process recordings in the form of captured narrated programming sessions are a simple, cheap, and efficient way of providing the revelation.We identify seven different elements of the programming...... process for which process recordings are a valuable communication media in order to enhance the learning process. Student feedback indicates both high learning outcome and superior learning potential compared to traditional classroom teaching....

  8. Thank You, Challenges!

    Institute of Scientific and Technical Information of China (English)

    陈晨; 陈传光

    2016-01-01

    A person may meet many challenges in his or her life.Some people think challenges are terrible.But I think they’re great.And I want to say,"Thank you,challenges!"For some people,it’s hard to face the challenges because they are afraid of failing in the end.However,it’s necessary for a person to face the challenges.Challenges are good to~①you.

  9. Proteomics Technologies and Challenges

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Proteomics is the study of proteins and their interactions in a cell. With the completion of the Human Genome Project, the emphasis is shifting to the protein compliment of the human organism. Because proteome reflects more accurately on the dynamic state of a cell, tissue, or organism, much is expected from proteomics to yield better disease markers for diagnosis and therapy monitoring. The advent of proteomics technologies for global detection and quantitation of proteins creates new opportunities and challenges for those seeking to gain greater understanding of diseases. High-throughput proteomics technologies combining with advanced bioinformatics are extensively used to identify molecular signatures of diseases based on protein pathways and signaling cascades. Mass spectrometry plays a vital role in proteomics and has become an indispensable tool for molecular and cellular biology. While the potential is great, many challenges and issues remain to be solved, such as mining low abundant proteins and integration of proteomics with genomics and metabolomics data. Nevertheless, proteomics is the foundation for constructing and extracting useful knowledge to biomedical research. In this review, a snapshot of contemporary issues in proteomics technologies is discussed.

  10. Challenges and counter challenges in HIV/AIDS

    Institute of Scientific and Technical Information of China (English)

    Qingsheng Li; Charles Wood

    2010-01-01

    @@ Since the beginning of the HIV/AIDS pandemic, there has been significant progress in combating the virus.In addition to identifying HIV,1 scientists have developed an array of antiretroviral drugs and successfully converted the once deadly disease into a treatable and chronic condition.2 Nevertheless, this battle is far from over and HIV still outsmarts humans in multiple ways and poses tremendous challenges. Within this context, the Chinese Medical Journal has timely published this special issue on HIV/AIDS, highlighting the ongoing challenges posed by HIV and potential solutions to these problems.

  11. Overcoming Challenges of Renewable Energy on Future Smart Grid

    Directory of Open Access Journals (Sweden)

    Mohamed Shaaban

    2012-06-01

    Full Text Available The increasing complexity of the conventional grid due to population growth, advancement in technology and infrastructures which contribute immensely to instability, insecurity, and inefficiency and environmental energy sustainability calls for the use of renewable energy for sustainability of power supply. Intermittency and fluctuation of the renewable energy is a great challenge on the smart grid. This paper reveal the potential challenges of renewable energy on the smart grid and proffer solution with the application of high voltage DC (HVDC and Flexible AC transmission system (FACTS devices. The functions and advantages of FACTS devices are presented in this paper. Voltage control and stability control with FACTS application are also discussed. This was achieved because FACTS has fast controllability and capability to exchange active and reactive power independently.

  12. Stable isotope views on ecosystem function: challenging or challenged?

    Science.gov (United States)

    Resco, Víctor; Querejeta, José I.; Ogle, Kiona; Voltas, Jordi; Sebastià, Maria-Teresa; Serrano-Ortiz, Penélope; Linares, Juan C.; Moreno-Gutiérrez, Cristina; Herrero, Asier; Carreira, José A.; Torres-Cañabate, Patricia; Valladares, Fernando

    2010-01-01

    Stable isotopes and their potential for detecting various and complex ecosystem processes are attracting an increasing number of scientists. Progress is challenging, particularly under global change scenarios, but some established views have been challenged. The IX meeting of the Spanish Association of Terrestrial Ecology (AAET, Úbeda, 18–22 October 2009) hosted a symposium on the ecology of stable isotopes where the linear mixing model approach of partitioning sinks and sources of carbon and water fluxes within an ecosystem was challenged, and new applications of stable isotopes for the study of plant interactions were evaluated. Discussion was also centred on the need for networks that monitor ecological processes using stable isotopes and key ideas for fostering future research with isotopes. PMID:20015858

  13. Security challenge to using smartphones for SHM

    Science.gov (United States)

    Abueh, Yeka; Liu, Hong

    2016-04-01

    Pervasive smartphones have demonstrated great potential in structural health monitoring (SHM) of civil infrastructures. Their sensing, processing, and communication capabilities along with crowdsourcing facility ease technical difficulties and reduce financial burdens of instrumentation and monitoring for SHM in civil infrastructures. However, smartphones are vulnerable to unintentional misuses and malicious attacks. This paper analyzes the vulnerabilities of smartphones in performing SHM and reveals the exploitation of those vulnerabilities. The work probes the attack surface of both devices and data. Device attack scenarios include hacking individual smartphones to modify the data stored on them and orchestrating smartphones to launch a distributed denial-of-service attack. Specifically, experiments are conducted to remotely access an Android smartphone and modify the sensing data of structural health stored on it. The work also presents a case study that reveals the sensitivity of a popular perturbation analysis method to faulty data delivered by a smartphone. The paper provides the direction of meeting the security challenge to using smartphones for SHM. As the first line of defense, device authentication is implemented in the smartphone to stop spoofing. Subsequently, message authentication is devised to maintain data integrity. There is a need to apply data science for the SHM immunity system against the sensitivity to data inaccuracy. The work also evaluates the cost-effectiveness of the proposed security measures, recommending varying levels of security to mitigate the adversaries to smartphones used in SHM systems. It calls for security solutions at the design stage of SHM systems rather than patching up after their implementations.

  14. 78 FR 49296 - Centennial Challenges 2014 Sample Return Robot Challenge

    Science.gov (United States)

    2013-08-13

    ... SPACE ADMINISTRATION Centennial Challenges 2014 Sample Return Robot Challenge AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Notice of Centennial Challenges 2014 Sample Return Robot... Robot Challenge is scheduled and teams that wish to compete may register. Centennial Challenges is...

  15. National Drug IQ Challenge

    Science.gov (United States)

    ... Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2016 National Drug IQ Challenge ... Reto nacional del coeficiente intelectual (CI) sobre las drogas y el alcohol 2015 National Drug IQ Challenge ...

  16. Balance Trees Reveal Microbial Niche Differentiation.

    Science.gov (United States)

    Morton, James T; Sanders, Jon; Quinn, Robert A; McDonald, Daniel; Gonzalez, Antonio; Vázquez-Baeza, Yoshiki; Navas-Molina, Jose A; Song, Se Jin; Metcalf, Jessica L; Hyde, Embriette R; Lladser, Manuel; Dorrestein, Pieter C; Knight, Rob

    2017-01-01

    Advances in sequencing technologies have enabled novel insights into microbial niche differentiation, from analyzing environmental samples to understanding human diseases and informing dietary studies. However, identifying the microbial taxa that differentiate these samples can be challenging. These issues stem from the compositional nature of 16S rRNA gene data (or, more generally, taxon or functional gene data); the changes in the relative abundance of one taxon influence the apparent abundances of the others. Here we acknowledge that inferring properties of individual bacteria is a difficult problem and instead introduce the concept of balances to infer meaningful properties of subcommunities, rather than properties of individual species. We show that balances can yield insights about niche differentiation across multiple microbial environments, including soil environments and lung sputum. These techniques have the potential to reshape how we carry out future ecological analyses aimed at revealing differences in relative taxonomic abundances across different samples. IMPORTANCE By explicitly accounting for the compositional nature of 16S rRNA gene data through the concept of balances, balance trees yield novel biological insights into niche differentiation. The software to perform this analysis is available under an open-source license and can be obtained at https://github.com/biocore/gneiss. Author Video: An author video summary of this article is available.

  17. Balance Trees Reveal Microbial Niche Differentiation

    Science.gov (United States)

    Morton, James T.; Sanders, Jon; Quinn, Robert A.; McDonald, Daniel; Gonzalez, Antonio; Vázquez-Baeza, Yoshiki; Navas-Molina, Jose A.; Metcalf, Jessica L.; Hyde, Embriette R.; Lladser, Manuel; Dorrestein, Pieter C.

    2017-01-01

    ABSTRACT Advances in sequencing technologies have enabled novel insights into microbial niche differentiation, from analyzing environmental samples to understanding human diseases and informing dietary studies. However, identifying the microbial taxa that differentiate these samples can be challenging. These issues stem from the compositional nature of 16S rRNA gene data (or, more generally, taxon or functional gene data); the changes in the relative abundance of one taxon influence the apparent abundances of the others. Here we acknowledge that inferring properties of individual bacteria is a difficult problem and instead introduce the concept of balances to infer meaningful properties of subcommunities, rather than properties of individual species. We show that balances can yield insights about niche differentiation across multiple microbial environments, including soil environments and lung sputum. These techniques have the potential to reshape how we carry out future ecological analyses aimed at revealing differences in relative taxonomic abundances across different samples. IMPORTANCE By explicitly accounting for the compositional nature of 16S rRNA gene data through the concept of balances, balance trees yield novel biological insights into niche differentiation. The software to perform this analysis is available under an open-source license and can be obtained at https://github.com/biocore/gneiss. Author Video: An author video summary of this article is available. PMID:28144630

  18. New challenges in gas

    Energy Technology Data Exchange (ETDEWEB)

    Mandil, C. [Institut Francais du Petrole (IFP), 92 - Rueil-Malmaison (France); Chabrelie, M.F. [Cedigaz, 92 - Rueil Malmaison (France); Streicher, C. [Prosernat, 92 - Paris la Defense (France)] [and others

    2003-07-01

    New developments in the area of gas treatment will be to a large extent driven by the need to find appropriate solutions to the fundamental need of sustainable development. New gas treatment processes are developed with the aim to minimise contaminant emissions and meet most stringent environmental specifications. A new major challenge for the industry will be to implement new cost effective technologies for reducing CO{sub 2} emissions. Industry has also to minimise its costs, and therefore, in order to ensure at the same time a better protection of the environment and a better safety, it is necessary to innovate. The purpose of this seminar is precisely to identify better the innovations which are required in the area of gas treatment. These proceedings comprise 8 papers and a summary of the contributions to a round-table discussion dealing with the options for CO{sub 2} capture and sequestration. The presentations treat of: the future prospects for the gas industry (M.F. Chabrelie, Cedigaz); the solutions for offshore gas treatment (C. Streicher, Prosernat); gas treatment with membranes (H. Meyer, GTI); the Axens Multibed{sub TM} technology for natural gas treatment (G. Jochem, Axens); the potentials and applications for the Propure co-current contactors (F.P. Nilsen, ProPure); the production of very-sour and super-sour large gas reserves: the new challenges (F. Lallemand, TotalFinaElf); Hybrisol, a new gas treatment process for sour natural gases (F. Lecomte, IFP); and the conception and building of large acid-gas removal units (J. Castel, Technip-Coflexip). (J.S.)

  19. The Backpack Design Challenge

    Science.gov (United States)

    Roman, Harry T.

    2010-01-01

    Something as simple as carrying books to school can be an interesting design challenge for students. It's an old problem that gets reinvented from time to time. In this article, the author discusses a backpack design challenge in which teachers work with students to design another way to carry books to school. The challenge started by trying to…

  20. Functional network overlap as revealed by fMRI using sICA and its potential relationships with functional heterogeneity, balanced excitation and inhibition, and sparseness of neuron activity.

    Science.gov (United States)

    Xu, Jiansong; Calhoun, Vince D; Worhunsky, Patrick D; Xiang, Hui; Li, Jian; Wall, John T; Pearlson, Godfrey D; Potenza, Marc N

    2015-01-01

    Functional magnetic resonance imaging (fMRI) studies traditionally use general linear model-based analysis (GLM-BA) and regularly report task-related activation, deactivation, or no change in activation in separate brain regions. However, several recent fMRI studies using spatial independent component analysis (sICA) find extensive overlap of functional networks (FNs), each exhibiting different task-related modulation (e.g., activation vs. deactivation), different from the dominant findings of GLM-BA. This study used sICA to assess overlap of FNs extracted from four datasets, each related to a different cognitive task. FNs extracted from each dataset overlapped with each other extensively across most or all brain regions and showed task-related concurrent increases, decreases, or no changes in activity. These findings indicate that neural substrates showing task-related concurrent but different modulations in activity intermix with each other and distribute across most of the brain. Furthermore, spatial correlation analyses found that most FNs were highly consistent in spatial patterns across different datasets. This finding indicates that these FNs probably reflect large-scale patterns of task-related brain activity. We hypothesize that FN overlaps as revealed by sICA might relate to functional heterogeneity, balanced excitation and inhibition, and population sparseness of neuron activity, three fundamental properties of the brain. These possibilities deserve further investigation.

  1. Machine Learning wins the Higgs Challenge

    CERN Multimedia

    Abha Eli Phoboo

    2014-01-01

    The winner of the four-month-long Higgs Machine Learning Challenge, launched on 12 May, is Gábor Melis from Hungary, followed closely by Tim Salimans from the Netherlands and Pierre Courtiol from France. The challenge explored the potential of advanced machine learning methods to improve the significance of the Higgs discovery.   Winners of the Higgs Machine Learning Challenge: Gábor Melis and Tim Salimans (top row), Tianqi Chen and Tong He (bottom row). Participants in the Higgs Machine Learning Challenge were tasked with developing an algorithm to improve the detection of Higgs boson signal events decaying into two tau particles in a sample of simulated ATLAS data* that contains few signal and a majority of non-Higgs boson “background” events. No knowledge of particle physics was required for the challenge but skills in machine learning - the training of computers to recognise patterns in data – were essential. The Challenge, hosted by Ka...

  2. Challenges in Teaching Mathematics: Perspectives From Students’ Learning Difficulties

    Directory of Open Access Journals (Sweden)

    Steve Chinn

    2016-04-01

    Full Text Available Alcock et al (2016, this issue have set out and discussed a potential research agenda for mathematical cognition. It is timely that research topics, along with knowledge uncovered to date, should be incorporated into a coordinated agenda for further research. This commentary focuses on the perspectives that learning difficulties, and dyscalculia, reveal. These perspectives potentially add much to that research agenda. [Commentary on: Alcock, L., Ansari, D., Batchelor, S., Bisson, M.-J., De Smedt, B., Gilmore, C., . . . Weber, K. (2016. Challenges in mathematical cognition: A collaboratively-derived research agenda. Journal of Numerical Cognition, 2, 20-41. doi:10.5964/jnc.v2i1.10

  3. An Internal Standard-Assisted Synthesis and Degradation Proteomic Approach Reveals the Potential Linkage between VPS4B Depletion and Activation of Fatty Acid β-Oxidation in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Zhongping Liao

    2013-01-01

    Full Text Available The endosomal/lysosomal system, in particular the endosomal sorting complexes required for transport (ESCRTs, plays an essential role in regulating the trafficking and destination of endocytosed receptors and their associated signaling molecules. Recently, we have shown that dysfunction and down-regulation of vacuolar protein sorting 4B (VPS4B, an ESCRT-III associated protein, under hypoxic conditions can lead to the abnormal accumulation of epidermal growth factor receptor (EGFR and aberrant EGFR signaling in breast cancer. However, the pathophysiological consequences of VPS4B dysfunction remain largely elusive. In this study, we used an internal standard-assisted synthesis and degradation mass spectrometry (iSDMS method, which permits the direct measurement of protein synthesis, degradation and protein dynamic expression, to address the effects of VPS4B dysfunction in altering EGF-mediated protein expression. Our initial results indicate that VPS4B down-regulation decreases the expression of many proteins involved in glycolytic pathways, while increased the expression of proteins with roles in mitochondrial fatty acid β-oxidation were up-regulated in VPS4B-depleted cells. This observation is also consistent with our previous finding that hypoxia can induce VPS4B down-regulated, suggesting that the adoption of fatty acid β-oxidation could potentially serve as an alternative energy source and survival mechanism for breast cancer cells in response to hypoxia-mediated VPS4B dysfunction.

  4. The molecular anatomy of human Hsp60 and its similarity with that of bacterial orthologs and acetylcholine receptor reveal a potential pathogenetic role of anti-chaperonin immunity in myasthenia gravis.

    Science.gov (United States)

    Gammazza, Antonella Marino; Bucchieri, Fabio; Grimaldi, Luigi M E; Benigno, Arcangelo; de Macario, Everly Conway; Macario, Alberto J L; Zummo, Giovanni; Cappello, Francesco

    2012-08-01

    Heat-shock protein 60 (Hsp60) is ubiquitous and highly conserved being present in eukaryotes and prokaryotes, including pathogens. This chaperonin, although typically a mitochondrial protein, can also be found in other intracellular sites, extracellularly, and in circulation. Thus, it can signal the immune system and participate in the development of inflammation and immune reactions. Both phenomena can be elicited by human and foreign Hsp60 (e.g., bacterial GroEL), when released into the blood by infectious agents. Consequently, all these Hsp60 proteins become part of a complex autoimmune response characterized by multiple cross reactions because of their structural similarities. In this study, we demonstrate that Hsp60 proteins from humans and two common pathogens, Chlamydia trachomatis and Chlamydia pneumoniae, share various sequence segments of potentially highly immunogenic epitopes with acetylcholine receptor α1 subunit (AChRα1). The structural data indicate that AChRα1 antibodies, implicated in the pathogenesis of myasthenia gravis, could very well be elicited and/or maintained by self- and/or bacterial Hsp60.

  5. Challenges in Mathematical Cognition

    Directory of Open Access Journals (Sweden)

    Lara Alcock

    2016-04-01

    Full Text Available This paper reports on a collaborative exercise designed to generate a coherent agenda for research on mathematical cognition. Following an established method, the exercise brought together 16 mathematical cognition researchers from across the fields of mathematics education, psychology and neuroscience. These participants engaged in a process in which they generated an initial list of research questions with the potential to significantly advance understanding of mathematical cognition, winnowed this list to a smaller set of priority questions, and refined the eventual questions to meet criteria related to clarity, specificity and practicability. The resulting list comprises 26 questions divided into six broad topic areas: elucidating the nature of mathematical thinking, mapping predictors and processes of competence development, charting developmental trajectories and their interactions, fostering conceptual understanding and procedural skill, designing effective interventions, and developing valid and reliable measures. In presenting these questions in this paper, we intend to support greater coherence in both investigation and reporting, to build a stronger base of information for consideration by policymakers, and to encourage researchers to take a consilient approach to addressing important challenges in mathematical cognition.

  6. Genetic variation in a grapevine progeny (Vitis vinifera L. cvs Grenache×Syrah) reveals inconsistencies between maintenance of daytime leaf water potential and response of transpiration rate under drought.

    Science.gov (United States)

    Coupel-Ledru, Aude; Lebon, Éric; Christophe, Angélique; Doligez, Agnès; Cabrera-Bosquet, Llorenç; Péchier, Philippe; Hamard, Philippe; This, Patrice; Simonneau, Thierry

    2014-11-01

    In the face of water stress, plants evolved with different abilities to limit the decrease in leaf water potential, notably in the daytime (ΨM). So-called isohydric species efficiently maintain high ΨM, whereas anisohydric species cannot prevent ΨM from dropping as soil water deficit develops. The genetic and physiological origins of these differences in (an)isohydric behaviours remain to be clarified. This is of particular interest within species such as Vitis vinifera L. where continuous variation in the level of isohydry has been observed among cultivars. With this objective, a 2 year experiment was conducted on the pseudo-F1 progeny from a cross between the two widespread cultivars Syrah and Grenache using a phenotyping platform coupled to a controlled-environment chamber. Potted plants of all the progeny were analysed for ΨM, transpiration rate, and soil-to-leaf hydraulic conductance, under both well-watered and water deficit conditions. A high genetic variability was found for all the above traits. Four quantitative trait loci (QTLs) were detected for ΨM under water deficit conditions, and 28 other QTLs were detected for the different traits in either condition. Genetic variation in ΨM maintenance under water deficit weakly correlated with drought-induced reduction in transpiration rate in the progeny, and QTLs for both traits did not completely co-localize. This indicates that genetic variation in the control of ΨM under water deficit was not due simply to variation in transpiration sensitivity to soil drying. Possible origins of the diversity in (an)isohydric behaviours in grapevine are discussed on the basis of concurrent variations in soil-to-leaf hydraulic conductance and stomatal control of transpiration.

  7. Recruiting and Advising Challenges in Actuarial Science

    Science.gov (United States)

    Case, Bettye Anne; Guan, Yuanying Michelle; Paris, Stephen

    2014-01-01

    Some challenges to increasing actuarial science program size through recruiting broadly among potential students are identified. Possible solutions depend on the structures and culture of the school. Up to three student cohorts may result from partition of potential students by the levels of academic progress before program entry: students…

  8. Biomedical engineering at UCT - challenges and opportunities.

    Science.gov (United States)

    Douglas, Tania S

    2012-03-02

    The biomedical engineering programme at the University of Cape Town has the potential to address some of South Africa's unique public health challenges and to contribute to growth of the local medical device industry, directly and indirectly, through research activities and postgraduate education. Full realisation of this potential requires engagement with the clinical practice environment and with industry.

  9. Indirect airway challenges

    NARCIS (Netherlands)

    Joos, GF; O'Connor, B; Anderson, SD; Chung, F; Cockcroft, DW; Dahlen, B; DiMaria, G; Foresi, A; Hargreave, FE; Holgate, ST; Inman, M; Lotvall, J; Magnussen, H; Polosa, R; Postma, DS; Riedler, J

    2003-01-01

    Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle. Di

  10. Science Challenge Day

    Science.gov (United States)

    Siegel, Deborah

    2013-01-01

    Science fairs can be good motivators, but as extracurricular activities, they leave some students behind. However, by staging a Science Challenge Day at school, educators can involve all students in doing everything from choosing activities to judging projects. This article presents a model for running a successful Science Challenge Day. The…

  11. Challenge and Change

    Science.gov (United States)

    Mehaffy, George L.

    2012-01-01

    In the past twenty years, various industries have been forever altered by technology: newspapers, book publishing, the photography business, and many more. Higher education too faces unprecedented challenges primarily driven by rapid changes in technology. To meet these challenges and adapt to these changes, new models are needed. Six challenges…

  12. Challenges of the management of severe hemophilia A with inhibitors: two case reports emphasizing the potential interest of a high-purity human Factor VIII/von Willebrand factor concentrate and individually tailored prophylaxis guided by thrombin-generation test.

    Science.gov (United States)

    Mathieu, Sophie; Crampe, Carine; Dargaud, Yesim; Lavigne-Lissalde, Géraldine; Escuriola-Ettingshausen, Carmen; Tardy, Brigitte; Meley, Roland; Thouvenin, Sandrine; Stephan, Jean L; Berger, Claire

    2015-12-01

    Severe hemophilia A is an X-linked bleeding disorder. Immune tolerance induction (ITI) is the best strategy of treatment when patients develop inhibitors. The objective is to illustrate the benefit of a high-purity human factor VIII/von Willebrand factor (VWF) concentrate (Octanate) in the management of ITI. We also wanted to raise the potential interest of laboratory assays such as thrombin-generation test (TGT) and epitope mapping. Two patients were treated during ITI, first with a recombinant FVIII and then with plasma-derived factor VIII without success, and, finally, with Octanate. Bypassing agents were used based on the results of TGT. Epitope mapping was performed during ITI therapy. These observations suggest the potential contribution of Octanate in the management of ITI in difficult cases. The use of bypassing agents can be necessary in prophylaxis or to treat bleedings, and may be guided by TGT results. Epitope mapping is used to describe the inhibitor. This article shows a decrease of the inhibitor directed against the C2 domain after initiation of Octanate. A high-purity human factor VIII/von Willebrand factor concentrate (Octanate) may be a valuable therapeutical option for ITI therapy. TGT and epitope mapping could be of help in the management of ITI.

  13. DIGITAL PAKISTAN: OPPORTUNITIES & CHALLENGES

    Directory of Open Access Journals (Sweden)

    Ghulam Muhammad Kundi

    2008-12-01

    Full Text Available ABSTRACT IT has revolutionized the social and organizational life around the globe. Given the newness of IT as a technology, there is a lot of potential that needs to be explored. It is however, argued that as IT can revolutionize the economic development, by the same coin, although its mismanagement in adoption process can end up in problems or even straight failure of the technology at the business-end. This study was conducted with reference to opportunities and challenges in the IT adoption process in Pakistan. The aim of the study was to point out the barriers that are impeding the country’s computerization process in order to provide facts to the policy makers for smooth computerization. The primary data collected through structured questionnaires was analyzed and tested through correlation, regressions analysis and t-test. Out of 10 hypotheses, 3 were accepted while in the rest null hypotheses were not substantiated. Based on primary and secondary data analysis this study has found that all independent bureaucratic, political, education and social and cultural variables are mutually correlated and have significant impact on shaping and reshaping of IT in Pakistan, while the Pakistan IT policy is inconsistent, administrative machinery attitude is negative and non cooperative, procedures are cumbersome and implementation is weak and ineffective, not to mention the lack of IT knowledge on the bureaucratic side. The political environment is instable and law and order is worse which is discouraging the investment. Moreover, physical and legal infrastructure is insufficient and the country is lacking good quality IT professionals. IT organization alignment is another serious issue in Pakistan. However, government incentives and growing interest from the private sector indicate positive attitude towards computerization of the country.

  14. DIGITAL PAKISTAN: OPPORTUNITIES & CHALLENGES

    Directory of Open Access Journals (Sweden)

    Ghulam Muhammad Kundi

    2008-10-01

    Full Text Available IT has revolutionized the social and organizational life around the globe. Given the newness of IT as a technology, there is a lot of potential that needs to be explored. It is however, argued that as IT can revolutionize the economic development, by the same coin, although its mismanagement in adoption process can end up in problems or even straight failure of the technology at the business-end. This study was conducted with reference to opportunities and challenges in the IT adoption process in Pakistan. The aim of the study was to point out the barriers that are impeding the country’s computerization process in order to provide facts to the policy makers for smooth computerization. The primary data collected through structured questionnaires was analyzed and tested through correlation, regressions analysis and t-test. Out of 10 hypotheses, 3 were accepted while in the rest null hypotheses were not substantiated. Based on primary and secondary data analysis this study has found that all independent bureaucratic, political, education and social and cultural variables are mutually correlated and have significant impact on shaping and reshaping of IT in Pakistan, while the Pakistan IT policy is inconsistent, administrative machinery attitude is negative and non cooperative, procedures are cumbersome and implementation is weak and ineffective, not to mention the lack of IT knowledge on the bureaucratic side. The political environment is instable and law and order is worse which is discouraging the investment. Moreover, physical and legal infrastructure is insufficient and the country is lacking good quality IT professionals. IT organization alignment is another serious issue in Pakistan. However, government incentives and growing interest from the private sector indicate positive attitude towards computerization of the country.

  15. Big Data and Analytics in Higher Education: Opportunities and Challenges

    Science.gov (United States)

    Daniel, Ben

    2015-01-01

    Institutions of higher education are operating in an increasingly complex and competitive environment. This paper identifies contemporary challenges facing institutions of higher education worldwide and explores the potential of Big Data in addressing these challenges. The paper then outlines a number of opportunities and challenges associated…

  16. Challenges to Public School Reading Textbooks.

    Science.gov (United States)

    Patterson, Frances R. A.

    1996-01-01

    Analyzes five cases related to challenges to public school textbooks. Five different U.S. Courts of Appeal have considered the objections of parents to textbooks, and all five found for the defendant school districts. Reveals that what began as a grassroots parental movement evolved into a nationwide crusade that has embroiled communities. (129…

  17. Representations of physical plausibility revealed by event-related potentials.

    Science.gov (United States)

    Roser, Matthew E; Fugelsang, Jonathan A; Handy, Todd C; Dunbar, Kevin N; Gazzaniga, Michael S

    2009-08-05

    Maintaining an accurate mental representation of the current environment is crucial to detecting change in that environment and ensuring behavioral coherence. Past experience with interactions between objects, such as collisions, has been shown to influence the perception of object interactions. To assess whether mental representations of object interactions derived from experience influence the maintenance of a mental model of the current stimulus environment, we presented physically plausible and implausible collision events while recording brain electrical activity. The parietal P300 response to 'oddball' events was found to be modulated by the physical plausibility of the stimuli, suggesting that past experience of object interactions can influence working memory processes involved in monitoring ongoing changes to the environment.

  18. The human oral metaproteome reveals potential biomarkers for caries disease

    DEFF Research Database (Denmark)

    Belda-Ferre, Pedro; Williamson, James; Simón-Soro, Áurea

    2015-01-01

    diversity. Healthy individuals appeared to have significantly higher amounts of L-lactate dehydrogenase and the arginine deiminase system, both implicated in pH buffering. Other proteins found to be at significantly higher levels in healthy individuals were involved in exopolysaccharide synthesis, iron...... metabolism and immune response. We applied multivariate analysis in order to find the minimum set of proteins that better allows discrimination of healthy and caries-affected dental plaque samples, detecting seven bacterial and five human protein functions that allow determining the health status...

  19. Wind Energy Status and Future Wind Engineering Challenges: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Thresher, R.; Schreck, S.; Robinson, M.; Veers, P.

    2008-08-01

    This paper describes the current status of wind energy technology, the potential for future wind energy development and the science and engineering challenges that must be overcome for the technology to meet its potential.

  20. Big Data Challenges

    Directory of Open Access Journals (Sweden)

    Alexandru Adrian TOLE

    2013-10-01

    Full Text Available The amount of data that is traveling across the internet today, no