WorldWideScience

Sample records for regulates human natural

  1. Natural Gas Regulation

    International Nuclear Information System (INIS)

    1995-01-01

    The regulation of Natural Gas. Natural gas Regulation clarifies and consolidates the legal and institutional framework for development of the industry through six principal elements: 1) Establishment of a vision of the industry. 2) Development of regulatory objectives. 3) Determination of relationships among industry participants. 4) Clear specification of the role of PEMEX in the industry. 5) Definition of the functions of the Regulatory authority. 6) Creation of a transition regime. In parallel with the development of the substantive legal framework, the law of the Comision Reguladora de Energia (CRE) was also enacted by Congress in October 1995 to strength the institutional framework and implement the legal changes. This law defines the CRE as an agency of the Energy Ministry with technical, operational, and budgetary autonomy, and responsibility for implementing natural gas industry regulation. (Author)

  2. Ancient and recent positive selection transformed opioid cis-regulation in humans.

    Directory of Open Access Journals (Sweden)

    Matthew V Rockman

    2005-12-01

    Full Text Available Changes in the cis-regulation of neural genes likely contributed to the evolution of our species' unique attributes, but evidence of a role for natural selection has been lacking. We found that positive natural selection altered the cis-regulation of human prodynorphin, the precursor molecule for a suite of endogenous opioids and neuropeptides with critical roles in regulating perception, behavior, and memory. Independent lines of phylogenetic and population genetic evidence support a history of selective sweeps driving the evolution of the human prodynorphin promoter. In experimental assays of chimpanzee-human hybrid promoters, the selected sequence increases transcriptional inducibility. The evidence for a change in the response of the brain's natural opioids to inductive stimuli points to potential human-specific characteristics favored during evolution. In addition, the pattern of linked nucleotide and microsatellite variation among and within modern human populations suggests that recent selection, subsequent to the fixation of the human-specific mutations and the peopling of the globe, has favored different prodynorphin cis-regulatory alleles in different parts of the world.

  3. Human niche, human behaviour, human nature.

    Science.gov (United States)

    Fuentes, Agustin

    2017-10-06

    The concept of a 'human nature' or 'human natures' retains a central role in theorizing about the human experience. In Homo sapiens it is clear that we have a suite of capacities generated via our evolutionary past, and present, and a flexible capacity to create and sustain particular kinds of cultures and to be shaped by them. Regardless of whether we label these capacities 'human natures' or not, humans occupy a distinctive niche and an evolutionary approach to examining it is critical. At present we are faced with a few different narratives as to exactly what such an evolutionary approach entails. There is a need for a robust and dynamic theoretical toolkit in order to develop a richer, and more nuanced, understanding of the cognitively sophisticated genus Homo and the diverse sorts of niches humans constructed and occupied across the Pleistocene, Holocene, and into the Anthropocene. Here I review current evolutionary approaches to 'human nature', arguing that we benefit from re-framing our investigations via the concept of the human niche and in the context of the extended evolutionary synthesis (EES). While not a replacement of standard evolutionary approaches, this is an expansion and enhancement of our toolkit. I offer brief examples from human evolution in support of these assertions.

  4. Effects of butyltin exposures on MAP kinase dependent transcription regulators in human natural killer cells

    Science.gov (United States)

    Person, Rachel J.; Whalen, Margaret M.

    2010-01-01

    Natural Killer (NK) cells are a major immune defense mechanism against cancer development and viral infection. The butyltins (BTs), tributyltin (TBT) and dibutyltin (DBT) have been widely used in industrial and other applications and significantly contaminate the environment. Both TBT and DBT have been detected in human blood. These compounds inhibit the lytic and binding function of human NK cells and thus could increase the incidence of cancer and viral infections. Butyltin (BT)-induced loss of NK function is accompanied by activation of mitogen activated protein kinases (MAPKs) and decreases in expression of cell-surface and cytolytic proteins. MAPKs activate components of the transcription regulator AP-1 and activate the transcription regulator Elk-1. Based on the fact that BTs activate MAPKs and alter protein expression, the current study examined the effect of BT exposures on the levels and phosphorylation states of the components of AP-1 and the phosphorylation state of Elk-1. Exposure to 300 nM TBT for 10 min increased the phosphorylation of c-Jun in NK cells. 1 h exposures to 300 nM and 200 nM TBT increased the phosphorylation and overall level of c-Jun. During a 300 nM treatment with TBT for 1 h the binding activity of AP-1 was significantly decreased. There were no significant alterations of AP-1 components or of Elk-1 with DBT exposures. Thus, it appears that TBT-induced alterations on phosphorylation, total levels and binding activity of c-Jun might contribute to, but are not fully responsible for, TBT-induced alterations of NK protein expression. PMID:20370538

  5. The human PINK1 locus is regulated in vivo by a non-coding natural antisense RNA during modulation of mitochondrial function

    Directory of Open Access Journals (Sweden)

    Wahlestedt Claes

    2007-03-01

    Full Text Available Abstract Background Mutations in the PTEN induced putative kinase 1 (PINK1 are implicated in early-onset Parkinson's disease. PINK1 is expressed abundantly in mitochondria rich tissues, such as skeletal muscle, where it plays a critical role determining mitochondrial structural integrity in Drosophila. Results Herein we characterize a novel splice variant of PINK1 (svPINK1 that is homologous to the C-terminus regulatory domain of the protein kinase. Naturally occurring non-coding antisense provides sophisticated mechanisms for diversifying genomes and we describe a human specific non-coding antisense expressed at the PINK1 locus (naPINK1. We further demonstrate that PINK1 varies in vivo when human skeletal muscle mitochondrial content is enhanced, supporting the idea that PINK1 has a physiological role in mitochondrion. The observation of concordant regulation of svPINK1 and naPINK1 during in vivo mitochondrial biogenesis was confirmed using RNAi, where selective targeting of naPINK1 results in loss of the PINK1 splice variant in neuronal cell lines. Conclusion Our data presents the first direct observation that a mammalian non-coding antisense molecule can positively influence the abundance of a cis-transcribed mRNA under physiological abundance conditions. While our analysis implies a possible human specific and dsRNA-mediated mechanism for stabilizing the expression of svPINK1, it also points to a broader genomic strategy for regulating a human disease locus and increases the complexity through which alterations in the regulation of the PINK1 locus could occur.

  6. Human nature, human culture: the case of cultural evolution.

    Science.gov (United States)

    Lewens, Tim

    2017-10-06

    In recent years, far from arguing that evolutionary approaches to our own species permit us to describe the fundamental character of human nature, a prominent group of cultural evolutionary theorists has instead argued that the very idea of 'human nature' is one we should reject. It makes no sense, they argue, to speak of human nature in opposition to human culture. The very same sceptical arguments have also led some thinkers-usually from social anthropology-to dismiss the intimately related idea that we can talk of human culture in opposition to human nature. How, then, are we supposed to understand the cultural evolutionary project itself, whose proponents seem to deny the distinction between human nature and human culture, while simultaneously relying on a closely allied distinction between 'genetic' (or sometimes 'organic') evolution and 'cultural' evolution? This paper defends the cultural evolutionary project against the charge that, in refusing to endorse the concept of human nature, it has inadvertently sabotaged itself.

  7. Improving efficiency and effectiveness in natural gas regulation : discussion paper

    International Nuclear Information System (INIS)

    Rounding, M.C.

    2004-11-01

    Energy market liberalization is a world trend that has prompted the deregulation of natural gas and electricity over the past twenty years in North America. The Ontario Energy Board and the National Energy Board are conducting public hearings on natural gas regulation in response to the request by Canadian energy industries for better regulatory streamlining. The following 5 issues regarding natural gas regulation in Canada have been examined: (1) system gas in a regulated market, (2) natural gas infrastructure investments and capital renewal, (3) improving efficiency in gas regulation, (4) expectations of performance-based regulation (PBR) in the natural gas industry, and (5) the debate whether further deregulation of the natural gas industry is beneficial. This paper discusses the impact that natural gas regulation has had on the efficiency and competitiveness of the industry and its affect on customers and other stakeholders. It focuses on the efficiency of the regulatory process and examines regulatory objectives, best practices and performance indicators. The factors that determine the efficiency of natural gas regulation include alternative regulatory models, structure of the regulatory agency, regulatory framework approaches, and outcomes for the natural gas industry. The relationship between the government and the regulator was also examined in terms of their abilities to implement policy. A comparative evaluation between energy regulators in Canada, the United States, Australia and the United Kingdom was presented. The balancing of short-term and long-term objectives for gas supply and planning issues was also addressed. 17 refs

  8. Regulators debate support of natural gas in electricity

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    State regulators recently tabled a controversial proposal to encourage natural gas use in electricity generation. Proponents of natural gas support such an endorsement since state regulators can influence utility fuel-supply choices through planning incentives and disincentives. Members of the National Association of Regulatory Utility Commissioners vowed to take up the matter at their Winter Committee Meetings, February 28 to March 4 in Washington, DC. NARUC's Gas Committee offered the resolution at the NARUC Annual Convention in Los Angeles in November. Presentations and debate covered the merits and drawbacks of formal support for natural gas. Natural gas generation has fast construction and low capital-cost benefits, air quality and fuel handling advantages over other fossil fuels. Still, regulators and utility representatives expressed concern over long-term availability, over reliance on one resource and price

  9. Neural Network Models of Regulating Natural Capital Funds for Renewable Energy

    OpenAIRE

    Alsayyed, Nidal; Zhu, Weihang

    2016-01-01

    Natural Capital (NC) is the limited form of capital assets or service (tangible or intangible) that satisfies basic and social conditions for human existence and protection The aim of this paper is twofold; First we examine and test empirically the conventional financing models and discuss their performance in regulating the financing structure of NC funds using a parametric estimating approach Generalized Moments Method (GMM). Second we estimate the NC dynamics using a nonparametric approach...

  10. Do natural methods for fertility regulation increase the risks of genetic errors?

    Science.gov (United States)

    Serra, A

    1981-09-01

    Genetic errors of many kinds are connected with the reproductive processes and are favored by a nunber of largely uncontrollable, endogenous, and/or exogenous factors. For a long time human beings have taken into their own hands the control of this process. The regulation of fertility is clearly a forceful request to any family, to any community, were it only to lower the level of the consequences of genetic errors. In connection with this request, and in the context of the Congress for the Family of Africa and Europe (Catholic University, January 1981), 1 question must still be raised and possibly answered. The question is: do or can the so called "natural methods" for the regulation of fertility increase the risks of genetic errors with their generally dramatic effects on families and on communities. It is important to try to give as far as possible a scientifically based answer to this question. Fr. Haring, a moral theologian, citing scientific evidence finds it shocking that the rhythm method, so strongly and recently endorsed again by Church authorities, should be classified among the means of "birth control" by way of spontaneous abortion or at least by spontaneous loss of a large number of zygotes which, due to the concrete application of the rhythm method, lack of necessary vitality for survival. He goes on to state that the scientific research provides overwhelming evidence that the rhythm method in its traditional form is responsible for a disproportionate waste of zygotes and a disproportionate frequency of spontaneous abortions and a defective childern. Professor Hilgers, a reproductive physiologist, takes on opposite view, maintaining that the hypotheses are arbitrary and the alarm false. The strongest evidence upon which Fr. Haring bases his moral principles about the use of the natural methods of fertility regulation is a paper by Guerrero and Rojos (1975). These authors examined, retrospectively, the success of 965 pregnancies which occurred in

  11. Urban warming trumps natural enemy regulation of herbivorous pests.

    Science.gov (United States)

    Dale, Adam G; Frank, Steven D

    Trees provide ecosystem services that counter negative effects of urban habitats on human and environmental health. Unfortunately, herbivorous arthropod pests are often more abundant on urban than rural trees, reducing tree growth, survival, and ecosystem services. Previous research where vegetation complexity was reduced has attributed elevated urban pest abundance to decreased regulation by natural enemies. However, reducing vegetation complexity, particularly the density of overstory trees, also makes cities hotter than natural habitats. We ask how urban habitat characteristics influence an abiotic factor, temperature, and a biotic factor, natural enemy abundance, in regulating the abundance of an urban forest pest, the gloomy scale, (Melanaspis tenebricosa). We used a map of surface temperature to select red maple trees (Acer rubrum) at warmer and cooler sites in Raleigh, North Carolina, USA. We quantified habitat complexity by measuring impervious surface cover, local vegetation structural complexity, and landscape scale vegetation cover around each tree. Using path analysis, we determined that impervious surface (the most important habitat variable) increased scale insect abundance by increasing tree canopy temperature, rather than by reducing natural enemy abundance or percent parasitism. As a mechanism for this response, we found that increasing temperature significantly increases scale insect fecundity and contributes to greater population increase. Specifically, adult female M. tenebricosa egg sets increased by approximately 14 eggs for every 1°C increase in temperature. Climate change models predict that the global climate will increase by 2–3°C in the next 50–100 years, which we found would increase scale insect abundance by three orders of magnitude. This result supports predictions that urban and natural forests will face greater herbivory in the future, and suggests that a primary cause could be direct, positive effects of warming on herbivore

  12. Curcumin as a natural regulator of monocyte chemoattractant protein-1.

    Science.gov (United States)

    Karimian, Maryam Saberi; Pirro, Matteo; Majeed, Muhammed; Sahebkar, Amirhossein

    2017-02-01

    Monocyte chemoattractant/chemotactic protein-1 (MCP-1), a member of the CC chemokine family, is one of the key chemokines that regulate migration and tissue infiltration of monocytes/macrophages. Its role in the pathophysiology of several inflammatory diseases has been widely recognized, thus making MCP-1 a possible target for anti-inflammatory treatments. Curcumin (diferuloylmethane) is a natural polyphenol derived from the rhizomes of Curcuma Longa L. (turmeric). Anti-inflammatory action underlies numerous pharmacological effects of curcumin in the control and prevention of several diseases. The purpose of this review is to evaluate the effects of curcumin on the regulation of MCP-1 as a key mediator of chemotaxis and inflammation, and the biological consequences thereof. In vitro studies have shown that curcumin can decrease MCP-1 production in various cell lines. Animal studies have also revealed that curcumin can attenuate MCP-1 expression and improve a range of inflammatory diseases through multiple molecular targets and mechanisms of action. There is limited data from human clinical trials showing the decreasing effect of curcumin on MCP-1 concentrations and improvement of the course of inflammatory diseases. Most of the in vitro and animal studies confirm that curcumin exert its MCP-1-lowering and anti-inflammatory effects by down-regulating the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathway. As yet, there is limited data from human clinical trials showing the effect of curcumin on MCP-1 levels and improvement of the course of inflammatory diseases. More evidence, especially from human studies, is needed to better assess the effects of curcumin on circulating MCP-1 in different human diseases and the role of this modulatory effect in the putative anti-inflammatory properties of curcumin. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. A state regulator's perspective on the natural gas industry

    International Nuclear Information System (INIS)

    Heintz, F.O.

    1992-01-01

    This paper reviews the history of the natural gas distribution industry and the role of state regulation in controlling pricing and supply. The paper discusses the results of national policies such as the Fuel Use Act and the subsequent Natural Gas Policy Act. It then discusses the resulting market and prices resulting from both regulation and deregulation of the natural gas industry. The paper goes on to discuss the market potential for natural gas and the reliability of this fuel source for future demand

  14. The effect of natural whey proteins on mechanisms of blood pressure regulation

    Directory of Open Access Journals (Sweden)

    Halina Car

    2014-02-01

    Full Text Available Whey is a rich natural source of peptides and amino acids. It has been reported in numerous studies that biological active peptides isolated from cow’s milk whey may affect blood pressure regulation. Studies on animals and humans have shown that α-lactalbumin and β-lactoglobulin obtained from enzymatically hydrolysed whey inhibit angiotensin converting enzyme (ACE, while lactorphins lower blood pressure by normalizing endothelial function or by opioid receptors dependent mechanism. Whey proteins or their bioactive fragments decrease total cholesterol, LDL fraction and triglycerides, thus reducing the risk factors of cardiovascular diseases. The aim of this review is to discuss the effects of whey proteins on the mechanisms of blood pressure regulation.

  15. Human, nature, society: synergetic dimension

    Directory of Open Access Journals (Sweden)

    Н. А. Вахнин

    2016-11-01

    Full Text Available The paper gives an overview of the major directions of development in the system ‘human – society – nature’ and their philosophical and scientific contemplation. The fundamental achievements of the society and responsibility of the mankind for its progressive development have been analyzed. The distinctive features of changes in human interactions with nature in the era of globalization and intensive progress in science and technology are presented. It is reported that numerous studies of human intervention in the biosphere processes prove that it can become the most profound anomaly in the development of not only the biosphere but of the entire Earth system, i.e. become a cause of such conditions on the Earth that would be alien to the general biological process in its ontological sense.  The consequence of this is a dissonance in the rate of social evolution (social form of matter and nature evolution (all pre-social forms of matter, which is translated into the disturbed ‘functional optimum’ of intensive development of the ‘human-society-nature’ system, a threat of environmental crisis and disturbances in the very biological nature  of a human. It is asserted that synergetics today still remains appealing due to a need to find adequate answers to global civilization challenges in the world living through a crisis. According to estimations, human synergetic activities come to the fore in the 21st century, it is especially true for small and large self-organizing groups, which shall not only live in harmony with the nature, but also successfully manage all different-level subsystems. It is shown that synergetics is a new dialogue between human and nature, a new synthesis of the human knowl- edge and wisdom. This is a new approach to gaining insight into the evolution crises, instability and chaos, to mastering complicated systems in the state of volatility.

  16. Synthesis of human-nature feedbacks

    Directory of Open Access Journals (Sweden)

    Vanessa Hull

    2015-09-01

    Full Text Available In today's globalized world, humans and nature are inextricably linked. The coupled human and natural systems (CHANS framework provides a lens with which to understand such complex interactions. One of the central components of the CHANS framework involves examining feedbacks among human and natural systems, which form when effects from one system on another system feed back to affect the first system. Despite developments in understanding feedbacks in single disciplines, interdisciplinary research on CHANS feedbacks to date is scant and often site-specific, a shortcoming that prevents complex coupled systems from being fully understood. The special feature "Exploring Feedbacks in Coupled Human and Natural Systems (CHANS" makes strides to fill this critical gap. Here, as an introduction to the special feature, we provide an overview of CHANS feedbacks. In addition, we synthesize key CHANS feedbacks that emerged in the papers of this special feature across agricultural, forest, and urban landscapes. We also examine emerging themes explored across the papers, including multilevel feedbacks, time lags, and surprises as a result of feedbacks. We conclude with recommendations for future research that can build upon the foundation provided in the special feature.

  17. Regulation Strategy in Natural Gas Sector. The Romanian Case

    Directory of Open Access Journals (Sweden)

    Coralia Angelescu

    2006-10-01

    Full Text Available This study provides a methodological analysis to evaluate the regulation strategy in Romanian natural gas sector. The market oriented reforms are not only associated with the gap between internal prices and world prices. In the same time, the market oriented reforms are mixed with the other forms of government intervention. The industry network theory provides a good pillar for maintaining natural monopoly in public utilities. The conclusions which are presented in this article offer a good theory for the activity of the National Authority of Regulation in Romanian natural gas sector.

  18. Hauntings of Human Nature

    DEFF Research Database (Denmark)

    Clasen, Mathias

    2017-01-01

    The central conflicts of Stephen King’s horror novel The Shining are rooted in human nature and reflect evolutionarily recurrent adaptive problems—the problem of balancing conflicting evolved motives, such as motives for selfish status striving versus motives for affiliative nurturing behavior......, and the problem of surviving the hostile forces of nature. Moreover, the supernatural elements of the novel resonate with evolved intuitions about non-material, moral forces at work in the world. That is why the novel continues to engage readers worldwide. Most critics, however, have overlooked or distorted...... the psychological underpinnings of the novel and the crucial function of the supernatural elements in the meaning structure of the novel. Hence we need an evolutionary psychological perspective which builds on recent findings in the sciences of human nature to account for the novel’s meaning, effects, and continued...

  19. The exposures to natural radioactivity as a result of human activities

    International Nuclear Information System (INIS)

    Rannou, A.; Dupuis, M.; Bottollier-Depois, J.F.; Leprieur, F.; Pasquier, J.L.; Doremus, P.; Pierre, J.P.; Bernhard, S.; Delporte, V.; Servent, J.P.; Marchand, D.; Dupuis, M.; Bottollier-Depois, J.F.; Leprieur, F.; Pasquier, J.L.; Doremus, P.; Pierre, J.P.; Surbeck, H.; Degrange, J.P.

    2005-01-01

    The new regulation in matter of radiation protection, coming from the transposition of the European directive 96/29/EURATOM modifies the code of the public health and the labour code. The exposures to natural radioactivity by the very fact of human activities are the object of specific dispositions. These new dispositions apply to professional areas that were, until now, little concerned by the regulation relative to ionizing radiations. The S.F.R.P., in relationship with the Minister in charge of labour, and the A.F.T.I.M. (French organisation of safety technicians and engineers and labour physicians) organizes two days of information and exchange on the subject. This meeting concerns industry and research departments but also inspectors and labour physicians and other actors having a look on the risk management in societies. After some reminder on radioactivity and its effects, the regulation and the global risk management on working place, several actual examples are presented, covering the different known situations of exposure to the natural radioactivity ( radon, cosmic rays, use of radioactive material in an industrial process, production of radioactive waste). The days finish by a round table conference on the stakes and practical entailment of the new regulation. (N.C.)

  20. The nature of human rights

    Directory of Open Access Journals (Sweden)

    Krivokapić Boris

    2016-01-01

    Full Text Available In the first part of the paper, the author points out that, unlike in the past, in our time human rights developed into a fair legal institution, and even a special system. They are formulated and protected both internally and internationally. The second part deals with the approach according to which human rights are part of the so-called. natural law. The author notes that the theory of natural law can not be accepted for many reasons. It is pure construction, which is far from reality, and besides it is unnecessary. Law and thus human rights as a part of it, is a social creation, developing along with the society itself, whereby, in the longer term, advanced norms in the matter of human rights replace obsolete ones. Life and human needs are the ones who impose such development. In the third part the writer notes that since under human rights one can have in mind various things, at least such a special concept and, on the other hand, specific rights, it is not possible to give a single answer to what is the nature of human rights. It is even harder as human rights, have a variety of dimensions - legal, philosophical, ideological, political, economic, social, educational, etc. However, he gives his view of the main characteristics of the modern concept of human rights. In the fourth part, the author notes that, speaking not about the concept, but human rights as such, their main characteristics are that they are: 1 source - belong to anyone on the grounds that he is a human being (general rights or a member specific vulnerable groups (special rights; 2 universal - belong to everyone or all members of vulnerable groups, without any discrimination based on personal characteristics, and on the other hand, the most important such rights shall be recognized in all states; 3 inalienable - one can not give up or else share his basic human rights, such as the right to life, the right to vote, etc.; 4 somewhat different - although, in principle, all

  1. Nature of Human Rights

    Directory of Open Access Journals (Sweden)

    Carlos López Dawson

    2016-07-01

    Full Text Available In the formation of a new Constitution the constituents will require to know or reach an agreement on the nature of human rights; then, to determine how the State will enforce the respect to those rights. To do so, it is necessary to resort to the history and evolution of these rights, and the present work aims to contribute to an efficient productive debate about the nature of human rights, so that citizens can decide on the understanding that this is a thoughtful democratic and humanistic founded decision. The analysis is in the actual technical-ideological republican system which correspond to the current state of international law

  2. Medicine as combining natural and human science.

    Science.gov (United States)

    Dreyfus, Hubert L

    2011-08-01

    Medicine is unique in being a combination of natural science and human science in which both are essential. Therefore, in order to make sense of medical practice, we need to begin by drawing a clear distinction between the natural and the human sciences. In this paper, I try to bring the old distinction between the Geistes and Naturwissenschaften up to date by defending the essential difference between a realist explanatory theoretical study of nature including the body in which the scientist discovers the causal properties of natural kinds and the interpretive understanding of human beings as embodied agents which, as Charles Taylor has convincingly argued, requires a hermeneutic account of self-interpreting human practices.

  3. Do we have to choose between feeding the human population and conserving nature? Modelling the global dependence of people on ecosystem services.

    Science.gov (United States)

    Cazalis, Victor; Loreau, Michel; Henderson, Kirsten

    2018-09-01

    The ability of the human population to continue growing depends strongly on the ecosystem services provided by nature. Nature, however, is becoming more and more degraded as the number of individuals increases, which could potentially threaten the future well-being of the human population. We use a dynamic model to conceptualise links between the global proportion of natural habitats and human demography, through four categories of ecosystem services (provisioning, regulating, cultural recreational and informational) to investigate the common future of nature and humanity in terms of size and well-being. Our model shows that there is generally a trade-off between the quality of life and human population size and identifies four short-term scenarios, corresponding to three long-term steady states of the model. First, human population could experience declines if nature becomes too degraded and regulating services diminish; second the majority of the population could be in a famine state, where the population continues to grow with minimal food provision. Between these scenarios, a desirable future scenario emerges from the model. It occurs if humans convert enough land to feed all the population, while maintaining biodiversity and ecosystem services. Finally, we find a fourth scenario, which combines famine and a decline in the population because of an overexploitation of land leading to a decrease in food production. Human demography is embedded in natural dynamics; the two factors should be considered together if we are to identify a desirable future for both nature and humans. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Cultivating human nature

    NARCIS (Netherlands)

    Derksen, Maarten

    2007-01-01

    Evolutionary psychology claims to offer a unified perspective on human nature and culture, which can serve to further the integration of psychology and the social sciences. I describe four approaches to evolutionary psychology, and note increasing attention to the agency of the individual in

  5. Conveyance of natural gas. Organization and regulation

    International Nuclear Information System (INIS)

    1995-01-01

    This International Energy Agency (IEA) study deals with the conveyance of natural gas. The socio-economic factors are given as well as the different organization and regulations modes of natural gas conveyance and storage in the IEA countries and in central and eastern Europe. The main questions forming the subject of discussions in the IEA countries are analyzed too. (O.L.). 50 refs., 55 figs., 16 tabs

  6. A Business-Relevant View of Human Nature

    OpenAIRE

    Mitreanu, Cristian

    2007-01-01

    The article, "A Business-Relevant View of Human Nature," provides a new theory of human nature, and aims to bring it to the center of our understanding of business, or commerce, creating a strong foundation for new business and economic principles and practices. The article has three parts. In the first section, the author identifies and discusses the fundamental drives that characterize all forms of life. Building upon these findings, he then develops the unique view of human nature in the s...

  7. Human Disturbance during Early Life Impairs Nestling Growth in Birds Inhabiting a Nature Recreation Area.

    Science.gov (United States)

    Remacha, Carolina; Delgado, Juan Antonio; Bulaic, Mateja; Pérez-Tris, Javier

    2016-01-01

    Nature recreation conflicts with conservation, but its impacts on wildlife are not fully understood. Where recreation is not regulated, visitors to natural areas may gather in large numbers on weekends and holidays. This may increase variance in fitness in wild populations, if individuals whose critical life cycle stages coincide with periods of high human disturbance are at a disadvantage. We studied nestling development of blue tits (Cyanistes caeruleus) in a natural area where recreation activities intensify during weekends and other public holidays at picnic and leisure facilities, but not in the surrounding woods. In nests located near recreation facilities, blue tit nestlings that hatched during holidays developed slowly, and fledged with low body mass and poor body condition. However, nestlings that hatched outside of holidays and weekends in these nest boxes developed normally, eventually attaining similar phenotypes as those hatching in the surrounding woods. Within-brood variance in body mass was also higher in broods that began growing during holidays in disturbed areas. Our results show that early disturbance events may have negative consequences for wild birds if they overlap with critical stages of development, unveiling otherwise cryptic impacts of human activities. These new findings may help managers better regulate nature recreation.

  8. Human Disturbance during Early Life Impairs Nestling Growth in Birds Inhabiting a Nature Recreation Area.

    Directory of Open Access Journals (Sweden)

    Carolina Remacha

    Full Text Available Nature recreation conflicts with conservation, but its impacts on wildlife are not fully understood. Where recreation is not regulated, visitors to natural areas may gather in large numbers on weekends and holidays. This may increase variance in fitness in wild populations, if individuals whose critical life cycle stages coincide with periods of high human disturbance are at a disadvantage. We studied nestling development of blue tits (Cyanistes caeruleus in a natural area where recreation activities intensify during weekends and other public holidays at picnic and leisure facilities, but not in the surrounding woods. In nests located near recreation facilities, blue tit nestlings that hatched during holidays developed slowly, and fledged with low body mass and poor body condition. However, nestlings that hatched outside of holidays and weekends in these nest boxes developed normally, eventually attaining similar phenotypes as those hatching in the surrounding woods. Within-brood variance in body mass was also higher in broods that began growing during holidays in disturbed areas. Our results show that early disturbance events may have negative consequences for wild birds if they overlap with critical stages of development, unveiling otherwise cryptic impacts of human activities. These new findings may help managers better regulate nature recreation.

  9. 76 FR 7695 - Iranian Human Rights Abuses Sanctions Regulations

    Science.gov (United States)

    2011-02-11

    ... DEPARTMENT OF THE TREASURY Office of Foreign Assets Control 31 CFR Part 562 Iranian Human Rights... Iranian Human Rights Abuses Sanctions Regulations, 31 CFR part 562 (the ``Regulations''), to implement E.O...--IRANIAN HUMAN RIGHTS ABUSES SANCTIONS REGULATIONS Subpart A--Relation of This Part to Other Laws and...

  10. Natural disasters and human mobility

    NARCIS (Netherlands)

    Mbaye, L.; Zimmermann, K.

    2016-01-01

    This paper reviews the effect of natural disasters on human mobility or migration. Although there is an increase of natural disasters and migration recently and more patterns to observe, the relationship remains complex. While some authors find that disasters increase migration, others show that

  11. Human economy and natural economy

    Directory of Open Access Journals (Sweden)

    Masullo Andrea

    2014-03-01

    Full Text Available The decline of economy is due to its dependency from a virtual value, the currency, the coin, that in the recent phase of consumerism is so far from real value: human capital and natural capital. If human economy wants to continue to produce wellbeing, it must accept to be a subset of natural economy, intercept flux of matter produced by its circular mechanisms, put constraints in it, i.e. machines and structures, to direct it temporarily for our advantage, and finally release it to the same original flux, in an still usable state. In this way it will assume a function no more parasitic but symbiotic. It will be connected to natural cycles without destroying it, recovering the co-evolutionary link between nature and culture, building an economic web suited to the ecological web; thus we will have a mosaic characterised by biodiversity, technological diversity, and cultural diversity, able to produce a durable prosperity.

  12. Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism.

    Science.gov (United States)

    Li, Jian; Yu, Haiyang; Wang, Sijian; Wang, Wei; Chen, Qian; Ma, Yanmin; Zhang, Yi; Wang, Tao

    2018-01-01

    Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound-multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs.

  13. Formation of Human Subjectivity in Psychological Interactions with Nature

    Directory of Open Access Journals (Sweden)

    S A Mudrak

    2014-12-01

    Full Text Available The article outlines the current trends in the environmental psychological research of the peculiarities of developing the subject-subjective human relationship with nature: considering human habitat environment as a set of natural objects; studying certain natural sites as psychologically attributive elements of the environment; determining the psychological meaning of the «Human Habitat Environment»; giving the analysis of the problem of the subjectivity development in human interaction with the natural objects.

  14. [Human nature and the enhancement of human beings in the light of the transhumanist program].

    Science.gov (United States)

    Goffi, Jean-Yves

    2011-01-01

    There are three main approaches about the question of Human Nature. essentialists consider that there exists a permanent Human Nature, shared by every human being. Existentialists consider that there is no such thing as human nature, but inescapable modes of being in the world. A moderate approach would consider that Human Nature can be modified within the limits of anthropological invariants. Transhumanists are conservative in that they think that there is a Human Nature; but they are radical in that they believe that it can (and must) be transcended by bio-technnologies and computer technologies. This project is evaluated as a caricature of suitable human enhancement.

  15. The Energy Regulatory Commission. The Regulation of Natural Gas in Mexico

    International Nuclear Information System (INIS)

    1995-01-01

    In May of 1995 the Congress approved amendments to the Regulatory Law of Constitutional article 27 on Petroleum. This legal reform fundamentally redefined the petroleum industry and authorizes the private sector to construct, operate, and own natural gas transportation, storage and distribution systems-activities previously reserved to the state. To complement these reforms and to implement the legislative mandate of the Regulatory Law on Petroleum, the Natural Gas Regulation (Reglamento de Gas Natural) was issued in November 1995. The regulation reconciles the interests of the various natural gas industry participants and signifies a Federal Commitment to promote comprehensive development of the industry. In parallel with the development of the substantive legal framework, the law of the Comision Reguladora de Energia (CRE) was also enacted by Congress in October 1995 to strength the institutional framework and implemented the legal changes. This law defines the CRE as an agency of the Energy Ministry with technical, operational, and budgetary autonomy, and responsibility for implementing natural gas industry regulation. (Author)

  16. A natural human hand model

    NARCIS (Netherlands)

    Van Nierop, O.A.; Van der Helm, A.; Overbeeke, K.J.; Djajadiningrat, T.J.P.

    2007-01-01

    We present a skeletal linked model of the human hand that has natural motion. We show how this can be achieved by introducing a new biology-based joint axis that simulates natural joint motion and a set of constraints that reduce an estimated 150 possible motions to twelve. The model is based on

  17. The historical character of human nature in Freud's theories.

    Science.gov (United States)

    Zilbersheid, Uri

    2013-06-01

    In Freud' theories of human development, human nature is described and analyzed as essentially historical. At the core of human history is the restructuring of the sexual instinct and the death instinct (or its unique form as destructive impulses). The conscious, asked-for shaping of these two instincts, under the rule of the "reality principle", forms the basis of human society at all stages. This conscious restructuring has also unintended, unasked-for results, which are part of the historically developing human nature. The historical choice has been the building of human society as a social complex based on the de-eroticization of both the individual and society. Freud suggested that the historical process of changing human nature and maintaining the achieved new structure has mainly been an enterprise of enlightened political elite, which has imposed (in all societies) the various elements of the new nature upon the ordinary people. Human history is essentially a deed of the political sphere. In viewing human nature as consisting of both asked-for and unasked-for results of human conscious purposeful activity Freud belongs to the same historical school as Marx.

  18. Essential Building Blocks of Human Nature

    CERN Document Server

    Frey, Ulrich J; Willführ, Kai P

    2011-01-01

    To understand why we humans are as we are, it is necessary to look at the essential building blocks that comprise our nature. The foundations of this structure are our evolutionary origins as primates and our social roots. Upon these rest features such as our emotions, language and aesthetic preferences, with our self-perceptions, self-deceptions and thirst for knowledge right at the top. The unifying force holding these blocks together is evolutionary theory. Evolution provides a deeper understanding of human nature and, in particular, of the common roots of these different perspectives. To build a reliable and coherent model of man, leading authors from fields as diverse as primatology, anthropology, neurobiology and philosophy have joined forces to present essays  each describing their own expert perspective. Together they provide a convincing and complete picture of our own human nature.

  19. Theorising Learning and Nature: Post-Human Possibilities and Problems

    Science.gov (United States)

    Quinn, Jocey

    2013-01-01

    In their predominantly theoretical turn to the material, post-humanist feminists often focus on "nature", arguing that the nature/culture binary has collapsed and that fixed distinctions between human and non-human spheres no longer hold. Conversely, outdoor learning sees nature as a space where humans act and has been more concerned…

  20. An innovative model for regulating supplement products: Natural health products in Canada

    International Nuclear Information System (INIS)

    Nestmann, Earle R.; Harwood, Melody; Martyres, Stephanie

    2006-01-01

    On 1 January 2004, Health Canada officially added a new term to the global list of synonyms for dietary supplements: natural health products (NHP). Developed with the intent of providing Canadian consumers with ready access to NHP that are safe, effective, and of high quality, the Natural Health Products Regulations (the NHP regulations) are applicable to the sale, manufacture, packaging, labelling, importation, distribution, and storage of NHP, and are administered by the recently formed Natural Health Products Directorate (NHPD) within Health Canada. This paper provides an overview of the process for regulating supplement products in Canada

  1. YY1 positively regulates human UBIAD1 expression

    International Nuclear Information System (INIS)

    Funahashi, Nobuaki; Hirota, Yoshihisa; Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato; Suhara, Yoshitomo; Okano, Toshio

    2015-01-01

    Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K 1 ) and a series of bacterial menaquionones (MK-n; vitamin K 2 ). Menadione (vitamin K 3 ) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1 promoter

  2. YY1 positively regulates human UBIAD1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Funahashi, Nobuaki, E-mail: nfunahashi@ri.ncgm.go.jp [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Hirota, Yoshihisa [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka (Japan); Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Suhara, Yoshitomo [Department of Bioscience and Engineering, Shibaura Institute of Technology, Saitama (Japan); Okano, Toshio [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan)

    2015-05-01

    Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K{sub 1}) and a series of bacterial menaquionones (MK-n; vitamin K{sub 2}). Menadione (vitamin K{sub 3}) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1

  3. 16 CFR 1.8 - Nature, authority and use of trade regulation rules.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Nature, authority and use of trade regulation rules. 1.8 Section 1.8 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND... Nature, authority and use of trade regulation rules. (a) For the purpose of carrying out the provisions...

  4. "Human Nature": Chemical Engineering Students' Ideas about Human Relationships with the Natural World

    Science.gov (United States)

    Goldman, Daphne; Assaraf, Orit Ben-Zvi; Shemesh, Julia

    2014-01-01

    While importance of environmental ethics, as a component of sustainable development, in preparing engineers is widely acknowledged, little research has addressed chemical engineers' environmental concerns. This study aimed to address this void by exploring chemical engineering students' values regarding human-nature relationships. The study was…

  5. The 'Disadapted' Animal: Niko Tinbergen on Human Nature and the Human Predicament.

    Science.gov (United States)

    Vicedo, Marga

    2018-06-01

    This paper explores ethologist Niko Tinbergen's path from animal to human studies in the 1960s and 1970s and his views about human nature. It argues, first, that the confluence of several factors explains why Tinbergen decided to cross the animal/human divide in the mid 1960s: his concern about what he called "the human predicament," his relations with British child psychiatrist John Bowlby, the success of ethological explanations of human behavior, and his professional and personal situation. It also argues that Tinbergen transferred his general adaptationist view of animal behavior to the realm of human biology; here, his concern about disadaptation led him to a view of human behavior that was strongly determined by the species' evolutionary past, a position that I call evolutionary determinism. These ideas can be seen in the work he carried out with his wife, Elisabeth Tinbergen, on autism. The paper concludes that Tinbergen's vision of human nature constitutes another version of what anthropologist Clifford Geertz called in 1966 the "stratigraphic" conception of the human: a view of human nature as a composite of levels in which a universal ancestral biological core is superimposed by psychological and cultural layers that represent accidental variation at best and pathological deviation at worst.

  6. Actin retrograde flow controls natural killer cell response by regulating the conformation state of SHP-1.

    Science.gov (United States)

    Matalon, Omri; Ben-Shmuel, Aviad; Kivelevitz, Jessica; Sabag, Batel; Fried, Sophia; Joseph, Noah; Noy, Elad; Biber, Guy; Barda-Saad, Mira

    2018-03-01

    Natural killer (NK) cells are a powerful weapon against viral infections and tumor growth. Although the actin-myosin (actomyosin) cytoskeleton is crucial for a variety of cellular processes, the role of mechanotransduction, the conversion of actomyosin mechanical forces into signaling cascades, was never explored in NK cells. Here, we demonstrate that actomyosin retrograde flow (ARF) controls the immune response of primary human NK cells through a novel interaction between β-actin and the SH2-domain-containing protein tyrosine phosphatase-1 (SHP-1), converting its conformation state, and thereby regulating NK cell cytotoxicity. Our results identify ARF as a master regulator of the NK cell immune response. Since actin dynamics occur in multiple cellular processes, this mechanism might also regulate the activity of SHP-1 in additional cellular systems. © 2018 The Authors.

  7. The human right to sustainable development in solidarity with Nature

    Directory of Open Access Journals (Sweden)

    Anya Teresa Parrilla Díaz

    2017-06-01

    Full Text Available This article addresses the issue of human development as a universal right subjected to the welfare of Nature. Nature is presented as supporter of life and supplier of the essential resources needed to achieve a complete human development. In light of the global ecological crisis, the author proposes sustainable development as the central framework for a new human development that can be fairer to Nature and to mankind. The challenge of sustainable human development consists in viewing Nature from an ethical perspective of human rights and solidarity.

  8. Structural basis of SUFU–GLI interaction in human Hedgehog signalling regulation

    International Nuclear Information System (INIS)

    Cherry, Amy L.; Finta, Csaba; Karlström, Mikael; Jin, Qianren; Schwend, Thomas; Astorga-Wells, Juan; Zubarev, Roman A.; Del Campo, Mark; Criswell, Angela R.; Sanctis, Daniele de; Jovine, Luca; Toftgård, Rune

    2013-01-01

    Crystal and small-angle X-ray scattering structures of full-length human SUFU alone and in complex with the conserved SYGHL motif from GLI transcription factors show major conformational changes associated with binding and reveal an intrinsically disordered region crucial for pathway activation. Hedgehog signalling plays a fundamental role in the control of metazoan development, cell proliferation and differentiation, as highlighted by the fact that its deregulation is associated with the development of many human tumours. SUFU is an essential intracellular negative regulator of mammalian Hedgehog signalling and acts by binding and modulating the activity of GLI transcription factors. Despite its central importance, little is known about SUFU regulation and the nature of SUFU–GLI interaction. Here, the crystal and small-angle X-ray scattering structures of full-length human SUFU and its complex with the key SYGHL motif conserved in all GLIs are reported. It is demonstrated that GLI binding is associated with major conformational changes in SUFU, including an intrinsically disordered loop that is also crucial for pathway activation. These findings reveal the structure of the SUFU–GLI interface and suggest a mechanism for an essential regulatory step in Hedgehog signalling, offering possibilities for the development of novel pathway modulators and therapeutics

  9. Structural basis of SUFU–GLI interaction in human Hedgehog signalling regulation

    Energy Technology Data Exchange (ETDEWEB)

    Cherry, Amy L.; Finta, Csaba; Karlström, Mikael; Jin, Qianren; Schwend, Thomas [Karolinska Institutet, Novum, Hälsovägen 7, SE-141 83 Huddinge (Sweden); Astorga-Wells, Juan [Karolinska Institutet, Scheeles väg 2, SE-171 77 Stockholm (Sweden); Biomotif AB, Enhagsvägen 7, SE-182 12 Danderyd (Sweden); Zubarev, Roman A. [Karolinska Institutet, Scheeles väg 2, SE-171 77 Stockholm (Sweden); Del Campo, Mark; Criswell, Angela R. [Rigaku Americas Corporation, 9009 New Trails Drive, The Woodlands, TX 77381 (United States); Sanctis, Daniele de [European Synchrotron Radiation Facility, 6 Rue Jules Horowitz, 38043 Grenoble (France); Jovine, Luca, E-mail: luca.jovine@ki.se; Toftgård, Rune, E-mail: luca.jovine@ki.se [Karolinska Institutet, Novum, Hälsovägen 7, SE-141 83 Huddinge (Sweden)

    2013-12-01

    Crystal and small-angle X-ray scattering structures of full-length human SUFU alone and in complex with the conserved SYGHL motif from GLI transcription factors show major conformational changes associated with binding and reveal an intrinsically disordered region crucial for pathway activation. Hedgehog signalling plays a fundamental role in the control of metazoan development, cell proliferation and differentiation, as highlighted by the fact that its deregulation is associated with the development of many human tumours. SUFU is an essential intracellular negative regulator of mammalian Hedgehog signalling and acts by binding and modulating the activity of GLI transcription factors. Despite its central importance, little is known about SUFU regulation and the nature of SUFU–GLI interaction. Here, the crystal and small-angle X-ray scattering structures of full-length human SUFU and its complex with the key SYGHL motif conserved in all GLIs are reported. It is demonstrated that GLI binding is associated with major conformational changes in SUFU, including an intrinsically disordered loop that is also crucial for pathway activation. These findings reveal the structure of the SUFU–GLI interface and suggest a mechanism for an essential regulatory step in Hedgehog signalling, offering possibilities for the development of novel pathway modulators and therapeutics.

  10. `Human nature': Chemical engineering students' ideas about human relationships with the natural world

    Science.gov (United States)

    Goldman, Daphne; Ben-Zvi Assaraf, Orit; Shemesh, Julia

    2014-05-01

    While importance of environmental ethics, as a component of sustainable development, in preparing engineers is widely acknowledged, little research has addressed chemical engineers' environmental concerns. This study aimed to address this void by exploring chemical engineering students' values regarding human-nature relationships. The study was conducted with 247 3rd-4th year chemical engineering students in Israeli Universities. It employed the New Ecological Paradigm (NEP)-questionnaire to which students added written explanations. Quantitative analysis of NEP-scale results shows that the students demonstrated moderately ecocentric orientation. Explanations to the NEP-items reveal diverse, ambivalent ideas regarding the notions embodied in the NEP, strong scientific orientation and reliance on technology for addressing environmental challenges. Endorsing sustainability implies that today's engineers be equipped with an ecological perspective. The capacity of Higher Education to enable engineers to develop dispositions about human-nature interrelationships requires adaptation of curricula towards multidisciplinary, integrative learning addressing social-political-economic-ethical perspectives, and implementing critical-thinking within the socio-scientific issues pedagogical approach.

  11. ECONOMIC NATURE OF THE FINANCIAL REGULATION OF INSURANCE MARKET

    Directory of Open Access Journals (Sweden)

    L. Shirinyan

    2013-07-01

    Full Text Available Author made critical review of researches and found out the existance of the problem of determination and differentiation in a scientific literature the concepts “financial regulation of the insurance market”, “government financial regulation of the insurance market” and “government regulation of the insurance market”. It is offered the consideration of the insurance market from positions of analysis of the complex systems as being the component part of the greater system. It is disclosured the economic nature and determined the mentioned notions.

  12. Regulation of naturally occurring radioactive materials in non-nuclear industries

    International Nuclear Information System (INIS)

    Scott, L.M.

    1997-01-01

    The volume and concentrations of naturally occurring radioactive material is large across a variety of industries commonly thought not to involve radioactive material. The regulation of naturally occurring radioactive material in the United States is in a state of flux. Inventory of naturally occurring radioactive materials is given, along with a range of concentrations. Current and proposed regulatory limits are presented. (author)

  13. Rousseau’s View of Human Nature and Values Education

    OpenAIRE

    TÜFENKÇİ, Semra; ÇETİN, Mustafa

    2017-01-01

    Rousseau considers human nature and everything arising from this nature as good as theiroriginal instances. Therefore, education should reveal the positive emotions in human nature,rather than to sculpt them. Rousseau’s thoughts in Emile, have been a great influence on theeducators, especially on the values education approaches of modern education. In this article,we examine Rousseau’s negative education approach which acknowledges that human natureis merely good; and the importance of negati...

  14. Analysis of meiosis regulators in human gonads

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Nielsen, John E; Jensen, Martin Blomberg

    2012-01-01

    The mitosis-meiosis switch is a key event in the differentiation of germ cells. In humans, meiosis is initiated in fetal ovaries, whereas in testes meiotic entry is inhibited until puberty. The purpose of this study was to examine the expression pattern of meiosis regulators in human gonads...... with their role in initiation and progression of meiosis. The putative meiosis inhibitors, CYP26B1 and NANOS2, were primarily expressed in Leydig cells and spermatocytes, respectively. In conclusion, the expression pattern of the investigated meiotic regulators is largely conserved in the human gonads compared...... with rodents, but with some minor differences, such as a stable expression of CYP26B1 in human fetal ovaries. The sexually dimorphic expression pattern of DMRT1 indicates a similar role in the mitosis-meiosis switch in human gonads as previously demonstrated in mice. The biological importance of the changes...

  15. Humanism and nature – some reflections on a complex relationship

    Directory of Open Access Journals (Sweden)

    Jörn Rüsen

    2006-04-01

    Full Text Available The paper starts with a systematical analysis of the interrelationship of humanism and nature. It proceeds to a historical reconstruction of this relationship in the development of Western humanism from ancient Rome via Renaissance till the Enlightenment of the 18th century. In both respects the result of the analysis is the same: The Western tradition of humanism is characterised by a gap between an emphasis on the cultural quality of human life on the one hand and nature on the other one. Men are entitled to dominate and govern nature and use it for their purpose. This fits into an idea of a progressing destructive relationship between man and nature in the West. On the other the tradition of humanism has put the gap between man and nature into a harmonising cosmological or theological context. In this context a simple destructive relationship between man and nature is not possible. The humanism of today has to pick up the challenge of the ecological crisis and to refer to its tradition where man and nature are mediated into a meaningful and sense-bearing interrelationship. Instead of simply referring to the traditional cosmology a convincing idea of this mediation or even synthesis can only be made plausible by referring to the already pre-given synthesis between nature and culture, the human body.

  16. Human Nature and its Implications for the Legal System | Obioha ...

    African Journals Online (AJOL)

    This paper examines the implications the various conceptions of human nature hold for the legal system. No doubt, there are various and conflicting theories of human nature such that the concept of human nature seems to have remained elusive and pervasive. Some conceive man as nothing but matter pure and simple; ...

  17. Positron emission tomography radiopharmaceutical studies in humans: a guide to regulations for academic researchers.

    Science.gov (United States)

    Fleming, Ian N; Whelan, Mark; Baxendale, Roy; Gilbert, Fiona J; Matthews, Paul P; Aigbirhio, Franklin I

    2012-09-01

    All clinical trials are covered by a series of regulations that seek to protect the rights, safety and welfare of participating patients. The regulations covering PET studies are especially complex to interpret because of the specialized nature of the language of the regulations and of PET studies themselves. It is often unclear whether the application demands that the radiotracer used be treated as an investigational medical product. This paper is intended to act as a general guide for UK researchers planning to perform PET research in humans by clarifying key aspects of the regulations that may affect the study and/or the radiopharmaceutical manufacturing process, providing links to useful information sources, introducing the concept of a UK Medicines and Healthcare products Regulatory Agency (MHRA) PET expert panel and outlining the value of sharing investigational medical product dossiers.

  18. All-trans retinoic acid negatively regulates cytotoxic activities of nature killer cell line 92

    International Nuclear Information System (INIS)

    Li Ang; He Meilan; Wang Hui; Qiao Bin; Chen Ping; Gu Hua; Zhang Mengjie; He Shengxiang

    2007-01-01

    NK cells are key components of innate immune systems and their activities are regulated by cytokines and hormones. All-trans retinoic acid (ATRA), as a metabolite of vitamin A and an immunomodulatory hormone, plays an important role in regulating immune responses. In the present study, we investigated the effect of ATRA on human NK cell line NK92. We found that ATRA dose-dependently suppressed cytotoxic activities of NK92 cells without affecting their proliferation. To explore the mechanisms underlying the ATRA influence on NK92 cells, we examined the production of cytokines (TNF-α, IFN-γ), gene expression of cytotoxic-associated molecules (perforin, granzyme B, nature killer receptors (NCRs), and NKG2D), and the activation of NF-κB pathways related with immune response. Our results demonstrated that ATRA suppressed NF-κB activity and prevented IκBα degradation in a dose-dependent way, inhibited IFN-γ production and gene expression of granzyme B and NKp46. Our findings suggest that ATRA is a negative regulator of NK92 cell activation and may act as a potential regulator of anti-inflammatory functions in vivo

  19. Status, Antimicrobial Mechanism, and Regulation of Natural Preservatives in Livestock Food Systems.

    Science.gov (United States)

    Lee, Na-Kyoung; Paik, Hyun-Dong

    2016-01-01

    This review discusses the status, antimicrobial mechanisms, application, and regulation of natural preservatives in livestock food systems. Conventional preservatives are synthetic chemical substances including nitrates/nitrites, sulfites, sodium benzoate, propyl gallate, and potassium sorbate. The use of artificial preservatives is being reconsidered because of concerns relating to headache, allergies, and cancer. As the demand for biopreservation in food systems has increased, new natural antimicrobial compounds of various origins are being developed, including plant-derived products (polyphenolics, essential oils, plant antimicrobial peptides (pAMPs)), animal-derived products (lysozymes, lactoperoxidase, lactoferrin, ovotransferrin, antimicrobial peptide (AMP), chitosan and others), and microbial metabolites (nisin, natamycin, pullulan, ε-polylysine, organic acid, and others). These natural preservatives act by inhibiting microbial cell walls/membranes, DNA/RNA replication and transcription, protein synthesis, and metabolism. Natural preservatives have been recognized for their safety; however, these substances can influence color, smell, and toxicity in large amounts while being effective as a food preservative. Therefore, to evaluate the safety and toxicity of natural preservatives, various trials including combinations of other substances or different food preservation systems, and capsulation have been performed. Natamycin and nisin are currently the only natural preservatives being regulated, and other natural preservatives will have to be legally regulated before their widespread use.

  20. Are Humans Still Evolving? A Natural Selection Discussion Lesson

    Science.gov (United States)

    Shields, Martin

    2004-01-01

    A study is conducted to develop sound comprehension of natural selection theory by prompting students to use its concept to explain the evolutionary status of humans. In relation to the current existence of human it is stated that human populations currently undergo microevolutionary changes in allele frequencies due to natural selection and other…

  1. Human Nature in the Adaptation of Trust

    OpenAIRE

    Nooteboom, B.

    2006-01-01

    This chapter pleads for more inspiration from human nature, in agent-based modeling.As an illustration of an effort in that direction, it summarizes and discusses an agentbased model of the build-up and adaptation of trust between multiple producers and suppliers.The central question is whether, and under what conditions, trust and loyalty are viable in markets.While the model incorporates some well known behavioural phenomena from the trust literature, more extended modeling of human nature ...

  2. Regulation of natural health products in Canada.

    Science.gov (United States)

    Smith, Alysyn; Jogalekar, Sumedha; Gibson, Adam

    2014-12-02

    In Canada, all natural health products (NHPs) are regulated by Health Canada (HC) under the Food and Drugs Act and the Natural Health Product Regulations. All authorized products undergo pre-market assessment for safety, efficacy and quality and the degree of pre-market oversight varies depending on the risk of the product. In Canada, over 70,000 products have been authorized for sale and over 2000 sites have been licensed to produce NHPs. In the management of NHPs on the Canadian market, HC employs a number of active and collaborative methods to address the most common issues such as contamination, adulteration and deceptive or misleading advertising practices. HC is currently evolving its approaches to NHPs to recognize them as part of the larger group of health products available without a prescription. As such, the regulatory responsibility for all over-the-counter (OTC) drugs, including non-prescription drugs and NHPs, has been transferred to a single federal division. As a result of this transition a number of benefits are being realized with respect to government efficiency, clarity for industry, support for new innovations and consolidated government interactions with the Canadian market. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Human-Nature for Climate Action: Nature-Based Solutions for Urban Sustainability

    Directory of Open Access Journals (Sweden)

    Helen Santiago Fink

    2016-03-01

    Full Text Available The global climate change agenda proceeds at an incremental pace while the Earth is approaching critical tipping points in its development trajectory. Climate action at this pinnacle juncture needs to be greatly accelerated and rooted in the fundamentals of the problem—human beings’ disconnection from nature. This paper underscores the valuable role nature and nature-based solutions can play in addressing climate change at the city scale and its implications for broader sustainability. Urban ecosystems (nature in cities are seen as an integral part of a proposed local climate action rubric wherein policy measures and integrated planning guide lowcarbon/impact development to create more resilient and sustainable urban environments. The use of green infrastructure is highlighted as a cost-effective means to contribute to mitigation and adaptation needs as well as to promote human wellbeing. The paper takes an exploratory view of the influence of ecosystem services, particularly cultural services, and its economics in relation to the individual and society to understand how biophilia can be nurtured to promote environmental stewardship and climate action.

  4. Selenium-regulated hierarchy of human selenoproteome in cancerous and immortalized cells lines.

    Science.gov (United States)

    Touat-Hamici, Zahia; Bulteau, Anne-Laure; Bianga, Juliusz; Jean-Jacques, Hélène; Szpunar, Joanna; Lobinski, Ryszard; Chavatte, Laurent

    2018-04-13

    Selenoproteins (25 genes in human) co-translationally incorporate selenocysteine using a UGA codon, normally used as a stop signal. The human selenoproteome is primarily regulated by selenium bioavailability with a tissue-specific hierarchy. We investigated the hierarchy of selenoprotein expression in response to selenium concentration variation in four cell lines originating from kidney (HEK293, immortalized), prostate (LNCaP, cancer), skin (HaCaT, immortalized) and liver (HepG2, cancer), using complementary analytical methods. We performed (i) enzymatic activity, (ii) RT-qPCR, (iii) immuno-detection, (iv) selenium-specific mass spectrometric detection after non-radioactive 76 Se labeling of selenoproteins, and (v) luciferase-based reporter constructs in various cell extracts. We characterized cell-line specific alterations of the selenoproteome in response to selenium variation that, in most of the cases, resulted from a translational control of gene expression. We established that UGA-selenocysteine recoding efficiency, which depends on the nature of the SECIS element, dictates the response to selenium variation. We characterized that selenoprotein hierarchy is cell-line specific with conserved features. This analysis should be done prior to any experiments in a novel cell line. We reported a strategy based on complementary methods to evaluate selenoproteome regulation in human cells in culture. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Dialectical Model of Human Nature

    OpenAIRE

    Cachat, Jonathan

    2013-01-01

    The DMoHN is a graphical representation of my current understanding and conceptualization of human nature, in addition to embodying the guiding ethos of social neuroscience. The dialectic is a logic, or way of thinking that joins opposite elements together in a uniting fashion to create emergent attributes not present in the elements alone. The dialectical structure of this model explicitly links Culture and Biology within the human brain in order to convey the symbiotic and dynamic interacti...

  6. The nature of student teachers' regulation of learning in teacher education.

    Science.gov (United States)

    Endedijk, Maaike D; Vermunt, Jan D; Verloop, Nico; Brekelmans, Mieke

    2012-09-01

    Self-regulated learning (SRL) has mainly been conceptualized to involve student learning within academic settings. In teacher education, where learning from theory and practice is combined, student teachers also need to regulate their learning. Hence, there is an urgent need to extend SRL theories to the domain of teacher learning and to obtain scientific knowledge on the nature of student teachers' SRL to enable support of these processes in teacher education. This study was aimed at exploring the nature of student teachers' regulation of learning across various theoretical and practical contexts in teacher education. Twenty-eight students from a post-graduate academic teacher education institute participated in this study. For the measurement of student teachers' regulation activities, an open question log, called Learning Report, was developed. Content analysis and multiple correspondence analyses of 133 Learning Reports were used to identify qualitative differences in regulation activities and the underlying structure in the data. The analyses resulted in the identification and description of the variety and frequency of student teachers' regulation activities. The relations among the regulation activities were described by an underlying structure of two dimensions: passive versus active regulation of learning and prospective versus retrospective regulation of learning. Active regulation dominated in practice schools, passive regulation at the university. It is argued that for learning to teach, a different conceptualization of SRL is needed, focusing less on setting initial learning goals and more on retrospective aspects of SRL. Building blocks for such a conceptualization are offered. ©2011 The British Psychological Society.

  7. Natural selection and infectious disease in human populations

    Science.gov (United States)

    Karlsson, Elinor K.; Kwiatkowski, Dominic P.; Sabeti, Pardis C.

    2015-01-01

    The ancient biological 'arms race' between microbial pathogens and humans has shaped genetic variation in modern populations, and this has important implications for the growing field of medical genomics. As humans migrated throughout the world, populations encountered distinct pathogens, and natural selection increased the prevalence of alleles that are advantageous in the new ecosystems in both host and pathogens. This ancient history now influences human infectious disease susceptibility and microbiome homeostasis, and contributes to common diseases that show geographical disparities, such as autoimmune and metabolic disorders. Using new high-throughput technologies, analytical methods and expanding public data resources, the investigation of natural selection is leading to new insights into the function and dysfunction of human biology. PMID:24776769

  8. Kinome analysis of receptor-induced phosphorylation in human natural killer cells.

    Directory of Open Access Journals (Sweden)

    Sebastian König

    Full Text Available BACKGROUND: Natural killer (NK cells contribute to the defense against infected and transformed cells through the engagement of multiple germline-encoded activation receptors. Stimulation of the Fc receptor CD16 alone is sufficient for NK cell activation, whereas other receptors, such as 2B4 (CD244 and DNAM-1 (CD226, act synergistically. After receptor engagement, protein kinases play a major role in signaling networks controlling NK cell effector functions. However, it has not been characterized systematically which of all kinases encoded by the human genome (kinome are involved in NK cell activation. RESULTS: A kinase-selective phosphoproteome approach enabled the determination of 188 kinases expressed in human NK cells. Crosslinking of CD16 as well as 2B4 and DNAM-1 revealed a total of 313 distinct kinase phosphorylation sites on 109 different kinases. Phosphorylation sites on 21 kinases were similarly regulated after engagement of either CD16 or co-engagement of 2B4 and DNAM-1. Among those, increased phosphorylation of FYN, KCC2G (CAMK2, FES, and AAK1, as well as the reduced phosphorylation of MARK2, were reproducibly observed both after engagement of CD16 and co-engagement of 2B4 and DNAM-1. Notably, only one phosphorylation on PAK4 was differentally regulated. CONCLUSIONS: The present study has identified a significant portion of the NK cell kinome and defined novel phosphorylation sites in primary lymphocytes. Regulated phosphorylations observed in the early phase of NK cell activation imply these kinases are involved in NK cell signaling. Taken together, this study suggests a largely shared signaling pathway downstream of distinct activation receptors and constitutes a valuable resource for further elucidating the regulation of NK cell effector responses.

  9. On the normativity of human nature: some epistemological remarks.

    Science.gov (United States)

    Corradini, Antonella

    2003-04-01

    This paper examines the role played by the concept of human nature in ethical theory. The focus is on the epistemological problems that arise from application of this notion to the foundation of ethics. From this viewpoint, two theories, the neoscholastic and the neoclassical ones, are expounded, analyzed and compared. The aim is to highlight their opposite ways of relating the "ought-to-be" (of norms) to the "is" (of human nature). The conclusion is drawn that an adequate solution of the dispute depends on a correct interpretation of Hume's law. Reflection is conducted in the last section on the implications of metaethical discourse on human nature for applied ethics.

  10. Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation.

    Directory of Open Access Journals (Sweden)

    Lianghua Bin

    Full Text Available The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq profiling approach, we found that forkhead box c 1 (FOXC1 was significantly up-regulated in human normal primary KC during the course of differentiation. This observation was validated in human normal primary KC from several different donors and human skin biopsies. Silencing FOXC1 in human normal primary KC undergoing differentiation led to significant down-regulation of late terminal differentiation genes markers including epidermal differentiation complex genes, keratinization genes, sphingolipid/ceramide metabolic process genes and epidermal specific cell-cell adhesion genes. We further demonstrated that FOXC1 works down-stream of ZNF750 and KLF4, and upstream of GRHL3. Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network.

  11. On the nature and meaning of human finitude.

    Science.gov (United States)

    Frie, Roger

    2013-06-01

    This article considers the interaction between psychoanalysis and philosophy by examining the meaning of human finitude in the work of Freud and Heidegger. Although Freud and Heidegger develop radically different systems of thought, they are surprisingly close in their examination of the human attitude toward death. Freud's philosophical reflections on the nature of death are ultimately subsumed in his speculative theory of the death instinct, which is far removed from the lived experience of finitude. Heidegger's ontological account of death draws from lived experience but neglects the relational nature of finitude. Drawing on the connection between the work of Binswanger and Stolorow, I maintain that finitude is a fundamentally relational phenomenon. While philosophy can help us to understand and formulate an account of human finitude, the relational nature of psychoanalysis can help us bear the trauma associated with death.

  12. The feed-back regulation of erythropoietin production in healthy humans

    International Nuclear Information System (INIS)

    Klausen, T.

    1998-01-01

    The proposed oxygen-dependent feed-back loop regulation of EPO (erythropoietin) production is mainly supported by data from studies in animals and cell cultures. The feed-back loop and its dependence on oxygen was therefore challenged by studies in healthy humans: Exposure of humans to different levels of acute and continued altitude hypobaria provided evidence for an oxygen dependence of the EPO response. This response is consistent with the proposed feed-back loop regulation of EPO production; Exposure to continued altitude hypobaria demonstrated that the decline in human EPO production is initiated before an EPO-induced erythopoiesis is detectable, and that this decline is related to a concomitant decrease in the haemoglobin-oxygen affinity. Contrary to the feed-back loop, this time-relation indicate that the feed-back regulation of EPO production during continued hypobaric hypoxia is exerted primarily through a decrease in the haemoglobin-oxygen affinity, rather than by the effects of an EPO-stimulated erythropoiesis; Increased circulating levels of the proinflammatory cytokine IL-6 was found in healthy humans during four days of altitude exposure as compared with sea level. The other proinflammatory cytokines IL-1 beta, and TNF alpha remained unchanged, and the increased serum IL-6 did not induce production of c-reactive protein; Comparable circadian variations in human EPO production were shown in sedentary subjects, athletes, and healthy but hypoxaemic subjects. Human EPO production could not be triggered by one hour of high-intensity exercise, whereas longitudinal changes in exercise showed a trend of relation between human EPO production, serum concentration of free testosterone, and indices of body composition. These results have demonstrated and endogenous, probably hormonal, and oxygen-independent regulation of human EPO production, which is at variance with the oxygen dependent feed-back loop regulation of EPO production. Conclusively, the present

  13. The effect of nonhuman’s external regulation on detecting the natural development process of young children’s self-regulation during learning tasks

    NARCIS (Netherlands)

    Agina, Adel Masaud; Agina, Adel M.; Kommers, Petrus A.M.; Steehouder, M.F.

    2011-01-01

    The present study explored the effect of nonhuman’s external regulation on children’s natural development of self-regulation and the effect of each natural developed class on children’s spontaneous thinking aloud and satisfaction. The Aginian’s methodology (Agina et al., 2011a) that relied on

  14. Homo Ethicus : Understanding the Human Nature that Underlies ...

    African Journals Online (AJOL)

    Abstract. The themes of human rights and human rights education in South Africa's multi-cultural society are central to the work of Cornelia Roux. This article discusses the human reality and ethics underlying those themes, using an approach based on a view of human nature. It has six sections, starting with an introduction ...

  15. Incorporating Ecosystem Processes Controlling Carbon Balance Into Models of Coupled Human-Natural Systems

    Science.gov (United States)

    Currie, W.; Brown, D. G.; Brunner, A.; Fouladbash, L.; Hadzick, Z.; Hutchins, M.; Kiger, S. E.; Makino, Y.; Nassauer, J. I.; Robinson, D. T.; Riolo, R. L.; Sun, S.

    2012-12-01

    A key element in the study of coupled human-natural systems is the interactions of human populations with vegetation and soils. In human-dominated landscapes, vegetation production and change results from a combination of ecological processes and human decision-making and behavior. Vegetation is often dramatically altered, whether to produce food for humans and livestock, to harvest fiber for construction and other materials, to harvest fuel wood or feedstock for biofuels, or simply for cultural preferences as in the case of residential lawns with sparse trees in the exurban landscape. This alteration of vegetation and its management has a substantial impact on the landscape carbon balance. Models can be used to simulate scenarios in human-natural systems and to examine the integration of processes that determine future trajectories of carbon balance. However, most models of human-natural systems include little integration of the human alteration of vegetation with the ecosystem processes that regulate carbon balance. Here we illustrate a few case studies of pilot-study models that strive for this integration from our research across various types of landscapes. We focus greater detail on a fully developed research model linked to a field study of vegetation and soils in the exurban residential landscape of Southeastern Michigan, USA. The field study characterized vegetation and soil carbon storage in 5 types of ecological zones. Field-observed carbon storage in the vegetation in these zones ranged widely, from 150 g C/m2 in turfgrass zones, to 6,000 g C/m2 in zones defined as turfgrass with sparse woody vegetation, to 16,000 g C/m2 in a zone defined as dense trees and shrubs. Use of these zones facilitated the scaling of carbon pools to the landscape, where the areal mixtures of zone types had a significant impact on landscape C storage. Use of these zones also facilitated the use of the ecosystem process model Biome-BGC to simulate C trajectories and also

  16. Out of gas: Tenneco in the era of natural gas regulation, 1938--1978

    Science.gov (United States)

    Raley, David

    2011-12-01

    Federal regulation over the natural gas industry spanned 1938--1978, during which time both the industry and the nature of the regulation changed. The original intent of the law was to reform an industry stagnating because of the Depression, but regulation soon evolved into a public-private partnership to win World War II, then to a framework for the creation and management of a nationwide natural gas grid in the prosperous post-war years, and finally to a confused and chaotic system of wellhead price regulation which produced shortages and discouraged new production during the 1950s and 1960s. By the 1970s, regulation had become ineffective, leading to deregulation in 1978. The natural gas industry operated under the oversight of the Federal Power Commission (FPC) which set gas rates, regulated profits and competition, and established rules for entry and exit into markets. Over the course of four decades, the FPC oversaw the development of a truly national industry built around a system of large diameter pipelines. Tennessee Gas Transmission Company (later Tenneco) was an integral part of this industry. At first, Tenneco prospered under regulation. Regulation provided Tenneco with the means to build its first pipeline and a secure revenue stream for decades. A series of conflicts with the FPC and the difficulties imposed by the Phillips vs. Wisconsin case in 1954 soon interfered with the ambitious long-term goals of Tenneco CEO and president Gardiner Symonds. Tenneco first diversified into unregulated businesses in the 1940s, which accelerated as regulatory changes constrained the company's growth. By the 1960s the company was at the forefront of the conglomeration movement, when Tenneco included a variety of disparate businesses, including oil and gas production, chemicals, consumer packaging, manufacturing, shipbuilding, and food production, among others. Gas transmission became a minority interest in Tenneco's portfolio as newer and larger divisions

  17. Is anyone regulating naturally occurring radioactive material? A state survey

    International Nuclear Information System (INIS)

    Gross, E.M.; Barisas, S.G.

    1993-08-01

    As far as we know, naturally occurring radioactive material (NORM) has surrounded humankind since the beginning of time. However, recent data demonstrating that certain activities concentrate NORM have increased concern regarding its proper handling and disposal and precipitated the development of new NORM-related regulations. The regulation of NORM affects the management of government facilities as well as a broad range of industrial processes. Recognizing that NORM regulation at the federal level is extremely limited, Argonne National Laboratory (ANL) conducted a 50-state survey to determine the extent to which states have assumed the responsibility for regulating NORM as well as the NORM standards that are currently being applied at the state level. Though the survey indicates that NORM regulation comprises a broad spectrum of controls from full licensing requirements to virtually no regulation at afl, a trend is emerging toward recognition of the need for increased regulation of potential NORM hazards, particularly in the absence of federal standards

  18. Biological and social understanding of human nature: biopolitical dimension

    Directory of Open Access Journals (Sweden)

    S. K. Kostiuchkov

    2014-07-01

    Full Text Available This paper examines the position of the biopolitical nature of man as a biosocial being given supplies of both the two spheres of life – natural, biological and social. The necessity of understanding of human nature, which by definition are bio-social importance of the approach to the definition of man as an integral, binary-konnotovanoyi of the «social individual – a species» which is characterized by symmetrical opposition – upposition social and biological. It was found that the main task of modern political science, and in particular bio-political studies presented appeals to rethink the political picture of the world in order to predict the development of a new order or a new chaos. Understanding the formation of a new global civilization worldview is today one of the most important problems, which is connected with the main problem of the modern world – the task of preserving life on the planet. It is concluded that the contradictions of human nature – between the biological and the social, physical and spiritual, universal and the particular, natural and artificial, rational and emotional – in today’s conditions are extremely sharp. The said situation requires more in-depth scientific analysis of human nature, the study of the structural level as human biosocial system.

  19. Hypoxia regulates microRNA expression in the human carotid body

    International Nuclear Information System (INIS)

    Mkrtchian, Souren; Lee, Kian Leong; Kåhlin, Jessica; Ebberyd, Anette; Poellinger, Lorenz; Fagerlund, Malin Jonsson; Eriksson, Lars I.

    2017-01-01

    The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins. - Highlights: • Hypoxia triggers differential expression of many miRNAs in the human carotid body. • This can lead to the upregulation of proliferation and immune response functions. • CB expression profile in the carotid body resembles the miRNA expression pattern in the brain. • miRNAs are involved in the regulation of carotid body functions including oxygen sensing.

  20. Hypoxia regulates microRNA expression in the human carotid body

    Energy Technology Data Exchange (ETDEWEB)

    Mkrtchian, Souren, E-mail: souren.mkrtchian@ki.se [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Lee, Kian Leong, E-mail: csilkl@nus.edu.sg [Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore (Singapore); Kåhlin, Jessica [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm (Sweden); Ebberyd, Anette [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Poellinger, Lorenz [Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore (Singapore); Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Fagerlund, Malin Jonsson; Eriksson, Lars I. [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm (Sweden)

    2017-03-15

    The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins. - Highlights: • Hypoxia triggers differential expression of many miRNAs in the human carotid body. • This can lead to the upregulation of proliferation and immune response functions. • CB expression profile in the carotid body resembles the miRNA expression pattern in the brain. • miRNAs are involved in the regulation of carotid body functions including oxygen sensing.

  1. Exceptionalist naturalism: Human agency and the causal order.

    Science.gov (United States)

    Turri, John

    2018-02-01

    This paper addresses a fundamental question in folk metaphysics: How do we ordinarily view human agency? According to the transcendence account, we view human agency as standing outside of the causal order and imbued with exceptional powers. According to a naturalistic account, we view human agency as subject to the same physical laws as other objects and completely open to scientific investigation. According to exceptionalist naturalism, the truth lies somewhere in between: We view human agency as fitting broadly within the causal order while still being exceptional in important respects. In this paper, I report seven experiments designed to decide between these three competing theories. Across a variety of contexts and types of action, participants agreed that human agents can resist outcomes described as inevitable, guaranteed, and causally determined. Participants viewed non-human animal agents similarly, whereas they viewed computers, robots, and simple inanimate objects differently. At the same time, participants judged that human actions are caused by many things, including psychological, neurological, and social events. Overall, in folk metaphysics, human and non-human animals are viewed as exceptional parts of the natural world.

  2. Review of codes, standards, and regulations for natural gas locomotives.

    Science.gov (United States)

    2014-06-01

    This report identified, collected, and summarized relevant international codes, standards, and regulations with potential : applicability to the use of natural gas as a locomotive fuel. Few international or country-specific codes, standards, and regu...

  3. Empowering Learning through Natural, Human, and Building Ecologies.

    Science.gov (United States)

    Kobet, Robert J.

    This article asserts that it is critical to understand the connections between human ecology and building ecology to create humane environments that show inspiration and creativity and that also serve diverse needs. It calls for efforts to: (1) construct an environmental education approach that fuses the three ecologies (natural, human, and…

  4. The Canadian Natural Health Products (NHP regulations: industry perceptions and compliance factors

    Directory of Open Access Journals (Sweden)

    Boon Heather

    2006-05-01

    Full Text Available Abstract Background The use of natural health products, such as vitamins, minerals, and herbs, by Canadians has been increasing with time. As a result of consumer concern about the quality of these products, the Canadian Department of Health created the Natural Health Products (NHP Regulations. The new Canadian regulations raise questions about whether and how the NHP industry will be able to comply and what impact they will have on market structure. The objectives of this study were to explore who in the interview sample is complying with Canada's new NHP Regulations (i.e., submitted product licensing applications on time; and explore the factors that affect regulatory compliance. Methods Twenty key informant interviews were conducted with employees of the NHP industry. The structured interviews focused on the level of satisfaction with the Regulations and perceptions of compliance and non-compliance. Interviews were tape recorded and then transcribed verbatim. Data were independently coded, using qualitative content analysis. Team meetings were held after every three to four interviews to discuss emerging themes. Results The major finding of this study is that most (17 out of 20 companies interviewed were beginning to comply with the new regulatory regime. The factors that contribute to likelihood of regulatory compliance were: perceptions and knowledge of the regulations and business size. Conclusion The Canadian case can be instructive for other countries seeking to implement regulatory standards for natural health products. An unintended consequence of the Canadian NHP regulations may be the exit of smaller firms, leading to industry consolidation.

  5. Uterine Natural Killer Cells: Functional Distinctions and Influence on Pregnancy in Humans and Mice

    Directory of Open Access Journals (Sweden)

    Francesco Colucci

    2017-04-01

    Full Text Available Our understanding of development and function of natural killer (NK cells has progressed significantly in recent years. However, exactly how uterine NK (uNK cells develop and function is still unclear. To help investigators that are beginning to study tissue NK cells, we summarize in this review our current knowledge of the development and function of uNK cells, and what is yet to be elucidated. We compare and contrast the biology of human and mouse uNK cells in the broader context of the biology of innate lymphoid cells and with reference to peripheral NK cells. We also review how uNK cells may regulate trophoblast invasion and uterine spiral arterial remodeling in human and murine pregnancy.

  6. Role of natural antisense transcripts pertaining to tumor suppressor genes in human carcinomas

    International Nuclear Information System (INIS)

    Pelicci, G.; Pierotti, M.

    2009-01-01

    Overlapping transcripts in opposite orientations can potentially form perfect sense-antisense duplex RNA. Recently, several studies have revealed the extent of natural antisense transcripts (NATs) and their role in important biological phenomena also in higher organisms. In order to test the hypothesis that the function of NATs in man might represent an essential element in the regulation of gene expression, especially at transcriptional level, in this study we planned to look for, systematically examine, and characterize NATs belonging in the human genome to the tumour suppressor class of genes, so to identify physiological (and potentially pathological) modulators in this gene class

  7. Novel transcriptional networks regulated by CLOCK in human neurons.

    Science.gov (United States)

    Fontenot, Miles R; Berto, Stefano; Liu, Yuxiang; Werthmann, Gordon; Douglas, Connor; Usui, Noriyoshi; Gleason, Kelly; Tamminga, Carol A; Takahashi, Joseph S; Konopka, Genevieve

    2017-11-01

    The molecular mechanisms underlying human brain evolution are not fully understood; however, previous work suggested that expression of the transcription factor CLOCK in the human cortex might be relevant to human cognition and disease. In this study, we investigated this novel transcriptional role for CLOCK in human neurons by performing chromatin immunoprecipitation sequencing for endogenous CLOCK in adult neocortices and RNA sequencing following CLOCK knockdown in differentiated human neurons in vitro. These data suggested that CLOCK regulates the expression of genes involved in neuronal migration, and a functional assay showed that CLOCK knockdown increased neuronal migratory distance. Furthermore, dysregulation of CLOCK disrupts coexpressed networks of genes implicated in neuropsychiatric disorders, and the expression of these networks is driven by hub genes with human-specific patterns of expression. These data support a role for CLOCK-regulated transcriptional cascades involved in human brain evolution and function. © 2017 Fontenot et al.; Published by Cold Spring Harbor Laboratory Press.

  8. Dialectics of nature: Temporal and spatial regulation in material sciences

    Institute of Scientific and Technical Information of China (English)

    Jianlong Xia; Lei Jiang

    2017-01-01

    The cooperative interaction distance measure has been proposed as a novel law pertaining to dialectics of nature,and has been extensively carried out in the design of functional nanomaterials.However,the temporal and spatial dimensions are akin to yin and yang,and thus temporal regulation needs to be accounted for when implementing the above-mentioned principle.Here,we summarize recent advances in temporally and spatially regulated materials and devices.We showcase the temporal regulation of organic semiconductors for organic photovoltaics (OPVs) using the example of exciton lifetime manipulation.As an example of spatial regulation,we consider the distribution of charge carriers in core-shell quantum dot (QD) nanocrystals for modulating their optical properties.Long exciton lifetime can in principle increase the exciton diffussion length,which is desiable for high-efficiency large-area OPV devices.Spatially regulated QDs are highly valuable emitters for light-emitting applications.We aim to show that cooperative spatio-temporal regulation of nanomaterils is of vital importance to the development of functional devices.

  9. Human exposure, health hazards, and environmental regulations

    International Nuclear Information System (INIS)

    Steinemann, Anne

    2004-01-01

    United States environmental regulations, intended to protect human health, generally fail to address major sources of pollutants that endanger human health. These sources are surprisingly close to us and within our control, such as consumer products and building materials that we use within our homes, workplaces, schools, and other indoor environments. Even though these indoor sources account for nearly 90% of our pollutant exposure, they are virtually unregulated by existing laws. Even pollutant levels found in typical homes, if found outdoors, would often violate federal environmental standards. This article examines the importance of human exposure as a way to understand and reduce effects of pollutants on human health. Results from exposure studies challenge traditional thinking about pollutant hazards, and reveal deficiencies in our patchwork of laws. And results from epidemiological studies, showing increases in exposure-related diseases, underscore the need for new protections. Because we cannot rely solely on regulations to protect us, and because health effects from exposures can develop insidiously, greater efforts are needed to reduce and prevent significant exposures before they occur. Recommendations include the development and use of safer alternatives to common products, public education on ways to reduce exposure, systematic monitoring of human exposure to pollutants, and a precautionary approach in decision-making

  10. Contemporary assumptions on human nature and work and approach to human potential managing

    Directory of Open Access Journals (Sweden)

    Vujić Dobrila

    2006-01-01

    Full Text Available A general problem of this research is to identify if there is a relationship between the assumption on human nature and work (Mcgregor, Argyris, Schein, Steers and Porter and a general organizational model preference, as well as a mechanism of human resource management? This research was carried out in 2005/2006. The sample consisted of 317 subjects (197 managers, 105 highly educated subordinates and 15 entrepreneurs in 7 big enterprises in a group of small business enterprises differentiating in terms of the entrepreneur’s structure and a type of activity. A general hypothesis "that assumptions on human nature and work are statistically significant in connection to the preference approach (models, of work motivation commitment", has been confirmed. A specific hypothesis have been also confirmed: ·The assumptions on a human as a rational economic being are statistically significant in correlation with only two mechanisms of traditional models, the mechanism of method work control and the working discipline mechanism. ·Statistically significant assumptions on a human as a social being are correlated with all mechanisms of engaging employees, which belong to the model of the human relations, except the mechanism introducing the adequate type of prizes for all employees independently of working results. ·The assumptions on a human as a creative being are statistically significant, positively correlating with preference of two mechanisms belonging to the human resource model by investing into education and training and making conditions for the application of knowledge and skills. The young with assumptions on a human as a creative being prefer much broader repertoire of mechanisms belonging to the human resources model from the remaining category of subjects in the pattern. The connection between the assumption on human nature and preference models of engaging appears especially in the sub-pattern of managers, in the category of young subjects

  11. INHUMAN HUMAN NATURE: LOIS LOWRY’S THE GIVER

    Directory of Open Access Journals (Sweden)

    Oznur Cengiz

    2017-06-01

    Full Text Available Lois Lowry (1937- is a prolific author having a number of books – Number the Stars (1989, Gathering Blue (2000, and Messenger (2004 – and awards especially in the field of children’s literature. Her significant science fiction novel, The Giver (1993, presents a social panorama in order to thoroughly analyze the society’s mechanical life style. As an example of dystopia, the author delineates a systematically organized social order where people abide by the rules naturally. Nevertheless, Jonas, the protagonist and Receiver of Memory, is the first person to discern robotic/mechanical order in the society which is transformed into “sameness” eliminating all individual differences and emotions such as pain, happiness, cold, colors, and so on. Therefore, Receiver of Memory storing past memories of the society is the only one who is aware of human characteristics. The crucial point is that human figure, far from the current one, displays inhuman (non-human features without memories and hope. Mechanical association between individuals and social structure ascertains artificial form of life in which there is no chance to choose. After learning truths behind the strict order, Jonas is in pursuit of real world with all kinds of feelings; however, his recognition is not able to change the whole society. Hence, this paper aims at delving into the relationship between human nature and society with regard to posthuman approach and inhuman human form in accordance with transformation of human nature.

  12. DESCARTES’ COMPREHENSION OF HUMAN NATURE IN «DISCOURSE ON THE METHOD»

    Directory of Open Access Journals (Sweden)

    A. M. Malivskyi

    2014-12-01

    Full Text Available The purpose of the article is to analyze the text "Discourse on the Method" as one of the first experiences of understanding human’s nature in modern age philosophy. The condition of realization the designated purpose is to solve the following problems: 1 To Define the diversity of Descartes position on the issue of essentiality to the true knowledge of human nature; 2 To find out the manner influence of methodology of understanding the mathematical truth to the way of interpretation of human nature; 3 To clarify the question of Descartes awareness of boundaries rationalist methodology in understanding of human nature. Methodology. As the methodological base is proposed to use the heuristic potential of phenomenology and existentialism, as well as those publications of foreign Descartes’ researchers of recent times, which introduce the new way for understanding of Descartes’ philosophical heritage. Scientific novelty. For the first time ever in the scientific literature Descartes text "Discourse on Method" becomes the object of special attention as a form of deployment the substantial request for the development of the anthropological project. The affinity and heredity of philosophical doctrines of Aristotle and Descartes on the problem of human nature are accented that is the recognition of the key importance of the need for truth in human nature. It is argued that beyond Descartes’ vision there was no limitation of rationalistic methodology during the comprehension of human nature. Conclusions. The implemented analysis confirms the validity of the thesis about text of the "Discourse on Method" by Descartes as a request of substantial unfolding of the anthropological project. The determining influence methodology of comprehension the mathematical truths to the way of interpretation of human nature were shown. The fact of Descartes’ awareness the limitation of methodology of mathematics in the understanding of human nature and

  13. Climate Regulation Services of Natural and Managed Ecosystems of the Americas

    Science.gov (United States)

    Anderson-Teixeira, K. J.; Snyder, P. K.; Twine, T. E.; Costa, M. H.; Cuadra, S.; DeLucia, E. H.

    2011-12-01

    Terrestrial ecosystems regulate climate through both biogeochemical mechanisms (greenhouse gas regulation) and biophysical mechanisms (regulation of water and energy). Land management therefore provides some of the most effective strategies for climate change mitigation. However, most policies aimed at climate protection through land management, including UNFCCC mechanisms and bioenergy sustainability standards, account only for biogeochemical climate services. By ignoring biophysical climate regulation services that in some cases offset the biogeochemical regulation services, these policies run the risk of failing to advance the best climate solutions. Quantifying the combined value of biogeochemical and biophysical climate regulation services remains an important challenge. Here, we use a combination of data synthesis and modeling to quantify how biogeochemical and biophysical effects combine to shape the climate regulation value (CRV) of 18 natural and managed ecosystem types across the Western Hemisphere. Natural ecosystems generally had higher CRVs than agroecosystems, largely driven by differences in biogeochemical services. Biophysical contributions ranged from minimal to dominant. They were highly variable in space and across ecosystem types, and their relative importance varied strongly with the spatio-temporal scale of analysis. Our findings pertain to current efforts to protect climate through land management. Specifically, they reinforce the importance of protecting tropical forests and recent findings that the climatic effects of bioenergy production may be somewhat more positive than previously estimated. Given that biophysical effects in some cases dominate, ensuring effective climate protection through land management requires consideration of combined biogeochemical and biophysical climate regulation services. While quantification of ecosystem climate services is necessarily complex, our CRV index serves as one potential approach to measure the

  14. 78 FR 2229 - Health and Human Services Acquisition Regulation

    Science.gov (United States)

    2013-01-10

    ... information (regardless of the form or method of the recording) of a scientific or technical nature (including... (HHSAR)--to add two clauses, ``Patent Rights-- Exceptional Circumstances'' and ``Rights in Data....227-11 and 352.227-14'' by any of the following methods: Regulations.gov : http://www.regulations.gov...

  15. Maryland air toxics regulation applicable to a natural gas compressor station

    International Nuclear Information System (INIS)

    Weidemann, H.A.; Hoffman, P.M.

    1992-01-01

    Columbia Gas Transmission Corporation submitted an air permit application to the Maryland Department of the Environment to construct a natural gas compressor station near Rutledge, Maryland. The station consists of three natural gas-fueled internal combustion reciprocating engines, each rated at 3200 horsepower. Maximum potential pollutant emissions associated with the station operation did not trigger Prevention of Significant Deterioration review or nonattainment area New Source review. However, a minor source air permit cannot be issued without addressing Maryland's toxic air regulations. Columbia initiated a detailed investigation of toxic air pollutants, including a stack test of an identical engine. Based on this information, the proposed station was subject to the toxic air regulation for acetaldehyde, acrolein, benzene, crotonaldehyde, and formaldehyde. Compliance with the toxic air regulation for crotonaldehyde was demonstrated by having an emission rate less than the threshold emission rate, specified in the regulation. The ambient air quality impact of the other four pollutants was determined using the Industrial Source Complex dispersion model and resulted in predicted concentrations below the pollutant-specific acceptable ambient level. A carcinogenic impact analysis was performed for acetaldehyde, benzene, and formaldehyde to demonstrate compliance with the accepted risk of one in one hundred thousand

  16. Regulating corporate social and human rights responsibilities at the UN plane

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2009-01-01

    Globalisation's unprecedented growth and transborder activities of business coupled with increasing awareness of the impact of business on societies and human rights has resulted in demands for the international society to regulate corporate social and human rights responsibilities. This not only...... challenges traditional notions of duty bearers under international law, but also calls for novel approaches for the United Nations (UN) to implement central parts of the Charter's human rights aims and to address corporate behaviour in a state-centred international law-making order that lacks the willingness...... businesses' impact on human rights. The pattern of using these forms suggests an institutionalisation of reflexive regulation as a regulatory process drawing on public-private regulation, and of an emerging UN based 'Global Administrative Law' in order to meet regulatory challenges in living up to the human...

  17. Nature and Nurture of Human Pain

    Directory of Open Access Journals (Sweden)

    Inna Belfer

    2013-01-01

    Full Text Available Humans are very different when it comes to pain. Some get painful piercings and tattoos; others can not stand even a flu shot. Interindividual variability is one of the main characteristics of human pain on every level including the processing of nociceptive impulses at the periphery, modification of pain signal in the central nervous system, perception of pain, and response to analgesic strategies. As for many other complex behaviors, the sources of this variability come from both nurture (environment and nature (genes. Here, I will discuss how these factors contribute to human pain separately and via interplay and how epigenetic mechanisms add to the complexity of their effects.

  18. Human nature: neither material nor spiritually being

    Directory of Open Access Journals (Sweden)

    M. Alba Martínez Amorós

    2017-08-01

    Full Text Available The idea of «human nature» defended by Ortega y Gasset is as original as opposite to what is usually understood. We are making a mistake if the starting point is to conceive Man as one living being among others. Neither science nor philosophy, while remaining in the Eleatic tradition, can give a clear explanation. Science, because if we look at Man, as he is presented to us, it is impossible to distinguish in him materially from spiritually; his body and his psyche. Philosophy, because the concept of «human nature» is an invention of our reason, a fantasy. That nature doesn’t exist because the being of man is so strange and different from other beings that its consistency is just going to be what it never manages to be. Therefore, it is what happens, a journey, a history that is running within a circumstance. This is my life, and that of everyone.

  19. Human Dignity and the Ethics and Regulation of Technology

    NARCIS (Netherlands)

    Duwell, M.

    2017-01-01

    This chapter investigates how human dignity might be understood as a normative concept for the regulation of technologies. First, various distinctions that are relevant for the way human dignity can be understood are discussed. It is argued that it is particularly important that we should see human

  20. Criteria for radiological protection against exposure to natural radiation

    International Nuclear Information System (INIS)

    Cardenas Herrera, Juan

    2012-01-01

    Exposure of humans to natural sources of radiation has been a continuous and inevitable feature of life on earth. This exposure exceeds all due to artificial sources combined for most people. Many exposures to natural radiation sources are modified by human action. In particular, natural radionuclides are released into the environment in mineral processing and in activities such as the production of phosphate fertilizers and the use of fossil fuels. An increase of exposures to this natural radiation is caused. The relevance of exposure to natural radiation is confirmed by the fact that, for most people, the exposures to natural background radiation have been much more significant than exposures to artificial sources, with exceptions. Among these exceptions have been noted: medical exposures, accidents with release of radionuclides and some specific workplaces. In all cases, however, the natural background radiation has formed the basis on which all the others exposures are added and is a common level serving as compared to other exposures. Regulations and instructions have begun to establish in some countries to regulate natural radiation, countries like Spain, have already incorporated into its regulations on health protection against ionizing radiation the subject of natural radiation. (author) [es

  1. The natural radioactivity of plants, animals and humans. 3. enl. ed.

    International Nuclear Information System (INIS)

    Schewtschenko, I.N.; Danilenko, A.I.

    2007-01-01

    The natural radioactivity of plants, animals and humans are of important scientific relevance for radiobiology and medicine. The possible effects of micro doses during life span are still controversially discussed. Part I of the book (the natural radioactivity of plants, animals and humans for the normal case and in case of pathological changes) covers the following topics: the natural radioisotopes in living organisms (plants, animals, humans) and their environment; methodologies of qualitative and quantitative determination of beta-activity in biological objects; the radioactivity of atmospheric precipitations; the beta-activity of plants; the beta-activity of animals; beta-activity of human organs and tissues. Part II (dynamics of radionuclides in the biological chains in the period 1960 to 2007): the modern conceptions on the biological role of natural radioactive elements, biological indications during early stages of low-dose ionizing irradiation; the radioactivity of the human blood; radiation and carcerogenesis

  2. Deciphering flood frequency curves from a coupled human-nature system perspective

    Science.gov (United States)

    Li, H. Y.; Abeshu, G. W.; Wang, W.; Ye, S.; Guo, J.; Bloeschl, G.; Leung, L. R.

    2017-12-01

    Most previous studies and applications in deriving or applying FFC are underpinned by the stationarity assumption. To examine the theoretical robustness of this basic assumption, we analyzed the observed FFCs at hundreds of catchments in the contiguous United States along the gradients of climate conditions and human influences. The shape of FFCs is described using three similarity indices: mean annual floods (MAF), coefficient of variance (CV), and a seasonality index defined using circular statistics. The characteristics of catchments are quantified with a small number of dimensionless indices, including particularly: 1) the climatic aridity index, AI, which is a measure of the competition between energy and water availability; 2) reservoir impact index, defined as the total upstream reservoir storage capacity normalized by the annual streamflow volume. The linkages between these two sets of indices are then explored based on a combination of mathematical derivations of the Budyko formula, simple but physically based reservoir operation models, and other auxiliary data. It is found that the shape of FFCs shifts from arid to humid climate, and from periods with weak human influences to periods with strong influences. The seasonality of floods is found to be largely controlled by the synchronization between the seasonal cycles of precipitation and solar radiation in pristine catchments, but also by the reservoir regulation capacity in managed catchments. Our findings may help improve flood-risk assessment and mitigation in both natural and regulated river systems across various climate gradients.

  3. Regulating edible insects: the challenge of adressing food security, nature conservation, and the erosion of traditional food culture

    DEFF Research Database (Denmark)

    Halloran, Afton Marina Szasz; Vantomme, Paul; Hanboonsong, Y.

    2015-01-01

    Entomophagy is a common practice in many regions of the world but there are few examples of national regulations that govern insects for human consumption. Where entomophagy is not common, the current regulatory discourse focuses primarily on food safety and consumer protection. In countries where...... species, they do not appear explicitly in dietary guidelines. Although food safety is a major concern, it can undermine the importance of nature conservation, traditional food culture, food security, and potential economic development. Thus, entomophagy should be viewed holistically and development...

  4. Decorin gene expression and its regulation in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Velez-DelValle, Cristina; Marsch-Moreno, Meytha; Castro-Munozledo, Federico [Department of Cell Biology, Centro de Investigacion y de Estudios Avanzados del IPN, Apdo. Postal 14-740, Mexico D.F. 07000 (Mexico); Kuri-Harcuch, Walid, E-mail: walidkuri@gmail.com [Department of Cell Biology, Centro de Investigacion y de Estudios Avanzados del IPN, Apdo. Postal 14-740, Mexico D.F. 07000 (Mexico)

    2011-07-22

    Highlights: {yields} We showed that cultured human diploid epidermal keratinocytes express and synthesize decorin. {yields} Decorin is found intracytoplasmic in suprabasal cells of cultures and in human epidermis. {yields} Decorin mRNA expression in cHEK is regulated by pro-inflammatory and proliferative cytokines. {yields} Decorin immunostaining of psoriatic lesions showed a lower intensity and altered intracytoplasmic arrangements. -- Abstract: In various cell types, including cancer cells, decorin is involved in regulation of cell attachment, migration and proliferation. In skin, decorin is seen in dermis, but not in keratinocytes. We show that decorin gene (DCN) is expressed in the cultured keratinocytes, and the protein is found in the cytoplasm of differentiating keratinocytes and in suprabasal layers of human epidermis. RT-PCR experiments showed that DCN expression is regulated by pro-inflammatory and proliferative cytokines. Our data suggest that decorin should play a significant role in keratinocyte terminal differentiation, cutaneous homeostasis and dermatological diseases.

  5. The Debates in Marx's Scholarship on Dimensions of Human nature ...

    African Journals Online (AJOL)

    Debates in Marx scholarship revolve around whether Karl Marx recognizes the individual and social dimensions of human nature and which of the two he prefers. This paper considers the debates in two ways. The first relates to Marx scholarship in favour of the individual dimension of human nature. The second concerns ...

  6. Src-family kinases negatively regulate NFAT signaling in resting human T cells.

    Directory of Open Access Journals (Sweden)

    Alan Baer

    Full Text Available T cell signaling is required for activation of both natural and therapeutic T cells including chimeric antigen receptor (CAR T cells. Identification of novel factors and pathways regulating T cell signaling may aid in development of effective T cell therapies. In resting human T cells, the majority of Src-family of tyrosine kinases (SFKs are inactive due to phosphorylation of a conserved carboxy-terminal tyrosine residue. Recently, a pool of enzymatically active SFKs has been identified in resting T cells; however, the significance of these is incompletely understood. Here, we characterized the role of active SFKs in resting human T cells. Pharmacologic inhibition of active SFKs enhanced distal TCR signaling as measured by IL-2 release and CD25 surface expression following TCR-independent activation. Mechanistically, inhibition of the active pool of SFKs induced nuclear translocation of NFAT1, and enhanced NFAT1-dependent signaling in resting T cells. The negative regulation of NFAT1 signaling was in part mediated by the Src-kinase Lck as human T cells lacking Lck had increased levels of nuclear NFAT1 and demonstrated enhanced NFAT1-dependent gene expression. Inhibition of active SFKs in resting primary human T cells also increased nuclear NFAT1 and enhanced NFAT1-dependent signaling. Finally, the calcineurin inhibitor FK506 and Cyclosporin A reversed the effect of SFKs inhibition on NFAT1. Together, these data identified a novel role of SFKs in preventing aberrant NFAT1 activation in resting T cells, and suggest that maintaining this pool of active SFKs in therapeutic T cells may increase the efficacy of T cell therapies.

  7. From nature-dominated to human-dominated environmental changes

    Science.gov (United States)

    Messerli, Bruno; Grosjean, Martin; Hofer, Thomas; Núñez, Lautaro; Pfister, Christian

    2000-01-01

    To what extent is it realistic and useful to view human history as a sequence of changes from highly vulnerable societies of hunters and gatherers through periods with less vulnerable, well buffered and highly productive agrarian-urban societies to a world with regions of extreme overpopulation and overuse of life support systems, so that vulnerability to climatic-environmental changes and extreme events is again increasing? This question cannot be fully answered in our present state of knowledge, but at least we can try to illustrate, with three case studies from different continents, time periods and ecosystems, some fundamental changes in the relationship between natural processes and human activities that occur, as we pass from a nature-dominated to a human dominated environment. 1. Early-mid Holocene: Nature dominated environment — human adaptation, mitigation, and migration. In the central Andes, the Holocene climate changed from humid (10,800-8000 BP) to extreme arid (8000-3600 BP) conditions. Over the same period, prehistoric hunting communities adopted a more sedentary pattern of resource use by settling close to the few perennial water bodies, where they began the process of domesticating camelids around 5000 BP and irrigation from about 3100 BP. 2. Historical period: An agrarian society in transition from an "enduring" to an innovative human response. Detailed documentary evidence from Western Europe may be used to reconstruct quite precisely the impacts of climatic variations on agrarian societies. The period considered spans a major transition from an apparently passive response to the vagaries of the environment during the 16th century to an active and innovative attitude from the onset of the agrarian revolution in the late 18th century through to the present day. The associated changes in technology and in agricultural practices helped to create a society better able to survive the impact of climatic extremes. 3. The present day: A human dominated

  8. Why do humans behave as they do? Answers based on “human nature" and their critique

    Directory of Open Access Journals (Sweden)

    Ciro Flamarion Cardoso

    2012-12-01

    Full Text Available This article focus on one of the possible kinds of answers to the question: what can explain the behavior and the actions of human beings? Namely, it analyses the answers to this question that stress a determinant human nature, be it genetic, otherwise natural, or not clearly attributed to natural factors. Critiques and alternatives, supported by the paper’s author, are also examined.

  9. Position paper on the impact of including methane number in natural gas regulation

    International Nuclear Information System (INIS)

    2014-01-01

    GIIGNL has developed a position paper to describe methane number and the possible impact on the LNG market of a future regulation/specification for this parameter which is linked to natural gas quality. Currently, there are several standards describing calculation methods of natural gas methane number, but there are doubts about their reliability and the results differ from each other. No official regulation which states a minimum value for methane number of natural gas has been identified. A methane number of 80, as recommended by some organisations in Europe, would endanger the LNG supply to the market, limiting acceptable LNG sources, or would require expensive gas treatment. In the long term, if there is a market for high methane number natural gas, this may be an opportunity for LNG terminals able to adjust or manage supplies to the desired methane number

  10. Dormancy and activation of human oocytes from primordial and primary follicles: molecular clues to oocyte regulation

    DEFF Research Database (Denmark)

    Ernst, Emil Hagen; Grøndahl, Marie Louise; Grund, Simon

    2017-01-01

    ® software. Finally, qPCR and immunohistochemistry were employed to explore expression and localization of selected genes and products in human ovarian tissue. MAIN RESULTS AND THE ROLE OF CHANCE: We found 223 and 268 genes down-regulated and up-regulated, respectively, in the oocytes during the human...... SCALE DATA: http://users-birc.au.dk/biopv/published_data/ernst_2017/. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive analysis and no functional studies were performed. The study was based on a limited number of patients and the experimental design could not take into account the natural.......H. and S.F. were supported by an MRC (UK) project grant MR/M012638/1. K.L.H. was supported by grants from Fonden til Lægevidenskabens Fremme, Kong Christian Den Tiendes Fond. K.L.H. and L.S. were supported by the IDEAS grant from Aarhus University Research Foundation (AUFF). There are no conflicts...

  11. Human/Nature Discourse in Environmental Science Education Resources

    Science.gov (United States)

    Chambers, Joan M.

    2008-01-01

    It is argued that the view of nature and the relationship between human beings and nature that each of us holds impacts our decisions, actions, and notions of environmental responsibility and consciousness. In this study, I investigate the discursive patterns of selected environmental science classroom resources produced by three disparate…

  12. Air quality in natural areas: Interface between the public, science and regulation

    International Nuclear Information System (INIS)

    Percy, K.E.; Karnosky, D.F.

    2007-01-01

    Natural areas are important interfaces between air quality, the public, science and regulation. In the United States and Canada, national parks received over 315 million visits during 2004. Many natural areas have been experiencing decreased visibility, increased ozone (O 3 ) levels and elevated nitrogen deposition. Ozone is the most pervasive air pollutant in North American natural areas. There is an extensive scientific literature on O 3 exposure-tree response in chambered environments and, lately, free-air exposure systems. Yet, less is known about O 3 impacts on natural terrestrial ecosystems. To advance scientifically defensible O 3 risk assessment for natural forest areas, species-level measurement endpoints must be socially, economically and ecologically relevant. Exposure-based indices, based on appropriate final endpoints, present an underused opportunity to meet this need. Exposure-plant indices should have a high degree of statistical significance, have high goodness of fit, be biologically plausible and include confidence intervals to define uncertainty. They must be supported by exposure-response functions and be easy to use within an air quality regulation context. Ozone exposure-response indices developed within an ambient air context have great potential for improving risk assessment in natural forest areas and enhancing scientific literacy. - Appropriate endpoints and exposure-response indices can improve assessment of air pollutant risk to forests in natural areas

  13. Air quality in natural areas: Interface between the public, science and regulation

    Energy Technology Data Exchange (ETDEWEB)

    Percy, K.E. [Natural Resources Canada, Canadian Forest Service - Atlantic Forestry Centre, 1350 Regent Street, Fredericton, New Brunswick E3B 5P7 (Canada)], E-mail: kpercy@nrcan.gc.ca; Karnosky, D.F. [School of Forest Resources and Environmental Science, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931 (United States)

    2007-10-15

    Natural areas are important interfaces between air quality, the public, science and regulation. In the United States and Canada, national parks received over 315 million visits during 2004. Many natural areas have been experiencing decreased visibility, increased ozone (O{sub 3}) levels and elevated nitrogen deposition. Ozone is the most pervasive air pollutant in North American natural areas. There is an extensive scientific literature on O{sub 3} exposure-tree response in chambered environments and, lately, free-air exposure systems. Yet, less is known about O{sub 3} impacts on natural terrestrial ecosystems. To advance scientifically defensible O{sub 3} risk assessment for natural forest areas, species-level measurement endpoints must be socially, economically and ecologically relevant. Exposure-based indices, based on appropriate final endpoints, present an underused opportunity to meet this need. Exposure-plant indices should have a high degree of statistical significance, have high goodness of fit, be biologically plausible and include confidence intervals to define uncertainty. They must be supported by exposure-response functions and be easy to use within an air quality regulation context. Ozone exposure-response indices developed within an ambient air context have great potential for improving risk assessment in natural forest areas and enhancing scientific literacy. - Appropriate endpoints and exposure-response indices can improve assessment of air pollutant risk to forests in natural areas.

  14. Ontological And Anthropological Aspects of the Concept of Human Nature

    Directory of Open Access Journals (Sweden)

    R. Asha Nimali Fernando

    2011-12-01

    Full Text Available Anthropology is the study of the origin of the man. It is basically concern with the concept of Homo sapiens, and it is scientifically questioning what are human physical traits as well how do men behave and the variation among different groups of  human with his social and cultural dimensions. Ontology is a subfield in traditional philosophy which is mainly focuses on the nature of being, existence or reality as such. There are some similarities and differences among these two areas. However when we deeply study the philosophical basis of the anthropology it is proof that it was derived from ontology.Anthropology discusses the social and cultural world or the physical entity of human nature. Ontology focuses the invisible aspect of human nature along with the ultimate reality. Therefore, it has a metaphysical aspect of human being; this philosophical notion has in fact, contributed to the development of the subject of anthropology. The present modern day has given very little attention to this philosophical combination of  ontolog y to anthropology, rendering further investigation into the philosophical roots of anthropology.This research paper seeks to evaluate the relationship between ontology and anthropology by paying attention to the ontological arguments about the concept of man and human nature within Greek and modern western thoughts, in comparing with modern anthropological arguments.

  15. The Canadian Natural Health Products (NHP) regulations: industry compliance motivations.

    Science.gov (United States)

    Laeeque, Hina; Boon, Heather; Kachan, Natasha; Cohen, Jillian Clare; D'Cruz, Joseph

    2007-06-01

    This qualitative study explores corporations' motivations to comply with new natural health products (NHP) Regulations in Canada. Interviews were conducted with representatives from 20 Canadian NHP companies. Findings show that the rationale for compliance differs for large compared to small and medium-sized enterprises (SMEs). Large firms are motivated to comply with the regulations because of the deterrent fear of negative media coverage, social motivations, ability to comply and maintaining a competitive market advantage. In contrast, SMEs are motivated to comply due to the deterrent fear of legal prosecution and a sense of duty.

  16. Ecology and Ethics: Some Relationships for Nature Conservation

    Science.gov (United States)

    Abedi-Sarvestani, Ahmad; Shahvali, Mansoor

    These days, the reality of environmental crises creates grave doubts about the future of the natural environment. Many believe that if present human behavior toward the natural environment continues, there will be no hope for a sustainable life. Therefore, it is vital that human behavior toward nature be modified and corrected. Although, ethic is traditionally concerned about relations between individuals, but it is getting more attention for modifying human behavior in order to correct human-nature interaction and establish a well-intentioned one. In this respect, we need science of ecology and ethics together. Ecology helps us to understand natural ecosystems and respective regulations and laws, whereas ethics teach us how to define right and wrong behaviors toward the natural environment. This research discusses some possible relationships that might exist between ecology and ethics toward nature conservation.

  17. Rangeland Ecosystem Services: Nature's Supply and Humans' Demand

    Science.gov (United States)

    Ecosystem services are the benefits that society receives from nature and they include the regulation of climate, the pollination of crops, the provisioning of intellectual inspiration and recreational environment, as well as many essential goods such as food, fiber, and wood. Rangeland ecosystem se...

  18. Urgent Biophilia: Human-Nature Interactions and Biological Attractions in Disaster Resilience

    Directory of Open Access Journals (Sweden)

    Keith G. Tidball

    2012-06-01

    Full Text Available This contribution builds upon contemporary work on principles of biological attraction as well as earlier work on biophilia while synthesizing literatures on restorative environments, community-based ecological restoration, and both community and social-ecological disaster resilience. It suggests that when humans, faced with a disaster, as individuals and as communities and populations, seek engagement with nature to further their efforts to summon and demonstrate resilience in the face of a crisis, they exemplify an urgent biophilia. This urgent biophilia represents an important set of human-nature interactions in SES characterized by hazard, disaster, or vulnerability, often appearing in the 'backloop' of the adaptive cycle. The relationships that human-nature interactions have to other components within interdependent systems at many different scales may be one critical source of resilience in disaster and related contexts. In other words, the affinity we humans have for the rest of nature, the process of remembering that attraction, and the urge to express it through creation of restorative environments, which may also restore or increase ecological function, may confer resilience across multiple scales. In making this argument, the paper also represents a novel contribution to further theorizing alternatives to anthropocentric understandings of human-nature relations, and strongly makes the case for humans as part of, not separate from, ecosystems.

  19. Human-nature interactions and the consequences and drivers of provisioning wildlife.

    Science.gov (United States)

    Cox, Daniel T C; Gaston, Kevin J

    2018-05-05

    Many human populations are undergoing an extinction of experience, with a progressive decline in interactions with nature. This is a consequence both of a loss of opportunity for, and orientation towards, such experiences. The trend is of concern in part because interactions with nature can be good for human health and wellbeing. One potential means of redressing these losses is through the intentional provision of resources to increase wildlife populations in close proximity to people, thereby increasing the potential for positive human-nature experiences, and thence the array of benefits that can result. In this paper, we review the evidence that these resource subsidies have such a cascade of effects. In some Westernized countries, the scale of provision is extraordinarily high, and doubtless leads to both positive and negative impacts for wildlife. In turn, these impacts often lead to more frequent, reliable and closer human-nature interactions, with a greater variety of species. The consequences for human wellbeing remain poorly understood, although benefits documented in the context of human-nature interactions more broadly seem likely to apply. There are also some important feedback loops that need to be better characterized if resource provisioning is to contribute effectively towards averting the extinction of experience.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'. © 2018 The Authors.

  20. Human uniqueness on the brink of a new axial age: From separation to reintegration of humans and nature

    Directory of Open Access Journals (Sweden)

    Cornel W. du Toit

    2016-11-01

    Full Text Available Karl Jaspers’ Axial Age concept is used to depict the way humans interact with their environment. The first Axial Age (800-200 BC can be typified among others as the age in which humans started to objectify nature. Nature was dispossessed of spirits, gods and vital forces that humans previously feared and used as explanation for the origin of things. Secularised and objectified nature became a source of wealth for humans to use and abuse as they like. This has peaked in the post-industrial era which also introduced the Second Axial Age in which we presently live. The Second Axial Age can be typified by a new approach to nature mediated among others by insights from the side of the natural sciences, especially developments in cosmology, our understanding of the quantum world and new insights into the nature of consciousness. Another development in the Second Axial Age is the emergence of the nonhuman turn, new materialism, panpsychism, the notion of the post-human and theological concepts like the ‘entangled God’. These developments are discussed with reference to leading thinkers. The nonhuman turn is welcomed as it introduces respect for nature which may contribute to the survival of our planet.

  1. Regulation of AMP-activated protein kinase by natural and synthetic activators

    Directory of Open Access Journals (Sweden)

    David Grahame Hardie

    2016-01-01

    Full Text Available The AMP-activated protein kinase (AMPK is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells. While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner, during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level, by responding to hormones that act primarily on the hypothalamus. AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP, and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed. Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans, such as type 2 diabetes, cancer and inflammatory disorders, there has been a major drive to develop pharmacological activators of AMPK. Many such activators have been described, and the various mechanisms by which these activate AMPK will be discussed. A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines. While the mechanism by which most of these activate AMPK has not yet been addressed, I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores, and that many of them will turn out to be inhibitors of mitochondrial function.

  2. Relative significance of natural irradiation vs all human exposures

    International Nuclear Information System (INIS)

    Jammet, H.

    1985-01-01

    A review is made of the fundamentals allowing to quantitatively express the importance of the various sources of human exposure by an individual or collective approach. Following a summary of the components of normal exposure to natural sources, the various human actions at the origin of enhanced exposure are studied: 1) those modifying the relationship between natural sources and man (dwelling conditions, coal burning, geothermal energy production, exploitation of phosphate rock); 2) those creating new artificial sources (nuclear explosions in the atmosphere, nuclear power production, medical use of radiation and radionuclides). The effective dose equivalent commitments for these sources are compared with those necessarily involved by continuous normal exposure to the natural sources of exposure [fr

  3. Signaling hierarchy regulating human endothelial cell development

    Science.gov (United States)

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these stud...

  4. Biotinylation is a natural, albeit rare, modification of human histones

    Science.gov (United States)

    Kuroishi, Toshinobu; Rios-Avila, Luisa; Pestinger, Valerie; Wijeratne, Subhashinee S. K.; Zempleni, Janos

    2011-01-01

    Previous studies suggest that histones H3 and H4 are posttranslationally modified by binding of the vitamin biotin, catalyzed by holocarboxylase synthetase (HCS). Albeit a rare epigenetic mark, biotinylated histones were repeatedly shown to be enriched in repeat regions and repressed loci, participating in the maintenance of genome stability and gene regulation. Recently, a team of investigators failed to detect biotinylated histones and proposed that biotinylation is not a natural modification of histones, but rather an assay artifact. Here, we describe the results of experiments, including the comparison of various analytical protocols, antibodies, cell lines, classes of histones, and radiotracers. These studies provide unambiguous evidence that biotinylation is a natural, albeit rare, histone modification. Less than 0.001% of human histones H3 and H4 are biotinylated, raising concerns that the abundance might too low to elicit biological effects in vivo. We integrated information from this study, previous studies, and ongoing research efforts to present a new working model in which biological effects are caused by a role of HCS in multiprotein complexes in chromatin. In this model, docking of HCS in chromatin causes the occasional binding of biotin to histones as a tracer for HCS binding sites. PMID:21930408

  5. TECHNOLOGY VS NATURE: HUMAN ERROR IN DEALING WITH NATURE IN CRICHTON'S JURASSIC PARK

    Directory of Open Access Journals (Sweden)

    Sarah Prasasti

    2000-01-01

    Full Text Available Witnessing the euphoria of the era of biotechnology in the late twentieth century, Crichton exposes the theme of biotechnology in his works. In Jurassic Park, he voices his concern about the impact of the use of biotechnology to preserve nature and its living creatures. He further describes how the purpose of preserving nature and the creatures has turned out to be destructive. This article discusses Crichton's main character, Hammond, who attempts to control nature by genetically recreating the extinct fossil animals. It seems that the attempt ignores his human limitations. Although he is confident that has been equipped with the technology, he forgets to get along with nature. His way of using technology to accomplish his purpose proves not to be in harmony with nature. As a consequence, nature fights back. And he is conquered.

  6. Humans make efficient use of natural image statistics when performing spatial interpolation.

    Science.gov (United States)

    D'Antona, Anthony D; Perry, Jeffrey S; Geisler, Wilson S

    2013-12-16

    Visual systems learn through evolution and experience over the lifespan to exploit the statistical structure of natural images when performing visual tasks. Understanding which aspects of this statistical structure are incorporated into the human nervous system is a fundamental goal in vision science. To address this goal, we measured human ability to estimate the intensity of missing image pixels in natural images. Human estimation accuracy is compared with various simple heuristics (e.g., local mean) and with optimal observers that have nearly complete knowledge of the local statistical structure of natural images. Human estimates are more accurate than those of simple heuristics, and they match the performance of an optimal observer that knows the local statistical structure of relative intensities (contrasts). This optimal observer predicts the detailed pattern of human estimation errors and hence the results place strong constraints on the underlying neural mechanisms. However, humans do not reach the performance of an optimal observer that knows the local statistical structure of the absolute intensities, which reflect both local relative intensities and local mean intensity. As predicted from a statistical analysis of natural images, human estimation accuracy is negligibly improved by expanding the context from a local patch to the whole image. Our results demonstrate that the human visual system exploits efficiently the statistical structure of natural images.

  7. Functional Dynamics within the Human Ribosome Regulate the Rate of Active Protein Synthesis.

    Science.gov (United States)

    Ferguson, Angelica; Wang, Leyi; Altman, Roger B; Terry, Daniel S; Juette, Manuel F; Burnett, Benjamin J; Alejo, Jose L; Dass, Randall A; Parks, Matthew M; Vincent, C Theresa; Blanchard, Scott C

    2015-11-05

    The regulation of protein synthesis contributes to gene expression in both normal physiology and disease, yet kinetic investigations of the human translation mechanism are currently lacking. Using single-molecule fluorescence imaging methods, we have quantified the nature and timing of structural processes in human ribosomes during single-turnover and processive translation reactions. These measurements reveal that functional complexes exhibit dynamic behaviors and thermodynamic stabilities distinct from those observed for bacterial systems. Structurally defined sub-states of pre- and post-translocation complexes were sensitive to specific inhibitors of the eukaryotic ribosome, demonstrating the utility of this platform to probe drug mechanism. The application of three-color single-molecule fluorescence resonance energy transfer (smFRET) methods further revealed a long-distance allosteric coupling between distal tRNA binding sites within ribosomes bearing three tRNAs, which contributed to the rate of processive translation. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Human Nature and the Social Order | Opafola | Annals of ...

    African Journals Online (AJOL)

    This paper takes cognizance of the fact that the ideas of human beings or human persons and a social order are mutually re-in forcing or mutually inclusive. It argues that a stable, peaceful, and progressive social order will be promoted to some extent if the differences in the elements of human nature are acknowledged and ...

  9. Natural resources, redistribution and Human capital formation

    OpenAIRE

    Aguero, Jorge; Balcazar, Carlos Felipe; Maldonado, Stanislao; Ñopo, Hugo

    2016-01-01

    How do resource booms affect human capital accumulation? We exploit time and spatial variation generated by the commodity boom across local governments in Peru to measure the effect of natural resources on human capital formation. We explore the effect of both mining production and tax revenues on test scores, finding a substantial and statistically significant effect for the latter. Transfers to local governments from mining tax revenues are linked to an increase in math test scores of aroun...

  10. Distancing Students From Nature: Science Camp and the Representation of the Human-Nature Relationship

    Science.gov (United States)

    Terrill, Laura Anne

    This study investigated the curricular representations of the environment and the human-environment relationship at one residential school sponsored science camp. Data gathered included field notes from observational time at the camp, interviews with staff and classroom teachers, and documents from the site's website, guides, manuals, and curricular guides. These data were analyzed to understand how the camp represented the human-environment relationship and the "proper" human-environment relationship to its participants. Analysis indicated that the camp's official and enacted curriculum was shaped in response to two perceived problems, (1) students were perceived as having a disconnected relationship with the outdoors and lacking in outdoor experiences; and (2) staff members of the camp believed that time for science during the school day had diminished and that students were not receiving adequate science instruction at school. In response, the goal of the camp was to connect students to the outdoors through hands-on, sensory, experience based science and outdoor education experiences. However, key aspects of the camp experience and the formal and enacted curriculum unintentionally positioned students as separate from nature. The camp experience presented a vacation like understanding of the human-environment relationship as students became tourists of the outdoors. Despite the site's goal of connecting students to the outdoors, the science camp experience worked to distance students from the outdoors by unintentionally representing the outdoors as a place that existed away from home and students' everyday lives. Notably, nature became a place that existed in the past, separate from modernity. Students were tourists in an exotic location - nature. They received tours of the foreign outdoors, had fun, and returned home to their ordinary lives that were separate and distinct from the natural world.

  11. From Environmental Connectedness to Sustainable Futures: Topophilia and Human Affiliation with Nature

    Directory of Open Access Journals (Sweden)

    Thomas Beery

    2015-07-01

    Full Text Available Human affiliation with nonhuman nature is an important dimension of environmental concern and support for pro-environmental attitudes. A significant theory of human connectedness with nature, the Biophilia Hypothesis, suggests that there exists a genetically based inclination for human affiliation with the biological world. Both support and challenge to the Biophilia Hypothesis are abundant in the literature of environmental psychology. One response that both challenges and builds upon the Biophilia Hypothesis is the Topophilia Hypothesis. The Topophilia Hypothesis has extended the ideas of biophilia to incorporate a broader conception of nonhuman nature and a co-evolutionary theory of genetic response and cultural learning. While the Topophilia Hypothesis is a new idea, it is built upon long-standing scholarship from humanistic geography and theories in human evolution. The Topophilia Hypothesis expands previous theory and provides a multidisciplinary consideration of how biological selection and cultural learning may have interacted during human evolution to promote adaptive mechanisms for human affiliation with nonhuman nature via specific place attachment. Support for this possible co-evolutionary foundation for place-based human affiliation with nonhuman nature is explored from multiple vantage points. We raise the question of whether this affiliation may have implications for multifunctional landscape management. Ultimately, we propose that nurturing potential topophilic tendencies may be a useful method to promote sustainable efforts at the local level with implications for the global.

  12. CONSIDERATIONS REGARDING THE INTEGRATION OF FUNDAMENTAL HUMAN RIGHTS IN THE SYSTEM OF NATURAL LAW

    OpenAIRE

    Claudiu Ramon D. Butculescu

    2016-01-01

    This article studies the relationships and interactions between fundamental human rights and natural law school. The objectives of this paper are circumscribed to the way fundamental human rights, by their nature, can be integrated within the doctrine of natural law or to the contrary, may be related to various branches of legal positivism. In specialized literature, it was pointed out that fundamental human rights constitute genuine natural rights which have the same natural law ...

  13. Expression, processing and transcriptional regulation of granulysin in short-term activated human lymphocytes

    Directory of Open Access Journals (Sweden)

    Groscurth Peter

    2007-06-01

    Full Text Available Abstract Background Granulysin, a cytotoxic protein expressed in human natural killer cells and activated T lymphocytes, exhibits cytolytic activity against a variety of intracellular microbes. Expression and transcription have been partially characterised in vitro and four transcripts (NKG5, 519, 520, and 522 were identified. However, only a single protein product of 15 kDa was found, which is subsequently processed to an active 9 kDa protein. Results In this study we investigated generation of granulysin in lymphokine activated killer (LAK cells and antigen (Listeria specific T-cells. Semiquantitative RT-PCR revealed NKG5 to be the most prominent transcript. It was found to be up-regulated in a time-dependent manner in LAK cells and antigen specific T-cells and their subsets. Two isoforms of 519 mRNA were up-regulated under IL-2 and antigen stimulation. Moreover, two novel transcripts, without any known function, comprising solely parts of the 5 prime region of the primary transcript, were detected. A significant increase of granulysin expressing LAK cells as well as antigen specific T-cells was shown by fluorescence microscopy. On the subset level, increase in CD4+ granulysin expressing cells was found only under antigen stimulation. Immunoblotting showed the 15 kDa form of granulysin to be present in the first week of stimulation either with IL-2 or with bacterial antigen. Substantial processing to the 9 kDa form was detected during the first week in LAK cells and in the second week in antigen specific T-cells. Conclusion This first comprehensive study of granulysin gene regulation in primary cultured human lymphocytes shows that the regulation of granulysin synthesis in response to IL-2 or bacterial antigen stimulation occurs at several levels: RNA expression, extensive alternative splicing and posttranslational processing.

  14. Regulation of the skeletal muscle blood flow in humans

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Saltin, Bengt

    2014-01-01

    In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators including nitric oxide (NO) and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and very importantly can offset local...... concentration does not increase during exercise. In the skeletal muscle interstitium, there is a marked increase in the concentration of ATP and adenosine and this increase is tightly coupled to the increase in blood flow. The sources of interstitial ATP and adenosine are thought to be skeletal muscle cells...... hyperaemia whereas the role of ATP remains uncertain due to lack of specific purinergic receptor blockers for human use. The purpose of this review is to address the interaction between vasodilator systems and to discuss the multiple proposed roles of ATP in human skeletal muscle blood flow regulation...

  15. Food and Natural Materials Target Mechanisms to Effectively Regulate Allergic Responses.

    Science.gov (United States)

    Shin, Hee Soon; Shon, Dong-Hwa

    2015-01-01

    An immune hypersensitivity disorder called allergy is caused by diverse allergens entering the body via skin contact, injection, ingestion, and/or inhalation. These allergic responses may develop into allergic disorders, including inflammations such as atopic dermatitis, asthma, anaphylaxis, food allergies, and allergic rhinitis. Several drugs have been developed to treat these allergic disorders; however, long-term intake of these drugs could have adverse effects. As an alternative to these medicines, food and natural materials that ameliorate allergic disorder symptoms without producing any side effects can be consumed. Food and natural materials can effectively regulate successive allergic responses in an allergic chain-reaction mechanism in the following ways: [1] Inhibition of allergen permeation via paracellular diffusion into epithelial cells, [2] suppression of type 2 T-helper (Th) cell-related cytokine production by regulating Th1/Th2 balance, [3] inhibition of pathogenic effector CD4(+) T cell differentiation by inducing regulatory T cells (Treg), and [4] inhibition of degranulation in mast cells. The immunomodulatory effects of food and natural materials on each target mechanism were scientifically verified and shown to alleviate allergic disorder symptoms. Furthermore, consumption of certain food and natural materials such as fenugreek, skullcap, chitin/chitosan, and cheonggukjang as anti-allergics have merits such as safety (no adverse side effects), multiple suppressive effects (as a mixture would contain various components that are active against allergic responses), and ease of consumption when required. These merits and anti-allergic properties of food and natural materials help control various allergic disorders.

  16. Sympathetic regulation of cerebral blood flow in humans : a review

    NARCIS (Netherlands)

    ter Laan, M.; van Dijk, J. M. C.; Elting, J. W. J.; Staal, M. J.; Absalom, A. R.

    Cerebral blood flow (CBF) is regulated by vasomotor, chemical, metabolic, and neurogenic mechanisms. Even though the innervation of cerebral arteries is quite extensively described and reviewed in the literature, its role in regulation of CBF in humans remains controversial. We believe that

  17. Natural goodness and the political form of human life

    Directory of Open Access Journals (Sweden)

    Müller Jan

    2015-01-01

    Full Text Available Ethical Naturalism attempts to explain the objective normativity effective in human practices by reference to the relation between a living individual and the life-form it exhibits. This explanation falls short in the case of human beings (1 - not merely because of their essential rationality, but because the idea of normativity implicit in practice is dependent on the form of normativity’s being made explicit (2. I argue that this explicit form of normativity’s force and claim - the law in general - implies a tension between an explicit norm’s claim to absoluteness and the particularity of the situational case it is applied to. This tension may seem to produce an inherent violence corrupting the very idea of objective normativity inherent in the human form of life (3; in fact, it shows that the human form of life is essentially political. That the human form of life is essentially political does not contradict the idea of objective normativity - provided that this objectivity is not derived from a conception of “natural goodness”, but rather from the actuality of human practice and its principle, justice (4.

  18. VOLTAIRE’S PHILOSOPHY: HUMAN NATURE AND INTERPRETATION OF RELIGION

    Directory of Open Access Journals (Sweden)

    Yu. Zimaryova

    2013-12-01

    Full Text Available The purpose of the article is to determine and reconsider Voltaire’s ideas concerning religion and human nature. In order to achieve this purpose it is necessary to complete the following tasks: to analyse academic literature on Voltaire’s interpretation of the phenomenon of religion; to expose Voltaire’s basic ideas about human nature; to substantiate the importance of anthropological approach to the phenomenon of religion with the ideas of Voltaire’s philosophical works. Methodology. The achievements of anthropocentric philosophical thought of the XIX century possess great potential in the process of constructive comprehension and theoretical reconstruction of the anthropological intention that accompanies the process of philosophising. The research extensively applies hermeneutical method for interpreting Voltaire’s philosophy. Scientific novelty. In academic literature on Voltaire’s works we have ascertained the basic anthropological component of his philosophy and reconsider Voltaire’s ideas about religion as something that is rooted in human nature. Conclusions. In academic literature the interpretation of the phenomenon of religion in Voltaire’s heritage is a rather controversial one. At the one hand, Voltaire criticizes religion for its superstitions and fanaticism. On the other hand, he recognises the existence of God. In our opinion, the phenomenon of religion should be examined in the context of human nature and basic problems related to it such as the problem of soul and the problem of free will. The anthropological approach to the phenomenon of religion allows to avoid the extremity of atheistic and metaphysical approaches and to enable its anthropological interpretation.

  19. Identification of a natural human serotype 3 parainfluenza virus

    Directory of Open Access Journals (Sweden)

    Wang Xiao-Jing

    2011-02-01

    Full Text Available Abstract Parainfluenza virus is an important pathogen threatening the health of animals and human, which brings human many kinds of disease, especially lower respiratory tract infection involving infants and young children. In order to control the virus, it is necessary to fully understand the molecular basis resulting in the genetic diversity of the virus. Homologous recombination is one of mechanisms for the rapid change of genetic diversity. However, as a negative-strand virus, it is unknown whether the recombination can naturally take place in human PIV. In this study, we isolated and identified a mosaic serotype 3 human PIV (HPIV3 from in China, and also provided several putative PIV mosaics from previous reports to reveal that the recombination can naturally occur in the virus. In addition, two swine PIV3 isolates transferred from cattle to pigs were found to have mosaic genomes. These results suggest that homologous recombination can promote the genetic diversity and potentially bring some novel biologic characteristics of HPIV.

  20. The Human-Nature Relationship and Its Impact on Health: A Critical Review.

    Science.gov (United States)

    Seymour, Valentine

    2016-01-01

    Within the past four decades, research has been increasingly drawn toward understanding whether there is a link between the changing human-nature relationship and its impact on people's health. However, to examine whether there is a link requires research of its breadth and underlying mechanisms from an interdisciplinary approach. This article begins by reviewing the debates concerning the human-nature relationship, which are then critiqued and redefined from an interdisciplinary perspective. The concept and chronological history of "health" is then explored, based on the World Health Organization's definition. Combining these concepts, the human-nature relationship and its impact on human's health are then explored through a developing conceptual model. It is argued that using an interdisciplinary perspective can facilitate a deeper understanding of the complexities involved for attaining optimal health at the human-environmental interface.

  1. Investing in the electricity and natural gas grids. Movements in the regulation framework

    International Nuclear Information System (INIS)

    Van Eeuwen, M.

    2011-01-01

    In this article, an overview is given of the regulation framework for investing in the electricity and natural gas grids. The overview describes which options regulations and regulation practice offer to grid operators for recovering the cost of investing in grids. Attention is paid to possible discrepancies between the European and the Dutch regulation framework. The article illustrates that grid operators currently lack any clarity and hence certainty about the options for recovering their investment costs. At the same time the fact that investments are needed to secure quality and capacity is not under debate. [nl

  2. let-7 miRNAs Can Act through Notch to Regulate Human Gliogenesis

    Directory of Open Access Journals (Sweden)

    M. Patterson

    2014-11-01

    Full Text Available It is clear that neural differentiation from human pluripotent stem cells generates cells that are developmentally immature. Here, we show that the let-7 plays a functional role in the developmental decision making of human neural progenitors, controlling whether these cells make neurons or glia. Through gain- and loss-of-function studies on both tissue and pluripotent derived cells, our data show that let-7 specifically regulates decision making in this context by regulation of a key chromatin-associated protein, HMGA2. Furthermore, we provide evidence that the let-7/HMGA2 circuit acts on HES5, a NOTCH effector and well-established node that regulates fate decisions in the nervous system. These data link the let-7 circuit to NOTCH signaling and suggest that this interaction serves to regulate human developmental progression.

  3. Regulation of naturally occurring and accelerator-produced radioactive materials: an update

    International Nuclear Information System (INIS)

    Bolling, L.A.; Lubenau, J.O.; Nussbaumer, D.A.

    1984-10-01

    In 1977, NRC published a report (NUREG-0301) of a task force review of the need for, and feasibility of, the Federal government regulating naturally occurring and accelerator-produced radioactive materials (NARM). Since that time, the Federal regulatory role has not significantly changed but State calls for increased Federal involvment have continued. In 1983, a National Governors' Association report on the NRC Agreement State program recommended amendment of the Atomic Energy Act to authorize NRC regulation of these materials. Based on that recommendation, and with the cooperation of the Conference of Radiation Control Program Directors, Inc., NRC staff undertook a review of the current status of use and regulation of NARM. This report contains the results of that review. 10 references

  4. New pre-heating system for natural gas pressure regulating stations

    International Nuclear Information System (INIS)

    Zullo, G.; Vertuani, C.; Borghesani, O.; Vignoli, F.

    1999-01-01

    Costs for running natural gas pressure regulating stations are mainly due to operation and maintenance of a natural gas preheating system, usually equipment with a hot water boiler or an armour-plated electric resistance immersed in a fluid. The article describe a system, considering a natural circulation boiler which uses steam/condensate (at 100 degrees C and 0,5 bar) as a thermal conductor, in thermodynamic balance and in absence of un condensable. This new boiler, already operating with satisfactory results in heating system for industrial buildings, does not require testing, notifications, periodical inspections by the competent authorities, constant monitoring by trained or patented staff. Besides, it allows easier installations procedures and running cost savings. The system, to be considered as static because it has no moving parts, is a good alternative to conventional forced hot water circulation or electric heating system [it

  5. Human Nature in the Adaptation of Trust

    NARCIS (Netherlands)

    Nooteboom, B.

    2006-01-01

    This chapter pleads for more inspiration from human nature, in agent-based modeling.As an illustration of an effort in that direction, it summarizes and discusses an agentbased model of the build-up and adaptation of trust between multiple producers and suppliers.The central question is whether, and

  6. The worth of land use: a GIS-emergy evaluation of natural and human-made capital.

    Science.gov (United States)

    Mellino, Salvatore; Buonocore, Elvira; Ulgiati, Sergio

    2015-02-15

    Natural systems make their natural capital and ecosystem services available to human economy. A careful analysis of the interplay between natural and human-made capital is needed to prevent natural capital being overexploited for present economic benefits, affecting lifestyles and wellbeing of future generations. In this study, the emergy synthesis is used to evaluate the natural and the human-made capital of Campania region (southern Italy) by accounting for the environmental support directly and indirectly provided by nature to resource generation. Furthermore, geographic information system (GIS) models are integrated with the emergy accounting procedure to generate maps of the spatial patterns of both natural and human-made capital distribution. Regional storages of natural and human-made capital are identified and evaluated in emergy units (seJ). The human-made capital of the Campania region (6.29E+24seJ) results to be about 11 times higher than the natural capital (5.69E+23seJ) due to the past and present exploitation of the natural resources needed to generate it over time. Moreover, by overlaying the total natural capital map and the total human-made capital map with a map of the protected areas within the region, only the 19% of the regional natural capital appears to be concentrated within protected areas, while most of it (81%) is concentrated outside. These findings suggest that the conservation of natural resources is also necessary outside protected areas by means of suitable policies, directives and investments. The human-made capital is mainly concentrated (88%) inside non-protected areas and interacts with the local natural capital. A management of the interactions between the two categories of wealth is crucial to prevent that the growth of human-made storages degrades the natural ecosystems and the environment. The proposed emergy-GIS framework reveals to be a useful tool for environmental planning and resource management aimed to conserve and

  7. Linking human and natural systems in the planning process

    Science.gov (United States)

    Susan I. Stewart; Miranda H. Mockrin; Roger B. Hammer

    2012-01-01

    Planning links human and natural systems in the urban-rural interface by engaging people in consideration of the future of natural resources. We review evolving ideas about what planning entails, who it involves, and what its outcomes should be. Sense of place, collaboration, emergent planning, and other new developments in planning are discussed. Smaller plans,...

  8. The Natural Antimicrobial Enzyme Lysozyme is Up-Regulated in Gastrointestinal Inflammatory Conditions

    Directory of Open Access Journals (Sweden)

    Carlos A. Rubio

    2014-01-01

    Full Text Available The cells that line the mucosa of the human gastrointestinal tract (GI, that is, oral cavity, oesophagus, stomach, small intestine, large intestine, and rectum are constantly challenged by adverse micro-environmental factors, such as different pH, enzymes, and bacterial flora. With exception of the oral cavity, these microenvironments also contain remnant cocktails of secreted enzymes and bacteria from upper organs along the tract. The density of the GI bacteria varies, from 103/mL near the gastric outlet, to 1010/mL at the ileocecal valve, to 1011 to 1012/mL in the colon. The total microbial population (ca. 1014 exceeds the total number of cells in the tract. It is, therefore, remarkable that despite the prima facie inauspicious mixture of harmful secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To counteract the hostile microenvironment, the GI epithelia react by speeding cell exfoliation (the GI mucosa has a turnover time of two to three days, by increasing peristalsis, by eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial compounds, such as defensin-5 and lysozyme. Only recently, lysozyme was found up-regulated in Barrett’s oesophagitis, chronic gastritis, gluten-induced atrophic duodenitis (coeliac disease, collagenous colitis, lymphocytic colitis, and Crohn’s colitis. This up-regulation is a response directed to the special types of bacteria recently detected in these diseases. The aim of lysozyme up-regulation is to protect individual mucosal segments to chronic inflammation. The molecular mechanisms connected to the crosstalk between the intraluminal bacterial flora and the production of lysozyme released by the GI mucosae, are discussed. Bacterial resistance continues to exhaust our supply of commercial antibiotics. The potential use of lysozyme to treat infectious diseases is receiving much attention.

  9. An Alternative to Liquid Human Nature at the Crossroads of the Technological Era

    Directory of Open Access Journals (Sweden)

    José Antonio Santos Arnaiz

    2017-08-01

    Full Text Available This paper discusses the idea of an ethic of weakness, expressing distrust about the rise of exacerbated capitalist individualism that drives a technological perfectionism. The extended modernity, as uncompleted project, provides context around the strong separation between humanity and nature. Both concepts posts in relation to perfectionism of the human beings eventually devalue and even deny a more or less permanent human nature. It therefore urges return to a concept of human nature understood as the development program of a free human being, which includes a number of common elements due to genotypic and phenotypic traits, while an ontological concept of human dignity that stems from political equity of all human beings. Historical time must be rethought to make ethical, medical and legal decisions in technology with prudence and responsibility, considering that unfortunately processes undertaken are irreversible.

  10. Natural Regulation of Energy Flow in a Green Quantum Photocell

    OpenAIRE

    Arp, Trevor B.; Barlas, Yafis; Aji, Vivek; Gabor, Nathaniel M.

    2015-01-01

    Manipulating the flow of energy in nanoscale and molecular photonic devices is of both fundamental interest and central importance for applications in light harvesting optoelectronics. Under erratic solar irradiance conditions, unregulated power fluctuations in a light harvesting photocell lead to inefficient energy storage in conventional solar cells and potentially fatal oxidative damage in photosynthesis. Here, we show that regulation against these fluctuations arises naturally within a tw...

  11. Limitations on the concentration of radioactive elements substances (natural or enhanced by human activity) in building materials - a proposal for draft Israeli regulations

    International Nuclear Information System (INIS)

    Schlesinger, T.; Hareuveny, R.; Margaliot, M.

    1997-01-01

    Natural radioactive elements 40 K 228 U and 232 Th and their decay product such as 226 Ra and its short lived daughters occur in building materials in relatively high concentrations. 40 K and part of the above mentioned radionuclides cause external exposure while the inhalation of 222 Ra and its short lived progeny lead to internal exposure of the respiratory tract to alpha particles. In recent years there is a growing tendency to use new construction materials with naturally or technologically enhanced levels of radioactivity (e.g. phosphogypsum, fly ash, exotic minerals etc). This trend causes a growing health concern.The result of this concern is legislation activity and publication of guidance notes by national authorities and international professional organizations related to the radiological implications of these novel technologies. The Ministry of the Environment in Israel is authorized by Israeli legislation to control the exposure of the public to ionising radiation. The ministry asked in 1996 a professional group in the Radiation Protection Division in the Soreq NRC (the authors of this presentation) to study the radiological implications of the use of building materials with naturally or technologically enhanced concentrations of radioactive substances, and to submit draft regulations setting primary limits on excess exposure of the public to ionizing radiation from building materials, and derived limits related to concentrations of specific radionuclides in these materials.The draft regulations will be presented and the way of their derivation will be reviewed (authors)

  12. Record of proceedings: Conference on state regulation and the market potential for natural gas: Challenges and opportunities

    International Nuclear Information System (INIS)

    1992-01-01

    This conference was convened by the US Department of Energy and the National Association of Regulatory Utility Commissioners to provide a forum for state and federal policymakers, sate and federal regulators, and all segments of the natural gas industry to address issues of significance to the current and future use of natural gas, with particular emphasis on sate regulation. The conference brought together a cross-section of interested parties to begin the process of identifying the barriers to natural gas achieving its market potential and developing better communication between Federal officials, State officials and different segments of the natural gas and electric industries

  13. Stealth and Natural Disasters: Science, Policy and Human Behavior

    Science.gov (United States)

    Kieffer, S. W.

    2008-12-01

    Geophysicists, earth scientists, and other natural scientists play a key role in studying disasters, and are challenged to convey the science to the public and policy makers (including government and business). I have found it useful to introduce the concept of two general types of disasters to these audiences: natural and stealth. Natural disasters are geological phenomena over which we humans have some, but relatively little, control. Earthquakes, tsunamis, floods and volcanic eruptions are the most familiar examples, but exogenous events such as meteorite impacts, solar flares, and supernovae are also possibly disruptive. Natural disasters typically have an abrupt onset, cause immediate major change, are familiar from the historic record, and get much media and public attention. They cannot be prevented, but preplanning can ameliorate their effects. Natural disasters are increasingly amplified by us (humans), and we are increasingly affected by them due to our expanding presence on the planet. Less familiar disasters are unfolding in the near-term, but they are not happening in the minds of most people. They are approaching us stealthily, and for this reason I propose that we call them stealth disasters. They differ from natural disasters in several important ways: stealth disasters are primarily caused by, or driven by, the interaction of humans with complex cycles of processes on the planet. Examples are: fresh water shortages and contamination, soil degradation and loss, climate changes, ocean degradation. The onset of stealth disasters is incremental rather than abrupt. They may not unfold significantly during the course of one term of political office, but they are unfolding in our lifetime. We as individuals may or may not escape their consequences, but they will affect our children and grandchildren. If humans are familiar with stealth disasters at all, it is from a relatively local experience, e.g., flooding of the Mississippi or the Dust Bowl in the U

  14. Diverse Regulators of Human Ribosome Biogenesis Discovered by Changes in Nucleolar Number

    Directory of Open Access Journals (Sweden)

    Katherine I. Farley-Barnes

    2018-02-01

    Full Text Available Ribosome biogenesis is a highly regulated, essential cellular process. Although studies in yeast have established some of the biological principles of ribosome biogenesis, many of the intricacies of its regulation in higher eukaryotes remain unknown. To understand how ribosome biogenesis is globally integrated in human cells, we conducted a genome-wide siRNA screen for regulators of nucleolar number. We found 139 proteins whose depletion changed the number of nucleoli per nucleus from 2–3 to only 1 in human MCF10A cells. Follow-up analyses on 20 hits found many (90% to be essential for the nucleolar functions of rDNA transcription (7, pre-ribosomal RNA (pre-rRNA processing (16, and/or global protein synthesis (14. This genome-wide analysis exploits the relationship between nucleolar number and function to discover diverse cellular pathways that regulate the making of ribosomes and paves the way for further exploration of the links between ribosome biogenesis and human disease.

  15. Natural asynchronies in audiovisual communication signals regulate neuronal multisensory interactions in voice-sensitive cortex.

    Science.gov (United States)

    Perrodin, Catherine; Kayser, Christoph; Logothetis, Nikos K; Petkov, Christopher I

    2015-01-06

    When social animals communicate, the onset of informative content in one modality varies considerably relative to the other, such as when visual orofacial movements precede a vocalization. These naturally occurring asynchronies do not disrupt intelligibility or perceptual coherence. However, they occur on time scales where they likely affect integrative neuronal activity in ways that have remained unclear, especially for hierarchically downstream regions in which neurons exhibit temporally imprecise but highly selective responses to communication signals. To address this, we exploited naturally occurring face- and voice-onset asynchronies in primate vocalizations. Using these as stimuli we recorded cortical oscillations and neuronal spiking responses from functional MRI (fMRI)-localized voice-sensitive cortex in the anterior temporal lobe of macaques. We show that the onset of the visual face stimulus resets the phase of low-frequency oscillations, and that the face-voice asynchrony affects the prominence of two key types of neuronal multisensory responses: enhancement or suppression. Our findings show a three-way association between temporal delays in audiovisual communication signals, phase-resetting of ongoing oscillations, and the sign of multisensory responses. The results reveal how natural onset asynchronies in cross-sensory inputs regulate network oscillations and neuronal excitability in the voice-sensitive cortex of macaques, a suggested animal model for human voice areas. These findings also advance predictions on the impact of multisensory input on neuronal processes in face areas and other brain regions.

  16. Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

    International Nuclear Information System (INIS)

    Tachibana, Keisuke; Takeuchi, Kentaro; Inada, Hirohiko; Yamasaki, Daisuke; Ishimoto, Kenji; Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko; Doi, Takefumi

    2009-01-01

    Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial β-oxidation. The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor that plays an important role in the regulation of β-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPARα and found that PPARα induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPARα regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

  17. From Human Nature to Moral Judgments : Reframing Debates about Disability and Enhancement

    NARCIS (Netherlands)

    Harnacke, C.E.

    2015-01-01

    My goal in my dissertation is to develop an account of how a theory of human nature should be integrated into bioethics and to show what bioethics can gain from using this account. I explore the relevance of human nature for moral argumentation, and especially for bioethics. Thereby, I focus on

  18. Regulating private human suborbital flight at the international and European level: Tendencies and suggestions

    Science.gov (United States)

    Masson-Zwaan, Tanja; Moro-Aguilar, Rafael

    2013-12-01

    In the context of the FAST20XX project (Future High-Altitude High-Speed Transport) that started in 2009 under the 7th Framework Programme of the European Union (EU), the authors reexamined the legal status of private human suborbital flight, and researched whether it might be regulated as aviation or as spaceflight. International space law is ambiguous as to accommodating suborbital activities. While some provisions of the UN outer space treaties would seem to exclude them, generally there is not any explicit condition in terms of reaching orbit as a requirement for application. International air law presents equal difficulties in dealing with this activity. The classic definition of "aircraft" as contained in the Annexes to the Chicago Convention does not really encompass the kind of rocket-powered vehicles that are envisaged here. As a result, it is unclear whether the United Nations Committee on the Peaceful Uses of Outer Space (COPUOS), the International Civil Aviation Organization (ICAO), or both could be involved in an eventual international regulation of suborbital flight. In the absence of a uniform international regime, each state has the sovereign right to regulate human suborbital flights operating within its airspace. So far, two practical solutions have been realised or proposed, and will be analyzed. On the one hand, the USA granted power for regulation and licensing over private human suborbital flight to the Office of Commercial Space Transportation of the Federal Aviation Administration (FAA/AST). Subsequent regulations by the FAA have set out a series of requirements for companies that want to operate these flights, enabling a market to develop. On the other side of the Atlantic, both the European Space Agency (ESA) and a group of representatives of the European Aviation Safety Agency (EASA) of the European Union (EU) seem to rather regard this activity as aviation, potentially subject to the regulation and certification competences of EASA

  19. Protection of the human race against natural hazards (asteroids, comets, volcanoes, earthquakes)

    Science.gov (United States)

    Smith, Joseph V.

    1985-10-01

    Although we justifiably worry about the danger of nuclear war to civilization, and perhaps even to survival of the human race, we tend to consider natural hazards (e.g., comets, asteroids, volcanoes, earthquakes) as unavoidable acts of God. In any human lifetime, a truly catastrophic natural event is very unlikely, but ultimately one will occur. For the first time in human history we have sufficient technical skills to begin protection of Earth from some natural hazards. We could decide collectively throughout the world to reassign resources: in particular, reduction of nuclear and conventional weapons to a less dangerous level would allow concomitant increase of international programs for detection and prevention of natural hazards. Worldwide cooperation to mitigate natural hazards might help psychologically to lead us away from the divisive bickering that triggers wars. Future generations could hail us as pioneers of peace and safety rather than curse us as agents of death and destruction.

  20. Interleukin 1 is an autocrine regulator of human endothelial cell growth

    International Nuclear Information System (INIS)

    Cozzolino, F.; Torcia, M.; Aldinucci, D.; Ziche, M.; Bani, D.; Almerigogna, F.; Stern, D.M.

    1990-01-01

    Proliferation of endothelial cells is regulated through the autocrine production of growth factors and the expression of cognate surface receptors. In this study, the authors demonstrate that interleukin 1 (IL-1) is an inhibitor of endothelial growth in vitro and in vivo. IL-1 arrested growing, cultured endothelial cells in G 1 phase; inhibition of proliferation was dose dependent and occurred in parallel with occupancy of endothelial surface IL-1 receptors. In an angiogenesis model, IL-1 could inhibit fibroblast growth factor-induced vessel formation. The autocrine nature of the IL-1 effect on endothelial proliferation was demonstrated by the observation that occupancy of cell-surface receptors by endogenous IL-1 depressed cell growth. The potential significance of this finding was emphasized by the detection of IL-1 in the native endothelium of human umbilical veins. A mechanism by which IL-1 may exert its inhibitory effect on endothelial cell growth was suggested by studies showing that IL-1 decreased the expression of high-affinity fibroblast growth factor binding sites on endothelium. These results point to a potentially important role of IL-1 in regulating blood vessel growth the suggest that autocrine production of inhibitory factors may be a mechanism controlling proliferation of normal cells

  1. Maslow Revisited: Constructing a Road Map of Human Nature

    Science.gov (United States)

    O'Connor, Dennis; Yballe, Leodones

    2007-01-01

    Given the scope and intent of Maslow's work, the current textbook treatment is wanting. Therefore, an inductive exercise has been created and is offered here to build "the road map of human nature." This age-old, philosophic focus on our true nature has been a way to successfully engage and inspire both our students and our pedagogy. In the spirit…

  2. Signaling hierarchy regulating human endothelial cell development.

    Science.gov (United States)

    Kelly, Melissa A; Hirschi, Karen K

    2009-05-01

    Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these studies. Using human embryonic stem cells as a model system, we were able to reproducibly and robustly generate differentiated endothelial cells via coculture on OP9 marrow stromal cells. We found that, in contrast to studies in the mouse, bFGF and VEGF had no specific effects on the initiation of human vasculogenesis. However, exogenous Ihh promoted endothelial cell differentiation, as evidenced by increased production of cells with cobblestone morphology that coexpress multiple endothelial-specific genes and proteins, form lumens, and exhibit DiI-AcLDL uptake. Inhibition of BMP signaling using Noggin or BMP4, specifically, using neutralizing antibodies suppressed endothelial cell formation; whereas, addition of rhBMP4 to cells treated with the hedgehog inhibitor cyclopamine rescued endothelial cell development. Our studies revealed that Ihh promoted human endothelial cell differentiation from pluripotent hES cells via BMP signaling, providing novel insights applicable to modulating human endothelial cell formation and vascular regeneration for human clinical therapies.

  3. Nature Contact and Human Health: A Research Agenda.

    Science.gov (United States)

    Frumkin, Howard; Bratman, Gregory N; Breslow, Sara Jo; Cochran, Bobby; Kahn, Peter H; Lawler, Joshua J; Levin, Phillip S; Tandon, Pooja S; Varanasi, Usha; Wolf, Kathleen L; Wood, Spencer A

    2017-07-31

    At a time of increasing disconnectedness from nature, scientific interest in the potential health benefits of nature contact has grown. Research in recent decades has yielded substantial evidence, but large gaps remain in our understanding. We propose a research agenda on nature contact and health, identifying principal domains of research and key questions that, if answered, would provide the basis for evidence-based public health interventions. We identify research questions in seven domains: a ) mechanistic biomedical studies; b ) exposure science; c ) epidemiology of health benefits; d ) diversity and equity considerations; e ) technological nature; f ) economic and policy studies; and g ) implementation science. Nature contact may offer a range of human health benefits. Although much evidence is already available, much remains unknown. A robust research effort, guided by a focus on key unanswered questions, has the potential to yield high-impact, consequential public health insights. https://doi.org/10.1289/EHP1663.

  4. Critical human-factors issues in nuclear-power regulation and a recommended comprehensive human-factors long-range plan. Executive summary

    International Nuclear Information System (INIS)

    Hopkins, C.O.; Snyder, H.L.; Price, H.E.; Hornick, R.J.; Mackie, R.R.; Smillie, R.J.; Sugarman, R.C.

    1982-08-01

    This comprehensive long-range human factors plan for nuclear reactor regulation was developed by a Study Group of the Human Factors Society, Inc. This Study Group was selected by the Executive Council of the Society to provide a balanced, experienced human factors perspective to the applications of human factors scientific and engineering knowledge to nuclear power generation. The report is presented in three volumes. Volume 1 contains an Executive Summary of the 18-month effort and its conclusions. Volume 2 summarizes all known nuclear-related human factors activities, evaluates these activities wherever adequate information is available, and describes the recommended long-range (10-year) plan for human factors in regulation. Volume 3 elaborates upon each of the human factors issues and areas of recommended human factors involvement contained in the plan, and discusses the logic that led to the recommendations

  5. Consequences of the Chernobyl accident for the natural and human environments

    Energy Technology Data Exchange (ETDEWEB)

    Dreicer, M. [Lawrence Livermore National Lab., CA (United States); Aarkog, A. [Risoe National Lab., Roskilde (Denmark); Alexakhin, R. [Russian Inst. of Agricultural Radiology and Agroecology (Russian Federation); Anspaugh, L. [Lawrence Livermore National Lab., CA (United States); Arkhipov, N.P. [Scientific and Technical Centre of the RIA `Pripyat` (Ukraine); Johansson, K.-J. [Swedish Univ. of Agricultural Sciences, Uppsala (Sweden)

    1996-07-01

    In the ten years since the Chernobyl accident, an enormous amount of work has been done to assess the consequences to the natural and human environment. Although it is difficult to summarize such a large and varied field, some general conclusions can be drawn. This background paper includes the main findings concerning the direct impacts of radiation on the flora and fauna; the general advances of knowledge in the cycling of radionuclides in natural, seminatural and agricultural environments; some evaluation of countermeasures that were used; and a summary of the human radiation doses resulting from the environmental contamination. although open questions still remain, it can be concluded that: (1) at high radiation levels, the natural environment has shown short term impacts but any significant long term impacts remain to be seen; (2) effective countermeasures can be taken to reduce the transfer of contamination from the environment to humans but these are highly site specific and must be evaluated in terms of practicality as well as population does reduction; (3) the majority of the doses have already been received by the human population. If agricultural countermeasures are appropriately taken, the main source of future doses will be the gathering of food and recreational activities in natural and seminatural ecosystems.

  6. Consequences of the Chernobyl accident for the natural and human environments

    International Nuclear Information System (INIS)

    Dreicer, M.; Aarkog, A.; Alexakhin, R.; Anspaugh, L.; Arkhipov, N.P.; Johansson, K.-J.

    1996-07-01

    In the ten years since the Chernobyl accident, an enormous amount of work has been done to assess the consequences to the natural and human environment. Although it is difficult to summarize such a large and varied field, some general conclusions can be drawn. This background paper includes the main findings concerning the direct impacts of radiation on the flora and fauna; the general advances of knowledge in the cycling of radionuclides in natural, seminatural and agricultural environments; some evaluation of countermeasures that were used; and a summary of the human radiation doses resulting from the environmental contamination. although open questions still remain, it can be concluded that: (1) at high radiation levels, the natural environment has shown short term impacts but any significant long term impacts remain to be seen; (2) effective countermeasures can be taken to reduce the transfer of contamination from the environment to humans but these are highly site specific and must be evaluated in terms of practicality as well as population does reduction; (3) the majority of the doses have already been received by the human population. If agricultural countermeasures are appropriately taken, the main source of future doses will be the gathering of food and recreational activities in natural and seminatural ecosystems

  7. Natural Tendency towards Beauty in Humans: Evidence from Binocular Rivalry.

    Science.gov (United States)

    Mo, Ce; Xia, Tiansheng; Qin, Kaixin; Mo, Lei

    2016-01-01

    Although human preference for beauty is common and compelling in daily life, it remains unknown whether such preference is essentially subserved by social cognitive demands or natural tendency towards beauty encoded in the human mind intrinsically. Here we demonstrate experimentally that humans automatically exhibit preference for visual and moral beauty without explicit cognitive efforts. Using a binocular rivalry paradigm, we identified enhanced gender-independent perceptual dominance for physically attractive persons, and the results suggested universal preference for visual beauty based on perceivable forms. Moreover, we also identified perceptual dominance enhancement for characters associated with virtuous descriptions after controlling for facial attractiveness and vigilance-related attention effects, which suggested a similar implicit preference for moral beauty conveyed in prosocial behaviours. Our findings show that behavioural preference for beauty is driven by an inherent natural tendency towards beauty in humans rather than explicit social cognitive processes.

  8. Regulation of human renin expression in chorion cell primary cultures

    International Nuclear Information System (INIS)

    Duncan, K.G.; Haidar, M.A.; Baxter, J.D.; Reudelhuber, T.L.

    1990-01-01

    The human renin gene is expressed in the kidney, placenta, and several other sites. The release of renin or its precursor, prorenin, can be affected by several regulatory agents. In this study, primary cultures of human placental cells were used to examine the regulation of prorenin release and renin mRNA levels and of the transfected human renin promoter linked to chloramphenicol acetyltransferase reporter sequences. Treatment of the cultures with a calcium ionophore alone, calcium ionophore plus forskolin (that activates adenylate cyclase), or forskolin plus a phorbol ester increased prorenin release and renin mRNA levels 1.3 endash to 6 endash fold, but several classes of steroids did not affect prorenin secretion or renin RNA levels. These results suggest that (i) the first 584 base pairs of the renin gene 5'endash flanking DNA do not contain functional glucocorticoid or estrogen response elements, (ii) placental prorenin release and renin mRNA are regulated by calcium ion and by the combinations of cAMP with either C kinase or calcium ion, and (iii) the first 100 base pairs of the human renin 5'endash flanking DNA direct accurate initiation of transcription and can be regulated by cAMP. Thus, some control of renin release in the placenta (and by inference in other tissues) occurs via transcriptional influences on its promoter

  9. An empirically informed critique of Habermas' argument from human nature.

    Science.gov (United States)

    Morar, Nicolae

    2015-02-01

    In a near-future world of bionics and biotechnology, the main ethical and political issue will be the definition of who we are. Could biomedical enhancements transform us to such an extent that we would be other than human? Habermas argues that any genetic enhancement intervention that could potentially alter 'human nature' should be morally prohibited since it alters the child's nature or the very essence that makes the child who he is. This practice also commits the child to a specific life project or, in any case, it puts specific restrictions on his freedom to choose a life of his own. Ultimately, genetic enhancement jeopardizes the very foundations of moral equality. I contend that Habermas' argument is based either on a series of presuppositions that imply a gross misunderstanding of evolution or the relevant factual information concerning the action we are about to morally assess is not empirically supported. Hence, the argument from human nature is based on a series of false or problematic assumptions, and, as such, it fails to play the normative role intended by Habermas.

  10. Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Tachibana, Keisuke, E-mail: nya@phs.osaka-u.ac.jp [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Takeuchi, Kentaro; Inada, Hirohiko [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yamasaki, Daisuke [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ishimoto, Kenji [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko [Laboratory for System Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904 (Japan); Doi, Takefumi [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2009-11-20

    Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial {beta}-oxidation. The peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is a ligand-activated transcription factor that plays an important role in the regulation of {beta}-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPAR{alpha} and found that PPAR{alpha} induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPAR{alpha} regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

  11. Essentialism Regarding Human Nature in the Defence of Gender Equality in Education

    Science.gov (United States)

    Holma, Katariina

    2007-01-01

    In this article I consider contemporary philosophical conceptions of human nature from the point of view of the ideal of gender equality. My main argument is that an essentialist account of human nature, unlike what I take to be its two main alternatives (the subjectivist account and the cultural account), is able coherently to justify the…

  12. Regulator preferences and utility prices: evidence from natural gas distribution utilities

    International Nuclear Information System (INIS)

    Klein, C.C.; Sweeney, G.H.

    1999-01-01

    We investigate the determinants of regulators' relative weighting of the social welfare of customer groups and utilities using panel data on natural gas distribution utilities in the US state of Tennessee. In contrast to previous empirical work on cross-sections of electric utilities, our results are statistically robust and consistent with the interest group theory of regulation. Intervention in rate cases, settlement vs. litigation of cases, and prices of alternative energy sources, as well as the size characteristics of customer groups and the firm, are significant determinants of the elasticity-weighted price-cost margin (Ramsey number) for each group. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  13. Signaling pathways in PACAP regulation of VIP gene expression in human neuroblastoma cells

    DEFF Research Database (Denmark)

    Falktoft, B.; Georg, B.; Fahrenkrug, J.

    2009-01-01

    Ganglia expressing the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) innervate vasoactive intestinal peptide (VIP) containing neurons suggesting a role of PACAP in regulating VIP expression. Human NB-1 neuroblastoma cells were applied to study PACAP regulated VIP gene...... in PACAP regulation of the FOS and VIP gene expressions suggest for the first time a role of FOS in PACAP-induced VIP gene expression in human NB-1 neuroblastoma cells. (C) 2009 Elsevier Ltd. All rights reserved Udgivelsesdato: 2009/10...

  14. Personality psychology : Domains of knowledge about human nature

    NARCIS (Netherlands)

    Larsen, Randy J.; Buss, David M.; Wismeijer, Andreas; Song, John; van den Berg, Stéphanie Martine

    Using a unique organizational framework that emphasizes six domains of knowledge about human nature, Personality Psychology presents an accessible, contemporary look at personality as a collection of interrelated topics and themes. The book focuses on the scientific basis of our knowledge about

  15. Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency

    Science.gov (United States)

    Cacchiarelli, Davide; Trapnell, Cole; Ziller, Michael J.; Soumillon, Magali; Cesana, Marcella; Karnik, Rahul; Donaghey, Julie; Smith, Zachary D.; Ratanasirintrawoot, Sutheera; Zhang, Xiaolan; Ho Sui, Shannan J.; Wu, Zhaoting; Akopian, Veronika; Gifford, Casey A.; Doench, John; Rinn, John L.; Daley, George Q.; Meissner, Alexander; Lander, Eric S.; Mikkelsen, Tarjei S.

    2015-01-01

    Summary Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered reactivation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. PMID:26186193

  16. Preserving human potential as freedom: a framework for regulating epigenetic harms.

    Science.gov (United States)

    Khan, Fazal

    2010-01-01

    Epigenetics is a rapidly evolving scientific field of inquiry examining how a wide range of environmental, social, and nutritional exposures can dramatically control how genes are expressed without changing the underlying DNA. Research has demonstrated that epigenetics plays a large role in human development and in disease causation. In a sense, epigenetics blurs the distinction between "nature" and "nurture" as experiences (nurture) become a part of intrinsic biology (nature). Remarkably, some epigenetic modifications are durable across generations, meaning that exposures from our grandparents' generation might affect our health now, even if we have not experienced the same exposures. In the same vein, current exposures could affect the health of not only individuals currently living but also future generations. Given the relative novelty of epigenetics research and the multifactorial nature of human development and disease causation, it is unlikely that conclusive proof can be established showing that particular exposures lead to epigenetic risks that manifest into specific conditions. Using the Capabilities Approach ("CA") developed by Amartya Sen and Martha Nussbaum, this article argues that epigenetic risk is not merely a medical issue, but that it more generally implicates the underlying fairness and justice of our social contract. For instance, how we develop mentally or physically has a tremendous impact upon our inherent capabilities and our set of life options. The CA prompts us to ask questions such as: (1) what impact do particular epigenetic risks have on our ability to exercise free choices; (2) are these risks avoidable; and (3) how are these risks distributed across society? Due to the complex nature of epigenetic risk, tort law is predictably incapable of addressing this harm. Further, while regulatory agencies possess the statutory authority to begin addressing epigenetic harms, currently these agencies are not attuned to measure or to respond to

  17. Regulation of naturally occurring and accelerator-produced radioactive materials. A Task Force review

    International Nuclear Information System (INIS)

    Nussbaumer, D.A.; Lubenau, J.O.; Cool, W.S.; Cunningham, L.J.; Mapes, J.R.; Schwartz, S.A.; Smith, D.A.

    1977-06-01

    The use of accelerator-produced radioisotopes (NARM), particularly in medicine, is growing rapidly. One NARM radioisotope, 226 Ra, is one of the most hazardous of radioactive materials, and 226 Ra is used by about 1 / 5 of all radioactive material users. Also, there are about 85,000 medical treatments using 226 Ra each year. All of the 25 Agreement States and 5 non-Agreement States have licensing programs covering NARM users. The Agreement States' programs for regulating NARM are comparable to their programs for regulating byproduct, source, and special nuclear materials under agreements with NRC. But there are 7 states who exercise no regulatory control over NARM users, and the remaining States have control programs which are variable in scope. There are no national, uniformly applied programs to regulate the design, fabrication and quality of sources and devices containing NARM or consumer products containing NARM which are distributed in interstate commerce. Naturally occurring radioactive material (except source material) associated with the nuclear fuel cycle is only partially subject to NRC regulation, i.e., when it is associated with source or special nuclear material being used under an active NRC license. The Task Force recommends that the NRC seek legislative authority to regulate naturally occurring and accelerator-produced radioactive materials for the reason that these materials present significant radiation exposure potential and present controls are fragmentary and non-uniform at both the State and Federal level

  18. Plato, Freud and Marx on Human Nature: A Comparative Analysis ...

    African Journals Online (AJOL)

    This paper examines the conceptions of human nature by Plato, Sigmund Freud and Karl Marx, with a view to revealing and explaining the convergence and divergence between these conceptions. It shows that agreement or disagreement on the distinguishing characteristics of human individuals can be situated on ...

  19. Tribbles-1: a novel regulator of hepatic lipid metabolism in humans.

    Science.gov (United States)

    Bauer, Robert C; Yenilmez, Batuhan O; Rader, Daniel J

    2015-10-01

    The protein tribbles-1, encoded by the gene TRIB1, is increasingly recognized as a major regulator of multiple cellular and physiological processes in humans. Recent human genetic studies, as well as molecular biological approaches, have implicated this intriguing protein in the aetiology of multiple human diseases, including myeloid leukaemia, Crohn's disease, non-alcoholic fatty liver disease (NAFLD), dyslipidaemia and coronary artery disease (CAD). Genome-wide association studies (GWAS) have repeatedly identified variants at the genomic TRIB1 locus as being significantly associated with multiple plasma lipid traits and cardiovascular disease (CVD) in humans. The involvement of TRIB1 in hepatic lipid metabolism has been validated through viral-mediated hepatic overexpression of the gene in mice; increasing levels of TRIB1 decreased plasma lipids in a dose-dependent manner. Additional studies have implicated TRIB1 in the regulation of hepatic lipogenesis and NAFLD. The exact mechanisms of TRIB1 regulation of both plasma lipids and hepatic lipogenesis remain undetermined, although multiple signalling pathways and transcription factors have been implicated in tribbles-1 function. Recent reports have been aimed at developing TRIB1-based lipid therapeutics. In summary, tribbles-1 is an important modulator of human energy metabolism and metabolic syndromes and worthy of future studies aimed at investigating its potential as a therapeutic target. © 2015 Authors; published by Portland Press Limited.

  20. Regulation of naturally occurring radioactive material (NORM) -- an international perspective

    International Nuclear Information System (INIS)

    Davis, M.W.

    1997-01-01

    Naturally Occurring Radioactive Material (NORM) was first recognized as a potential problem as long ago as 1904 in the oil fields of Canada. NORM later became an issue in the North Sea oil and gas production facilities in the early 1980's and became more widely recognized in the United States in 1986 during a routine well workover in the state of Mississippi. NORM contamination of oil and gas industry production equipment has since been identified world wide. The United States, including Alaska and the Gulf of Mexico region, the North Sea region, the United Kingdom, Canada, Australia and several Middle Eastern countries have all reported NORM contamination. The purpose of this paper is to discuss some of the international regulations or guidelines that have been promulgated concerning NORM in the oil and gas industry. Additionally, the impact of these regulations or guidelines on non-oil and gas industries will also be discussed. A comparison of these regulations or guidelines to those generally found in the United States shall be drawn

  1. Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells.

    Science.gov (United States)

    Min, Kyoung-Jin; Nam, Ju-Ock; Kwon, Taeg Kyu

    2017-08-02

    Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki) cells. Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose) polymerase (PARP), which is a marker of apoptosis, and increased caspase activation. We found that pan-caspase inhibitor (z-VAD-fmk) inhibited fisetin-induced apoptosis. In addition, fisetin induced death receptor 5 (DR5) expression at the transcriptional level, and down-regulation of DR5 by siRNA blocked fisetin-induced apoptosis. Furthermore, fisetin induced p53 protein expression through up-regulation of protein stability, whereas down-regulation of p53 by siRNA markedly inhibited fisetin-induced DR5 expression. In contrast, fisetin induced up-regulation of CHOP expression and reactive oxygen species production, which had no effect on fisetin-induced apoptosis. Taken together, our study demonstrates that fisetin induced apoptosis through p53 mediated up-regulation of DR5 expression at the transcriptional level.

  2. Epigenetic Regulation of Inflammatory Cytokines and Associated Genes in Human Malignancies

    Directory of Open Access Journals (Sweden)

    Rehana Yasmin

    2015-01-01

    Full Text Available Inflammation is a multifaceted defense response of immune system against infection. Chronic inflammation has been implicated as an imminent threat for major human malignancies and is directly linked to various steps involved in tumorigenesis. Inflammatory cytokines, interleukins, interferons, transforming growth factors, chemokines, and adhesion molecules have been associated with chronic inflammation. Numerous cytokines are reported to be aberrantly regulated by different epigenetic mechanisms like DNA methylation and histone modifications in tumor tissues, contributing to pathogenesis of tumor in multiple ways. Some of these cytokines also work as epigenetic regulators of other crucial genes in tumor biology, either directly or indirectly. Such regulations are reported in lung, breast, cervical, gastric, colorectal, pancreatic, prostate, and head and neck cancers. Epigenetics of inflammatory mediators in cancer is currently subject of extensive research. These investigations may help in understanding cancer biology and to develop effective therapeutic strategies. The purpose of this paper is to have a brief view of the aberrant regulation of inflammatory cytokines in human malignancies.

  3. Mindsets and Human Nature: Promoting Change in the Middle East, the Schoolyard, the Racial Divide, and Willpower

    Science.gov (United States)

    Dweck, Carol S.

    2012-01-01

    Debates about human nature often revolve around what is built in. However, the hallmark of human nature is how much of a person's identity is not built in; rather, it is humans' great capacity to adapt, change, and grow. This nature versus nurture debate matters--not only to students of human nature--but to everyone. It matters whether people…

  4. Critical human-factors issues in nuclear-power regulation and a recommended comprehensive human-factors long-range plan. Critical discussion of human factors areas of concern

    International Nuclear Information System (INIS)

    Hopkins, C.O.; Snyder, H.L.; Price, H.E.; Hornick, R.J.; Mackie, R.R.; Smillie, R.J.; Sugarman, R.C.

    1982-08-01

    This comprehensive long-range human factors plan for nuclear reactor regulation was developed by a Study Group of the Human Factors Society, Inc. This Study Group was selected by the Executive Council of the Society to provide a balanced, experienced human factors perspective to the applications of human factors scientific and engineering knowledge to nuclear power generation. The report is presented in three volumes. Volume 1 contains an Executive Summary of the 18-month effort and its conclusions. Volume 2 summarizes all known nuclear-related human factors activities, evaluates these activities wherever adequate information is available, and describes the recommended long-range (10-year) plan for human factors in regulation. Volume 3 elaborates upon each of the human factors issues and areas of recommended human factors involvement contained in the plan, and discusses the logic that led to the recommendations

  5. Study of 'inadvertent human intrusion or rare natural event scenarios' for sub-surface disposal of radioactive waste

    International Nuclear Information System (INIS)

    Nakatani, Takayoshi; Ishitoya, Kimihide; Funabashi, Hideyuki; Sugaya, Toshikatsu; Sone, Tomoyuki; Shimada, Hidemitsu; Nakai, Kunihiro

    2010-03-01

    Japan Atomic Energy Agency (JAEA) is making preparations for the sub-surface disposal of radioactive wastes, in an integrated fashion according to the properties of the waste material regardless of the generators or waste sources. In this study, 'Inadvertent Human Intrusion or Rare Natural Event Scenarios' of 'Three Types scenarios' was considered according to the standard of the Atomic Energy Society of Japan (AESJ) on the sub-surface disposal system that was based on 'Basic Policy for Safety Regulation Concerning Land Disposal of Low-Level Radioactive Waste (Interim Report)' by Nuclear Safety Commission of Japan (NSC). Selection of the assessed scenarios, development of the assessment tool and preliminary exposure dose assessment for general public were conducted. Among the assessed scenarios, the exposure dose of 'well water drinking scenario' was the highest under the very conservative assessment condition. This scenario assumed that the groundwater in Excavation Disturbed Zone (EDZ) was directly used as drinking water without any dilution. Although this was very conservative condition and the result exceeded 10 mSv/y, it stayed under the upper limit of standard dose value for 'Inadvertent Human Intrusion or Rare Natural Event Scenarios' (10 - 100 mSv/y). (author)

  6. Art and human nature

    Directory of Open Access Journals (Sweden)

    Mirta Toledo

    2008-06-01

    Full Text Available This article presents a visual artist’s point of view about art. This view confronts the Eurocentric traditional cannon with some ignored, but valuable traditions, thus proposing a contra-canon. These ideas are examined on the light of a variety of sources, including prehistoric, pre-Columbian, and 20th century art expressions, in a variety of media, from sculpture to literature. Recent art expressions are characterized by their incorporation of minority values and perspectives that challenge “universal” views. Using samples of works from Latino and African American artists, the author shows that, even today, art is a means to know the world and its people, to exhibit personal life, to create personal symbolism, and to show one’s identity or the search for it. Like the human nature it represents, art has multiple faces.

  7. Direct Neural Conversion from Human Fibroblasts Using Self-Regulating and Nonintegrating Viral Vectors

    Directory of Open Access Journals (Sweden)

    Shong Lau

    2014-12-01

    Full Text Available Summary: Recent findings show that human fibroblasts can be directly programmed into functional neurons without passing via a proliferative stem cell intermediate. These findings open up the possibility of generating subtype-specific neurons of human origin for therapeutic use from fetal cell, from patients themselves, or from matched donors. In this study, we present an improved system for direct neural conversion of human fibroblasts. The neural reprogramming genes are regulated by the neuron-specific microRNA, miR-124, such that each cell turns off expression of the reprogramming genes once the cell has reached a stable neuronal fate. The regulated system can be combined with integrase-deficient vectors, providing a nonintegrative and self-regulated conversion system that rids problems associated with the integration of viral transgenes into the host genome. These modifications make the system suitable for clinical use and therefore represent a major step forward in the development of induced neurons for cell therapy. : Lau et al. now use miRNA targeting to build a self-regulating neural conversion system. Combined with nonintegrating vectors, this system can efficiently drive conversion of human fibroblasts into functional induced neurons (iNs suitable for clinical applications.

  8. Characterization of gene expression regulated by human OTK18 ...

    Indian Academy of Sciences (India)

    ing regulated by interactions with the Tat protein (Carlson et al. 2004a). In contrast, OTK18 is ubiquitously expressed in all normal human tissues, and OTK18 expression in HIV-1 ..... and Social Sciences and the UNK Biology Department.

  9. Natural hazards, disasters and human kind: Whither ecosystem management?

    Digital Repository Service at National Institute of Oceanography (India)

    Mascarenhas, A.; Mudholkar, A.V.

    in the way of powerful natural forces. Abandoning vulnerable geomorphic features, managed retreat, or safer setback with intervening forested landforms are feasible long-term options. The incalculable human misery that ultimately follows ia an ideal...

  10. Regulation of naturally occurring radioactive materials in Australia

    International Nuclear Information System (INIS)

    Jeffries, C.; Akber, R.; Johnston, A.; Cassels, B.

    2011-01-01

    In order to promote uniformity between jurisdictions, the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) has developed the National Directory for Radiation Protection, which is a regulatory framework that all Australian governments have agreed to adopt. There is a large and diverse range of industries involved in mining or mineral processing, and the production of fossil fuels in Australia. Enhanced levels of naturally occurring radionuclides can be associated with mineral extraction and processing, other industries (e.g. metal recycling) and some products (e.g. plasterboard). ARPANSA, in conjunction with industry and State regulators, has undertaken a review and assessment of naturally occurring radioactive material (NORM) management in Australian industries. This review has resulted in guidance on the management of NORM that will be included in the National Directory for Radiation Protection. The first NORM safety guide provides the framework for NORM management and addresses specific NORM issues in oil and gas production, bauxite, aluminium and phosphate industries. Over time further guidance material for other NORM-related industries will be developed. This presentation will provide an overview of the regulatory approach to managing NORM industries in Australia. (authors)

  11. Natural Compounds Regulate Glycolysis in Hypoxic Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Jian-Li Gao

    2015-01-01

    Full Text Available In the early twentieth century, Otto Heinrich Warburg described an elevated rate of glycolysis occurring in cancer cells, even in the presence of atmospheric oxygen (the Warburg effect. Recently it became a therapeutically interesting strategy and is considered as an emerging hallmark of cancer. Hypoxia inducible factor-1 (HIF-1 is one of the key transcription factors that play major roles in tumor glycolysis and could directly trigger Warburg effect. Thus, how to inhibit HIF-1-depended Warburg effect to assist the cancer therapy is becoming a hot issue in cancer research. In fact, HIF-1 upregulates the glucose transporters (GLUT and induces the expression of glycolytic enzymes, such as hexokinase, pyruvate kinase, and lactate dehydrogenase. So small molecules of natural origin used as GLUT, hexokinase, or pyruvate kinase isoform M2 inhibitors could represent a major challenge in the field of cancer treatment. These compounds aim to suppress tumor hypoxia induced glycolysis process to suppress the cell energy metabolism or enhance the susceptibility of tumor cells to radio- and chemotherapy. In this review, we highlight the role of natural compounds in regulating tumor glycolysis, with a main focus on the glycolysis under hypoxic tumor microenvironment.

  12. Regulation of naturally occurring radioactive materials in Australia.

    Science.gov (United States)

    Jeffries, Cameron; Akber, Riaz; Johnston, Andrew; Cassels, Brad

    2011-07-01

    In order to promote uniformity between jurisdictions, the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) has developed the National Directory for Radiation Protection, which is a regulatory framework that all Australian governments have agreed to adopt. There is a large and diverse range of industries involved in mining or mineral processing, and the production of fossil fuels in Australia. Enhanced levels of naturally occurring radionuclides can be associated with mineral extraction and processing, other industries (e.g. metal recycling) and some products (e.g. plasterboard). ARPANSA, in conjunction with industry and State regulators, has undertaken a review and assessment of naturally occurring radioactive material (NORM) management in Australian industries. This review has resulted in guidance on the management of NORM that will be included in the National Directory for Radiation Protection. The first NORM safety guide provides the framework for NORM management and addresses specific NORM issues in oil and gas production, bauxite, aluminium and phosphate industries. Over time further guidance material for other NORM-related industries will be developed. This presentation will provide an overview of the regulatory approach to managing NORM industries in Australia.

  13. Proposed changes for part N of suggested state regulations

    Energy Technology Data Exchange (ETDEWEB)

    Paris, R.

    1997-02-01

    This paper discusses proposed changes for Part N regulations regarding naturally occuring radioactive materials. It describes the work of the Commission on NORM of the Conference of Radiation Control Program Directors (CRCPD), toward adjusting the regulations. A set of questions was formulated and a review panel established to address these questions and come back with recommended actions. The panel recommended the distinction that the material being regulated is `Technologically Enhanced Naturally Occurring Radioactive Material` (TENORM). By this they mean `naturally occurring radioactive material not regulated under the Atomic Energy Act (AEA) whose radionuclide concentrations have been increased by or as a result of human practices.` Recommendations also include: using a dose based instead of concentration based standard; refined definition of exemptions from regulations; exclusion of radon from Total Effective Dose Equivalent (TEDE) calculations; provide states flexibility in implementation; inclusion of prospective remedial and operations aspects for TENORM; provision of institutional controls.

  14. Major and trace elements regulation in natural granitic waters: Application to deep radioactive waste disposals

    International Nuclear Information System (INIS)

    Michard, G.; Negrel, G.; Toulhoat, P.; Beaucaire, C.; Ouzounian, G.

    1991-01-01

    In order to forecast the evolution of deep groundwaters in the environment of a radioactive waste disposal, one must be able to understand the behaviour of major and trace elements in natural systems. From granitic geothermal and groundwater systems the authors establish that major elements are controlled by mineral precipitation. Regulation levels depend both on equilibration temperature and mobile anion concentration (mainly C1). From empirical laws, the regulation levels with temperature of some trace elements (alkaline and most divalent) elements can be estimated, although a precise explanation for the regulation mechanism is not yet available. They demonstrate that some transition metals are controlled by sulphide precipitation; that uranium is controlled by uraninite solubility; that trivalent and tetravalent metals are present in association with colloidal particles. Maximum regulation levels can be estimated. Such studies can also be useful to forecast the concentration levels of many elements related to nuclear wastes, mainly fission products, uranium, thorium and by analogy artificial actinide elements, as the behaviour of corresponding natural elements can be evaluated

  15. Human natural killer cell development in secondary lymphoid tissues

    Science.gov (United States)

    Freud, Aharon G.; Yu, Jianhua; Caligiuri, Michael A.

    2014-01-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34+CD45RA+ hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field. PMID:24661538

  16. The exposures to natural radioactivity as a result of human activities; Les expositions a la radioactivite naturelle du fait des activites humaines

    Energy Technology Data Exchange (ETDEWEB)

    Rannou, A.; Dupuis, M.; Bottollier-Depois, J.F.; Leprieur, F.; Pasquier, J.L.; Doremus, P.; Pierre, J.P. [Institut de Radioprotection et de Surete Nucleaire, 92 - Clamart (France); Bernhard, S. [ALGADE, 87 6 Bessines sur Gartempe (France); Delporte, V. [Drection Generale de la Surete Nucleaire et de la Radioprotection, 75 - Paris (France); Servent, J.P. [Institut National de Recherche et de Securite, 75 - Paris (France); Marchand, D. [DRASS Bretagne (France); Dupuis, M.; Bottollier-Depois, J.F.; Leprieur, F.; Pasquier, J.L.; Doremus, P.; Pierre, J.P. [Institut de Radioprotection et de Surete Nucleaire, 92 - Clamart (France); Surbeck, H. [Neuchatel Univ. (Switzerland); Degrange, J.P. [Centre d' Etude sur l' Evaluation de la Protection dans le Domaine Nucleaire, 92 - Fontenay aux Roses (France)

    2005-07-01

    The new regulation in matter of radiation protection, coming from the transposition of the European directive 96/29/EURATOM modifies the code of the public health and the labour code. The exposures to natural radioactivity by the very fact of human activities are the object of specific dispositions. These new dispositions apply to professional areas that were, until now, little concerned by the regulation relative to ionizing radiations. The S.F.R.P., in relationship with the Minister in charge of labour, and the A.F.T.I.M. (French organisation of safety technicians and engineers and labour physicians) organizes two days of information and exchange on the subject. This meeting concerns industry and research departments but also inspectors and labour physicians and other actors having a look on the risk management in societies. After some reminder on radioactivity and its effects, the regulation and the global risk management on working place, several actual examples are presented, covering the different known situations of exposure to the natural radioactivity ( radon, cosmic rays, use of radioactive material in an industrial process, production of radioactive waste). The days finish by a round table conference on the stakes and practical entailment of the new regulation. (N.C.)

  17. Where humans meet machines innovative solutions for knotty natural-language problems

    CERN Document Server

    Markowitz, Judith

    2013-01-01

    Where Humans Meet Machines: Innovative Solutions for Knotty Natural-Language Problems brings humans and machines closer together by showing how linguistic complexities that confound the speech systems of today can be handled effectively by sophisticated natural-language technology. Some of the most vexing natural-language problems that are addressed in this book entail   recognizing and processing idiomatic expressions, understanding metaphors, matching an anaphor correctly with its antecedent, performing word-sense disambiguation, and handling out-of-vocabulary words and phrases. This fourteen-chapter anthology consists of contributions from industry scientists and from academicians working at major universities in North America and Europe. They include researchers who have played a central role in DARPA-funded programs and developers who craft real-world solutions for corporations. These contributing authors analyze the role of natural language technology in the global marketplace; they explore the need f...

  18. Siderophore-mediated iron trafficking in humans is regulated by iron

    Science.gov (United States)

    Liu, Zhuoming; Lanford, Robert; Mueller, Sebastian; Gerhard, Glenn S.; Luscieti, Sara; Sanchez, Mayka; Devireddy, L.

    2013-01-01

    Siderophores are best known as small iron binding molecules that facilitate microbial iron transport. In our previous study we identified a siderophore-like molecule in mammalian cells and found that its biogenesis is evolutionarily conserved. A member of the short chain dehydrogenase family of reductases, 3-OH butyrate dehydrogenase (BDH2) catalyzes a rate-limiting step in the biogenesis of the mammalian siderophore. We have shown that depletion of the mammalian siderophore by inhibiting expression of bdh2 results in abnormal accumulation of cellular iron and mitochondrial iron deficiency. These observations suggest that the mammalian siderophore is a critical regulator of cellular iron homeostasis and facilitates mitochondrial iron import. By utilizing bioinformatics, we identified an iron-responsive element (IRE; a stem-loop structure that regulates genes expression post-transcriptionally upon binding to iron regulatory proteins or IRPs) in the 3′-untranslated region (3′-UTR) of the human BDH2 (hBDH2) gene. In cultured cells as well as in patient samples we now demonstrate that the IRE confers iron-dependent regulation on hBDH2 and binds IRPs in RNA electrophoretic mobility shift assays. In addition, we show that the hBDH2 IRE associates with IRPs in cells and that abrogation of IRPs by RNAi eliminates the iron-dependent regulation of hBDH2 mRNA. The key physiologic implication is that iron-mediated post-transcriptional regulation of hBDH2 controls mitochondrial iron homeostasis in human cells. These observations provide a new and an unanticipated mechanism by which iron regulates its intracellular trafficking. PMID:22527885

  19. Telomeres and the natural lifespan limit in humans

    DEFF Research Database (Denmark)

    Steenstrup, Troels; Kark, Jeremy D; Verhulst, Simon

    2017-01-01

    An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal...... natural lifespan limit. We define leukocyte telomere length of 5 kb as the 'telomeric brink', which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus, secular trends...

  20. Neural networks of human nature and nurture

    Directory of Open Access Journals (Sweden)

    Daniel S. Levine

    2009-11-01

    Full Text Available Neural network methods have facilitated the unification of several unfortunate splits in psychology, including nature versus nurture. We review the contributions of this methodology and then discuss tentative network theories of caring behavior, of uncaring behavior, and of how the frontal lobes are involved in the choices between them. The implications of our theory are optimistic about the prospects of society to encourage the human potential for caring.

  1. Can we adequately represent the spatial interplay between humans and nature?

    Science.gov (United States)

    One of the challenges remaining before ecosystem services assessments can become part of mainstream decision making is how to spatially represent the interplay of nature as a whole and humans. Nature’s ecosystems act as natural capital by producing things (i.e. stocks and ...

  2. IGF-1 promotes the development and cytotoxic activity of human NK cells

    OpenAIRE

    Ni, Fang; Sun, Rui; Fu, Binqing; Wang, Fuyan; Guo, Chuang; Tian, Zhigang; Wei, Haiming

    2013-01-01

    Insulin-like growth factor 1 (IGF-1) is a critical regulator of many physiological functions, ranging from longevity to immunity. However, little is known about the role of IGF-1 in natural killer cell development and function. Here, we identify an essential role for IGF-1 in the positive regulation of human natural killer cell development and cytotoxicity. Specifically, we show that human natural killer cells have the ability to produce IGF-1 and that differential endogenous IGF-1 expression...

  3. Limits to human enhancement: nature, disease, therapy or betterment?

    Science.gov (United States)

    Hofmann, Bjørn

    2017-10-10

    New technologies facilitate the enhancement of a wide range of human dispositions, capacities, or abilities. While it is argued that we need to set limits to human enhancement, it is unclear where we should find resources to set such limits. Traditional routes for setting limits, such as referring to nature, the therapy-enhancement distinction, and the health-disease distinction, turn out to have some shortcomings. However, upon closer scrutiny the concept of enhancement is based on vague conceptions of what is to be enhanced. Explaining why it is better to become older, stronger, and more intelligent presupposes a clear conception of goodness, which is seldom provided. In particular, the qualitative better is frequently confused with the quantitative more. We may therefore not need "external" measures for setting its limits - they are available in the concept of enhancement itself. While there may be shortcomings in traditional sources of limit setting to human enhancement, such as nature, therapy, and disease, such approaches may not be necessary. The specification-of-betterment problem inherent in the conception of human enhancement itself provides means to restrict its unwarranted proliferation. We only need to demand clear, sustainable, obtainable goals for enhancement that are based on evidence, and not on lofty speculations, hypes, analogies, or weak associations. Human enhancements that specify what will become better, and provide adequate evidence, are good and should be pursued. Others should not be accepted.

  4. Innate-like behavior of human invariant natural killer T cells during herpes simplex virus infection.

    Science.gov (United States)

    Novakova, Lucie; Nevoralova, Zuzana; Novak, Jan

    2012-01-01

    Invariant natural killer T (iNKT) cells, CD1d restricted T cells, are involved in the immune responses against various infection agents. Here we describe their behavior during reactivation of human herpes simplex virus (HSV). iNKT cells exhibit only discrete changes, which however, reached statistically significant level due to the relatively large patient group. Higher percentage of iNKT cells express NKG2D. iNKT cells down-regulate NKG2A in a subset of patients. Finally, iNKT cells enhance their capacity to produce TNF-α. Our data suggests that iNKT cells are involved in the immune response against HSV and contribute mainly to its early, innate phase. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. The Human - Nature Relationship i n t he Context o f Theo - Centric Environmental Ethics

    Directory of Open Access Journals (Sweden)

    Gülşen YAYLI

    2015-07-01

    Full Text Available The environmental problems are one of the issues that intensively occupy the agenda of humankind. This fact mainly derives from the ambiguity of the s pan and the content of the issue. The concept of environmental problems can not be confined to th e soil, air and water pollution for the reason that it covers a scope wider than a classical pollution issues. Initially the form of the relations hip between h uman and nature has been relying on the “consumption at the level of content” which stands for a level that is enough to sustain the living. The perception of the nature used to be described with the metaphor of mother while natural environment was defined as the “mother earth”. However subsequent to natural environment definition of the Cartesian philosophy with its approach to the human nature relationship, the core metaphor to describe the natural environment has changed from the metaphor of “mother” to the “slave” which should serve by any means. The human - nature relationship within the context of ethics, both the parties an d their respective statues bear an importance. In terms of ethics of human - nature relationship, it is possible to mention three main approaches. First one is the anthropo - centric approach. Within the scope of historical process, human - nature relationship is addressed according to anthropo - centric ethics comprehension so human has remained at the center of discussion. Following the change of the perception regarding the issue of environment, new approaches have emerged that give emphasis not only on human beings but also others; on li ving and non - living beings with in the eco - system. In principle, this represents a departure from an anthropo - centric ethics to a new ethic approach which fall s into two categories, bio centric and eco - centric. The theo - centric ethics should also be included to these ethics approaches that are shaped within the sphere of positive sciences. The Abrahamic

  6. NATURAL USER INTERFACE SENSORS FOR HUMAN BODY MEASUREMENT

    Directory of Open Access Journals (Sweden)

    J. Boehm

    2012-08-01

    Full Text Available The recent push for natural user interfaces (NUI in the entertainment and gaming industry has ushered in a new era of low cost three-dimensional sensors. While the basic idea of using a three-dimensional sensor for human gesture recognition dates some years back it is not until recently that such sensors became available on the mass market. The current market leader is PrimeSense who provide their technology for the Microsoft Xbox Kinect. Since these sensors are developed to detect and observe human users they should be ideally suited to measure the human body. We describe the technology of a line of NUI sensors and assess their performance in terms of repeatability and accuracy. We demonstrate the implementation of a prototype scanner integrating several NUI sensors to achieve full body coverage. We present the results of the obtained surface model of a human body.

  7. Natural User Interface Sensors for Human Body Measurement

    Science.gov (United States)

    Boehm, J.

    2012-08-01

    The recent push for natural user interfaces (NUI) in the entertainment and gaming industry has ushered in a new era of low cost three-dimensional sensors. While the basic idea of using a three-dimensional sensor for human gesture recognition dates some years back it is not until recently that such sensors became available on the mass market. The current market leader is PrimeSense who provide their technology for the Microsoft Xbox Kinect. Since these sensors are developed to detect and observe human users they should be ideally suited to measure the human body. We describe the technology of a line of NUI sensors and assess their performance in terms of repeatability and accuracy. We demonstrate the implementation of a prototype scanner integrating several NUI sensors to achieve full body coverage. We present the results of the obtained surface model of a human body.

  8. Sp1 and CREB regulate basal transcription of the human SNF2L gene

    International Nuclear Information System (INIS)

    Xia Yu; Jiang Baichun; Zou Yongxin; Gao Guimin; Shang Linshan; Chen Bingxi; Liu Qiji; Gong Yaoqin

    2008-01-01

    Imitation Switch (ISWI) is a member of the SWI2/SNF2 superfamily of ATP-dependent chromatin remodelers, which are involved in multiple nuclear functions, including transcriptional regulation, replication, and chromatin assembly. Mammalian genomes encode two ISWI orthologs, SNF2H and SNF2L. In order to clarify the molecular mechanisms governing the expression of human SNF2L gene, we functionally examined the transcriptional regulation of human SNF2L promoter. Reporter gene assays demonstrated that the minimal SNF2L promoter was located between positions -152 to -86 relative to the transcription start site. In this region we have identified a cAMP-response element (CRE) located at -99 to -92 and a Sp1-binding site at -145 to -135 that play a critical role in regulating basal activity of human SNF2L gene, which were proven by deletion and mutation of specific binding sites, EMSA, and down-regulating Sp1 and CREB via RNAi. This study provides the first insight into the mechanisms that control basal expression of human SNF2L gene

  9. Impact of training state on fasting-induced regulation of adipose tissue metabolism in humans

    DEFF Research Database (Denmark)

    Bertholdt, Lærke; Gudiksen, Anders; Stankiewicz, Tomasz

    2018-01-01

    Recruitment of fatty acids from adipose tissue is essential during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore, the aim of the present study was to investig......Recruitment of fatty acids from adipose tissue is essential during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore, the aim of the present study...... was to investigate 1) fasting-induced regulation of lipolysis and glyceroneogenesis in human adipose tissue as well as 2) the impact of training state on basal oxidative capacity and fasting-induced metabolic regulation in human adipose tissue. Untrained (VO2max 55ml......RNA content were higher in trained subjects than untrained subjects. In addition, trained subjects had higher adipose tissue hormone sensitive lipase Ser660 phosphorylation and adipose triglyceride lipase protein content as well as higher plasma free fatty acids concentration than untrained subjects during...

  10. The Integration Hypothesis of Human Language Evolution and the Nature of Contemporary Languages

    Directory of Open Access Journals (Sweden)

    Shigeru eMiyagawa

    2014-06-01

    Full Text Available How human language arose is a mystery in the evolution of Homo sapiens. Miyagawa, Berwick, & Okanoya (Frontiers 2013 put forward a proposal, which we will call the Integration Hypothesis of human language evolution, which holds that human language is composed of two components, E for expressive, and L for lexical. Each component has an antecedent in nature: E as found, for example, in birdsong, and L in, for example, the alarm calls of monkeys. E and L integrated uniquely in humans to give rise to language. A challenge to the Integration Hypothesis is that while these non-human systems are finite-state in nature, human language is known to require characterization by a non-finite state grammar. Our claim is that E and L, taken separately, are finite-state; when a grammatical process crosses the boundary between E and L, it gives rise to the non-finite state character of human language. We provide empirical evidence for the Integration Hypothesis by showing that certain processes found in contemporary languages that have been characterized as non-finite state in nature can in fact be shown to be finite-state. We also speculate on how human language actually arose in evolution through the lens of the Integration Hypothesis.

  11. On the nature and evolution of the neural bases of human language

    Science.gov (United States)

    Lieberman, Philip

    2002-01-01

    The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on

  12. Natural and human impacts on ecosystem services in Guanzhong - Tianshui economic region of China.

    Science.gov (United States)

    Li, Jing; Zhou, Z X

    2016-04-01

    Due to the accelerated growth of society, the gaps between the capacity of ecosystems to provide services and human needs are steadily widening. Natural, semi-natural, or managed ecosystems had been able to provide ecosystem services to meet the needs of social development. Four agricultural ecosystem services (net primary production (NPP), carbon sequestration and oxygen production (CSOP), water interception, soil conservation and agriculture production) were quantified in Guanzhong-Tianshui economic region. Estimates of ecosystem services were obtained from the analysis of satellite imagery and the use of well-known models. Based on the ecological services in Guanzhong-Tianshui economic region, this study mainly analysed the driving mechanism of the changes from the two aspects of natural drivers and human drivers. Natural drivers (climate, soil, elevation, land cover) had incentive to the ecological services. Human activity was quantified by an integrated human activity index (HAI) based on population density, farmland ratio, and the influence of road networks and residential areas. We found relationships between ecosystem services, human activities and many natural factors, however these varied according to the service studied. Human activities were mostly negatively related to each ecosystem services, while population and residential land ware positively related to agricultural production. Land use change had made a contribution to ecosystem services. Based on the selected ecosystem services and HAI, we provided sustainable ecosystem management suggestions.

  13. Evaluating the best available social science for natural resource management decision-making

    Science.gov (United States)

    Susan Charnley; Courtney Carothers; Terre Satterfield; Arielle Levine; Melissa R. Poe; Karma Norman; Jamie Donatuto; Sara Jo Breslow; Michael B. Mascia; Phillip S. Levin; Xavier Basurto; Christina C. Hicks; Carlos García-Quijano; Kevin St. Martin

    2017-01-01

    Increasing recognition of the human dimensions of natural resource management issues, and of social and ecological sustainability and resilience as being inter-related, highlights the importance of applying social science to natural resource management decision-making. Moreover, a number of laws and regulations require natural resource management agencies to consider...

  14. Dietary methanol regulates human gene activity.

    Directory of Open Access Journals (Sweden)

    Anastasia V Shindyapina

    Full Text Available Methanol (MeOH is considered to be a poison in humans because of the alcohol dehydrogenase (ADH-mediated conversion of MeOH to formaldehyde (FA, which is toxic. Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and a modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC from volunteers after pectin intake showed various responses for 30 significantly differentially regulated mRNAs, most of which were somehow involved in the pathogenesis of Alzheimer's disease (AD. There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes were not significantly expressed. A qRT-PCR analysis of volunteer WBCs after pectin and red wine intake confirmed the complicated relationship between the plasma MeOH content and the mRNA accumulation of both genes that were previously identified, namely, GAPDH and SNX27, and genes revealed in this study, including MME, SORL1, DDIT4, HBA and HBB. We hypothesized that human plasma MeOH has an impact on the WBC mRNA levels of genes involved in cell signaling.

  15. Leukocyte-associated immunoglobulin-like receptor-1 is expressed on human megakaryocytes and negatively regulates the maturation of primary megakaryocytic progenitors and cell line

    International Nuclear Information System (INIS)

    Xue, Jiangnan; Zhang, Xiaoshu; Zhao, Haiya; Fu, Qiang; Cao, Yanning; Wang, Yuesi; Feng, Xiaoying; Fu, Aili

    2011-01-01

    Research highlights: → LAIR-1 is expressed on human megakaryocytes from an early stage. → Up-regulation of LAIR-1 negatively regulates megakaryocytic differentiation of cell line. → LAIR-1 negatively regulates the differentiation of primary megakaryocytic progenitors. -- Abstract: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory collagen receptor which belongs to the immunoglobulin (Ig) superfamily. Although the inhibitory function of LAIR-1 has been extensively described in multiple leukocytes, its role in megakaryocyte (MK) has not been explored so far. Here, we show that LAIR-1 is expressed on human bone marrow CD34 + CD41a + and CD41a + CD42b + cells. LAIR-1 is also detectable in a fraction of human cord blood CD34 + cell-derived MK that has morphological characteristics of immature MK. In megakaryoblastic cell line Dami, the membrane protein expression of LAIR-1 is up-regulated significantly when cells are treated with phorbol ester phorbol 12-myristate 13-acetate (PMA). Furthermore, cross-linking of LAIR-1 in Dami cells with its natural ligand or anti-LAIR-1 antibody leads to the inhibition of cell proliferation and PMA-promoted differentiation when examined by the MK lineage-specific markers (CD41a and CD42b) and polyploidization. In addition, we also observed that cross-linking of LAIR-1 results in decreased MK generation from primary human CD34 + cells cultured in a cytokines cocktail that contains TPO. These results suggest that LAIR-1 is a likely candidate for an early marker of MK differentiation, and provide initial evidence indicating that LAIR-1 serves as a negative regulator of megakaryocytopoiesis.

  16. A conceptual framework to evaluate human-wildlife interactions within coupled human and natural systems

    Directory of Open Access Journals (Sweden)

    Anita T. Morzillo

    2014-09-01

    Full Text Available Landscape characteristics affect human-wildlife interactions. However, there is a need to better understand mechanisms that drive those interactions, particularly feedbacks that exist between wildlife-related impacts, human reaction to and behavior as a result of those impacts, and how land use and landscape characteristics may influence those components within coupled human and natural systems. Current conceptual models of human-wildlife interactions often focus on species population size as the independent variable driving those interactions. Such an approach potentially overlooks important feedbacks among and drivers of human-wildlife interactions that result from mere wildlife presence versus absence. We describe an emerging conceptual framework that focuses on wildlife as a driver of human behavior and allows us to better understand linkages between humans, wildlife, and the broader landscape. We also present results of a pilot analysis related to our own ongoing study of urban rodent control behavior to illustrate one application of this framework within a study of urban landscapes.

  17. Regulation of natural gas: the issue of open access; Regulacao em materia de gas natural: a questao do livre acesso

    Energy Technology Data Exchange (ETDEWEB)

    Sandes, Ingrid; Siqueira, Mariana [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Faculdade de Direito

    2004-07-01

    The present work discusses the question of the open access to the natural gas ducts, trying to show the most relevant aspects of it. Analyzing the regulation existent in Brazil and the main important characteristics of the natural gas activities, it will be tried to suggest new directions to be taken in the future. The open access it is a very important way to introduce new agents on the sector and, in that way, the discussions that try to show new aspects of it, are very relevant (author)

  18. Peer effects on self-regulation in adolescence depend on the nature and quality of the peer interaction.

    Science.gov (United States)

    King, Kevin M; McLaughlin, Katie A; Silk, Jennifer; Monahan, Kathryn C

    2017-11-21

    Adolescence is a critical period for the development of self-regulation, and peer interactions are thought to strongly influence regulation ability. Simple exposure to peers has been found to alter decisions about risky behaviors and increase sensitivity to rewards. The link between peer exposure and self-regulation is likely to vary as a function of the type and quality of peer interaction (e.g., rejection or acceptance). Little is known about how the nature of interactions with peers influences different dimensions of self-regulation. We examined how randomization to acceptance or rejection by online "virtual" peers influenced multiple dimensions of self-regulation in a multisite community sample of 273 adolescents aged 16-17 years. Compared to a neutral condition, exposure to peers produced increases in cold cognitive control, but decreased hot cognitive control. Relative to peer acceptance, peer rejection reduced distress tolerance and increased sensitivity to losses. These findings suggest that different dimensions of adolescent self-regulation are influenced by the nature of the peer context: basic cognitive functions are altered by mere exposure to peers, whereas more complex decision making and emotion regulation processes are influenced primarily by the quality of that exposure.

  19. mTORC1 directly phosphorylates and regulates human MAF1.

    OpenAIRE

    Michels Annemieke A; Robitaille Aaron M; Buczynski-Ruchonnet Diane; Hodroj Wassim; Reina Jaime H; Hall Michael N; Hernandez Nouria

    2010-01-01

    mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the p...

  20. Gene therapy, human nature and the churches.

    Science.gov (United States)

    Dunstan, G R

    1991-12-01

    Moral analysis must begin with respect for the empirical features, the "facts of the case". Major advances in genetic knowledge and technology -- as in other sciences -- inevitably change mental attitudes. But they could not change human nature, a product of the distinctively human cerebral cortex. Human capacities like compassion and justice are our own and for us to guard. To ask (as some do) about a "right" to inherit a non-manipulated genome is to ask an unanswerable question: the language of rights is inappropriate in this context. Parents have a duty to safeguard and to serve the interests of their potential child. The medical duty is to help in that task in ways which they have limited freedom to choose. The role of churches is to be faithful to their deposit of faith and their theological principles, including that of freedom of conscience. Churches are too easily led in practice to over-rule conscience on grounds of authority, ecclesiastical or biblical, not sustained by convincing reason. This is most evident in some declarations concerning human reproduction. Better were it for them to help their faithful in moral reasoning, the ethics of choice; to keep consciences tender.

  1. Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells

    Directory of Open Access Journals (Sweden)

    Kyoung-jin Min

    2017-08-01

    Full Text Available Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki cells. Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose polymerase (PARP, which is a marker of apoptosis, and increased caspase activation. We found that pan-caspase inhibitor (z-VAD-fmk inhibited fisetin-induced apoptosis. In addition, fisetin induced death receptor 5 (DR5 expression at the transcriptional level, and down-regulation of DR5 by siRNA blocked fisetin-induced apoptosis. Furthermore, fisetin induced p53 protein expression through up-regulation of protein stability, whereas down-regulation of p53 by siRNA markedly inhibited fisetin-induced DR5 expression. In contrast, fisetin induced up-regulation of CHOP expression and reactive oxygen species production, which had no effect on fisetin-induced apoptosis. Taken together, our study demonstrates that fisetin induced apoptosis through p53 mediated up-regulation of DR5 expression at the transcriptional level.

  2. Molecular basis of retinol anti-ageing properties in naturally aged human skin in vivo.

    Science.gov (United States)

    Shao, Y; He, T; Fisher, G J; Voorhees, J J; Quan, T

    2017-02-01

    Retinoic acid has been shown to improve the aged-appearing skin. However, less is known about the anti-ageing effects of retinol (ROL, vitamin A), a precursor of retinoic acid, in aged human skin in vivo. This study aimed to investigate the molecular basis of ROL anti-ageing properties in naturally aged human skin in vivo. Sun-protected buttock skin (76 ± 6 years old, n = 12) was topically treated with 0.4% ROL and its vehicle for 7 days. The effects of topical ROL on skin epidermis and dermis were evaluated by immunohistochemistry, in situ hybridization, Northern analysis, real-time RT-PCR and Western analysis. Collagen fibrils nanoscale structure and surface topology were analysed by atomic force microscopy. Topical ROL shows remarkable anti-ageing effects through three major types of skin cells: epidermal keratinocytes, dermal endothelial cells and fibroblasts. Topical ROL significantly increased epidermal thickness by stimulating keratinocytes proliferation and upregulation of c-Jun transcription factor. In addition to epidermal changes, topical ROL significantly improved dermal extracellular matrix (ECM) microenvironment; increasing dermal vascularity by stimulating endothelial cells proliferation and ECM production (type I collagen, fibronectin and elastin) by activating dermal fibroblasts. Topical ROL also stimulates TGF-β/CTGF pathway, the major regulator of ECM homeostasis, and thus enriched the deposition of ECM in aged human skin in vivo. 0.4% topical ROL achieved similar results as seen with topical retinoic acid, the biologically active form of ROL, without causing noticeable signs of retinoid side effects. 0.4% topical ROL shows remarkable anti-ageing effects through improvement of the homeostasis of epidermis and dermis by stimulating the proliferation of keratinocytes and endothelial cells, and activating dermal fibroblasts. These data provide evidence that 0.4% topical ROL is a promising and safe treatment to improve the naturally aged human skin

  3. Learning from the continuities in humanity and nature

    Science.gov (United States)

    William R., Jr. Burch

    1977-01-01

    Though the emphasis in American life is upon dramatic social change, the firmer reality is our great continuity in social behavior and institutions. For example, though many strategies of child rearing have cycled through human society, the basic problems and responsible social unit remain the same. Of necessity, children have an ordered and holistic view of nature and...

  4. 15 CFR 990.20 - Relationship to the CERCLA natural resource damage assessment regulations.

    Science.gov (United States)

    2010-01-01

    ...., and the Federal Water Pollution Control Act (Clean Water Act), 33 U.S.C. 1321 et seq., are codified at... Relating to Commerce and Foreign Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OIL POLLUTION ACT REGULATIONS NATURAL RESOURCE DAMAGE ASSESSMENTS Authorities § 990.20...

  5. TXNIP regulates peripheral glucose metabolism in humans

    DEFF Research Database (Denmark)

    Parikh, Hemang; Carlsson, Emma; Chutkow, William A

    2007-01-01

    combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein (TXNIP) as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose. In healthy individuals, its expression was inversely correlated...... expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM. CONCLUSIONS: TXNIP regulates both insulin-dependent and insulin......-independent pathways of glucose uptake in human skeletal muscle. Combined with recent studies that have implicated TXNIP in pancreatic beta-cell glucose toxicity, our data suggest that TXNIP might play a key role in defective glucose homeostasis preceding overt T2DM....

  6. Regulation of autophagy in human skeletal muscle: effects of exercise, exercise training and insulin stimulation

    DEFF Research Database (Denmark)

    Fritzen, Andreas Mæchel; Madsen, Agnete Louise Bjerregaard; Kleinert, Maximilian

    2016-01-01

    Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one-legged exercise, one-legged exer......Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one-legged exercise, one......-legged exercise training as well as in response to subsequent insulin stimulation in exercised and non-exercised human muscle. Acute one-legged exercise decreased (phuman muscle....... The decrease in LC3-II/LC3-I ratio did not correlate with activation of AMPK trimer complexes in human muscle. Consistently, pharmacological AMPK activation with AICAR in mouse muscle did not affect the LC3-II/LC3-I ratio. Four hours after exercise, insulin further reduced (p

  7. Tension in the Natural History of Human Thinking

    Directory of Open Access Journals (Sweden)

    Moll Henrike

    2016-03-01

    Full Text Available Michael Tomasello has greatly expanded our knowledge of human cognition and how it differs from that of other animals. In this commentary to his recent book A Natural History of Human Thinking, I first critique some of the presuppositions and arguments of his evolutionary story about how homo sapiens’ cognition emerged. For example, I question the strategy of relying on the modern chimpanzee as a model for our last shared ancestor, and I doubt the idea that what changed first over evolutionary time was hominin behavior, which then in turn brought about changes in cognition. In the second half of the commentary I aim to show that the author oscillates between an additive and a transformative account of human shared intentionality. I argue that shared intentionality shapes cognition in its entirety and therefore precludes the possibility that humans have the same, individual intentionality (as shown in, e.g. their instrumental reasoning as other apes.

  8. Regulation of the natural gas distribution sector: a comparison of Brazilian and Colombian industries; Regulacao do setor de distribuicao de gas natural: uma comparacao dos casos brasileiro e colombiano

    Energy Technology Data Exchange (ETDEWEB)

    Domingues, Mariana Peralva; Ferraro, Marcelo Colomer [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil)

    2008-07-01

    The Bolivia oil industry nationalization in 2006 and the high price of oil on the international market called the public and government attention to the problems of the natural gas industry regulation in Brazil. Recently, the establishment of a specific law for the natural gas industry had been debated in academic circles and in government institutions. In Brazil, the absence of an integrated energy policy and the absence of a homogeneous regulatory framework interfere with natural gas industry development, especially in distribution. Thus, the objective of the work will be contrast the Colombia distribution natural gas regulatory structure sector to the Brazilian natural gas regulatory framework. The comparison of the Brazilian regulatory framework and the Colombian natural gas regulation shows that the existence of different kinds of concession contracts in distribution is one of the explanations for the different levels of investment in Brazil. The contract with exclusive right to explore the distribution service in geographic territories also contributes to explain the low coverage rate of public distribution companies. Thus, the rapid expansion of the natural gas distribution network in Colombia after the regulatory reforms shows the importance of the establishment of a regulatory structure to push private investment. The Colombian case can be considered a good model for other countries in South America, especially to the natural gas distribution regulation. (author)

  9. Natural autoantibodies and complement promote the uptake of a self antigen, human thyroglobulin, by B cells and the proliferation of thyroglobulin-reactive CD4(+) T cells in healthy individuals

    DEFF Research Database (Denmark)

    Nielsen, C H; Leslie, R G; Jepsen, B S

    2001-01-01

    Serum from normal individuals contains substantial amounts of natural antibodies (NA) capable of recognizing self antigens. However, the physiological implications of this autoreactivity remain unclear. We have examined the role of self-reactive NA and complement in mediating the uptake of human...... cells are prerequisites for the proliferation of Tg-reactive CD4(+) T cells, suggesting a novel role for natural autoantibodies and complement in the regulation of autoreactivity under physiological conditions....

  10. mTORC1 directly phosphorylates and regulates human MAF1.

    Science.gov (United States)

    Michels, Annemieke A; Robitaille, Aaron M; Buczynski-Ruchonnet, Diane; Hodroj, Wassim; Reina, Jaime H; Hall, Michael N; Hernandez, Nouria

    2010-08-01

    mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the phosphorylations nor the kinase involved is known. We find that human MAF1 is absolutely required for pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. The protein is phosphorylated mainly on residues S60, S68, and S75, and this inhibits its pol III repression function. The responsible kinase is mTORC1, which phosphorylates MAF1 directly. Our results describe molecular mechanisms by which mTORC1 controls human MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1.

  11. IGF-1 promotes the development and cytotoxic activity of human NK cells

    Science.gov (United States)

    Ni, Fang; Sun, Rui; Fu, Binqing; Wang, Fuyan; Guo, Chuang; Tian, Zhigang; Wei, Haiming

    2013-01-01

    Insulin-like growth factor 1 (IGF-1) is a critical regulator of many physiological functions, ranging from longevity to immunity. However, little is known about the role of IGF-1 in natural killer cell development and function. Here, we identify an essential role for IGF-1 in the positive regulation of human natural killer cell development and cytotoxicity. Specifically, we show that human natural killer cells have the ability to produce IGF-1 and that differential endogenous IGF-1 expression leads to disparate cytotoxicity in human primary natural killer cells. Moreover, miR-483-3p is identified as a critical regulator of IGF-1 expression in natural killer cells. Overexpression of miR-483-3p has an effect similar to IGF-1 blockade and decreased natural killer cell cytotoxicity, whereas inhibition of miR-483-3p has the opposite effect, which is reversible with IGF-1 neutralizing antibody. These findings indicate that IGF-1 and miR-483-3p belong to a new class of natural killer cell functional modulators and strengthen the prominent role of IGF-1 in innate immunity. PMID:23403580

  12. The impacts of nature experience on human cognitive function and mental health.

    Science.gov (United States)

    Bratman, Gregory N; Hamilton, J Paul; Daily, Gretchen C

    2012-02-01

    Scholars spanning a variety of disciplines have studied the ways in which contact with natural environments may impact human well-being. We review the effects of such nature experience on human cognitive function and mental health, synthesizing work from environmental psychology, urban planning, the medical literature, and landscape aesthetics. We provide an overview of the prevailing explanatory theories of these effects, the ways in which exposure to nature has been considered, and the role that individuals' preferences for nature may play in the impact of the environment on psychological functioning. Drawing from the highly productive but disparate programs of research in this area, we conclude by proposing a system of categorization for different types of nature experience. We also outline key questions for future work, including further inquiry into which elements of the natural environment may have impacts on cognitive function and mental health; what the most effective type, duration, and frequency of contact may be; and what the possible neural mechanisms are that could be responsible for the documented effects. © 2012 New York Academy of Sciences.

  13. Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries.

    Directory of Open Access Journals (Sweden)

    Sonya Hui

    Full Text Available We recently identified sphingosine-1-phosphate (S1P signaling and the cystic fibrosis transmembrane conductance regulator (CFTR as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i express critical S1P signaling elements, (ii constrict in response to S1P and (iii lose myogenic responsiveness following S1P receptor antagonism (JTE013. However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.

  14. Anthropologia transscendentalis. Kant's theory of human nature.

    Science.gov (United States)

    Battaglia, F

    2012-01-01

    In recent years mankind has greatly extended its knowledge of living things, in general, and itself, in particular. Such a wide-ranging body of knowledge has consequently led to the need for a theory to encompass it, that is, a coherent framework in which to systematically arrange mankind's understanding of itself, not only with regard to its physical nature, but to its individuality and sociality as well. Such a theory would moreover provide the means to mediate between the various domains of scientific and technological enquiry, on the one hand, and the cultural dimensions of human society, on the other. Already in the 18th century, Immanuel Kant strove to establish a discipline that was systematic, yet at the same time accessible. It was due to his efforts that philosophical anthropology was introduced into university curricula, to the benefit not only of philosophers, but of physicians and jurists as well. Kant's position is by no means prejudicial towards science. To the contrary, he was quite careful to appraise the impact of the sciences on the overall cognitive horizons of mankind and therefore on their potential to influence humankind's idea of itself. Clearly such a perspective is relevant to today's strongly felt need to reconcile modern neuroscience's revolutionary findings on the biological bases of the mind - of man's experience and behaviour - with the idea man needs of himself in order to orient his actions not only as individual but also as "citizen of the world" as well - something on which Kant worked with unremitting commitment throughout his entire research career. This article traces Kant's anthropological conception with regard to four specific issues: (1) its relation to science; (2) the relationship between empirical and transcendental in the speculative use and in practical use of reason; (3) the dialectic between what nature does and what human beings does, in the construction of humanity itself; (4) and finally about the character of the

  15. Worldwide Regulations of Standard Values of Pesticides for Human Health Risk Control: A Review

    Science.gov (United States)

    Jennings, Aaron

    2017-01-01

    The impact of pesticide residues on human health is a worldwide problem, as human exposure to pesticides can occur through ingestion, inhalation, and dermal contact. Regulatory jurisdictions have promulgated the standard values for pesticides in residential soil, air, drinking water, and agricultural commodity for years. Until now, more than 19,400 pesticide soil regulatory guidance values (RGVs) and 5400 pesticide drinking water maximum concentration levels (MCLs) have been regulated by 54 and 102 nations, respectively. Over 90 nations have provided pesticide agricultural commodity maximum residue limits (MRLs) for at least one of the 12 most commonly consumed agricultural foods. A total of 22 pesticides have been regulated with more than 100 soil RGVs, and 25 pesticides have more than 100 drinking water MCLs. This research indicates that those RGVs and MCLs for an individual pesticide could vary over seven (DDT drinking water MCLs), eight (Lindane soil RGVs), or even nine (Dieldrin soil RGVs) orders of magnitude. Human health risk uncertainty bounds and the implied total exposure mass burden model were applied to analyze the most commonly regulated and used pesticides for human health risk control. For the top 27 commonly regulated pesticides in soil, there are at least 300 RGVs (8% of the total) that are above all of the computed upper bounds for human health risk uncertainty. For the top 29 most-commonly regulated pesticides in drinking water, at least 172 drinking water MCLs (5% of the total) exceed the computed upper bounds for human health risk uncertainty; while for the 14 most widely used pesticides, there are at least 310 computed implied dose limits (28.0% of the total) that are above the acceptable daily intake values. The results show that some worldwide standard values were not derived conservatively enough to avoid human health risk by the pesticides, and that some values were not computed comprehensively by considering all major human exposure

  16. Worldwide Regulations of Standard Values of Pesticides for Human Health Risk Control: A Review.

    Science.gov (United States)

    Li, Zijian; Jennings, Aaron

    2017-07-22

    Abstract : The impact of pesticide residues on human health is a worldwide problem, as human exposure to pesticides can occur through ingestion, inhalation, and dermal contact. Regulatory jurisdictions have promulgated the standard values for pesticides in residential soil, air, drinking water, and agricultural commodity for years. Until now, more than 19,400 pesticide soil regulatory guidance values (RGVs) and 5400 pesticide drinking water maximum concentration levels (MCLs) have been regulated by 54 and 102 nations, respectively. Over 90 nations have provided pesticide agricultural commodity maximum residue limits (MRLs) for at least one of the 12 most commonly consumed agricultural foods. A total of 22 pesticides have been regulated with more than 100 soil RGVs, and 25 pesticides have more than 100 drinking water MCLs. This research indicates that those RGVs and MCLs for an individual pesticide could vary over seven (DDT drinking water MCLs), eight (Lindane soil RGVs), or even nine (Dieldrin soil RGVs) orders of magnitude. Human health risk uncertainty bounds and the implied total exposure mass burden model were applied to analyze the most commonly regulated and used pesticides for human health risk control. For the top 27 commonly regulated pesticides in soil, there are at least 300 RGVs (8% of the total) that are above all of the computed upper bounds for human health risk uncertainty. For the top 29 most-commonly regulated pesticides in drinking water, at least 172 drinking water MCLs (5% of the total) exceed the computed upper bounds for human health risk uncertainty; while for the 14 most widely used pesticides, there are at least 310 computed implied dose limits (28.0% of the total) that are above the acceptable daily intake values. The results show that some worldwide standard values were not derived conservatively enough to avoid human health risk by the pesticides, and that some values were not computed comprehensively by considering all major human

  17. Human Rights Degradations Related to Natural Law: Philosophical-Juridic Self-Legitimation of Franquism

    Directory of Open Access Journals (Sweden)

    César López Rodríguez

    2017-11-01

    Full Text Available This essay identifies the problematic theoretical nature of human rights under Franco's regime, in the light of either a traditionalist or a totalitarian objective natural right's discursive hegemony. This contradictory theoretical alternative was already present in Ramiro de Maeztu's legal-political doctrine, which as the theoretical seed of the regime, led to those contradictions as embodied in two authors: F. Elías de Tejada and L. Legaz Lacambra. Drawing on a political critique of the text itself, the conclusion evinces the doctrinal state of human rights in the current Spanish constitutional system, exposing its contradictions as derived not from a traditionalist or a totalitarian objective natural right but from a subjective natural right.

  18. Natural Regulation of Energy Flow in a Green Quantum Photocell.

    Science.gov (United States)

    Arp, Trevor B; Barlas, Yafis; Aji, Vivek; Gabor, Nathaniel M

    2016-12-14

    Manipulating the flow of energy in nanoscale and molecular photonic devices is of both fundamental interest and central importance for applications in light energy harvesting optoelectronics. Under erratic solar irradiance conditions, unregulated power fluctuations in a light-harvesting photocell lead to inefficient energy storage in conventional solar cells and potentially fatal oxidative damage in photosynthesis. Here, we compare the theoretical minimum energy fluctuations in nanoscale quantum heat engine photocells that incorporate one or two photon-absorbing channels and show that fluctuations are naturally suppressed in the two-channel photocell. This intrinsic suppression acts as a passive regulation mechanism that enables the efficient conversion of varying incident solar power into a steady output for absorption over a broad range of the solar spectrum on Earth. Remarkably, absorption in the green portion of the spectrum provides no inherent regulatory benefit, indicating that green light should be rejected in a photocell whose primary role is the regulation of energy flow.

  19. Regulation of lipid deposition in farm animals: Parallels between agriculture and human physiology.

    Science.gov (United States)

    Bergen, Werner G; Brandebourg, Terry D

    2016-06-01

    For many years, clinically oriented scientists and animal scientists have focused on lipid metabolism and fat deposition in various fat depots. While dealing with a common biology across species, the goals of biomedical and food animals lipid metabolism research differ in emphasis. In humans, mechanisms and regulation of fat synthesis, accumulation of fat in regional fat depots, lipid metabolism and dysmetabolism in adipose, liver and cardiac tissues have been investigated. Further, energy balance and weight control have also been extensively explored in humans. Finally, obesity and associated maladies including high cholesterol and atherosclerosis, cardiovascular disease, insulin resistance, hypertension, metabolic syndrome and health outcomes have been widely studied. In food animals, the emphasis has been on regulation of fatty acid synthesis and lipid deposition in fat depots and deposition of intramuscular fat. For humans, understanding the regulation of energy balance and body weight and of prevention or treatment of obesity and associated maladies have been important clinical outcomes. In production of food animals lowering fat content in muscle foods while enhancing intramuscular fat (marbling) have been major targets. In this review, we summarize how our laboratories have addressed the goal of providing lean but yet tasty and juicy muscle food products to consumers. In addition, we here describe efforts in the development of a new porcine model to study regulation of fat metabolism and obesity. Commonalities and differences in regulation of lipid metabolism between humans, rodents and food animals are emphasized throughout this review. © 2016 by the Society for Experimental Biology and Medicine.

  20. CONSIDERATIONS REGARDING THE INTEGRATION OF FUNDAMENTAL HUMAN RIGHTS IN THE SYSTEM OF NATURAL LAW

    Directory of Open Access Journals (Sweden)

    Claudiu Ramon D. Butculescu

    2016-11-01

    Full Text Available This article studies the relationships and interactions between fundamental human rights and natural law school. The objectives of this paper are circumscribed to the way fundamental human rights, by their nature, can be integrated within the doctrine of natural law or to the contrary, may be related to various branches of legal positivism. In specialized literature, it was pointed out that fundamental human rights constitute genuine natural rights which have the same natural law recognized attributes: immutability, non-alienable nature et. al. However, in the context of contemporary changes within the European Union, generated by cultural differences which are becoming ever more significant, the question rises of whether those rights are in fact a creation of legal positivism. Within the paperthere are several doctrine opinions described, as well as some arguments for reconsidering the placement of fundamental rights within the sphere of legal positivism. Using the comparative method, the study analyzes the common points and the points of divergence between fundamental rights and the doctrines of natural law and legal positivism, seen through the prism of the general theory of systems, legal culture, legal colonialism and legal ethnocentrism.

  1. How do different humanness measures relate? Confronting the attribution of secondary emotions, human uniqueness, and human nature traits.

    Science.gov (United States)

    Martínez, Rocío; Rodriguez-Bailon, Rosa; Moya, Miguel; Vaes, Jeroen

    2017-01-01

    The present research examines the relationship between the infrahumanization approach and the two-dimensional model of humanness: an issue that has received very little empirical attention. In Study 1, we created three unknown groups (Humanized, Animalized, and Mechanized) granting/denying them Human Nature (HN) and Human Uniqueness (HU) traits. The attribution of primary/secondary emotions was measured. As expected, participants attributed more secondary emotions to the humanized compared to dehumanized groups. Importantly, both animalized and mechanized groups were attributed similar amounts of secondary emotions. In Study 2, the groups were described in terms of their capacity to express secondary emotions. We measured the attribution of HN/HU traits. Results showed that the infrahumanized group was denied both HU/HN traits. The results highlight the importance of considering the common aspects of both approaches in understanding processes of dehumanization.

  2. Antigen Presenting Cells and Stromal Cells Trigger Human Natural Killer Lymphocytes to Autoreactivity: Evidence for the Involvement of Natural Cytotoxicity Receptors (NCR and NKG2D

    Directory of Open Access Journals (Sweden)

    Alessandro Poggi

    2006-01-01

    Full Text Available Human natural killer (NK lymphocytes should not damage autologous cells due to the engagement of inhibitory receptor superfamily (IRS members by HLA-I. Nevertheless, NK cells kill self cells expressing low levels or lacking HLA-I, as it may occur during viral infections (missing-self hypothesis. Herein, we show that human NK cells can be activated upon binding with self antigen presenting cells or stromal cells despite the expression of HLA-I. Indeed, NK cells can kill and produce pro-inflammatory and regulating cytokines as IFN-γ, TNF-α and IL10 during interaction with autologous dendritic cells or bone marrow stromal cells or skin fibroblasts. The killing of antigen presenting and stromal cells is dependent on LFA1/ICAM1 interaction. Further, the natural cytotoxicity receptors (NCR NKp30 and NKp46 are responsible for the delivery of lethal hit to DC, whereas NKG2D activating receptor, the ligand of the MHC-related molecule MIC-A and the UL16 binding protein, is involved in stromal cell killing. These findings indicate that different activating receptors are involved in cell to self cell interaction. Finally, NK cells can revert the veto effect of stromal cells on mixed lymphocyte reaction further supporting the idea that NK cells may alter the interaction between T lymphocytes and microenvironment leading to autoreactivity.

  3. Biology, politics, and the emerging science of human nature.

    Science.gov (United States)

    Fowler, James H; Schreiber, Darren

    2008-11-07

    In the past 50 years, biologists have learned a tremendous amount about human brain function and its genetic basis. At the same time, political scientists have been intensively studying the effect of the social and institutional environment on mass political attitudes and behaviors. However, these separate fields of inquiry are subject to inherent limitations that may only be resolved through collaboration across disciplines. We describe recent advances and argue that biologists and political scientists must work together to advance a new science of human nature.

  4. Interleukin-6 receptor expression in contracting human skeletal muscle: regulating role of IL-6

    DEFF Research Database (Denmark)

    Keller, Pernille; Penkowa, Milena; Keller, Charlotte

    2005-01-01

    Contracting muscle fibers produce and release IL-6, and plasma levels of this cytokine are markedly elevated in response to physical exercise. We recently showed autocrine regulation of IL-6 in human skeletal muscle in vivo and hypothesized that this may involve up-regulation of the IL-6 receptor....... Infusion of rhIL-6 to humans had no effect on the mRNA level of the IL-6 receptor, whereas there was an increase at the protein level. IL-6 receptor mRNA increased similarly in muscle of both IL-6 KO mice and wild-type mice in response to exercise. In conclusion, exercise increases IL-6 receptor production....... Therefore, we investigated IL-6 receptor regulation in response to exercise and IL-6 infusion in humans. Furthermore, using IL-6-deficient mice, we investigated the role of IL-6 in the IL-6 receptor response to exercise. Human skeletal muscle biopsies were obtained in relation to: 3 h of bicycle exercise...

  5. Examining fire-prone forest landscapes as coupled human and natural systems

    Science.gov (United States)

    Thomas A. Spies; Eric M. White; Jeffrey D. Kline; A. Paige Fisher; Alan Ager; John Bailey; John Bolte; Jennifer Koch; Emily Platt; Christine S. Olsen; Derric Jacobs; Bruce Shindler; Michelle M. Steen-Adams; Roger. Hammer

    2014-01-01

    Fire-prone landscapes are not well studied as coupled human and natural systems (CHANS) and present many challenges for understanding and promoting adaptive behaviors and institutions. Here, we explore how heterogeneity, feedbacks, and external drivers in this type of natural hazard system can lead to complexity and can limit the development of more adaptive approaches...

  6. The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue.

    LENUS (Irish Health Repository)

    Ryan, James

    2011-01-01

    The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro.

  7. Patterns and Limitations of Urban Human Mobility Resilience under the Influence of Multiple Types of Natural Disaster.

    Science.gov (United States)

    Wang, Qi; Taylor, John E

    2016-01-01

    Natural disasters pose serious threats to large urban areas, therefore understanding and predicting human movements is critical for evaluating a population's vulnerability and resilience and developing plans for disaster evacuation, response and relief. However, only limited research has been conducted into the effect of natural disasters on human mobility. This study examines how natural disasters influence human mobility patterns in urban populations using individuals' movement data collected from Twitter. We selected fifteen destructive cases across five types of natural disaster and analyzed the human movement data before, during, and after each event, comparing the perturbed and steady state movement data. The results suggest that the power-law can describe human mobility in most cases and that human mobility patterns observed in steady states are often correlated with those in perturbed states, highlighting their inherent resilience. However, the quantitative analysis shows that this resilience has its limits and can fail in more powerful natural disasters. The findings from this study will deepen our understanding of the interaction between urban dwellers and civil infrastructure, improve our ability to predict human movement patterns during natural disasters, and facilitate contingency planning by policymakers.

  8. Regulation of human skeletal stem cells differentiation by Dlk1/Pref-1

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Jensen, Charlotte H; Gutierrez, Gloria

    2004-01-01

    Dlk-1/Pref-1 was identified as a novel regulator of human skeletal stem cell differentiation. Dlk1/Pref-1 is expressed in bone and cultured osteoblasts, and its constitutive overexpression led to inhibition of osteoblast and adipocyte differentiation of human marrow stromal cells. INTRODUCTION......: Molecular control of human mesenchymal stem cell (hMSC) differentiation into osteoblasts and adipocytes is not known. In this study, we examined the role of delta-like 1/preadipocyte factor-1 (Dlk1/Pref-1) in regulating the differentiation of hMSCs. MATERIALS AND METHODS: As a model for hMSCs, we have...... was used to confirm the in vitro effect of Dlk/Pref-1 on bone formation. RESULTS: Dlk1/Pref-1 was found to be expressed in fetal and adult bone, hMSCs, and some osteoblastic cell lines. A retroviral vector containing the human Dlk1/Pref-1 cDNA was used to create a cell line (hMSC-dlk1) expressing high...

  9. Curcumin induces down-regulation of EZH2 expression through the MAPK pathway in MDA-MB-435 human breast cancer cells.

    Science.gov (United States)

    Hua, Wen-Feng; Fu, Yong-Shui; Liao, Yi-Ji; Xia, Wen-Jie; Chen, Yang-Chao; Zeng, Yi-Xin; Kung, Hsiang-Fu; Xie, Dan

    2010-07-10

    Curcumin, a natural compound isolated from turmeric, may inhibit cell proliferation in various tumor cells through a mechanism that is not fully understood. The enhancer of zeste homolog 2 (EZH2) gene is overexpressed in human breast cancers with poor prognosis. In this study, we observed a dose- and time-dependent down-regulation of expression of EZH2 by curcumin that correlates with decreased proliferation in the MDA-MB-435 breast cancer cell line. The curcumin treatment resulted in an accumulation of cells in the G(1) phase of the cell cycle. Further investigation revealed that curcumin-induced down-regulation of EZH2 through stimulation of three major members of the mitogen-activated protein kinase (MAPK) pathway: c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 kinase. These data suggest that an underlying mechanism of the MAPK pathway mediates the down-regulation of EZH2, thus contributing to the anti-proliferative effects of curcumin against breast cancer. Copyright 2010 Elsevier B.V. All rights reserved.

  10. Self-regulated dynamical criticality in human ECoG

    Directory of Open Access Journals (Sweden)

    Guillermo eSolovey

    2012-07-01

    Full Text Available Mounting experimental and theoretical results indicate that neural systems are poised near a critical state. In human subjects, however, most evidence comes from functional MRI studies, an indirect measurement of neuronal activity with poor temporal resolution. Electrocorticography (ECoG provides a unique window into human brain activity: each electrode records, with high temporal resolution, the activity resulting from the sum of the local field potentials of sim 10^5 neurons. We show that the human brain ECoG recordings display features of self-regulated dynamical criticality: dynamical modes of activation drift around the critical stability threshold, moving in and out of the unstable region and equilibrating the global dynamical state at a very fast time scale. Moreover, the analysis also reveals differences between the resting state and a motor task, associated with increased stability of a fraction of the dynamical modes.

  11. The idea of human prehistory: the natural sciences, the human sciences, and the problem of human origins in Victorian Britain.

    Science.gov (United States)

    Goodrum, Matthew R

    2012-01-01

    The idea of human prehistory was a provocative and profoundly influential new notion that took shape gradually during the nineteenth century. While archaeology played an important role in providing the evidence for this idea many other sciences such as geology, paleontology, ethnology, and physical anthropology all made critical contributions to discussions about human prehistory. Many works have explored the history of prehistoric archaeology but this paper examines the conceptual content of the idea of "human prehistory" as it developed in the British scientific community. Both the natural and the human sciences contributed to what was in fact a complex collection of individual elements that together constituted the prevailing idea of human prehistory, although there were other competing conceptions of human prehistory endorsed by various scientists and critics of the new view of early human history.

  12. Mindsets and human nature: promoting change in the Middle East, the schoolyard, the racial divide, and willpower.

    Science.gov (United States)

    Dweck, Carol S

    2012-11-01

    Debates about human nature often revolve around what is built in. However, the hallmark of human nature is how much of a person's identity is not built in; rather, it is humans' great capacity to adapt, change, and grow. This nature versus nurture debate matters-not only to students of human nature-but to everyone. It matters whether people believe that their core qualities are fixed by nature (an entity theory, or fixed mindset) or whether they believe that their qualities can be developed (an incremental theory, or growth mindset). In this article, I show that an emphasis on growth not only increases intellectual achievement but can also advance conflict resolution between long-standing adversaries, decrease even chronic aggression, foster cross-race relations, and enhance willpower. I close by returning to human nature and considering how it is best conceptualized and studied. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  13. Cognitive Emotional Regulation Model in Human-Robot Interaction

    OpenAIRE

    Liu, Xin; Xie, Lun; Liu, Anqi; Li, Dan

    2015-01-01

    This paper integrated Gross cognitive process into the HMM (hidden Markov model) emotional regulation method and implemented human-robot emotional interaction with facial expressions and behaviors. Here, energy was the psychological driving force of emotional transition in the cognitive emotional model. The input facial expression was translated into external energy by expression-emotion mapping. Robot’s next emotional state was determined by the cognitive energy (the stimulus after cognition...

  14. Science, human nature, and a new paradigm for ethics education.

    Science.gov (United States)

    Lampe, Marc

    2012-09-01

    For centuries, religion and philosophy have been the primary basis for efforts to guide humans to be more ethical. However, training in ethics and religion and imparting positive values and morality tests such as those emanating from the categorical imperative and the Golden Rule have not been enough to protect humankind from its bad behaviors. To improve ethics education educators must better understand aspects of human nature such as those that lead to "self-deception" and "personal bias." Through rationalizations, faulty reasoning and hidden bias, individuals trick themselves into believing there is little wrong with their own unethical behavior. The application of science to human nature offers the possibility of improving ethics education through better self-knowledge. The author recommends a new paradigm for ethics education in contemporary modern society. This includes the creation of a new field called "applied evolutionary neuro-ethics" which integrates science and social sciences to improve ethics education. The paradigm can merge traditional thinking about ethics from religious and philosophical perspectives with new ideas from applied evolutionary neuro-ethics.

  15. Are Human and Natural Systems Decoupling?

    Science.gov (United States)

    Ehrlich, P. R.; Ehrlich, A. H.

    2012-12-01

    Typically, studies of coupled human and natural systems focus on reciprocating interactions and feedbacks between social systems and their biophysical environments. A major challenge today for CHANS scholars is to determine whether significant coupling remains or whether society is simply plunging ahead without reacting effectively to the deterioration of the environment. Thresholds for serious climate disruption are passing, toxification of Earth is proceeding apace and producing worrying symptoms, losses of vital biodiversity are at a 65 million-year high with serious consequences for ecosystem services, the epidemiological environment is deteriorating and a race is building to control water flows and extract the last high-quality resources, increasing the chances of ending civilization in an environment-wrecking nuclear war. The social system has attempted to respond to this perfect storm of problems. In the 1960s, building on much earlier work, scientists began assessing the consequences of an ever-growing human population and expanding consumption, overuse of pesticides, radioactive fallout, air and water pollution, and other environmental issues - and to recommend ameliorative steps. In the mid-1980s, biologists formed the discipline of conservation biology with the explicit purpose of stemming the hemorrhage of biodiversity. In the late 1980s, perhaps the single most important reaction to the worsening environmental situation was the development of the Montreal Protocol to preserve the vital stratospheric ozone layer. Around the same time, it dawned on the scientific community that climate disruption was going to be more immediate and dangerous than previously thought, but attempts by the world community to take mitigating steps have been pathetic. Action to deal with other dimensions of the environmental dilemma has been utterly inadequate. To see the growing disconnect, one only has to consider the attention paid in public discourse to the relatively

  16. Regulation of bone blood flow in humans

    DEFF Research Database (Denmark)

    Heinonen, Ilkka; Boushel, Robert; Hellsten, Ylva

    2018-01-01

    of cyclooxygenase (COX) enzyme, thus prostaglandin (PG) synthesis on femoral bone marrow blood flow by positron emission tomography in healthy young men at rest and during one leg dynamic exercise. In an additional group of healthy men, the role of adenosine (ADO) in the regulation of BBF during exercise......The mechanisms that regulate bone blood flow (BBF) in humans are largely unknown. Animal studies suggest that nitric oxide (NO) could be involved and in the present study we investigated the effects of inhibition of nitric oxide synthase (NOS) alone and in combination with inhibition.......036), but did not affect BBF significantly during exercise (5.5±1.4 ml/100g/min, p=0.25). On the other hand, while combined NOS and COX inhibition did not cause any further reduction of blood flow at rest (0.6±0.2 ml/100g/min), the combined blockade reduced BBF during exercise by ~21%, to 5.0±1.8 ml/100g/min (p...

  17. Conflict and cooperation with respect to European natural-gas regulations

    International Nuclear Information System (INIS)

    Austvik, O.G.

    2003-01-01

    Significant economies of scale and scope in the European gas industry make many transmission and local distribution companies natural monopolies in the markets in which they operate. Often, this gives them a strong market power and they experience little competitive pressure. Hence public interventions into the functioning of the market, as seen under the initiatives taken by the European Commission, such as the 'Gas Directive' occur. This paper discusses a game between the public authority and the transporters, where various levels of conflict and cooperation will influence how far regulations will go and how they will be designed. (author)

  18. Nonlinear impacts of small-scale natural events on Nineteenth Century human decision-making

    Science.gov (United States)

    McCormack, S. M.; Schlichting, K. M.; Urbanova, T.; Allen, T. L.; Ruffing, C. M.; Hermans, C. M.

    2009-12-01

    Natural climatological events that occurred throughout the Nineteenth Century, such as floods, droughts and hurricanes had long-lived, far-reaching consequences on the human decision-making processes occurring in the northeast United States. These events impacted the hydrological cycle, both directly -though the building of various structures- and indirectly - through an increased understanding of science; and the changing relationship between humans and their environment. This paper examines these events and associated processes through: 1) identifying specific natural events throughout the time period, occurring globally, with initial conditions conducive to long-lived consequences; 2) examining the relationship between scientific enquiry, natural events and the proliferation of dams in the northeast landscape; and 3) the growth of public health concerns, awareness of bacteriology, and municipal water supply systems. Results of this research indicate that the relationship between knowledge systems, natural events and subsequent engineering or technological fixes is complex and highly dependent on initial conditions. It highlights the time period where humans became increasingly dependent on engineered solutions to environmental problems, many of which still hold fast in our contemporary landscape. It is relevant to natural, social and governance structures in place today. The principles behind the occurrence of the natural phenomena and subsequent research and design have not changed; and understanding key events or stages in the past is tantamount to making predictions for the future.

  19. Phages in the Human Body.

    Science.gov (United States)

    Navarro, Ferran; Muniesa, Maite

    2017-01-01

    Bacteriophages, viruses that infect bacteria, have re-emerged as powerful regulators of bacterial populations in natural ecosystems. Phages invade the human body, just as they do other natural environments, to such an extent that they are the most numerous group in the human virome. This was only revealed in recent metagenomic studies, despite the fact that the presence of phages in the human body was reported decades ago. The influence of the presence of phages in humans has yet to be evaluated; but as in marine environments, a clear role in the regulation of bacterial populations could be envisaged, that might have an impact on human health. Moreover, phages are excellent vehicles of genetic transfer, and they contribute to the evolution of bacterial cells in the human body by spreading and acquiring DNA horizontally. The abundance of phages in the human body does not pass unnoticed and the immune system reacts to them, although it is not clear to what extent. Finally, the presence of phages in human samples, which most of the time is not considered, can influence and bias microbiological and molecular results; and, in view of the evidences, some studies suggest that more attention needs to be paid to their interference.

  20. Leptin regulates the pro-inflammatory response in human epidermal keratinocytes.

    Science.gov (United States)

    Lee, Moonyoung; Lee, Eunyoung; Jin, Sun Hee; Ahn, Sungjin; Kim, Sae On; Kim, Jungmin; Choi, Dalwoong; Lim, Kyung-Min; Lee, Seung-Taek; Noh, Minsoo

    2018-05-01

    The role of leptin in cutaneous wound healing process has been suggested in genetically obese mouse studies. However, the molecular and cellular effects of leptin on human epidermal keratinocytes are still unclear. In this study, the whole-genome-scale microarray analysis was performed to elucidate the effect of leptin on epidermal keratinocyte functions. In the leptin-treated normal human keratinocytes (NHKs), we identified the 151 upregulated and 53 downregulated differentially expressed genes (DEGs). The gene ontology (GO) enrichment analysis with the leptin-induced DEGs suggests that leptin regulates NHKs to promote pro-inflammatory responses, extracellular matrix organization, and angiogenesis. Among the DEGs, the protein expression of IL-8, MMP-1, fibronectin, and S100A7, which play roles in which is important in the regulation of cutaneous inflammation, was confirmed in the leptin-treated NHKs. The upregulation of the leptin-induced proteins is mainly regulated by the STAT3 signaling pathway in NHKs. Among the downregulated DEGs, the protein expression of nucleosome assembly-associated centromere protein A (CENPA) and CENPM was confirmed in the leptin-treated NHKs. However, the expression of CENPA and CENPM was not coupled with those of other chromosome passenger complex like Aurora A kinase, INCENP, and survivin. In cell growth kinetics analysis, leptin had no significant effect on the cell growth curves of NHKs in the normal growth factor-enriched condition. Therefore, leptin-dependent downregulation of CENPA and CENPM in NHKs may not be directly associated with mitotic regulation during inflammation.

  1. The safety and regulation of natural products used as foods and food ingredients.

    Science.gov (United States)

    Abdel-Rahman, Ali; Anyangwe, Njwen; Carlacci, Louis; Casper, Steve; Danam, Rebecca P; Enongene, Evaristus; Erives, Gladys; Fabricant, Daniel; Gudi, Ramadevi; Hilmas, Corey J; Hines, Fred; Howard, Paul; Levy, Dan; Lin, Ying; Moore, Robert J; Pfeiler, Erika; Thurmond, T Scott; Turujman, Saleh; Walker, Nigel J

    2011-10-01

    The use of botanicals and dietary supplements derived from natural substances as an adjunct to an improved quality of life or for their purported medical benefits has become increasingly common in the United States. This review addresses the safety assessment and regulation of food products containing these substances by the U.S. Food and Drug Administration (FDA). The issue of safety is particularly critical given how little information is available on the toxicity of some of these products. The first section uses case studies for stevia and green tea extracts as examples of how FDA evaluates the safety of botanical and herbal products submitted for consideration as Generally Recognized as Safe under the Federal Food, Drug, and Cosmetics Act. The 1994 Dietary Supplement Health Education Act (DSHEA) created a regulatory framework for dietary supplements. The article also discusses the regulation of this class of dietary supplements under DSHEA and addresses the FDA experience in analyzing the safety of natural ingredients described in pre-market safety submissions. Lastly, we discuss an ongoing interagency collaboration to conduct safety testing of nominated dietary supplements.

  2. Fisetin Enhances the Cytotoxicity of Gemcitabine by Down-regulating ERK-MYC in MiaPaca-2 Human Pancreatic Cancer Cells.

    Science.gov (United States)

    Kim, Nayoung; Kang, Min-Jung; Lee, Sang Hyub; Son, Jun Hyuk; Lee, Ji Eun; Paik, Woo Hyun; Ryu, Ji Kon; Kim, Yong-Tae

    2018-06-01

    Pancreatic cancer is a highly lethal malignancy with a poor prognosis. This study was set up to investigate the combined effect of gemcitabine and fisetin, a natural flavonoid from plants, on human pancreatic cancer cells. Meterials and Methods: Cytotoxic effect of fisetin in combination with gemcitabine on MiaPaca-2 cells was evaluated by the MTT assay, caspase 3/7 assay and propidium iodide/Annexin V. Extracellular signal-regulated kinase (ERK)-v-myc avian myelocytomatosis viral oncogene homolog (MYC) pathway was investigated by western blotting and quantitative real-time polymerase chain reaction. Combination treatment with fisetin and gemcitabine inhibited the proliferation of pancreatic cancer cells within 72 h and induced apoptosis, as indicated by activation of caspase 3/7. Fisetin down-regulated ERK at the protein and mRNA levels, and reduced ERK-induced MYC instability at the protein level. Fisetin sensitized human pancreatic cancer cells to gemcitabine-induced cytotoxicity through inhibition of ERK-MYC signaling. These results suggest that the combination of fisetin and gemcitabine could be developed as a novel potent therapeutic. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Genetic radiation effects and natural radioactivity of human population in Brazil

    International Nuclear Information System (INIS)

    Freire-Maia, A.

    1972-01-01

    A study on areas of natural radioactivity is done, covering the genetic effects on human population. The study is done in depth dealing with aspecto such as radioactive area involved, discussion of materials and methods, errors and fallacies, influential factors, models, buildup and natural radioactivity, hypotheses, results and perspectives, etc. It covers 24 localites, 8.572 couples and 43.930 pregnancy cases [pt

  4. Coupled human and natural systems approach to wildlife research and conservation

    Directory of Open Access Journals (Sweden)

    Neil H. Carter

    2014-09-01

    Full Text Available Conserving wildlife while simultaneously meeting the resource needs of a growing human population is a major sustainability challenge. As such, using combined social and environmental perspectives to understand how people and wildlife are interlinked, together with the mechanisms that may weaken or strengthen those linkages, is of utmost importance. However, such integrated information is lacking. To help fill this information gap, we describe an integrated coupled human and natural systems (CHANS approach for analyzing the patterns, causes, and consequences of changes in wildlife population and habitat, human population and land use, and their interactions. Using this approach, we synthesize research in two sites, Wolong Nature Reserve in China and Chitwan National Park in Nepal, to explicate key relationships between people and two globally endangered wildlife conservation icons, the giant panda and the Bengal tiger. This synthesis reveals that local resident characteristics such as household socioeconomics and demography, as well as community-level attributes such as resource management organizations, affect wildlife and their habitats in complex and even countervailing ways. Human impacts on wildlife and their habitats are in turn modifying the suite of ecosystem services that they provide to local residents in both sites, including access to forest products and cultural values. These interactions are further complicated by human and natural disturbance (e.g., civil wars, earthquakes, feedbacks (including policies, and telecouplings (socioeconomic and environmental interactions over distances that increasingly link the focal systems with other distant systems. We highlight several important implications of using a CHANS approach for wildlife research and conservation that is useful not only in China and Nepal but in many other places around the world facing similar challenges.

  5. Regulation of autophagy in human skeletal muscle: effects of exercise, exercise training and insulin stimulation

    Science.gov (United States)

    Fritzen, Andreas M.; Madsen, Agnete B.; Kleinert, Maximilian; Treebak, Jonas T.; Lundsgaard, Anne‐Marie; Jensen, Thomas E.; Richter, Erik A.; Wojtaszewski, Jørgen; Kiens, Bente

    2016-01-01

    Key points Regulation of autophagy in human muscle in many aspects differs from the majority of previous reports based on studies in cell systems and rodent muscle.An acute bout of exercise and insulin stimulation reduce human muscle autophagosome content.An acute bout of exercise regulates autophagy by a local contraction‐induced mechanism.Exercise training increases the capacity for formation of autophagosomes in human muscle.AMPK activation during exercise seems insufficient to regulate autophagosome content in muscle, while mTORC1 signalling via ULK1 probably mediates the autophagy‐inhibiting effect of insulin. Abstract Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one‐legged exercise, one‐legged exercise training and subsequent insulin stimulation in exercised and non‐exercised human muscle. Acute one‐legged exercise decreased (Pexercise in human muscle. The decrease in LC3‐II/LC3‐I ratio did not correlate with activation of 5′AMP activated protein kinase (AMPK) trimer complexes in human muscle. Consistently, pharmacological AMPK activation with 5‐aminoimidazole‐4‐carboxamide riboside (AICAR) in mouse muscle did not affect the LC3‐II/LC3‐I ratio. Four hours after exercise, insulin further reduced (Pexercised and non‐exercised leg in humans. This coincided with increased Ser‐757 phosphorylation of Unc51 like kinase 1 (ULK1), which is suggested as a mammalian target of rapamycin complex 1 (mTORC1) target. Accordingly, inhibition of mTOR signalling in mouse muscle prevented the ability of insulin to reduce the LC3‐II/LC3‐I ratio. In response to 3 weeks of one‐legged exercise training, the LC3‐II/LC3‐I ratio decreased (Pexercise and insulin stimulation reduce muscle autophagosome content, while exercise

  6. Audit report on GDF Suez supply costs in natural gas sale regulated tariffs. 4 April 2013

    International Nuclear Information System (INIS)

    2013-01-01

    After a recall of the context and objectives of this audit performed by the French Commission for Energy Regulation or CRE (legal framework, previously published opinion), this report first presents and comments the main evolutions of the European supply portfolio of GDF Suez in 2012: long term contracts to be negotiated again on significant volumes, a diversified portfolio with 30 per cent of short term purchases. In the second part, it analyses the adequacy between noticed and provisional supply costs on the one hand, and those estimated by means of the tariff formula for the calculation of natural gas sale regulated tariffs on the other hand. The third part gives recommendations regarding future decisions on the evolution of GDF-Suez natural gas regulated sale tariffs: discussion of the relevance of the formula used since January 2013, of perspectives for reviewing this tariff formula, of market share to be integrated, should the occasion occur, in the modified formula, and of the supply range to be taken into account

  7. Regulating hematology/oncology research involving human participants.

    Science.gov (United States)

    Kapp, Marshall B

    2002-12-01

    The conduct of hematology/oncology research, particularly clinical trials involving human participants, is an extensively regulated enterprise. Professionals in the specialty of hematology/oncology have important stakes in the success of biomedical research endeavors. Knowledge about and compliance strategies regarding the pertinent regulatory parameters are essential for avoiding negative legal repercussions for involved professionals. At the same time, there is a need to be aware of and actively resist the danger that strong [legal] protectionism might inadvertently result in undermining physician investigators' sense of personal moral responsibility in the conduct of human experiments. For all the limitations of that virtue in the protection of human subjects, it is surely not one that we would want medical scientists to be without [47]. Members of the potential participant pool, financial sponsors, and the general public must be convinced that everyone involved in the research enterprise is committed to operating within acceptable legal and ethical boundaries if the atmosphere of confidence and trust that is indispensable to the continued process and progress of investigation aimed at extending and improving quality of life for all of us in the future is to continue and flourish [48].

  8. The infra-value of human rights in the context of assisted regulation in México.

    Science.gov (United States)

    Esparza-Pérez, Rosa Verónica

    Infertility represents a problem in the context of reproductive health; to treat it were developed the techniques of assisted human reproduction, despite medical advances, the practice of techniques is subject to medical, legal and ethical dysfunctions. In Mexico, since the late 1980s assisted reproduction clinics were set up in public and private sector hospitals; however, they do not yet have a legal framework to regulate them in a specific way, which causes human rights violations that could be avoided with adequate regulation. This article advances the need to provide Mexico with such regulation as a means of guaranteeing both human rights and the rights of physicians and other health workers involved in these techniques. Copyright: © 2017 SecretarÍa de Salud.

  9. Rethinking urban nature to promote human well-being and livelihoods

    DEFF Research Database (Denmark)

    Raymond, Christopher; Gulsrud, Natalie Marie; Rodela, Romina

    On the 25thJanuary, 25 researchers, social entrepreneurs and policy makers attended a MOVIUM and SLU Urban Futures funded workshop on “Rethinking urban nature to promote human well-being and livelihoods”. The objectives of the workshop wereto identify and discuss integrated digital, social...... of urbannature in Malmö. Each group was asked to present their presentation to the wider group, what inspired them the most from the workshop activity and how their understanding of integrated solutions in urban nature changed over the day.This report presents a summary of each group’screations and findings...... and nature solutions for the use, management and governance of urban nature in the City of Malmö;and to provide a platform for knowledge sharing and networking between researchers and practitioners.Multiple enlightening presentations on how to plan, design and manage urban nature were provided by the cities...

  10. Why Do People Regulate Their Emotions? A Taxonomy of Motives in Emotion Regulation.

    Science.gov (United States)

    Tamir, Maya

    2016-08-01

    Emotion regulation involves the pursuit of desired emotional states (i.e., emotion goals) in the service of superordinate motives. The nature and consequences of emotion regulation, therefore, are likely to depend on the motives it is intended to serve. Nonetheless, limited attention has been devoted to studying what motivates emotion regulation. By mapping the potential benefits of emotion to key human motives, this review identifies key classes of motives in emotion regulation. The proposed taxonomy distinguishes between hedonic motives that target the immediate phenomenology of emotions, and instrumental motives that target other potential benefits of emotions. Instrumental motives include behavioral, epistemic, social, and eudaimonic motives. The proposed taxonomy offers important implications for understanding the mechanism of emotion regulation, variation across individuals and contexts, and psychological function and dysfunction, and points to novel research directions. © 2015 by the Society for Personality and Social Psychology, Inc.

  11. Megascale processes: Natural disasters and human behavior

    Science.gov (United States)

    Kieffer, S.W.; Barton, P.; Chesworth, W.; Palmer, A.R.; Reitan, P.; Zen, E.-A.

    2009-01-01

    Megascale geologic processes, such as earthquakes, tsunamis, volcanic eruptions, floods, and meteoritic impacts have occurred intermittently throughout geologic time, and perhaps on several planets. Unlike other catastrophes discussed in this volume, a unique process is unfolding on Earth, one in which humans may be the driving agent of megadisasters. Although local effects on population clusters may have been catastrophic in the past, human societies have never been interconnected globally at the scale that currently exists. We review some megascale processes and their effects in the past, and compare present conditions and possible outcomes. We then propose that human behavior itself is having effects on the planet that are comparable to, or greater than, these natural disasters. Yet, unlike geologic processes, human behavior is potentially under our control. Because the effects of our behavior threaten the stability, or perhaps even existence, of a civilized society, we call for the creation of a body to institute coherent global, credible, scientifi cally based action that is sensitive to political, economic, religious, and cultural values. The goal would be to institute aggressive monitoring, identify and understand trends, predict their consequences, and suggest and evaluate alternative actions to attempt to rescue ourselves and our ecosystems from catastrophe. We provide a template modeled after several existing national and international bodies. ?? 2009 The Geological Society of America.

  12. Integrating social science into empirical models of coupled human and natural systems

    Science.gov (United States)

    Jeffrey D. Kline; Eric M. White; A Paige Fischer; Michelle M. Steen-Adams; Susan Charnley; Christine S. Olsen; Thomas A. Spies; John D. Bailey

    2017-01-01

    Coupled human and natural systems (CHANS) research highlights reciprocal interactions (or feedbacks) between biophysical and socioeconomic variables to explain system dynamics and resilience. Empirical models often are used to test hypotheses and apply theory that represent human behavior. Parameterizing reciprocal interactions presents two challenges for social...

  13. Digital technology and human development: A charter for nature conservation

    NARCIS (Netherlands)

    Maffey, G.; Homans, H.; Banks, K.; Arts, K.A.J.

    2015-01-01

    The application of digital technology in conservation holds much potential for advancing the understanding of, and facilitating interaction with, the natural world. In other sectors, digital technology has long been used to engage communities and share information. Human development—which holds

  14. A Natural Light/Dark Cycle Regulation of Carbon-Nitrogen Metabolism and Gene Expression in Rice Shoots.

    Science.gov (United States)

    Li, Haixing; Liang, Zhijun; Ding, Guangda; Shi, Lei; Xu, Fangsen; Cai, Hongmei

    2016-01-01

    Light and temperature are two particularly important environmental cues for plant survival. Carbon and nitrogen are two essential macronutrients required for plant growth and development, and cellular carbon and nitrogen metabolism must be tightly coordinated. In order to understand how the natural light/dark cycle regulates carbon and nitrogen metabolism in rice plants, we analyzed the photosynthesis, key carbon-nitrogen metabolites, and enzyme activities, and differentially expressed genes and miRNAs involved in the carbon and nitrogen metabolic pathway in rice shoots at the following times: 2:00, 6:00, 10:00, 14:00, 18:00, and 22:00. Our results indicated that more CO2 was fixed into carbohydrates by a high net photosynthetic rate, respiratory rate, and stomatal conductance in the daytime. Although high levels of the nitrate reductase activity, free ammonium and carbohydrates were exhibited in the daytime, the protein synthesis was not significantly facilitated by the light and temperature. In mRNA sequencing, the carbon and nitrogen metabolism-related differentially expressed genes were obtained, which could be divided into eight groups: photosynthesis, TCA cycle, sugar transport, sugar metabolism, nitrogen transport, nitrogen reduction, amino acid metabolism, and nitrogen regulation. Additionally, a total of 78,306 alternative splicing events have been identified, which primarily belong to alternative 5' donor sites, alternative 3' acceptor sites, intron retention, and exon skipping. In sRNA sequencing, four carbon and nitrogen metabolism-related miRNAs (osa-miR1440b, osa-miR2876-5p, osa-miR1877 and osa-miR5799) were determined to be regulated by natural light/dark cycle. The expression level analysis showed that the four carbon and nitrogen metabolism-related miRNAs negatively regulated their target genes. These results may provide a good strategy to study how natural light/dark cycle regulates carbon and nitrogen metabolism to ensure plant growth and

  15. A natural light/dark cycle regulation of carbon-nitrogen metabolism and gene expression in rice shoots

    Directory of Open Access Journals (Sweden)

    Haixing Li

    2016-08-01

    Full Text Available Light and temperature are two particularly important environmental cues for plant survival. Carbon and nitrogen are two essential macronutrients required for plant growth and development, and cellular carbon and nitrogen metabolism must be tightly coordinated. In order to understand how the natural light/dark cycle regulates carbon and nitrogen metabolism in rice plants, we analyzed the photosynthesis, key carbon-nitrogen metabolites and enzyme activities, and differentially expressed genes and miRNAs involved in the carbon and nitrogen metabolic pathway in rice shoots at the following times: 2:00, 6:00, 10:00, 14:00, 18:00 and 22:00. Our results indicated that more CO2 was fixed into carbohydrates by a high net photosynthetic rate, respiratory rate and stomatal conductance in the daytime. Although high levels of the nitrate reductase activity, free ammonium and carbohydrates were exhibited in the daytime, the protein synthesis was not significantly facilitated by the light and temperature. In mRNA sequencing, the carbon and nitrogen metabolism-related differentially expressed genes were obtained, which could be divided into eight groups: photosynthesis, TCA cycle, sugar transport, sugar metabolism, nitrogen transport, nitrogen reduction, amino acid metabolism and nitrogen regulation. Additionally, a total of 78,306 alternative splicing events have been identified, which primarily belong to alternative 5' donor sites, alternative 3' acceptor sites, intron retention and exon skipping. In sRNA sequencing, four carbon and nitrogen metabolism-related miRNAs (osa-miR1440b, osa-miR2876-5p, osa-miR1877 and osa-miR5799 were determined to be regulated by natural light/dark cycle. The expression level analysis showed that the four carbon and nitrogen metabolism-related miRNAs negatively regulated their target genes. These results may provide a good strategy to study how natural light/dark cycle regulates carbon and nitrogen metabolism to ensure plant

  16. Effects of Butyltins (BTs) on Mitogen-Activated-Protein Kinase Kinase Kinase (MAP3K) and Ras Activity in Human Natural Killer Cells

    Science.gov (United States)

    Celada, Lindsay J.; Whalen, Margaret M.

    2013-01-01

    Butyltins (BTs) contaminate the environment and are found in human blood. BTs, tributyltin (TBT) and dibutyltin (DBT), diminish the cytotoxic function and levels of key proteins of human natural killer (NK) cells. NK cells are an initial immune defense against tumors, virally-infected cells and antibody-coated cells and thus critical to human health. The signaling pathways that regulate NK cell functions include mitogen-activated protein kinases (MAPKs). Studies have shown that exposure to BTs leads to the activation of specific MAPKs and MAPK kinases (MAP2Ks) in human NK cells. MAP2K kinases (MAP3Ks) are upstream activators of MAP2Ks, which then activate MAPKs. The current study examined if BT-induced activation of MAP3Ks was responsible for MAP2K and thus, MAPK activation. This study examines the effects of TBT and DBT on the total levels of two MAP3Ks, c-Raf and ASK1, as well as activating and inhibitory phosphorylation sites on these MAP3Ks. In addition, the immediate upstream activator of c-Raf, Ras, was examined for BT-induced alterations. Our results show significant activation of the MAP3K, c-Raf, in human NK cells within 10 minutes of TBT exposure and the MAP3K, ASK1, after one hour exposures to TBT. In addition, our results suggest that both TBT and DBT are impacting the regulation of c-Raf. PMID:24038145

  17. mTORC1 Directly Phosphorylates and Regulates Human MAF1▿

    Science.gov (United States)

    Michels, Annemieke A.; Robitaille, Aaron M.; Buczynski-Ruchonnet, Diane; Hodroj, Wassim; Reina, Jaime H.; Hall, Michael N.; Hernandez, Nouria

    2010-01-01

    mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the phosphorylations nor the kinase involved is known. We find that human MAF1 is absolutely required for pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. The protein is phosphorylated mainly on residues S60, S68, and S75, and this inhibits its pol III repression function. The responsible kinase is mTORC1, which phosphorylates MAF1 directly. Our results describe molecular mechanisms by which mTORC1 controls human MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1. PMID:20516213

  18. The significance of regulation and land use patterns on natural gas resource estimates in the Marcellus shale

    International Nuclear Information System (INIS)

    Blohm, Andrew; Peichel, Jeremy; Smith, Caroline; Kougentakis, Alexandra

    2012-01-01

    Recent advancements in natural gas extraction (e.g. hydraulic fracturing) have significantly increased natural gas reserves in the United States. Estimates of the technically recoverable natural gas (TRR) in the Marcellus range between 141 trillion cubic feet (TCF) and 489 TCF. However, TRR estimation does not incorporate existing policies, regulations, or land use. We find that approximately 48% of the Marcellus in New York and Pennsylvania is inaccessible given land use patterns and current policy. In New York, approximately 83% of the Marcellus is inaccessible; while in Pennsylvania about 32% of the Marcellus is off limits to drilling. The New York portion of the Marcellus is estimated to have a TRR of between 19.9 TCF and 68.9 TCF. We estimate that 79% of the resource is inaccessible, which results in an accessible resource estimate of between 4.2 TCF and 14.4 TCF. In Pennsylvania, the shale gas TRR is estimated at 86.6–300 TCF. However, we estimate that 31% of the resource is inaccessible, which results in an accessible resource estimate of between 60.0 TCF and 208 TCF. - Highlights: ► Existing natural gas reserve estimation techniques ignore land use, regulations, and policies. ► The impact of land use and regulation on the recoverable natural gas resource is significant. ► 48% of the Marcellus Shale in New York and Pennsylvania is inaccessible to drilling. ► In New York, approximately 83% of the Marcellus is inaccessible. ► In Pennsylvania about 32% of the Marcellus is off limits to drilling.

  19. Transposable element activity, genome regulation and human health.

    Science.gov (United States)

    Wang, Lu; Jordan, I King

    2018-03-02

    A convergence of novel genome analysis technologies is enabling population genomic studies of human transposable elements (TEs). Population surveys of human genome sequences have uncovered thousands of individual TE insertions that segregate as common genetic variants, i.e. TE polymorphisms. These recent TE insertions provide an important source of naturally occurring human genetic variation. Investigators are beginning to leverage population genomic data sets to execute genome-scale association studies for assessing the phenotypic impact of human TE polymorphisms. For example, the expression quantitative trait loci (eQTL) analytical paradigm has recently been used to uncover hundreds of associations between human TE insertion variants and gene expression levels. These include population-specific gene regulatory effects as well as coordinated changes to gene regulatory networks. In addition, analyses of linkage disequilibrium patterns with previously characterized genome-wide association study (GWAS) trait variants have uncovered TE insertion polymorphisms that are likely causal variants for a variety of common complex diseases. Gene regulatory mechanisms that underlie specific disease phenotypes have been proposed for a number of these trait associated TE polymorphisms. These new population genomic approaches hold great promise for understanding how ongoing TE activity contributes to functionally relevant genetic variation within and between human populations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Integrating human and natural systems in community psychology: an ecological model of stewardship behavior.

    Science.gov (United States)

    Moskell, Christine; Allred, Shorna Broussard

    2013-03-01

    Community psychology (CP) research on the natural environment lacks a theoretical framework for analyzing the complex relationship between human systems and the natural world. We introduce other academic fields concerned with the interactions between humans and the natural environment, including environmental sociology and coupled human and natural systems. To demonstrate how the natural environment can be included within CP's ecological framework, we propose an ecological model of urban forest stewardship action. Although ecological models of behavior in CP have previously modeled health behaviors, we argue that these frameworks are also applicable to actions that positively influence the natural environment. We chose the environmental action of urban forest stewardship because cities across the United States are planting millions of trees and increased citizen participation in urban tree planting and stewardship will be needed to sustain the benefits provided by urban trees. We used the framework of an ecological model of behavior to illustrate multiple levels of factors that may promote or hinder involvement in urban forest stewardship actions. The implications of our model for the development of multi-level ecological interventions to foster stewardship actions are discussed, as well as directions for future research to further test and refine the model.

  1. Adapting to extreme events related to natural variability and climate change: the imperative of coupling technology with strong regulation and governance.

    Science.gov (United States)

    Kythreotis, A P; Mercer, T G; Frostick, L E

    2013-09-03

    In recent years there has been an increase in extreme events related to natural variability (such as earthquakes, tsunamis and hurricanes) and climate change (such as flooding and more extreme weather). Developing innovative technologies is crucial in making society more resilient to such events. However, little emphasis has been placed on the role of human decision-making in maximizing the positive impacts of technological developments. This is exacerbated by the lack of appropriate adaptation options and the privatization of existing infrastructure, which can leave people exposed to increasing risk. This work examines the need for more robust government regulation and legislation to complement developments and innovations in technology in order to protect communities against such extreme events.

  2. Inducible, tunable and multiplex human gene regulation using CRISPR-Cpf1-based transcription factors | Office of Cancer Genomics

    Science.gov (United States)

    Targeted and inducible regulation of mammalian gene expression is a broadly important research capability that may also enable development of novel therapeutics for treating human diseases. Here we demonstrate that a catalytically inactive RNA-guided CRISPR-Cpf1 nuclease fused to transcriptional activation domains can up-regulate endogenous human gene expression. We engineered drug-inducible Cpf1-based activators and show how this system can be used to tune the regulation of endogenous gene transcription in human cells.

  3. Aryl hydrocarbon receptor nuclear translocator in human liver is regulated by miR-24

    Energy Technology Data Exchange (ETDEWEB)

    Oda, Yuki; Nakajima, Miki; Mohri, Takuya [Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medical Science, Kanazawa University, Kakuma-machi, Kanazawa 920-1192 (Japan); Takamiya, Masataka; Aoki, Yasuhiro [Department of Legal Medicine, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505 (Japan); Fukami, Tatsuki [Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medical Science, Kanazawa University, Kakuma-machi, Kanazawa 920-1192 (Japan); Yokoi, Tsuyoshi, E-mail: tyokoi@kenroku.kanazawa-u.ac.jp [Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medical Science, Kanazawa University, Kakuma-machi, Kanazawa 920-1192 (Japan)

    2012-05-01

    Aryl hydrocarbon receptor nuclear translocator (ARNT) forms a heterodimer with aryl hydrocarbon receptor or hypoxia inducible factor 1α to mediate biological responses to xenobiotic exposure and hypoxia. Although the regulation mechanism of the ARNT expression is largely unknown, earlier studies reported that the human ARNT protein level was decreased by hydrogen peroxide or reactive oxygen species. These stimuli increase the miR-24 level in various human cell lines. In silico analysis predicts that some microRNAs including miR-16 and miR-23b may bind to ARNT mRNA. This background prompted us to investigate whether human ARNT is regulated by microRNAs. Overexpression of miR-24 into HuH-7 and HepG2 cells significantly decreased the ARNT protein level, but not the ARNT mRNA level, indicating translational repression. However, overexpression of miR-16 or miR-23b caused no change in the ARNT expression. The miR-24-dependent down-regulation of ARNT decreased the expression of its downstream genes such as CYP1A1 and carbonic anhydrase IX. Luciferase assay was performed to determine the element on the ARNT mRNA to which miR-24 binds. Finally, it was demonstrated that the miR-24 levels in a panel of 26 human livers were inversely correlated with the protein levels or the translational efficiency of ARNT. Taken together, we found that miR-24 negatively regulates ARNT expression in human liver, affecting the expression of its downstream genes. miR-24 would be one of the factors underlying the mechanisms by which ARNT protein is decreased by reactive oxygen species. -- Highlights: ► Overexpression of miR-24 into human cell lines decreased the ARNT protein level. ► miR-24-dependent down-regulation of ARNT affected the expression of CYP1A1 and CA IX. ► Luciferase assay was performed to identify functional MREs for miR-24 in ARNT mRNA. ► The miR-24 levels inversely correlated with the ARNT protein levels in human liver.

  4. Expression, purification, cocrystallization and preliminary crystallographic analysis of sucrose octasulfate/human complement regulator factor H SCRs 6–8

    Energy Technology Data Exchange (ETDEWEB)

    Prosser, Beverly E.; Johnson, Steven; Roversi, Pietro [The Sir William Dunn School of Pathology, The University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Clark, Simon J. [Faculty of Life Sciences, Manchester University, Michael Smith Building, Oxford Road, Manchester M13 9PT (United Kingdom); Tarelli, Edward [Medical Biomics Centre, St George’s, University of London, Cranmer Terrace, London SW17 0RE (United Kingdom); Sim, Robert B. [The MRC Immunochemistry Unit, The University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Day, Antony J. [Faculty of Life Sciences, Manchester University, Michael Smith Building, Oxford Road, Manchester M13 9PT (United Kingdom); Lea, Susan M., E-mail: susan.lea@bnc.ox.ac.uk [The Sir William Dunn School of Pathology, The University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom)

    2007-06-01

    The crystallization of human complement regulator FH-678{sub 402H} with a glycosaminoglycan analogue is described. Human plasma protein complement factor H (FH) is an inhibitor of the spontaneously activated alternative complement pathway. An allotypic variant of FH, 402His, has been associated with age-related macular degeneration, the leading cause of blindness in the elderly. Crystals of FH domains 6–8 (FH678) containing 402His have been grown in the presence of a polyanionic sucrose octasulfate ligand (an analogue of the natural glycosaminoglycan ligands of FH) using both native and selenomethionine-derivatized protein. Native data sets diffracting to 2.3 Å and SeMet data sets of up to 2.8 Å resolution have been collected. An anomalous difference Patterson map reveals self- and cross-peaks from two incorporated Se atoms. The corresponding selenium substructure has been solved.

  5. Human and natural influences on the changing thermal structure of the atmosphere.

    Science.gov (United States)

    Santer, Benjamin D; Painter, Jeffrey F; Bonfils, Céline; Mears, Carl A; Solomon, Susan; Wigley, Tom M L; Gleckler, Peter J; Schmidt, Gavin A; Doutriaux, Charles; Gillett, Nathan P; Taylor, Karl E; Thorne, Peter W; Wentz, Frank J

    2013-10-22

    Since the late 1970s, satellite-based instruments have monitored global changes in atmospheric temperature. These measurements reveal multidecadal tropospheric warming and stratospheric cooling, punctuated by short-term volcanic signals of reverse sign. Similar long- and short-term temperature signals occur in model simulations driven by human-caused changes in atmospheric composition and natural variations in volcanic aerosols. Most previous comparisons of modeled and observed atmospheric temperature changes have used results from individual models and individual observational records. In contrast, we rely on a large multimodel archive and multiple observational datasets. We show that a human-caused latitude/altitude pattern of atmospheric temperature change can be identified with high statistical confidence in satellite data. Results are robust to current uncertainties in models and observations. Virtually all previous research in this area has attempted to discriminate an anthropogenic signal from internal variability. Here, we present evidence that a human-caused signal can also be identified relative to the larger "total" natural variability arising from sources internal to the climate system, solar irradiance changes, and volcanic forcing. Consistent signal identification occurs because both internal and total natural variability (as simulated by state-of-the-art models) cannot produce sustained global-scale tropospheric warming and stratospheric cooling. Our results provide clear evidence for a discernible human influence on the thermal structure of the atmosphere.

  6. Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells

    International Nuclear Information System (INIS)

    Anisowicz, A.; Bardwell, L.; Sager, R.

    1987-01-01

    Comparison by subtractive hybridization of mRNAs revealed a moderately abundant message in highly tumorigenic CHEF/16 cells present at very low levels in closely related nontumorigenic CHEF/18 cells. After cloning and sequencing the corresponding cDNA, computer comparison showed closest homology with the human connective tissue-activating peptide III (CTAP III). The human tumor cell cDNA hybridizing with the Chinese hamster clone was isolated, sequenced, and found to have closer similarity to the Chinese hamster gene than to CTAP III. Thus, the cloned cDNAs from Chinese hamster and human cells represent a different gene, named gro. Studies of its transcriptional regulation have shown that expression is tightly regulated by growth status in normal Chinese hamster and human cells and relaxed in the tumorigenic cells so far examined

  7. Natural radionuclides in the human body; Natuerliche Radionuklide im menschlichen Koerper

    Energy Technology Data Exchange (ETDEWEB)

    Voelkle, Hansruedi [Fribourg Univ. (Switzerland). Physikdept.

    2017-08-01

    Natural radionuclides in the human body produce worldwide a medium annual radiation exposure of 0.31 mSv. 0.17 mSv are due to potassium-40 (K-40) per year, 0.12 mSv per year are due to radionuclides from the uranium and thorium decay series, less than 0.02 mSv due to cosmogenic radionuclides. Natural radioactivity is therefore the largest exposure source, anthropogenic exposure is comparatively marginal.

  8. O-GlcNAc transferase regulates transcriptional activity of human Oct4.

    Science.gov (United States)

    Constable, Sandii; Lim, Jae-Min; Vaidyanathan, Krithika; Wells, Lance

    2017-10-01

    O-linked β-N-acetylglucosamine (O-GlcNAc) is a single sugar modification found on many different classes of nuclear and cytoplasmic proteins. Addition of this modification, by the enzyme O-linked N-acetylglucosamine transferase (OGT), is dynamic and inducible. One major class of proteins modified by O-GlcNAc is transcription factors. O-GlcNAc regulates transcription factor properties through a variety of different mechanisms including localization, stability and transcriptional activation. Maintenance of embryonic stem (ES) cell pluripotency requires tight regulation of several key transcription factors, many of which are modified by O-GlcNAc. Octamer-binding protein 4 (Oct4) is one of the key transcription factors required for pluripotency of ES cells and more recently, the generation of induced pluripotent stem (iPS) cells. The action of Oct4 is modulated by the addition of several post-translational modifications, including O-GlcNAc. Previous studies in mice found a single site of O-GlcNAc addition responsible for transcriptional regulation. This study was designed to determine if this mechanism is conserved in humans. We mapped 10 novel sites of O-GlcNAc attachment on human Oct4, and confirmed a role for OGT in transcriptional activation of Oct4 at a site distinct from that found in mouse that allows distinction between different Oct4 target promoters. Additionally, we uncovered a potential new role for OGT that does not include its catalytic function. These results confirm that human Oct4 activity is being regulated by OGT by a mechanism that is distinct from mouse Oct4. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. About social and cultural aspects of human nature in the context of philosophical anthropology

    Directory of Open Access Journals (Sweden)

    S. K. Kostiuchkov

    2015-02-01

    Full Text Available In the paper the approaches to socio­cultural understanding of human nature in the context of philosophical anthropology, analyzes the essence of human nature contradictions inherent in the contradiction between biological and social components; author focuses attention on the concept of «identity» in the context of philosophical anthropology and characterization of the status of human life; put forward a reasoned statement that outlook, as the level of philosophical understanding of the world, combining both biological and social components of human nature. It is emphasized that universal principle transistorychnym public attitudes towards human life is the recognition of its absolute value in different dimensions ­ religious, philosophical, scientific. The author notes that religious, especially biblical doctrine emphasizes the value of human life that flows from dignity of man, created in God’s image, a rational being who comes to Earth as, in a sense, a representative of God. The article stresses the urgency of a new philosophical paradigm as an important ideological guideline that requires perceive and understand the biological basis of man is not as indispensable, but neutral background of social life, but as a basis upon which and through which a person is transformed into a cultural and civilized being.

  10. Dissolved nutrient exports from natural and human-impacted Neotropical catchments

    DEFF Research Database (Denmark)

    Gücker, Björn; Silva, Ricky C. S.; Graeber, Daniel

    2016-01-01

    Aim Neotropical biomes are highly threatened by land-use changes, but the catchment-wide biogeochemical effects are poorly understood. Here, we aim to compare exports of dissolved nitrogen (N) and phosphorus (P) from natural and human-impacted catchments in the Neotropics. Location Neotropics. Me...

  11. Overview of naturally occurring Earth materials and human health concerns

    Science.gov (United States)

    Ernst, W. G.

    2012-10-01

    The biosphere and the Earth's critical zone have maintained a dynamic equilibrium for more than 3.5 billion years. Except for solar energy, almost all terrestrial substances necessary for life have been derived from near-surface portions of the land, hydrosphere, and atmosphere. If aggregate biological activities are less than the rate of nutrient supply and/or resource renewal, sustained population growth is possible. Where the replenishment rate of a life-sustaining Earth material is finite, usage may reach a condition of dynamic equilibrium in which biological consumption equals but on average cannot exceed the overall supply. Although large, most natural resources are present in finite abundances; for such commodities, excessive present-day human utilization reduces future availability, and thus the ultimate planetary carrying capacity for civilization. Intensive use of Earth materials has enhanced the quality of life, especially in the developed nations. Still, natural background levels, and Earth processes such as volcanic eruptions, as well as human activities involving agriculture, construction, and the extraction, refining, and transformation of mineral resources have led to harmful side effects involving environmental degradation and public health hazards. Among naturally and anthropogenically induced risks are bioaccessible airborne dusts and gases, soluble pollutants in agricultural, industrial, and residential waters, and toxic chemical species in foods and manufactured products. At appropriate levels of ingestion, many Earth materials are necessary for existence, but underdoses and overdoses have mild to serious consequences for human health and longevity. This overview briefly sketches several natural resource health hazards. Included are volcanic ash + aerosols + gases, mineral dusts, non-volcanic aerosols + nanoparticles, asbestos + fibrous zeolites, arsenic, fluorine, iodine, uranium + thorium + radium + radon + polonium, selenium, mercury, copper

  12. Role of Natural IgM Autoantibodies (IgM-NAA) and IgM Anti-Leukocyte Antibodies (IgM-ALA) in Regulating Inflammation.

    Science.gov (United States)

    Lobo, Peter I

    2017-01-01

    Natural IgM autoantibodies (IgM-NAA) are rapidly produced to inhibit pathogens and abrogate inflammation mediated by invading microorganisms and host neoantigens. IgM-NAA achieve this difficult task by being polyreactive with low binding affinity but with high avidity, characteristics that allow these antibodies to bind antigenic determinants shared by pathogens and neoantigens. Hence the same clones of natural IgM can bind and mask host neoantigens as well as inhibit microorganisms. In addition, IgM-NAA regulate the inflammatory response via mechanisms involving binding of IgM to apoptotic cells to enhance their removal and binding of IgM to live leukocytes to regulate their function. Secondly, we review how natural IgM prevents autoimmune disorders arising from pathogenic IgG autoantibodies as well as by autoreactive B and T cells that have escaped tolerance mechanisms. Thirdly, using IgM knockout mice, we show that regulatory B and T cells require IgM to effectively regulate inflammation mediated by innate, adaptive and autoimmune mechanisms. It is therefore not surprising why the host positively selects such autoreactive B1 cells that generate protective IgM-NAA, which are also evolutionarily conserved. Fourthly, we show that IgM anti-leukocyte autoantibodies (IgM-ALA) levels and their repertoire can vary in normal humans and disease states and this variation may partly explain the observed differences in the inflammatory response after infection, ischemic injury or after a transplant. Finally we also show how protective IgM-NAA can be rendered pathogenic under non-physiological conditions. IgM-NAA have therapeutic potential. Polyclonal IgM infusions can be used to abrogate ongoing inflammation. Additionally, inflammation arising after ischemic kidney injury, e.g., during high-risk elective cardiac surgery or after allograft transplantation, can be prevented by pre-emptively infusing polyclonal IgM, or DC pretreated ex vivo with IgM, or by increasing in vivo Ig

  13. PKCα expression regulated by Elk-1 and MZF-1 in human HCC cells

    International Nuclear Information System (INIS)

    Hsieh, Y.-H.; Wu, T.-T.; Tsai, J.-H.; Huang, C.-Y.; Hsieh, Y.-S.; Liu, J.-Y.

    2006-01-01

    Our previous study found that PKCα was highly expressed in the poor-differentiated human HCC cells and associated with cell migration and invasion. In this study, we further investigated the gene regulation of this enzyme. We showed that PKCα expression enhancement in the poor-differentiated human HCC cells was found neither by DNA amplification nor by increasing mRNA stability using differential PCR and mRNA decay assays. After screening seven transcription factors in the putative cis-acting regulatory elements of human PKCα promoters, only Elk-1 and MZF-1 antisense oligonucleotide showed a significant reduction in the PKCα mRNA level. They also reduced cell proliferation, cell migratory and invasive capabilities, and DNA binding activities in the PKCα promoter region. Over-expression assay confirmed that the PKCα expression may be modulated by these two factors at the transcriptional level. Therefore, these results may provide a novel mechanism for PKCα expression regulation in human HCC cells

  14. Top 40 questions in coupled human and natural systems (CHANS research

    Directory of Open Access Journals (Sweden)

    Daniel Boyd. Kramer

    2017-06-01

    Full Text Available Understanding and managing coupled human and natural systems (CHANS is a central challenge of the 21st century, but more focus is needed to pursue the most important questions within this vast field given limited research capacity and funding. We present 40 important questions for CHANS research, identified through a two-part crowdsourcing exercise within the CHANS community. We solicited members of the International Network of Research on Coupled Human and Natural Systems (CHANS-Net to submit up to three questions that they considered transformative, receiving 540 questions from 207 respondents. After editing for clarity and consistency, we asked the network's members to each evaluate a random subset of 20 questions in importance on a scale from 1 (least important to 7 (extremely important. Questions on land use and agriculture topped the list, with a median importance ranking of 5.7, followed by questions of scale, climate change and energy, sustainability and development, adaptation and resilience, in addition to seven other categories. We identified 40 questions with a median importance of 6.0 or above, which we highlight as the current view of researchers active in the field as research questions to pursue in order to maximize impact on understanding and managing coupled human and natural systems for achieving sustainable development goals and addressing emerging global challenges.

  15. Regulation of MT1-MMP/MMP-2/TIMP-2 axis in human placenta

    Directory of Open Access Journals (Sweden)

    Vincent ZL

    2015-10-01

    Full Text Available Zoë L Vincent,1,2 Murray D Mitchell,l,3 Anna P Ponnampalam1,2 1Liggins Institute, 2Gravida: National Centre for Growth and Development, University of Auckland, Auckland, New Zealand; 3University of Queensland Centre for Clinical Research, Brisbane, QLD, Australia Abstract: Matrix metalloproteinases (MMPs and specific endogenous tissue inhibitors of metalloproteinases (TIMPs mediate rupture of the fetal membranes in both physiological and pathological conditions. MMPs and TIMPs are subject to regulation by DNA methylation in human malignancies and pre-eclampsia. To determine if membrane type 1 MMP (MT1-MMP, MMP2, and TIMP2 are regulated by DNA methylation in human placentas, we employed an in vitro model where human placental tissues were collected at term gestation and cultured with methylation inhibiting agent 5-aza-2′deoxycytidine (AZA and lipopolysaccharide. The results suggest that DNA methylation is not directly involved in the regulation of MT1-MMP in placental tissue; however, remodeling of chromatin by a pharmacologic agent such as AZA potentiates an infection-related increase in MT1-MMP. MT1-MMP is a powerful activator of MMP2 and this action, coupled with either no change or a decrease in TIMP2 concentrations, favors a gelatinolytic state leading to extracellular matrix degradation, which could predispose fetal membranes to rupture prematurely during inflammation. Keywords: placenta, epigenetic regulation, DNA methylation, MMPs, labor

  16. Influences of Antagonistic Views of Nature on Understanding of Humanity : In the Case of Rousseau and Nietzsche

    OpenAIRE

    宮島, 光志

    2003-01-01

    The aim of this study lies in considering, in the case of Rousseau and Nietzsche, how strongly the antagonistic views of nature influenced the understanding of humanity (human nature). Both Rousseau and Nietzsche criticized the modern European civilization and sought to recover the "nature" in human beings. However, at least, Nietzsche didn't assume that Rousseau was his forerunner. On the contrary, he criticized Rousseau as the greatest enemy. The reason for it can be explained from the diff...

  17. Human haemodynamic frequency harmonics regulate the inflammatory phenotype of vascular endothelial cells.

    Science.gov (United States)

    Feaver, Ryan E; Gelfand, Bradley D; Blackman, Brett R

    2013-01-01

    Haemodynamic variations are inherent to blood vessel geometries (such as bifurcations) and correlate with regional development of inflammation and atherosclerosis. However, the complex frequency spectrum characteristics from these haemodynamics have never been exploited to test whether frequency variations are critical determinants of endothelial inflammatory phenotype. Here we utilize an experimental Fourier transform analysis to systematically manipulate individual frequency harmonics from human carotid shear stress waveforms applied in vitro to human endothelial cells. The frequency spectrum, specifically the 0 th and 1st harmonics, is a significant regulator of inflammation, including NF-κB activity and downstream inflammatory phenotype. Further, a harmonic-based regression-model predicts eccentric NF-κB activity observed in the human internal carotid artery. Finally, short interfering RNA-knockdown of the mechanosensor PECAM-1 reverses frequency-dependent regulation of NF-κB activity. Thus, PECAM-1 may have a critical role in the endothelium's exquisite sensitivity to complex shear stress frequency harmonics and provide a mechanism for the focal development of vascular inflammation.

  18. The Human Genome Project: Information access, management, and regulation. Final report

    Energy Technology Data Exchange (ETDEWEB)

    McInerney, J.D.; Micikas, L.B.

    1996-08-31

    The Human Genome Project is a large, internationally coordinated effort in biological research directed at creating a detailed map of human DNA. This report describes the access of information, management, and regulation of the project. The project led to the development of an instructional module titled The Human Genome Project: Biology, Computers, and Privacy, designed for use in high school biology classes. The module consists of print materials and both Macintosh and Windows versions of related computer software-Appendix A contains a copy of the print materials and discs containing the two versions of the software.

  19. High throughput Screening to Identify Natural Human Monoamine Oxidase B Inhibitors

    Science.gov (United States)

    Mazzio, E; Deiab, S; Park, K; Soliman, KFA

    2012-01-01

    Age-related increase in monoamine oxidase B (MAO-B) may contribute to CNS neurodegenerative diseases. Moreover, MAO-B inhibitors are used in the treatment of idiopathic Parkinson disease as preliminary monotherapy or adjunct therapy with L-dopa. To date, meager natural sources of MAO-B inhibitors have been identified, and the relative strength, potency and rank of many plants relative to standard drugs such as Selegiline (L-deprenyl, Eldepryl) are not known. In this work, we developed and utilized a high throughput enzyme microarray format to screen and evaluate 905 natural product extracts (0.025–.7 mg/ml) to inhibit human MAO-B derived from BTI-TN-5B1-4 cells infected with recombinant baculovirus. The protein sequence of purified enzyme was confirmed using 1D gel electrophoresis-matrix assisted laser desorption ionization-time-of-flight-tandem mass spectroscopy, and enzyme activity was confirmed by [1] substrate conversion (3-mM benzylamine) to H202 and [2] benzaldehyde. Of the 905 natural extracts tested, the lowest IC50s [Comfrey, Bringraj, Skullcap, Kava-kava, Wild Indigo, Gentian and Green Tea. In conclusion, the data reflect relative potency information by rank of commonly used herbs and plants that contain human MAO-B inhibitory properties in their natural form. PMID:22887993

  20. The Economic Development of Natural Resources: Fracking and Self-Regulation in the Market for Land

    Directory of Open Access Journals (Sweden)

    Paul J. Kubik

    2013-06-01

    Full Text Available The purpose of this piece is to apply some of the lessons learned during the period of industrialization in 19th century Europe to the study of the effects and appropriate regulation of the contemporary process of hydraulic fracturing, or fracking, in the natural gas industry. An attempt is made to support the conclusion that the harmful side effects associated with the creation of self-regulating markets for land, labor and money during the 19th century is paralleled today by the self-regulating character of the process of hydraulic fracturing. As a result, the negative consequences associated with industrialization are been visited again on present day market economies.

  1. Small RNAs and the regulation of cis-natural antisense transcripts in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Lonardi Stefano

    2008-01-01

    Full Text Available Abstract Background In spite of large intergenic spaces in plant and animal genomes, 7% to 30% of genes in the genomes encode overlapping cis-natural antisense transcripts (cis-NATs. The widespread occurrence of cis-NATs suggests an evolutionary advantage for this type of genomic arrangement. Experimental evidence for the regulation of two cis-NAT gene pairs by natural antisense transcripts-generated small interfering RNAs (nat-siRNAs via the RNA interference (RNAi pathway has been reported in Arabidopsis. However, the extent of siRNA-mediated regulation of cis-NAT genes is still unclear in any genome. Results The hallmarks of RNAi regulation of NATs are 1 inverse regulation of two genes in a cis-NAT pair by environmental and developmental cues and 2 generation of siRNAs by cis-NAT genes. We examined Arabidopsis transcript profiling data from public microarray databases to identify cis-NAT pairs whose sense and antisense transcripts show opposite expression changes. A subset of the cis-NAT genes displayed negatively correlated expression profiles as well as inverse differential expression changes under at least one of the examined developmental stages or treatment conditions. By searching the Arabidopsis Small RNA Project (ASRP and Massively Parallel Signature Sequencing (MPSS small RNA databases as well as our stress-treated small RNA dataset, we found small RNAs that matched at least one gene in 646 pairs out of 1008 (64% protein-coding cis-NAT pairs, which suggests that siRNAs may regulate the expression of many cis-NAT genes. 209 putative siRNAs have the potential to target more than one gene and half of these small RNAs could target multiple members of a gene family. Furthermore, the majority of the putative siRNAs within the overlapping regions tend to target only one transcript of a given NAT pair, which is consistent with our previous finding on salt- and bacteria-induced nat-siRNAs. In addition, we found that genes encoding plastid- or

  2. Uncovering packaging features of co-regulated modules based on human protein interaction and transcriptional regulatory networks

    Directory of Open Access Journals (Sweden)

    He Weiming

    2010-07-01

    Full Text Available Abstract Background Network co-regulated modules are believed to have the functionality of packaging multiple biological entities, and can thus be assumed to coordinate many biological functions in their network neighbouring regions. Results Here, we weighted edges of a human protein interaction network and a transcriptional regulatory network to construct an integrated network, and introduce a probabilistic model and a bipartite graph framework to exploit human co-regulated modules and uncover their specific features in packaging different biological entities (genes, protein complexes or metabolic pathways. Finally, we identified 96 human co-regulated modules based on this method, and evaluate its effectiveness by comparing it with four other methods. Conclusions Dysfunctions in co-regulated interactions often occur in the development of cancer. Therefore, we focussed on an example co-regulated module and found that it could integrate a number of cancer-related genes. This was extended to causal dysfunctions of some complexes maintained by several physically interacting proteins, thus coordinating several metabolic pathways that directly underlie cancer.

  3. Cyclin-dependent kinase 5 regulates degranulation in human eosinophils.

    Science.gov (United States)

    Odemuyiwa, Solomon O; Ilarraza, Ramses; Davoine, Francis; Logan, Michael R; Shayeganpour, Anooshirvan; Wu, Yingqi; Majaesic, Carina; Adamko, Darryl J; Moqbel, Redwan; Lacy, Paige

    2015-04-01

    Degranulation from eosinophils in response to secretagogue stimulation is a regulated process that involves exocytosis of granule proteins through specific signalling pathways. One potential pathway is dependent on cyclin-dependent kinase 5 (Cdk5) and its effector molecules, p35 and p39, which play a central role in neuronal cell exocytosis by phosphorylating Munc18, a regulator of SNARE binding. Emerging evidence suggests a role for Cdk5 in exocytosis in immune cells, although its role in eosinophils is not known. We sought to examine the expression of Cdk5 and its activators in human eosinophils, and to assess the role of Cdk5 in eosinophil degranulation. We used freshly isolated human eosinophils and analysed the expression of Cdk5, p35, p39 and Munc18c by Western blot, RT-PCR, flow cytometry and immunoprecipitation. Cdk5 kinase activity was determined following eosinophil activation. Cdk5 inhibitors were used (roscovitine, AT7519 and small interfering RNA) to determine its role in eosinophil peroxidase (EPX) secretion. Cdk5 was expressed in association with Munc18c, p35 and p39, and phosphorylated following human eosinophil activation with eotaxin/CCL11, platelet-activating factor, and secretory IgA-Sepharose. Cdk5 inhibitors (roscovitine, AT7519) reduced EPX release when cells were stimulated by PMA or secretory IgA. In assays using small interfering RNA knock-down of Cdk5 expression in human eosinophils, we observed inhibition of EPX release. Our findings suggest that in activated eosinophils, Cdk5 is phosphorylated and binds to Munc18c, resulting in Munc18c release from syntaxin-4, allowing SNARE binding and vesicle fusion, with subsequent eosinophil degranulation. Our work identifies a novel role for Cdk5 in eosinophil mediator release by agonist-induced degranulation. © 2014 John Wiley & Sons Ltd.

  4. Detection of human muscle glycogen by natural abundance 13C NMR

    International Nuclear Information System (INIS)

    Avison, M.J.; Rothman, D.L.; Nadel, E.; Shulman, R.G.

    1988-01-01

    Natural abundance 13 C nuclear magnetic resonance spectroscopy was used to detect signals from glycogen in the human gastrocnemius muscle. The reproducibility of the measurement was demonstrated, and the ability to detect dynamic changes was confirmed by measuring a decrease in muscle glycogen levels after exercise and its subsequent repletion. Single frequency gated 1 H decoupling was used to obtain decoupled natural abundance 13 C NMR spectra of the C-1 position of muscle glycogen

  5. Natural phenolic antioxidants in human fluids: analytical approaches and antioxidant capacity studies

    International Nuclear Information System (INIS)

    Zhang, K.; Zuo, Y.

    2006-01-01

    Phenolic compounds are the most abundant natural antioxidants in our diet. Epidemiological studies have shown the possible prevention effects of consumption of fruits and vegetables rich in phenolic compounds on degenerative diseases, such as cardiovascular diseases and cancers. However, there is a serious lack of fundamental knowledge on the uptake and metabolism of phenolic compounds in humans. It is clear that phenolic molecules, only absorbed by humans, can exert biological effects. This review presents a current knowledge on the analytical methods, antioxidant capacity measurements, as well as research strategies related to natural phenolic antioxidants on human health. Both GC-MS and LC-MS have proved to be very useful analytical techniques that can be employed to identify and quantitate targeted phenolic antioxidants and their metabolites in biofluids. Free radical quenching tests provide a direct measurement of antioxidant capacity but lack specificity and may oversimplify the in vivo human physiological environment. Research strategies are diverse and mainly focused on positive health effect of antioxidants. In the future studies, multiple potential bioactivities, both positive and negative, should be considered. (author)

  6. Genome-Wide RNAi Ionomics Screen Reveals New Genes and Regulation of Human Trace Element Metabolism

    OpenAIRE

    Malinouski, Mikalai; Hasan, Nesrin M.; Zhang, Yan; Seravalli, Javier; Lin, Jie; Avanesov, Andrei; Lutsenko, Svetlana; Gladyshev, Vadim N.

    2017-01-01

    Trace elements are essential for human metabolism and dysregulation of their homeostasis is associated with numerous disorders. Here we characterize mechanisms that regulate trace elements in human cells by designing and performing a genome-wide high-throughput siRNA/ionomics screen, and examining top hits in cellular and biochemical assays. The screen reveals high stability of the ionomes, especially the zinc ionome, and yields known regulators and novel candidates. We further uncover fundam...

  7. Paucity of natural killer and cytotoxic T cells in human neuromyelitis optica lesions

    Science.gov (United States)

    Saadoun, Samira; Bridges, Leslie R.; Verkman, A. S.; Papadopoulos, Marios C.

    2013-01-01

    Neuromyelitis optica is a severe inflammatory demyelinating disease of the central nervous system. Most patients with neuromyelitis optica have circulating immunoglobulin G (IgG) antibodies against the astrocytic water channel protein aquaporin-4 (AQP4), which are pathogenic. Anti-AQP4 IgG-mediated complement-dependent astrocyte toxicity is a key mechanism of central nervous system damage in neuromyelitis optica, but the role of natural killer and cytotoxic T cells is unknown. Our objective was to determine whether natural killer and cytotoxic T cells play a role in human neuromyelitis optica lesions. We immunostained four actively demyelinating lesions, obtained from patients with anti-AQP4 IgG positive neuromyelitis optica, for Granzyme B and Perforin. The inflammatory cells were perivascular neutrophils, eosinophils and macrophages, with only occasional Granzyme B+ or Perforin + cells. Greater than 95% of inflamed vessels in each lesion had no surrounding Granzyme B+ or Perforin + cells. Granzyme B+ or Perforin+ cells were abundant in human spleen (positive control). Although natural killer cells produce central nervous system damage in mice injected with anti-AQP4 IgG, our findings here indicate that natural killer-mediated and T cell-mediated cytotoxicity are probably not involved in central nervous system damage in human neuromyelitis optica. PMID:23108041

  8. Endogenous cannabinoid receptor ligand induces the migration of human natural killer cells.

    Science.gov (United States)

    Kishimoto, Seishi; Muramatsu, Mayumi; Gokoh, Maiko; Oka, Saori; Waku, Keizo; Sugiura, Takayuki

    2005-02-01

    2-Arachidonoylglycerol is an endogenous ligand for the cannabinoid receptors (CB1 and CB2). Evidence is gradually accumulating which shows that 2-arachidonoylglycerol plays important physiological roles in several mammalian tissues and cells, yet the details remain ambiguous. In this study, we first examined the effects of 2-arachidonoylglycerol on the motility of human natural killer cells. We found that 2-arachidonoylglycerol induces the migration of KHYG-1 cells (a natural killer leukemia cell line) and human peripheral blood natural killer cells. The migration of natural killer cells induced by 2-arachidonoylglycerol was abolished by treating the cells with SR144528, a CB2 receptor antagonist, suggesting that the CB2 receptor is involved in the 2-arachidonoylglycerol-induced migration. In contrast to 2-arachidonoylglycerol, anandamide, another endogenous cannabinoid receptor ligand, did not induce the migration. Delta9-tetrahydrocannabinol, a major psychoactive constituent of marijuana, also failed to induce the migration; instead, the addition of delta9-tetrahydrocannabinol together with 2-arachidonoylglycerol abolished the migration induced by 2-arachidonoylglycerol. It is conceivable that the endogenous ligand for the cannabinoid receptor, that is, 2-arachidonoylglycerol, affects natural killer cell functions such as migration, thereby contributing to the host-defense mechanism against infectious viruses and tumor cells.

  9. Random genetic drift, natural selection, and noise in human cranial evolution.

    Science.gov (United States)

    Roseman, Charles C

    2016-08-01

    This study assesses the extent to which relationships among groups complicate comparative studies of adaptation in recent human cranial variation and the extent to which departures from neutral additive models of evolution hinder the reconstruction of population relationships among groups using cranial morphology. Using a maximum likelihood evolutionary model fitting approach and a mixed population genomic and cranial data set, I evaluate the relative fits of several widely used models of human cranial evolution. Moreover, I compare the goodness of fit of models of cranial evolution constrained by genomic variation to test hypotheses about population specific departures from neutrality. Models from population genomics are much better fits to cranial variation than are traditional models from comparative human biology. There is not enough evolutionary information in the cranium to reconstruct much of recent human evolution but the influence of population history on cranial variation is strong enough to cause comparative studies of adaptation serious difficulties. Deviations from a model of random genetic drift along a tree-like population history show the importance of environmental effects, gene flow, and/or natural selection on human cranial variation. Moreover, there is a strong signal of the effect of natural selection or an environmental factor on a group of humans from Siberia. The evolution of the human cranium is complex and no one evolutionary process has prevailed at the expense of all others. A holistic unification of phenome, genome, and environmental context, gives us a strong point of purchase on these problems, which is unavailable to any one traditional approach alone. Am J Phys Anthropol 160:582-592, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Human Nature and Social Order: A Comparative Critique of Hobbes ...

    African Journals Online (AJOL)

    Central to most intellectual debates on political organization is the issue of human nature, for one's understanding of it influences one's prescriptions on how best society can be governed. This paper examines the contractarian theories of Hobbes and Locke in their attempts to identify the conditions for social order.

  11. Economic regulation of Canada's natural gas delivery industry : policy and regulatory principles

    International Nuclear Information System (INIS)

    Gormley, B.

    2006-03-01

    This policy paper demonstrated how restoring balance and clarity to Canada's regulatory environment will ensure the continued strength of the economy, environment, and communities. It was noted that regulatory outcomes that reflect the broad public interest can be achieved if 4 basic principles for economic regulation are pursued. These principles include strength, balance, efficiency, and clarity. In particular, this paper addressed the challenge facing Canada's natural gas delivery industry in terms of increased energy demand, tight supply, ageing infrastructure and increasing cost pressures on the energy system. It emphasized that transparent, efficient energy policy developed through informed debate can provide the foundation for a reliable, environmentally acceptable and sustainable energy future. It was suggested that immediate attention be given to rebalancing the regulatory processes that have placed short term considerations above the longer term strength of the natural gas system; improving the support for new natural gas supply development; reconsidering pricing in some energy markets where information has been distorted; and revisiting the regulatory processes that have become inefficient

  12. Natural and human dimensions of a quasi-wild species: The case of kudzu

    Science.gov (United States)

    Li, Z.; Dong, Q.; Albright, Thomas P.; Guo, Q.

    2011-01-01

    The human dimensions of biotic invasion are generally poorly understood, even among the most familiar invasive species. Kudzu (Pueraria montana (Lour.) Merr.) is a prominent invasive plant and an example of quasi-wild species, which has experienced repeated introduction, cultivation, and escape back to the wild. Here, we review a large body of primary scientific and historic records spanning thousands of years to characterize the complex relationships among kudzu, its natural enemies, and humans, and provide a synthesis and conceptual model relevant to the ecology and management of quasi-wild invasive species. We documented over 350, mostly insect, natural enemy species and their impacts on kudzu in its native East Asian range. These natural enemies play a minor role in limiting kudzu in its native range, rarely generating severe impacts on populations of wild kudzu. We identified a number of significant influences of humans including dispersal, diverse cultural selection, and facilitation through disturbances, which catalyzed the expansion and exuberance of kudzu. On the other hand, harvest by humans appears to be the major control mechanism in its native areas. Humans thus have a complex relationship with kudzu. They have acted as both friend and foe, affecting the distribution and abundance of kudzu in ways that vary across its range and over time. Our conceptual model of kudzu emphasizes the importance of multiple human dimensions in shaping the biogeography of a species and illustrates how kudzu and other quasi-wild species are more likely to be successful invaders. ?? 2011 Springer Science+Business Media B.V.(outside the USA).

  13. Effects of Social Isolation on Glucocorticoid Regulation in Social Mammals

    Science.gov (United States)

    Hawkley, Louise C.; Cole, Steve W.; Capitanio, John P.; Norman, Greg J.; Cacioppo, John T.

    2012-01-01

    The regulation and function of the hypothalamic-pituitary-adrenocortical (HPA) axis and glucocorticoids have been well conserved across vertebrate species. Glucocorticoids influence a wide range of physiological functions that include glucose regulation, metabolism, inflammatory control, as well as cardiovascular, reproductive, and neuronal effects. Some of these are relatively quick-acting non-genomic effects, but most are slower-acting genomic effects. Thus, any stimulus that affects HPA function has the potential to exert wide-ranging short-term and long-term effects on much of vertebrate physiology. Here, we review the effects of social isolation on the functioning of the HPA axis in social species, and on glucocorticoid physiology in social mammals in particular. Evidence indicates that objective and perceived social isolation alter HPA regulation, although the nature and direction of the HPA response differs among species and across age. The inconsistencies in the direction and nature of HPA effects have implications for drawing cross-species conclusions about the effects of social isolation, and are particularly problematic for understanding HPA-related physiological processes in humans. The animal and human data are incommensurate because, for example, animal studies of objective isolation have typically not been modeled on, or for comparability with, the subjective experience of isolation in humans. An animal model of human isolation must be taken more seriously if we want to advance our understanding of the mechanisms for the effects of objective and perceived isolation in humans. PMID:22663934

  14. Normality and naturalness: a comparison of the meanings of concepts used within veterinary medicine and human medicine.

    Science.gov (United States)

    Lerner, Henrik; Hofmann, Bjørn

    2011-12-01

    This article analyses the different connotations of "normality" and "being natural," bringing together the theoretical discussion from both human medicine and veterinary medicine. We show how the interpretations of the concepts in the different areas could be mutually fruitful. It appears that the conceptions of "natural" are more elaborate in veterinary medicine, and can be of value to human medicine. In particular they can nuance and correct conceptions of nature in human medicine that may be too idealistic. Correspondingly, the wide ranging conceptions of "normal" in human medicine may enrich conceptions in veterinary medicine, where the discussions seem to be sparse. We do not argue that conceptions from veterinary medicine should be used in human medicine and vice versa, but only that it could be done and that it may well be fruitful. Moreover, there are overlaps between some notions of normal and natural, and further conceptual analysis on this overlap is needed.

  15. The Goal of Evolutionary and Neoclassical Economics as a Consequence of the Changes in Concepts of Human Nature

    Directory of Open Access Journals (Sweden)

    Anna Horodecka

    2015-11-01

    Full Text Available The economics depends on the concept of human nature very strongly. The concepts of human nature can be understood as a set of assumptions made about the individual (on different levels: behavior, motives, meaning and his interactions with other people, with groups and diverse institutions. It corresponds with the image of world people have. The concept of human nature together with an image of the world builds the basis of thinking about the economics and about such fundamental element of it as its goal. Therefore if those images of men change, the way of thinking about economics and their elements adjust to those changes as well. The goal of the paper is to present the impact of these alterations of image of man on the economics. This impact will be illustrated on the example of the evolutionary economics, which is contrasted with the orthodox concept of human nature persisting in the neoclassical economics – homo economicus. The method applied to this research is, among others, a content analysis of the most important texts developed within neoclassical and evolutionary economics. To reach this goal, the following steps will be conducted: firstly, the concepts of human nature will be defined in regards of their particularity depending on the discipline by which they are defined; secondly, the main differences between concepts of human nature in neoclassical and evolutionary economics will be analyzed, and thirdly the differences in understanding of the goal and field between those two schools will be explained as resulting from the diverse concepts of human nature. The analysis proved that the main differences in those economic schools might be explained by the changed assumptions about the human nature and the image of the world.

  16. The Paradox of Freedom: John Dewey on Human Nature, Culture, and Education

    Science.gov (United States)

    Keall, Cherilyn

    2013-01-01

    In this paper, I argue that John Dewey's view of human nature entails that culture is a necessary but not sufficient condition for freedom. A surprising corollary of this argument is that, if left to run its natural course, culture in fact tends not to enable but rather to preclude freedom. Hence, there are specific cultural practices--habits…

  17. BMP signaling in the human fetal ovary is developmentally regulated and promotes primordial germ cell apoptosis.

    Science.gov (United States)

    Childs, Andrew J; Kinnell, Hazel L; Collins, Craig S; Hogg, Kirsten; Bayne, Rosemary A L; Green, Samira J; McNeilly, Alan S; Anderson, Richard A

    2010-08-01

    Primordial germ cells (PGCs) are the embryonic precursors of gametes in the adult organism, and their development, differentiation, and survival are regulated by a combination of growth factors collectively known as the germ cell niche. Although many candidate niche components have been identified through studies on mouse PGCs, the growth factor composition of the human PGC niche has not been studied extensively. Here we report a detailed analysis of the expression of components of the bone morphogenetic protein (BMP) signaling apparatus in the human fetal ovary, from postmigratory PGC proliferation to the onset of primordial follicle formation. We find developmentally regulated and reciprocal patterns of expression of BMP2 and BMP4 and identify germ cells to be the exclusive targets of ovarian BMP signaling. By establishing long-term cultures of human fetal ovaries in which PGCs are retained within their physiological niche, we find that BMP4 negatively regulates postmigratory PGC numbers in the human fetal ovary by promoting PGC apoptosis. Finally, we report expression of both muscle segment homeobox (MSX)1 and MSX2 in the human fetal ovary and reveal a selective upregulation of MSX2 expression in human fetal ovary in response to BMP4, suggesting this gene may act as a downstream effector of BMP-induced apoptosis in the ovary, as in other systems. These data reveal for the first time growth factor regulation of human PGC development in a physiologically relevant context and have significant implications for the development of cultures systems for the in vitro maturation of germ cells, and their derivation from pluripotent stem cells.

  18. MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human Vitiligo.

    Science.gov (United States)

    Sahoo, Anupama; Lee, Bongyong; Boniface, Katia; Seneschal, Julien; Sahoo, Sanjaya K; Seki, Tatsuya; Wang, Chunyan; Das, Soumen; Han, Xianlin; Steppie, Michael; Seal, Sudipta; Taieb, Alain; Perera, Ranjan J

    2017-09-01

    Vitiligo is a common chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic, environmental, and biochemical causes, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. In this study we characterized the human vitiligo cell line PIG3V and the normal human melanocyte line HEM-l by RNA sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched microRNA-211, a known metabolic switch in nonpigmented melanoma cells, was severely down-regulated in vitiligo cell line PIG3V and skin biopsy samples from vitiligo patients, whereas its predicted targets PPARGC1A, RRM2, and TAOK1 were reciprocally up-regulated. microRNA-211 binds to PGC1-α 3' untranslated region locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated microRNA-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of microRNA-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. The cultural animal human nature, meaning, and social life

    CERN Document Server

    Baumeister, Roy F

    2005-01-01

    What makes us human? Why do people think, feel, and act as they do? What is the essence of human nature? What is the basic relationship between the individual and society? These questions have fascinated both great thinkers and ordinary humans for centuries. Now, at last, there is a solid basis for answering them, in the form of the accumulated efforts and studies by thousands of psychology researchers. We no longer have to rely on navel-gazing and speculation to understand why people are the way they are - we can instead turn to solid, objective findings. This book, by an eminent social psychologist at the peak of his career, not only summarizes what we know about people - it also offers a coherent, easy-to-understand, through radical, explanation. Turning conventional wisdom on its head, the author argues that culture shaped human evolution. Contrary to theories that depict the individual's relation to society as one of victimization, endless malleability, or just a square peg in a round hole, he proposes t...

  20. Rethinking the area of protection "natural resources" in life cycle assessment.

    Science.gov (United States)

    Dewulf, Jo; Benini, Lorenzo; Mancini, Lucia; Sala, Serenella; Blengini, Gian Andrea; Ardente, Fulvio; Recchioni, Marco; Maes, Joachim; Pant, Rana; Pennington, David

    2015-05-05

    Life cycle impact assessment (LCIA) in classical life cycle assessment (LCA) aims at analyzing potential impacts of products and services typically on three so-called areas of protection (AoPs): Natural Environment, Human Health, and Natural Resources. This paper proposes an elaboration of the AoP Natural Resources. It starts with analyzing different perspectives on Natural Resources as they are somehow sandwiched in between the Natural Environment (their cradle) and the human-industrial environment (their application). Reflecting different viewpoints, five perspectives are developed with the suggestion to select three in function of classical LCA. They result in three safeguard subjects: the Asset of Natural Resources, their Provisioning Capacity, and their role in Global Functions. Whereas the Provisioning Capacity is fully in function of humans, the global functions go beyond provisioning as they include nonprovisioning functions for humans and regulating and maintenance services for the globe as a whole, following the ecosystem services framework. A fourth and fifth safeguard subject has been identified: recognizing the role Natural Resources for human welfare, either specifically as building block in supply chains of products and services as such, either with or without their functions beyond provisioning. But as these are far broader as they in principle should include characterization of mechanisms within the human industrial society, they are considered as subjects for an integrated sustainability assessment (LCSA: life cycle sustainability assessment), that is, incorporating social, economic and environmental issues.

  1. Network analysis of microRNAs and their regulation in human ovarian cancer

    KAUST Repository

    Schmeier, Sebastian; Schaefer, Ulf; Essack, Magbubah; Bajic, Vladimir B.

    2011-01-01

    Background: MicroRNAs (miRNAs) are small non-coding RNA molecules that repress the translation of messenger RNAs (mRNAs) or degrade mRNAs. These functions of miRNAs allow them to control key cellular processes such as development, differentiation and apoptosis, and they have also been implicated in several cancers such as leukaemia, lung, pancreatic and ovarian cancer (OC). Unfortunately, the specific machinery of miRNA regulation, involving transcription factors (TFs) and transcription co-factors (TcoFs), is not well understood. In the present study we focus on computationally deciphering the underlying network of miRNAs, their targets, and their control mechanisms that have an influence on OC development.Results: We analysed experimentally verified data from multiple sources that describe miRNA influence on diseases, miRNA targeting of mRNAs, and on protein-protein interactions, and combined this data with ab initio transcription factor binding site predictions within miRNA promoter regions. From these analyses, we derived a network that describes the influence of miRNAs and their regulation in human OC. We developed a methodology to analyse the network in order to find the nodes that have the largest potential of influencing the network's behaviour (network hubs). We further show the potentially most influential miRNAs, TFs and TcoFs, showing subnetworks illustrating the involved mechanisms as well as regulatory miRNA network motifs in OC. We find an enrichment of miRNA targeted OC genes in the highly relevant pathways cell cycle regulation and apoptosis.Conclusions: We combined several sources of interaction and association data to analyse and place miRNAs within regulatory pathways that influence human OC. These results represent the first comprehensive miRNA regulatory network analysis for human OC. This suggests that miRNAs and their regulation may play a major role in OC and that further directed research in this area is of utmost importance to enhance our

  2. Network analysis of microRNAs and their regulation in human ovarian cancer

    KAUST Repository

    Schmeier, Sebastian

    2011-11-03

    Background: MicroRNAs (miRNAs) are small non-coding RNA molecules that repress the translation of messenger RNAs (mRNAs) or degrade mRNAs. These functions of miRNAs allow them to control key cellular processes such as development, differentiation and apoptosis, and they have also been implicated in several cancers such as leukaemia, lung, pancreatic and ovarian cancer (OC). Unfortunately, the specific machinery of miRNA regulation, involving transcription factors (TFs) and transcription co-factors (TcoFs), is not well understood. In the present study we focus on computationally deciphering the underlying network of miRNAs, their targets, and their control mechanisms that have an influence on OC development.Results: We analysed experimentally verified data from multiple sources that describe miRNA influence on diseases, miRNA targeting of mRNAs, and on protein-protein interactions, and combined this data with ab initio transcription factor binding site predictions within miRNA promoter regions. From these analyses, we derived a network that describes the influence of miRNAs and their regulation in human OC. We developed a methodology to analyse the network in order to find the nodes that have the largest potential of influencing the network\\'s behaviour (network hubs). We further show the potentially most influential miRNAs, TFs and TcoFs, showing subnetworks illustrating the involved mechanisms as well as regulatory miRNA network motifs in OC. We find an enrichment of miRNA targeted OC genes in the highly relevant pathways cell cycle regulation and apoptosis.Conclusions: We combined several sources of interaction and association data to analyse and place miRNAs within regulatory pathways that influence human OC. These results represent the first comprehensive miRNA regulatory network analysis for human OC. This suggests that miRNAs and their regulation may play a major role in OC and that further directed research in this area is of utmost importance to enhance

  3. Bacterial natural products : Prediction, regulation and characterization of biosynthetic gene clusters in Actinobacteria

    NARCIS (Netherlands)

    Ceniceros, Ana

    2017-01-01

    Secondary metabolites are produced by many microbes. They are not essential for life, but may provide a competitive advantage in the natural environment. Antibiotics are an important example, crucial agents in the human health system, widely used to combat infectious diseases. In view of the

  4. The Biosphere as a Living System. On the Harmonization of Human and Biosphere Relationship

    Directory of Open Access Journals (Sweden)

    Alexey Yablokov

    2017-02-01

    Full Text Available The evolution of the biosphere has led to creation of astrophysical and telluric stable perfect system biotic regulation, which based on a high degree of closure of natural cycles. The development of human beings as bio-social, beyond the biological patterns, break these closed cycles, and dramatically broke the biotic regulation of the biosphere. As results — sustainable biosphere has become unsustainable anthroposphere. As with the origin of life physico-chemical regularities of the structure of matter turned out to be “mastered” life, as soon as with the emergence of anthroposphere physical-chemicalbiological regularities of evolution are complemented by social ones (including technology development and of the technosphere — as the essential content of anthroposphere. The result of the violation of natural biotic regulation broke a global environmental crisis that boomerang begins it is dangerous to human. It is theoretically possible to overcome this ecological crisis by the transition from the Neolithic paradigm of “nature conquest”, to the organization of “crisis management” of the biosphere (world system governance by the activity of the society restore and “repair” the damaged processes in the biosphere. This requires a new organization in all areas of human activity, i.e., a fundamentally new paradigm of human behavior on the planet. Development within the paradigm of the Neolithic culture (extensive use of natural resources, is inevitably associated with different kinds of wars in their redistribution, leads to an increasing accumulation of non-degradable waste (tertiary anthropogenic products, determines the fatal instability of anthroposphere and, therefore, unsustainable development of civilization. It is a mistake to assume that human’s dependence on nature is reduced — it takes a different form. The forces of human as an intelligence being, “recollecting himself”, about the offense with lifesupporting

  5. Androgen regulated genes in human prostate xenografts in mice: relation to BPH and prostate cancer.

    Directory of Open Access Journals (Sweden)

    Harold D Love

    2009-12-01

    Full Text Available Benign prostatic hyperplasia (BPH and prostate carcinoma (CaP are linked to aging and the presence of androgens, suggesting that androgen regulated genes play a major role in these common diseases. Androgen regulation of prostate growth and development depends on the presence of intact epithelial-stromal interactions. Further, the prostatic stroma is implicated in BPH. This suggests that epithelial cell lines are inadequate to identify androgen regulated genes that could contribute to BPH and CaP and which could serve as potential clinical biomarkers. In this study, we used a human prostate xenograft model to define a profile of genes regulated in vivo by androgens, with an emphasis on identifying candidate biomarkers. Benign transition zone (TZ human prostate tissue from radical prostatectomies was grafted to the sub-renal capsule site of intact or castrated male immunodeficient mice, followed by the removal or addition of androgens, respectively. Microarray analysis of RNA from these tissues was used to identify genes that were; 1 highly expressed in prostate, 2 had significant expression changes in response to androgens, and, 3 encode extracellular proteins. A total of 95 genes meeting these criteria were selected for analysis and validation of expression in patient prostate tissues using quantitative real-time PCR. Expression levels of these genes were measured in pooled RNAs from human prostate tissues with varying severity of BPH pathologic changes and CaP of varying Gleason score. A number of androgen regulated genes were identified. Additionally, a subset of these genes were over-expressed in RNA from clinical BPH tissues, and the levels of many were found to correlate with disease status. Our results demonstrate the feasibility, and some of the problems, of using a mouse xenograft model to characterize the androgen regulated expression profiles of intact human prostate tissues.

  6. Introduction to naturally occurring radioactive material

    Energy Technology Data Exchange (ETDEWEB)

    Egidi, P.

    1997-08-01

    Naturally occurring radioactive material (NORM) is everywhere; we are exposed to it every day. It is found in our bodies, the food we eat, the places where we live and work, and in products we use. We are also bathed in a sea of natural radiation coming from the sun and deep space. Living systems have adapted to these levels of radiation and radioactivity. But some industrial practices involving natural resources concentrate these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. Other activities, such as flying at high altitudes, expose us to elevated levels of NORM. This session will concentrate on diffuse sources of technologically-enhanced (TE) NORM, which are generally large-volume, low-activity waste streams produced by industries such as mineral mining, ore benefication, production of phosphate Fertilizers, water treatment and purification, and oil and gas production. The majority of radionuclides in TENORM are found in the uranium and thorium decay chains. Radium and its subsequent decay products (radon) are the principal radionuclides used in characterizing the redistribution of TENORM in the environment by human activity. We will briefly review other radionuclides occurring in nature (potassium and rubidium) that contribute primarily to background doses. TENORM is found in many waste streams; for example, scrap metal, sludges, slags, fluids, and is being discovered in industries traditionally not thought of as affected by radionuclide contamination. Not only the forms and volumes, but the levels of radioactivity in TENORM vary. Current discussions about the validity of the linear no dose threshold theory are central to the TENORM issue. TENORM is not regulated by the Atomic Energy Act or other Federal regulations. Control and regulation of TENORM is not consistent from industry to industry nor from state to state. Proposed regulations are moving from concentration-based standards to dose

  7. Human factor H-related protein 2 (CFHR2 regulates complement activation.

    Directory of Open Access Journals (Sweden)

    Hannes U Eberhardt

    Full Text Available Mutations and deletions within the human CFHR gene cluster on chromosome 1 are associated with diseases, such as dense deposit disease, CFHR nephropathy or age-related macular degeneration. Resulting mutant CFHR proteins can affect complement regulation. Here we identify human CFHR2 as a novel alternative pathway complement regulator that inhibits the C3 alternative pathway convertase and terminal pathway assembly. CFHR2 is composed of four short consensus repeat domains (SCRs. Two CFHR2 molecules form a dimer through their N-terminal SCRs, and each of the two C-terminal ends can bind C3b. C3b bound CFHR2 still allows C3 convertase formation but the CFHR2 bound convertases do not cleave the substrate C3. Interestingly CFHR2 hardly competes off factor H from C3b. Thus CFHR2 likely acts in concert with factor H, as CFHR2 inhibits convertases while simultaneously allowing factor H assisted degradation by factor I.

  8. Connectedness to Nature and to Humanity: their association and personality correlates

    Science.gov (United States)

    Lee, Kibeom; Ashton, Michael C.; Choi, Julie; Zachariassen, Kayla

    2015-01-01

    People differ in the extent to which they identify with humans beyond their ingroup and with non-human living things. We refer to the former as the Connectedness to Humanity (CH) and to the latter as the Connectedness to Nature (CN). In a sample of 324 undergraduate students, CH and CN were operationalized using the Identification with All Humanity Scale (McFarland et al., 2012) and the CN Scale (Mayer and Frantz, 2004), respectively. These variables correlated moderately with each other (r = 0.44) and shared Openness to Experience and Honesty–Humility as their primary personality correlates. CN was found to play an important role in mediating the relationships between the two personality variables and some specific pro-environmental/pro-animal attitudes and ecological behaviors. PMID:26257669

  9. Introduction to naturally occurring radioactive material

    International Nuclear Information System (INIS)

    Egidi, P.

    1997-01-01

    Naturally occurring radioactive material (NORM) is everywhere; we are exposed to it every day. It is found in our bodies, the food we eat, the places where we live and work, and in products we use. Some industrial practices involving natural resources concentrate these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. This session will concentrate on diffuse sources of technologically-enhanced (TE) NORM, which are generally large-volume, low-activity waste streams produced by industries such as mineral mining, ore benefication, production of phosphate Fertilizers, water treatment and purification, and oil and gas production. The majority of radionuclides in TENORM are found in the uranium and thorium decay chains. Radium and its subsequent decay products (radon) are the principal radionuclides used in characterizing the redistribution of TENORM in the environment by human activity. We will briefly review other radionuclides occurring in nature (potassium and rubidium) that contribute primarily to background doses. TENORM is found in many waste streams; for example, scrap metal, sludges, slags, fluids, and is being discovered in industries traditionally not thought of as affected by radionuclide contamination. Not only the forms and volumes, but the levels of radioactivity in TENORM vary. Current discussions about the validity of the linear no dose threshold theory are central to the TENORM issue. TENORM is not regulated by the Atomic Energy Act or other Federal regulations. Control and regulation of TENORM is not consistent from industry to industry nor from state to state. Proposed regulations are moving from concentration-based standards to dose-based standards. So when is TENORM a problem? Where is it a problem? That depends on when, where, and whom you talk to exclamation point We will start by reviewing background radioactivity, then we will proceed to the geology, mobility, and variability of these

  10. Genome-Wide RNAi Ionomics Screen Reveals New Genes and Regulation of Human Trace Element Metabolism

    Science.gov (United States)

    Malinouski, Mikalai; Hasan, Nesrin M.; Zhang, Yan; Seravalli, Javier; Lin, Jie; Avanesov, Andrei; Lutsenko, Svetlana; Gladyshev, Vadim N.

    2017-01-01

    Trace elements are essential for human metabolism and dysregulation of their homeostasis is associated with numerous disorders. Here we characterize mechanisms that regulate trace elements in human cells by designing and performing a genome-wide high-throughput siRNA/ionomics screen, and examining top hits in cellular and biochemical assays. The screen reveals high stability of the ionomes, especially the zinc ionome, and yields known regulators and novel candidates. We further uncover fundamental differences in the regulation of different trace elements. Specifically, selenium levels are controlled through the selenocysteine machinery and expression of abundant selenoproteins; copper balance is affected by lipid metabolism and requires machinery involved in protein trafficking and posttranslational modifications; and the iron levels are influenced by iron import and expression of the iron/heme-containing enzymes. Our approach can be applied to a variety of disease models and/or nutritional conditions, and the generated dataset opens new directions for studies of human trace element metabolism. PMID:24522796

  11. Changing human relationships with nature: making and remaking wilderness science

    Science.gov (United States)

    Jill M. Belsky

    2000-01-01

    The paper identifies and discusses two major themes in wilderness social science. First, that wilderness studies (and its advocates) have been limited by an ontological tension between those who mainly approach the relationship between humans and nature on the basis of material factors and constraints and those who approach it through an examination of shifting...

  12. 21 CFR 110.110 - Natural or unavoidable defects in food for human use that present no health hazard.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Natural or unavoidable defects in food for human... PRACTICE IN MANUFACTURING, PACKING, OR HOLDING HUMAN FOOD Defect Action Levels § 110.110 Natural or... natural or unavoidable defects to the lowest level currently feasible. (d) The mixing of a food containing...

  13. UVA and UVB Irradiation Differentially Regulate microRNA Expression in Human Primary Keratinocytes

    Science.gov (United States)

    Kraemer, Anne; Chen, I-Peng; Henning, Stefan; Faust, Alexandra; Volkmer, Beate; Atkinson, Michael J.; Moertl, Simone; Greinert, Ruediger

    2013-01-01

    MicroRNA (miRNA)-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2), which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis. PMID:24391759

  14. UVA and UVB irradiation differentially regulate microRNA expression in human primary keratinocytes.

    Directory of Open Access Journals (Sweden)

    Anne Kraemer

    Full Text Available MicroRNA (miRNA-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2, which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis.

  15. Natural Tasking of Robots Based on Human Interaction Cues (CD-ROM)

    National Research Council Canada - National Science Library

    Brooks, Rodney A

    2005-01-01

    ...: 1 CD-ROM; 4 3/4 in.; 207 MB. ABSTRACT: We proposed developing the perceptual and intellectual abilities of robots so that in the field, war-fighters can interact with them in the same natural ways as they do with their human cohorts...

  16. Evaluating natural resource amenities in a human life expectancy production function

    Science.gov (United States)

    Neelam C. Poudyal; Donald G. Hodges; J.M. Bowker; H.K. Cordell

    2009-01-01

    This study examined the effect of natural resource amenities on human life expectancy. Extending theexisting model of the life expectancy production function, and correcting for spatial dependence, weevaluated the determinants of life expectancy using county level data. Results indicate that after controlling

  17. Regulation of human heme oxygenase-1 gene expression under thermal stress.

    Science.gov (United States)

    Okinaga, S; Takahashi, K; Takeda, K; Yoshizawa, M; Fujita, H; Sasaki, H; Shibahara, S

    1996-06-15

    Heme oxygenase-1 is an essential enzyme in heme catabolism, and its human gene promoter contains a putative heat shock element (HHO-HSE). This study was designed to analyze the regulation of human heme oxygenase-1 gene expression under thermal stress. The amounts of heme oxygenase-1 protein were not increased by heat shock (incubation at 42 degrees C) in human alveolar macrophages and in a human erythroblastic cell line, YN-1-0-A, whereas heat shock protein 70 (HSP70) was noticeably induced. However, heat shock factor does bind in vitro to HHO-HSE and the synthetic HHO-HSE by itself is sufficient to confer the increase in the transient expression of a reporter gene upon heat shock. The deletion of the sequence, located downstream from HHO-HSE, resulted in the activation of a reporter gene by heat shock. These results suggest that HHO-HSE is potentially functional but is repressed in vivo. Interestingly, heat shock abolished the remarkable increase in the levels of heme oxygenase-1 mRNA in YN-1-0-A cells treated with hemin or cadmium, in which HSP70 mRNA was noticeably induced. Furthermore, transient expression assays showed that heat shock inhibits the cadmium-mediated activation of the heme oxygenase-1 promoter, whereas the HSP70 gene promoter was activated upon heat shock. Such regulation of heme oxygenase-1 under thermal stress may be of physiologic significance in erythroid cells.

  18. Impact, adaptation and vulnerability of natural and human systems in Europe

    International Nuclear Information System (INIS)

    Martin, Eric; Salas y Melia, David; Delire, Christine; Lemonsu, Aude; Masson, Valery; Badeau, Vincent; Gattuso, Jean-Pierre; Pigeon, Gregoire; Regimbeau, Mathieu; Viguie, Vincent

    2015-01-01

    This article analyses the observed and projected impacts of climate change on human and natural systems, their vulnerability and adaptation options. It provides insight into the main results related to hydrology, agriculture, natural ecosystems, transport, energy, tourism, infrastructures, health and social aspects. This article presents the main results concerning Europe that were compiled in the contribution of Working Group II to the IPCC fifth assessment report published in 2014. Several studies focused on mainland France are also presented, without claiming to be exhaustive. (authors)

  19. Managing Watersheds as Couple Human-Natural Systems: A Review of Research Opportunities

    Science.gov (United States)

    Cai, X.

    2011-12-01

    Many watersheds around the world are impaired with severe social and environmental problems due to heavy anthropogenic stresses. Humans have transformed hydrological and biochemical processes in watersheds from a stationary to non-stationary status through direct (e.g., water withdrawals) and indirect (e.g., altering vegetation and land cover) interferences. It has been found that in many watersheds that socio-economic drivers, which have caused increasingly intensive alteration of natural processes, have even overcome natural variability to become the dominant factor affecting the behavior of watershed systems. Reversing this trend requires an understanding of the drivers of this intensification trajectory, and needs tremendous policy reform and investment. As stressed by several recent National Research Council (NRC) reports, watershed management will pose an enormous challenge in the coming decades. Correspondingly, the focus of research has started an evolution from the management of reservoir, stormwater and aquifer systems to the management of integrated watershed systems, to which policy instruments designed to make more rational economic use of water resources are likely to be applied. To provide a few examples: reservoir operation studies have moved from a local to a watershed scale in order to consider upstream best management practices in soil conservation and erosion control and downstream ecological flow requirements and water rights; watersheds have been modeled as integrated hydrologic-economic systems with multidisciplinary modeling efforts, instead of traditional isolated physical systems. Today's watershed management calls for a re-definition of watersheds from isolated natural systems to coupled human-natural systems (CHNS), which are characterized by the interactions between human activities and natural processes, crossing various spatial and temporal scales within the context of a watershed. The importance of the conceptual innovation has been

  20. Regulation of coagulation factor XI expression by microRNAs in the human liver.

    Directory of Open Access Journals (Sweden)

    Salam Salloum-Asfar

    Full Text Available High levels of factor XI (FXI increase the risk of thromboembolic disease. However, the genetic and environmental factors regulating FXI expression are still largely unknown. The aim of our study was to evaluate the regulation of FXI by microRNAs (miRNAs in the human liver. In silico prediction yielded four miRNA candidates that might regulate FXI expression. HepG2 cells were transfected with miR-181a-5p, miR-23a-3p, miR-16-5p and miR-195-5p. We used mir-494, which was not predicted to bind to F11, as a negative control. Only miR-181a-5p caused a significant decrease both in FXI protein and F11 mRNA levels. In addition, transfection with a miR-181a-5p inhibitor in PLC/PRF/5 hepatic cells increased both the levels of F11 mRNA and extracellular FXI. Luciferase assays in human colon cancer cells deficient for Dicer (HCT-DK demonstrated a direct interaction between miR-181a-5p and 3'untranslated region of F11. Additionally, F11 mRNA levels were inversely and significantly correlated with miR-181a-5p levels in 114 healthy livers, but not with miR-494. This study demonstrates that FXI expression is directly regulated by a specific miRNA, miR-181a-5p, in the human liver. Future studies are necessary to further investigate the potential consequences of miRNA dysregulation in pathologies involving FXI.

  1. Local flow regulation and irrigation raise global human water consumption and footprint.

    Science.gov (United States)

    Jaramillo, Fernando; Destouni, Georgia

    2015-12-04

    Flow regulation and irrigation alter local freshwater conditions, but their global effects are highly uncertain. We investigated these global effects from 1901 to 2008, using hydroclimatic observations in 100 large hydrological basins. Globally, we find consistent and dominant effects of increasing relative evapotranspiration from both activities, and decreasing temporal runoff variability from flow regulation. The evapotranspiration effect increases the long-term average human consumption of fresh water by 3563 ± 979 km(3)/year from 1901-1954 to 1955-2008. This increase raises a recent estimate of the current global water footprint of humanity by around 18%, to 10,688 ± 979 km(3)/year. The results highlight the global impact of local water-use activities and call for their relevant account in Earth system modeling. Copyright © 2015, American Association for the Advancement of Science.

  2. Insulin resistance in human subjects having impaired glucose regulation

    International Nuclear Information System (INIS)

    Khan, S.H.; Khan, F.A.; Ijaz, A.

    2007-01-01

    To determine insulin resistance in human subjects having impaired glucose regulation (IGR) by Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). A total of 100 subjects with impaired glucose regulation were selected for evaluation of metabolic syndrome as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III), along with 47 healthy age and gender-matched controls. Physical examination to determine blood pressure and waist circumference was carried out and so was sampling for plasma glucose, serum triglycerides, HDL-cholesterol and insulin. Insulin resistance was calculated by the HOMA-IR. Finally, subjects with and without metabolic syndrome were compared with controls (n=47), using one-way ANOVA for studying insulin resistance between groups, with Tukey's post-hoc comparison. The frequency of finding metabolic syndrome in cases of IGR remained 47%. The insulin resistance demonstrated stepwise worsening from control population (mean=1.54, 95 % CI: 1.77 - 2.37) to subjects suffering from only IGR (mean=2.07, 95 % CI: 1.77- 2.37) to metabolic syndrome (mean=2.67, 95 %, CI: 2.34 - 3.00) (p < 0.001). Patients with impaired glucose regulation may have significant insulin resistance. It is, thus, recommended that a vigorous search be made to measure insulin resistance in all cases diagnosed to have impaired glucose regulation. (author)

  3. Let-7 microRNAs are developmentally regulated in circulating human erythroid cells

    Directory of Open Access Journals (Sweden)

    Reed Christopher

    2009-11-01

    Full Text Available Abstract Background MicroRNAs are ~22nt-long small non-coding RNAs that negatively regulate protein expression through mRNA degradation or translational repression in eukaryotic cells. Based upon their importance in regulating development and terminal differentiation in model systems, erythrocyte microRNA profiles were examined at birth and in adults to determine if changes in their abundance coincide with the developmental phenomenon of hemoglobin switching. Methods Expression profiling of microRNA was performed using total RNA from four adult peripheral blood samples compared to four cord blood samples after depletion of plasma, platelets, and nucleated cells. Labeled RNAs were hybridized to custom spotted arrays containing 474 human microRNA species (miRBase release 9.1. Total RNA from Epstein-Barr virus (EBV-transformed lymphoblastoid cell lines provided a hybridization reference for all samples to generate microRNA abundance profile for each sample. Results Among 206 detected miRNAs, 79% of the microRNAs were present at equivalent levels in both cord and adult cells. By comparison, 37 microRNAs were up-regulated and 4 microRNAs were down-regulated in adult erythroid cells (fold change > 2; p let-7 miRNA family consistently demonstrated increased abundance in the adult samples by array-based analyses that were confirmed by quantitative PCR (4.5 to 18.4 fold increases in 6 of 8 let-7 miRNA. Profiling studies of messenger RNA (mRNA in these cells additionally demonstrated down-regulation of ten let-7 target genes in the adult cells. Conclusion These data suggest that a consistent pattern of up-regulation among let-7 miRNA in circulating erythroid cells occurs in association with hemoglobin switching during the fetal-to-adult developmental transition in humans.

  4. Surgery via natural orifices in human beings: yesterday, today, tomorrow.

    Science.gov (United States)

    Moris, Demetrios N; Bramis, Konstantinos J; Mantonakis, Eleftherios I; Papalampros, Efstathios L; Petrou, Athanasios S; Papalampros, Alexandros E

    2012-07-01

    We performed an evaluation of models, techniques, and applicability to the clinical setting of natural orifice surgery (mainly natural orifice transluminal endoscopic surgery [NOTES]) primarily in general surgery procedures. NOTES has attracted much attention recently for its potential to establish a completely alternative approach to the traditional surgical procedures performed entirely through a natural orifice. Beyond the potentially scar-free surgery and abolishment of dermal incision-related complications, the safety and efficacy of this new surgical technology must be evaluated. Studies were identified by searching MEDLINE, EMBASE, Cochrane Library, and Entrez PubMed from 2007 to February 2011. Most of the references were identified from 2009 to 2010. There were limitations as far as the population that was evaluated (only human beings, no cadavers or animals) was concerned, but there were no limitations concerning the level of evidence of the studies that were evaluated. The studies that were deemed applicable for our review were published mainly from 2007 to 2010 (see Methods section). All the evaluated studies were conducted only in human beings. We studied the most common referred in the literature orifices such as vaginal, oral, gastric, esophageal, anal, or urethral. The optimal access route and method could not be established because of the different nature of each procedure. We mainly studied procedures in the field of general surgery such as cholecystectomy, intestinal cancers, renal cancers, appendectomy, mediastinoscopy, and peritoneoscopy. All procedures were feasible and most of them had an uneventful postoperative course. A number of technical problems were encountered, especially as far as pure NOTES procedures are concerned, which makes the need of developing new endoscopic instruments, to facilitate each approach, undeniable. NOTES is still in the early stages of development and more robust technologies will be needed to achieve reliable

  5. Using Landsat time series for characterizing forest disturbance dynamics in the coupled human and natural systems of Central Europe.

    Science.gov (United States)

    Senf, Cornelius; Pflugmacher, Dirk; Hostert, Patrick; Seidl, Rupert

    2017-08-01

    Remote sensing is a key information source for improving the spatiotemporal understanding of forest ecosystem dynamics. Yet, the mapping and attribution of forest change remains challenging, particularly in areas where a number of interacting disturbance agents simultaneously affect forest development. The forest ecosystems of Central Europe are coupled human and natural systems, with natural and human disturbances affecting forests both individually and in combination. To better understand the complex forest disturbance dynamics in such systems, we utilize 32-year Landsat time series to map forest disturbances in five sites across Austria, the Czech Republic, Germany, Poland, and Slovakia. All sites consisted of a National Park and the surrounding forests, reflecting three management zones of different levels of human influence (managed, protected, strictly protected). This allowed for a comparison of spectral, temporal, and spatial disturbance patterns across a gradient from natural to coupled human and natural disturbances. Disturbance maps achieved overall accuracies ranging from 81% to 93%. Disturbance patches were generally small, with 95% of the disturbances being smaller than 10 ha. Disturbance rates ranged from 0.29% yr -1 to 0.95% yr -1 , and differed substantially among management zones and study sites. Natural disturbances in strictly protected areas were longer in duration (median of 8 years) and slightly less variable in magnitude compared to human-dominated disturbances in managed forests (median duration of 1 year). However, temporal dynamics between natural and human-dominated disturbances showed strong synchrony, suggesting that disturbance peaks are driven by natural events affecting managed and unmanaged areas simultaneously. Our study demonstrates the potential of remote sensing for mapping forest disturbances in coupled human and natural systems, such as the forests of Central Europe. Yet, we also highlight the complexity of such systems in

  6. Brief Report: Robo1 Regulates the Migration of Human Subventricular Zone Neural Progenitor Cells During Development.

    Science.gov (United States)

    Guerrero-Cazares, Hugo; Lavell, Emily; Chen, Linda; Schiapparelli, Paula; Lara-Velazquez, Montserrat; Capilla-Gonzalez, Vivian; Clements, Anna Christina; Drummond, Gabrielle; Noiman, Liron; Thaler, Katrina; Burke, Anne; Quiñones-Hinojosa, Alfredo

    2017-07-01

    Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit-Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents. Slit and Robo proteins expressed in the rodent brain help guide neuroblast migration from the SVZ through the rostral migratory stream to the olfactory bulb. Here, we present the first study on the role that Slit and Robo proteins play in human-derived fetal neural progenitor cell migration (hfNPC). We describe that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore, we demonstrate that Slit2 is able to induce a chemorepellent effect on the migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1 expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of mice when injected in the anterior SVZ. Our findings indicate that the migration of human NPCs from the SVZ is partially regulated by the Slit-Robo axis. This pathway could be regulated to direct the migration of NPCs in human endogenous neural cell therapy. Stem Cells 2017;35:1860-1865. © 2017 AlphaMed Press.

  7. Natural selection affects multiple aspects of genetic variation at putatively peutral sites across the human genome

    DEFF Research Database (Denmark)

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui

    2011-01-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries...... these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination...... and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations...

  8. Thunder on the Yellowstone revisited: An assessment of management of native ungulates by natural regulation, 1968-1993

    Science.gov (United States)

    Singer, F.J.; Swift, D.M.; Coughenour, M.B.; Varley, J.D.

    1998-01-01

    Natural regulation of native ungulates was initiated in 1968 in Yellowstone National Park (YNP) based on the premise that ungulates would reach an equilibrium with their plant resources. The natural-regulation management model stated: density dependence will regulate ungulates (i.e., a dynamic equilibrium will result between ungulates and their food supply, within some bounds of vegetation and soil effects); and no retrogression of soil and vegetation will occur from elk (Cervus elaphus) grazing during this process. The historical record indicated that elk were abundant in the system and elk were primarily food limited before settlement by European man (i.e., wolves [Canis lupus] and Native Americans were only an adjunct to the density dependent population regulation of ungulates). Density dependence was demonstrated in elk, but not in bison (Bison bison). No widespread evidence of overgrazing was observed through 1993 in study sites within vegetation communities that comprised about 97% of the winter range. No evidence of increased exotics, increased sediment yield, warming or drying of the soil, changes in soil nutrients, or differences in aboveground standing-crop biomass of plants was found between grazed and ungrazed plots. Ungulate herbivory apparently stimulated aboveground production of grasses, enhanced nitrogen and macronutrients in grasses, increased nutrient cycling, and enhanced measures of fitness in 6 common plants. However, exposed soil surface (bare ground and pebbles combined) was 11-18% greater on grazed than ungrazed plots, apparently due to a 71% decline in dead and standing litter on grazed plots. Percent live-plant basal cover, however, did not differ on grazed versus ungrazed plots, and there was no difference in soil microclimate or sediment yield. Differences in the abundance of 12% of the herbaceous species were found in grazed versus ungrazed sites (16 of 128 species); 10 were declines and 6 were increases. Willow (Salix spp.) and aspen

  9. Down-regulation of telomerase activity in DLD-1 human colorectal adenocarcinoma cells by tocotrienol

    International Nuclear Information System (INIS)

    Eitsuka, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Teruo

    2006-01-01

    As high telomerase activity is detected in most cancer cells, inhibition of telomerase by drug or dietary food components is a new strategy for cancer prevention. Here, we investigated the inhibitory effect of vitamin E, with particular emphasis on tocotrienol (unsaturated vitamin E), on human telomerase in cell-culture study. As results, tocotrienol inhibited telomerase activity of DLD-1 human colorectal adenocarcinoma cells in time- and dose-dependent manner, interestingly, with δ-tocotrienol exhibiting the highest inhibitory activity. Tocotrienol inhibited protein kinase C activity, resulting in down-regulation of c-myc and human telomerase reverse transcriptase (hTERT) expression, thereby reducing telomerase activity. In contrast to tocotrienol, tocopherol showed very weak telomerase inhibition. These results provide novel evidence for First time indicating that tocotrienol acts as a potent candidate regulator of telomerase and supporting the anti-proliferative function of tocotrienol

  10. Teachers' Perspectives on the Human-Nature Relationship: Implications for Environmental Education

    Science.gov (United States)

    Almeida, Antonio; Vasconcelos, Clara

    2013-01-01

    This study based on a theoretical framework of three main environmental perspectives in the human-nature relationship (anthropocentrism, biocentrism and ecocentrism), aimed to identify their incidence in teachers involved with environmental projects when confronted with diverse environmental issues. 60 teachers drawn from four school cycles in…

  11. Assessment of human-natural system characteristics influencing global freshwater supply vulnerability

    Science.gov (United States)

    Padowski, Julie C.; Gorelick, Steven M.; Thompson, Barton H.; Rozelle, Scott; Fendorf, Scott

    2015-10-01

    Global freshwater vulnerability is a product of environmental and human dimensions, however, it is rarely assessed as such. Our approach identifies freshwater vulnerability using four broad categories: endowment, demand, infrastructure, and institutions, to capture impacts on natural and managed water systems within the coupled human-hydrologic environment. These categories are represented by 19 different endogenous and exogenous characteristics affecting water supply vulnerability. By evaluating 119 lower per capita income countries (Yemen and Djibouti nearly as vulnerable. Surprising similarities in vulnerability were also found among geographically disparate nations such as Vietnam, Sri Lanka, and Guatemala. Determining shared patterns of freshwater vulnerability provides insights into why water supply vulnerabilities are manifested in human-water systems at the national scale.

  12. Anthropology from a Kantian point of view: toward a cosmopolitan conception of human nature.

    Science.gov (United States)

    Louden, Robert B

    2008-12-01

    Anthropology was a new field of study when Kant first began lecturing on it in 1772, and Kant himself was the first academic to teach regular courses in this area. As is well known, his own approach to anthropology is self-described as 'pragmatic', and Kant's pragmatic anthropology differs markedly from the anthropologies that other early contributors to the new discipline were advocating. In this essay I focus on a fundamental feature of Kant's anthropology that has been under-appreciated in previous discussions; namely, the particular conception of human nature that he believes anthropology, when pursued properly, leads to. I call this conception a cosmopolitan conception of human nature. In addition to establishing the central importance of this idea for Kant's project in anthropology, I also try in this essay to unravel some of its ambiguities and tensions as well as to highlight its underlying moral motives. The cosmopolitan conception of human nature that is central to Kant's anthropology is a further indication of the significance of his anthropology for ethics.

  13. Synergistic role of Sprouty2 inactivation and c-Met up-regulation in mouse and human hepatocarcinogenesis.

    Science.gov (United States)

    Lee, Susie A; Ladu, Sara; Evert, Matthias; Dombrowski, Frank; De Murtas, Valentina; Chen, Xin; Calvisi, Diego F

    2010-08-01

    Sprouty2 (Spry2), a negative feedback regulator of the Ras/mitogen-activated protein kinase (MAPK) pathway, is frequently down-regulated in human hepatocellular carcinoma (HCC). We tested the hypothesis that loss of Spry2 cooperates with unconstrained activation of the c-Met protooncogene to induce hepatocarcinogenesis via in vitro and in vivo approaches. We found coordinated down-regulation of Spry2 protein expression and activation of c-Met as well as its downstream effectors extracellular signal-regulated kinase (ERK) and v-akt murine thymoma viral oncogene homolog (AKT) in a subset of human HCC samples with poor outcome. Mechanistic studies revealed that Spry2 function is disrupted in human HCC via multiple mechanisms at both transcriptional and post-transcriptional level, including promoter hypermethylation, loss of heterozygosity, and proteosomal degradation by neural precursor cell expressed, developmentally down-regulated 4 (NEDD4). In HCC cell lines, Spry2 overexpression inhibits c-Met-induced cell proliferation as well as ERK and AKT activation, whereas loss of Spry2 potentiates c-Met signaling. Most importantly, we show that blocking Spry2 activity via a dominant negative form of Spry2 cooperates with c-Met to promote hepatocarcinogenesis in the mouse liver by sustaining proliferation and angiogenesis. The tumors exhibited high levels of activated ERK and AKT, recapitulating the subgroup of human HCC with a clinically aggressive phenotype. The occurrence of frequent genetic, epigenetic, and biochemical events leading to Spry2 inactivation provides solid evidence that Spry2 functions as a tumor suppressor gene in liver cancer. Coordinated deregulation of Spry2 and c-Met signaling may be a pivotal oncogenic mechanism responsible for unrestrained activation of ERK and AKT pathways in human hepatocarcinogenesis.

  14. Confucius' Analysis of the Human Nature of Irrationality and His Quest for Moral Education

    Science.gov (United States)

    Jiawei, Xing

    2015-01-01

    This study uses mainly Confucian classic Lunyu to explore Confucius' insightful thinking about humans' strong innate nature of irrationality out of their physical needs. Irrationality causes interpersonal disturbances and chaos, and as such moral education is indispensable. Confucius advocated humanity, the principles of conscientiousness and…

  15. Cancer risk assessments and environmental regulation

    International Nuclear Information System (INIS)

    Scroggin, D.G.

    1990-01-01

    Governmental regulation of toxic substances, such as carcinogens and radiation, prompts both legal and scientific controversies. Industry, environmental activist groups, government regulators, and the general public are all concerned with the question of how environmental risk to public health is to be measured and what level of risk warrants government action under the environmental laws. Several recent events shed light on the fundamental scientific and legal problems inherent in such regulation, and these events may affect the direction of future developments. These events include implementation of generic Risk Assessment Guidelines by the US EPA, litigation challenging EPA's regulation of carcinogenic substances, new scientific understanding of the relative risks from human exposure to natural and man-made sources, and the continuing growth of toxic tort litigation in which victims of cancer seek large damages from industrial emitters of pollution

  16. Profiling of Human Molecular Pathways Affected by Retrotransposons at the Level of Regulation by Transcription Factor Proteins

    Science.gov (United States)

    Nikitin, Daniil; Penzar, Dmitry; Garazha, Andrew; Sorokin, Maxim; Tkachev, Victor; Borisov, Nicolas; Poltorak, Alexander; Prassolov, Vladimir; Buzdin, Anton A.

    2018-01-01

    Endogenous retroviruses and retrotransposons also termed retroelements (REs) are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBSs). We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. By using ENCODE data, we identified ~2 million TFBS overlapping with putatively regulation-competent human REs located in 5-kb gene promoter neighborhood (~17% of all TFBS in promoter neighborhoods; ~9% of all RE-linked TFBS). Most of REs hosting TFBS were highly diverged repeats, and for the evolutionary young (0–8% diverged) elements we identified only ~7% of all RE-linked TFBS. The gene-specific distributions of RE-linked TFBS generally correlated with the distributions for all TFBS. However, several groups of molecular processes were highly enriched in the RE-linked TFBS regulation. They were strongly connected with the immunity and response to pathogens, with the negative regulation of gene transcription, ubiquitination, and protein degradation, extracellular matrix organization, regulation of STAT signaling, fatty acids metabolism, regulation of GTPase activity, protein targeting to Golgi, regulation of cell division and differentiation, development and functioning of perception organs and reproductive system. By contrast, the processes most weakly affected by the REs were linked with the conservative aspects of embryo development. We also identified differences in the regulation features by the younger and older fractions of the REs. The regulation by the older fraction of the REs was linked mainly with the immunity, cell adhesion, cAMP, IGF1R, Notch, Wnt, and integrin signaling, neuronal development, chondroitin sulfate and heparin metabolism, and endocytosis. The younger REs regulate other aspects of immunity, cell cycle progression and

  17. Profiling of Human Molecular Pathways Affected by Retrotransposons at the Level of Regulation by Transcription Factor Proteins

    Directory of Open Access Journals (Sweden)

    Daniil Nikitin

    2018-01-01

    Full Text Available Endogenous retroviruses and retrotransposons also termed retroelements (REs are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBSs. We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. By using ENCODE data, we identified ~2 million TFBS overlapping with putatively regulation-competent human REs located in 5-kb gene promoter neighborhood (~17% of all TFBS in promoter neighborhoods; ~9% of all RE-linked TFBS. Most of REs hosting TFBS were highly diverged repeats, and for the evolutionary young (0–8% diverged elements we identified only ~7% of all RE-linked TFBS. The gene-specific distributions of RE-linked TFBS generally correlated with the distributions for all TFBS. However, several groups of molecular processes were highly enriched in the RE-linked TFBS regulation. They were strongly connected with the immunity and response to pathogens, with the negative regulation of gene transcription, ubiquitination, and protein degradation, extracellular matrix organization, regulation of STAT signaling, fatty acids metabolism, regulation of GTPase activity, protein targeting to Golgi, regulation of cell division and differentiation, development and functioning of perception organs and reproductive system. By contrast, the processes most weakly affected by the REs were linked with the conservative aspects of embryo development. We also identified differences in the regulation features by the younger and older fractions of the REs. The regulation by the older fraction of the REs was linked mainly with the immunity, cell adhesion, cAMP, IGF1R, Notch, Wnt, and integrin signaling, neuronal development, chondroitin sulfate and heparin metabolism, and endocytosis. The younger REs regulate other aspects of immunity, cell cycle

  18. Regulation of lipoprotein lipase in primary cultures of isolated human adipocytes

    International Nuclear Information System (INIS)

    Kern, P.A.; Marshall, S.; Eckel, R.H.

    1985-01-01

    To study the regulation of adipose tissue lipoprotein lipase (LPL) in human adipocytes, omental adipose tissue was obtained from healthy subjects and digested in collagenase. The isolated adipocytes thus obtained were suspended in Medium 199 and cultured at 37 degrees C. Cell viability was demonstrated in adipocytes cultured for up to 72 h by constancy of cell number, cell size, trypan-blue exclusion, and specific 125 I-insulin binding. In addition, chloroquine induced an increase in cell-associated 125 I-insulin at 24, 48, and 72 h after preparation. Thus, isolated adipocytes retained their ability to bind, internalize, and degrade insulin. LPL was measured as activity secreted into the culture medium (CM), released from cells by heparin (HR), and extracted from cell digests. A broad range of heparin concentrations produced a prompt release of LPL from a rapidly replenishable pool of cellular activity. When cells were cultured in medium containing 10% fetal bovine serum, there was a marked stimulation of CM and HR. The secretory response to serum (CM) correlated strongly with HR 24 h after preparation. In addition, HR was found to correlate logarithmically and inversely with body mass index. Insulin, at 400 ng/ml only, increased HR by 36 +/- 10%, an effect simulated by lower concentrations of insulin-like growth factor-1 (IGF1). Thus, LPL is produced and regulated in isolated human adipocytes. The degree of adiposity and serum are important regulators of HR activity, whereas insulin is stimulatory only at a pharmacologic concentration. This effect of insulin may be mediated through the IGF1 receptor. Isolated human adipocytes represent a novel and useful system for the study of LPL and lipid metabolism as well as for other aspects of adipocyte biology

  19. Estrogen regulates progesterone production by human placental trophoblast cells in culture

    International Nuclear Information System (INIS)

    Grimes, R.W.

    1990-01-01

    We have suggested that estrogen regulates placental low-density lipoprotein (LDL) uptake and thus progesterone (P 4 ) production during primate pregnancy based on results obtained in antiestrogen-treated baboons. The objectives of the present study, were to determine whether estrogen is also important to regulation of P 4 formation by the human placenta, and whether effects of estrogen were mediated by availability of cholesterol substrate via the LDL, de novo, or deesterification pathways. Term human placenta were dispersed in 0.125% trypsin, cytotrophoblasts were purified via a 70-5% Percoll gradient, incubated 72 h in DMEM with 10% FBS to stimulate formation of syncytia, then incubated an additional 48 h with estradiol (E2). In Experiment 1, 1 μg/ml E 2 and 500 μg/MI LDL-protein, stimulated P 4 (P 2 increased LDL uptake. Scatchard analysis indicated that trophoblast uptake of [ 125 I]LDL (ng/mg cell protein) was 50% greater (P 2 (mean ± SE, 638 +/- 23; n = 6) than DMEM in the presence of antiestrogen MER-25. Moreover, uptake and degradation of LDL, and cellular content of free and esterified cholesterol, increased in a dose-dependent manner with 0.1 to 1000 ng/ml E 2 . These results suggest that estrogen regulates placental cell uptake of LDL and thus availability of cholesterol for P 4 biosynthesis during human pregnancy. In Experiment 2, E 2 Stimulated P 4 formation (ng/mg cell protein/48 h) from a control level of 194 ± 25 to 357 ± 62, in the absence of LDL. Under these conditions, cholesterol for P 4 biosynthesis must have been derived from de novo synthesis and/or deesterification of cholesteryl ester stores

  20. Neural Mechanisms of Circadian Regulation of Natural and Drug Reward

    Directory of Open Access Journals (Sweden)

    Lauren M. DePoy

    2017-01-01

    Full Text Available Circadian rhythms are endogenously generated near 24-hour variations of physiological and behavioral functions. In humans, disruptions to the circadian system are associated with negative health outcomes, including metabolic, immune, and psychiatric diseases, such as addiction. Animal models suggest bidirectional relationships between the circadian system and drugs of abuse, whereby desynchrony, misalignment, or disruption may promote vulnerability to drug use and the transition to addiction, while exposure to drugs of abuse may entrain, disrupt, or perturb the circadian timing system. Recent evidence suggests natural (i.e., food and drug rewards may influence overlapping neural circuitry, and the circadian system may modulate the physiological and behavioral responses to these stimuli. Environmental disruptions, such as shifting schedules or shorter/longer days, influence food and drug intake, and certain mutations of circadian genes that control cellular rhythms are associated with altered behavioral reward. We highlight the more recent findings associating circadian rhythms to reward function, linking environmental and genetic evidence to natural and drug reward and related neural circuitry.

  1. A Simple Model for Human and Nature Interaction

    Science.gov (United States)

    Motesharrei, S.; Rivas, J.; Kalnay, E.

    2012-12-01

    There are widespread concerns that current trends in population and resource-use are unsustainable, but the possibilities of an overshoot and collapse remain unclear and controversial. Collapses of civilizations have occurred many times in the past 5000 years, often followed by centuries of economic, intellectual, and population decline. Many different natural and social phenomena have been invoked to explain specific collapses, but a general explanation remains elusive. Two important features seem to appear across societies that have collapsed: Ecological Strain and Economic Stratification. Our new model (Human And Nature DYnamics, HANDY) has just four equations that describe the evolution of Elites, Commoners, Nature, and Wealth. Mechanisms leading to collapse are discussed and the measure "Carrying Capacity" is developed and defined. The model shows that societal collapse can happen due to either one of two independent factors: (1) over-consumption of natural resources, and/or (2) deep inequity between Elites and Commoners. The model also portrays two distinct types of collapse: (i) collapse followed by recovery of nature, and (ii) full collapse. The model suggests that the estimation of Carrying Capacity is a practical means for early detection of a collapse. Collapse can be avoided, and population can reach a sustainable equilibrium, if the rate of depletion of nature is reduced to a sustainable level, and if resources are distributed in a reasonably equitable fashion.; A type-ii (full) collapse is shown in this figure. With high inequality and high depletion, societies are doomed to collapse. Wealth starts to decrease when population rises above the carrying capacity. The large gap between carrying capacity and its maximum is a result of depletion factor being much larger than the sustainable limit. ; It is possible to overshoot, oscillate, and eventually converge to an equilibrium, even in an inequitable society. However, it requires policies that control

  2. School Principals' Assumptions about Human Nature: Implications for Leadership in Turkey

    Science.gov (United States)

    Sabanci, Ali

    2008-01-01

    This article considers principals' assumptions about human nature in Turkey and the relationship between the assumptions held and the leadership style adopted in schools. The findings show that school principals hold Y-type assumptions and prefer a relationship-oriented style in their relations with assistant principals. However, both principals…

  3. Natural HIV-1 NEF accelerates virus replication in primary human lymphocytes

    NARCIS (Netherlands)

    de Ronde, A.; Klaver, B.; Keulen, W.; Smit, L.; Goudsmit, J.

    1992-01-01

    HIV-1 NEF genes were isolated directly from peripheral blood lymphocyte DNA of two HIV-1-infected individuals and cloned into an HXB-2-infectious molecular clone. The effect of NEF on virus production in T-cell lines and primary human lymphocytes was studied. Naturally occurring NEF accelerates

  4. Tumor necrosis factor beta and ultraviolet radiation are potent regulators of human keratinocyte ICAM-1 expression

    International Nuclear Information System (INIS)

    Krutmann, J.; Koeck, A.S.; Schauer, E.; Parlow, F.; Moeller, A.K.; Kapp, A.; Foerster, E.S.; Schoepf, E.L.; Luger, T.A.

    1990-01-01

    Intercellular adhesion molecule-1 (ICAM-1) functions as a ligand of leukocyte function-associated antigen-1 (LFA-1), as well as a receptor for human picorna virus, and its regulation thus affects various immunologic and inflammatory reactions. The weak, constitutive ICAM-1 expression on human keratinocytes (KC) can be up-regulated by cytokines such as interferon-gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha). In order to further examine the regulation of KC ICAM-1 expression, normal human KC or epidermoid carcinoma cells (KB) were incubated with different cytokines and/or exposed to ultraviolet (UV) radiation. Subsequently, ICAM-1 expression was monitored cytofluorometrically using a monoclonal anti-ICAM-1 antibody. Stimulation of cells with recombinant human (rh) interleukin (IL) 1 alpha, rhIL-4, rhIL-5, rhIL-6, rh granulocyte/macrophage colony-stimulating factor (GM-CSF), rh interferon alpha (rhIFN alpha), and rh transforming growth factor beta (TGF beta) did not increase ICAM-1 surface expression. In contrast, rhTNF beta significantly up-regulated ICAM-1 expression in a time- and dose-dependent manner. Moreover, the combination of rhTNF beta with rhIFN gamma increased the percentage of ICAM-1-positive KC synergistically. This stimulatory effect of rhTNF beta was further confirmed by the demonstration that rhTNF beta was capable of markedly enhancing ICAM-1 mRNA expression in KC. Finally, exposure of KC in vitro to sublethal doses of UV radiation (0-100 J/m2) prior to cytokine (rhIFN tau, rhTNF alpha, rhTNF beta) stimulation inhibited ICAM-1 up-regulation in a dose-dependent fashion. These studies identify TNF beta and UV light as potent regulators of KC ICAM-1 expression, which may influence both attachment and detachment of leukocytes and possibly viruses to KC

  5. Natural gas industry regulations

    International Nuclear Information System (INIS)

    Clo, A.

    1999-01-01

    In the reception of the EU Directive on the internal gas market, it is quite necessary to avoid the mistakes already made in the case of electricity. A possible cause is there suggested which may help rearrange the natural gas industry and market in Italy. It's four points are: general interests, national peculiarities, public policies, regulatory framework [it

  6. Friends-enemies: endogenous retroviruses are major transcriptional regulators of human DNA

    Science.gov (United States)

    Buzdin, Anton A.; Prassolov, Vladimir; Garazha, Andrew V.

    2017-06-01

    Endogenous retroviruses are mobile genetic elements hardly distinguishable from infectious, or “exogenous”, retroviruses at the time of insertion in the host DNA. Human endogenous retroviruses (HERVs) are not rare. They gave rise to multiple families of closely related mobile elements that occupy 8% of the human genome. Together, they shape genomic regulatory landscape by providing at least 320,000 human transcription factor binding sites (TFBS) located on 110,000 individual HERV elements. The HERVs host as many as 155,000 mapped DNaseI hypersensitivity sites, which denote loci active in the regulation of gene expression or chromatin structure. The contemporary view of the HERVs evolutionary dynamics suggests that at the early stages after insertion, the HERV is treated by the host cells as a foreign genetic element, and is likely to be suppressed by the targeted methylation and mutations. However, at the later stages, when significant number of mutations has been already accumulated and when the retroviral genes are broken, the regulatory potential of a HERV may be released and recruited to modify the genomic balance of transcription factor binding sites. This process goes together with further accumulation and selection of mutations, which reshape the regulatory landscape of the human DNA. However, developmental reprogramming, stress or pathological conditions like cancer, inflammation and infectious diseases, can remove the blocks limiting expression and HERV-mediated host gene regulation. This, in turn, can dramatically alter the gene expression equilibrium and shift it to a newer state, thus further amplifying instability and exacerbating the stressful situation.

  7. Enhanced functional connectivity properties of human brains during in-situ nature experience.

    Science.gov (United States)

    Chen, Zheng; He, Yujia; Yu, Yuguo

    2016-01-01

    In this study, we investigated the impacts of in-situ nature and urban exposure on human brain activities and their dynamics. We randomly assigned 32 healthy right-handed college students (mean age = 20.6 years, SD = 1.6; 16 males) to a 20 min in-situ sitting exposure in either a nature (n = 16) or urban environment (n = 16) and measured their Electroencephalography (EEG) signals. Analyses revealed that a brief in-situ restorative nature experience may induce more efficient and stronger brain connectivity with enhanced small-world properties compared with a stressful urban experience. The enhanced small-world properties were found to be correlated with "coherent" experience measured by Perceived Restorativeness Scale (PRS). Exposure to nature also induces stronger long-term correlated activity across different brain regions with a right lateralization. These findings may advance our understanding of the functional activities during in-situ environmental exposures and imply that a nature or nature-like environment may potentially benefit cognitive processes and mental well-being.

  8. Natural levels of {sup 210}Po in human urine

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Frances, I.; Manjon, G.; Mantero, J.; Diaz, J. [Departament of Applied Phisic II, University of Seville, P.O. Box 41012 Seville (Spain); Garcia-Tenorio, R. [Departament of Applied Phisic II, University of Seville, P.O. Box 41012 Seville (Spain); National Accelerator Centre, P.O. Box 41092 Seville (Spain)

    2014-07-01

    Since the secret agent Alexander Litvinenko was murdered in 2006 by a {sup 210}Po lethal dose, presumably ingested, there is renovated interest on the toxicity of this radionuclide in humans. {sup 210}Po is a radioactive isotope naturally found in nature, mainly incorporated by humans via food and water ingestion, as well as inhaled through its progenitor, the {sup 222}Rn. The total amount of natural {sup 210}Po in the human body can vary from person to person depending on their lifestyle: dietary habits, drinking water source, place of residence (associated with exposure to {sup 222}Rn), etc- and therefore in the concentrations of this element to be found in urine. To analyze the influence of dietary habits on the amount of {sup 210}Po excreted in urine, two volunteers in Seville had a well-defined and time-varying diet for a month, following a daily collection of their urine and determination of the concentrations therein of this radionuclide. The results obtained and the conclusions derived from them form the core of this communication. {sup 210}Po determinations were performed daily in 200 ml aliquots of urine using the technique of high resolution alpha spectrometry. This has involved the application of a single radiochemical method for the concentration and isolation {sup 210}Po, followed by its auto-deposition on copper planchets for proper measure. Daily {sup 210}Po activity concentrations in voluntary urine analyzed during the month of study show high variability with a difference of up to an order of magnitude between maximum and minimum values obtained, and a clear dependence on the diet type followed in the various stages of the experiment. The lowest concentrations obtained are associated with a diet rich in carbohydrates and proteins 'terrestrial' (pork, beef,...), while the highest concentrations were obtained in the final phase of the experiment when the diet was enriched with presence of marine products in fair correspondence with the

  9. Goddess Science, Primates and Feminism. Primatology and Human Nature Seeking

    Directory of Open Access Journals (Sweden)

    Aleksandra Derra

    2015-12-01

    Full Text Available The Author introduces basic aims, notions, methodological tools and theories of primatology. Underlining crucial role this discipline has played in defining human nature, she points out how it has changed due to its social duties, close relations to popular culture and growing impact of female researchers with feminist sensitivity. She posits the question about female or feminist character of primatology, indicating that the answer depends on taking for granted certain disputable assumptions about femininity and female scientific methods. Subsequently she presents androcentric bias of primatology studies (concerning sexuality, reproduction, male domination, female roles, aggression, and its later critique. Finally she problematizes culture/nature division which is used both in scientific and everyday discourse.

  10. MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo

    DEFF Research Database (Denmark)

    Eskildsen, Tilde; Taipaleenmäki, Hanna; Stenvang, Jan

    2011-01-01

    Elucidating the molecular mechanisms that regulate human stromal (mesenchymal) stem cell (hMSC) differentiation into osteogenic lineage is important for the development of anabolic therapies for treatment of osteoporosis. MicroRNAs (miRNAs) are short, noncoding RNAs that act as key regulators......-regulated during osteoblast differentiation of hMSCs. Overexpression of miR-138 inhibited osteoblast differentiation of hMSCs in vitro, whereas inhibition of miR-138 function by antimiR-138 promoted expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Furthermore...

  11. Recognition of lyso-phospholipids by human natural killer T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Lisa M Fox

    2009-10-01

    Full Text Available Natural killer T (NKT cells are a subset of T lymphocytes with potent immunoregulatory properties. Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however, the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear. Here, we have analyzed human NKT cell recognition of CD1d cellular ligands. The most clearly antigenic species was lyso-phosphatidylcholine (LPC. Diacylated phosphatidylcholine and lyso-phosphoglycerols differing in the chemistry of the head group stimulated only weak responses from human NKT cells. However, lyso-sphingomyelin, which shares the phosphocholine head group of LPC, also activated NKT cells. Antigen-presenting cells pulsed with LPC were capable of stimulating increased cytokine responses by NKT cell clones and by freshly isolated peripheral blood lymphocytes. These results demonstrate that human NKT cells recognize cholinated lyso-phospholipids as antigens presented by CD1d. Since these lyso-phospholipids serve as lipid messengers in normal physiological processes and are present at elevated levels during inflammatory responses, these findings point to a novel link between NKT cells and cellular signaling pathways that are associated with human disease pathophysiology.

  12. French regulations for countering external violent forces affecting nuclear power stations

    International Nuclear Information System (INIS)

    Dupraz, B.

    1986-01-01

    This article describes the general principles underlying nuclear safety regulations to counter external violent forces to which plants can be exposed. It then examines the statutory directives concerning external violences connected with human activities or originating from natural phenomena. 3 refs [fr

  13. Symmetries in nature

    International Nuclear Information System (INIS)

    Mainzer, K.

    1988-01-01

    Symmetry, disymmetry, chirality etc. are well-known topics in chemistry. But they cannot only be found on the molecular level of matter. Atoms and elementary particles in physics are also characterized by particular symmetry groups. Even living organisms and populations on the macroscopic level have functional properties of symmetry. The whole physical, chemical, and biological evolution seems to be regulated by the emergence of new symmetries and the breaking down of old ones. One is reminded of Heisenberg's famous statement: 'Die letzte Wurzel der Erscheinungen ist also nicht die Materie, sondern das mathematische Gesetz, die Symmetrie, die mathematische Form' (Wandlungen in den Grundlagen der Naturwissenschaften, 1959). Historically the belief in symmetry and simplicity of nature has a long philosophical tradition from the Pythagoreans, Plato and Greek astronomers to Kepler and modern scientists. Today, 'symmetries in nature' is a common topic of mathematics, physics, chemistry, and biology. A lot of Nobel prizes were given in honour of inquiries concerning symmetries in nature. The fascination of symmetries is not only motivated by science, but by art and religion too. Therefore 'symmetris in nature' is an interdisciplinary topic which may help to overcome C.P. Snow's 'Two Cultures' of natural sciences and humanities. (author) 17 refs., 21 figs

  14. Symmetries in nature

    Energy Technology Data Exchange (ETDEWEB)

    Mainzer, K

    1988-05-01

    Symmetry, disymmetry, chirality etc. are well-known topics in chemistry. But they cannot only be found on the molecular level of matter. Atoms and elementary particles in physics are also characterized by particular symmetry groups. Even living organisms and populations on the macroscopic level have functional properties of symmetry. The whole physical, chemical, and biological evolution seems to be regulated by the emergence of new symmetries and the breaking down of old ones. One is reminded of Heisenberg's famous statement: 'Die letzte Wurzel der Erscheinungen ist also nicht die Materie, sondern das mathematische Gesetz, die Symmetrie, die mathematische Form' (Wandlungen in den Grundlagen der Naturwissenschaften, 1959). Historically the belief in symmetry and simplicity of nature has a long philosophical tradition from the Pythagoreans, Plato and Greek astronomers to Kepler and modern scientists. Today, 'symmetries in nature' is a common topic of mathematics, physics, chemistry, and biology. A lot of Nobel prizes were given in honour of inquiries concerning symmetries in nature. The fascination of symmetries is not only motivated by science, but by art and religion too. Therefore 'symmetris in nature' is an interdisciplinary topic which may help to overcome C.P. Snow's 'Two Cultures' of natural sciences and humanities. (author) 17 refs., 21 figs.

  15. The Nature of Geography and Its Perspectives in AP® Human Geography

    Science.gov (United States)

    Murphy, Alexander B.; Hare, Phillip R.

    2016-01-01

    AP Human Geography students need to develop an understanding of what it means to examine the world around them from a geographic perspective. Focusing attention on geography's concern with spatial relationships, place characteristics, and geographic context helps student appreciate the nature of the discipline and the insights it offers. These…

  16. EML proteins in microtubule regulation and human disease.

    Science.gov (United States)

    Fry, Andrew M; O'Regan, Laura; Montgomery, Jessica; Adib, Rozita; Bayliss, Richard

    2016-10-15

    The EMLs are a conserved family of microtubule-associated proteins (MAPs). The founding member was discovered in sea urchins as a 77-kDa polypeptide that co-purified with microtubules. This protein, termed EMAP for echinoderm MAP, was the major non-tubulin component present in purified microtubule preparations made from unfertilized sea urchin eggs [J. Cell Sci. (1993) 104: , 445-450; J. Cell Sci. (1987) 87: (Pt 1), 71-84]. Orthologues of EMAP were subsequently identified in other echinoderms, such as starfish and sand dollar, and then in more distant eukaryotes, including flies, worms and vertebrates, where the name of ELP or EML (both for EMAP-like protein) has been adopted [BMC Dev. Biol. (2008) 8: , 110; Dev. Genes Evol. (2000) 210: , 2-10]. The common property of these proteins is their ability to decorate microtubules. However, whether they are associated with particular microtubule populations or exercise specific functions in different microtubule-dependent processes remains unknown. Furthermore, although there is limited evidence that they regulate microtubule dynamics, the biochemical mechanisms of their molecular activity have yet to be explored. Nevertheless, interest in these proteins has grown substantially because of the identification of EML mutations in neuronal disorders and oncogenic fusions in human cancers. Here, we summarize our current knowledge of the expression, localization and structure of what is proving to be an interesting and important class of MAPs. We also speculate about their function in microtubule regulation and highlight how the studies of EMLs in human diseases may open up novel avenues for patient therapy. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  17. Investigating microenvironmental regulation of human chordoma cell behaviour.

    Directory of Open Access Journals (Sweden)

    Priya Patel

    Full Text Available The tumour microenvironment is complex and composed of many different constituents, including matricellular proteins such as connective tissue growth factor (CCN2, and is characterized by gradients in oxygen levels. In various cancers, hypoxia and CCN2 promote stem and progenitor cell properties, and regulate the proliferation, migration and phenotype of cancer cells. Our study was aimed at investigating the effects of hypoxia and CCN2 on chordoma cells, using the human U-CH1 cell line. We demonstrate that under basal conditions, U-CH1 cells express multiple CCN family members including CCN1, CCN2, CCN3 and CCN5. Culture of U-CH1 cells in either hypoxia or in the presence of recombinant CCN2 peptide promoted progenitor cell-like characteristics specific to the notochordal tissue of origin. Specifically, hypoxia induced the most robust increase in progenitor-like characteristics in U-CH1 cells, including increased expression of the notochord-associated markers T, CD24, FOXA1, ACAN and CA12, increased cell growth and tumour-sphere formation, and a decrease in the percentage of vacuolated cells present in the heterogeneous population. Interestingly, the effects of recombinant CCN2 peptide on U-CH1 cells were more pronounced under normoxia than hypoxia, promoting increased expression of CCN1, CCN2, CCN3 and CCN5, the notochord-associated markers SOX5, SOX6, T, CD24, and FOXA1 as well as increased tumour-sphere formation. Overall, this study highlights the importance of multiple factors within the tumour microenvironment and how hypoxia and CCN2 may regulate human chordoma cell behaviour.

  18. Demethoxycurcumin inhibited human epithelia ovarian cancer cells' growth via up-regulating miR-551a.

    Science.gov (United States)

    Du, Zhenhua; Sha, Xianqun

    2017-03-01

    Curcumin is a natural agent that has ability to dampen tumor cells' growth. However, the natural form of curcumin is prone to degrade and unstable in vitro. Here, we demonstrated that demethoxycurcumin (a curcumin-related demethoxy compound) could inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Moreover, IRS2/PI3K/Akt axis was inactivated in cells treated with demethoxycurcumin. Quantitative real-time reverse transcription polymerase chain reaction demonstrated that miR-551a was down-regulated in ovarian cancer tissues and ovarian cancer cell lines. Over-expression of miR-551a inhibited cell proliferation and induced apoptosis of ovarian cancer cells, whereas down-regulation of miR-551a exerted the opposite function. Luciferase assays confirmed that there was a binding site of miR-551a in IRS2, and we found that miR-551a exerted tumor-suppressive function by targeting IRS2 in ovarian cancer cells. Remarkably, miR-551a was up-regulated in the cells treated with demethoxycurcumin, and demethoxycurcumin suppressed IRS2 by restoration of miR-551a. In conclusion, demethoxycurcumin hindered ovarian cancer cells' malignant progress via up-regulating miR-551a.

  19. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L; White, Mitchell R; Tecle, Tesfaldet

    2007-01-01

    BACKGROUND: Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection. Common human polymorphisms of SP-D have been found in many human populations and associated with increased risk of certain infections. We recently reported that the Thr...... on the CRD of SP-D were found to have differing effects on antiviral activity. Using an mAb that did not interfere with antiviral activity of SP-D, we confirm that natural SP-D trimers had reduced ability to bind to IAV. In addition, the trimers had reduced ability to neutralize IAV as compared to natural...... indicate that a common human polymorphic form of SP-D may modulate host defense against IAV and give impetus to clinical studies correlating this genotype with risk for IAV infection in susceptible groups. We also show that mAbs directed against different areas on the carbohydrate recognition domain of SP...

  20. Coordinated action of histone modification and microRNA regulations in human genome.

    Science.gov (United States)

    Wang, Xuan; Zheng, Guantao; Dong, Dong

    2015-10-10

    Both histone modifications and microRNAs (miRNAs) play pivotal role in gene expression regulation. Although numerous studies have been devoted to explore the gene regulation by miRNA and epigenetic regulations, their coordinated actions have not been comprehensively examined. In this work, we systematically investigated the combinatorial relationship between miRNA and epigenetic regulation by taking advantage of recently published whole genome-wide histone modification data and high quality miRNA targeting data. The results showed that miRNA targets have distinct histone modification patterns compared with non-targets in their promoter regions. Based on this finding, we proposed a machine learning approach to fit predictive models on the task to discern whether a gene is targeted by a specific miRNA. We found a considerable advantage in both sensitivity and specificity in diverse human cell lines. Finally, we found that our predicted miRNA targets are consistently annotated with Gene Ontology terms. Our work is the first genome-wide investigation of the coordinated action of miRNA and histone modification regulations, which provide a guide to deeply understand the complexity of transcriptional regulation. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Myostatin acts as an autocrine/paracrine negative regulator in myoblast differentiation from human induced pluripotent stem cells.

    Science.gov (United States)

    Gao, Fei; Kishida, Tsunao; Ejima, Akika; Gojo, Satoshi; Mazda, Osam

    2013-02-08

    Myostatin, also known as growth differentiation factor (GDF-8), regulates proliferation of muscle satellite cells, and suppresses differentiation of myoblasts into myotubes via down-regulation of key myogenic differentiation factors including MyoD. Recent advances in stem cell biology have enabled generation of myoblasts from pluripotent stem cells, but it remains to be clarified whether myostatin is also involved in regulation of artificial differentiation of myoblasts from pluripotent stem cells. Here we show that the human induced pluripotent stem (iPS) cell-derived cells that were induced to differentiate into myoblasts expressed myostatin and its receptor during the differentiation. An addition of recombinant human myostatin (rhMyostatin) suppressed induction of MyoD and Myo5a, resulting in significant suppression of myoblast differentiation. The rhMyostatin treatment also inhibited proliferation of the cells at a later phase of differentiation. RNAi-mediated silencing of myostatin promoted differentiation of human iPS-derived embryoid body (EB) cells into myoblasts. These results strongly suggest that myostatin plays an important role in regulation of myoblast differentiation from iPS cells of human origin. The present findings also have significant implications for potential regenerative medicine for muscular diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Regulation of gene expression in human mammary epithelium: effect of breast pumping

    Science.gov (United States)

    Little is known of the molecular regulation of human milk production because of limitations in obtaining mammary tissue from lactating women. Our objectives were to evaluate whether RNA isolated from breast milk fat globules (MFGs) could be an alternative to mammary biopsies and to determine whether...

  3. Critical Studies on Integrating Land-Use Induced Effects on Climate Regulation Services into Impact Assessment for Human Well-Being

    Directory of Open Access Journals (Sweden)

    Zhihui Li

    2013-01-01

    Full Text Available It is commonly acknowledged that land use changes (LUC and climate changes have exerted significant effects on ecosystem services which are essential and vital to human well-being. Among all the services provided by ecosystem, climate regulation services are relatively sensitive to LUC and climate changes. This study aims to comprehensively review studies on the complex effects of LUC and climate changes on climate regulation services and further integrates the effects on climate regulation services into impact assessment for human well-being. In this study, we firstly introduced research efforts in which the drivers of and their corresponding effects on climate regulation services are briefly identified. Then, we explicitly reviewed the researches on the effects of LUC and climate changes on climate regulation services, especially focused on the certain methods and models used to quantify the effects on the major drivers of climate regulation services. After that, the effects of LUC and climate changes on human well-being via climate regulation services were revisited and commented accordingly. Finally, this paper discussed the current research gaps and proposed some research prospects in future studies.

  4. The Impact of Regulating Social Science Research with Biomedical Regulations

    Science.gov (United States)

    Durosinmi, Brenda Braxton

    2011-01-01

    The Impact of Regulating Social Science Research with Biomedical Regulations Since 1974 Federal regulations have governed the use of human subjects in biomedical and social science research. The regulations are known as the Federal Policy for the Protection of Human Subjects, and often referred to as the "Common Rule" because 18 Federal…

  5. Regulation No. 100/2006 Coll. of the Ministry of Health of the Slovak Republic dated as of February 6, 2006 laying down the requirements for natural healing water and natural mineral water, Balneology details of the report, distribution, extent of monitoring and content analysis of natural healing waters and natural mineral waters and their products and requirements for entry to the list of accredited laboratories maintained by the State Commission bathroom

    International Nuclear Information System (INIS)

    2006-01-01

    This Regulation provides: (a) requirements for natural healing water and natural mineral water; (b) requirements for the recognition of natural mineral water; (c) details of balneology report; (d) distribution of natural healing waters and natural mineral water; (e) the extent of tracking of natural healing waters and natural mineral waters and their products; (f) content analysis of natural healing waters and natural mineral waters and their products; (g) registration requirements for accredited laboratories in the list maintained by the State Commission bathroom. This Regulation came into force on March 1, 2006.

  6. The Utilization Of Resources And Regulation Along With Companys Strategies In Managing Oil And Natural Gas Industry In Indonesia

    Directory of Open Access Journals (Sweden)

    Sigit Rahardjo

    2015-08-01

    Full Text Available Oil and gas production in Indonesia has been declined since 1995 up to now the effort to increase the production has been done but it does not result yet. In contrast day by day the investment is getting increased and huge on the other hands it becomes a problem and a challenge for Indonesia to meet oil needs as raw material for refined fuel oil either for transportation or industries. Day by day the needs of refined fuel oil is getting increased and huge as it is correlated to the increasing of the number of motorcycles either two-wheeled or four-wheeled as well as the increasing of oil and gas or non-oil and gas industries. Oil and natural industry Resource Base has specific characteristics those are internal factor that uses resource such as high technology huge investment cost as well as competent human resources. Besides the external factor those are good regulations either in the central and regional levels as well as the sector which is very important toward the production performance and the of company managements strategies to manage this industry. This paper attempts to figure out the impact of internal factor in the form of resources and external factor in the form of regulation as well as the effect of production performance toward petroleum companies of upstream sectors in Indonesia and managements role especially petroleum industrialists in managing the company. The wane of oil production and the increasing of refined fuel oil need in Indonesia as well as the increasing of oil production cost then it will affect the industrialists strategies in managing the companies. The resources consist of human resource oil reserve as well as petroleum technologies. While regulation consists of law central and regional government regulations and rules in oil and gas sector. Whereas the companys strategies are explained by production volume and selling volume of oil. Companys performance which sets to work in upstream sector is influenced by

  7. Naturally occurring products of proglucagon 111-160 in the porcine and human small intestine

    DEFF Research Database (Denmark)

    Buhl, T; Thim, L; Kofod, Hans

    1988-01-01

    to release proglucagon 111-123 (designated spacer peptide 2), which, like proglucagon 126-158 must be considered a potential hormonal entity. By isocratic high pressure liquid chromatography human spacer peptide 2 was indistinguishable from synthetic proglucagon 111-122 amide, suggesting...... that this is the structure of the naturally occurring human peptide....

  8. Myostatin acts as an autocrine/paracrine negative regulator in myoblast differentiation from human induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Fei; Kishida, Tsunao; Ejima, Akika [Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto (Japan); Gojo, Satoshi [Department of Cardiac Support, Kyoto Prefectural University of Medicine, Kyoto (Japan); Mazda, Osam, E-mail: mazda@koto.kpu-m.ac.jp [Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto (Japan)

    2013-02-08

    Highlights: ► iPS-derived cells express myostatin and its receptor upon myoblast differentiation. ► Myostatin inhibits myoblast differentiation by inhibiting MyoD and Myo5a induction. ► Silencing of myostatin promotes differentiation of human iPS cells into myoblasts. -- Abstract: Myostatin, also known as growth differentiation factor (GDF-8), regulates proliferation of muscle satellite cells, and suppresses differentiation of myoblasts into myotubes via down-regulation of key myogenic differentiation factors including MyoD. Recent advances in stem cell biology have enabled generation of myoblasts from pluripotent stem cells, but it remains to be clarified whether myostatin is also involved in regulation of artificial differentiation of myoblasts from pluripotent stem cells. Here we show that the human induced pluripotent stem (iPS) cell-derived cells that were induced to differentiate into myoblasts expressed myostatin and its receptor during the differentiation. An addition of recombinant human myostatin (rhMyostatin) suppressed induction of MyoD and Myo5a, resulting in significant suppression of myoblast differentiation. The rhMyostatin treatment also inhibited proliferation of the cells at a later phase of differentiation. RNAi-mediated silencing of myostatin promoted differentiation of human iPS-derived embryoid body (EB) cells into myoblasts. These results strongly suggest that myostatin plays an important role in regulation of myoblast differentiation from iPS cells of human origin. The present findings also have significant implications for potential regenerative medicine for muscular diseases.

  9. Myostatin acts as an autocrine/paracrine negative regulator in myoblast differentiation from human induced pluripotent stem cells

    International Nuclear Information System (INIS)

    Gao, Fei; Kishida, Tsunao; Ejima, Akika; Gojo, Satoshi; Mazda, Osam

    2013-01-01

    Highlights: ► iPS-derived cells express myostatin and its receptor upon myoblast differentiation. ► Myostatin inhibits myoblast differentiation by inhibiting MyoD and Myo5a induction. ► Silencing of myostatin promotes differentiation of human iPS cells into myoblasts. -- Abstract: Myostatin, also known as growth differentiation factor (GDF-8), regulates proliferation of muscle satellite cells, and suppresses differentiation of myoblasts into myotubes via down-regulation of key myogenic differentiation factors including MyoD. Recent advances in stem cell biology have enabled generation of myoblasts from pluripotent stem cells, but it remains to be clarified whether myostatin is also involved in regulation of artificial differentiation of myoblasts from pluripotent stem cells. Here we show that the human induced pluripotent stem (iPS) cell-derived cells that were induced to differentiate into myoblasts expressed myostatin and its receptor during the differentiation. An addition of recombinant human myostatin (rhMyostatin) suppressed induction of MyoD and Myo5a, resulting in significant suppression of myoblast differentiation. The rhMyostatin treatment also inhibited proliferation of the cells at a later phase of differentiation. RNAi-mediated silencing of myostatin promoted differentiation of human iPS-derived embryoid body (EB) cells into myoblasts. These results strongly suggest that myostatin plays an important role in regulation of myoblast differentiation from iPS cells of human origin. The present findings also have significant implications for potential regenerative medicine for muscular diseases

  10. The antibiotic resistome: gene flow in environments, animals and human beings.

    Science.gov (United States)

    Hu, Yongfei; Gao, George F; Zhu, Baoli

    2017-06-01

    The antibiotic resistance is natural in bacteria and predates the human use of antibiotics. Numerous antibiotic resistance genes (ARGs) have been discovered to confer resistance to a wide range of antibiotics. The ARGs in natural environments are highly integrated and tightly regulated in specific bacterial metabolic networks. However, the antibiotic selection pressure conferred by the use of antibiotics in both human medicine and agriculture practice leads to a significant increase of antibiotic resistance and a steady accumulation of ARGs in bacteria. In this review, we summarized, with an emphasis on an ecological point of view, the important research progress regarding the collective ARGs (antibiotic resistome) in bacterial communities of natural environments, human and animals, i.e., in the one health settings.We propose that the resistance gene flow in nature is "from the natural environments" and "to the natural environments"; human and animals, as intermediate recipients and disseminators, contribute greatly to such a resistance gene "circulation."

  11. Epigenetic regulation of normal human mammary cell type-specific miRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Vrba, Lukas [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center; Inst. of Plant Molecular Biology, Ceske Budejovice (Czech Republic). Biology Centre ASCR; Garbe, James C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Center; Stampfer, Martha R. [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Center; Futscher, Bernard W. [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center and Dept. of Pharmacology & Toxicology

    2011-08-26

    Epigenetic mechanisms are important regulators of cell type–specific genes, including miRNAs. In order to identify cell type-specific miRNAs regulated by epigenetic mechanisms, we undertook a global analysis of miRNA expression and epigenetic states in three isogenic pairs of human mammary epithelial cells (HMEC) and human mammary fibroblasts (HMF), which represent two differentiated cell types typically present within a given organ, each with a distinct phenotype and a distinct epigenotype. While miRNA expression and epigenetic states showed strong interindividual concordance within a given cell type, almost 10% of the expressed miRNA showed a cell type–specific pattern of expression that was linked to the epigenetic state of their promoter. The tissue-specific miRNA genes were epigenetically repressed in nonexpressing cells by DNA methylation (38%) and H3K27me3 (58%), with only a small set of miRNAs (21%) showing a dual epigenetic repression where both DNA methylation and H3K27me3 were present at their promoters, such as MIR10A and MIR10B. Individual miRNA clusters of closely related miRNA gene families can each display cell type–specific repression by the same or complementary epigenetic mechanisms, such as the MIR200 family, and MIR205, where fibroblasts repress MIR200C/141 by DNA methylation, MIR200A/200B/429 by H3K27me3, and MIR205 by both DNA methylation and H3K27me3. Since deregulation of many of the epigenetically regulated miRNAs that we identified have been linked to disease processes such as cancer, it is predicted that compromise of the epigenetic control mechanisms is important for this process. Overall, these results highlight the importance of epigenetic regulation in the control of normal cell type–specific miRNA expression.

  12. Transcriptional and epigenetic regulation of KIAA1199 gene expression in human breast cancer.

    Directory of Open Access Journals (Sweden)

    Cem Kuscu

    Full Text Available Emerging evidence has demonstrated that upregulated expression of KIAA1199 in human cancer bodes for poor survival. The regulatory mechanism controlling KIAA1199 expression in cancer remains to be characterized. In the present study, we have isolated and characterized the human KIAA1199 promoter in terms of regulation of KIAA1199 gene expression. A 3.3 kb fragment of human genomic DNA containing the 5'-flanking sequence of the KIAA1199 gene possesses both suppressive and activating elements. Employing a deletion mutagenesis approach, a 1.4 kb proximal region was defined as the basic KIAA1199 promoter containing a TATA-box close to the transcription start site. A combination of 5'-primer extension study with 5'RACE DNA sequencing analysis revealed one major transcription start site that is utilized in the human KIAA1199 gene. Bioinformatics analysis suggested that the 1.4 kb KIAA1199 promoter contains putative activating regulatory elements, including activator protein-1(AP-1, Twist-1, and NF-κB sites. Sequential deletion and site-direct mutagenesis analysis demonstrated that the AP-1 and distal NF-κB sites are required for KIAA1199 gene expression. Further analyses using an electrophoretic mobility-shift assay and chromatin immunoprecipitation confirmed the requirement of these cis- and trans-acting elements in controlling KIAA1199 gene expression. Finally, we found that upregulated KIAA1199 expression in human breast cancer specimens correlated with hypomethylation of the regulatory region. Involvement of DNA methylation in regulation of KIAA1199 expression was recapitulated in human breast cancer cell lines. Taken together, our study unraveled the regulatory mechanisms controlling KIAA1199 gene expression in human cancer.

  13. The Anthropocene, Ethics, and the Nature of Nature

    Science.gov (United States)

    Trachtenberg, Z.

    2012-12-01

    For Earth scientists the Anthropocene has a strict meaning, tied to evidence that human activities have produced pervasive impacts on the Earth. But it is also significant for scholars outside the Earth sciences. Social scientists study the ways human societies transform the landscape to make it more suited to human habitation; the Anthropocene idea has already served to reveal conceptual linkages among physical and social science research programs. And the Anthropocene has important implications for normative theorists who enquire into the basis of ethical standards that, ideally, guide human activities within the environment. An influential view has held the condition of the Earth's systems in the absence of human interference as such a standard. This view emphasizes the preservation of environmental systems in (or restoration to) their "natural" condition—either because that condition is the most advantageous for human beings, or because those systems have an intrinsic moral value human beings ought to respect. However, Anthropocene research destabilizes the concept of nature. For the "natural" is typically opposed to the artificial, i.e. to the results of human action, and although nature obviously provides the context for human activity, that context is taken to be exogenously given. For virtually all of Earth's history, its systems were "natural" in this sense. However, since the appearance of life on Earth, organisms engaging in what is called niche construction have fundamentally transformed those systems up to the planetary scale. There is no reason to regard human niche construction (e.g. agriculture) as different in kind—though of course anthropogenic impacts are greater than the impacts of other species. It follows that the Anthropocene demands that we move away from an outlook based on a strict opposition between a "natural" condition and the human activities which change it, towards one that conceives of the natural not as a condition, but as a

  14. Enhanced functional connectivity properties of human brains during in-situ nature experience

    Directory of Open Access Journals (Sweden)

    Zheng Chen

    2016-07-01

    Full Text Available In this study, we investigated the impacts of in-situ nature and urban exposure on human brain activities and their dynamics. We randomly assigned 32 healthy right-handed college students (mean age = 20.6 years, SD = 1.6; 16 males to a 20 min in-situ sitting exposure in either a nature (n = 16 or urban environment (n = 16 and measured their Electroencephalography (EEG signals. Analyses revealed that a brief in-situ restorative nature experience may induce more efficient and stronger brain connectivity with enhanced small-world properties compared with a stressful urban experience. The enhanced small-world properties were found to be correlated with “coherent” experience measured by Perceived Restorativeness Scale (PRS. Exposure to nature also induces stronger long-term correlated activity across different brain regions with a right lateralization. These findings may advance our understanding of the functional activities during in-situ environmental exposures and imply that a nature or nature-like environment may potentially benefit cognitive processes and mental well-being.

  15. Role of natural radiations in human leukemogenesis

    International Nuclear Information System (INIS)

    Jacobson, A.P.; Plato, P.A.; Frigerio, N.A.

    1976-01-01

    Some 3 billion years ago, life arose from a warm pool of primordial ooze amid a constant drizzle of radiation. Steadily, man evolved from the lesser forms of life because of or in spite of his natural background-radiation environment. This study is an attempt to determine to what extent these background radiations are responsible for human disease, namely leukemia. Dose rate data were compared with data on all forms of leukemia in the 50 United States for four population subgroups. For the total U. S., no relation between background radiation and leukemia is apparent. A positive correlation appears, however, if various states are deleted from the analysis. It appears that conditions relative to populations and their environment could mask a radiation effect if in fact one is present

  16. ER-16 regulation. Requirements for granting the permit exceptional use of medical devices in humans

    International Nuclear Information System (INIS)

    2015-01-01

    The purpose of this regulation is to establish requirements for applying for a permit exceptional use of medical equipment in Human Beings, the procedures for the evaluation process and bestowal. This regulation is aimed at researchers and designers of medical equipment, related to or associated with National Health Service's priority programs of interest to health.

  17. Toward a formal definition of water scarcity in natural human systems

    Science.gov (United States)

    W.K. Jaeger; A.J. Plantinga; H. Chang; K. Dello; G. Grant; D. Hulse; J.J. McDonnell; S. Lancaster; H. Moradkhani; A.T. Morzillo; P. Mote; A. Nolin; M. Santlemann; J. Wu

    2013-01-01

    Water scarcity may appear to be a simple concept, but it can be difficult to apply to complex natural-human systems. While aggregate scarcity indices are straightforward to compute, they do not adequately represent the spatial and temporal variations in water scarcity that arise from complex systems interactions. The uncertain effects of future climate change on water...

  18. Regulation of lipogenesis by glucocorticoids and insulin in human adipose tissue.

    Directory of Open Access Journals (Sweden)

    Laura L Gathercole

    Full Text Available Patients with glucocorticoid (GC excess, Cushing's syndrome, develop a classic phenotype characterized by central obesity and insulin resistance. GCs are known to increase the release of fatty acids from adipose, by stimulating lipolysis, however, the impact of GCs on the processes that regulate lipid accumulation has not been explored. Intracellular levels of active GC are dependent upon the activity of 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1 and we have hypothesized that 11β-HSD1 activity can regulate lipid homeostasis in human adipose tissue (Chub-S7 cell line and primary cultures of human subcutaneous (sc and omental (om adipocytes. Across adipocyte differentiation, lipogenesis increased whilst β-oxidation decreased. GC treatment decreased lipogenesis but did not alter rates of β-oxidation in Chub-S7 cells, whilst insulin increased lipogenesis in all adipocyte cell models. Low dose Dexamethasone pre-treatment (5 nM of Chub-S7 cells augmented the ability of insulin to stimulate lipogenesis and there was no evidence of adipose tissue insulin resistance in primary sc cells. Both cortisol and cortisone decreased lipogenesis; selective 11β-HSD1 inhibition completely abolished cortisone-mediated repression of lipogenesis. GCs have potent actions upon lipid homeostasis and these effects are dependent upon interactions with insulin. These in vitro data suggest that manipulation of GC availability through selective 11β-HSD1 inhibition modifies lipid homeostasis in human adipocytes.

  19. Legal regulation of the protection of animals in human care

    OpenAIRE

    Kubánková, Lenka

    2014-01-01

    This diploma thesis summarizes regulation of animal in human care protection. It describes international conventions and also European Union and Czech laws. It includes definition of animal and categorizations of animals. The status of animal in Czech civil law is content of this thesis too. On international level are the most important conventions of Council of Europe. The part of this work concerning European Union includes conceptual tools, primary law and secondary law. The main law in Cz...

  20. A quorum sensing-mediated switch contributes to natural transformation of Vibrio cholerae

    OpenAIRE

    Blokesch Melanie

    2013-01-01

    There is a fundamental gap in our understanding of how horizontal gene transfer contributes to the enormous range of genetic variations that are observed among bacteria. The objective of our study was to better understand how the acquisition of genetic material by natural transformation is regulated within a population of Vibrio cholerae cells. V. cholerae is an aquatic bacterium and a facultative human pathogen. It acquires natural competence for transformation in response to changing enviro...

  1. "Everything Has to Die One Day:" Children's Explorations of the Meanings of Death in Human-Animal-Nature Relationships

    Science.gov (United States)

    Russell, Joshua

    2017-01-01

    Children's experiences of death are a potentially vital component of their developing sense of relatedness to non-human others and nature. Environmental education theory and practice would benefit from a broader understanding of how children view death and loss within ecological systems as well as within human-animal-nature relationships, but such…

  2. Genetic variability of aryl hydrocarbon receptor (AhR)-mediated regulation of the human UDP glucuronosyltransferase (UGT) 1A4 gene

    Energy Technology Data Exchange (ETDEWEB)

    Erichsen, Thomas J; Ehmer, Ursula; Kalthoff, Sandra; Lankisch, Tim O; Mueller, Tordis M [Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Medical School, Hannover (Germany); Munzel, Peter A [Department of Toxicology, Institute of Pharmacology and Toxicology, University of Tubingen, Tubingen (Germany); Manns, Michael P [Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Medical School, Hannover (Germany); Strassburg, Christian P. [Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Medical School, Hannover (Germany)], E-mail: strassburg.christian@mh-hannover.de

    2008-07-15

    UDP glucuronosyltransferases (UGTs) play an important role for drug detoxification and toxicity. UGT function is genetically modulated by single nucleotide polymorphisms (SNPs) which lead to the expression of functionally altered protein, or altered expression levels. UGT1A4 activity includes anticonvulsants, antidepressants and environmental mutagens. In this study the induction of the human UGT1A4 gene and a potential influence of genetic variation in its promoter region were analyzed. SNPs at bp - 219 and - 163 occurred in 9% among 109 blood donors reducing UGT1A4 transcription by 40%. UGT1A4 transcription was dioxin inducible. Reporter gene experiments identified 2 xenobiotic response elements (XRE), which were functionally confirmed by mutagenesis analyses, and binding was demonstrated by electromobility shift assays. Constitutive human UGT1A4 gene expression and induction was aryl hydrocarbon receptor (AhR)-dependent, and reduced in the presence of SNPs at bp - 219 and - 163. AhR-mediated regulation of the human UGT1A4 gene by two XRE and a modulation by naturally occurring genetic variability by SNPs is demonstrated, which indicates gene-environment interaction with potential relevance for drug metabolism.

  3. Genetic variability of aryl hydrocarbon receptor (AhR)-mediated regulation of the human UDP glucuronosyltransferase (UGT) 1A4 gene

    International Nuclear Information System (INIS)

    Erichsen, Thomas J.; Ehmer, Ursula; Kalthoff, Sandra; Lankisch, Tim O.; Mueller, Tordis M.; Munzel, Peter A.; Manns, Michael P.; Strassburg, Christian P.

    2008-01-01

    UDP glucuronosyltransferases (UGTs) play an important role for drug detoxification and toxicity. UGT function is genetically modulated by single nucleotide polymorphisms (SNPs) which lead to the expression of functionally altered protein, or altered expression levels. UGT1A4 activity includes anticonvulsants, antidepressants and environmental mutagens. In this study the induction of the human UGT1A4 gene and a potential influence of genetic variation in its promoter region were analyzed. SNPs at bp - 219 and - 163 occurred in 9% among 109 blood donors reducing UGT1A4 transcription by 40%. UGT1A4 transcription was dioxin inducible. Reporter gene experiments identified 2 xenobiotic response elements (XRE), which were functionally confirmed by mutagenesis analyses, and binding was demonstrated by electromobility shift assays. Constitutive human UGT1A4 gene expression and induction was aryl hydrocarbon receptor (AhR)-dependent, and reduced in the presence of SNPs at bp - 219 and - 163. AhR-mediated regulation of the human UGT1A4 gene by two XRE and a modulation by naturally occurring genetic variability by SNPs is demonstrated, which indicates gene-environment interaction with potential relevance for drug metabolism

  4. Cultural variation is part of human nature : Literary universals, context-sensitivity, and "shakespeare in the bush".

    Science.gov (United States)

    Sugiyama, Michelle Scalise

    2003-12-01

    In 1966, Laura Bohannan wrote her classic essay challenging the supposition that great literary works speak to universal human concerns and conditions and, by extension, that human nature is the same everywhere. Her evidence: the Tiv of West Africa interpret Hamlet differently from Westerners. While Bohannan's essay implies that cognitive universality and cultural variation are mutually exclusive phenomena, adaptationist theory suggests otherwise. Adaptive problems ("the human condition") and cognitive adaptations ("human nature") are constant across cultures. What differs between cultures is habitat: owing to environmental variation, the means and information relevant to solving adaptive problems differ from place to place. Thus, we find differences between cultures not because human minds differ in design but largely because human habitats differ in resources and history. On this view, we would expect world literature to express both human universals and cultural particularities. Specifically, we should expect to find literary universality at the macro level (e.g., adaptive problems, cognitive adaptations) and literary variation at the micro level (e.g., local solutions to adaptive problems).

  5. Neuroendocrine regulation of appetitive ingestive behavior

    Directory of Open Access Journals (Sweden)

    Erin eKeen-Rhinehart

    2013-11-01

    Full Text Available Food availability in nature is often irregular, and famine is commonplace. Increased motivation to engage in ingestive behaviors increases the chance of survival, providing additional potential opportunities for reproduction. Because of the advantages conferred by entraining ingestive behavior to environmental conditions, neuroendocrine mechanisms regulating the motivation to acquire and ingest food have evolved to be responsive to exogenous (i.e. food stored for future consumption and endogenous (i.e. body fat stores fuel availability. Motivated behaviors like eating occur in two phases. The appetitive phase brings animals into contact with food (e.g. foraging, food hoarding, and the more reflexive consummatory phase results in ingestion (e.g., chewing, swallowing. Quantifiable appetitive behaviors are part of many the natural ingestive behavioral repertoire of species such as hamsters and humans. This review summarizes current knowledge about neuroendocrine regulators of ingestive behavior, with an emphasis appetitive behavior. We will discuss hormonal regulators of appetitive ingestive behaviors, including the orexigenic hormone ghrelin, which potently stimulates foraging and food hoarding in Siberian hamsters. This section includes a discussion of the hormone leptin, its relation to endogenous fat stores, and its role in food deprivation-induced increases in appetitive ingestive behaviors. Next, we discuss how hormonal regulators interact with neurotransmitters involved in the regulation of ingestive behaviors, such as NPY, AgRP and alpha-MSH, to regulate ingestive behavior. Finally, we discuss the potential impact that perinatal nutrient availability can have on the neuroendocrine regulation of ingestive behavior. Understanding the hormonal mechanisms that connect metabolic fuel availability to central appetite regulatory circuits should provide a better understanding of the neuroendocrine regulation of the motivation to engage in ingestive

  6. Human physiological benefits of viewing nature: EEG responses to exact and statistical fractal patterns.

    Science.gov (United States)

    Hagerhall, C M; Laike, T; Küller, M; Marcheschi, E; Boydston, C; Taylor, R P

    2015-01-01

    Psychological and physiological benefits of viewing nature have been extensively studied for some time. More recently it has been suggested that some of these positive effects can be explained by nature's fractal properties. Virtually all studies on human responses to fractals have used stimuli that represent the specific form of fractal geometry found in nature, i.e. statistical fractals, as opposed to fractal patterns which repeat exactly at different scales. This raises the question of whether human responses like preference and relaxation are being driven by fractal geometry in general or by the specific form of fractal geometry found in nature. In this study we consider both types of fractals (statistical and exact) and morph one type into the other. Based on the Koch curve, nine visual stimuli were produced in which curves of three different fractal dimensions evolve gradually from an exact to a statistical fractal. The patterns were shown for one minute each to thirty-five subjects while qEEG was continuously recorded. The results showed that the responses to statistical and exact fractals differ, and that the natural form of the fractal is important for inducing alpha responses, an indicator of a wakefully relaxed state and internalized attention.

  7. CCAAT/enhancer-binding proteins regulate expression of the human steroidogenic acute regulatory protein (StAR) gene.

    Science.gov (United States)

    Christenson, L K; Johnson, P F; McAllister, J M; Strauss, J F

    1999-09-10

    Two putative CCAAT/enhancer-binding protein (C/EBP) response elements were identified in the proximal promoter of the human steroidogenic acute regulatory protein (StAR) gene, which encodes a key protein-regulating steroid hormone synthesis. Expression of C/EBPalpha and -beta increased StAR promoter activity in COS-1 and HepG2 cells. Cotransfection of C/EBPalpha or -beta and steroidogenic factor 1, a transcription factor required for cAMP regulation of StAR expression, into COS-1 augmented 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP)-stimulated promoter activity. When the putative C/EBP response elements were mutated, individually or together, a pronounced decline in basal StAR promoter activity in human granulosa-lutein cells resulted, but the fold stimulation of promoter activity by 8-Br-cAMP was unaffected. Recombinant C/EBPalpha and -beta bound to the two identified sequences but not the mutated elements. Human granulosa-lutein cell nuclear extracts also bound these elements but not the mutated sequences. An antibody to C/EBPbeta, but not C/EBPalpha, supershifted the nuclear protein complex associated with the more distal element. The complex formed by nuclear extracts with the proximal element was not supershifted by either antibody. Western blot analysis revealed the presence of C/EBPalpha and C/EBPbeta in human granulosa-lutein cell nuclear extracts. C/EBPbeta levels were up-regulated 3-fold by 8-Br-cAMP treatment. Our studies demonstrate a role for C/EBPbeta as well as yet to be identified proteins, which can bind to C/EBP response elements, in the regulation of StAR gene expression and suggest a mechanism by which C/EBPbeta participates in the cAMP regulation of StAR gene transcription.

  8. MicroRNAs regulate human adipocyte lipolysis: effects of miR-145 are linked to TNF-α.

    Directory of Open Access Journals (Sweden)

    Silvia Lorente-Cebrián

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs that regulate gene expression and have multiple effects in various tissues including adipose inflammation, a condition characterized by increased local release of the pro-lipolytic cytokine tumor necrosis factor-alpha (TNF-α. Whether miRNAs regulate adipocyte lipolysis is unknown. We set out to determine whether miRNAs affect adipocyte lipolysis in human fat cells. To this end, eleven miRNAs known to be present in human adipose tissue were over-expressed in human in vitro differentiated adipocytes followed by assessments of TNF-α and glycerol levels in conditioned media after 48 h. Three miRNAs (miR-145, -26a and let-7d modulated both parameters in parallel. However, while miR-26a and let-7d decreased, miR-145 increased both glycerol release and TNF-α secretion. Further studies were focused therefore on miR-145 since this was the only stimulator of lipolysis and TNF-α secretion. Time-course analysis demonstrated that miR-145 over-expression up-regulated TNF-α expression/secretion followed by increased glycerol release. Increase in TNF-α production by miR-145 was mediated via activation of p65, a member of the NF-κB complex. In addition, miR-145 down-regulated the expression of the protease ADAM17, resulting in an increased fraction of membrane bound TNF-α, which is the more biologically active form of TNF-α. MiR-145 overexpression also increased the phosphorylation of activating serine residues in hormone sensitive lipase and decreased the mRNA expression of phosphodiesterase 3B, effects which are also observed upon TNF-α treatment in human adipocytes. We conclude that miR-145 regulates adipocyte lipolysis via multiple mechanisms involving increased production and processing of TNF-α in fat cells.

  9. Weather Regulates Location, Timing, and Intensity of Dengue Virus Transmission between Humans and Mosquitoes.

    Science.gov (United States)

    Campbell, Karen M; Haldeman, Kristin; Lehnig, Chris; Munayco, Cesar V; Halsey, Eric S; Laguna-Torres, V Alberto; Yagui, Martín; Morrison, Amy C; Lin, Chii-Dean; Scott, Thomas W

    2015-01-01

    % resolution. Local duration in limited areas of temperature-humidity weather-space identifies potential locations, timing, and magnitude of transmission. The weather-space profile of transmission-potential provides needed data that define a systematic and highly-sensitive weather-disease connection, demonstrating separate but coupled roles of temperature and humidity. New insights regarding natural regulation of human-mosquito transmission across diverse ecological settings advance our understanding of risk locally and globally for dengue and other mosquito-borne diseases and support advances in public health policy/operations, providing an evidence-base for modeling, predicting risk, and surveillance-prevention planning.

  10. Weather Regulates Location, Timing, and Intensity of Dengue Virus Transmission between Humans and Mosquitoes.

    Directory of Open Access Journals (Sweden)

    Karen M Campbell

    -100% at 1°C x 2% resolution.Local duration in limited areas of temperature-humidity weather-space identifies potential locations, timing, and magnitude of transmission. The weather-space profile of transmission-potential provides needed data that define a systematic and highly-sensitive weather-disease connection, demonstrating separate but coupled roles of temperature and humidity. New insights regarding natural regulation of human-mosquito transmission across diverse ecological settings advance our understanding of risk locally and globally for dengue and other mosquito-borne diseases and support advances in public health policy/operations, providing an evidence-base for modeling, predicting risk, and surveillance-prevention planning.

  11. A landslide on a mudslide? Natural hazards and the right to life under the European Convention of Human Rights

    DEFF Research Database (Denmark)

    Lauta, Kristian Cedervall; Rytter, Jens Elo

    2016-01-01

    This paper investigates the protection of individuals’ lives against natural hazards under the European Convention on Human Rights. In 2008, the European Court of Human Rights decided to include natural hazards in a well-established doctrine developed to protect individuals from life-threatening ...

  12. Natural gas marketing and transportation

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    This book covers: Overview of the natural gas industry; Federal regulation of marketing and transportation; State regulation of transportation; Fundamentals of gas marketing contracts; Gas marketing options and strategies; End user agreements; Transportation on interstate pipelines; Administration of natural gas contracts; Structuring transactions with the nonconventional source fuels credit; Take-or-pay wars- a cautionary analysis for the future; Antitrust pitfalls in the natural gas industry; Producer imbalances; Natural gas futures for the complete novice; State non-utility regulation of production, transportation and marketing; Natural gas processing agreements and Disproportionate sales, gas balancing, and accounting to royalty owners

  13. The Importance of Ecology-Based Nature Education Project in Terms of Nature Integration and Understanding the Human-Ecosystem Relationship

    Science.gov (United States)

    Meydan, Ali

    2011-01-01

    The aim of this project is to define the importance of 12-day ecology-based education training upon integration with nature and understanding the human-ecosystem relationship. In accordance with this purpose, there has been collected some survey data interviewing with the participants of "Lake Beysehir National Park and Ecology-based Nature…

  14. Flood Protection Decision Making Within a Coupled Human and Natural System

    Science.gov (United States)

    O'Donnell, Greg; O'Connell, Enda

    2013-04-01

    Due to the perceived threat from climate change, prediction under changing climatic and hydrological conditions has become a dominant theme of hydrological research. Much of this research has been climate model-centric, in which GCM/RCM climate projections have been used to drive hydrological system models to explore potential impacts that should inform adaptation decision-making. However, adaptation fundamentally involves how humans may respond to increasing flood and drought hazards by changing their strategies, activities and behaviours which are coupled in complex ways to the natural systems within which they live and work. Humans are major agents of change in hydrological systems, and representing human activities and behaviours in coupled human and natural hydrological system models is needed to gain insight into the complex interactions that take place, and to inform adaptation decision-making. Governments and their agencies are under pressure to make proactive investments to protect people living in floodplains from the perceived increasing flood hazard. However, adopting this as a universal strategy everywhere is not affordable, particularly in times of economic stringency and given uncertainty about future climatic conditions. It has been suggested that the assumption of stationarity, which has traditionally been invoked in making hydrological risk assessments, is no longer tenable. However, before the assumption of hydrologic nonstationarity is accepted, the ability to cope with the uncertain impacts of global warming on water management via the operational assumption of hydrologic stationarity should be carefully examined. Much can be learned by focussing on natural climate variability and its inherent changes in assessing alternative adaptation strategies. A stationary stochastic multisite flood hazard model has been developed that can exhibit increasing variability/persistence in annual maximum floods, starting with the traditional assumption of

  15. Legal regulation of the reuse of water resources in the oil, natural gas and biofuels industry; A regulamentacao juridica do reuso dos recursos hidricos na Industria do petroleo, gas natural e biocombustiveis

    Energy Technology Data Exchange (ETDEWEB)

    Azevedo, Flaviana Marques de; Guimaraes, Patricia Borba Vilar [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil)

    2010-07-01

    The Constitution of 1988 is a guide for protect natural resources in the country, it was from her that the right to an ecologically balanced environment was elevated to the category of fundamental human right of all was changed understanding regarding the use water resources, irrigation water is characterized as a resource with economic value. In this scenario emerging legal standards for protecting the environment and water resources, which must necessarily be committed to the development of economic activities that use natural resources, and still worry about their conservation and preservation for the use of present and future generations, in line with the desires dictated by sustainable development. Therefore, this work has the scope to verify the legal regulation of reuse of water resources in the context of activities developed by the oil industry, natural gas and biofuels, to promote optimum use of water resources in the country, and this can lead to benefits social, economic and environmental. The importance of the study emerges precisely in the industrial sector, and specifically in the oil industry, natural gas and biofuels, in order that through these activities is increased the negative potential of natural resources, consequently increasing the ability to cause negative externalities either by adopting systematic contrary to sustainable development, as the high standards of environmental degradation caused by the activities of this kind. The methodology for conducting this study is theoretical and descriptive, developing through the analysis and interpretation of data obtained from the verification of magazines, books and monographs, concerning the subject of water resources and, by examining done about the current environmentalist doctrine and appreciation of constitutional and legislative documents infra constitutional above existing on the subject. (author)

  16. Klotho down-regulates Egr-1 by inhibiting TGF-β1/Smad3 signaling in high glucose treated human mesangial cells

    International Nuclear Information System (INIS)

    Li, Yang; Hu, Fang; Xue, Meng; Jia, Yi-Jie; Zheng, Zong-Ji; Wang, Ling; Guan, Mei-Ping; Xue, Yao-Ming

    2017-01-01

    Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide and is associated with glomerular mesangial cell (MC) proliferation and excessive extracellular matrix (ECM) production. Klotho can attenuate renal fibrosis in part by inhibiting TGF-β1/Smad3 signaling in DKD. Early growth response factor 1 (Egr-1) has been shown to play a key role in renal fibrosis in part by facilitating the formation of a positive feedback loop involving TGF-β1. However, whether Klotho down-regulates Egr-1 by inhibiting TGF-β1/Smad3 signaling in DKD is unclear. In the present study, we assessed human MCs that were incubated under high-glucose conditions to mimic diabetes. Then, we transfected the cells with Klotho plasmid or siRNA to overexpress or knock down Klotho gene and protein expression. Klotho, Egr-1, fibronectin (FN), collagen type I (Col I), Smad3 and phosphorylated Smad3 (p-Smad3) gene and protein expression levels were determined by RT-qPCR and western blotting respectively. High glucose time-dependently down-regulated Klotho mRNA and protein expression in cultured human MCs. pcDNA3.1-Klotho transfection-mediated Klotho overexpression down-regulated Egr-1, FN and Col I expression and the p-Smad3/Smad3 ratio in human MCs. Conversely, siRNA-mediated Klotho silencing up-regulated Egr-1, FN, and Col I expression and the p-Smad3/Smad3 ratio. Moreover, the effects of si-Klotho on Egr-1 expression were abolished by the TGF-β1 inhibitor SB-431542. Klotho overexpression can prevent mesangial ECM production in high-glucose-treated human MCs, an effect that has been partially attributed to Egr-1 down-regulation facilitated by TGF-β1/Smad3 signaling inhibition. - Highlights: • High glucose time-dependently down-regulated Klotho mRNA and protein expression in cultured human MCs. • Klotho overexpression down-regulated Egr-1 and prevented mesangial ECM production in high-glucose-treated human MCs. • Klotho down-regulated Egr-1 by inhibiting

  17. Self-regulation, ego depletion, and inhibition.

    Science.gov (United States)

    Baumeister, Roy F

    2014-12-01

    Inhibition is a major form of self-regulation. As such, it depends on self-awareness and comparing oneself to standards and is also susceptible to fluctuations in willpower resources. Ego depletion is the state of reduced willpower caused by prior exertion of self-control. Ego depletion undermines inhibition both because restraints are weaker and because urges are felt more intensely than usual. Conscious inhibition of desires is a pervasive feature of everyday life and may be a requirement of life in civilized, cultural society, and in that sense it goes to the evolved core of human nature. Intentional inhibition not only restrains antisocial impulses but can also facilitate optimal performance, such as during test taking. Self-regulation and ego depletion- may also affect less intentional forms of inhibition, even chronic tendencies to inhibit. Broadly stated, inhibition is necessary for human social life and nearly all societies encourage and enforce it. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Human-itarian aid? Two forms of dehumanization and willingness to help after natural disasters.

    Science.gov (United States)

    Andrighetto, Luca; Baldissarri, Cristina; Lattanzio, Sara; Loughnan, Steve; Volpato, Chiara

    2014-09-01

    The present research explores the distinct effects of animalistic and mechanistic dehumanization on willingness to help natural disaster victims. We examined Japanese and Haitians, two national groups recently struck by earthquakes. We showed that Italian participants differently dehumanized the two outgroups: Japanese were attributed low human nature (dehumanized as automata), whereas Haitians were attributed low human uniqueness (dehumanized as animal-like). Ninety participants were then randomly assigned to the Japanese or Haitian target group condition. Mediation analyses showed that animalistic dehumanization decreased willingness to help Haitians, whereas mechanistic dehumanization decreased willingness to help Japanese, even when controlling for attitudes. Importantly, reduced empathy explained the effects of both forms of dehumanization on intergroup helping. © 2014 The British Psychological Society.

  19. 21 century perspective in radiation protection of humans and human population

    International Nuclear Information System (INIS)

    Vassilev, G.

    2003-01-01

    In 21 century ionizing radiation is applied in all field of human activities. In parallel, the radiobiology and radiation medicine are developing as separate branches for the purposes of the radiation protection: for risk estimation and regulation of the human irradiation. Main features of radiation protection at the beginning of the century are: 1.Well developed conservative theoretical background, based on the linear non-threshold concept 'dose-effect' towards the carcinogenesis and genetic effects; 2. Developed international and national structures, including organizations as ICRP, UNSCEAR, ICRU, IAEA, WHO, FAO, BEIR, OECD/NEA, ILO, NCRP, NRPB etc. 3. Detailed regulative legislation for all cases of human irradiation, combines with effective control structures. Ionizing radiation is the most strictly regulated factor affecting humans among the all adverse impacts of the living environment. The expectations for the radiation protection in 21 century are: 1. A radical reassessment of the concept for low doses and the linear non-threshold concept since data for existing of a threshold on the human population level. 2. Taking into consideration of the the adaptation to the irradiation, comparable with the natural radiation background. 3. Taking into consideration of the radiation hormesis, which are now ignored by the risk theory. 4. Clarification of the questions of the genetic effects, which are not yet determined for the human population. 5. Radical solutions of the radioactive waste problem, which will be crucial for the future of the nuclear energy production. 6. Gradual overcoming of the fear from ionizing radiation, which is an important social factor

  20. Structural insights into central hypertension regulation by human aminopeptidase A.

    Science.gov (United States)

    Yang, Yang; Liu, Chang; Lin, Yi-Lun; Li, Fang

    2013-08-30

    Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, zinc-dependent aminopeptidase A (APA) up-regulates blood pressure by specifically cleaving the N-terminal aspartate, but not the adjacent arginine, from angiotensin II, a process facilitated by calcium. Here, we determined the crystal structures of human APA and its complexes with different ligands and identified a calcium-binding site in the S1 pocket of APA. Without calcium, the S1 pocket can bind both acidic and basic residues through formation of salt bridges with the charged side chains. In the presence of calcium, the binding of acidic residues is enhanced as they ligate the cation, whereas the binding of basic residues is no longer favorable due to charge repulsion. Of the peptidomimetic inhibitors of APA, amastatin has higher potency than bestatin by fitting better in the S1 pocket and interacting additionally with the S3' subsite. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation and can guide the design and development of brain-targeting antihypertensive APA inhibitors.

  1. Structural Insights into Central Hypertension Regulation by Human Aminopeptidase A*

    Science.gov (United States)

    Yang, Yang; Liu, Chang; Lin, Yi-Lun; Li, Fang

    2013-01-01

    Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, zinc-dependent aminopeptidase A (APA) up-regulates blood pressure by specifically cleaving the N-terminal aspartate, but not the adjacent arginine, from angiotensin II, a process facilitated by calcium. Here, we determined the crystal structures of human APA and its complexes with different ligands and identified a calcium-binding site in the S1 pocket of APA. Without calcium, the S1 pocket can bind both acidic and basic residues through formation of salt bridges with the charged side chains. In the presence of calcium, the binding of acidic residues is enhanced as they ligate the cation, whereas the binding of basic residues is no longer favorable due to charge repulsion. Of the peptidomimetic inhibitors of APA, amastatin has higher potency than bestatin by fitting better in the S1 pocket and interacting additionally with the S3′ subsite. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation and can guide the design and development of brain-targeting antihypertensive APA inhibitors. PMID:23888046

  2. Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.

    Directory of Open Access Journals (Sweden)

    Alicja Pacholewska

    Full Text Available Recurrent airway obstruction (RAO is a common and potentially debilitating lower airway disease in horses, which shares many similarities with human asthma. In susceptible horses RAO exacerbation is caused by environmental allergens and irritants present in hay dust. The objective of this study was the identification of genes and pathways involved in the pathology of RAO by global transcriptome analyses in stimulated peripheral blood mononuclear cells (PBMCs. We performed RNA-seq on PBMCs derived from 40 RAO affected and 45 control horses belonging to three cohorts of Warmblood horses: two half-sib families and one group of unrelated horses. PBMCs were stimulated with hay dust extract, lipopolysaccharides, a recombinant parasite antigen, or left unstimulated. The total dataset consisted of 561 individual samples. We detected significant differences in the expression profiles between RAO and control horses. Differential expression (DE was most marked upon stimulation with hay dust extract. An important novel finding was a strong upregulation of CXCL13 together with many genes involved in cell cycle regulation in stimulated samples from RAO affected horses, in addition to changes in the expression of several HIF-1 transcription factor target genes. The RAO condition alters systemic changes observed as differential expression profiles of PBMCs. Those changes also depended on the cohort and stimulation of the samples and were dominated by genes involved in immune cell trafficking, development, and cell cycle regulation. Our findings indicate an important role of CXCL13, likely macrophage or Th17 derived, and the cell cycle regulator CDC20 in the immune response in RAO.

  3. Cathepsin H indirectly regulates morphogenetic protein-4 (BMP-4) in various human cell lines

    Science.gov (United States)

    Rojnik, Matija; Jevnikar, Zala; Mirkovic, Bojana; Janes, Damjan; Zidar, Nace; Kikelj, Danijel; Kos, Janko

    2011-01-01

    Background Cathepsin H is a cysteine protease considered to play a major role in tumor progression, however, its precise function in tumorigenesis is unclear. Cathepsin H was recently proposed to be involved in processing of bone morphogenetic protein 4 (BMP-4) in mice. In order to clarify whether cathepsin H also regulates BMP-4 in humans, its impact on BMP-4 expression, processing and degradation was investigated in prostate cancer (PC-3), osteosarcoma (HOS) and pro-monocytic (U937) human cell lines. Materials and methods BMP-4 expression was founded to be regulated by cathepsin H using PCR array technology and confirmed by real time PCR. Immunoassays including Western blot and confocal microscopy were used to evaluate the influence of cathepsin H on BMP-4 processing. Results In contrast to HOS, the expression of BMP-4 mRNA in U937 and PC3 cells was significantly decreased by cathepsin H. The different regulation of BMP-4 synthesis could be associated with the absence of the mature 28 kDa cathepsin H form in HOS cells, where only the intermediate 30 kDa form was observed. No co-localization of BMP-4 and cathepsin H was observed in human cell lines and the multistep processing of BMP-4 was not altered in the presence of specific cathepsin H inhibitor. Isolated cathepsin H does not cleave mature recombinant BMP-4, neither with its amino- nor its endopeptidase activity. Conclusions Our results exclude direct proteolytic processing of BMP-4 by cathepsin H, however, they provide support for its involvement in the regulation of BMP-4 expression. PMID:22933963

  4. Transcriptional regulation of human RANK ligand gene expression by E2F1

    International Nuclear Information System (INIS)

    Hu Yan; Sun Meng; Nadiminty, Nagalakshmi; Lou Wei; Pinder, Elaine; Gao, Allen C.

    2008-01-01

    Receptor activator of nuclear factor kappa B ligand (RANKL) is a critical osteoclastogenic factor involved in the regulation of bone resorption, immune function, the development of mammary gland and cardiovascular system. To understand the transcriptional regulation of RANKL, we amplified and characterized a 1890 bp 5'-flanking sequence of human RANKL gene (-1782 bp to +108 bp relative to the transcription start site). Using a series of deletion mutations of the 1890 bp RANKL promoter, we identified a 72 bp region (-172 to -100 bp) mediating RANKL basal transcriptional activity. Sequence analysis revealed a putative E2F binding site within this 72 bp region in the human RANKL promoter. Overexpression of E2F1 increased RANKL promoter activity, while down-regulation of E2F1 expression by small interfering RNA decreased RANKL promoter activity. RT-PCR and enzyme linked immunosorbent assays (ELISA) further demonstrated that E2F1 induced the expression of RANKL. Electrophoretic gel mobility shift assays (EMSA) and antibody competition assays confirmed that E2F1 proteins bind to the consensus E2F binding site in the RANKL promoter. Mutation of the E2F consensus binding site in the RANKL promoter profoundly reduced the basal promoter activity and abolished the transcriptional modulation of RANKL by E2F1. These results suggest that E2F1 plays an important role in regulating RANKL transcription through binding to the E2F consensus binding site

  5. European Communities (Drinking water) Regulations, 2000

    International Nuclear Information System (INIS)

    2000-12-01

    These Regulations were adopted as Statutory Instrument No. 439 of 2000 on 18 December 2000 and come in to operation on 1 January 2004. The regulations give effect to provisions of EU Council Directive 98/83/EC on the quality of water intended for human consumption.. They prescribe quality standards to be applied in relation to certain supplies of drinking water. S.I. 439 of 2000 stipulates that the radiation dose arising from one year's consumption of drinking water should not exceed 0.1 mSv. It further stipulates that the dose calculation should include contributions from all natural and artificial radionuclides with the exception of tritium, potassium-40, radon and radon decay products

  6. Mechanism research of miR-181 regulating human lens epithelial cell apoptosis

    Directory of Open Access Journals (Sweden)

    Yu Qin

    2015-05-01

    Full Text Available AIM: To investigate the expression of miR-181 in the lens tissue of cataract and the regulating mechanism of miR-181 on apoptosis of human lens epithelial cell.METHODS:Real time q-PCR was used to measure the expression of miR-181 in the anterior lens capsules of age-related cataract and human lens epithelial cell apoptosis model. miR-181 mimic and inhibitor were transfected using Lipofectamine 2 000 to regulate the expression of miR-181, and then Real time q-PCR was used to verify transfection efficiency. Flow cytometry was used to detect the change of cell apoptosis rate. RESULTS: Compared with control group, the expression of miR-181 was significantly higher in both the anterior lens capsules of age-related cataract and human lens epithelial cell apoptosis model; the relative expression of miR-181 in lens epithelial cells transfected with miR-181 mimic was increased, whereas decreased in cells transfected with miR-181 inhibitor; the apoptosis rate of cells transfected with miR-181 mimic was increased, while reduced in miR-181 inhibitor group. Each result was statistically significant(PCONCLUSION: High expression of miR-181 is detected in anterior lens capsule of age-related cataract. miR-181 might play a certain role in the pathogenesis of cataract via promoting human lens epithelial cell apoptosis. miR-181 probably becomes a new approach for the nonoperative treatment of cataract, but the concrete mechanism still needs to be further studied.

  7. Guides to Sustainable Connections? Exploring Human-Nature Relationships among Wilderness Travel Leaders

    Science.gov (United States)

    Grimwood, Bryan S. R.; Haberer, Alexa; Legault, Maria

    2015-01-01

    This paper explores and critically interprets the role wilderness travel may play in fostering environmental sustainability. The paper draws upon two qualitative studies that sought to understand human-nature relationships as experienced by different groups of wilderness travel leaders in Canada. According to leaders involved in the studies,…

  8. Insights into the regulation of human CNV-miRNAs from the view of their target genes

    Directory of Open Access Journals (Sweden)

    Wu Xudong

    2012-12-01

    Full Text Available Abstract Background microRNAs (miRNAs represent a class of small (typically 22 nucleotides in length non-coding RNAs that can degrade their target mRNAs or block their translation. Recent research showed that copy number alterations of miRNAs and their target genes are highly prevalent in cancers; however, the evolutionary and biological functions of naturally existing copy number variable miRNAs (CNV-miRNAs among individuals have not been studied extensively throughout the genome. Results In this study, we comprehensively analyzed the properties of genes regulated by CNV-miRNAs, and found that CNV-miRNAs tend to target a higher average number of genes and prefer to synergistically regulate the same genes; further, the targets of CNV-miRNAs tend to have higher variability of expression within and between populations. Finally, we found the targets of CNV-miRNAs are more likely to be differentially expressed among tissues and developmental stages, and participate in a wide range of cellular responses. Conclusions Our analyses of CNV-miRNAs provide new insights into the impact of copy number variations on miRNA-mediated post-transcriptional networks. The deeper interpretation of patterns of gene expression variation and the functional characterization of CNV-miRNAs will help to broaden the current understanding of the molecular basis of human phenotypic diversity.

  9. PKA- and PKC-dependent regulation of angiopoietin 2 mRNA in human granulosa lutein cells.

    Science.gov (United States)

    Witt, P S; Pietrowski, D; Keck, C

    2004-02-01

    New blood vessels develop from preexisting vessels in response to growth factors or hypoxic conditions. Recent studies have shown that angiopoietin 2 (ANGPT-2) plays an important role in the modulation of angiogenesis and vasculogenesis in humans and mice. The signaling pathways that lead to the regulation of ANGPT-2 are largely unclear. Here, we report that protein kinase C and protein kinase A activators (ADMB, 8-Cl-cAMP) increased the mRNA levels of ANGPT-2 in human Granulosa cells, whereas PKC and PKA Inhibitors (Rp-cAMP, GO 6983) decreased markedly the level of ANGPT-2 mRNA. Due to varying specificity of the modulators for certain protein kinases subunits, we conclude that the conventional PKCs, but not PKC alpha and beta1, the atypical PKCs and the PKA I, are involved in the regulation of ANGPT-2. These findings may help to explain the role of both PKA and PKC dependent signaling cascades in the regulation of ANGPT-2 mRNA.

  10. Humans, elephants, diamonds and gold: patterns of intentional design in Girolamo Cardano's natural philosophy.

    Science.gov (United States)

    Giglioni, Guido

    2014-01-01

    Distancing himself from both Aristotelian and Epicurean models of natural change, and resisting delusions of anthropocentric grandeur, Cardano advanced a theory of teleology centred on the notion of non-human selfhood. In keeping with Plato, he argued that nature was ruled by the mind, meaning by "mind" a universal paragon of intelligibility instantiated through patterns of purposive action ("noetic" teleology). This allowed Cardano to defend a theory of natural finalism in which life was regarded as a primordial attribute of being, already in evidence in the most elementary forms of nature, whose main categories were ability to feign, self-interest, self-preservation and indefinite persistence.

  11. Natural background radioactivity of the earth's surface -- essential information for environmental impact studies

    International Nuclear Information System (INIS)

    Tauchid, M.; Grasty, R.L.

    2002-01-01

    An environmental impact study is basically a study of change. This change is compared to the preexisting conditions that are usually perceived to be the original one or the 'pristine' stage. Unfortunately reliable information on the 'so called' pristine stage is far from adequate. One of the essential parts of this information is a good knowledge of the earth's chemical make up, or its geochemistry. Presently available data on the geochemistry of the earth's surface, including those related to radioactive elements, are incomplete and inconsistent. The main reason why a number of regulations are judged to be too strict and disproportional to the risks that might be caused by some human activities, is the lack of reliable information on the natural global geochemical background on which environmental regulations should be based. The main objective of this paper is to present a view on the need for complete baseline information on the earth's surface environment and in particular its geochemical character. It is only through the availability of complete information, including reliable baseline information on the natural radioactivity, that an appropriate study on the potential effect of the various naturally occurring elements on human health be carried out. Presented here are a number of examples where the natural radioactivity of an entire country has been mapped, or is in progress. Also described are the ways these undertakings were accomplished. There is a general misconception that elevated radioactivity can be found only around uranium mines, nuclear power reactors and similar nuclear installations. As can be seen from some of these maps, the natural background radioactivity of the earth's surface closely reflects the underlying geological formations and their alteration products. In reality, properly regulated and managed facilities, the levels of radioactivity associated with many of these facilities are generally quite low relative to those associated with

  12. Natural Radium-226 accumulation in the human thyroid gland

    International Nuclear Information System (INIS)

    Simon, Steven L.; Ibrahim, Shawki A.; Barden, Adam O.; VanMiddlesworth, Lester

    2008-01-01

    Full text: Small amounts of Ra-226 and other radium isotopes routinely enter the human body through normal dietary intake and, in some cases, through occupational exposure. Currently accepted biokinetic models for radium in the human body assume a uniform distribution among all soft tissues and a short retention time in those tissues. These assumptions persist despite publications in the mid-1980s indicating that radium concentrations in tissue are related to calcium levels in each organ, implying that the thyroid gland could accumulate greater concentrations of radium isotopes than any other tissue. Moreover, the natural intake or production of sulfate or barium compounds in the body could serve to precipitate radium in the thyroid gland, thereby immobilizing it, with the result that the radionuclide stays resident for many years. Evidence of both accumulation and immobilization of Ra-226 in thyroids of grazing animals has been documented since the 1960s by one of us (LVM). Little is known, however, about the concentration and retention of radium in the human thyroid. Reported here, for the first time, are Ra-226 measurement data from about 100 human thyroids collected from over 95 persons with no known occupational exposure to radium with lifetime residences in the US and other countries, one person who routinely ingested a homeopathic preparation containing Ra-226, and three uranium miners. Sensitive measurements were made using the radon emanation technique. Regardless of the origin of the thyroid sample, Ra-226 activity was almost always detected above the detection limit of 0.65 mBq when at least 10 g of thyroid tissue were available. Our analyses to-date suggests a background concentration in human thyroids of about 0.1 ±0.01 Bq/kg, considerably greater than the commonly reported literature value of 0.003 Bq/kg in soft tissues. In addition, our measurements indicate concentrations of Ra-226 in the three uranium miners (whose exact job description was

  13. hCG-dependent regulation of angiogenic factors in human granulosa lutein cells.

    Science.gov (United States)

    Phan, B; Rakenius, A; Pietrowski, D; Bettendorf, H; Keck, C; Herr, D

    2006-07-01

    As prerequisite for development and maintenance of many diseases angiogenesis is of particular interest in medicine. Pathologic angiogenesis takes place in chronic arthritis, collagen diseases, arteriosclerosis, retinopathy associated with diabetes, and particularly in cancers. However, angiogenesis as a physiological process regularly occurs in the ovary. After ovulation the corpus luteum is formed by rapid vascularization of initially avascular granulosa lutein cell tissue. This process is regulated by gonadotropic hormones. In order to gain further insights in the regulatory mechanisms of angiogenesis in the ovary, we investigated these mechanisms in cell culture of human granulosa lutein cells. In particular, we determined the expression and production of several angiogenic factors including tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), Leptin, connective tissue growth factor (CTGF), meningioma-associated complimentary DNA (Mac25), basic fibroblast growth factor (bFGF), and Midkine. In addition, we showed that human chorionic gonadotropin (hCG) has distinct effects on their expression and production. hCG enhances the expression and production of TIMP-1, whereas it downregulates the expression of CTGF and Mac25. Furthermore it decreases the expression of Leptin. Our results provide evidence that hCG determines growth and development of the corpus luteum by mediating angiogenic pathways in human granulosa lutein cells. Hence we describe a further approach to understand the regulation of angiogenesis in the ovary.

  14. Natural selection and the distribution of identity-by-descent in the human genome

    DEFF Research Database (Denmark)

    Albrechtsen, Anders; Moltke, Ida; Nielsen, Rasmus

    2010-01-01

    There has recently been considerable interest in detecting natural selection in the human genome. Selection will usually tend to increase identity-by-descent (IBD) among individuals in a population, and many methods for detecting recent and ongoing positive selection indirectly take advantage...... of this. In this article we show that excess IBD sharing is a general property of natural selection and we show that this fact makes it possible to detect several types of selection including a type that is otherwise difficult to detect: selection acting on standing genetic variation. Motivated by this......, we use a recently developed method for identifying IBD sharing among individuals from genome-wide data to scan populations from the new HapMap phase 3 project for regions with excess IBD sharing in order to identify regions in the human genome that have been under strong, very recent selection...

  15. RFX6 Regulates Insulin Secretion by Modulating Ca2+ Homeostasis in Human β Cells

    Directory of Open Access Journals (Sweden)

    Vikash Chandra

    2014-12-01

    Full Text Available Development and function of pancreatic β cells involve the regulated activity of specific transcription factors. RFX6 is a transcription factor essential for mouse β cell differentiation that is mutated in monogenic forms of neonatal diabetes. However, the expression and functional roles of RFX6 in human β cells, especially in pathophysiological conditions, are poorly explored. We demonstrate the presence of RFX6 in adult human pancreatic endocrine cells. Using the recently developed human β cell line EndoC-βH2, we show that RFX6 regulates insulin gene transcription, insulin content, and secretion. Knockdown of RFX6 causes downregulation of Ca2+-channel genes resulting in the reduction in L-type Ca2+-channel activity that leads to suppression of depolarization-evoked insulin exocytosis. We also describe a previously unreported homozygous missense RFX6 mutation (p.V506G that is associated with neonatal diabetes, which lacks the capacity to activate the insulin promoter and to increase Ca2+-channel expression. Our data therefore provide insights for understanding certain forms of neonatal diabetes.

  16. Substrate Specificity, Membrane Topology, and Activity Regulation of Human Alkaline Ceramidase 2 (ACER2)*

    OpenAIRE

    Sun, Wei; Jin, Junfei; Xu, Ruijuan; Hu, Wei; Szulc, Zdzislaw M.; Bielawski, Jacek; Obeid, Lina M.; Mao, Cungui

    2010-01-01

    Human alkaline ceramidase 2 (ACER2) plays an important role in cellular responses by regulating the hydrolysis of ceramides in cells. Here we report its biochemical characterization, membrane topology, and activity regulation. Recombinant ACER2 was expressed in yeast mutant cells (Δypc1Δydc1) that lack endogenous ceramidase activity, and microsomes from ACER2-expressiong yeast cells were used to biochemically characterize ACER2. ACER2 catalyzed the hydrolysis of various ceramides and followed...

  17. Getting past nature as a guide to the human sex ratio.

    Science.gov (United States)

    Murphy, Timothy F

    2013-05-01

    Sex selection of children by pre-conception and post-conception techniques remains morally controversial and even illegal in some jurisdictions. Among other things, some critics fear that sex selection will distort the sex ratio, making opposite-sex relationships more difficult to secure, while other critics worry that sex selection will tilt some nations toward military aggression. The human sex ratio varies depending on how one estimates it; there is certainly no one-to-one correspondence between males and females either at birth or across the human lifespan. Complications about who qualifies as 'male' and 'female' complicate judgments about the ratio even further. Even a judiciously estimated sex ratio does not have, however, the kind of normative status that requires society to refrain from antenatal sex selection. Some societies exhibit lopsided sex ratios as a consequence of social policies and practices, and pragmatic estimates of social needs are a better guide to what the sex ratio should be, as against looking to 'nature'. The natural sex ratio cannot be a sound moral basis for prohibiting parents from selecting the sex of their children, since it ultimately lacks any normative meaning for social choices. © 2011 Blackwell Publishing Ltd.

  18. A human intervention study with foods containing natural Ah-receptor agonists does not significantly show AhR-mediated effects as measured in blood cells and urine.

    Science.gov (United States)

    de Waard, Pim W J; Peijnenburg, Ad A C M; Baykus, Hakan; Aarts, Jac M M J G; Hoogenboom, Ron L A P; van Schooten, Frederik J; de Kok, Theo M C M

    2008-10-22

    Binding and activation of the aryl hydrocarbon receptor (AhR) is thought to be an essential step in the toxicity of the environmental pollutants dioxins and dioxin-like PCBs. However, also a number of natural compounds, referred to as NAhRAs (natural Ah-receptor agonists), which are present in, for example, fruits and vegetables, can bind and activate this receptor. To study their potential effects in humans, we first investigated the effect of the prototypical AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression in ex vivo exposed freshly isolated human lymphocytes, and compared the resulting gene expression profile with those caused by the well-known NAhRA indolo[3,2-b]carbazole (ICZ), originating from cruciferous vegetables, and by a hexane extract of NAhRA-containing grapefruit juice (GJE). Only ICZ induced a gene expression profile similar to TCDD in the lymphocytes, and both significantly up-regulated CYP1B1 and TIPARP (TCDD-inducible poly (ADP-ribose) polymerase) mRNA. Next, we performed a human intervention study with NAhRA-containing cruciferous vegetables and grapefruit juice. The expression of the prototypical AhR-responsive genes CYP1A1, CYP1B1 and NQO1 in whole blood cells and in freshly isolated lymphocytes was not significantly affected. Also enzyme activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO), as judged by caffeine metabolites in urine, were unaffected, except for a small down-regulation of NAT2 activity by grapefruit juice. Examination of blood plasma with DR CALUX showed a 12% increased AhR agonist activity 3 and 24 h after consumption of cruciferous vegetables, but did not show a significant effect of grapefruit juice consumption. We conclude that intake of NAhRAs from food may result in minor AhR-related effects measurable in human blood and urine.

  19. Transcriptional factor PU.1 regulates decidual C1q expression in early pregnancy in human

    Directory of Open Access Journals (Sweden)

    Priyaa Madhukaran Raj

    2015-02-01

    Full Text Available C1q is the first recognition subcomponent of the complement classical pathway, which in addition to being synthesized in the liver, is also expressed by macrophages and dendritic cells. Trophoblast invasion during early placentation results in accumulation of debris that triggers the complement system. Hence, both early and late components of the classical pathway are widely distributed in the placenta and decidua. In addition, C1q has recently been shown to significantly contribute to feto-maternal tolerance, trophoblast migration, and spiral artery remodeling, although the exact mechanism remains unknown. Pregnancy in mice, genetically deficient in C1q, mirrors symptoms similar to that of human preeclampsia. Thus, regulated complement activation has been proposed as an essential requirement for normal successful pregnancy. Little is known about the molecular pathways that regulate C1q expression in pregnancy. PU.1, an Ets-family transcription factor, is required for the development of hematopoietic myeloid lineage immune cells, and its expression is tissue- specific. Recently, PU.1 has been shown to regulate C1q gene expression in dendritic cells and macrophages. Here, we have examined if PU.1 transcription factor regulates decidual C1q expression. We used immune-histochemical analysis, PCR and immunostaining to localize and study the gene expression of PU.1 transcription factor in early human decidua. PU.1 was highly expressed at gene and protein level in early human decidual cells including trophoblast and stromal cells. Surprisingly, nuclear as well as cytoplasmic PU.1 expression was observed. Decidual cells with predominantly nuclear PU.1 expression had higher C1q expression. It is likely that nuclear and cytoplasmic PU.1 localization has a role to play in early pregnancy via regulating C1q expression in the decidua during implantation.

  20. Human-like PB2 627K influenza virus polymerase activity is regulated by importin-α1 and -α7.

    Directory of Open Access Journals (Sweden)

    Ben Hudjetz

    2012-01-01

    Full Text Available Influenza A viruses may cross species barriers and transmit to humans with the potential to cause pandemics. Interplay of human- (PB2 627K and avian-like (PB2 627E influenza polymerase complexes with unknown host factors have been postulated to play a key role in interspecies transmission. Here, we have identified human importin-α isoforms (α1 and α7 as positive regulators of human- but not avian-like polymerase activity. Human-like polymerase activity correlated with efficient recruitment of α1 and α7 to viral ribonucleoprotein complexes (vRNPs without affecting subcellular localization. We also observed that human-like influenza virus growth was impaired in α1 and α7 downregulated human lung cells. Mice lacking α7 were less susceptible to human- but not avian-like influenza virus infection. Thus, α1 and α7 are positive regulators of human-like polymerase activity and pathogenicity beyond their role in nuclear transport.

  1. Human action in a Genomic Era: debates on human nature Ação humana na Era do Genoma: debates sobre a natureza humana

    Directory of Open Access Journals (Sweden)

    Tatiana Gomes Rotondaro

    2009-03-01

    Full Text Available The supposed properties of 'genes' have led natural scientists to claim authority to explain the reasons of human action, behavior, and even human nature, which has traditionally been the object of study of the humanities. The aim of this paper is to discuss the possibilities of sociological theory dealing with the biological reductionism that establishes the strict articulation between 'human nature' and 'human action', presented in several speeches and papers by scientists and journalists and supported by features of 'genes'. I intend to argue that sociological theories may broaden their scope of analysis by encompassing biological dimensions, which does not necessarily mean adopting a biological reductionist approach.As supostas propriedades dos 'genes' levam os cientistas naturais a reivindicar autoridade para explicar as razões de atos, comportamentos e até a natureza humana, tradicional objeto de estudo das ciências humanas. O objetivo deste artigo é discutir as possibilidades de a teoria sociológica lidar com o reducionismo biológico, que estabelece uma articulação exata entre 'natureza humana' e 'ação humana'. Tal reducionismo está presente em discursos e artigos de cientistas e jornalistas, e é embasado por características dos 'genes'. Argumento que as teorias sociológicas podem ampliar suas possibilidades de análise se incorporarem dimensões biológicas, o que não implica necessariamente adotar uma abordagem reducionista.

  2. Effects of electromagnetic fields on human beings. Technical aspects and research results. - Regulations

    International Nuclear Information System (INIS)

    Kieback, D.

    1996-01-01

    The present brochure of the Professional Association for Fine Mechanics and Electrical Engineering gives a selective account on the effects of electromagnetic fields on human beings. The second part deals with regulations for safety and health protection at working places exposed to electromagnetic fields. (VHE) [de

  3. New regulations, combustion, environment: responses for natural gas; Nouvelles reglementations, combustion, environnement: les reponses pour le gaz naturel

    Energy Technology Data Exchange (ETDEWEB)

    Le Peltier-Marc, A. [Gaz de France (GDF), 75 - Paris (France). Direction Commerciale

    1997-12-31

    The impacts of the new French regulations concerning low- to medium-power combustion equipment with regards to their energy sources, energy efficiency and pollution control, on natural gas fired boilers, are discussed: lower pollutant emission limits are set for SO{sub 2}, NO{sub x} and ashes. The decree gives new regulations concerning plant location, combustion control systems, plant monitoring and maintenance, and air pollution control measures such as chimney stack height and emission limits. The French national gas utility promotes environmental high performance boilers

  4. Development of waste management regulations

    International Nuclear Information System (INIS)

    Elnour, E.G.

    2012-04-01

    Radioactive wastes are generated during nuclear fuel cycle operation, production and application of radioisotope in medicine, industry, research, and agriculture, and as a by product of natural resource exploitation, which includes mining and processing of ores. To ensure the protection of human health and the environment from the hazard of these wastes, a planned integrated radioactive waste management practice should be applied. The purpose of this study is to develop regulations for radioactive waste management for low and intermediate radioactive level waste (LILW), and other purpose of regulations is to establish requirements with which all organizations must comply in Sudan from LILW in particular disused/spent sources, not including radioactive waste for milling and mining practices. The national regulations regarding the radioactive waste management, should prescribe the allocation of responsibilities and roles of the Country, the regulatory body, user/owner, waste management organization, including regulations on transport packaging of waste and applied a quality assurance programme, to ensure that radioactive waste management is done safely and securely. (author)

  5. Safety Evaluation Test on Human for Radiation Pre vulcanised Natural Rubber Latex (RVNRL)

    International Nuclear Information System (INIS)

    Pairu Ibrahim; Wan Manshol Wan Zain; Chai, Chee Keong; Sofian Ibrahim; Saadiah Sulaiman; Sharifah Ismail

    2010-01-01

    This paper discussed about clinical test conducted to determine safety evaluations on human for latex examination gloves and latex films made from Radiation Vulcanized Natural Rubber Latex (RVNRL). Two types of test were being adopted which are i) Modified Draize-95 test and ii) Patch Test on Sensitized Individuals. Modified Draize-95 test was conducted on 200 non-sensitized human subjects and Patch Test on Sensitized Individuals was conducted on 25 individuals who are allergic to the defined major chemical sensitizer presents in natural rubber product. It was found that Modified Draize-95 test has prove that there is no clinical evidence on the presence of residual chemical additives at the level that may induce Type IV allergy in the un sensitized general user population in the RVNRL gloves. Meanwhile Patch Test on Sensitized Individuals has proved that the patch test conducted using the test article on 25 individuals who are allergic to the defined major chemical sensitizers present in natural rubber products, thiuram, carbamates or thiazoles produced a negative response, meeting the pre requirement for the claim of reduced reaction-inducing potential. (author)

  6. The Nature of Human Disposition: al-Ghazālī's Contribution to an Islamic Concept of Personality

    Directory of Open Access Journals (Sweden)

    Abbas Husein Ali

    1995-06-01

    Full Text Available The paper provides a critique of contemporary psychological models of human nature and highlights the contribution of al-Ghazālī towards a better conceptualization of human disposition. A brief outline of the philosophical foundations of the three major psychological approaches–Freudian psychoanalysis, Skinnerian behaviorism, and Rogerian and Maslowvian Humanism– are provided. Consequently, the metaphors they adopted for human nature are discussed. The paper also highlights the shortcomings of these models by looking at their practical implications, particularly for psychology of personality. The last part of the paper dwells on al-Ghazālī’s contribution to an Islamic abstraction of human disposition and personality.

  7. Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, Katharine J. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Holloway, Adele [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Cook, Anthony L. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Chin, Suyin P. [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Snow, Elizabeth T., E-mail: elizabeth.snow@utas.edu.au [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia)

    2014-11-15

    Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

  8. Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

    International Nuclear Information System (INIS)

    Herbert, Katharine J.; Holloway, Adele; Cook, Anthony L.; Chin, Suyin P.; Snow, Elizabeth T.

    2014-01-01

    Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

  9. Characterization of DNA binding, transcriptional activation, and regulated nuclear association of recombinant human NFATp

    Directory of Open Access Journals (Sweden)

    Seto Anita G

    2000-11-01

    Full Text Available Abstract Background NFATp is one member of a family of transcriptional activators whose nuclear accumulation and hence transcriptional activity is regulated in mammalian cells. Human NFATp exists as a phosphoprotein in the cytoplasm of naive T cells. Upon antigen stimulation, NFATp is dephosphorylated, accumulates in nuclei, and functions to regulate transcription of genes including those encoding cytokines. While the properties of the DNA binding domain of NFATp have been investigated in detail, biochemical studies of the transcriptional activation and regulated association with nuclei have remained unexplored because of a lack of full length, purified recombinant NFATp. Results We developed methods for expressing and purifying full length recombinant human NFATp that has all of the properties known to be associated with native NFATp. The recombinant NFATp binds DNA on its own and cooperatively with AP-1 proteins, activates transcription in vitro, is phosphorylated, can be dephosphorylated by calcineurin, and exhibits regulated association with nuclei in vitro. Importantly, activation by recombinant NFATp in a reconstituted transcription system required regions of the protein outside of the central DNA binding domain. Conclusions We conclude that NFATp is a bona fide transcriptional activator. Moreover, the reagents and methods that we developed will facilitate future studies on the mechanisms of transcriptional activation and nuclear accumulation by NFATp, a member of an important family of transcriptional regulatory proteins.

  10. Nature and autonomy: an organizational view of social and neurobiological aspects of self-regulation in behavior and development.

    Science.gov (United States)

    Ryan, R M; Kuhl, J; Deci, E L

    1997-01-01

    The concepts of self-regulation and autonomy are examined within an organizational framework. We begin by retracing the historical origins of the organizational viewpoint in early debates within the field of biology between vitalists and reductionists, from which the construct of self-regulation emerged. We then consider human autonomy as an evolved behavioral, developmental, and experiential phenomenon that operates at both neurobiological and psychological levels and requires very specific supports within higher order social organizations. We contrast autonomy or true self-regulation with controlling regulation (a nonautonomous form of intentional behavior) in phenomenological and functional terms, and we relate the forms of regulation to the developmental processes of intrinsic motivation and internalization. Subsequently, we describe how self-regulation versus control may be characterized by distinct neurobiological underpinnings, and we speculate about some of the adaptive advantages that may underlie the evolution of autonomy. Throughout, we argue that disturbances of autonomy, which have both biological and psychological etiologies, are central to many forms of psychopathology and social alienation.

  11. Human health improvement in Sub-Saharan Africa through integrated management of arthropod transmitted diseases and natural resources

    Directory of Open Access Journals (Sweden)

    Baumgärtner Johann

    2001-01-01

    Full Text Available A concept of an ecosystem approach to human health improvement in Sub-Saharan Africa is presented here. Three factors mainly affect the physical condition of the human body: the abiotic environment, vector-transmitted diseases, and natural resources. Our concept relies on ecological principles embedded in a social context and identifies three sets of subsystems for study and management: human disease subsystems, natural resource subsystems, and decision-support subsystems. To control human diseases and to secure food from resource subsystems including livestock or crops, integrated preventive approaches are preferred over exclusively curative and sectorial approaches. Environmental sustainability - the basis for managing matter and water flows - contributes to a healthy human environment and constitutes the basis for social sustainability. For planning and implementation of the human health improvement scheme, participatory decision-support subsystems adapted to the local conditions need to be designed through institutional arrangements. The applicability of this scheme is demonstrated in urban and rural Ethiopia.

  12. Human health improvement in Sub-Saharan Africa through integrated management of arthropod transmitted diseases and natural resources

    Directory of Open Access Journals (Sweden)

    Johann Baumgärtner

    Full Text Available A concept of an ecosystem approach to human health improvement in Sub-Saharan Africa is presented here. Three factors mainly affect the physical condition of the human body: the abiotic environment, vector-transmitted diseases, and natural resources. Our concept relies on ecological principles embedded in a social context and identifies three sets of subsystems for study and management: human disease subsystems, natural resource subsystems, and decision-support subsystems. To control human diseases and to secure food from resource subsystems including livestock or crops, integrated preventive approaches are preferred over exclusively curative and sectorial approaches. Environmental sustainability - the basis for managing matter and water flows - contributes to a healthy human environment and constitutes the basis for social sustainability. For planning and implementation of the human health improvement scheme, participatory decision-support subsystems adapted to the local conditions need to be designed through institutional arrangements. The applicability of this scheme is demonstrated in urban and rural Ethiopia.

  13. Human health improvement in Sub-Saharan Africa through integrated management of arthropod transmitted diseases and natural resources.

    Science.gov (United States)

    Baumgärtner, J; Bieri, M; Buffoni, G; Gilioli, G; Gopalan, H; Greiling, J; Tikubet, G; Van Schayk, I

    2001-01-01

    A concept of an ecosystem approach to human health improvement in Sub-Saharan Africa is presented here. Three factors mainly affect the physical condition of the human body: the abiotic environment, vector-transmitted diseases, and natural resources. Our concept relies on ecological principles embedded in a social context and identifies three sets of subsystems for study and management: human disease subsystems, natural resource subsystems, and decision-support subsystems. To control human diseases and to secure food from resource subsystems including livestock or crops, integrated preventive approaches are preferred over exclusively curative and sectorial approaches. Environmental sustainability - the basis for managing matter and water flows - contributes to a healthy human environment and constitutes the basis for social sustainability. For planning and implementation of the human health improvement scheme, participatory decision-support subsystems adapted to the local conditions need to be designed through institutional arrangements. The applicability of this scheme is demonstrated in urban and rural Ethiopia.

  14. Human Computer Collaboration at the Edge: Enhancing Collective Situation Understanding with Controlled Natural Language

    Science.gov (United States)

    2016-09-06

    conversational agent with information exchange disabled until the end of the experiment run. The meaning of the indicator in the top- right of the agent... Human Computer Collaboration at the Edge: Enhancing Collective Situation Understanding with Controlled Natural Language Alun Preece∗, William...email: PreeceAD@cardiff.ac.uk †Emerging Technology Services, IBM United Kingdom Ltd, Hursley Park, Winchester, UK ‡US Army Research Laboratory, Human

  15. Neuroendocrine regulation of appetitive ingestive behavior.

    Science.gov (United States)

    Keen-Rhinehart, Erin; Ondek, Katelynn; Schneider, Jill E

    2013-11-15

    Food availability in nature is often irregular, and famine is commonplace. Increased motivation to engage in ingestive behaviors increases the chance of survival, providing additional potential opportunities for reproduction. Because of the advantages conferred by entraining ingestive behavior to environmental conditions, neuroendocrine mechanisms regulating the motivation to acquire and ingest food have evolved to be responsive to exogenous (i.e., food stored for future consumption) and endogenous (i.e., body fat stores) fuel availability. Motivated behaviors like eating occur in two phases. The appetitive phase brings animals into contact with food (e.g., foraging, food hoarding), and the more reflexive consummatory phase results in ingestion (e.g., chewing, swallowing). Quantifiable appetitive behaviors are part of the natural ingestive behavioral repertoire of species such as hamsters and humans. This review summarizes current knowledge about neuroendocrine regulators of ingestive behavior, with an emphasis appetitive behavior. We will discuss hormonal regulators of appetitive ingestive behaviors, including the orexigenic hormone ghrelin, which potently stimulates foraging and food hoarding in Siberian hamsters. This section includes a discussion of the hormone leptin, its relation to endogenous fat stores, and its role in food deprivation-induced increases in appetitive ingestive behaviors. Next, we discuss how hormonal regulators interact with neurotransmitters involved in the regulation of ingestive behaviors, such as neuropeptide Y (NPY), agouti-related protein (AgRP) and α-melanocyte stimulating hormone (α-MSH), to regulate ingestive behavior. Finally, we discuss the potential impact that perinatal nutrient availability can have on the neuroendocrine regulation of ingestive behavior. Understanding the hormonal mechanisms that connect metabolic fuel availability to central appetite regulatory circuits should provide a better understanding of the

  16. T3 Regulates a Human Macrophage-Derived TSH-β Splice Variant: Implications for Human Bone Biology.

    Science.gov (United States)

    Baliram, R; Latif, R; Morshed, S A; Zaidi, M; Davies, T F

    2016-09-01

    TSH and thyroid hormones (T3 and T4) are intimately involved in bone biology. We have previously reported the presence of a murine TSH-β splice variant (TSH-βv) expressed specifically in bone marrow-derived macrophages and that exerted an osteoprotective effect by inducing osteoblastogenesis. To extend this observation and its relevance to human bone biology, we set out to identify and characterize a TSH-β variant in human macrophages. Real-time PCR analyses using human TSH-β-specific primers identified a 364-bp product in macrophages, bone marrow, and peripheral blood mononuclear cells that was sequence verified and was homologous to a human TSH-βv previously reported. We then examined TSH-βv regulation using the THP-1 human monocyte cell line matured into macrophages. After 4 days, 46.1% of the THP-1 cells expressed the macrophage markers CD-14 and macrophage colony-stimulating factor and exhibited typical morphological characteristics of macrophages. Real-time PCR analyses of these cells treated in a dose-dependent manner with T3 showed a 14-fold induction of human TSH-βv mRNA and variant protein. Furthermore, these human TSH-βv-positive cells, induced by T3 exposure, had categorized into both M1 and M2 macrophage phenotypes as evidenced by the expression of macrophage colony-stimulating factor for M1 and CCL-22 for M2. These data indicate that in hyperthyroidism, bone marrow resident macrophages have the potential to exert enhanced osteoprotective effects by oversecreting human TSH-βv, which may exert its local osteoprotective role via osteoblast and osteoclast TSH receptors.

  17. Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

    Science.gov (United States)

    Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

    2013-01-01

    Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Human, Nature, Dynamism: The Effects of Content and Movement Perception on Brain Activations during the Aesthetic Judgment of Representational Paintings.

    Science.gov (United States)

    Di Dio, Cinzia; Ardizzi, Martina; Massaro, Davide; Di Cesare, Giuseppe; Gilli, Gabriella; Marchetti, Antonella; Gallese, Vittorio

    2015-01-01

    Movement perception and its role in aesthetic experience have been often studied, within empirical aesthetics, in relation to the human body. No such specificity has been defined in neuroimaging studies with respect to contents lacking a human form. The aim of this work was to explore, through functional magnetic imaging (f MRI), how perceived movement is processed during the aesthetic judgment of paintings using two types of content: human subjects and scenes of nature. Participants, untutored in the arts, were shown the stimuli and asked to make aesthetic judgments. Additionally, they were instructed to observe the paintings and to rate their perceived movement in separate blocks. Observation highlighted spontaneous processes associated with aesthetic experience, whereas movement judgment outlined activations specifically related to movement processing. The ratings recorded during aesthetic judgment revealed that nature scenes received higher scored than human content paintings. The imaging data showed similar activation, relative to baseline, for all stimuli in the three tasks, including activation of occipito-temporal areas, posterior parietal, and premotor cortices. Contrast analyses within aesthetic judgment task showed that human content activated, relative to nature, precuneus, fusiform gyrus, and posterior temporal areas, whose activation was prominent for dynamic human paintings. In contrast, nature scenes activated, relative to human stimuli, occipital and posterior parietal cortex/precuneus, involved in visuospatial exploration and pragmatic coding of movement, as well as central insula. Static nature paintings further activated, relative to dynamic nature stimuli, central and posterior insula. Besides insular activation, which was specific for aesthetic judgment, we found a large overlap in the activation pattern characterizing each stimulus dimension (content and dynamism) across observation, aesthetic judgment, and movement judgment tasks. These

  19. Sustaining Economic Exploitation of Complex Ecosystems in Computational Models of Coupled Human-Natural Networks

    OpenAIRE

    Martinez, Neo D.; Tonin, Perrine; Bauer, Barbara; Rael, Rosalyn C.; Singh, Rahul; Yoon, Sangyuk; Yoon, Ilmi; Dunne, Jennifer A.

    2012-01-01

    Understanding ecological complexity has stymied scientists for decades. Recent elucidation of the famously coined "devious strategies for stability in enduring natural systems" has opened up a new field of computational analyses of complex ecological networks where the nonlinear dynamics of many interacting species can be more realistically mod-eled and understood. Here, we describe the first extension of this field to include coupled human-natural systems. This extension elucidates new strat...

  20. Induction of the metabolic regulator Txnip in fasting-induced and natural torpor.

    Science.gov (United States)

    Hand, Laura E; Saer, Ben R C; Hui, Simon T; Jinnah, Hyder A; Steinlechner, Stephan; Loudon, Andrew S I; Bechtold, David A

    2013-06-01

    Torpor is a physiological state characterized by controlled lowering of metabolic rate and core body temperature, allowing substantial energy savings during periods of reduced food availability or harsh environmental conditions. The hypothalamus coordinates energy homeostasis and thermoregulation and plays a key role in directing torpor. We recently showed that mice lacking the orphan G protein-coupled receptor Gpr50 readily enter torpor in response to fasting and have now used these mice to conduct a microarray analysis of hypothalamic gene expression changes related to the torpor state. This revealed a strong induction of thioredoxin-interacting protein (Txnip) in the hypothalamus of torpid mice, which was confirmed by quantitative RT-PCR and Western blot analyses. In situ hybridization identified the ependyma lining the third ventricle as the principal site of torpor-related expression of Txnip. To characterize further the relationship between Txnip and torpor, we profiled Txnip expression in mice during prolonged fasting, cold exposure, and 2-deoxyglucose-induced hypometabolism, as well as in naturally occurring torpor bouts in the Siberian hamster. Strikingly, pronounced up-regulation of Txnip expression was only observed in wild-type mice when driven into torpor and during torpor in the Siberian hamster. Increase of Txnip was not limited to the hypothalamus, with exaggerated expression in white adipose tissue, brown adipose tissue, and liver also demonstrated in torpid mice. Given the recent identification of Txnip as a molecular nutrient sensor important in the regulation of energy metabolism, our data suggest that elevated Txnip expression is critical to regulating energy expenditure and fuel use during the extreme hypometabolic state of torpor.

  1. Natural radioactivity in water supplies

    International Nuclear Information System (INIS)

    Horner, J.K.

    1985-01-01

    This book outlines the scientific aspects of the control of natural radioactivity in water supplies, as well as the labyrinthine uncertainties in water quality regulation concerning natural radiocontamination of water. The author provides an introduction to the theory of natural radioactivity; addresses risk assessment, sources of natural radiocontamination of water, radiobiology of natural radioactivity in water, and federal water law concerning natural radiocontamination. It presents an account of how one city dealt with the perplexes that mark the rapidly evolving area of water quality regulation. The contents include: radioactivity and risk; an introduction to the atomic theory; an introduction to natural radioactivity; risk assessment; uranium and radium contamination of water; radiobiology of uranium and radium in water. Determination of risk from exposure to uranium and radium in water; the legal milieu; one city's experience; and summary: the determinants of evolving regulation

  2. Identification of antisense long noncoding RNAs that function as SINEUPs in human cells.

    Science.gov (United States)

    Schein, Aleks; Zucchelli, Silvia; Kauppinen, Sakari; Gustincich, Stefano; Carninci, Piero

    2016-09-20

    Mammalian genomes encode numerous natural antisense long noncoding RNAs (lncRNAs) that regulate gene expression. Recently, an antisense lncRNA to mouse Ubiquitin carboxyl-terminal hydrolase L1 (Uchl1) was reported to increase UCHL1 protein synthesis, representing a new functional class of lncRNAs, designated as SINEUPs, for SINE element-containing translation UP-regulators. Here, we show that an antisense lncRNA to the human protein phosphatase 1 regulatory subunit 12A (PPP1R12A), named as R12A-AS1, which overlaps with the 5' UTR and first coding exon of the PPP1R12A mRNA, functions as a SINEUP, increasing PPP1R12A protein translation in human cells. The SINEUP activity depends on the aforementioned sense-antisense interaction and a free right Alu monomer repeat element at the 3' end of R12A-AS1. In addition, we identify another human antisense lncRNA with SINEUP activity. Our results demonstrate for the first time that human natural antisense lncRNAs can up-regulate protein translation, suggesting that endogenous SINEUPs may be widespread and present in many mammalian species.

  3. Analyses of natural resources in 10 CFR Part 60 as related to inadvertent human intrusion

    International Nuclear Information System (INIS)

    Miklas, M.P.; Lefevre, H.E.

    1993-01-01

    The purpose of this paper is to examine the intent of the regulatory language of the portions of 10 CFR Part 60 which deal with considerations of the natural resources of a proposed geologic repository for high-level radioactive wastes as they relate to inadvertent human intrusion. Four Potentially Adverse Conditions (PAC) the requirements of 10 CFR 60.21(c)(13) are shown to be related to natural resources. Groundwater is identified as a natural resource known to be present at Yucca Mountain, Nevada. For economic considerations of natural resources, the open-quotes foreseeable futureclose quotes is thought to be no more than 50 years. Two of the topics addressed by the PACs, subsurface mining and drilling at a proposed repository site, are pre-site-characterization activities which must be evaluated in the context of repository performance criteria set by the US EPA standard, 40 CFR Part 191. An alternative US DOE compliance demonstration to another PAC, 10 CFR 60.122(c)(17), might be to use an open-quotes explorationist perspectiveclose quotes of natural resource assessment. The Commission intends for DOE to evaluate the likelihood and consequence of inadvertent human intrusion into a geologic repository as a result of exploration or exploitation of natural resources within or near a proposed high-level radioactive waste geologic repository

  4. Science and Ecological Economics: Integrating of the Study of Humans and the Rest of Nature

    Science.gov (United States)

    Costanza, Robert

    2009-01-01

    Ecological economics is a transdisciplinary field that seeks to integrate the study of humans and the rest of nature as the basis for the creation of a sustainable and desirable future. It seeks to dissolve the barriers between the traditional disciplines and achieve a true "consilience" of all the sciences and humanities. This consilient,…

  5. Natural disaster vulnerability and human-induced pressure assessment in small islands developing states: A case study in the Union of the Comoros

    Science.gov (United States)

    Burak, S.; Meddeb, R.

    2012-04-01

    The Comoros Islands are part of the Small Island Developing States (SIDS) located in the Indian Ocean. SIDS are islands and low-lying coastal nations that face common barriers to sustainable development, including limited resources, poor economic resilience, and vulnerability to sea level rise and natural disasters. The Comoros Archipelago is made up of four islands but the present study was conducted on three islands, namely Mwali (Mohéli), Ngazidja (Grande Comore) and Dzwani (Anjouan) that are aligned in the Mozambique Channel and spread over a surface area of 1862 km2. These islands are exposed to natural disaster coupled with human-induced pressure on natural resources. The major natural disaster vulnerability has been identified by the National AdaptationProgramme of Action (NAPA, 2006) as climate change, whose likely adverse impacts on the Comoros Islands are: i) changes in rainfall patterns; ii) increases in temperature; iii) salinization of coastal aquifers as a result of salt water intrusion due to sea level rise; and iv) increased frequency of severe weather conditions (such as tropical cyclones, droughts, heavy rainfall and flooding). In addition, existing practices related to natural resources management (primarily land, forest and water management) are very poor and this failure is increasingly threatening water and food security, resulting in a decline of economic growth and standards of living within the Comoros. Human-induced pressure combined with climate change impact is the inherent vulnerabilities of these islands. The government of the Union of the Comoros is aware of the alarming nature of climate change impact and has put in place several projects aiming at implementing adaptation measures in order to help increase the resilience of the vulnerable population in the face of this threat. These projects involve strengthening institutions, policy and regulations so as to improve the management of natural resources, among other measures. The

  6. Towards modelling flood protection investment as a coupled human and natural system

    Science.gov (United States)

    O'Connell, P. E.; O'Donnell, G.

    2014-01-01

    Due to a number of recent high-profile flood events and the apparent threat from global warming, governments and their agencies are under pressure to make proactive investments to protect people living in floodplains. However, adopting a proactive approach as a universal strategy is not affordable. It has been argued that delaying expensive and essentially irreversible capital decisions could be a prudent strategy in situations with high future uncertainty. This paper firstly uses Monte Carlo simulation to explore the performance of proactive and reactive investment strategies using a rational cost-benefit approach in a natural system with varying levels of persistence/interannual variability in annual maximum floods. It is found that, as persistence increases, there is a change in investment strategy optimality from proactive to reactive. This could have implications for investment strategies under the increasingly variable climate that is expected with global warming. As part of the emerging holistic approaches to flood risk management, there is increasing emphasis on stakeholder participation in determining where and when flood protection investments are made, and so flood risk management is becoming more people-centred. As a consequence, multiple actors are involved in the decision-making process, and the social sciences are assuming an increasingly important role in flood risk management. There is a need for modelling approaches which can couple the natural and human system elements. It is proposed that coupled human and natural system (CHANS) modelling could play an important role in understanding the motivations, actions and influence of citizens and institutions and how these impact on the effective delivery of flood protection investment. A framework for using agent-based modelling of human activities leading to flood investments is outlined, and some of the challenges associated with implementation are discussed.

  7. Natural gas purchasing

    International Nuclear Information System (INIS)

    Freedenthal, C.

    1993-01-01

    In recent years, natural gas has gained new momentum because of changes in marketing and regulations. The gas industry has always received an inordinate amount of regulatory control starting at the well head where the gas is produced to the consuming burner tip. Regulations have drastically impacted the availability of gas. Changes in the marketing and regulations have made the natural gas market sensitive at the point of production, the well head. Now, with plentiful supply and ease of transportation to bring the gas from the producing fields to the consumer, natural gas markets are taking advantage of the changed conditions. At the same time, new markets are developing to take advantage of the changes. This section shows consumers, especially the energy planners for large buyers of fuel, the advantages, sources and new methods of securing natural gas supplies. Background on how natural gas is produced and marketed are given. This section lists marketing sources, regulatory agencies and information groups available to help buyers and consumers of this important fuel for US industries and residences. 7 figs., 8 tabs

  8. Natural selection on protein-coding genes in the human genome

    DEFF Research Database (Denmark)

    Bustamente, Carlos D.; Fledel-Alon, Adi; Williamson, Scott

    2005-01-01

    , showing an excess of deleterious variation within local populations 9, 10 . Here we contrast patterns of coding sequence polymorphism identified by direct sequencing of 39 humans for over 11,000 genes to divergence between humans and chimpanzees, and find strong evidence that natural selection has shaped......Comparisons of DNA polymorphism within species to divergence between species enables the discovery of molecular adaptation in evolutionarily constrained genes as well as the differentiation of weak from strong purifying selection 1, 2, 3, 4 . The extent to which weak negative and positive darwinian...... selection have driven the molecular evolution of different species varies greatly 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 , with some species, such as Drosophila melanogaster, showing strong evidence of pervasive positive selection 6, 7, 8, 9 , and others, such as the selfing weed Arabidopsis thaliana...

  9. Cyclin E-Mediated Human Proopiomelanocortin Regulation as a Therapeutic Target for Cushing Disease.

    Science.gov (United States)

    Liu, Ning-Ai; Araki, Takako; Cuevas-Ramos, Daniel; Hong, Jiang; Ben-Shlomo, Anat; Tone, Yukiko; Tone, Masahide; Melmed, Shlomo

    2015-07-01

    Cushing disease, due to pituitary corticotroph tumor ACTH hypersecretion, drives excess adrenal cortisol production with adverse morbidity and mortality. Loss of glucocorticoid negative feedback on the hypothalamic-pituitary-adrenal axis leads to autonomous transcription of the corticotroph precursor hormone proopiomelanocortin (POMC), consequent ACTH overproduction, and adrenal hypercortisolism. We previously reported that R-roscovitine (CYC202, seliciclib), a 2,6,9-trisubstituted purine analog, suppresses cyclin-dependent-kinase 2/cyclin E and inhibits ACTH in mice and zebrafish. We hypothesized that intrapituitary cyclin E signaling regulates corticotroph tumor POMC transcription independently of cell cycle progression. The aim was to investigate whether R-roscovitine inhibits human ACTH in corticotroph tumors by targeting the cyclin-dependent kinase 2/cyclin E signaling pathway. Primary cell cultures of surgically resected human corticotroph tumors were treated with or without R-roscovitine, ACTH measured by RIA and quantitative PCR, and/or Western blot analysis performed to investigate ACTH and lineage-specific transcription factors. Cyclin E and E2F transcription factor 1 (E2F1) small interfering RNA (siRNA) transfection was performed in murine corticotroph tumor AtT20 cells to elucidate mechanisms for drug action. POMC gene promoter activity in response to R-roscovitine treatment was analyzed using luciferase reporter and chromatin immunoprecipitation assays. R-roscovitine inhibits human corticotroph tumor POMC and Tpit/Tbx19 transcription with decreased ACTH expression. Cyclin E and E2F1 exhibit reciprocal positive regulation in corticotroph tumors. R-roscovitine disrupts E2F1 binding to the POMC gene promoter and suppresses Tpit/Tbx19 and other lineage-specific POMC transcription cofactors via E2F1-dependent and -independent pathways. R-roscovitine inhibits human pituitary corticotroph tumor ACTH by targeting the cyclin E/E2F1 pathway. Pituitary cyclin E

  10. Does post-humanism still need ethics? The normativity of an open nature.

    Science.gov (United States)

    Murillo, José Ignacio

    2014-01-01

    In the current era, post-humanism usually adopts two forms. One of these is related to postmodern thought and its critique of Enlightenment ideals, while the other, which is usually referred to as transhumanism, declares itself the heir to optimistic belief in the technological progress of modernity. Nevertheless, both seem like new versions of the struggle between an individualist version of liberalism and its critics. In so far as they are ethical proposals, we may hold them to account for the vagueness of their moral objectives, which only seem to advocate - each in its own way - emancipation and the removal of barriers that may impede an increase in power. This defect is not, though, independent of their rejection of the notion of nature. By contrast, classical ethics does not focus so much on power or emancipation as on the nature of human telos and of his true growth, and it is only from this standpoint that it concerns itself with the means by which this can be achieved.

  11. Ecological Wisdom and Inspiration Underlying the Planning and Construction of Ancient Human Settlements: Case Study of Hongcun UNESCO World Heritage Site in China

    Directory of Open Access Journals (Sweden)

    Shanwen Zheng

    2018-04-01

    Full Text Available Human settlements are social-economic-natural complex ecosystems centered on human activities and the most prominent site for the contradictions between humans and the environment. Taking Hongcun, a UNESCO World Heritage site in China, as an example, this paper analyzes the methods and effect of coupling man and nature in Hongcun, summarizes the ecological wisdom of dealing with the relationship between human and nature, and uses this wisdom to shed light on the planning, construction, and management of contemporary urban and rural settlements. Firstly, the study introduces the Human-Natural Intergraded Ecological Planning (HNIEP model’s hypothesis, explaining its foundation and potential principles or approaches. Secondly, using the case study of Hongcun to explain, support, and validate the HNIEP model and its framework, the study found that the unique planning and construction of Hongcun has greatly promoted ecosystem services, such as local microclimate regulation, rainwater runoff regulation, water conservation, landscape aesthetic, and engagement with nature. Thirdly, Hongcun reflects the concept of harmonious coexistence between human and nature, the wisdom of rational use of ecosystem structures, processes and functions, and the wisdom of coupling human activities with the living environment and natural ecosystem. Finally, the paper summarizes the enlightenment brought by both the HNIEP model and Hongcun wisdom to contemporary urban-rural planning and construction management.

  12. Epiphytic lichen diversity in central European oak forests: Assessment of the effects of natural environmental factors and human influences

    International Nuclear Information System (INIS)

    Svoboda, David; Peksa, Ondrej; Vesela, Jana

    2010-01-01

    We investigated lichen diversity in temperate oak forests using standardized protocols. Forty-eight sites were sampled in the Czech Republic, Slovakia and Hungary. The effects of natural environmental predictors and human influences on lichen diversity (lichen diversity value, species richness) were analysed by means of correlation tests. We found that lichen diversity responded differently to environmental predictors between two regions with different human impact. In the industrial region, air pollution was the strongest factor. In the agricultural to highly forested regions, lichen diversity was strongly influenced by forest age and forest fragmentation. We found that several natural factors can in some cases obscure the effect of human influences. Thus, factors of naturality gradient must be considered (both statistically and interpretively) when studying human impact on lichen diversity. - We detected the different responses of lichens to ecological predictors in polluted and unpolluted areas.

  13. Review of the general regulation of radiological protection

    International Nuclear Information System (INIS)

    Cortes C, A.

    2008-12-01

    As a result of advances in radiation protection at the international level, the National Commission of Nuclear Safety and Safeguards has been given the task of revising the General Regulation of Radiation Safety to cover such developments, especially those contained in the safety basic standards No. 115 of the IAEA, published in 1977. In addition, the working group has considered issues that need to be regulated to avoid unnecessary dose received by the public due to exposure to ionizing radiation. Related to the public exposure believes the preliminary deal with situations of chronic exposure in homes, as well as human activities involving natural sources of ionizing radiation exposure to cause the public to levels that exceed the dose limits laid down in the Regulation. It is also envisaged that they will be subject to monitoring by the Commission, the concentration levels due to radon in homes, radon outdoor, radio and radon in drinking water, and external radiation levels due to naturally occurring radionuclides in building materials. Thus, the processes that may be subject to surveillance by the National Commission of Nuclear Safety and Safeguards include water treatment, some metallurgical processes, some of the mining industry and some industrial processes in which waste increase activity concentration of naturally occurring radionuclides. With the revision of the General Regulation of Radiation Safety, certain standards must be reviewed and further developed such as the concentration of radon levels in homes room, outdoor radon, radon and radio in drinking water, radiation levels out sourcing due to naturally occurring radionuclides in building materials, and standards governing (and identify) the radioactive material generation in the processes mentioned previously. (Author)

  14. A Review of State Licensing Regulations to Determine Alignment with Best Practices to Prevent Human Norovirus Infections in Child-Care Centers.

    Science.gov (United States)

    Leone, Cortney M; Jaykus, Lee-Ann; Cates, Sheryl M; Fraser, Angela M

    2016-01-01

    Close, frequent contact between children and care providers in child-care centers presents many opportunities to spread human noroviruses. We compared state licensing regulations for child-care centers with national guidelines written to prevent human noroviruses. We reviewed child-care licensing regulations for all 50 U.S. states and the District of Columbia in effect in June 2015 to determine if these regulations fully, partially, or did not address 14 prevention practices in four topic areas: (1) hand hygiene, (2) exclusion of ill people, (3) environmental sanitation, and (4) diapering. Approximately two-thirds (8.9) of the 14 practices across all state regulations were partially or fully addressed, with few (2.6) fully addressed. Practices related to exclusion of ill people and diapering were fully addressed most often, while practices related to hand hygiene and environmental sanitation were fully addressed least often. Regulations based on guidelines for best practices are one way to prevent the spread of human noroviruses in child-care facilities, if the regulations are enforced. Our findings show that, in mid-2015, many state child-care regulations did not fully address these guidelines, suggesting the need to review these regulations to be sure they are based on best practices.

  15. Human skin gene expression: Natural (trans) resveratrol versus five resveratrol analogs for dermal applications.

    Science.gov (United States)

    Lephart, Edwin D; Andrus, Merritt B

    2017-09-01

    Resveratrol (RV) is a polyphenolic compound naturally produced by plants. Polyphenolic compounds incorporated into medicinal products are beneficial but, RV is rapidly metabolized with an associated decline in biological activity. This study tested RV as the standard and compared five structurally modified RV analogs: butyrate, isobutyrate, palmitoate, acetate, and diacetate (to improve functionality) at 1% concentration(s) for 24 h in epiderm full thickness cultures by gene array/qPCR mRNA analysis. When silent mating type information regulation 2 homolog 1, extracellular elements (collagen1A1, 3A1, 4A1; elastin, tissue inhibitor of matrix metalloproteinase 1, fibrillin 1 laminin beta1 and matrix metalloproteinase 9), anti-aging and aging genes, inflammatory biomarkers (interleukin-1A [IL1A], IL1R2, IL-6 and IL-8), nerve growth factor, and the antioxidants (proliferating cell nuclear antigen, catalase, superoxide dismutase and metallothionein 1H/2H) were evaluated, ranking each from highest-to-lowest for gene expression: butyrate > isobutyrate > diacetate > acetate > palmitoate. This study showed that the butyrate and isobutyrate analogs are more biologically active compared to resveratrol and have potential use in topical applications to improve dermal and other health applications. Impact statement Resveratrol has been reported to have a wide variety of health benefits but its rapid metabolism especially after oral ingestion results in very low bioavailability. Notably, the first human skin gene expression study of resveratrol was not published until 2014. The purpose of this study was to determine if increased stability and biological activity could be obtained by modifying the chemical structure of natural (trans) resveratrol and quantifying human gene expression by qPCR of skin biomarkers that enhance dermal health. Five resveratrol analogs were synthesized that increased their lipophilic index to enhance tissue penetration and augment

  16. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Sandra C. [Translational Sciences - Translational Medicine, Novartis Institutes for Biomedical Research, Inc., 220 Massachusetts Avenue, Cambridge, MA 02139 (United States); Chau, Mary D.L.; Yang, Qing [Cardiovascular and Metabolism Disease Area, Novartis Institutes for Biomedical Research, Inc., 100 Technology Square, Cambridge, MA 02139 (United States); Gauthier, Marie-Soleil [Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02140 (United States); Clairmont, Kevin B.; Wu, Zhidan; Gromada, Jesper [Cardiovascular and Metabolism Disease Area, Novartis Institutes for Biomedical Research, Inc., 100 Technology Square, Cambridge, MA 02139 (United States); Dole, William P., E-mail: bill.dole@novartis.com [Translational Sciences - Translational Medicine, Novartis Institutes for Biomedical Research, Inc., 220 Massachusetts Avenue, Cambridge, MA 02139 (United States)

    2011-07-08

    Highlights: {yields} Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). {yields} ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. {yields} ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. {yields} Exposure of human adipocytes to fatty acids and (TNF{alpha}) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I mediated-stimulation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation. Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and

  17. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK

    International Nuclear Information System (INIS)

    Souza, Sandra C.; Chau, Mary D.L.; Yang, Qing; Gauthier, Marie-Soleil; Clairmont, Kevin B.; Wu, Zhidan; Gromada, Jesper; Dole, William P.

    2011-01-01

    Highlights: → Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). → ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. → ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. → Exposure of human adipocytes to fatty acids and (TNFα) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I mediated-stimulation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation. Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and peroxisome proliferator

  18. Corrigendum: Free Will and Punishment: A Mechanistic View of Human Nature Reduces Retribution.

    Science.gov (United States)

    2018-02-01

    Original article: Shariff, A. F., Greene, J. D., Karremans, J. C., Luguri, J. B., Clark, C. J., Schooler, J. W., . . . Vohs, K. D. (2014). Free will and punishment: A mechanistic view of human nature reduces retribution. Psychological Science, 25, 1563-1570. doi:10.1177/0956797614534693.

  19. Corrigendum: Free will and punishment: A mechanistic view of human nature reduces retribution

    NARCIS (Netherlands)

    Shariff, A.F.; Greene, J.D.; Karremans, J.C.T.M.; Luguri, J.B.; Clark, C.J.; Schooler, J.W.; Baumeister, R.F.; Vohs, K.D.

    2018-01-01

    Original article: Shariff, A. F., Greene, J. D., Karremans, J. C., Luguri, J. B., Clark, C. J., Schooler, J. W., . . . Vohs, K. D. (2014). Free will and punishment: A mechanistic view of human nature reduces retribution. Psychological Science, 25, 1563-1570. doi:10.1177/0956797614534693

  20. BMP6 down-regulates GDNF expression through SMAD1/5 and ERK1/2 signaling pathways in human granulosa-lutein cells.

    Science.gov (United States)

    Zhang, Xin-Yue; Chang, Hsun-Ming; Taylor, Elizabeth L; Leung, Peter C K; Liu, Rui-Zhi

    2018-05-09

    Bone morphogenetic protein 6 (BMP6) is a critical regulator of follicular development that is expressed in mammalian oocytes and granulosa cells. Glial cell line-derived neurotrophic factor (GDNF) is an intraovarian neurotrophic factor that plays an essential role in regulating mammalian oocyte maturation. The aim of this study was to investigate the effect of BMP6 on the regulation of GDNF expression and the potential underlying mechanisms. We used an established immortalized human granulosa cell line (SVOG cells) and primary human granulosa-lutein cells as in vitro cell models. Our results showed that BMP6 significantly down-regulated the expression of GDNF in both SVOG and primary human granulosa-lutein cells. Using dual inhibition approaches (kinase receptor inhibitor and small interfering RNA knockdown), our results showed that both ALK2 and ALK3 are involved in BMP6-induced down-regulation of GDNF. In addition, BMP6 induced the phosphorylation of SMAD1/5/8 and ERK1/2 but not AKT or p38. Among three downstream mediators, both SMAD1 and SMAD5 are involved in BMP6-induced down-regulation of GDNF. Moreover, concomitant knockdown of endogenous SMAD4 and inhibition of ERK1/2 activity completely reversed BMP6-induced down-regulation of GDNF, indicating that both SMAD and ERK1/2 signaling pathways are required for the regulatory effect of BMP6 on GDNF expression. Our findings suggest an additional role for an intrafollicular growth factor in regulating follicular function through their paracrine interactions in human granulosa cells.

  1. Neutral Theory: From Complex Population History to Natural Selection and Sociocultural Phenomena in Human Populations.

    Science.gov (United States)

    Austerlitz, Frédéric; Heyer, Evelyne

    2018-06-01

    Here, we present a synthetic view on how Kimura's Neutral theory has helped us gaining insight on the different evolutionary forces that shape human evolution. We put this perspective in the frame of recent emerging challenges: the use of whole genome data for reconstructing population histories, natural selection on complex polygenic traits, and integrating cultural processes in human evolution.

  2. A reliability analysis of a natural-gas pressure-regulating installation

    International Nuclear Information System (INIS)

    Gerbec, Marko

    2010-01-01

    A case study involving analyses of the operability, reliability and availability was made for a selected, typical, high-pressure, natural-gas, pressure-regulating installation (PRI). The study was commissioned by the national operator of the natural-gas, transmission-pipeline network for the purpose of validating the existing operability and maintenance practices and policies. The study involved a failure-risk analysis (HAZOP) of the selected typical installation, retrieval and analysis of the available corrective maintenance data for the PRI's equipment at the network level in order to obtain the failure rates followed by an elaboration of the quantitative fault trees. Thus, both operator-specific and generic literature data on equipment failure rates were used. The results obtained show that two failure scenarios need to be considered: the first is related to the PRI's failure to provide gas to the consumer(s) due to a low-pressure state and the second is related to a failure of the gas pre-heating at the high-pressure reduction stage, leading to a low temperature (a non-critical, but unfavorable, PRI state). Related to the first scenario, the most important cause of failure was found to be a transient pressure disturbance back from the consumer side. The network's average PRI failure frequency was assessed to be about once per 32 years, and the average unavailability to be about 4 minutes per year (the confidence intervals were also assessed). Based on the results obtained, some improvements to the monitoring of the PRI are proposed.

  3. A reliability analysis of a natural-gas pressure-regulating installation

    Energy Technology Data Exchange (ETDEWEB)

    Gerbec, Marko, E-mail: marko.gerbec@ijs.s [Jozef Stefan Institute, Jamova 39, 1000 Ljubljana (Slovenia)

    2010-11-15

    A case study involving analyses of the operability, reliability and availability was made for a selected, typical, high-pressure, natural-gas, pressure-regulating installation (PRI). The study was commissioned by the national operator of the natural-gas, transmission-pipeline network for the purpose of validating the existing operability and maintenance practices and policies. The study involved a failure-risk analysis (HAZOP) of the selected typical installation, retrieval and analysis of the available corrective maintenance data for the PRI's equipment at the network level in order to obtain the failure rates followed by an elaboration of the quantitative fault trees. Thus, both operator-specific and generic literature data on equipment failure rates were used. The results obtained show that two failure scenarios need to be considered: the first is related to the PRI's failure to provide gas to the consumer(s) due to a low-pressure state and the second is related to a failure of the gas pre-heating at the high-pressure reduction stage, leading to a low temperature (a non-critical, but unfavorable, PRI state). Related to the first scenario, the most important cause of failure was found to be a transient pressure disturbance back from the consumer side. The network's average PRI failure frequency was assessed to be about once per 32 years, and the average unavailability to be about 4 minutes per year (the confidence intervals were also assessed). Based on the results obtained, some improvements to the monitoring of the PRI are proposed.

  4. Regulating (for the benefit of) future persons: a different perspective on the FDA's jurisdiction to regulate human reproductive cloning.

    Science.gov (United States)

    Javitt, Gail H; Hudson, Kathy

    2003-01-01

    The Food and Drug Administration (FDA) has taken the position that human reproductive cloning falls within its regulatory jurisdiction. This position has been subject to criticism on both procedural and substantive grounds. Some have contended that the FDA has failed to follow administrative law principles in asserting its jurisdiction, while others claim the FDA is ill suited to the task of addressing the ethical and social implications of human cloning. This Article argues, that, notwithstanding these criticisms, the FDA could plausibly assert jurisdiction over human cloning as a form of human gene therapy, an area in which the FDA is already regarded as having primary regulatory authority. Such an assertion would require that the FDA's jurisdiction extend to products affecting future persons, i.e., those not yet born. This Article demonstrates, for the first time, that such jurisdiction was implicit in the enactment of the 1962 Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act and that the FDA has historically relied on such authority in promulgating regulations for drugs and devices.

  5. Piezo1 regulates mechanotransductive release of ATP from human RBCs.

    Science.gov (United States)

    Cinar, Eyup; Zhou, Sitong; DeCourcey, James; Wang, Yixuan; Waugh, Richard E; Wan, Jiandi

    2015-09-22

    Piezo proteins (Piezo1 and Piezo2) are recently identified mechanically activated cation channels in eukaryotic cells and associated with physiological responses to touch, pressure, and stretch. In particular, human RBCs express Piezo1 on their membranes, and mutations of Piezo1 have been linked to hereditary xerocytosis. To date, however, physiological functions of Piezo1 on normal RBCs remain poorly understood. Here, we show that Piezo1 regulates mechanotransductive release of ATP from human RBCs by controlling the shear-induced calcium (Ca(2+)) influx. We find that, in human RBCs treated with Piezo1 inhibitors or having mutant Piezo1 channels, the amounts of shear-induced ATP release and Ca(2+) influx decrease significantly. Remarkably, a critical extracellular Ca(2+) concentration is required to trigger significant ATP release, but membrane-associated ATP pools in RBCs also contribute to the release of ATP. Our results show how Piezo1 channels are likely to function in normal RBCs and suggest a previously unidentified mechanotransductive pathway in ATP release. Thus, we anticipate that the study will impact broadly on the research of red cells, cellular mechanosensing, and clinical studies related to red cell disorders and vascular disease.

  6. Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver.

    Directory of Open Access Journals (Sweden)

    Marta Moya

    Full Text Available Triglyceride accumulation in nonalcoholic fatty liver (NAFL results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2 however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB. Moreover, Foxa1 represses the fatty acid transporter protein FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing peroxisomal fatty acid β-oxidation and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolic pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance.

  7. Using a Coupled Human-Natural System to Assess the Vulnerability of the Karst Landform Region in China

    Directory of Open Access Journals (Sweden)

    Xiang He

    2015-09-01

    Full Text Available Guizhou Plateau is a region in China that typically shows the contradictory human-earth system. A vulnerability assessment indicator system was constructed to explore the coupled human-natural system characteristic of the karst landform based on the grey correlation analysis mathematic model. The quantitative assessment results show that Qiandongnan and Tongren Districts belong to the slight degree of the sensitivity evaluation index. Bijie district belongs to the middle degree and the other districts of Guizhou Plateau belong to the light degree. In terms of the exposure and resilience evaluation index, only Guiyang City belongs to the slight degree and other districts are in the middle degree. Thus, Guizhou Plateau could be divided into three level zones based on the comprehensive vulnerability degree of the coupled human-natural system. The strong degree vulnerability zone includes Liupanshui City, Bijie City, Anshun City, and Qiannan District. The middle degree vulnerability zone includes the districts of Qiandongnan, Qianxinan, and Tongren and the city of Zunyi. The slight degree vulnerability zone only includes Guiyang City. The research results suggest that the coupled human-natural system in Guizhou Plateau has a high vulnerability.

  8. Human Long Noncoding RNA Regulation of Stem Cell Potency and Differentiation

    Directory of Open Access Journals (Sweden)

    Seahyoung Lee

    2017-01-01

    Full Text Available Because of their capability of differentiation into lineage-specific cells, stem cells are an attractive therapeutic modality in regenerative medicine. To develop an effective stem cell-based therapeutic strategy with predictable results, deeper understanding of the underlying molecular mechanisms of stem cell differentiation and/or pluripotency maintenance is required. Thus, reviewing the key factors involved in the transcriptional and epigenetic regulation of stem cell differentiation and maintenance is important. Accumulating data indicate that long noncoding RNAs (lncRNAs mediate numerous biological processes, including stem cell differentiation and maintenance. Here, we review recent findings on the human lncRNA regulation of stem cell potency and differentiation. Although the clinical implication of these lncRNAs is only beginning to be elucidated, it is anticipated that lncRNAs will become important therapeutic targets in the near future.

  9. β-Glucan Size Controls Dectin-1-Mediated Immune Responses in Human Dendritic Cells by Regulating IL-1β Production

    Directory of Open Access Journals (Sweden)

    Matthew J. Elder

    2017-07-01

    Full Text Available Dectin-1/CLEC7A is a pattern recognition receptor that recognizes β-1,3 glucans, and its stimulation initiates signaling events characterized by the production of inflammatory cytokines from human dendritic cells (DCs required for antifungal immunity. β-glucans differ greatly in size, structure, and ability to activate effector immune responses from DC; as such, small particulate β-glucans are thought to be poor activators of innate immunity. We show that β-glucan particle size is a critical factor contributing to the secretion of cytokines from human DC; large β-glucan-stimulated DC generate significantly more IL-1β, IL-6, and IL-23 compared to those stimulated with the smaller β-glucans. In marked contrast, the secretion of TSLP and CCL22 were found to be insensitive to β-glucan particle size. Furthermore, we show that the capacity to induce phagocytosis, and the relative IL-1β production determined by β-glucan size, regulates the composition of the cytokine milieu generated from DC. This suggests that β-glucan particle size is critically important in orchestrating the nature of the immune response to fungi.

  10. Effects of the Ordering of Natural Selection and Population Regulation Mechanisms on Wright-Fisher Models.

    Science.gov (United States)

    He, Zhangyi; Beaumont, Mark; Yu, Feng

    2017-07-05

    We explore the effect of different mechanisms of natural selection on the evolution of populations for one- and two-locus systems. We compare the effect of viability and fecundity selection in the context of the Wright-Fisher model with selection under the assumption of multiplicative fitness. We show that these two modes of natural selection correspond to different orderings of the processes of population regulation and natural selection in the Wright-Fisher model. We find that under the Wright-Fisher model these two different orderings can affect the distribution of trajectories of haplotype frequencies evolving with genetic recombination. However, the difference in the distribution of trajectories is only appreciable when the population is in significant linkage disequilibrium. We find that as linkage disequilibrium decays the trajectories for the two different models rapidly become indistinguishable. We discuss the significance of these findings in terms of biological examples of viability and fecundity selection, and speculate that the effect may be significant when factors such as gene migration maintain a degree of linkage disequilibrium. Copyright © 2017 He et al.

  11. Factoring out natural and indirect human effects on terrestrial carbon sources and sinks

    Energy Technology Data Exchange (ETDEWEB)

    Canadell, J.G. [Global Carbon Project, CSIRO Marine and Atmospheric Research, GPO Box 3023, Canberra, ACT 2601 (Australia); Kirschbaum, M.U.F. [Environmental Biology Group, RSBS, Australian National University, GPO Box 475, Canberra, ACT 2601 (Australia); Kurz, W.A. [Natural Resources Canada, Canadian Forest Service, 506 West Burnside Road, Victoria, BC V8Z 1M5 (Canada); Sanz, M.J. [Fundacion CEAM, Parque Tecnologico, Charles H. Darwin 14, 46980 Paterna, Valencia (Spain); Schlamadinger, B. [Joanneum Research, Elisabethstrasse 11, Graz A-8010 (Austria); Yamagata, Y. [Center for Global Environmental Research, National Institute of Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506 (Japan)

    2007-06-15

    The capacity to partition natural, indirect, and direct human-induced effects on terrestrial carbon (C) sources and sinks is necessary to be able to predict future terrestrial C dynamics and thus their influence on atmospheric CO2 growth. However, it will take a number of years before we can better attribute quantitative estimates of the contribution of various C processes to the net C balance. In a policy context, factoring out natural and indirect human-induced effects on C sources and sinks from the direct human-induced influences, is seen as a requirement of a C accounting approach that establishes a clear and unambiguous connection between human activities and the assignment of C credits and debits. We present options for factoring out various groups of influences including climate variability, CO2 and N fertilization, and legacies from forest management. These are: (1) selecting longer accounting or measurement periods to reduce the effects of inter-annual variability; (2) correction of national inventories for inter-annual variability; (3) use of activity-based accounting and C response curves; (4) use of baseline scenarios or benchmarks at the national level; (5) stratification of the landscape into units with distinct average C stocks. Other, more sophisticated modeling approaches (e.g., demographic models in combination with forest inventories; process-based models) are possible options for future C accounting systems but their complexity and data requirements make their present adoption more difficult in an inclusive international C accounting system.

  12. Factoring out natural and indirect human effects on terrestrial carbon sources and sinks

    International Nuclear Information System (INIS)

    Canadell, J.G.; Kirschbaum, M.U.F.; Kurz, W.A.; Sanz, M.J.; Schlamadinger, B.; Yamagata, Y.

    2007-01-01

    The capacity to partition natural, indirect, and direct human-induced effects on terrestrial carbon (C) sources and sinks is necessary to be able to predict future terrestrial C dynamics and thus their influence on atmospheric CO2 growth. However, it will take a number of years before we can better attribute quantitative estimates of the contribution of various C processes to the net C balance. In a policy context, factoring out natural and indirect human-induced effects on C sources and sinks from the direct human-induced influences, is seen as a requirement of a C accounting approach that establishes a clear and unambiguous connection between human activities and the assignment of C credits and debits. We present options for factoring out various groups of influences including climate variability, CO2 and N fertilization, and legacies from forest management. These are: (1) selecting longer accounting or measurement periods to reduce the effects of inter-annual variability; (2) correction of national inventories for inter-annual variability; (3) use of activity-based accounting and C response curves; (4) use of baseline scenarios or benchmarks at the national level; (5) stratification of the landscape into units with distinct average C stocks. Other, more sophisticated modeling approaches (e.g., demographic models in combination with forest inventories; process-based models) are possible options for future C accounting systems but their complexity and data requirements make their present adoption more difficult in an inclusive international C accounting system

  13. The human oxytocin gene promoter is regulated by estrogens.

    Science.gov (United States)

    Richard, S; Zingg, H H

    1990-04-15

    Gonadal steroids affect brain function primarily by altering the expression of specific genes, yet the specific mechanisms by which neuronal target genes undergo such regulation are unknown. Recent evidence suggests that the expression of the neuropeptide gene for oxytocin (OT) is modulated by estrogens. We therefore examined the possibility that this regulation occurred via a direct interaction of the estrogen-receptor complex with cis-acting elements flanking the OT gene. DNA-mediated gene transfer experiments were performed using Neuro-2a neuroblastoma cells and chimeric plasmids containing portions of the human OT gene 5'-glanking region linked to the chloramphenicol acetyltransferase gene. We identified a 19-base pair region located at -164 to -146 upstream of the transcription start site which is capable of conferring estrogen responsiveness to the homologous as well as to a heterologous promoter. The hormonal response is strictly dependent on the presence of intracellular estrogen receptors, since estrogen induced stimulation occurred only in Neuro-2a cells co-transfected with an expression vector for the human estrogen receptor. The identified region contains a novel imperfect palindrome (GGTGACCTTGACC) with sequence similarity to other estrogen response elements (EREs). To define cis-acting elements that function in synergism with the ERE, sequences 3' to the ERE were deleted, including the CCAAT box, two additional motifs corresponding to the right half of the ERE palindrome (TGACC), as well as a CTGCTAA heptamer similar to the "elegans box" found in Caenorhabditis elegans. Interestingly, optimal function of the identified ERE was fully independent of these elements and only required a short promoter region (-49 to +36). Our studies define a molecular mechanism by which estrogens can directly modulate OT gene expression. However, only a subset of OT neurons are capable of binding estrogens, therefore, direct action of estrogens on the OT gene may be

  14. Alexandria's Eastern Harbor, Egypt: Pollen, microscopic charcoal, and the transition from natural to human-modified basin

    Science.gov (United States)

    Stanley, J.-D.; Bernhardt, C.E.

    2010-01-01

    Pollen and microscopic charcoal examined in Holocene sediment core samples record major environmental modifications affecting Alexandria's Eastern Harbor through time. We assess whether such changes on Egypt's coastal margin were influenced primarily by natural, or natural plus human, or primarily human factors. We focus on (1) the times when pollen assemblages and microscopic charcoal content changed in the core, (2) how they changed, and (3) why this occurred. The analysis takes into account the core's stratigraphy, regional climate variability, human history, and local archaeological record. Four pollenmicroscopic charcoal zones are identified. The earliest change occurred at ca. 6000 YBP, during Egypt's earlier Predynastic (Neolithic) period, coinciding with a lithologic break from sand to muddy sand. Pollen during this time indicates a transition to a much drier climate rather than effects of human activity. The second change in pollen occurred 3600-2900 YBP, during a period of continued aridity with no lithologic variation in this core interval. Pollen (cereal taxa, agricultural weeds, grape) and a sharp increase in microscopic charcoal indicate that human activity became prevalent at least 700 y before Alexander the Great's arrival in this region, and these results highlight the transition from a largely natural climatecontrolled environment to one influenced by both climate and anthropogenic activity. The third shift up-core in pollen assemblages is dated at ca. 2300 YBP, at the boundary between a sand and mud unit. It coincides with construction by the Ptolemies of the Heptastadion between Alexandria and Pharos Island. From this time onward, harbor sediment in the nearly enclosed catchment basin indicates a near-continuous record of dominant proximal human activity. ?? 2010 Coastal Education and Research Foundation.

  15. Human Rights in Natural Science and Technology Professions’ Codes of Ethics?

    OpenAIRE

    Haugen, Hans Morten

    2013-01-01

    Abstract: No global professional codes for the natural science and technology professions exist. In light of how the application of new technology can affect individuals and communities, this discrepancy warrants greater scrutiny. This article analyzes the most relevant processes and seeks to explain why these processes have not resulted in global codes. Moreover, based on a human rights approach, the article gives recommendations on the future process and content of codes for ...

  16. Transcriptional regulation of human and rat hepatic lipid metabolism by the grapefruit flavonoid naringenin: role of PPARalpha, PPARgamma and LXRalpha.

    Directory of Open Access Journals (Sweden)

    Jonathan Goldwasser

    2010-08-01

    Full Text Available Disruption of lipid and carbohydrate homeostasis is an important factor in the development of prevalent metabolic diseases such as diabetes, obesity, and atherosclerosis. Therefore, small molecules that could reduce insulin dependence and regulate dyslipidemia could have a dramatic effect on public health. The grapefruit flavonoid naringenin has been shown to normalize lipids in diabetes and hypercholesterolemia, as well as inhibit the production of HCV. Here, we demonstrate that naringenin regulates the activity of nuclear receptors PPARalpha, PPARgamma, and LXRalpha. We show it activates the ligand-binding domain of both PPARalpha and PPARgamma, while inhibiting LXRalpha in GAL4-fusion reporters. Using TR-FRET, we show that naringenin is a partial agonist of LXRalpha, inhibiting its association with Trap220 co-activator in the presence of TO901317. In addition, naringenin induces the expression of PPARalpha co-activator, PGC1alpha. The flavonoid activates PPAR response element (PPRE while suppressing LXRalpha response element (LXRE in human hepatocytes, translating into the induction of PPAR-regulated fatty acid oxidation genes such as CYP4A11, ACOX, UCP1 and ApoAI, and inhibition of LXRalpha-regulated lipogenesis genes, such as FAS, ABCA1, ABCG1, and HMGR. This effect results in the induction of a fasted-like state in primary rat hepatocytes in which fatty acid oxidation increases, while cholesterol and bile acid production decreases. Our findings explain the myriad effects of naringenin and support its continued clinical development. Of note, this is the first description of a non-toxic, naturally occurring LXRalpha inhibitor.

  17. Natural gas marketing II

    International Nuclear Information System (INIS)

    Anon.

    1988-01-01

    This book covers all aspects of gas marketing, from the basic regulatory structure to the latest developments in negotiating agreements and locating markets. Topics include: Federal regulation of the gas industry; Fundamentals of gas marketing contracts; FERC actions encouraging competitive markets; Marketing conditions from the pipelines' perspective; State non-utility regulation of natural gas production, transportation, and marketing; Natural gas wellhead agreements and tariffs; Natural gas processing agreements; Effective management of producer's natural gas contracts; Producer-pipeline litigation; Natural gas purchasing from the perspective of industrial gas users; Gas marketing by co-owners: problems of disproportionate sales, gas balancing, and accounting to royalty owners; Alternatives and new directions in marketing

  18. Screening natural libraries of human milk oligosaccharides against lectins using CaR-ESI-MS.

    Science.gov (United States)

    El-Hawiet, Amr; Chen, Yajie; Shams-Ud-Doha, Km; Kitova, Elena N; Kitov, Pavel I; Bode, Lars; Hage, Naim; Falcone, Franco H; Klassen, John S

    2018-01-15

    Human milk oligosaccharides (HMOs) afford many health benefits to breast-fed infants, such as protection against infection and regulation of the immune system, through the formation of non-covalent interactions with protein receptors. However, the molecular details of these interactions are poorly understood. Here, we describe the application of catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS) for screening natural libraries of HMOs against lectins. The HMOs in the libraries were first identified based on molecular weights (MWs), ion mobility separation arrival times (IMS-ATs) and collision-induced dissociation (CID) fingerprints of their deprotonated anions. The libraries were then screened against lectins and the ligands identified from the MWs, IMS-ATs and CID fingerprints of HMOs released from the lectin in the gas phase. To demonstrate the assay, four fractions, extracted from pooled human milk and containing ≥35 different HMOs, were screened against a C-terminal fragment of human galectin-3 (hGal-3C), for which the HMOs specificities have been previously investigated, and a fragment of the blood group antigen-binding adhesin (BabA) from Helicobacter pylori, for which the HMO specificities have not been previously established. The structures of twenty-one ligands, corresponding to both neutral and acidic HMOs, of hGal-3C were identified; all twenty-one were previously shown to be ligands for this lectin. The presence of HMO ligands at six other MWs was also ascertained. Application of the assay to BabA revealed nineteen specific HMO structures that are recognized by the protein and HMO ligands at two other MWs. Notably, it was found that BabA exhibits broad specificity for HMOs, and recognizes both neutral HMOs, including non-fucosylated ones, and acidic HMOs. The results of competitive binding experiments indicate that HMOs can interact with BabA at previously unknown binding sites. The affinities of eight purified HMOs for BabA were

  19. Toward a 21st-Century Understanding of Humans' Relation to Nature: Two Hats?

    Science.gov (United States)

    Rennie, Scott

    2008-01-01

    From its inception, environmental education (EE) has shouldered the imposition of impartiality on its methods and practices. Considering the reality of global climate change, the author urges the adoption of the more accurate theory of humans' relation to the natural world. This theory necessitates partiality toward healthy, functioning natural…

  20. Research on natural gas fuel injection system. Development of high-performance pressure regulator; Tennen gas yo nenryo funsha system no kenkyu kaihatsu. 1. Tennen gas nenryo funshayo no koseino regulator kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    Kato, S; Ishii, M; Takigawa, B; Makabe, K; Harada, S; Ono, H [Nippon Carburetor Co. Ltd., Tokyo (Japan)

    1997-10-01

    With the aim of further reducing the exhaust emissions of natural-gas vehicles, vigorous research and development work is under way today on multi point gas injection (MPGI) system. In this studies, a high-performance pressure regulator, which is one of the main components of this MPGI system, has been newly developed. The results showed that a significantly better accuracy of the regulated pressure level using this regulator was obtained under the wide range of operating conditions, including instantaneously greater changes of fuel flow rate. In addition, the advanced studies of gaseous fuel injectors (GFIs) would be also conducted. 4 refs., 8 figs.