Combat Risk and Pay: Theory and Some Evidence

Science.gov (United States)

2011-10-01

1776) theory of compensating differences, and Rosen (1986) devised what has become the standard neoclassical economic theory relating wages to the...I N S T I T U T E F O R D E F E N S E A N A L Y S E S IDA Paper P-4774 October 2011 Combat Risk and Pay: Theory and Some Evidence Curtis J. Simon...OCT 2011 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Combat Risk and Pay: Theory and Some Evidence 5a. CONTRACT NUMBER 5b

Theories of risk and safety: what is their relevance to nursing?

Science.gov (United States)

Cooke, Hannah

2009-03-01

The aim of this paper is to review key theories of risk and safety and their implications for nursing. The concept of of patient safety has only recently risen to prominence as an organising principle in healthcare. The paper considers the wider social context in which contemporary concepts of risk and safety have developed. In particular it looks at sociological debates about the rise of risk culture and the risk society and their influence on the patient safety movement. The paper discusses three bodies of theory which have attempted to explain the management of risk and safety in organisations: normal accident theory, high reliability theory, and grid-group cultural theory. It examine debates between these theories and their implications for healthcare. It discusses reasons for the dominance of high reliability theory in healthcare and its strengths and limitations. The paper suggest that high reliability theory has particular difficulties in explaining some aspects of organisational culture. It also suggest that the implementation of high reliability theory in healthcare has involved over reliance on numerical indicators. It suggests that patient safety could be improved by openness to a wider range of theoretical perspectives.

Comments on the theory of radiation risk I Systematic outline of the theory of radiation risk

CERN Document Server

Neufeld, J

1974-01-01

Presents a systematic outline of the current theory of radiation risk. The most basic ideas of the theory can be expressed by two quantities which represent the administrative approach to radiation risk. These quantities are 'specific dose', D/sub s/, which relates to individual organs or tissues and 'overall dose', D/sub 0/, which relates to the entire human body. By taking D/sub s/ and D/sub 0/ as a starting point and by using postulational methods, two auxiliary quantities have been derived which are 'dose equivalent', D/sub e/(r), and quality factor, Q. Dose equivalent, D/sub e/(r), is a macroscopic field quantity and is, therefore, different from the ICRP defined dose equivalent, H, which is microscopic.

Cell-size distribution in epithelial tissue formation and homeostasis.

Science.gov (United States)

Puliafito, Alberto; Primo, Luca; Celani, Antonio

2017-03-01

How cell growth and proliferation are orchestrated in living tissues to achieve a given biological function is a central problem in biology. During development, tissue regeneration and homeostasis, cell proliferation must be coordinated by spatial cues in order for cells to attain the correct size and shape. Biological tissues also feature a notable homogeneity of cell size, which, in specific cases, represents a physiological need. Here, we study the temporal evolution of the cell-size distribution by applying the theory of kinetic fragmentation to tissue development and homeostasis. Our theory predicts self-similar probability density function (PDF) of cell size and explains how division times and redistribution ensure cell size homogeneity across the tissue. Theoretical predictions and numerical simulations of confluent non-homeostatic tissue cultures show that cell size distribution is self-similar. Our experimental data confirm predictions and reveal that, as assumed in the theory, cell division times scale like a power-law of the cell size. We find that in homeostatic conditions there is a stationary distribution with lognormal tails, consistently with our experimental data. Our theoretical predictions and numerical simulations show that the shape of the PDF depends on how the space inherited by apoptotic cells is redistributed and that apoptotic cell rates might also depend on size. © 2017 The Author(s).

A reason to eat healthy: The role of meaning in life in maintaining homeostasis in modern society

Directory of Open Access Journals (Sweden)

Bettina F Piko

2016-02-01

Full Text Available Health is a state of homeostasis of four principle kinds, namely, biochemical, physiological, psychological, and social. In this article, we complete this theory with a fifth element, namely, spiritual balance. Existential attitudes have been found to be closely related to identity formation, moral development, value-related attitudes, personal goals, and lifestyle choices. Meaning in life and searching for meaning serve better health since they may encourage people to engage in health-promoting behaviors and avoid health-risking behaviors, such as obesity and eating disorders. The meaning-making model proposes that people’s perceptions may contribute to content/discontent with life, body, and the world.

Risk Aversion and Expected-Utility Theory: A Calibration Theorem.

OpenAIRE

Matthew Rabin.

2000-01-01

Within the expected-utility framework, the only explanation for risk aversion is that the utility function for wealth is concave: A person has lower marginal utility for additional wealth when she is wealthy than when she is poor. This paper provides a theorem showing that expected-utility theory is an utterly implausible explanation for appreciable risk aversion over modest stakes: Within expected-utility theory, for any concave utility function, even very little risk aversion over modest st...

Regulation of energy homeostasis via GPR120

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Atsuhiko eIchimura

2014-07-01

Full Text Available Free fatty acids (FFAs are fundamental units of key nutrients. FFAs exert various biological functions, depending on the chain length and degree of desaturation. Recent studies have shown that several FFAs act as ligands of G-protein-coupled receptors (GPCRs, activate intracellular signaling and exert physiological functions via these GPCRs. GPR120 (also known as free fatty acid receptor 4, FFAR4 is activated by unsaturated medium- to long-chain FFAs and has a critical role in various physiological homeostasis mechanisms such as incretin hormone secretion, food preference, anti-inflammation and adipogenesis. Recent studies showed that a lipid sensor GPR120 has a key role in sensing dietary fat in white adipose tissue and regulates the whole body energy homeostasis in both humans and rodents. Genetic study in human identified the loss-of-functional mutation of GPR120 associated with obesity and insulin resistance. In addition, dysfunction of GPR120 has been linked as a novel risk factor for diet-induced obesity. This review aims to provide evidence from the recent development in physiological function of GPR120 and discusses its functional roles in regulation of energy homeostasis and its potential as drug targets.

Stochastic models in risk theory and management accounting

NARCIS (Netherlands)

Brekelmans, R.C.M.

2000-01-01

This thesis deals with stochastic models in two fields: risk theory and management accounting. Firstly, two extensions of the classical risk process are analyzed. A method is developed that computes bounds of the probability of ruin for the classical risk rocess extended with a constant interest

Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity.

Science.gov (United States)

Wang, Jiawei; Light, Kelly; Henderson, Mélanie; O'Loughlin, Jennifer; Mathieu, Marie-Eve; Paradis, Gilles; Gray-Donald, Katherine

2014-01-01

Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P added sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.

Tourism at Risk: Failures and Dichotomies of Risk Perception Theory in Tourism (Opinion Piece

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Maximiliano E. KORSTANJE

2017-12-01

Full Text Available The turn of the century has brought a lot of radical shifts and risks for tourism industry, which ranged from terrorism to lethal virus outbreaks. Henceforth risk perception theory, which was formulated in psychology, was re-appropriated by policy makers and tourism-related scholars. However, from its inception this conceptual corpus was based on the economic-centred paradigm. This piece discusses critically the main limitations of risk perception theory and the rise of a new discipline, post disaster marketing, in view of the caveats and speculative assumption of “the precautionary principle”.

Economics versus psychology.Risk, uncertainty and the expected utility theory

OpenAIRE

Schilirò, Daniele

2017-01-01

The present contribution examines the emergence of expected utility theory by John von Neumann and Oskar Morgenstern, the subjective the expected utility theory by Savage, and the problem of choice under risk and uncertainty, focusing in particular on the seminal work “The Utility Analysis of Choices involving Risk" (1948) by Milton Friedman and Leonard Savage to show how the evolution of the theory of choice has determined a separation of economics from psychology.

On the consistency of risk acceptance criteria with normative theories for decision-making

Energy Technology Data Exchange (ETDEWEB)

Abrahamsen, E.B. [University of Stavanger, 4036 Stavanger (Norway)], E-mail: eirik.abrahamsen@uis.no; Aven, T. [University of Stavanger, 4036 Stavanger (Norway)

2008-12-15

In evaluation of safety in projects it is common to use risk acceptance criteria to support decision-making. In this paper, we discuss to what extent the risk acceptance criteria is in accordance with the normative theoretical framework of the expected utility theory and the rank-dependent utility theory. We show that the use of risk acceptance criteria may violate the independence axiom of the expected utility theory and the comonotonic independence axiom of the rank-dependent utility theory. Hence the use of risk acceptance criteria is not in general consistent with these theories. The level of inconsistency is highest for the expected utility theory.

On the consistency of risk acceptance criteria with normative theories for decision-making

International Nuclear Information System (INIS)

Abrahamsen, E.B.; Aven, T.

2008-01-01

In evaluation of safety in projects it is common to use risk acceptance criteria to support decision-making. In this paper, we discuss to what extent the risk acceptance criteria is in accordance with the normative theoretical framework of the expected utility theory and the rank-dependent utility theory. We show that the use of risk acceptance criteria may violate the independence axiom of the expected utility theory and the comonotonic independence axiom of the rank-dependent utility theory. Hence the use of risk acceptance criteria is not in general consistent with these theories. The level of inconsistency is highest for the expected utility theory

Sleep duration and sleep quality are associated differently with alterations of glucose homeostasis

DEFF Research Database (Denmark)

Byberg, Stine; Hansen, Anne-Louise Smidt; Christensen, Dirk Lund

2012-01-01

Abstract Aims  Studies suggest that inadequate sleep duration and poor sleep quality increase the risk of impaired glucose regulation and diabetes. However, associations with specific markers of glucose homeostasis are less well explained. The objective of this study was to explore possible...... associations of sleep duration and sleep quality with markers of glucose homeostasis and glucose tolerance status in a healthy population-based study sample. Methods  The study comprised 771 participants from the Danish, population-based cross-sectional ‘Health2008’ study. Sleep duration and sleep quality were...... measured by self-report. Markers of glucose homeostasis were derived from a 3-point oral glucose tolerance test and included fasting plasma glucose, 2-h plasma glucose, HbA1c, two measures of insulin sensitivity (the insulin sensitivity index0,120 and homeostasis model assessment of insulin sensitivity...

Vitamin D Level Between Calcium-Phosphorus Homeostasis and Immune System: New Perspective in Osteoporosis.

Science.gov (United States)

Bellavia, Daniele; Costa, Viviana; De Luca, Angela; Maglio, Melania; Pagani, Stefania; Fini, Milena; Giavaresi, Gianluca

2016-10-13

Vitamin D is a key molecule in calcium and phosphate homeostasis; however, increasing evidence has recently shown that it also plays a crucial role in the immune system, both innate and adaptive. A deregulation of vitamin D levels, due also to mutations and polymorphisms in the genes of the vitamin D pathway, determines severe alterations in the homeostasis of the organism, resulting in a higher risk of onset of some diseases, including osteoporosis. This review gives an overview of the influence of vitamin D levels on the pathogenesis of osteoporosis, between bone homeostasis and immune system.

Predicting Facebook users' online privacy protection: risk, trust, norm focus theory, and the theory of planned behavior.

Science.gov (United States)

Saeri, Alexander K; Ogilvie, Claudette; La Macchia, Stephen T; Smith, Joanne R; Louis, Winnifred R

2014-01-01

The present research adopts an extended theory of the planned behavior model that included descriptive norms, risk, and trust to investigate online privacy protection in Facebook users. Facebook users (N = 119) completed a questionnaire assessing their attitude, subjective injunctive norm, subjective descriptive norm, perceived behavioral control, implicit perceived risk, trust of other Facebook users, and intentions toward protecting their privacy online. Behavior was measured indirectly 2 weeks after the study. The data show partial support for the theory of planned behavior and strong support for the independence of subjective injunctive and descriptive norms. Risk also uniquely predicted intentions over and above the theory of planned behavior, but there were no unique effects of trust on intentions, nor of risk or trust on behavior. Implications are discussed.

Investment risk management by applying contemporary modern portfolio theory

Directory of Open Access Journals (Sweden)

Jakšić Milena

2015-01-01

Full Text Available Investment risk is the principal threat to the assets side of the balance sheets of financial institutions. It is evident that investors who concentrate their wealth on one type of securities can rarely be found. Instead, they tend to invest diversified portfolio of securities. This reduces the degree of risk of the expected return, which depends both on the absolute risk of each investment in the portfolio, and the relationship that exists between individual investments within the portfolio. The paper analyzes the investment risk management by using modern portfolio theory in both national and global financial f lows. At the same time, the paper considers the risk management models that ensures efficient portfolio diversification, aiming at investment risk reduction. It is pointed out that the investment risk management in modern financial f lows is a complex process, and that the development of financial theory goes towards improving, soft risk management method.

Gastrointestinal Transit Time, Glucose Homeostasis and Metabolic Health: Modulation by Dietary Fibers.

Science.gov (United States)

Müller, Mattea; Canfora, Emanuel E; Blaak, Ellen E

2018-02-28

Gastrointestinal transit time may be an important determinant of glucose homeostasis and metabolic health through effects on nutrient absorption and microbial composition, among other mechanisms. Modulation of gastrointestinal transit may be one of the mechanisms underlying the beneficial health effects of dietary fibers. These effects include improved glucose homeostasis and a reduced risk of developing metabolic diseases such as obesity and type 2 diabetes mellitus. In this review, we first discuss the regulation of gastric emptying rate, small intestinal transit and colonic transit as well as their relation to glucose homeostasis and metabolic health. Subsequently, we briefly address the reported health effects of different dietary fibers and discuss to what extent the fiber-induced health benefits may be mediated through modulation of gastrointestinal transit.

Network theory-based analysis of risk interactions in large engineering projects

International Nuclear Information System (INIS)

Fang, Chao; Marle, Franck; Zio, Enrico; Bocquet, Jean-Claude

2012-01-01

This paper presents an approach based on network theory to deal with risk interactions in large engineering projects. Indeed, such projects are exposed to numerous and interdependent risks of various nature, which makes their management more difficult. In this paper, a topological analysis based on network theory is presented, which aims at identifying key elements in the structure of interrelated risks potentially affecting a large engineering project. This analysis serves as a powerful complement to classical project risk analysis. Its originality lies in the application of some network theory indicators to the project risk management field. The construction of the risk network requires the involvement of the project manager and other team members assigned to the risk management process. Its interpretation improves their understanding of risks and their potential interactions. The outcomes of the analysis provide a support for decision-making regarding project risk management. An example of application to a real large engineering project is presented. The conclusion is that some new insights can be found about risks, about their interactions and about the global potential behavior of the project. - Highlights: ► The method addresses the modeling of complexity in project risk analysis. ► Network theory indicators enable other risks than classical criticality analysis to be highlighted. ► This topological analysis improves project manager's understanding of risks and risk interactions. ► This helps project manager to make decisions considering the position in the risk network. ► An application to a real tramway implementation project in a city is provided.

An application of extreme value theory in estimating liquidity risk

Directory of Open Access Journals (Sweden)

Sonia Benito Muela

2017-09-01

Full Text Available The last global financial crisis (2007–2008 has highlighted the weaknesses of value at risk (VaR as a measure of market risk, as this metric by itself does not take liquidity risk into account. To address this problem, the academic literature has proposed incorporating liquidity risk into estimations of market risk by adding the VaR of the spread to the risk price. The parametric model is the standard approach used to estimate liquidity risk. As this approach does not generate reliable VaR estimates, we propose estimating liquidity risk using more sophisticated models based on extreme value theory (EVT. We find that the approach based on conditional extreme value theory outperforms the standard approach in terms of accurate VaR estimates and the market risk capital requirements of the Basel Capital Accord.

Decisionmaking under risk in invasive species management: risk management theory and applications

Science.gov (United States)

Shefali V. Mehta; Robert G. Haight; Frances R. Homans

2010-01-01

Invasive species management is closely entwined with the assessment and management of risk that arises from the inherently random nature of the invasion process. The theory and application of risk management for invasive species with an economic perspective is reviewed in this synthesis. Invasive species management can be delineated into three general categories:...

The opportunity-threat theory of decision-making under risk

OpenAIRE

Mohan Pandey

2018-01-01

A new theory of decision-making under risk, the Opportunity-Threat Theory is proposed. Analysis of risk into opportunity and threat components allows description of behavior as a combination of opportunity seeking and threat aversion. Expected utility is a special case of this model. The final evaluation is an integration of the impacts of opportunity and threat with this expectation. The model can account for basic results as well as several ``new paradoxes'' that refuted c...

Improving measurement of injection drug risk behavior using item response theory.

Science.gov (United States)

Janulis, Patrick

2014-03-01

Recent research highlights the multiple steps to preparing and injecting drugs and the resultant viral threats faced by drug users. This research suggests that more sensitive measurement of injection drug HIV risk behavior is required. In addition, growing evidence suggests there are gender differences in injection risk behavior. However, the potential for differential item functioning between genders has not been explored. To explore item response theory as an improved measurement modeling technique that provides empirically justified scaling of injection risk behavior and to examine for potential gender-based differential item functioning. Data is used from three studies in the National Institute on Drug Abuse's Criminal Justice Drug Abuse Treatment Studies. A two-parameter item response theory model was used to scale injection risk behavior and logistic regression was used to examine for differential item functioning. Item fit statistics suggest that item response theory can be used to scale injection risk behavior and these models can provide more sensitive estimates of risk behavior. Additionally, gender-based differential item functioning is present in the current data. Improved measurement of injection risk behavior using item response theory should be encouraged as these models provide increased congruence between construct measurement and the complexity of injection-related HIV risk. Suggestions are made to further improve injection risk behavior measurement. Furthermore, results suggest direct comparisons of composite scores between males and females may be misleading and future work should account for differential item functioning before comparing levels of injection risk behavior.

Exaggerated risk: prospect theory and probability weighting in risky choice.

Science.gov (United States)

Kusev, Petko; van Schaik, Paul; Ayton, Peter; Dent, John; Chater, Nick

2009-11-01

In 5 experiments, we studied precautionary decisions in which participants decided whether or not to buy insurance with specified cost against an undesirable event with specified probability and cost. We compared the risks taken for precautionary decisions with those taken for equivalent monetary gambles. Fitting these data to Tversky and Kahneman's (1992) prospect theory, we found that the weighting function required to model precautionary decisions differed from that required for monetary gambles. This result indicates a failure of the descriptive invariance axiom of expected utility theory. For precautionary decisions, people overweighted small, medium-sized, and moderately large probabilities-they exaggerated risks. This effect is not anticipated by prospect theory or experience-based decision research (Hertwig, Barron, Weber, & Erev, 2004). We found evidence that exaggerated risk is caused by the accessibility of events in memory: The weighting function varies as a function of the accessibility of events. This suggests that people's experiences of events leak into decisions even when risk information is explicitly provided. Our findings highlight a need to investigate how variation in decision content produces variation in preferences for risk.

A tri-reference point theory of decision making under risk.

Science.gov (United States)

Wang, X T; Johnson, Joseph G

2012-11-01

The tri-reference point (TRP) theory takes into account minimum requirements (MR), the status quo (SQ), and goals (G) in decision making under risk. The 3 reference points demarcate risky outcomes and risk perception into 4 functional regions: success (expected value of x ≥ G), gain (SQ G > SQ. We present TRP assumptions and value functions and a mathematical formalization of the theory. We conducted empirical tests of crucial TRP predictions using both explicit and implicit reference points. We show that decision makers consider both G and MR and give greater weight to MR than G, indicating failure aversion (i.e., the disutility of a failure is greater than the utility of a success in the same task) in addition to loss aversion (i.e., the disutility of a loss is greater than the utility of the same amount of gain). Captured by a double-S shaped value function with 3 inflection points, risk preferences switched between risk seeking and risk aversion when the distribution of a gamble straddled a different reference point. The existence of MR (not G) significantly shifted choice preference toward risk aversion even when the outcome distribution of a gamble was well above the MR. Single reference point based models such as prospect theory cannot consistently account for these findings. The TRP theory provides simple guidelines for evaluating risky choices for individuals and organizational management. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Decision theory and the evaluation of risks and benefits of clinical trials.

Science.gov (United States)

Bernabe, Rosemarie D C; van Thiel, Ghislaine J M W; Raaijmakers, Jan A M; van Delden, Johannes J M

2012-12-01

Research ethics committees (RECs) are tasked to assess the risks and the benefits of a clinical trial. In previous studies, it was shown that RECs find this task difficult, if not impossible, to do. The current approaches to benefit-risk assessment (i.e. Component Analysis and the Net Risk Test) confound the various risk-benefit tasks, and as such, make balancing impossible. In this article, we show that decision theory, specifically through the expected utility theory and multiattribute utility theory, enable for an explicit and ethically weighted risk-benefit evaluation. This makes a balanced ethical justification possible, and thus a more rationally defensible decision making. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effect of high-dose pitavastatin on glucose homeostasis in patients at elevated risk of new-onset diabetes: insights from the CAPITAIN and PREVAIL-US studies.

Science.gov (United States)

Chapman, M J; Orsoni, A; Robillard, P; Hounslow, N; Sponseller, C A; Giral, P

2014-05-01

Statin treatment may impair glucose homeostasis and increase the risk of new-onset diabetes mellitus, although this may depend on the statin, dose and patient population. We evaluated the effects of pitavastatin 4 mg/day on glucose homeostasis in patients with metabolic syndrome in the CAPITAIN trial. Findings were validated in a subset of patients enrolled in PREVAIL-US. Participants with a well defined metabolic syndrome phenotype were recruited to CAPITAIN to reduce the influence of confounding factors. Validation and comparison datasets were selected comprising phenotypically similar subsets of individuals enrolled in PREVAIL-US and treated with pitavastatin or pravastatin, respectively. Mean change from baseline in parameters of glucose homeostasis (fasting plasma glucose [FPG], glycated hemoglobin [HbA1c], insulin, quantitative insulin-sensitivity check index [QUICKI] and homeostasis model of assessment-insulin resistance [HOMA-IR]) and plasma lipid profile were assessed at 6 months (CAPITAIN) and 3 months (PREVAIL-US) after initiating treatment. In CAPITAIN (n = 12), no significant differences from baseline in HbA1c, insulin, HOMA-IR and QUICKI were observed at day 180 in patients treated with pitavastatin. A small (4%) increase in FPG from baseline to day 180 (P  0.05). Similar results were observed for pravastatin in the comparison dataset (n = 14). Other than a small change in FPG in the CAPITAIN study, neutral effects of pitavastatin on glucose homeostasis were observed in two cohorts of patients with metabolic syndrome, independent of its efficacy in reducing levels of atherogenic lipoproteins. The small number of patients and relatively short follow-up period represent limitations of the study. Nevertheless, these data suggest that statin-induced diabetogenesis may not represent a class effect.

The PAr index, an indicator reflecting altered vitamin B-6 homeostasis, is associated with long-term risk of stroke in the general population: the Hordaland Health Study (HUSK).

Science.gov (United States)

Zuo, Hui; Tell, Grethe S; Ueland, Per M; Nygård, Ottar; Vollset, Stein E; Midttun, Øivind; Meyer, Klaus; Ulvik, Arve

2018-01-01

Vitamin B-6 homeostasis is altered during inflammation and immune activation. It is unknown whether altered vitamin B-6 homeostasis is associated with the risk of stroke. We investigated the relation between the ratio plasma 4-pyridoxic acid: (pyridoxal + pyridoxal-5'-phosphate) (PAr) as an indicator of altered vitamin B-6 homeostasis and the risk of stroke in the general population. We conducted a prospective analysis of the community-based Hordaland Health Study (HUSK) in 6891 adults (born during 1925-1927 and 1950-1951) without known stroke at baseline (1998-1999). Participants were followed via linkage to the CVDNOR (Cardiovascular Disease in Norway) project and the Cause of Death Registry. HRs and 95% CIs were calculated using Cox proportional hazards analyses. A total of 390 participants (193 men and 197 women) developed stroke over a median follow-up period of 11 y. Study participants with elevated PAr experienced a higher risk of incident stroke in an essentially linear dose-response fashion. The HR (95% CI) for the highest compared with the lowest quartile of PAr was 1.97 (1.42, 2.73; P-trend trend <0.001) for ischemic stroke after adjustment for age, sex, body mass index (BMI), smoking, education, physical activity, estimated glomerular filtration rate, hypertension, diabetes, total cholesterol, and statin use. PAr had greater predictive strength than did C-reactive protein, current smoking, diabetes, hypertension, estimated glomerular filtration rate, and physical activity. The associations were similar in subgroups stratified by age group, sex, BMI, current smoking, hypertension, diabetes, and statin use at baseline. Higher plasma PAr was independently associated with increased risk of incident stroke in all participants and across all subgroups stratified by conventional risk predictors. Our novel findings point to and expand the range of inflammation and immune activation processes that may be relevant for the pathogenesis and prevention of stroke

Glucocorticoid receptor polymorphism in obesity and glucose homeostasis.

Science.gov (United States)

Majer-Łobodzińska, Agnieszka; Adamiec-Mroczek, Joanna

2017-01-01

Glucocorticoid receptor (GR) activity plays a significant role in the etiology of obesity and is essential for glucose homeostasis, the development of hyperinsulinaemia and subsequent increased fat deposition. Several polymorphisms in the GR gene have been described, and at least three of them seem to be associated with altered glucocorticoid sensitivity and changes in glucose homeostasis, and other metabolic parameters. The N363S polymorphism has been associated with increased sensitivity to glucocorticoides, increased insulin response to dexamethasone and increased plasma glucose level. BclI polymorphism is associated with increased abdominal obesity, hyperinsulinaemia and increased insulin resistance. Another polymorphism, ER22/23EK, in contrast to the others, is associated with relative resistance to glucocoricides actions and more beneficial metabolic profile-lower insulin resistance level, decreased lower cardiovascular risk and subseuent prolongation of life time. More research is still needed to understand the mechanisms behind these associations at the molecular level.

Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.

Science.gov (United States)

Anandhan, Annadurai; Jacome, Maria S; Lei, Shulei; Hernandez-Franco, Pablo; Pappa, Aglaia; Panayiotidis, Mihalis I; Powers, Robert; Franco, Rodrigo

2017-07-01

The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantitative modeling of operational risk in finance and banking using possibility theory

CERN Document Server

Chaudhuri, Arindam

2016-01-01

This book offers a comprehensive guide to the modelling of operational risk using possibility theory. It provides a set of methods for measuring operational risks under a certain degree of vagueness and impreciseness, as encountered in real-life data. It shows how possibility theory and indeterminate uncertainty-encompassing degrees of belief can be applied in analysing the risk function, and describes the parametric g-and-h distribution associated with extreme value theory as an interesting candidate in this regard. The book offers a complete assessment of fuzzy methods for determining both value at risk (VaR) and subjective value at risk (SVaR), together with a stability estimation of VaR and SVaR. Based on the simulation studies and case studies reported on here, the possibilistic quantification of risk performs consistently better than the probabilistic model. Risk is evaluated by integrating two fuzzy techniques: the fuzzy analytic hierarchy process and the fuzzy extension of techniques for order prefere...

Risk Oriented Audit Methodology’s Improvement, based on the Fraud Theory

Directory of Open Access Journals (Sweden)

Sergei V. Arzhenovskii

2016-12-01

Full Text Available Modern economic development is accompanied by the increasing complexity of the relationship structure, intercompany transactions, the requirements for information disclosure on the entity’s activities. It leads to the opportunities growth of fraudulent representation public companies reporting. The external audit is considered as an institution that resists to negative processes. The issues of improving the tools that assessing the risk of material misstatement of the financial statements due to fraud from the standpoint the fraud theory have been examined here. Determining potential areas in which methodology for risk assessment of material misstatement of the financial statements due to fraud in an audit are based on the modern fraud theory interpretations will be develop. Functional and structural, comparative, logical and historical, deductive and inductive analyst methods have been used. Retrospective analysis on research areas in the fraud theory field has been performed. Perspective directions for improving methodology and methods for risk assessment of material misstatement of the financial statements in an audit have been identified. Methodology development for fraud risk assessment procedures in an audit of financial statements is based on “fraud diamond” theory. Creating new interpretations the fraud theory during last fifteen years is a consequence the expansion opportunities for corporate fraud, one of the most common species which is the financial statements falsification. Changing the list of factors that could initiate the fraud in the company's public reporting requires that the methods of its identification during the audit should be improved. Methodology and methods risk assessment of intentional material misstatement of the financial statements need to be improved in the direction both the modern modification of fraud theory.

Adaptive mechanisms of homeostasis disorders

Directory of Open Access Journals (Sweden)

Anna Maria Dobosiewicz

2017-08-01

Full Text Available The ability to preserve a permanent level of internal environment in a human organism, against internal and external factors, which could breach the consistency, can be define as homeostasis. Scientific proven influence on the homeostasis has the periodicity of biological processes, which is also called circadian rhythm. The effect of circadian rhythm is also to see in the functioning of autonomic nervous system and cardiovascular system. Sleep deprivation is an example of how the disorders in circadian rhythm could have the influence on the homeostasis.

The homeostasis solution – Mechanical homeostasis in architecturally homeostatic buildings

International Nuclear Information System (INIS)

Wang, Lin-Shu; Ma, Peizheng

2016-01-01

Highlights: • Architectural homeostatic buildings (AHBs) make sense because of the laws of physics. • However, high efficiency can be obtained only with AHBs and equipment considered as systems. • Mechanical homeostasis facilitates AHB-equipment system synergy with heat extraction. • Entropically speaking a building needs neither energy nor a fixed amount of heat, but its homeostatic existence. • Homeostatic buildings can reduce building energy consumption from 80% to 90%. - Abstract: We already know, for energy-saving potential, the necessary architectural features in well-designed buildings: high performance building envelope, sufficient interior thermal mass, and hydronic-network activated radiant surfaces for cooling and heating. Buildings with these features may be referred to as architecturally homeostatic buildings (AHBs); such a building-system is thermally semi-autonomous in the sense that its temperature variation stays within a certain range even without conditioning equipment, and, with conditioning equipment in operation, its thermal regulation is handled by its hydronic heat-distribution-network for controlling the temperature level of the building. At the present time conventional HVAC equipment is used for maintaining the heat-distribution-network: this arrangement, however, has resulted in great energy saving only for AHBs with accessible natural water bodies. In operation of general AHBs, a case is made here for a new kind of mechanical equipment having the attribute of mechanical homeostasis (MH). MH is a new energy transformation concept in a triadic framework. Superlative energy efficiency is predicted as a result of combined improvements in higher triadCOPs and lower total (inducted + removed) heat rates—evincing existence of synergy in architectural and mechanical homeostasis, which together will be referred to as the homeostasis solution.

A Physiologist's View of Homeostasis

Science.gov (United States)

Modell, Harold; Cliff, William; Michael, Joel; McFarland, Jenny; Wenderoth, Mary Pat; Wright, Ann

2015-01-01

Homeostasis is a core concept necessary for understanding the many regulatory mechanisms in physiology. Claude Bernard originally proposed the concept of the constancy of the "milieu interieur," but his discussion was rather abstract. Walter Cannon introduced the term "homeostasis" and expanded Bernard's notion of…

Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype.

Science.gov (United States)

Ngo, Kevin; Patil, Prashanti; McGowan, Sara J; Niedernhofer, Laura J; Robbins, Paul D; Kang, James; Sowa, Gwendolyn; Vo, Nam

2017-09-01

Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1 -/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss. Published by Elsevier B.V.

A theory-based approach to understanding suicide risk in shelter-seeking women.

Science.gov (United States)

Wolford-Clevenger, Caitlin; Smith, Phillip N

2015-04-01

Women seeking shelter from intimate partner violence are at an increased risk for suicide ideation and attempts compared to women in the general population. Control-based violence, which is common among shelter-seeking women, may play a pivotal role in the development of suicide ideation and attempts. Current risk assessment and management practices for shelter-seeking women are limited by the lack of an empirically grounded understanding of increased risk in this population. We argue that in order to more effectively promote risk assessment and management, an empirically supported theory that is sensitive to the experiences of shelter-seeking women is needed. Such a theory-driven approach has the benefits of identifying and prioritizing targetable areas for intervention. Here, we review the evidence for the link between coercive control and suicide ideation and attempts from the perspective of Baumeister's escape theory of suicide. This theory has the potential to explain the role of coercive control in the development of suicide ideation and eventual attempts in shelter-seeking women. Implications for suicide risk assessment and prevention in domestic violence shelters are discussed. © The Author(s) 2014.

Informal Risk Perceptions and Formal Theory

International Nuclear Information System (INIS)

Cayford, Jerry

2001-01-01

Economists have argued persuasively that our goals are wider than just risk minimization, and that they include a prudent weighing of costs and benefits. This economic line of thought recognizes that our policy goals are complex. As we widen the range of goals we are willing to entertain, though, we need to check that the methods we customarily employ are appropriate for the tasks to which we customarily apply them. This paper examines some economic methods of risk assessment, in light of the question of what our policy goals are and should be. Once the question of goals is open, more complexities than just cost intrude: what the public wants and why begs to be addressed. This leads us to the controversial issue of public risk perceptions. We have now examined a number of procedures that experts use to make public policy decisions. Behind all these issues is always the question of social welfare: what actions can we take, what policies should we embrace, to make the world a better place? In many cases, the public and the experts disagree about what the right choice is. In the first section, we saw a possible defense of the experts based on democratic theory: the people's participation, and even their will, can be legitimately set aside in the pursuit of their true interests. If this defense is to work, a great deal of weight rests on the question of the people's interests and the competence and integrity of the experts' pursuit of it. But at the same time, social preferences are ill-defined, and so are not good candidates for rational actor theory. Both the prescriptive legitimacy claim and the very workings of formal theory we have seen to depend on informal, qualitative, political judgments. Unfortunately, we have also seen a steady pattern of expert reliance on technical procedures even when they were manifestly unsuited to the task. The experts seem so intent on excluding informal thought that they would prefer even a bad quantitative process to a qualitative

Informal Risk Perceptions and Formal Theory

Energy Technology Data Exchange (ETDEWEB)

Cayford, Jerry [Resources for the Future, Washington, DC (United States)

2001-07-01

Economists have argued persuasively that our goals are wider than just risk minimization, and that they include a prudent weighing of costs and benefits. This economic line of thought recognizes that our policy goals are complex. As we widen the range of goals we are willing to entertain, though, we need to check that the methods we customarily employ are appropriate for the tasks to which we customarily apply them. This paper examines some economic methods of risk assessment, in light of the question of what our policy goals are and should be. Once the question of goals is open, more complexities than just cost intrude: what the public wants and why begs to be addressed. This leads us to the controversial issue of public risk perceptions. We have now examined a number of procedures that experts use to make public policy decisions. Behind all these issues is always the question of social welfare: what actions can we take, what policies should we embrace, to make the world a better place? In many cases, the public and the experts disagree about what the right choice is. In the first section, we saw a possible defense of the experts based on democratic theory: the people's participation, and even their will, can be legitimately set aside in the pursuit of their true interests. If this defense is to work, a great deal of weight rests on the question of the people's interests and the competence and integrity of the experts' pursuit of it. But at the same time, social preferences are ill-defined, and so are not good candidates for rational actor theory. Both the prescriptive legitimacy claim and the very workings of formal theory we have seen to depend on informal, qualitative, political judgments. Unfortunately, we have also seen a steady pattern of expert reliance on technical procedures even when they were manifestly unsuited to the task. The experts seem so intent on excluding informal thought that they would prefer even a bad quantitative process to

Cadm2 regulates body weight and energy homeostasis in mice

Directory of Open Access Journals (Sweden)

Xin Yan

2018-02-01

Full Text Available Objective: Obesity is strongly linked to genes regulating neuronal signaling and function, implicating the central nervous system in the maintenance of body weight and energy metabolism. Genome-wide association studies identified significant associations between body mass index (BMI and multiple loci near Cell adhesion molecule2 (CADM2, which encodes a mediator of synaptic signaling enriched in the brain. Here we sought to further understand the role of Cadm2 in the pathogenesis of hyperglycemia and weight gain. Methods: We first analyzed Cadm2 expression in the brain of both human subjects and mouse models and subsequently characterized a loss-of-function mouse model of Cadm2 for alterations in glucose and energy homeostasis. Results: We show that the risk variant rs13078960 associates with increased CADM2 expression in the hypothalamus of human subjects. Increased Cadm2 expression in several brain regions of Lepob/ob mice was ameliorated after leptin treatment. Deletion of Cadm2 in obese mice (Cadm2/ob resulted in reduced adiposity, systemic glucose levels, and improved insulin sensitivity. Cadm2-deficient mice exhibited increased locomotor activity, energy expenditure rate, and core body temperature identifying Cadm2 as a potent regulator of systemic energy homeostasis. Conclusions: Together these data illustrate that reducing Cadm2 expression can reverse several traits associated with the metabolic syndrome including obesity, insulin resistance, and impaired glucose homeostasis. Keywords: Cadm2/SynCAM2, Energy homeostasis, Insulin sensitivity, Genome-wide association studies, Leptin signaling

Social Science Theories on Adolescent Risk-Taking: The Relevance of Behavioral Inhibition and Activation

Science.gov (United States)

Vermeersch, Hans; T'Sjoen, Guy; Kaufman, Jean-Marc; Van Houtte, Mieke

2013-01-01

The major social science theories on adolescent risk-taking--strain, social control, and differential association theories--have received substantial empirical support. The relationships between variables central to these theories and individual differences in temperament related to risk-taking, however, have not been adequately studied. In a…

Cultural theory and risk perception: validity and utility explored in the French context

International Nuclear Information System (INIS)

Brenot, J.; Bonnefous, S.; Mays, C.

1996-01-01

Explaining perceived risk can draw upon factors related to the person (e.g. demographics, personality, social/professional status, political orientation), or to the risk source (e.g. health impacts, economic effects). According to Cultural Theory risk perceptions are culturally biased. Wildavsky and Dake operationalised the Cultural Theory with questionnaire scales and found that resulting 'cultural profiles' best predict individual differences in risk perception. A French version of their questionnaire was inserted into a representative national risk opinion survey of May 1993; 1022 adults (age 18 and over) were interviewed. Major results are presented. The four cultural scales (hierarchy, egalitarianism, fatalism and individualism) show high correlations with political orientation as expected, but also with, for example, age, gender, income and education level. However, scale relationships to perception of risk situations (twenty, mainly technological) are not as strong as expected. Sjoeberg found similar results in Sweden. The utility of the existing operationalisation of Cultural Theory for risk perception analysis is discussed. (author)

Cultural theory and risk perception: validity and utility explored in the French context

Energy Technology Data Exchange (ETDEWEB)

Brenot, J.; Bonnefous, S.; Mays, C. [CEA Centre d`Etudes de Fontenay-aux-Roses, 92 (France). Inst. de Protection et de Surete Nucleaire

1996-12-31

Explaining perceived risk can draw upon factors related to the person (e.g. demographics, personality, social/professional status, political orientation), or to the risk source (e.g. health impacts, economic effects). According to Cultural Theory risk perceptions are culturally biased. Wildavsky and Dake operationalised the Cultural Theory with questionnaire scales and found that resulting `cultural profiles` best predict individual differences in risk perception. A French version of their questionnaire was inserted into a representative national risk opinion survey of May 1993; 1022 adults (age 18 and over) were interviewed. Major results are presented. The four cultural scales (hierarchy, egalitarianism, fatalism and individualism) show high correlations with political orientation as expected, but also with, for example, age, gender, income and education level. However, scale relationships to perception of risk situations (twenty, mainly technological) are not as strong as expected. Sjoeberg found similar results in Sweden. The utility of the existing operationalisation of Cultural Theory for risk perception analysis is discussed. (author).

Forewarning model for water pollution risk based on Bayes theory.

Science.gov (United States)

Zhao, Jun; Jin, Juliang; Guo, Qizhong; Chen, Yaqian; Lu, Mengxiong; Tinoco, Luis

2014-02-01

In order to reduce the losses by water pollution, forewarning model for water pollution risk based on Bayes theory was studied. This model is built upon risk indexes in complex systems, proceeding from the whole structure and its components. In this study, the principal components analysis is used to screen out index systems. Hydrological model is employed to simulate index value according to the prediction principle. Bayes theory is adopted to obtain posterior distribution by prior distribution with sample information which can make samples' features preferably reflect and represent the totals to some extent. Forewarning level is judged on the maximum probability rule, and then local conditions for proposing management strategies that will have the effect of transforming heavy warnings to a lesser degree. This study takes Taihu Basin as an example. After forewarning model application and vertification for water pollution risk from 2000 to 2009 between the actual and simulated data, forewarning level in 2010 is given as a severe warning, which is well coincide with logistic curve. It is shown that the model is rigorous in theory with flexible method, reasonable in result with simple structure, and it has strong logic superiority and regional adaptability, providing a new way for warning water pollution risk.

Cellular copper homeostasis: current concepts on its interplay with glutathione homeostasis and its implication in physiology and human diseases.

Science.gov (United States)

Bhattacharjee, Ashima; Chakraborty, Kaustav; Shukla, Aditya

2017-10-18

Copper is a trace element essential for almost all living organisms. But the level of intracellular copper needs to be tightly regulated. Dysregulation of cellular copper homeostasis leading to various diseases demonstrates the importance of this tight regulation. Copper homeostasis is regulated not only within the cell but also within individual intracellular compartments. Inactivation of export machinery results in excess copper being redistributed into various intracellular organelles. Recent evidence suggests the involvement of glutathione in playing an important role in regulating copper entry and intracellular copper homeostasis. Therefore interplay of both homeostases might play an important role within the cell. Similar to copper, glutathione balance is tightly regulated within individual cellular compartments. This review explores the existing literature on the role of glutathione in regulating cellular copper homeostasis. On the one hand, interplay of glutathione and copper homeostasis performs an important role in normal physiological processes, for example neuronal differentiation. On the other hand, perturbation of the interplay might play a key role in the pathogenesis of copper homeostasis disorders.

Game Theory and Risk-Based Levee System Design

Science.gov (United States)

Hui, R.; Lund, J. R.; Madani, K.

2014-12-01

Risk-based analysis has been developed for optimal levee design for economic efficiency. Along many rivers, two levees on opposite riverbanks act as a simple levee system. Being rational and self-interested, land owners on each river bank would tend to independently optimize their levees with risk-based analysis, resulting in a Pareto-inefficient levee system design from the social planner's perspective. Game theory is applied in this study to analyze decision making process in a simple levee system in which the land owners on each river bank develop their design strategies using risk-based economic optimization. For each land owner, the annual expected total cost includes expected annual damage cost and annualized construction cost. The non-cooperative Nash equilibrium is identified and compared to the social planner's optimal distribution of flood risk and damage cost throughout the system which results in the minimum total flood cost for the system. The social planner's optimal solution is not feasible without appropriate level of compensation for the transferred flood risk to guarantee and improve conditions for all parties. Therefore, cooperative game theory is then employed to develop an economically optimal design that can be implemented in practice. By examining the game in the reversible and irreversible decision making modes, the cost of decision making myopia is calculated to underline the significance of considering the externalities and evolution path of dynamic water resource problems for optimal decision making.

Rethinking Risk: Prospect Theory Application in Health Message Framing Research.

Science.gov (United States)

Harrington, Nancy Grant; Kerr, Anna M

2017-02-01

Although prospect theory conceptualizes risk as uncertainty, health message framing research based on the theory typically conceptualizes risk as severity. This study reports the results of two experiments designed to explore these alternative conceptualizations of risk and their effect on health decision making. Participants (N 1  = 768, N 2  = 532) were randomly assigned to one of four conditions that presented a hypothetical scenario of a sexually transmitted disease (STD) outbreak. The conditions were defined by message prompt (deadly vs. easily curable STD) and response option frame (gain vs. loss). Participants selected which of two programs (certain outcome vs. uncertain outcome) they would prefer to combat the outbreak. Across both experiments, participants expressed strong preferences for certain (low risk) outcomes in the gain-framed conditions and no preferences in the loss-framed conditions. These differences held regardless of the consequence severity of the scenario. We discuss the theoretical and practical implications of these results and offer directions for future research.

A treasure trove of hypothalamic neurocircuitries governing body weight homeostasis.

Science.gov (United States)

Vianna, Claudia R; Coppari, Roberto

2011-01-01

Changes in physical activities and feeding habits have transformed the historically rare disease of obesity into a modern metabolic pandemic. Obesity occurs when energy intake exceeds energy expenditure over time. This energy imbalance significantly increases the risk for cardiovascular disease and type 2 diabetes mellitus and as such represents an enormous socioeconomic burden and health threat. To combat obesity, a better understanding of the molecular mechanisms and neurocircuitries underlying normal body weight homeostasis is required. In the 1940s, pioneering lesion experiments unveiled the importance of medial and lateral hypothalamic structures. In the 1980s and 1990s, several neuropeptides and peripheral hormones critical for appropriate feeding behavior, energy expenditure, and hence body weight homeostasis were identified. In the 2000s, results from metabolic analyses of genetically engineered mice bearing mutations only in selected neuronal groups greatly advanced our knowledge of the peripheral/brain feedback-loop modalities by which central neurons control energy balance. In this review, we will summarize these recent progresses with particular emphasis on the biochemical identities of hypothalamic neurons and molecular components underlying normal appetite, energy expenditure, and body weight homeostasis. We will also parse which of those neurons and molecules are critical components of homeostatic adaptive pathways against obesity induced by hypercaloric feeding.

A conceptual framework for homeostasis: development and validation

Science.gov (United States)

Wenderoth, Mary Pat; Michael, Joel; Cliff, William; Wright, Ann; Modell, Harold

2016-01-01

We have developed and validated a conceptual framework for understanding and teaching organismal homeostasis at the undergraduate level. The resulting homeostasis conceptual framework details critical components and constituent ideas underlying the concept of homeostasis. It has been validated by a broad range of physiology faculty members from community colleges, primarily undergraduate institutions, research universities, and medical schools. In online surveys, faculty members confirmed the relevance of each item in the framework for undergraduate physiology and rated the importance and difficulty of each. The homeostasis conceptual framework was constructed as a guide for teaching and learning of this critical core concept in physiology, and it also paves the way for the development of a concept inventory for homeostasis. PMID:27105740

Prospect theory on the brain? Toward a cognitive neuroscience of decision under risk.

Science.gov (United States)

Trepel, Christopher; Fox, Craig R; Poldrack, Russell A

2005-04-01

Most decisions must be made without advance knowledge of their consequences. Economists and psychologists have devoted much attention to modeling decisions made under conditions of risk in which options can be characterized by a known probability distribution over possible outcomes. The descriptive shortcomings of classical economic models motivated the development of prospect theory (D. Kahneman, A. Tversky, Prospect theory: An analysis of decision under risk. Econometrica, 4 (1979) 263-291; A. Tversky, D. Kahneman, Advances in prospect theory: Cumulative representation of uncertainty. Journal of Risk and Uncertainty, 5 (4) (1992) 297-323) the most successful behavioral model of decision under risk. In the prospect theory, subjective value is modeled by a value function that is concave for gains, convex for losses, and steeper for losses than for gains; the impact of probabilities are characterized by a weighting function that overweights low probabilities and underweights moderate to high probabilities. We outline the possible neural bases of the components of prospect theory, surveying evidence from human imaging, lesion, and neuropharmacology studies as well as animal neurophysiology studies. These results provide preliminary suggestions concerning the neural bases of prospect theory that include a broad set of brain regions and neuromodulatory systems. These data suggest that focused studies of decision making in the context of quantitative models may provide substantial leverage towards a fuller understanding of the cognitive neuroscience of decision making.

Gut Homeostasis, Microbial Dysbiosis, and Opioids.

Science.gov (United States)

Wang, Fuyuan; Roy, Sabita

2017-01-01

Gut homeostasis plays an important role in maintaining animal and human health. The disruption of gut homeostasis has been shown to be associated with multiple diseases. The mutually beneficial relationship between the gut microbiota and the host has been demonstrated to maintain homeostasis of the mucosal immunity and preserve the integrity of the gut epithelial barrier. Currently, rapid progress in the understanding of the host-microbial interaction has redefined toxicological pathology of opioids and their pharmacokinetics. However, it is unclear how opioids modulate the gut microbiome and metabolome. Our study, showing opioid modulation of gut homeostasis in mice, suggests that medical interventions to ameliorate the consequences of drug use/abuse will provide potential therapeutic and diagnostic strategies for opioid-modulated intestinal infections. The study of morphine's modulation of the gut microbiome and metabolome will shed light on the toxicological pathology of opioids and its role in the susceptibility to infectious diseases.

Small- and large-stakes risk aversion: implications of concavity calabration for decision theory

NARCIS (Netherlands)

Cox, J.C.; Sadiraj, V.

2006-01-01

A growing literature reports the conclusions that: (a) expected utility theory does not provide a plausible theory of risk aversion for both small-stakes and large-stakes gambles; and (b) this decision theory should be replaced with an alternative theory characterized by loss aversion. This paper

A review of game theory approach to cyber security risk management

African Journals Online (AJOL)

A review of game theory approach to cyber security risk management. ... This paper presents a review of game theoretic-based model for cyber security risk management. Specifically, issues on ... AJOL African Journals Online. HOW TO USE ...

a review of game theory approach to cyber security risk management

African Journals Online (AJOL)

HOD

Keywords: Cyber Security, Risk Management, Game Theory, Model. 1. INTRODUCTION. Risk is ... behaviors. This implies they are triggered by self- motivated goal .... embrace diligence verification of the recipient of the email as well as lack of ...

Study designs for identifying risk compensation behavior among users of biomedical HIV prevention technologies: balancing methodological rigor and research ethics.

Science.gov (United States)

Underhill, Kristen

2013-10-01

The growing evidence base for biomedical HIV prevention interventions - such as oral pre-exposure prophylaxis, microbicides, male circumcision, treatment as prevention, and eventually prevention vaccines - has given rise to concerns about the ways in which users of these biomedical products may adjust their HIV risk behaviors based on the perception that they are prevented from infection. Known as risk compensation, this behavioral adjustment draws on the theory of "risk homeostasis," which has previously been applied to phenomena as diverse as Lyme disease vaccination, insurance mandates, and automobile safety. Little rigorous evidence exists to answer risk compensation concerns in the biomedical HIV prevention literature, in part because the field has not systematically evaluated the study designs available for testing these behaviors. The goals of this Commentary are to explain the origins of risk compensation behavior in risk homeostasis theory, to reframe risk compensation as a testable response to the perception of reduced risk, and to assess the methodological rigor and ethical justification of study designs aiming to isolate risk compensation responses. Although the most rigorous methodological designs for assessing risk compensation behavior may be unavailable due to ethical flaws, several strategies can help investigators identify potential risk compensation behavior during Phase II, Phase III, and Phase IV testing of new technologies. Where concerns arise regarding risk compensation behavior, empirical evidence about the incidence, types, and extent of these behavioral changes can illuminate opportunities to better support the users of new HIV prevention strategies. This Commentary concludes by suggesting a new way to conceptualize risk compensation behavior in the HIV prevention context. Copyright © 2013 Elsevier Ltd. All rights reserved.

A conceptual framework for homeostasis: development and validation.

Science.gov (United States)

McFarland, Jenny; Wenderoth, Mary Pat; Michael, Joel; Cliff, William; Wright, Ann; Modell, Harold

2016-06-01

We have developed and validated a conceptual framework for understanding and teaching organismal homeostasis at the undergraduate level. The resulting homeostasis conceptual framework details critical components and constituent ideas underlying the concept of homeostasis. It has been validated by a broad range of physiology faculty members from community colleges, primarily undergraduate institutions, research universities, and medical schools. In online surveys, faculty members confirmed the relevance of each item in the framework for undergraduate physiology and rated the importance and difficulty of each. The homeostasis conceptual framework was constructed as a guide for teaching and learning of this critical core concept in physiology, and it also paves the way for the development of a concept inventory for homeostasis. Copyright © 2016 The American Physiological Society.

Applying Ecodevelopmental Theory and the Theory of Reasoned Action to Understand HIV Risk Behaviors Among Hispanic Adolescents.

Science.gov (United States)

Ortega, Johis; Huang, Shi; Prado, Guillermo

2012-01-03

HIV/AIDS is listed as one of the top 10 reasons for the death of Hispanics between the ages of 15 and 54 in the United States. This cross sectional, descriptive secondary study proposed that using both the systemic (ecodevelopmental) and the individually focused (theory of reasoned action) theories together would lead to an increased understanding of the risk and protective factors that influence HIV risk behaviors in this population. The sample consisted of 493 Hispanic adolescent 7th and 8th graders and their immigrant parents living in Miami, Florida. Structural Equation Modeling (SEM) was used for the data analysis. Family functioning emerged as the heart of the model, embedded within a web of direct and mediated relationships. The data support the idea that family can play a central role in the prevention of Hispanic adolescents' risk behaviors.

Metal ion transporters and homeostasis.

OpenAIRE

Nelson, N

1999-01-01

Transition metals are essential for many metabolic processes and their homeostasis is crucial for life. Aberrations in the cellular metal ion concentrations may lead to cell death and severe diseases. Metal ion transporters play a major role in maintaining the correct concentrations of the various metal ions in the different cellular compartments. Recent studies of yeast mutants revealed key elements in metal ion homeostasis, including novel transport systems. Several of the proteins discover...

Risk Route Choice Analysis and the Equilibrium Model under Anticipated Regret Theory

Directory of Open Access Journals (Sweden)

pengcheng yuan

2014-02-01

Full Text Available The assumption about travellers’ route choice behaviour has major influence on the traffic flow equilibrium analysis. Previous studies about the travellers’ route choice were mainly based on the expected utility maximization theory. However, with the gradually increasing knowledge about the uncertainty of the transportation system, the researchers have realized that there is much constraint in expected util­ity maximization theory, because expected utility maximiza­tion requires travellers to be ‘absolutely rational’; but in fact, travellers are not truly ‘absolutely rational’. The anticipated regret theory proposes an alternative framework to the tra­ditional risk-taking in route choice behaviour which might be more scientific and reasonable. We have applied the antici­pated regret theory to the analysis of the risk route choosing process, and constructed an anticipated regret utility func­tion. By a simple case which includes two parallel routes, the route choosing results influenced by the risk aversion degree, regret degree and the environment risk degree have been analyzed. Moreover, the user equilibrium model based on the anticipated regret theory has been established. The equivalence and the uniqueness of the model are proved; an efficacious algorithm is also proposed to solve the model. Both the model and the algorithm are demonstrated in a real network. By an experiment, the model results and the real data have been compared. It was found that the model re­sults can be similar to the real data if a proper regret degree parameter is selected. This illustrates that the model can better explain the risk route choosing behaviour. Moreover, it was also found that the traveller’ regret degree increases when the environment becomes more and more risky.

Neuronal regulation of homeostasis by nutrient sensing.

Science.gov (United States)

Lam, Tony K T

2010-04-01

In type 2 diabetes and obesity, the homeostatic control of glucose and energy balance is impaired, leading to hyperglycemia and hyperphagia. Recent studies indicate that nutrient-sensing mechanisms in the body activate negative-feedback systems to regulate energy and glucose homeostasis through a neuronal network. Direct metabolic signaling within the intestine activates gut-brain and gut-brain-liver axes to regulate energy and glucose homeostasis, respectively. In parallel, direct metabolism of nutrients within the hypothalamus regulates food intake and blood glucose levels. These findings highlight the importance of the central nervous system in mediating the ability of nutrient sensing to maintain homeostasis. Futhermore, they provide a physiological and neuronal framework by which enhancing or restoring nutrient sensing in the intestine and the brain could normalize energy and glucose homeostasis in diabetes and obesity.

Set-Point Theory and personality development : Reconciliation of a paradox

NARCIS (Netherlands)

Ormel, Johan; Von Korff, Michael; Jeronimus, Bertus F.; Riese, Harriette; Specht, Jule

Set-point trait theories presume homeostasis at a specified level (stability/trait) and a surrounding “bandwidth” (change/state). The theory has been productively applied in studies on subjective well-being (SWB) but hardly in research on stability and change in personality (e.g. neuroticism,

Pharmacological modulation of mitochondrial calcium homeostasis.

Science.gov (United States)

Arduino, Daniela M; Perocchi, Fabiana

2018-01-10

Mitochondria are pivotal organelles in calcium (Ca 2+ ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca 2+ homeostasis have been linked to a variety of pathological conditions and are critical in the aetiology of several human diseases. Efforts have been taken to harness mitochondrial Ca 2+ transport mechanisms for therapeutic intervention, but pharmacological compounds that direct and selectively modulate mitochondrial Ca 2+ homeostasis are currently lacking. New avenues have, however, emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca 2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca 2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progress towards a systems-level pharmacological targeting of mitochondrial Ca 2+ homeostasis. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Towards a General Theory of Immunity?

Science.gov (United States)

Eberl, Gérard; Pradeu, Thomas

2018-04-01

Theories are indispensable to organize immunological data into coherent, explanatory, and predictive frameworks. We propose to combine different models to develop a unifying theory of immunity which situates immunology in the wider context of physiology. We believe that the immune system will be increasingly understood as a central component of a network of partner physiological systems that interconnect to maintain homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of Amino Acids in Dairy Products on Glucose Homeostasis: The Clinical Evidence.

Science.gov (United States)

Chartrand, Dominic; Da Silva, Marine S; Julien, Pierre; Rudkowska, Iwona

2017-06-01

Dairy products have been hypothesized to protect against type 2 diabetes because of their high content of whey proteins, rich in branched-chain amino acids (BCAAs) - leucine, isoleucine and valine - and lysine, which may decrease postprandial glucose responses and stimulate insulin secretion. Paradoxically, epidemiologic studies also show that higher levels of plasma BCAAs have been linked to insulin resistance and type 2 diabetes. Therefore, the objective was to review the recent clinical evidence concerning the intake of amino acids found in dairy proteins so as to determine their impact on glucose homeostasis in healthy persons and in those with prediabetes and type 2 diabetes. Clinical studies have reported that the major dairy amino acids, namely, leucine, isoleucine, glutamine, phenylalanine, proline and lysine, have beneficial effects on glucose homeostasis. Yet the reported doses of amino acids investigated are too elevated to be reached through adequate dairy product intake. The minor dairy amino acids, arginine and glycine, may improve glucose homeostasis by improving other risk factors for type 2 diabetes. Further, the combination of amino acids may also improve glucose-related outcomes, suggesting additive or synergistic effects. Nevertheless, additional long-term studies in individuals with prediabetes and type 2 diabetes are needed to ascertain the benefits for glucose homeostasis of amino acids found in dairy foods. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Supply Chain Disruptions Theory and Practice of Managing Risk

CERN Document Server

Mehrotra, Anuj; Ray, Saibal

2012-01-01

One of the most critical issues facing supply chain managers in today’s globalized and highly uncertain business environments is how to deal proactively with disruptions that might affect the complicated supply networks characterizing modern enterprises. Supply Chain Disruptions: Theory and Practice of Managing Risk presents a state-of the-art perspective on this particular issue. Supply Chain Disruptions: Theory and Practice of Managing Risk demonstrates that effective management of supply disruptions necessitates both strategic and tactical measures – the former involving optimal design of supply networks; the latter involving inventory, finance and demand management. It shows that managers ought to use all available levers at their disposal throughout the supply network – like sourcing and pricing strategies, providing financial subsidies, encouraging information sharing and incentive alignment between supply chain partners – in order to tackle supply disruptions. The editors combine up-to-date aca...

Does prospect theory warrant a paradigm shift in the economics of risk?

Directory of Open Access Journals (Sweden)

PL Mohapi

2014-07-01

Full Text Available This paper assesses whether a paradigm shift should be made from expected utility framework to prospect theory framework – in the economics of choice under risk. A brief overview of the subject is outlined, starting with expected utility theory and noting its descriptive limitations. Proposed theories to make up for these limitations is also provided. Prospect theory emerged as the most serious challenger to expected utility theory. A review of some descriptive predictions of prospect theory, suggests that there is no scientific reason why expected utility should not be ousted from dominance by prospect theory. The shift to prospect theory however is not without costs. Conceptual complexities and non-universality of application associated with prospect theory should be embraced with the shift while not entirely abandoning expected utility theory.

Redox homeostasis: The Golden Mean of healthy living

Directory of Open Access Journals (Sweden)

Fulvio Ursini

2016-08-01

Full Text Available The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve “reactive oxygen species” rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles

Agency Theory, Futures Markets and Risk Shifting in Commodity Marketing Channels

NARCIS (Netherlands)

Kuwornu, J.K.M.; Kuiper, W.E.; Pennings, J.M.E.; Meulenberg, M.T.G.

2004-01-01

This paper applies agency theory to access risk shifting between the principal (marketing firms) and the agent (farmers) in a food marketing channel. It compares the case in which there is a futures market available for the risk-averse agents with the case in which there is no futures trading. The

Synthesis strategy: building a culturally sensitive mid-range theory of risk perception using literary, quantitative, and qualitative methods.

Science.gov (United States)

Siaki, Leilani A; Loescher, Lois J; Trego, Lori L

2013-03-01

This article presents a discussion of development of a mid-range theory of risk perception. Unhealthy behaviours contribute to the development of health inequalities worldwide. The link between perceived risk and successful health behaviour change is inconclusive, particularly in vulnerable populations. This may be attributed to inattention to culture. The synthesis strategy of theory building guided the process using three methods: (1) a systematic review of literature published between 2000-2011 targeting perceived risk in vulnerable populations; (2) qualitative and (3) quantitative data from a study of Samoan Pacific Islanders at high risk of cardiovascular disease and diabetes. Main concepts of this theory include risk attention, appraisal processes, cognition, and affect. Overarching these concepts is health-world view: cultural ways of knowing, beliefs, values, images, and ideas. This theory proposes the following: (1) risk attention varies based on knowledge of the health risk in the context of health-world views; (2) risk appraisals are influenced by affect, health-world views, cultural customs, and protocols that intersect with the health risk; (3) strength of cultural beliefs, values, and images (cultural identity) mediate risk attention and risk appraisal influencing the likelihood that persons will engage in health-promoting behaviours that may contradict cultural customs/protocols. Interventions guided by a culturally sensitive mid-range theory may improve behaviour-related health inequalities in vulnerable populations. The synthesis strategy is an intensive process for developing a culturally sensitive mid-range theory. Testing of the theory will ascertain its usefulness for reducing health inequalities in vulnerable groups. © 2012 Blackwell Publishing Ltd.

Anticipatory vigilance: A grounded theory study of minimising risk within the perioperative setting.

Science.gov (United States)

O'Brien, Brid; Andrews, Tom; Savage, Eileen

2018-01-01

To explore and explain how nurses minimise risk in the perioperative setting. Perioperative nurses care for patients who are having surgery or other invasive explorative procedures. Perioperative care is increasingly focused on how to improve patient safety. Safety and risk management is a global priority for health services in reducing risk. Many studies have explored safety within the healthcare settings. However, little is known about how nurses minimise risk in the perioperative setting. Classic grounded theory. Ethical approval was granted for all aspects of the study. Thirty-seven nurses working in 11 different perioperative settings in Ireland were interviewed and 33 hr of nonparticipant observation was undertaken. Concurrent data collection and analysis was undertaken using theoretical sampling. Constant comparative method, coding and memoing and were used to analyse the data. Participants' main concern was how to minimise risk. Participants resolved this through engaging in anticipatory vigilance (core category). This strategy consisted of orchestrating, routinising and momentary adapting. Understanding the strategies of anticipatory vigilance extends and provides an in-depth explanation of how nurses' behaviour ensures that risk is minimised in a complex high-risk perioperative setting. This is the first theory situated in the perioperative area for nurses. This theory provides a guide and understanding for nurses working in the perioperative setting on how to minimise risk. It makes perioperative nursing visible enabling positive patient outcomes. This research suggests the need for training and education in maintaining safety and minimising risk in the perioperative setting. © 2017 John Wiley & Sons Ltd.

Testing the cultural theory of risk in France

International Nuclear Information System (INIS)

Brenot, J.; Bonnefous, S.; Marris, C.

1998-01-01

Cultural Theory, as developed by Mary Douglas, argues that differing risk perceptions can be explained by reference to four distinct cultural biases: hierarchy, egalitarianism, individualism, and fatalism. This paper presents empirical results from a quantitative survey based on a questionnaire devised by Karl Dake to measure these cultural biases. A large representative sample was used to test this instrument in the French social context. Correlations between cultural biases and perceptions of 20 social and environmental risks were examined. These correlations were very weak, but were statistically significant: cultural biases explained 6%, at most, of the variance in risk perceptions. Standard socio-demographic variables were also weakly related to risk perceptions (especially gender, social class, and education), and cultural biases and socio-demographic variables were themselves intercorrelated (especially with age, social class, and political outlook). The authors compare these results with surveys conducted in other countries using the same instrument and conclude that new methods, more qualitative and contextual, still need to be developed to investigate the cultural dimensions of risk perceptions. The paper also discusses relationships between perceptions of personal and residual risk, and between perceived risk and demand for additional safety measures. These three dimensions were generally closely related, but interesting differences were observed for some risk issues. Included in the list of risk perceptions were pollution, hazardous materials, and radioactive wastes

Osmotic homeostasis and NKLy lymphoma cells radiosensitivity

International Nuclear Information System (INIS)

Tishchenko, V.V.; Magda, I.N.

1992-01-01

In experiments with cells of ascites NKLy lymphoma differing in ploidy and position in the cell cycle, a study was made of the radiosensitivity, osmotic homeostasis peculiarities and thermoradiation changes in potassium content. It was shown that the resistance of osmotic homeostasis of NKLy cells to thermoradiation correlated with their radioresistance

Executive Risk Propensity and Accounting Conservatism Through the Lens of Life History Theory

DEFF Research Database (Denmark)

Holm, Morten; Schneider, Melanie L.

First, we intend to investigate the impact of CFO risk propensity on accounting conservatism. Second, we will examine the role of CEOs in this context. By drawing on life history theory, we propose variables reflecting executive risk propensity. Based on this, we hypothesize that CFO risk...

Redox homeostasis: The Golden Mean of healthy living.

Science.gov (United States)

Ursini, Fulvio; Maiorino, Matilde; Forman, Henry Jay

2016-08-01

The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve "reactive oxygen species" rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles (parahormesis). In summary

Research on Liquidity Risk Evaluation of Chinese A-Shares Market Based on Extension Theory

Science.gov (United States)

Bai-Qing, Sun; Peng-Xiang, Liu; Lin, Zhang; Yan-Ge, Li

This research defines the liquidity risk of stock market in matter-element theory and affair-element theory, establishes the indicator system of the forewarning for liquidity risks,designs the model and the process of early warning using the extension set method, extension dependent function and the comprehensive evaluation model. And the paper studies empirically A-shares market through the data of 1A0001, which prove that the model can better describe liquidity risk of China’s A-share market. At last, it gives the corresponding policy recommendations.

DO SELF-THEORIES EXPLAIN OVERCONFIDENCE AND FINANCIAL RISK TAKING? A field experiment.

OpenAIRE

Bertrand Koebel; André Schmitt; Sandrine Spaeter

2015-01-01

How people develop beliefs about themselves (self-theories) plays an important role on motivation and achievement as shown by Carol Dweck’s life-long research. In this paper, we conduct a field experiment to investigate whether self-theories impact overconfidence and risk taking. Self-theories deal with how an individual perceives some of her attributes such as intelligence, personality or moral character. In this paper, we are interested by how people perceive their mindset (fixed or growth)...

Age-dependent transition from cell-level to population-level control in murine intestinal homeostasis revealed by coalescence analysis.

Directory of Open Access Journals (Sweden)

Zheng Hu

Full Text Available In multi-cellular organisms, tissue homeostasis is maintained by an exquisite balance between stem cell proliferation and differentiation. This equilibrium can be achieved either at the single cell level (a.k.a. cell asymmetry, where stem cells follow strict asymmetric divisions, or the population level (a.k.a. population asymmetry, where gains and losses in individual stem cell lineages are randomly distributed, but the net effect is homeostasis. In the mature mouse intestinal crypt, previous evidence has revealed a pattern of population asymmetry through predominantly symmetric divisions of stem cells. In this work, using population genetic theory together with previously published crypt single-cell data obtained at different mouse life stages, we reveal a strikingly dynamic pattern of stem cell homeostatic control. We find that single-cell asymmetric divisions are gradually replaced by stochastic population-level asymmetry as the mouse matures to adulthood. This lifelong process has important developmental and evolutionary implications in understanding how adult tissues maintain their homeostasis integrating the trade-off between intrinsic and extrinsic regulations.

Modeling OPEC behavior: theories of risk aversion for oil producer decisions

International Nuclear Information System (INIS)

Reynolds, D.B.

1999-01-01

Theories of OPEC such as price leadership, cartel, or game theoretic models suggest an incentive for OPEC members to expand their production capacity well above current levels in order to maximize revenues. Yet individual OPEC members consistently explore for and develop oil fields at a level well below their potential. The cause of low oil exploration and development efforts among OPEC members, and even some non-OPEC members, may have to do with risk aversion. This paper describes an alternative theory for OPEC behavior based on risk aversion using a two piece non-Neumann-Morgenstern utility function similar to Fishburn and Koehenberger (1979, Decision Science 10, 503-518), and Friedman and Savage (1948, Journal of political Economy 56). The model shows possible low oil production behavior. (author)

Managing Reputational Risk through Environmental Management and Reporting: An Options Theory Approach

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Juan Pineiro-Chousa

2017-03-01

Full Text Available Reputation is a complex and multidimensional concept that may be organized in downside and upside reputational risk. In this article, we present a formal modelling for the management capabilities of environmental management and reporting over reputational risk, considering that reputational risk is becoming increasingly important for organizations and it directly depends on the information available about companies’ environmental performances. As long as the effectiveness of communication and disclosure plays a key role in the process, the usefulness of environmental management and reporting as a hedging instrument for reputational risk is addressed through different levels of information transparency. When considering a scenario of voluntary reporting, we show that environmentally concerned companies can reduce the cost of environmental management as a reputational risk strategy, as well as reducing the potential loss of reputational value from reputational threats and increasing the potential profit from reputational opportunities. In the context of mandatory reporting, we highlight the role of assurance companies as bearers of the risk of bad reputations for non-concerned companies. As a result, this novel approach applies theoretical oriented research from options theory to reputational risk management literature, so that it benefits from the option’s well known theory, robustness, and conclusions.

Evaluating Risk Communication After the Fukushima Disaster Based on Nudge Theory.

Science.gov (United States)

Murakami, Michio; Tsubokura, Masaharu

2017-03-01

Using nudge theory and some examples of risk communication that followed the Fukushima disaster, this article discusses the influences and justifications of risk communication, in addition to how risk communication systems are designed. To assist people in making decisions based on their own value systems, we provide three suggestions, keeping in mind that people can be influenced (ie, "nudged") depending on how risk communication takes place: (1) accumulate knowledge on the process of evaluating how the method of risk communication and a system's default design could impact people; (2) clarify the purpose and outcomes of risk communication; and (3) see what risk communication might be ethically unjustifiable. Quantitative studies on risk communication and collective narratives will provide some ideas for how to design better risk communication systems and to help people make decisions. Furthermore, we have shown examples of unjustifiable risk communication.

Physical activity, fitness, glucose homeostasis, and brain morphology in twins.

Science.gov (United States)

Rottensteiner, Mirva; Leskinen, Tuija; Niskanen, Eini; Aaltonen, Sari; Mutikainen, Sara; Wikgren, Jan; Heikkilä, Kauko; Kovanen, Vuokko; Kainulainen, Heikki; Kaprio, Jaakko; Tarkka, Ina M; Kujala, Urho M

2015-03-01

The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity. From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses. According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.

Risk Taking under the Influence: A Fuzzy-Trace Theory of Emotion in Adolescence

Science.gov (United States)

Rivers, Susan E.; Reyna, Valerie F.; Mills, Britain

2008-01-01

Fuzzy-trace theory explains risky decision making in children, adolescents, and adults, incorporating social and cultural factors as well as differences in impulsivity. Here, we provide an overview of the theory, including support for counterintuitive predictions (e.g., when adolescents "rationally" weigh costs and benefits, risk taking increases,…

Can prospect theory explain risk-seeking behavior by terminally ill patients?

Science.gov (United States)

Rasiel, Emma B; Weinfurt, Kevin P; Schulman, Kevin A

2005-01-01

Patients with life-threatening conditions sometimes appear to make risky treatment decisions as their condition declines, contradicting the risk-averse behavior predicted by expected utility theory. Prospect theory accommodates such decisions by describing how individuals evaluate outcomes relative to a reference point and how they exhibit risk-seeking behavior over losses relative to that point. The authors show that a patient's reference point for his or her health is a key factor in determining which treatment option the patient selects, and they examine under what circumstances the more risky option is selected. The authors argue that patients' reference points may take time to adjust following a change in diagnosis, with implications for predicting under what circumstances a patient may select experimental or conventional therapies or select no treatment.

Three-component homeostasis control

Science.gov (United States)

Xu, Jin; Hong, Hyunsuk; Jo, Junghyo

2014-03-01

Two reciprocal components seem to be sufficient to maintain a control variable constant. However, pancreatic islets adapt three components to control glucose homeostasis. They are α (secreting glucagon), β (insulin), and δ (somatostatin) cells. Glucagon and insulin are the reciprocal hormones for increasing and decreasing blood glucose levels, while the role of somatostatin is unknown. However, it has been known how each hormone affects other cell types. Based on the pulsatile hormone secretion and the cellular interactions, this system can be described as coupled oscillators. In particular, we used the Landau-Stuart model to consider both amplitudes and phases of hormone oscillations. We found that the presence of the third component, δ cell, was effective to resist under glucose perturbations, and to quickly return to the normal glucose level once perturbed. Our analysis suggested that three components are necessary for advanced homeostasis control.

[Integral evaluation of immune homeostasis in rockets liquidators and role of this evaluation for prophylaxis].

Science.gov (United States)

2010-01-01

Long-standing clinical and immunologic monitoring and integral evaluation of immune homeostasis (through generalized parameter) in personnel of Center for liquid-fuel rockets liquidation demonstrated diagnostically reliable immunity parameters that enable to forecast changes in the workers' health state. The authors defined boundary values of the generalized parameter to form risk groups for specific entities formation.

MicroRNAs and Periodontal Homeostasis.

Science.gov (United States)

Luan, X; Zhou, X; Trombetta-eSilva, J; Francis, M; Gaharwar, A K; Atsawasuwan, P; Diekwisch, T G H

2017-05-01

MicroRNAs (miRNAs) are a group of small RNAs that control gene expression in all aspects of eukaryotic life, primarily through RNA silencing mechanisms. The purpose of the present review is to introduce key miRNAs involved in periodontal homeostasis, summarize the mechanisms by which they affect downstream genes and tissues, and provide an introduction into the therapeutic potential of periodontal miRNAs. In general, miRNAs function synergistically to fine-tune the regulation of biological processes and to remove expression noise rather than by causing drastic changes in expression levels. In the periodontium, miRNAs play key roles in development and periodontal homeostasis and during the loss of periodontal tissue integrity as a result of periodontal disease. As part of the anabolic phase of periodontal homeostasis and periodontal development, miRNAs direct periodontal fibroblasts toward alveolar bone lineage differentiation and new bone formation through WNT, bone morphogenetic protein, and Notch signaling pathways. miRNAs contribute equally to the catabolic aspect of periodontal homeostasis as they affect osteoclastogenesis and osteoclast function, either by directly promoting osteoclast activity or by inhibiting osteoclast signaling intermediaries or through negative feedback loops. Their small size and ability to target multiple regulatory networks of related sets of genes have predisposed miRNAs to become ideal candidates for drug delivery and tissue regeneration. To address the immense therapeutic potential of miRNAs and their antagomirs, an ever growing number of delivery approaches toward clinical applications have been developed, including nanoparticle carriers and secondary structure interference inhibitor systems. However, only a fraction of the miRNAs involved in periodontal health and disease are known today. It is anticipated that continued research will lead to a more comprehensive understanding of the periodontal miRNA world, and a systematic

Development and Validation of the Homeostasis Concept Inventory

Science.gov (United States)

McFarland, Jenny L.; Price, Rebecca M.; Wenderoth, Mary Pat; Martinková, Patrícia; Cliff, William; Michael, Joel; Modell, Harold; Wright, Ann

2017-01-01

We present the Homeostasis Concept Inventory (HCI), a 20-item multiple-choice instrument that assesses how well undergraduates understand this critical physiological concept. We used an iterative process to develop a set of questions based on elements in the Homeostasis Concept Framework. This process involved faculty experts and undergraduate…

Extreme Value Theory Approach to Simultaneous Monitoring and Thresholding of Multiple Risk Indicators

NARCIS (Netherlands)

Einmahl, J.H.J.; Li, J.; Liu, R.Y.

2006-01-01

Risk assessments often encounter extreme settings with very few or no occurrences in reality.Inferences about risk indicators in such settings face the problem of insufficient data.Extreme value theory is particularly well suited for handling this type of problems.This paper uses a multivariate

A THEORY OF CONSUMER’S PERCEIVED RISK UNDER THE HALO EFFECT

Directory of Open Access Journals (Sweden)

Dorian-Laurenţiu FLOREA

2015-06-01

Full Text Available Despite being largely tackled by a manifold of sciences, perceived risk is still a rather unclear concept concerning its formation and update. In today’s economy, where poor purchase decisions are so easy to make, consumers have developed mental shields residing in actions based on perceived risk. This paper develops and tests a theory of perceived risk formation under the halo effect, based on correlation analysis in two forms: rankings individuals on their contribution to the correlations increase and partial correlations. Both internal and external halo effects were found, emerging from the perceived risk component – functional risk, financial risk, social risk, physical risk, psychological risk and time risk –, brand attitude, product category attitude, consumer’s regret, others’ regret expressed through word-of-mouth, recency, and awareness of awareness. The intricate halo that was revealed needs further attention from the scientific community in order to better delimit halo sources and, eventually, to explain its variability.

Differential risk theory as a subset of social exchange theory: implications for making gay marriage culturally normative and for understanding stigma against homosexuals.

Science.gov (United States)

Schumm, Walter R

2004-02-01

Differential risk theory, a subset of social exchange and equity theories, is proposed as an explanation for stigma towards homosexuals and as a basis for normative preferences for heterosexual marriage. Numerous gender differences involved in long-term relationships require members of such close relationships to assume greater interpersonal and social risks and thus costs, compared to same-gender relationships. Without compensating rewards or reduced costs, heterosexual relationships would be unfairly disadvantaged. Resistance to making gay marriage normative and/or equivalent legally to heterosexual marriage may be traced, rather than to homophobia, to societal attempts to maintain equity between classes of relationships characterized by inherent differential risks.

A new theoretical approach to the functional meaning of sleep and dreaming in humans based on the maintenance of 'predictive psychic homeostasis'.

Science.gov (United States)

Agnati, Luigi F; Barlow, Peter W; Baluška, František; Tonin, Paolo; Guescini, Michele; Leo, Giuseppina; Fuxe, Kjell

2011-11-01

Different theories have been put forward during the last decade to explain the functional meaning of sleep and dreaming in humans. In the present paper, a new theory is presented which, while taking advantage of these earlier theories, introduces the following new and original aspects:   • Circadian rhythms relevant to various organs of the body affect the reciprocal interactions which operate to maintain constancy of the internal milieu and thereby also affect the sleep/wakefulness cycle. Particular attention is given to the constancy of natraemia and osmolarity and to the permissive role that the evolution of renal function has had for the evolution of the central nervous system and its integrative actions. • The resetting of neuro-endocrine controls at the onset of wakefulness leads to the acquisition of new information and its integration within previously stored memories. This point is dealt with in relation to Moore-Ede's proposal for the existence of a 'predictive homeostasis'. • The concept of 'psychic homeostasis' is introduced and is considered as one of the most important states since it is aimed at the well-being, or eudemonia, of the human psyche. Sleep and dreaming in humans are discussed as important functions for the maintenance of a newly proposed composite state: that of 'predictive psychic homeostasis'. On the basis of these assumptions, and in accordance with the available neurobiological data, the present paper puts forward the novel hypothesis that sleep and dreaming play important functions in humans by compensating for psychic allostatic overloads. Hence, both consolatory dreams and disturbing nightmares can be part of the vis medicatrix naturae, the natural healing power, in this case, the state of eudemonia.

Requirement of the ATM/p53 tumor suppressor pathway for glucose homeostasis.

Science.gov (United States)

Armata, Heather L; Golebiowski, Diane; Jung, Dae Young; Ko, Hwi Jin; Kim, Jason K; Sluss, Hayla K

2010-12-01

Ataxia telangiectasia (A-T) patients can develop multiple clinical pathologies, including neuronal degeneration, an elevated risk of cancer, telangiectasias, and growth retardation. Patients with A-T can also exhibit an increased risk of insulin resistance and type 2 diabetes. The ATM protein kinase, the product of the gene mutated in A-T patients (Atm), has been implicated in metabolic disease, which is characterized by insulin resistance and increased cholesterol and lipid levels, blood pressure, and atherosclerosis. ATM phosphorylates the p53 tumor suppressor on a site (Ser15) that regulates transcription activity. To test whether the ATM pathway that regulates insulin resistance is mediated by p53 phosphorylation, we examined insulin sensitivity in mice with a germ line mutation that replaces the p53 phosphorylation site with alanine. The loss of p53 Ser18 (murine Ser15) led to increased metabolic stress, including severe defects in glucose homeostasis. The mice developed glucose intolerance and insulin resistance. The insulin resistance correlated with the loss of antioxidant gene expression and decreased insulin signaling. N-Acetyl cysteine (NAC) treatment restored insulin signaling in late-passage primary fibroblasts. The addition of an antioxidant in the diet rendered the p53 Ser18-deficient mice glucose tolerant. This analysis demonstrates that p53 phosphorylation on an ATM site is an important mechanism in the physiological regulation of glucose homeostasis.

Impact of estradiol, estrogen receptor subtype-selective agonists and genistein on energy homeostasis

OpenAIRE

Weigt, Carmen

2013-01-01

The prevalence of obesity is dramatically increasing and thus constitutes a major risk factor for developing chronic diseases such as type 2 diabetes, dyslipidemia, cardiovascular diseases, and certain forms of cancer. High-caloric nutrition and a lack of physical activity are the main contributing factors for this global epidemic. Estrogen receptors (ERs) are recognized to be involved in many processes related to the control of energy homeostasis. In my studies, I investigated the impac...

Interest in and reactions to genetic risk information: The role of implicit theories and self-affirmation.

Science.gov (United States)

Taber, Jennifer M; Klein, William M P; Persky, Susan; Ferrer, Rebecca A; Kaufman, Annette R; Thai, Chan L; Harris, Peter R

2017-10-01

Implicit theories reflect core assumptions about whether human attributes are malleable or fixed: Incremental theorists believe a characteristic is malleable whereas entity theorists believe it is fixed. People with entity theories about health may be less likely to engage in risk-mitigating behavior. Spontaneous self-affirmation (e.g., reflecting on one's values when threatened) may lessen defensiveness and unhealthy behaviors associated with fixed beliefs, and reduce the likelihood of responding to health risk information with fixed beliefs. Across two studies conducted in the US from 2012 to 2015, we investigated how self-affirmation and implicit theories about health and body weight were linked to engagement with genetic risk information. In Study 1, participants in a genome sequencing trial (n = 511) completed cross-sectional assessments of implicit theories, self-affirmation, and intentions to learn, share, and use genetic information. In Study 2, overweight women (n = 197) were randomized to receive genetic or behavioral explanations for weight; participants completed surveys assessing implicit theories, self-affirmation, self-efficacy, motivation, and intentions. Fixed beliefs about weight were infrequently endorsed across studies (10.8-15.2%). In Study 1, participants with stronger fixed theories were less interested in learning and using genetic risk information about medically actionable disease; these associations were weaker among participants higher in self-affirmation. In Study 2, among participants given behavioral explanations for weight, stronger fixed theories about weight were associated with lower motivation and intentions to eat a healthy diet. Among participants given genetic explanations, being higher in self-affirmation was associated with less fixed beliefs. Stronger health-related fixed theories may decrease the likelihood of benefiting from genetic information, but less so for people who self-affirm. Published by Elsevier Ltd.

Commensal Homeostasis of Gut Microbiota-Host for the Impact of Obesity

Directory of Open Access Journals (Sweden)

Pengyi Zhang

2018-01-01

Full Text Available Gut microbiota and their metabolites have been linked to a series of chronic diseases such as obesity and other metabolic dysfunctions. Obesity is an increasingly serious international health issue that may lead to a risk of insulin resistance and other metabolic diseases. The relationship between gut microbiota and the host is both interdependent and relatively independent. In this review, the causality of gut microbiota and its role in the pathogenesis and intervention of obesity is comprehensively presented to include human genotype, enterotypes, interactions of gut microbiota with the host, microbial metabolites, and energy homeostasis all of which may be influenced by dietary nutrition. Diet can enhance, inhibit, or even change the composition and functions of the gut microbiota. The metabolites they produce depend upon the dietary substrates provided, some of which have indispensable functions for the host. Therefore, diet is a key factor that maintains or not a healthy commensal relationship. In addition, the specific genotype of the host may impact the phylogenetic compositions of gut microbiota through the production of host metabolites. The commensal homeostasis of gut microbiota is favored by a balance of microbial composition, metabolites, and energy. Ultimately the desired commensal relationship is one of mutual support. This article analyzes the clues that result in patterns of commensal homeostasis. A deeper understanding of these interactions is beneficial for developing effective prevention, diagnosis, and personalized therapeutic strategies to combat obesity and other metabolic diseases. The idea we discuss is meant to improve human health by shaping or modulating the beneficial gut microbiota.

Partial restoration of mutant enzyme homeostasis in three distinct lysosomal storage disease cell lines by altering calcium homeostasis.

Directory of Open Access Journals (Sweden)

Ting-Wei Mu

2008-02-01

Full Text Available A lysosomal storage disease (LSD results from deficient lysosomal enzyme activity, thus the substrate of the mutant enzyme accumulates in the lysosome, leading to pathology. In many but not all LSDs, the clinically most important mutations compromise the cellular folding of the enzyme, subjecting it to endoplasmic reticulum-associated degradation instead of proper folding and lysosomal trafficking. A small molecule that restores partial mutant enzyme folding, trafficking, and activity would be highly desirable, particularly if one molecule could ameliorate multiple distinct LSDs by virtue of its mechanism of action. Inhibition of L-type Ca2+ channels, using either diltiazem or verapamil-both US Food and Drug Administration-approved hypertension drugs-partially restores N370S and L444P glucocerebrosidase homeostasis in Gaucher patient-derived fibroblasts; the latter mutation is associated with refractory neuropathic disease. Diltiazem structure-activity studies suggest that it is its Ca2+ channel blocker activity that enhances the capacity of the endoplasmic reticulum to fold misfolding-prone proteins, likely by modest up-regulation of a subset of molecular chaperones, including BiP and Hsp40. Importantly, diltiazem and verapamil also partially restore mutant enzyme homeostasis in two other distinct LSDs involving enzymes essential for glycoprotein and heparan sulfate degradation, namely alpha-mannosidosis and type IIIA mucopolysaccharidosis, respectively. Manipulation of calcium homeostasis may represent a general strategy to restore protein homeostasis in multiple LSDs. However, further efforts are required to demonstrate clinical utility and safety.

A Formal Explication of the Concept of Family Homeostasis.

Science.gov (United States)

Ariel, Shlomo; And Others

1984-01-01

Presents three articles discussing the concept of family homeostasis and the related concepts of family rules and family feedback. Includes a reply by Paul Dell citing the need for family therapy to go beyond homeostasis and further comments by Ariel, Carel, and Tyano. (JAC)

Regulation of intestinal homeostasis and immunity with probiotic lactobacilli

NARCIS (Netherlands)

Baarlen, van P.; Wells, J.; Kleerebezem, M.

2013-01-01

The gut microbiota provide important stimuli to the human innate and adaptive immune system and co-mediate metabolic and immune homeostasis. Probiotic bacteria can be regarded as part of the natural human microbiota, and have been associated with improving homeostasis, albeit with different levels

The relevance of the early history of probability theory to current risk assessment practices in mental health care.

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Large, Matthew

2013-12-01

Probability theory is at the base of modern concepts of risk assessment in mental health. The aim of the current paper is to review the key developments in the early history of probability theory in order to enrich our understanding of current risk assessment practices.

Persistent hepatitis virus infection and immune homeostasis

OpenAIRE

ZHOU Yun

2014-01-01

Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the pr...

Neuroimmune regulation during intestinal development and homeostasis.

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Veiga-Fernandes, Henrique; Pachnis, Vassilis

2017-02-01

Interactions between the nervous system and immune system are required for organ function and homeostasis. Evidence suggests that enteric neurons and intestinal immune cells share common regulatory mechanisms and can coordinate their responses to developmental challenges and environmental aggressions. These discoveries shed light on the physiology of system interactions and open novel perspectives for therapy designs that target underappreciated neurological-immunological commonalities. Here we highlight findings that address the importance of neuroimmune cell units (NICUs) in intestinal development, homeostasis and disease.

Dysregulation of cellular calcium homeostasis in Alzheimer's disease: bad genes and bad habits.

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Mattson, M P; Chan, S L

2001-10-01

Calcium is one of the most important intracellular messengers in the brain, being essential for neuronal development, synaptic transmission and plasticity, and the regulation of various metabolic pathways. The findings reviewed in the present article suggest that calcium also plays a prominent role in the pathogenesis of Alzheimer's disease (AD). Associations between the pathological hallmarks ofAD (neurofibrillary tangles [NFT] and amyloid plaques) and perturbed cellular calcium homeostasis have been established in studies of patients, and in animal and cell culture models of AD. Studies of the effects of mutations in the beta-amyloid precursor protein (APP) and presenilins on neuronal plasticity and survival have provided insight into the molecular cascades that result in synaptic dysfunction and neuronal degeneration in AD. Central to the neurodegenerative process is the inability of neurons to properly regulate intracellular calcium levels. Increased levels of amyloid beta-peptide (Abeta) induce oxidative stress, which impairs cellular ion homeostasis and energy metabolism and renders neurons vulnerable to apoptosis and excitotoxicity. Subtoxic levels of Abeta may induce synaptic dysfunction by impairing multiple signal transduction pathways. Presenilin mutations perturb calcium homeostasis in the endoplasmic reticulum in a way that sensitizes neurons to apoptosis and excitotoxicity; links between aberrant calcium regulation and altered APP processing are emerging. Environmental risk factors for AD are being identified and may include high calorie diets, folic acid insufficiency, and a low level of intellectual activity (bad habits); in each case, the environmental factor impacts on neuronal calcium homeostasis. Low calorie diets and intellectual activity may guard against AD by stimulating production of neurotrophic factors and chaperone proteins. The emerging picture of the cell and molecular biology of AD is revealing novel preventative and therapeutic

Adolescent insomnia, suicide risk, and the interpersonal theory of suicide.

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Zullo, Lucas; Horton, Sarah; Eaddy, Michael; King, Jessica; Hughes, Jennifer; Diederich, Andrew; Kennard, Betsy; Emslie, Graham; Stewart, Sunita

2017-11-01

Although insomnia has been repeatedly linked with suicide ideation, the reason for the linkage is not clear. The Interpersonal Psychological Theory of Suicide (IPTS) proposes that three core variables (thwarted belongingness, perceived burdensomeness, and acquired capability) are the final common pathway for all risk factors for suicide ideation and behavior. Recent research has suggested that insomnia may be associated with suicide ideation independently of the IPTS. We examined cross-sectional data from 151 psychiatric inpatients (ages 12-17) to determine if the association between insomnia symptoms and a continuous measure of suicide risk (measured as increasingly severe ideation and plan) was explained by the framework of the IPTS. When all IPTS variables and depressive symptoms were included in the model, insomnia symptoms did not contribute unique variance to suicide risk. Perceived burdensomeness and depressive symptoms were found to explain the relationship between insomnia symptoms and suicide risk. Our findings suggest that improved sleep might reduce suicide risk, that management of interpersonal need cognitions might reduce risk in the presence of insomnia symptoms, and reinforce the independent role of depressive symptoms in suicide risk in clinical samples of adolescents. Copyright © 2017 Elsevier B.V. All rights reserved.

Pseudomonas aeruginosa Trent and zinc homeostasis.

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Davies, Corey B; Harrison, Mark D; Huygens, Flavia

2017-09-01

Pseudomonas aeruginosa is a Gram-negative pathogen and the major cause of mortality in patients with cystic fibrosis. The mechanisms that P. aeruginosa strains use to regulate intracellular zinc have an effect on infection, antibiotic resistance and the propensity to form biofilms. However, zinc homeostasis in P. aeruginosa strains of variable infectivity has not been compared. In this study, zinc homeostasis in P. aeruginosa Trent, a highly infectious clinical strain, was compared to that of a laboratory P. aeruginosa strain, ATCC27853. Trent was able to tolerate higher concentrations of additional zinc in rich media than ATCC27853. Further, pre-adaptation to additional zinc enhanced the growth of Trent at non-inhibitory concentrations but the impact of pre-adaption on the growth of ATCC27853 under the same conditions was minimal. The results establish clear differences in zinc-induced responses in Trent and ATCC27853, and how zinc homeostasis can be a promising target for the development of novel antimicrobial strategies for P. aeruginosa infection in cystic fibrosis patients. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Supply risk management from a transaction cost and social exchange theory perspective

OpenAIRE

Hoffmann, Petra; Schiele, Holger; Song, Michael; Krabbendam, Johannes Jacobus

2012-01-01

Supply risk management gained prominence over the last decade, both in the academic discourse and in practical application. This research examines the influence of Transaction Cost characteristics -behavioral uncertainty, environmental uncertainty and asset specificity on supply risk management performance. We also identify two antecedents of the transaction cost constructs based on social exchange theory: dependency and preferred customer status. We used survey data to discover a positive in...

Regulation of intestinal homeostasis and immunity with probiotic lactobacilli.

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van Baarlen, Peter; Wells, Jerry M; Kleerebezem, Michiel

2013-05-01

The gut microbiota provide important stimuli to the human innate and adaptive immune system and co-mediate metabolic and immune homeostasis. Probiotic bacteria can be regarded as part of the natural human microbiota, and have been associated with improving homeostasis, albeit with different levels of success. Composition of microbiota, probiotic strain identity, and host genetic differences may account for differential modulation of immune responses by probiotics. Here, we review the mechanisms of immunomodulating capacities of specific probiotic strains, the responses they can induce in the host, and how microbiota and genetic differences between individuals may co-influence host responses and immune homeostasis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Diminished stress resistance and defective adaptive homeostasis in age-related diseases.

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Lomeli, Naomi; Bota, Daniela A; Davies, Kelvin J A

2017-11-01

Adaptive homeostasis is defined as the transient expansion or contraction of the homeostatic range following exposure to subtoxic, non-damaging, signaling molecules or events, or the removal or cessation of such molecules or events ( Mol. Aspects Med. (2016) 49, 1-7 ). Adaptive homeostasis allows us to transiently adapt (and then de-adapt) to fluctuating levels of internal and external stressors. The ability to cope with transient changes in internal and external environmental stress, however, diminishes with age. Declining adaptive homeostasis may make older people more susceptible to many diseases. Chronic oxidative stress and defective protein homeostasis (proteostasis) are two major factors associated with the etiology of age-related disorders. In the present paper, we review the contribution of impaired responses to oxidative stress and defective adaptive homeostasis in the development of age-associated diseases. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Financial risk and derivatives a special issue of the geneva papers on risk and insurance theory

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Subrahmanyam, Marti

1996-01-01

Financial Risk and Derivatives provides an excellent illustration of the links that have developed in recent years between the theory of finance on one hand and insurance economics and actuarial science on the other. Advances in contingent claims analysis and developments in the academic and practical literature dealing with the management of financial risks reflect the close relationships between insurance and innovations in finance. The book represents an overview of the present state of the art in theoretical research dealing with financial issues of significance for insurance science. It will hopefully provide an impetus to further developments in applied insurance research.

Cellular Links between Neuronal Activity and Energy Homeostasis

OpenAIRE

Shetty, Pavan K.; Galeffi, Francesca; Turner, Dennis A.

2012-01-01

Neuronal activity, astrocytic responses to this activity, and energy homeostasis are linked together during baseline, conscious conditions, and short-term rapid activation (as occurs with sensory or motor function). Nervous system energy homeostasis also varies during long-term physiological conditions (i.e., development and aging) and with adaptation to pathological conditions, such as ischemia or low glucose. Neuronal activation requires increased metabolism (i.e., ATP generation) which lea...

Telomere Homeostasis: Interplay with Magnesium

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Donogh Maguire

2018-01-01

Full Text Available Telomere biology, a key component of the hallmarks of ageing, offers insight into dysregulation of normative ageing processes that accompany age-related diseases such as cancer. Telomere homeostasis is tightly linked to cellular metabolism, and in particular with mitochondrial physiology, which is also diminished during cellular senescence and normative physiological ageing. Inherent in the biochemistry of these processes is the role of magnesium, one of the main cellular ions and an essential cofactor in all reactions that use ATP. Magnesium plays an important role in many of the processes involved in regulating telomere structure, integrity and function. This review explores the mechanisms that maintain telomere structure and function, their influence on circadian rhythms and their impact on health and age-related disease. The pervasive role of magnesium in telomere homeostasis is also highlighted.

Ageing and water homeostasis

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Robertson, David; Jordan, Jens; Jacob, Giris; Ketch, Terry; Shannon, John R.; Biaggioni, Italo

2002-01-01

This review outlines current knowledge concerning fluid intake and volume homeostasis in ageing. The physiology of vasopressin is summarized. Studies have been carried out to determine orthostatic changes in plasma volume and to assess the effect of water ingestion in normal subjects, elderly subjects, and patients with dysautonomias. About 14% of plasma volume shifts out of the vasculature within 30 minutes of upright posture. Oral ingestion of water raises blood pressure in individuals with impaired autonomic reflexes and is an important source of noise in blood pressure trials in the elderly. On the average, oral ingestion of 16 ounces (473ml) of water raises blood pressure 11 mmHg in elderly normal subjects. In patients with autonomic impairment, such as multiple system atrophy, strikingly exaggerated pressor effects of water have been seen with blood pressure elevations greater than 75 mmHg not at all uncommon. Ingestion of water is a major determinant of blood pressure in the elderly population. Volume homeostasis is importantly affected by posture and large changes in plasma volume may occur within 30 minutes when upright posture is assumed.

Amyloid and immune homeostasis.

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Wang, Ying-Hui; Zhang, Yu-Gen

2018-03-01

Extracellular amyloid deposition defines a range of amyloidosis and amyloid-related disease. Addition to primary and secondary amyloidosis, amyloid-related disease can be observed in different tissue/organ that sharing the common pathogenesis based on the formation of amyloid deposition. Currently, both Alzheimer's disease and type 2 diabetes can be diagnosed with certainly only based on the autopsy results, by which amyloidosis of the associative tissue/organ is observed. Intriguingly, since it demonstrated that amyloid deposits trigger inflammatory reaction through the activation of cascaded immune response, wherein several lines of evidence implies a protective role of amyloid in preventing autoimmunity. Furthermore, attempts for preventing amyloid formation and/or removing amyloid deposits from the brain have caused meningoencephalitis and consequent deaths among the subjects. Hence, it is important to note that amyloid positively participates in maintaining immune homeostasis and contributes to irreversible inflammatory response. In this review, we will focus on the interactive relationship between amyloid and the immune system, discussing the potential functional roles of amyloid in immune tolerance and homeostasis. Copyright © 2017 Elsevier GmbH. All rights reserved.

The S(c)ensory Immune System Theory.

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Veiga-Fernandes, Henrique; Freitas, António A

2017-10-01

Viewpoints on the immune system have evolved across different paradigms, including the clonal selection theory, the idiotypic network, and the danger and tolerance models. Herein, we propose that in multicellular organisms, where panoplies of cells from different germ layers interact and immune cells are constantly generated, the behavior of the immune system is defined by the rules governing cell survival, systems physiology and organismic homeostasis. Initially, these rules were imprinted at the single cell-protist level, but supervened modifications in the transition to multicellular organisms. This context determined the emergence of the 'sensory immune system', which operates in a s(c)ensor mode to ensure systems physiology, organismic homeostasis, and perpetuation of its replicating molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

Do politicians take risks like the rest of us? An experimental test of prospect theory under MPs

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Linde, J.; Vis, B.

Political psychologists have been quick to use prospect theory in their work, realizing its potential for explaining decisions under risk. Applying prospect theory to political decision-making is not without problems, though, and here we address two of these: (1) Does prospect theory actually apply

Do Politicians Take Risks Like the Rest of Us? An Experimental Test of Prospect Theory Under MPs

NARCIS (Netherlands)

Linde, Jona; Vis, Barbara

Political psychologists have been quick to use prospect theory in their work, realizing its potential for explaining decisions under risk. Applying prospect theory to political decision-making is not without problems, though, and here we address two of these: (1) Does prospect theory actually apply

At-risk students and the role of implicit theories of intelligence in educational professionals’ actions

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Tiekstra, Marlous; Minnaert, Alexander

2017-01-01

Implicit theories of intelligence play a role in teacher's actions. Adaptive instruction in and out of the classroom is important to optimize learning processes, especially in the case of at-risk students. This study explored to what extent implicit theories of intelligence play a role in the

Lifespan extension by preserving proliferative homeostasis in Drosophila.

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Benoît Biteau

2010-10-01

Full Text Available Regenerative processes are critical to maintain tissue homeostasis in high-turnover tissues. At the same time, proliferation of stem and progenitor cells has to be carefully controlled to prevent hyper-proliferative diseases. Mechanisms that ensure this balance, thus promoting proliferative homeostasis, are expected to be critical for longevity in metazoans. The intestinal epithelium of Drosophila provides an accessible model in which to test this prediction. In aging flies, the intestinal epithelium degenerates due to over-proliferation of intestinal stem cells (ISCs and mis-differentiation of ISC daughter cells, resulting in intestinal dysplasia. Here we show that conditions that impair tissue renewal lead to lifespan shortening, whereas genetic manipulations that improve proliferative homeostasis extend lifespan. These include reduced Insulin/IGF or Jun-N-terminal Kinase (JNK signaling activities, as well as over-expression of stress-protective genes in somatic stem cell lineages. Interestingly, proliferative activity in aging intestinal epithelia correlates with longevity over a range of genotypes, with maximal lifespan when intestinal proliferation is reduced but not completely inhibited. Our results highlight the importance of the balance between regenerative processes and strategies to prevent hyperproliferative disorders and demonstrate that promoting proliferative homeostasis in aging metazoans is a viable strategy to extend lifespan.

Gambler Risk Perception: A Mental Model and Grounded Theory Analysis.

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Spurrier, Michael; Blaszczynski, Alexander; Rhodes, Paul

2015-09-01

Few studies have investigated how gamblers perceive risk or the role of risk perception in disordered gambling. The purpose of the current study therefore was to obtain data on lay gamblers' beliefs on these variables and their effects on decision-making, behaviour, and disordered gambling aetiology. Fifteen regular lay gamblers (non-problem/low risk, moderate risk and problem gamblers) completed a semi-structured interview following mental models and grounded theory methodologies. Gambler interview data was compared to an expert 'map' of risk-perception, to identify comparative gaps or differences associated with harmful or safe gambling. Systematic overlapping processes of data gathering and analysis were used to iteratively extend, saturate, test for exception, and verify concepts and themes emerging from the data. The preliminary findings suggested that gambler accounts supported the presence of expert conceptual constructs, and to some degree the role of risk perception in protecting against or increasing vulnerability to harm and disordered gambling. Gambler accounts of causality, meaning, motivation, and strategy were highly idiosyncratic, and often contained content inconsistent with measures of disordered gambling. Disordered gambling appears heavily influenced by relative underestimation of risk and overvaluation of gambling, based on explicit and implicit analysis, and deliberate, innate, contextual, and learned processing evaluations and biases.

The homeostatic psyche: Freudian theory and somatic markers.

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Arminjon, Mathieu; Ansermet, François; Magistretti, Pierre

2010-11-01

After years of reciprocal lack of interest, if not opposition, neuroscience and psychoanalysis are poised for a renewed dialogue. This article discusses some aspects of the Freudian metapsychology and its link with specific biological mechanisms. It highlights in particular how the physiological concept of homeostasis resonates with certain fundamental concepts of psychoanalysis. Similarly, the authors underline how the Freud and Damasio theories of brain functioning display remarkable complementarities, especially through their common reference to Meynert and James. Furthermore, the Freudian theory of drives is discussed in the light of current neurobiological evidences of neural plasticity and trace formation and of their relationships with the processes of homeostasis. The ensuing dynamics between traces and homeostasis opens novel avenues to consider inner life in reference to the establishment of fantasies unique to each subject. The lack of determinism, within a context of determinism, implied by plasticity and reconsolidation participates in the emergence of singularity, the creation of uniqueness and the unpredictable future of the subject. There is a gap in determinism inherent to biology itself. Uniqueness and discontinuity: this should today be the focus of the questions raised in neuroscience. Neuroscience needs to establish the new bases of a "discontinuous" biology. Psychoanalysis can offer to neuroscience the possibility to think of discontinuity. Neuroscience and psychoanalysis meet thus in an unexpected way with regard to discontinuity and this is a new point of convergence between them. Copyright © 2010 Elsevier Ltd. All rights reserved.

A Mental Value Perspective in Risk Decision Theory

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Alexandru Trifu

2006-09-01

Full Text Available This work is based on Prospect theory, which was developed by D. Kahneman and A. Tversky in 1979. This is one the most quoted and best-documented point of view in economic psychology. First of all, it replaces, once again, the notion of utility with value. But value is defined in terms of gains and losses and this, according with an irrational human tendency to be less willing to gamble with profits than with losses. So, we discover the great importance of these assumptions in the field of risk decision-making, especially for firms’ activity in the marketplace.

A Mental Value Perspective in Risk Decision Theory

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Roxana Davidescu

2006-07-01

Full Text Available This work is based on Prospect theory, which was developed by D. Kahneman and A. Tversky in 1979. This is one the most quoted and best-documented point of view in economic psychology. First of all, it replaces, once again, the notion of utility with value. But value is defined in terms of gains and losses and this, according with an irrational human tendency to be less willing to gamble with profits than with losses. So, we discover the great importance of these assumptions in the field of risk decision-making, especially for firms’ activity in the marketplace.

Mechanism for maintaining homeostasis in the immune system of the intestine.

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Taniguchi, Yoshie; Yoshioka, Noriko; Nakata, Kazue; Nishizawa, Takashi; Inagawa, Hiroyuki; Kohchi, Chie; Soma, Gen-Ichiro

2009-11-01

Every organism possesses a mechanism for maintaining homeostasis. We have focused on the immune system as a system that helps maintain homeostasis of the body, and particularly on the intestine as the largest organ of immunity in the body. We have also focused our research on the mechanism that responds to foreign substances in the intestine, especially the toll-like receptors (TLR). The activation of myeloid differentiation primary response gene 88 (MyD88) signal transduction as a response to TLR in the intestine is believed to contribute to the maintenance of homeostasis of the body through the homeostasis of the intestine. Furthermore, significant findings were reported in which signal transduction from TLR4 was essential for the maintenance and regulation of the intestine. These results strongly suggest the possibility that homeostasis in the intestine is maintained by TLR4, and signaling by TLR4 after exposure to lipopolysaccharide (LPS) probably has a role in regulating homeostasis. It is expected that the prevention and treatment of various diseases using TLR4 will continue to develop. As LPS is a substance that enhances the activity of TLR4, it will also attract attention as a valuable substance in its own right.

Prospect theory and body mass: characterizing psychological parameters for weight-related risk attitudes and weight-gain aversion.

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Lim, Seung-Lark; Bruce, Amanda S

2015-01-01

We developed a novel decision-making paradigm that allows us to apply prospect theory in behavioral economics to body mass. 67 healthy young adults completed self-report measures and two decision-making tasks for weight-loss, as well as for monetary rewards. We estimated risk-related preference and loss aversion parameters for each individual, separately for weight-loss and monetary rewards choice data. Risk-seeking tendency for weight-loss was positively correlated with body mass index in individuals who desired to lose body weight, whereas the risk-seeking for momentary rewards was not. Risk-seeking for weight-loss was correlated to excessive body shape preoccupations, while aversion to weight-gain was correlated with self-reports of behavioral involvement for successful weight-loss. We demonstrated that prospect theory can be useful in explaining the decision-making process related to body mass. Applying prospect theory is expected to advance our understanding of decision-making mechanisms in obesity, which might prove helpful for improving healthy choices.

Prospect theory and body mass: Characterizing psychological parameters for weight-related risk attitudes and weight-gain aversion

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Seung-Lark eLim

2015-03-01

Full Text Available We developed a novel decision-making paradigm that allows us to apply prospect theory in behavioral economics to body mass. 67 healthy young adults completed self-report measures and two decision-making tasks for weight-loss, as well as for monetary rewards. We estimated risk-related preference and loss aversion parameters for each individual, separately for weight-loss and monetary rewards choice data. Risk-seeking tendency for weight-loss was positively correlated with body mass index in individuals who desired to lose body weight, whereas the risk-seeking for momentary rewards was not. Risk-seeking for weight-loss was correlated to excessive body shape preoccupations, while aversion to weight-gain was correlated with self-reports of behavioral involvement for successful weight-loss. We demonstrated that prospect theory can be useful in explaining the decision-making process related to body mass. Applying prospect theory is expected to advance our understanding of decision-making mechanisms in obesity, which might prove helpful for improving healthy choices.

Epigenetic impact of endocrine disrupting chemicals on lipid homeostasis and atherosclerosis: a pregnane X receptor-centric view.

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Helsley, Robert N; Zhou, Changcheng

2017-10-01

Despite the major advances in developing diagnostic techniques and effective treatments, atherosclerotic cardiovascular disease (CVD) is still the leading cause of mortality and morbidity worldwide. While considerable progress has been achieved to identify gene variations and environmental factors that contribute to CVD, much less is known about the role of "gene-environment interactions" in predisposing individuals to CVD. Our chemical environment has significantly changed in the last few decades, and there are more than 100,000 synthetic chemicals in the market. Recent large-scale human population studies have associated exposure to certain chemicals including many endocrine disrupting chemicals (EDCs) with increased CVD risk, and animal studies have also confirmed that some EDCs can cause aberrant lipid homeostasis and increase atherosclerosis. However, the underlying mechanisms of how exposure to those EDCs influences CVD risk remain elusive. Numerous EDCs can activate the nuclear receptor pregnane X receptor (PXR) that functions as a xenobiotic sensor to regulate host xenobiotic metabolism. Recent studies have demonstrated the novel functions of PXR in lipid homeostasis and atherosclerosis. In addition to directly regulating transcription, PXR has been implicated in the epigenetic regulation of gene transcription. Exposure to many EDCs can also induce epigenetic modifications, but little is known about how the changes relate to the onset or progression of CVD. In this review, we will discuss recent research on PXR and EDCs in the context of CVD and propose that PXR may play a previously unrealized role in EDC-mediated epigenetic modifications that affect lipid homeostasis and atherosclerosis.

Impact of intermittent fasting on glucose homeostasis.

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Varady, Krista A

2016-07-01

This article provides an overview of the most recent human trials that have examined the impact of intermittent fasting on glucose homeostasis. Our literature search retrieved one human trial of alternate day fasting, and three trials of Ramadan fasting published in the past 12 months. Current evidence suggests that 8 weeks of alternate day fasting that produces mild weight loss (4% from baseline) has no effect on glucose homeostasis. As for Ramadan fasting, decreases in fasting glucose, insulin, and insulin resistance have been noted after 4 weeks in healthy normal weight individuals with mild weight loss (1-2% from baseline). However, Ramadan fasting may have little impact on glucoregulatory parameters in women with polycystic ovarian syndrome who failed to observe weight loss. Whether intermittent fasting is an effective means of regulating glucose homeostasis remains unclear because of the scarcity of studies in this area. Large-scale, longer-term randomized controlled trials will be required before the use of fasting can be recommended for the prevention and treatment of metabolic diseases.

Dysregulated homeostasis of target tissues or autoantigens - A novel principle in autoimmunity.

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Petersen, Frank; Yue, Xiaoyang; Riemekasten, Gabriela; Yu, Xinhua

2017-06-01

Monogenic autoimmune disorders provide a powerful tool for our understanding of the principles of autoimmunity due to the obvious impact of a single gene on the disease. So far, approximately 100 single gene defects causing murine monogenic autoimmune disorders have been reported and the functional characterization of these genes will provide significant progress in understanding the nature of autoimmunity. According to their function, genes leading to monogenic autoimmune disorders can be categorized into two groups. An expectable first group contains genes involved in the homeostasis of the immune system, including homeostasis of immune organs and immune cells. Intriguingly, the second group consists of genes functionally involved in the homeostasis of target tissues or autoantigens. According to our novel hypothesis, we propose that autoimmunity represents a consequence of a dysregulated homeostasis of the immune system and/or its targets including autoantigens and target tissues. In this review we refer to both aspects of homeostasis in autoimmunity with a highlight on the role of the homeostasis of target tissues and autoantigens. Copyright © 2017 Elsevier B.V. All rights reserved.

THE WORLD VIEW, IDENTITY AND SOCIOCULTUR HOMEOSTASIS

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Marina Yur’evna Neronova

2016-02-01

Full Text Available The paper presents the relationship between the phenomenon of world view and sociocultural identity both individuals and the community as a whole. The research is being carried out in the context of current crisis of world view accepted in so-called art Nouveau era. This paper also presents the identity crisis typical for modern civilized societies. A new notion of sociocultural homeostasis is introduced in connection with analyzable phenomena and their mutual relations.Purpose. Study of the relationship between the phenomenon of the world view and sociocultural identity as a structural and functional mechanism.Methodology. Phenomenological and systematic methods with the elements of historical method were employed. Cultural analysis is based on using both axiological and phenomenological approach, and also the elements of semiotic approach.Results. The dependence of identity on the world view is revealed (or is being revealed?, the phenomenon of sociocultural homeostasis is singled out (or is being singled out in the capacity of the mechanism setting up the correspondence in the contradictory unity between the world view as a subjective image and concrete reality as an objective part of this contradictory. The analysis of sociocultural homeostasis is carried out (or is being carried out and the conclusion is being drown that instability of the latter leads to serious problems in the identification of both individuals and communities as a whole. Besides, (moreover the relationship between the legitimacy level of the world view and stability of sociocultural homeostasis is established. (is being established.Practical implications: the system of education.

Exploring the feasibility of theory synthesis: a worked example in the field of health related risk-taking.

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Pound, Pandora; Campbell, Rona

2015-01-01

The idea of synthesising theory is receiving attention within public health as part of a drive to design theoretically informed interventions. Theory synthesis is not a new idea, however, having been debated by sociologists for several decades. We consider the various methodological approaches to theory synthesis and test the feasibility of one such approach by synthesising a small number of sociological theories relevant to health related risk-taking. The synthesis consisted of three stages: (i) synthesis preparation, wherein parts of relevant theories were extracted and summarised; (ii) synthesis which involved comparing theories for points of convergence and divergence and bringing together those points that converge; and (iii) synthesis refinement whereby the synthesis was interrogated for further theoretical insights. Our synthesis suggests that serious and sustained risk-taking is associated with social isolation, liminality and a person's position in relation to the dominant social group. We reflect upon the methodological and philosophical issues raised by the practice of theory synthesis, concluding that it has the potential to reinvigorate theory and make it more robust and accessible for practical application. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Oxidative stress homeostasis in grapevine (Vitis vinifera L.

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Luisa C Carvalho

2015-03-01

Full Text Available Plants can maintain growth and reproductive success by sensing changes in the environment and reacting through mechanisms at molecular, cellular, physiological and developmental levels. Each stress condition prompts a unique response although some overlap between the reactions to abiotic stress (drought, heat, cold, salt or high light and to biotic stress (pathogens does occur. A common feature in the response to all stresses is the onset of oxidative stress, through the production of reactive oxygen species (ROS. As hydrogen peroxide and superoxide are involved in stress signaling, a tight control in ROS homeostasis requires a delicate balance of systems involved in their generation and degradation. If the plant lacks the capacity to generate scavenging potential, this can ultimately lead to death. In grapevine, antioxidant homeostasis can be considered at whole plant levels and during the development cycle. The most striking example lies in berries and their derivatives, such as wine, with nutraceutical properties associated with their antioxidant capacity. Antioxidant homeostasis is tightly regulated in leaves, assuring a positive balance between photosynthesis and respiration, explaining the tolerance of many grapevine varieties to extreme environments.In this review we will focus on antioxidant metabolites, antioxidant enzymes, transcriptional regulation and cross-talk with hormones prompted by abiotic stress conditions. We will also discuss three situations that require specific homeostasis balance: biotic stress, the oxidative burst in berries at veraison and in vitro systems. The genetic plasticity of the antioxidant homeostasis response put in evidence by the different levels of tolerance to stress presented by grapevine varieties will be addressed. The gathered information is relevant to foster varietal adaptation to impending climate changes, to assist breeders in choosing the more adapted varieties and to suitable viticulture

Neutrophils in Homeostasis, Immunity, and Cancer.

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Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

2017-01-17

Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

microRNA Regulation of Peritoneal Cavity Homeostasis in Peritoneal Dialysis

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Melisa Lopez-Anton

2015-01-01

Full Text Available Preservation of peritoneal cavity homeostasis and peritoneal membrane function is critical for long-term peritoneal dialysis (PD treatment. Several microRNAs (miRNAs have been implicated in the regulation of key molecular pathways driving peritoneal membrane alterations leading to PD failure. miRNAs regulate the expression of the majority of protein coding genes in the human genome, thereby affecting most biochemical pathways implicated in cellular homeostasis. In this review, we report published findings on miRNAs and PD therapy, with emphasis on evidence for changes in peritoneal miRNA expression during long-term PD treatment. Recent work indicates that PD effluent- (PDE- derived cells change their miRNA expression throughout the course of PD therapy, contributing to the loss of peritoneal cavity homeostasis and peritoneal membrane function. Changes in miRNA expression profiles will alter regulation of key molecular pathways, with the potential to cause profound effects on peritoneal cavity homeostasis during PD treatment. However, research to date has mainly adopted a literature-based miRNA-candidate methodology drawing conclusions from modest numbers of patient-derived samples. Therefore, the study of miRNA expression during PD therapy remains a promising field of research to understand the mechanisms involved in basic peritoneal cell homeostasis and PD failure.

General Theory versus ENA Theory: Comparing Their Predictive Accuracy and Scope.

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Ellis, Lee; Hoskin, Anthony; Hartley, Richard; Walsh, Anthony; Widmayer, Alan; Ratnasingam, Malini

2015-12-01

General theory attributes criminal behavior primarily to low self-control, whereas evolutionary neuroandrogenic (ENA) theory envisions criminality as being a crude form of status-striving promoted by high brain exposure to androgens. General theory predicts that self-control will be negatively correlated with risk-taking, while ENA theory implies that these two variables should actually be positively correlated. According to ENA theory, traits such as pain tolerance and muscularity will be positively associated with risk-taking and criminality while general theory makes no predictions concerning these relationships. Data from Malaysia and the United States are used to test 10 hypotheses derived from one or both of these theories. As predicted by both theories, risk-taking was positively correlated with criminality in both countries. However, contrary to general theory and consistent with ENA theory, the correlation between self-control and risk-taking was positive in both countries. General theory's prediction of an inverse correlation between low self-control and criminality was largely supported by the U.S. data but only weakly supported by the Malaysian data. ENA theory's predictions of positive correlations between pain tolerance, muscularity, and offending were largely confirmed. For the 10 hypotheses tested, ENA theory surpassed general theory in predictive scope and accuracy. © The Author(s) 2014.

Breast Milk Hormones and Regulation of Glucose Homeostasis

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Francesco Savino

2011-01-01

Full Text Available Growing evidence suggests that a complex relationship exists between the central nervous system and peripheral organs involved in energy homeostasis. It consists in the balance between food intake and energy expenditure and includes the regulation of nutrient levels in storage organs, as well as in blood, in particular blood glucose. Therefore, food intake, energy expenditure, and glucose homeostasis are strictly connected to each other. Several hormones, such as leptin, adiponectin, resistin, and ghrelin, are involved in this complex regulation. These hormones play a role in the regulation of glucose metabolism and are involved in the development of obesity, diabetes, and metabolic syndrome. Recently, their presence in breast milk has been detected, suggesting that they may be involved in the regulation of growth in early infancy and could influence the programming of energy balance later in life. This paper focuses on hormones present in breast milk and their role in glucose homeostasis.

MicroRNAs at the epicenter of intestinal homeostasis.

Science.gov (United States)

Belcheva, Antoaneta

2017-03-01

Maintaining intestinal homeostasis is a key prerequisite for a healthy gut. Recent evidence points out that microRNAs (miRNAs) act at the epicenter of the signaling networks regulating this process. The fine balance in the interaction between gut microbiota, intestinal epithelial cells, and the host immune system is achieved by constant transmission of signals and their precise regulation. Gut microbes extensively communicate with the host immune system and modulate host gene expression. On the other hand, sensing of gut microbiota by the immune cells provides appropriate tolerant responses that facilitate the symbiotic relationships. While the role of many regulatory proteins, receptors and their signaling pathways in the regulation of the intestinal homeostasis is well documented, the involvement of non-coding RNA molecules in this process has just emerged. This review discusses the most recent knowledge about the contribution of miRNAs in the regulation of the intestinal homeostasis. © 2017 WILEY Periodicals, Inc.

A systematic review and meta-analysis of the impact of mineralocorticoid receptor antagonists on glucose homeostasis

OpenAIRE

Korol, Sandra; Mottet, Fannie; Perreault, Sylvie; Baker, William L.; White, Michel; de Denus, Simon

2017-01-01

Abstract Background: Spironolactone, a nonselective mineralocorticoid receptor antagonist (MRA), may have a deleterious effect on glycemia. The objective of this review was to assess current knowledge on MRAs’ influence (spironolactone, eplerenone, and canrenone) on glucose homeostasis and the risk of diabetes. Method: A systematic review was conducted using the Medline database on articles published from 1946 to January 2017 that studied the effects of MRAs on any glucose-related endpoints, ...

A mathematical model of brain glucose homeostasis

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Kimura Hidenori

2009-11-01

Full Text Available Abstract Background The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation. Methods In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in diabetes, a brain-oriented mathematical model was developed by considering the brain as the controlled object while the remaining body as the actuator. After approximating the body compartmentally, the concentration dynamics of glucose, as well as those of insulin and glucagon, are described in each compartment. The brain-endocrine crosstalk, which regulates blood glucose level for brain glucose homeostasis together with the peripheral interactions among glucose, insulin and glucagon, is modeled as a proportional feedback control of brain glucose. Correlated to the brain, long-term effects of psychological stress and effects of blood-brain-barrier (BBB adaptation to dysglycemia on the generation of hyperglycemia are also taken into account in the model. Results It is shown that simulation profiles obtained from the model are qualitatively or partially quantitatively consistent with clinical data, concerning the GIG regulatory system responses to bolus glucose, stepwise and continuous glucose infusion. Simulations also revealed that both stress and BBB adaptation contribute to the generation of hyperglycemia. Conclusion Simulations of the model of a healthy person under long-term severe stress demonstrated that feedback control of brain glucose concentration results in elevation of blood glucose level. In this paper, we try to suggest that hyperglycemia in diabetes may be a normal outcome of brain glucose homeostasis.

The role of CDX2 in intestinal homeostasis and inflammation

DEFF Research Database (Denmark)

Coskun, Mehmet; Troelsen, Jesper Thorvald; Nielsen, Ole Haagen

2011-01-01

a causal role in a large number of diseases and developmental disorders. Inflammatory bowel disease (IBD) is characterized by a chronically inflamed mucosa caused by dysregulation of the intestinal immune homeostasis. The aetiology of IBD is thought to be a combination of genetic and environmental factors......, including luminal bacteria. The Caudal-related homeobox transcription factor 2 (CDX2) is critical in early intestinal differentiation and has been implicated as a master regulator of the intestinal homeostasis and permeability in adults. When expressed, CDX2 modulates a diverse set of processes including...... of the intestinal homeostasis and further to reveal its potential role in inflammation....

Neuronal and molecular mechanisms of sleep homeostasis.

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Donlea, Jeffrey M

2017-12-01

Sleep is necessary for survival, and prolonged waking causes a homeostatic increase in the need for recovery sleep. Homeostasis is a core component of sleep regulation and has been tightly conserved across evolution from invertebrates to man. Homeostatic sleep regulation was first identified among insects in cockroaches several decades ago, but the characterization of sleep rebound in Drosophila melanogaster opened the use of insect model species to understand homeostatic functions and regulation of sleep. This review describes circuits in two neuropil structures, the central complex and mushroom bodies, that influence sleep homeostasis and neuromodulatory systems that influence the accrual of homeostatic sleep need. Copyright © 2017 Elsevier Inc. All rights reserved.

Theory of Financial Risk and Derivative Pricing - 2nd Edition

Science.gov (United States)

Bouchaud, Jean-Philippe; Potters, Marc

2003-12-01

Foreword; Preface; 1. Probability theory: basic notions; 2. Maximum and addition of random variables; 3. Continuous time limit, Ito calculus and path integrals; 4. Analysis of empirical data; 5. Financial products and financial markets; 6. Statistics of real prices: basic results; 7. Non-linear correlations and volatility fluctuations; 8. Skewness and price-volatility correlations; 9. Cross-correlations; 10. Risk measures; 11. Extreme correlations and variety; 12. Optimal portfolios; 13. Futures and options: fundamental concepts; 14. Options: hedging and residual risk; 15. Options: the role of drift and correlations; 16. Options: the Black and Scholes model; 17. Options: some more specific problems; 18. Options: minimum variance Monte-Carlo; 19. The yield curve; 20. Simple mechanisms for anomalous price statistics; Index of most important symbols; Index.

Risk communication: Framing versus interdependence theory

International Nuclear Information System (INIS)

Lawless, W.F.; Burns, Chad W.

1992-01-01

Prospect theory has gained wide acceptance since its introduction by Kahneman and Tversky, especially where it has been applied extensively by DOE and others. But as conceived, it is a static process theory that may not apply to dynamic environments or dynamic processes; indeed, the recent extension to group situations by one of its authors modified the original conclusions. Although most social science research is static in nature, if prospect theory is to apply to human behavior, as the authors do with their sweeping generalizations about human irrationality, because behavior is dynamic and not static, then the challenge is to study prospect theory in a dynamic environment. This study will briefly review prospect and interdependence theories, representative evidence that distinguishes between the two theories, and the implications for DOE nuclear waste management. (author)

Upper intestinal lipids regulate energy and glucose homeostasis.

Science.gov (United States)

Cheung, Grace W C; Kokorovic, Andrea; Lam, Tony K T

2009-09-01

Upon the entry of nutrients into the small intestine, nutrient sensing mechanisms are activated to allow the body to adapt appropriately to the incoming nutrients. To date, mounting evidence points to the existence of an upper intestinal lipid-induced gut-brain neuronal axis to regulate energy homeostasis. Moreover, a recent discovery has also revealed an upper intestinal lipid-induced gut-brain-liver neuronal axis involved in the regulation of glucose homeostasis. In this mini-review, we will focus on the mechanisms underlying the activation of these respective neuronal axes by upper intestinal lipids.

Guest editor's introduction: Energy homeostasis in context.

Science.gov (United States)

Schneider, Jill E

2014-06-01

This article is part of a Special Issue "Energy Balance". Energy homeostasis is achieved through neuroendocrine and metabolic control of energy intake, storage, and expenditure. Traditionally, these controls have been studied in an unrealistic and narrow context. The appetite for food, for example, is most often assumed to be independent of other motivations, such as sexual desire, fearfulness, and competition. Furthermore, our understanding of all aspects of energy homeostasis is based on studying males of only a few species. The baseline control subjects are most often housed in enclosed spaces, with continuous, unlimited access to food. In the last century, this approach has generated useful information, but all the while, the global prevalence of obesity has increased and remains at unprecedented levels (Ogden et al., 2013, 2014). It is likely, however, that the mechanisms that control ingestive behavior were molded by evolutionary forces, and that few, if any vertebrate species evolved in the presence of a limitless food supply, in an enclosed 0.5 × 1 ft space, and exposed to a constant ambient temperature of 22+2 °C. This special issue of Hormones and Behavior therefore contains 9 review articles and 7 data articles that consider energy homeostasis within the context of other motivations and physiological processes, such as early development, sexual differentiation, sexual motivation, reproduction, seasonality, hibernation, and migration. Each article is focused on a different species or on a set of species, and most vertebrate classes are represented. Energy homeostasis is viewed in the context of the selection pressures that simultaneously molded multiple aspects of energy intake, storage, and expenditure. This approach yields surprising conclusions regarding the function of those traits and their underlying neuroendocrine mechanisms. Copyright © 2014. Published by Elsevier Inc.

Air pollution particles and iron homeostasis

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Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, fun...

Association of SSTR2 Polymorphisms and Glucose Homeostasis Phenotypes

OpenAIRE

Sutton, Beth S.; Palmer, Nicholette D.; Langefeld, Carl D.; Xue, Bingzhong; Proctor, Alexandria; Ziegler, Julie T.; Haffner, Steven M.; Norris, Jill M.; Bowden, Donald W.

2009-01-01

OBJECTIVE This study evaluated the influence of somatostatin receptor type 2 (SSTR2) polymorphisms on measures of glucose homeostasis in the Insulin Resistance Atherosclerosis Family Study (IRASFS). SSTR2 is a G-protein?coupled receptor that, in response to somatostatin, mediates inhibition of insulin, glucagon, and growth hormone release and thus may affect glucose homeostasis. RESEARCH DESIGN AND METHODS Ten single nucleotide polymorphisms (SNPs) spanning the gene were chosen using a SNP de...

Physiological concepts in physical education and sports training: stress, homeostasis and allostasis

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Tácito Pessoa de Souza Junior

2008-07-01

Full Text Available http://dx.doi.org/10.5007/1980-0037.2008v10n2p206 The objective of this review article is to discuss the concepts of stress and homeostasis (homeos = equal; stasis = stable and to expose their limitations on the basis of recent evidence demonstrating that the supposed internal stability of living organisms is merely apparent, and is even independent of environmental factors. This internal instability is often observed by researchers investigating circadian rhythms (hormone secretion, temporal series (heart rate and behavior (hunger and satiety, who argue in favor of substituting the theory of homeostasis by the concept of allostasis (allo = different; stasis = stable. Indeed, these researchers suggest that the objective of regulation and control is not stability. There are two consequences for Physical Education and Sport if allostasis is accepted as a physiological paradigm: 1. Selye’s concept of stress requires a new defi nition and interpretation, with a clear impact on the concept of load and overload; 2. Noakes’ central governor hypothesis to explain the fatigue resulting from intense physical exercise loses its relevance, as will be discussed in this paper. Furthermore, it is very diffi cult for the model of stability by staying the same to explain why performance is improved by physical training or why we have a predisposition for this type of recognizedly anti-homeostatic activity. We intend to demonstrate the possibility that the allostatic concept of stability through change can explain these contradictions.

Homeostasis, inflammation, and disease susceptibility.

Science.gov (United States)

Kotas, Maya E; Medzhitov, Ruslan

2015-02-26

While modernization has dramatically increased lifespan, it has also witnessed the increasing prevalence of diseases such as obesity, hypertension, and type 2 diabetes. Such chronic, acquired diseases result when normal physiologic control goes awry and may thus be viewed as failures of homeostasis. However, while nearly every process in human physiology relies on homeostatic mechanisms for stability, only some have demonstrated vulnerability to dysregulation. Additionally, chronic inflammation is a common accomplice of the diseases of homeostasis, yet the basis for this connection is not fully understood. Here we review the design of homeostatic systems and discuss universal features of control circuits that operate at the cellular, tissue, and organismal levels. We suggest a framework for classification of homeostatic signals that is based on different classes of homeostatic variables they report on. Finally, we discuss how adaptability of homeostatic systems with adjustable set points creates vulnerability to dysregulation and disease. This framework highlights the fundamental parallels between homeostatic and inflammatory control mechanisms and provides a new perspective on the physiological origin of inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Components of calcium homeostasis in Archaeon Methanobacterium thermoautotrophicum

International Nuclear Information System (INIS)

Varecka, L.; Smigan, P.; Vancek, M.; Greksak, M.

1998-01-01

The cells of Archaea are interesting from several points of view. Among others there are: (a) the evolutionary relationship to procaryotes and eucaryotes and (b) the involvement of Na + and H + gradient in archaeal bio-energetics. The observations are presented which are devoted to the description of components of Ca 2+ homeostasis, an apparatus is vital for both procaryotic and eukaryotic organisms, in obligate anaerobe Methanobacterium thermoautotrophicum. This is, after the demonstration of the ATP-dependent Ca 2+ transport in Halobacterium halobium membrane vesicles, the first complex description of processes of Ca 2+ homeostasis in Archaea. The Ca 2+ influx and efflux was measured using radionuclide 4 5 Ca 2+ . The experiment were performed under strictly anaerobic conditions. The measurement of the membrane potential by means of 3 H-tetraphenyl phosphonium chloride showed that the presence of Na + depolarized the membrane from -110 to -60 mV. The growth of M. thermoautotrophicum and methanogenesis was suppressed but nor arrested by the presence EGTA suggesting that the Ca 2+ homeostasis may be involved in controlling these cellular functions. The results indicate the presence of three components involved in establishing the Ca 2+ homeostasis in cell of M. thermoautotrophicum. The first is the Ca 2+ -carrier mediating the CA 2+ influx driven by the proton motive force or the membrane potential. The Ca 2+ efflux is mediated by two transport systems, Na + /Ca 2+ and H + /Ca 2+ anti-porters. The evidence for the presence of the Ca 2+ -transporting ATPase was not obtained so far. (authors)

Engineering redox homeostasis to develop efficient alcohol-producing microbial cell factories.

Science.gov (United States)

Zhao, Chunhua; Zhao, Qiuwei; Li, Yin; Zhang, Yanping

2017-06-24

The biosynthetic pathways of most alcohols are linked to intracellular redox homeostasis, which is crucial for life. This crucial balance is primarily controlled by the generation of reducing equivalents, as well as the (reduction)-oxidation metabolic cycle and the thiol redox homeostasis system. As a main oxidation pathway of reducing equivalents, the biosynthesis of most alcohols includes redox reactions, which are dependent on cofactors such as NADH or NADPH. Thus, when engineering alcohol-producing strains, the availability of cofactors and redox homeostasis must be considered. In this review, recent advances on the engineering of cellular redox homeostasis systems to accelerate alcohol biosynthesis are summarized. Recent approaches include improving cofactor availability, manipulating the affinity of redox enzymes to specific cofactors, as well as globally controlling redox reactions, indicating the power of these approaches, and opening a path towards improving the production of a number of different industrially-relevant alcohols in the near future.

Gut commensal flora: tolerance and homeostasis

OpenAIRE

Rescigno, Maria

2009-01-01

Commensal microorganisms are not ignored by the intestinal immune system. Recent evidence shows that commensals actively participate in maintaining intestinal immune homeostasis by interacting with intestinal epithelial cells and delivering tolerogenic signals that are transmitted to the underlying cells of the immune system.

Imbalanced immune homeostasis in immune thrombocytopenia.

Science.gov (United States)

Yazdanbakhsh, Karina

2016-04-01

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Abnormal chloride homeostasis in the substancia nigra pars reticulata contributes to locomotor deficiency in a model of acute liver injury.

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Yan-Ling Yang

Full Text Available BACKGROUND: Altered chloride homeostasis has been thought to be a risk factor for several brain disorders, while less attention has been paid to its role in liver disease. We aimed to analyze the involvement and possible mechanisms of altered chloride homeostasis of GABAergic neurons within the substantia nigra pars reticulata (SNr in the motor deficit observed in a model of encephalopathy caused by acute liver failure, by using glutamic acid decarboxylase 67 - green fluorescent protein knock-in transgenic mice. METHODS: Alterations in intracellular chloride concentration in GABAergic neurons within the SNr and changes in the expression of two dominant chloride homeostasis-regulating genes, KCC2 and NKCC1, were evaluated in mice with hypolocomotion due to hepatic encephalopathy (HE. The effects of pharmacological blockade and/or activation of KCC2 and NKCC1 functions with their specific inhibitors and/or activators on the motor activity were assessed. RESULTS: In our mouse model of acute liver injury, chloride imaging indicated an increase in local intracellular chloride concentration in SNr GABAergic neurons. In addition, the mRNA and protein levels of KCC2 were reduced, particularly on neuronal cell membranes; in contrast, NKCC1 expression remained unaffected. Furthermore, blockage of KCC2 reduced motor activity in the normal mice and led to a further deteriorated hypolocomotion in HE mice. Blockade of NKCC1 was not able to normalize motor activity in mice with liver failure. CONCLUSION: Our data suggest that altered chloride homeostasis is likely involved in the pathophysiology of hypolocomotion following HE. Drugs aimed at restoring normal chloride homeostasis would be a potential treatment for hepatic failure.

[Reliability theory based on quality risk network analysis for Chinese medicine injection].

Science.gov (United States)

Li, Zheng; Kang, Li-Yuan; Fan, Xiao-Hui

2014-08-01

A new risk analysis method based upon reliability theory was introduced in this paper for the quality risk management of Chinese medicine injection manufacturing plants. The risk events including both cause and effect ones were derived in the framework as nodes with a Bayesian network analysis approach. It thus transforms the risk analysis results from failure mode and effect analysis (FMEA) into a Bayesian network platform. With its structure and parameters determined, the network can be used to evaluate the system reliability quantitatively with probabilistic analytical appraoches. Using network analysis tools such as GeNie and AgenaRisk, we are able to find the nodes that are most critical to influence the system reliability. The importance of each node to the system can be quantitatively evaluated by calculating the effect of the node on the overall risk, and minimization plan can be determined accordingly to reduce their influences and improve the system reliability. Using the Shengmai injection manufacturing plant of SZYY Ltd as a user case, we analyzed the quality risk with both static FMEA analysis and dynamic Bayesian Network analysis. The potential risk factors for the quality of Shengmai injection manufacturing were identified with the network analysis platform. Quality assurance actions were further defined to reduce the risk and improve the product quality.

Children neglected: Where cumulative risk theory fails.

Science.gov (United States)

O'Hara, Mandy; Legano, Lori; Homel, Peter; Walker-Descartes, Ingrid; Rojas, Mary; Laraque, Danielle

2015-07-01

Neglected children, by far the majority of children maltreated, experience an environment most deficient in cognitive stimulation and language exchange. When physical abuse co-occurs with neglect, there is more stimulation through negative parent-child interaction, which may lead to better cognitive outcomes, contrary to Cumulative Risk Theory. The purpose of the current study was to assess whether children only neglected perform worse on cognitive tasks than children neglected and physically abused. Utilizing LONGSCAN archived data, 271 children only neglected and 101 children neglected and physically abused in the first four years of life were compared. The two groups were assessed at age 6 on the WPPSI-R vocabulary and block design subtests, correlates of cognitive intelligence. Regression analyses were performed, controlling for additional predictors of poor cognitive outcome, including socioeconomic variables and caregiver depression. Children only neglected scored significantly worse than children neglected and abused on the WPPSI-R vocabulary subtest (p=0.03). The groups did not differ on the block design subtest (p=0.4). This study shows that for neglected children, additional abuse may not additively accumulate risk when considering intelligence outcomes. Children experiencing only neglect may need to be referred for services that address cognitive development, with emphasis on the linguistic environment, in order to best support the developmental challenges of neglected children. Copyright © 2015 Elsevier Ltd. All rights reserved.

Probabilities and Shannon's Entropy in the Everett Many-Worlds Theory

Directory of Open Access Journals (Sweden)

Andreas Wichert

2016-12-01

Full Text Available Following a controversial suggestion by David Deutsch that decision theory can solve the problem of probabilities in the Everett many-worlds we suggest that the probabilities are induced by Shannon's entropy that measures the uncertainty of events. We argue that a relational person prefers certainty to uncertainty due to fundamental biological principle of homeostasis.

Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

Directory of Open Access Journals (Sweden)

Shan Meltzer

2017-10-01

Full Text Available Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked (eas, which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE synthesis, and two other enzymes in this synthesis pathway are required cell autonomously in sensory neurons for dendrite growth and stability. Furthermore, we show that the level of Sterol Regulatory Element-Binding Protein (SREBP activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis.

Natural disaster risk analysis for critical infrastructure systems: An approach based on statistical learning theory

International Nuclear Information System (INIS)

Guikema, Seth D.

2009-01-01

Probabilistic risk analysis has historically been developed for situations in which measured data about the overall reliability of a system are limited and expert knowledge is the best source of information available. There continue to be a number of important problem areas characterized by a lack of hard data. However, in other important problem areas the emergence of information technology has transformed the situation from one characterized by little data to one characterized by data overabundance. Natural disaster risk assessments for events impacting large-scale, critical infrastructure systems such as electric power distribution systems, transportation systems, water supply systems, and natural gas supply systems are important examples of problems characterized by data overabundance. There are often substantial amounts of information collected and archived about the behavior of these systems over time. Yet it can be difficult to effectively utilize these large data sets for risk assessment. Using this information for estimating the probability or consequences of system failure requires a different approach and analysis paradigm than risk analysis for data-poor systems does. Statistical learning theory, a diverse set of methods designed to draw inferences from large, complex data sets, can provide a basis for risk analysis for data-rich systems. This paper provides an overview of statistical learning theory methods and discusses their potential for greater use in risk analysis

Market Mechanism Design for Renewable Energy based on Risk Theory

Science.gov (United States)

Yang, Wu; Bo, Wang; Jichun, Liu; Wenjiao, Zai; Pingliang, Zeng; Haobo, Shi

2018-02-01

Generation trading between renewable energy and thermal power is an efficient market means for transforming supply structure of electric power into sustainable development pattern. But the trading is hampered by the output fluctuations of renewable energy and the cost differences between renewable energy and thermal power at present. In this paper, the external environmental cost (EEC) is defined and the EEC is introduced into the generation cost. At same time, the incentive functions of renewable energy and low-emission thermal power are designed, which are decreasing functions of EEC. On these bases, for the market risks caused by the random variability of EEC, the decision-making model of generation trading between renewable energy and thermal power is constructed according to the risk theory. The feasibility and effectiveness of the proposed model are verified by simulation results.

Chaperone-protease networks in mitochondrial protein homeostasis.

Science.gov (United States)

Voos, Wolfgang

2013-02-01

As essential organelles, mitochondria are intimately integrated into the metabolism of a eukaryotic cell. The maintenance of the functional integrity of the mitochondrial proteome, also termed protein homeostasis, is facing many challenges both under normal and pathological conditions. First, since mitochondria are derived from bacterial ancestor cells, the proteins in this endosymbiotic organelle have a mixed origin. Only a few proteins are encoded on the mitochondrial genome, most genes for mitochondrial proteins reside in the nuclear genome of the host cell. This distribution requires a complex biogenesis of mitochondrial proteins, which are mostly synthesized in the cytosol and need to be imported into the organelle. Mitochondrial protein biogenesis usually therefore comprises complex folding and assembly processes to reach an enzymatically active state. In addition, specific protein quality control (PQC) processes avoid an accumulation of damaged or surplus polypeptides. Mitochondrial protein homeostasis is based on endogenous enzymatic components comprising a diverse set of chaperones and proteases that form an interconnected functional network. This review describes the different types of mitochondrial proteins with chaperone functions and covers the current knowledge of their roles in protein biogenesis, folding, proteolytic removal and prevention of aggregation, the principal reactions of protein homeostasis. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. Copyright © 2012 Elsevier B.V. All rights reserved.

The Specific Roles of Vitamins in the Regulation of Immunosurveillance and Maintenance of Immunologic Homeostasis in the Gut

OpenAIRE

Hosomi, Koji; Kunisawa, Jun

2017-01-01

Vitamins are micronutrients which are essential for the maintenance of biological responses including immune system. Hence, vitamin deficiency increases a risk of infectious, allergic, and inflammatory diseases. Accumulating evidence has recently revealed the molecular and cellular mechanisms of vitamin-mediated regulation in the active and quiescent immune responses. In this review, we focus on the immunologic roles of vitamins in the regulation of homeostasis and surveillance in the gut.

The Research on Safety Management Information System of Railway Passenger Based on Risk Management Theory

Science.gov (United States)

Zhu, Wenmin; Jia, Yuanhua

2018-01-01

Based on the risk management theory and the PDCA cycle model, requirements of the railway passenger transport safety production is analyzed, and the establishment of the security risk assessment team is proposed to manage risk by FTA with Delphi from both qualitative and quantitative aspects. The safety production committee is also established to accomplish performance appraisal, which is for further ensuring the correctness of risk management results, optimizing the safety management business processes and improving risk management capabilities. The basic framework and risk information database of risk management information system of railway passenger transport safety are designed by Ajax, Web Services and SQL technologies. The system realizes functions about risk management, performance appraisal and data management, and provides an efficient and convenient information management platform for railway passenger safety manager.

Risk Modeling of Interdependent Complex Systems of Systems: Theory and Practice.

Science.gov (United States)

Haimes, Yacov Y

2018-01-01

The emergence of the complexity characterizing our systems of systems (SoS) requires a reevaluation of the way we model, assess, manage, communicate, and analyze the risk thereto. Current models for risk analysis of emergent complex SoS are insufficient because too often they rely on the same risk functions and models used for single systems. These models commonly fail to incorporate the complexity derived from the networks of interdependencies and interconnectedness (I-I) characterizing SoS. There is a need to reevaluate currently practiced risk analysis to respond to this reality by examining, and thus comprehending, what makes emergent SoS complex. The key to evaluating the risk to SoS lies in understanding the genesis of characterizing I-I of systems manifested through shared states and other essential entities within and among the systems that constitute SoS. The term "essential entities" includes shared decisions, resources, functions, policies, decisionmakers, stakeholders, organizational setups, and others. This undertaking can be accomplished by building on state-space theory, which is fundamental to systems engineering and process control. This article presents a theoretical and analytical framework for modeling the risk to SoS with two case studies performed with the MITRE Corporation and demonstrates the pivotal contributions made by shared states and other essential entities to modeling and analysis of the risk to complex SoS. A third case study highlights the multifarious representations of SoS, which require harmonizing the risk analysis process currently applied to single systems when applied to complex SoS. © 2017 Society for Risk Analysis.

Mean-variance model for portfolio optimization with background risk based on uncertainty theory

Science.gov (United States)

Zhai, Jia; Bai, Manying

2018-04-01

The aim of this paper is to develop a mean-variance model for portfolio optimization considering the background risk, liquidity and transaction cost based on uncertainty theory. In portfolio selection problem, returns of securities and assets liquidity are assumed as uncertain variables because of incidents or lacking of historical data, which are common in economic and social environment. We provide crisp forms of the model and a hybrid intelligent algorithm to solve it. Under a mean-variance framework, we analyze the portfolio frontier characteristic considering independently additive background risk. In addition, we discuss some effects of background risk and liquidity constraint on the portfolio selection. Finally, we demonstrate the proposed models by numerical simulations.

Liver immunology and its role in inflammation and homeostasis.

Science.gov (United States)

Robinson, Mark W; Harmon, Cathal; O'Farrelly, Cliona

2016-05-01

The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the non-diseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear 'dangerous' stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease.

Risk analysis of gravity dam instability using credibility theory Monte Carlo simulation model.

Science.gov (United States)

Xin, Cao; Chongshi, Gu

2016-01-01

Risk analysis of gravity dam stability involves complicated uncertainty in many design parameters and measured data. Stability failure risk ratio described jointly by probability and possibility has deficiency in characterization of influence of fuzzy factors and representation of the likelihood of risk occurrence in practical engineering. In this article, credibility theory is applied into stability failure risk analysis of gravity dam. Stability of gravity dam is viewed as a hybrid event considering both fuzziness and randomness of failure criterion, design parameters and measured data. Credibility distribution function is conducted as a novel way to represent uncertainty of influence factors of gravity dam stability. And combining with Monte Carlo simulation, corresponding calculation method and procedure are proposed. Based on a dam section, a detailed application of the modeling approach on risk calculation of both dam foundation and double sliding surfaces is provided. The results show that, the present method is feasible to be applied on analysis of stability failure risk for gravity dams. The risk assessment obtained can reflect influence of both sorts of uncertainty, and is suitable as an index value.

Calcium homeostasis in fly photoreceptor cells

NARCIS (Netherlands)

Oberwinkler, J

2002-01-01

In fly photoreceptor cells, two processes dominate the Ca2+ homeostasis: light-induced Ca2+ influx through members of the TRP family of ion channels, and Ca2+ extrusion by Na+/Ca2+ exchange.Ca2+ release from intracellular stores is quantitatively insignificant. Both, the light-activated channels and

Molecular monitoring of equine joint homeostasis

NARCIS (Netherlands)

de Grauw, J.C.

2010-01-01

Chronic joint disorders are a major cause of impaired mobility and loss of quality of life in both humans and horses. Regardless of the primary insult, any joint disorder is characterized by an upset in normal joint homeostasis, the balance between tissue anabolism and catabolism that is normally

Control of Immune Cell Homeostasis and Function by lncRNAs.

Science.gov (United States)

Mowel, Walter K; Kotzin, Jonathan J; McCright, Sam J; Neal, Vanessa D; Henao-Mejia, Jorge

2018-01-01

The immune system is composed of diverse cell types that coordinate responses to infection and maintain tissue homeostasis. In each of these cells, extracellular cues determine highly specific epigenetic landscapes and transcriptional profiles to promote immunity while maintaining homeostasis. New evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in epigenetic and transcriptional regulation in mammals. Thus, lncRNAs have emerged as key regulatory molecules of immune cell gene expression programs in response to microbial and tissue-derived cues. We review here how lncRNAs control the function and homeostasis of cell populations during immune responses, emphasizing the diverse molecular mechanisms by which lncRNAs tune highly contextualized transcriptional programs. In addition, we discuss the new challenges faced in interrogating lncRNA mechanisms and function in the immune system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sleep Homeostasis and Synaptic Plasticity

Science.gov (United States)

2017-06-01

Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202...circuit (a homeostat) that operates in concert with the circadian circuitry or does sleep drive accumulate everywhere in the brain? To answer these...neurons is capable of generating sleep drive. RNAi-mediated knockdown of insomniac in R2 neurons abolished sleep homeostasis without affecting baseline

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

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

2011-06-01

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

Grasshoppers regulate N:p stoichiometric homeostasis by changing phosphorus contents in their frass.

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Zhang, Zijia; Elser, James J; Cease, Arianne J; Zhang, Ximei; Yu, Qiang; Han, Xingguo; Zhang, Guangming

2014-01-01

Nitrogen (N) and phosphorus (P) are important limiting nutrients for plant production and consumer performance in a variety of ecosystems. As a result, the N:P stoichiometry of herbivores has received increased attention in ecology. However, the mechanisms by which herbivores maintain N:P stoichiometric homeostasis are poorly understood. Here, using a field manipulation experiment we show that the grasshopper Oedaleus asiaticus maintains strong N:P stoichiometric homeostasis regardless of whether grasshoppers were reared at low or high density. Grasshoppers maintained homeostasis by increasing P excretion when eating plants with higher P contents. However, while grasshoppers also maintained constant body N contents, we found no changes in N excretion in response to changing plant N content over the range measured. These results suggest that O. asiaticus maintains P homeostasis primarily by changing P absorption and excretion rates, but that other mechanisms may be more important for regulating N homeostasis. Our findings improve our understanding of consumer-driven P recycling and may help in understanding the factors affecting plant-herbivore interactions and ecosystem processes in grasslands.

Development of iron homeostasis in infants and young children.

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Lönnerdal, Bo

2017-12-01

Healthy, term, breastfed infants usually have adequate iron stores that, together with the small amount of iron that is contributed by breast milk, make them iron sufficient until ≥6 mo of age. The appropriate concentration of iron in infant formula to achieve iron sufficiency is more controversial. Infants who are fed formula with varying concentrations of iron generally achieve sufficiency with iron concentrations of 2 mg/L (i.e., with iron status that is similar to that of breastfed infants at 6 mo of age). Regardless of the feeding choice, infants' capacity to regulate iron homeostasis is important but less well understood than the regulation of iron absorption in adults, which is inverse to iron status and strongly upregulated or downregulated. Infants who were given daily iron drops compared with a placebo from 4 to 6 mo of age had similar increases in hemoglobin concentrations. In addition, isotope studies have shown no difference in iron absorption between infants with high or low hemoglobin concentrations at 6 mo of age. Together, these findings suggest a lack of homeostatic regulation of iron homeostasis in young infants. However, at 9 mo of age, homeostatic regulatory capacity has developed although, to our knowledge, its extent is not known. Studies in suckling rat pups showed similar results with no capacity to regulate iron homeostasis at 10 d of age when fully nursing, but such capacity occurred at 20 d of age when pups were partially weaned. The major iron transporters in the small intestine divalent metal-ion transporter 1 (DMT1) and ferroportin were not affected by pup iron status at 10 d of age but were strongly affected by iron status at 20 d of age. Thus, mechanisms that regulate iron homeostasis are developed at the time of weaning. Overall, studies in human infants and experimental animals suggest that iron homeostasis is absent or limited early in infancy largely because of a lack of regulation of the iron transporters DMT1 and ferroportin

Decision theory, the context for risk and reliability analysis

International Nuclear Information System (INIS)

Kaplan, S.

1985-01-01

According to this model of the decision process then, the optimum decision is that option having the largest expected utility. This is the fundamental model of a decision situation. It is necessary to remark that in order for the model to represent a real-life decision situation, it must include all the options present in that situation, including, for example, the option of not deciding--which is itself a decision, although usually not the optimum one. Similarly, it should include the option of delaying the decision while the authors gather further information. Both of these options have probabilities, outcomes, impacts, and utilities like any option and should be included explicitly in the decision diagram. The reason for doing a quantitative risk or reliability analysis is always that, somewhere underlying there is a decision to be made. The decision analysis therefore always forms the context for the risk or reliability analysis, and this context shapes the form and language of that analysis. Therefore, they give in this section a brief review of the well-known decision theory diagram

Combination of uncertainty theories and decision-aiding methods for natural risk management in a context of imperfect information

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Tacnet, Jean-Marc; Dupouy, Guillaume; Carladous, Simon; Dezert, Jean; Batton-Hubert, Mireille

2017-04-01

In mountain areas, natural phenomena such as snow avalanches, debris-flows and rock-falls, put people and objects at risk with sometimes dramatic consequences. Risk is classically considered as a combination of hazard, the combination of the intensity and frequency of the phenomenon, and vulnerability which corresponds to the consequences of the phenomenon on exposed people and material assets. Risk management consists in identifying the risk level as well as choosing the best strategies for risk prevention, i.e. mitigation. In the context of natural phenomena in mountainous areas, technical and scientific knowledge is often lacking. Risk management decisions are therefore based on imperfect information. This information comes from more or less reliable sources ranging from historical data, expert assessments, numerical simulations etc. Finally, risk management decisions are the result of complex knowledge management and reasoning processes. Tracing the information and propagating information quality from data acquisition to decisions are therefore important steps in the decision-making process. One major goal today is therefore to assist decision-making while considering the availability, quality and reliability of information content and sources. A global integrated framework is proposed to improve the risk management process in a context of information imperfection provided by more or less reliable sources: uncertainty as well as imprecision, inconsistency and incompleteness are considered. Several methods are used and associated in an original way: sequential decision context description, development of specific multi-criteria decision-making methods, imperfection propagation in numerical modeling and information fusion. This framework not only assists in decision-making but also traces the process and evaluates the impact of information quality on decision-making. We focus and present two main developments. The first one relates to uncertainty and imprecision

High fat diet disrupts endoplasmic reticulum calcium homeostasis in the rat liver.

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Wires, Emily S; Trychta, Kathleen A; Bäck, Susanne; Sulima, Agnieszka; Rice, Kenner C; Harvey, Brandon K

2017-11-01

Disruption to endoplasmic reticulum (ER) calcium homeostasis has been implicated in obesity, however, the ability to longitudinally monitor ER calcium fluctuations has been challenging with prior methodologies. We recently described the development of a Gaussia luciferase (GLuc)-based reporter protein responsive to ER calcium depletion (GLuc-SERCaMP) and investigated the effect of a high fat diet on ER calcium homeostasis. A GLuc-based reporter cell line was treated with palmitate, a free fatty acid. Rats intrahepatically injected with GLuc-SERCaMP reporter were fed a cafeteria diet or high fat diet. The liver and plasma were examined for established markers of steatosis and compared to plasma levels of SERCaMP activity. Palmitate induced GLuc-SERCaMP release in vitro, indicating ER calcium depletion. Consumption of a cafeteria diet or high fat pellets correlated with alterations to hepatic ER calcium homeostasis in rats, shown by increased GLuc-SERCaMP release. Access to ad lib high fat pellets also led to a corresponding decrease in microsomal calcium ATPase activity and an increase in markers of hepatic steatosis. In addition to GLuc-SERCaMP, we have also identified endogenous proteins (endogenous SERCaMPs) with a similar response to ER calcium depletion. We demonstrated the release of an endogenous SERCaMP, thought to be a liver esterase, during access to a high fat diet. Attenuation of both GLuc-SERCaMP and endogenous SERCaMP was observed during dantrolene administration. Here we describe the use of a reporter for in vitro and in vivo models of high fat diet. Our results support the theory that dietary fat intake correlates with a decrease in ER calcium levels in the liver and suggest a high fat diet alters the ER proteome. Lay summary: ER calcium dysregulation was observed in rats fed a cafeteria diet or high fat pellets, with fluctuations in sensor release correlating with fat intake. Attenuation of sensor release, as well as food intake was observed during

Theory of planned behavior interventions for reducing heterosexual risk behaviors: A meta-analysis.

Science.gov (United States)

Tyson, Mandy; Covey, Judith; Rosenthal, Harriet E S

2014-12-01

The meta-analysis reported here examined interventions informed by the theory of planned behavior (TPB) or theory of reasoned action (TRA) aimed at reducing heterosexual risk behaviors (prevention of STDs and unwanted pregnancy). Studies were eligible for inclusion if they were either randomized control trials or quasi-experimental studies that compared the TPB-based intervention against a control group. Search strategy consisted of articles identified in previous reviews, keyword search through search engines, examination of key journals, and contacting key experts. Forty-seven intervention studies were included in the meta-analysis. Random effects models revealed that pooled effect sizes for TPB-based interventions had small but significant effects on behavior and other secondary outcomes (i.e., knowledge, attitudes, normative beliefs, perceived behavioral control, and intentions). Significant heterogeneity found between effect sizes was explored using metaregression. Larger effects were found for interventions that provided opportunities for social comparison. The TPB provides a valuable framework for designing interventions to change heterosexual risk behaviors. However, effect sizes varied quite substantially between studies, and further research is needed to explore the reasons why.

Mitochondrial Iron Transport and Homeostasis in Plants

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Anshika eJain

2013-09-01

Full Text Available Iron (Fe is an essential nutrient for plants and although the mechanisms controlling iron uptake from the soil are relatively well understood, comparatively little is known about subcellular trafficking of iron in plant cells. Mitochondria represent a significant iron sink within cells, as iron is required for the proper functioning of respiratory chain protein complexes. Mitochondria are a site of Fe-S cluster synthesis, and possibly heme synthesis as well. Here we review recent insights into the molecular mechanisms controlling mitochondrial iron transport and homeostasis. We focus on the recent identification of a mitochondrial iron uptake transporter in rice and a possible role for metalloreductases in iron uptake by mitochondria. In addition, we highlight recent advances in mitochondrial iron homeostasis with an emphasis on the roles of frataxin and ferritin in iron trafficking and storage within mitochondria.

On residual stresses and homeostasis: an elastic theory of functional adaptation in living matter.

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Ciarletta, P; Destrade, M; Gower, A L

2016-04-26

Living matter can functionally adapt to external physical factors by developing internal tensions, easily revealed by cutting experiments. Nonetheless, residual stresses intrinsically have a complex spatial distribution, and destructive techniques cannot be used to identify a natural stress-free configuration. This work proposes a novel elastic theory of pre-stressed materials. Imposing physical compatibility and symmetry arguments, we define a new class of free energies explicitly depending on the internal stresses. This theory is finally applied to the study of arterial remodelling, proving its potential for the non-destructive determination of the residual tensions within biological materials.

Enteric Virome Sensing—Its Role in Intestinal Homeostasis and Immunity

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Rebecca N. Metzger

2018-03-01

Full Text Available Pattern recognition receptors (PRRs sensing commensal microorganisms in the intestine induce tightly controlled tonic signaling in the intestinal mucosa, which is required to maintain intestinal barrier integrity and immune homeostasis. At the same time, PRR signaling pathways rapidly trigger the innate immune defense against invasive pathogens in the intestine. Intestinal epithelial cells and mononuclear phagocytes in the intestine and the gut-associated lymphoid tissues are critically involved in sensing components of the microbiome and regulating immune responses in the intestine to sustain immune tolerance against harmless antigens and to prevent inflammation. These processes have been mostly investigated in the context of the bacterial components of the microbiome so far. The impact of viruses residing in the intestine and the virus sensors, which are activated by these enteric viruses, on intestinal homeostasis and inflammation is just beginning to be unraveled. In this review, we will summarize recent findings indicating an important role of the enteric virome for intestinal homeostasis as well as pathology when the immune system fails to control the enteric virome. We will provide an overview of the virus sensors and signaling pathways, operative in the intestine and the mononuclear phagocyte subsets, which can sense viruses and shape the intestinal immune response. We will discuss how these might interact with resident enteric viruses directly or in context with the bacterial microbiome to affect intestinal homeostasis.

Enteric Virome Sensing-Its Role in Intestinal Homeostasis and Immunity.

Science.gov (United States)

Metzger, Rebecca N; Krug, Anne B; Eisenächer, Katharina

2018-03-23

Pattern recognition receptors (PRRs) sensing commensal microorganisms in the intestine induce tightly controlled tonic signaling in the intestinal mucosa, which is required to maintain intestinal barrier integrity and immune homeostasis. At the same time, PRR signaling pathways rapidly trigger the innate immune defense against invasive pathogens in the intestine. Intestinal epithelial cells and mononuclear phagocytes in the intestine and the gut-associated lymphoid tissues are critically involved in sensing components of the microbiome and regulating immune responses in the intestine to sustain immune tolerance against harmless antigens and to prevent inflammation. These processes have been mostly investigated in the context of the bacterial components of the microbiome so far. The impact of viruses residing in the intestine and the virus sensors, which are activated by these enteric viruses, on intestinal homeostasis and inflammation is just beginning to be unraveled. In this review, we will summarize recent findings indicating an important role of the enteric virome for intestinal homeostasis as well as pathology when the immune system fails to control the enteric virome. We will provide an overview of the virus sensors and signaling pathways, operative in the intestine and the mononuclear phagocyte subsets, which can sense viruses and shape the intestinal immune response. We will discuss how these might interact with resident enteric viruses directly or in context with the bacterial microbiome to affect intestinal homeostasis.

Molecular aspects of bacterial pH sensing and homeostasis

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Krulwich, Terry A.; Sachs, George; Padan, Etana

2011-01-01

Diverse mechanisms for pH-sensing and cytoplasmic pH homeostasis enable most bacteria to tolerate or grow at external pH values that are outside the cytoplasmic pH range they must maintain for growth. The most extreme cases are exemplified by the extremophiles that inhabit environments whose pH is below 3 or above 11. Here we describe how recent insights into the structure and function of key molecules and their regulators reveal novel strategies of bacterial pH-homeostasis. These insights may help us better target certain pathogens and better harness the capacities of environmental bacteria. PMID:21464825

A Cross-Age Study of Student Understanding of the Concept of Homeostasis.

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Westbrook, Susan L.; Marek, Edmund A.

1992-01-01

The conceptual views of homeostasis held by students (n=300) in seventh grade life science, tenth grade biology, and college zoology were examined. A biographical questionnaire, the results from two Piagetian-like developmental tasks, and a concept evaluation statement of homeostasis were collected from each student. Understanding of the concept…

Reducing skin cancer risk: an intervention based on protection motivation theory.

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McClendon, B T; Prentice-Dunn, S

2001-05-01

Caucasian college students who intentionally tanned participated in a brief skin cancer intervention based on protection motivation theory (PMT). This intervention targeted skin appearance and consisted of brief lectures, a comprehensive essay, video clips about a young man who died of melanoma, and short discussions. Compared to a waitlist control group, the intervention group showed increases on PMT variables and intentions at post-test. The waitlist group later received the intervention and showed similar increases. Additionally, all but one PMT variable maintained post-test levels at a one-month follow-up. Photographs taken at post-test and at the one-month follow-up were judged by raters blind to the hypothesis. Seventy-two percent of participants were judged to have lighter skin whereas only 16 percent had darker skin. These results provide additional support for theory-based methods for changing maladaptive attitudes and behaviors associated with skin cancer risk.

A Novel Dynamic Algorithm for IT Outsourcing Risk Assessment Based on Transaction Cost Theory

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Guodong Cong

2015-01-01

Full Text Available With the great risk exposed in IT outsourcing, how to assess IT outsourcing risk becomes a critical issue. However, most of approaches to date need to further adapt to the particular complexity of IT outsourcing risk for either falling short in subjective bias, inaccuracy, or efficiency. This paper proposes a dynamic algorithm of risk assessment. It initially forwards extended three layers (risk factors, risks, and risk consequences of transferring mechanism based on transaction cost theory (TCT as the framework of risk analysis, which bridges the interconnection of components in three layers with preset transferring probability and impact. Then, it establishes an equation group between risk factors and risk consequences, which assures the “attribution” more precisely to track the specific sources that lead to certain loss. Namely, in each phase of the outsourcing lifecycle, both the likelihood and the loss of each risk factor and those of each risk are acquired through solving equation group with real data of risk consequences collected. In this “reverse” way, risk assessment becomes a responsive and interactive process with real data instead of subjective estimation, which improves the accuracy and alleviates bias in risk assessment. The numerical case proves the effectiveness of the algorithm compared with the approach forwarded by other references.

Role of perisynaptic parameters in neurotransmitter homeostasis - computational study of a general synapse

Science.gov (United States)

Pendyam, Sandeep; Mohan, Ashwin; Kalivas, Peter W.; Nair, Satish S.

2015-01-01

Extracellular neurotransmitter concentrations vary over a wide range depending on the type of neurotransmitter and location in the brain. Neurotransmitter homeostasis near a synapse is achieved by a balance of several mechanisms including vesicular release from the presynapse, diffusion, uptake by transporters, non-synaptic production, and regulation of release by autoreceptors. These mechanisms are also affected by the glia surrounding the synapse. However, the role of these mechanisms in achieving neurotransmitter homeostasis is not well understood. A biophysical modeling framework was proposed to reverse engineer glial configurations and parameters related to homeostasis for synapses that support a range of neurotransmitter gradients. Model experiments reveal that synapses with extracellular neurotransmitter concentrations in the micromolar range require non-synaptic neurotransmitter sources and tight synaptic isolation by extracellular glial formations. The model was used to identify the role of perisynaptic parameters on neurotransmitter homeostasis, and to propose glial configurations that could support different levels of extracellular neurotransmitter concentrations. Ranking the parameters based on their effect on neurotransmitter homeostasis, non-synaptic sources were found to be the most important followed by transporter concentration and diffusion coefficient. PMID:22460547

Using the Ubiquitin-modified Proteome to Monitor Distinct and Spatially Restricted Protein Homeostasis Dysfunction.

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Gendron, Joshua M; Webb, Kristofor; Yang, Bing; Rising, Lisa; Zuzow, Nathan; Bennett, Eric J

2016-08-01

Protein homeostasis dysfunction has been implicated in the development and progression of aging related human pathologies. There is a need for the establishment of quantitative methods to evaluate global protein homoeostasis function. As the ubiquitin (ub) proteasome system plays a key role in regulating protein homeostasis, we applied quantitative proteomic methods to evaluate the sensitivity of site-specific ubiquitylation events as markers for protein homeostasis dysfunction. Here, we demonstrate that the ub-modified proteome can exceed the sensitivity of engineered fluorescent reporters as a marker for proteasome dysfunction and can provide unique signatures for distinct proteome challenges which is not possible with engineered reporters. We demonstrate that combining ub-proteomics with subcellular fractionation can effectively separate degradative and regulatory ubiquitylation events on distinct protein populations. Using a recently developed potent inhibitor of the critical protein homeostasis factor p97/VCP, we demonstrate that distinct insults to protein homeostasis function can elicit robust and largely unique alterations to the ub-modified proteome. Taken together, we demonstrate that proteomic approaches to monitor the ub-modified proteome can be used to evaluate global protein homeostasis and can be used to monitor distinct functional outcomes for spatially separated protein populations. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

[Glucose homeostasis and gut-brain connection].

Science.gov (United States)

De Vadder, Filipe; Mithieux, Gilles

2015-02-01

Since the XIX(th) century, the brain has been known for its role in regulating food intake (via the control of hunger sensation) and glucose homeostasis. Further interest has come from the discovery of gut hormones, which established a clear link between the gut and the brain in regulating glucose and energy homeostasis. The brain has two particular structures, the hypothalamus and the brainstem, which are sensitive to information coming either from peripheral organs or from the gut (via circulating hormones or nutrients) about the nutritional status of the organism. However, the efforts for a better understanding of these mechanisms have allowed to unveil a new gut-brain neural axis as a key regulator of the metabolic status of the organism. Certain nutrients control the hypothalamic homeostatic function via this axis. In this review, we describe how the gut is connected to the brain via different neural pathways, and how the interplay between these two organs drives the energy balance. © 2015 médecine/sciences – Inserm.

Innate immunity orchestrates adipose tissue homeostasis.

Science.gov (United States)

Lin, Yi-Wei; Wei, Li-Na

2017-06-23

Obesity is strongly associated with multiple diseases including insulin resistance, type 2 diabetes, cardiovascular diseases, fatty liver disease, neurodegenerative diseases and cancers, etc. Adipose tissue (AT), mainly brown AT (BAT) and white AT (WAT), is an important metabolic and endocrine organ that maintains whole-body homeostasis. BAT contributes to non-shivering thermogenesis in a cold environment; WAT stores energy and produces adipokines that fine-tune metabolic and inflammatory responses. Obesity is often characterized by over-expansion and inflammation of WAT where inflammatory cells/mediators are abundant, especially pro-inflammatory (M1) macrophages, resulting in chronic low-grade inflammation and leading to insulin resistance and metabolic complications. Macrophages constitute the major component of innate immunity and can be activated as a M1 or M2 (anti-inflammatory) phenotype in response to environmental stimuli. Polarized M1 macrophage causes AT inflammation, whereas polarized M2 macrophage promotes WAT remodeling into the BAT phenotype, also known as WAT browning/beiging, which enhances insulin sensitivity and metabolic health. This review will discuss the regulation of AT homeostasis in relation to innate immunity.

Sexual transmission-risk behaviour among HIV-positive persons: a multisite study using social action theory.

Science.gov (United States)

Sullivan, Kathleen M; Dawson Rose, Carol; Phillips, J Craig; Holzemer, William L; Webel, Allison R; Nicholas, Patrice; Corless, Inge B; Kirksey, Kenn; Sanzero Eller, Lucille; Voss, Joachim; Tyer-Viola, Lynda; Portillo, Carmen; Johnson, Mallory O; Brion, John; Sefcik, Elizabeth; Nokes, Kathleen; Reid, Paula; Rivero-Mendez, Marta; Chen, Wei-Ti

2017-01-01

Sexual risk behaviour was explored and described using Social Action Theory. The sexual transmission of HIV is complex and multi-factorial. Social Action Theory provides a framework for viewing self-regulation of modifiable behaviour such as condom use. Condom use is viewed within the context of social interaction and interdependence. Cross-sectional survey. Self-report questionnaire administered to adults living with HIV/AIDS, recruited from clinics, service organizations and by active outreach, between 2010 - 2011. Having multiple sex partners with inconsistent condom use during a 3-month recall period was associated with being male, younger age, having more years of education,substance use frequency and men having sex with men being a mode of acquiring HIV. In addition, lower self-efficacy for condom use scores were associated with having multiple sex partners and inconsistent condom use. Social Action Theory provided a framework for organizing data from an international sample of seropositive persons. Interventions for sexually active, younger, HIV positive men who have sex with men, that strengthen perceived efficacy for condom use, and reduce the frequency of substance use, may contribute to reducing HIV-transmission risk. © 2016 John Wiley & Sons Ltd.

Prospect theory or construal level theory? Diminishing sensitivity vs. psychological distance in risky decisions

NARCIS (Netherlands)

Trautmann, S.T.; van de Kuilen, G.

2012-01-01

Attitudes toward risks are central to organizational decisions. These attitudes are commonly modeled by prospect theory. Construal level theory has been proposed as an alternative theory of risky choice, accounting for psychological distance deriving from temporal, spatial and social aspects of risk

A Grey Theory Based Approach to Big Data Risk Management Using FMEA

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Maisa Mendonça Silva

2016-01-01

Full Text Available Big data is the term used to denote enormous sets of data that differ from other classic databases in four main ways: (huge volume, (high velocity, (much greater variety, and (big value. In general, data are stored in a distributed fashion and on computing nodes as a result of which big data may be more susceptible to attacks by hackers. This paper presents a risk model for big data, which comprises Failure Mode and Effects Analysis (FMEA and Grey Theory, more precisely grey relational analysis. This approach has several advantages: it provides a structured approach in order to incorporate the impact of big data risk factors; it facilitates the assessment of risk by breaking down the overall risk to big data; and finally its efficient evaluation criteria can help enterprises reduce the risks associated with big data. In order to illustrate the applicability of our proposal in practice, a numerical example, with realistic data based on expert knowledge, was developed. The numerical example analyzes four dimensions, that is, managing identification and access, registering the device and application, managing the infrastructure, and data governance, and 20 failure modes concerning the vulnerabilities of big data. The results show that the most important aspect of risk to big data relates to data governance.

Extreme Value Theory and Value at Risk. Application to oil market

International Nuclear Information System (INIS)

Marimoutou, Velayoudoum; Raggad, Bechir; Trabelsi, Abdelwahed

2009-01-01

Recent increases in energy prices, especially oil prices, have become a principal concern for consumers, corporations, and governments. Most analysts believe that oil price fluctuations have considerable consequences on economic activity. Oil markets have become relatively free, resulting in a high degree of oil-price volatility and generating radical changes to world energy and oil industries. Consequently, oil markets are naturally vulnerable to significant high price shifts. An example of such a case is the oil embargo crisis of 1973. In this newly created climate, protection against market risk has become a necessity. Value at Risk (VaR) measures risk exposure at a given probability level and is very important for risk management. Appealing aspects of Extreme Value Theory (EVT) have made convincing arguments for its use in managing energy price risks. In this paper, we model VaR for long and short trading positions in oil market by applying both unconditional and conditional EVT models to forecast Value at Risk. These models are compared to the performances of other well-known modelling techniques, such as GARCH, Historical Simulation and Filtered Historical Simulation. Both conditional EVT and Filtered Historical Simulation procedures offer a major improvement over the conventional methods. Furthermore, GARCH(1, 1)-t model may provide equally good results which are comparable to two combined procedures. Finally, our results confirm the importance of filtering process for the success of standard approaches. (author)

Extreme Value Theory and Value at Risk. Application to oil market

Energy Technology Data Exchange (ETDEWEB)

Marimoutou, Velayoudoum [GREQAM, Universite de la Mediterranee, Institut Francais de Pondichery (France); Raggad, Bechir; Trabelsi, Abdelwahed [BESTMOD, Institut Superieur de Gestion de Tunis (Tunisia)

2009-07-15

Recent increases in energy prices, especially oil prices, have become a principal concern for consumers, corporations, and governments. Most analysts believe that oil price fluctuations have considerable consequences on economic activity. Oil markets have become relatively free, resulting in a high degree of oil-price volatility and generating radical changes to world energy and oil industries. Consequently, oil markets are naturally vulnerable to significant high price shifts. An example of such a case is the oil embargo crisis of 1973. In this newly created climate, protection against market risk has become a necessity. Value at Risk (VaR) measures risk exposure at a given probability level and is very important for risk management. Appealing aspects of Extreme Value Theory (EVT) have made convincing arguments for its use in managing energy price risks. In this paper, we model VaR for long and short trading positions in oil market by applying both unconditional and conditional EVT models to forecast Value at Risk. These models are compared to the performances of other well-known modelling techniques, such as GARCH, Historical Simulation and Filtered Historical Simulation. Both conditional EVT and Filtered Historical Simulation procedures offer a major improvement over the conventional methods. Furthermore, GARCH(1, 1)-t model may provide equally good results which are comparable to two combined procedures. Finally, our results confirm the importance of filtering process for the success of standard approaches. (author)

State of immunity and homeostasis systems of Kiev inhabitants in 6 years after the Chernobyl NPP accident

International Nuclear Information System (INIS)

Babenko, A.Yu.; Mel'nik, V.V.; Ternovoj, K.S.; Khudyakova, E.V.; Bitko, V.N.; Dibrova, T.L.; Kulakovskij, V.I.; Salabaj, P.V.; Sobolevskij, V.M.; Selezneva, T.N.; Tarusina, V.N.; Vishnevskaya, E.Yu.; Karachentseva, A.I.; Ermekova, V.M.

1994-01-01

Changes in the immunological system and homeostasis in the blood serum of random Kiev's donors of 1992 in compare to Kiev's donors of 1986 and donors from different regions were shown. The activity of the Complement system and the thymac serum activity decreased; autoimmune antibodies to chromatin appeared in the blood of 15% of donors; the level of low molecular weight immune circulating complexes increased; the light-scattering technique supposed the elevation of risk of autoimmune diseases and leucosis for Kievite's donors

Exploring sexual risk taking among American Indian adolescents through protection motivation theory.

Science.gov (United States)

Chambers, Rachel; Tingey, Lauren; Mullany, Britta; Parker, Sean; Lee, Angelita; Barlow, Allison

2016-09-01

This paper examines decision-making around sexual behavior among reservation-based American Indian youth. Focus group discussions were conducted with youth ages 13-19 years old. Through these discussions, we explored youth's knowledge, attitudes and behaviors related to sexual risk taking through the lens of the protection motivation theory to inform the adaptation of an evidence-based HIV prevention intervention. Findings suggest that condom use self-efficacy and HIV prevention knowledge is low, vulnerability to sexually transmitted infections is lacking and alcohol plays a significant role in sexual risk taking in this population. In addition, parental monitoring and peer influence may contribute to or protect against sexual risk taking. Results suggest that future HIV prevention interventions should be delivered to gender-specific peer groups, include a parental component, teach sexual health education and communication skills, integrate substance-use prevention, and work to remove stigma around obtaining and using condoms.

Microbiota-Dependent Crosstalk Between Macrophages and ILC3 Promotes Intestinal Homeostasis

Science.gov (United States)

Mortha, Arthur; Chudnovskiy, Aleksey; Hashimoto, Daigo; Bogunovic, Milena; Spencer, Sean P.; Belkaid, Yasmine; Merad, Miriam

2014-01-01

The intestinal microbiota and tissue-resident myeloid cells promote immune responses that maintain intestinal homeostasis in the host. However, the cellular cues that translate microbial signals into intestinal homeostasis remain unclear. Here, we show that deficient granulocyte-macrophage colony-stimulating factor (GM-CSF) production altered mononuclear phagocyte effector functions and led to reduced regulatory T cell (Treg) numbers and impaired oral tolerance. We observed that RORγt+ innate lymphoid cells (ILCs) are the primary source of GM-CSF in the gut and that ILC-driven GM-CSF production was dependent on the ability of macrophages to sense microbial signals and produce interleukin-1β. Our findings reveal that commensal microbes promote a crosstalk between innate myeloid and lymphoid cells that leads to immune homeostasis in the intestine. PMID:24625929

Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis.

Science.gov (United States)

Mortha, Arthur; Chudnovskiy, Aleksey; Hashimoto, Daigo; Bogunovic, Milena; Spencer, Sean P; Belkaid, Yasmine; Merad, Miriam

2014-03-28

The intestinal microbiota and tissue-resident myeloid cells promote immune responses that maintain intestinal homeostasis in the host. However, the cellular cues that translate microbial signals into intestinal homeostasis remain unclear. Here, we show that deficient granulocyte-macrophage colony-stimulating factor (GM-CSF) production altered mononuclear phagocyte effector functions and led to reduced regulatory T cell (T(reg)) numbers and impaired oral tolerance. We observed that RORγt(+) innate lymphoid cells (ILCs) are the primary source of GM-CSF in the gut and that ILC-driven GM-CSF production was dependent on the ability of macrophages to sense microbial signals and produce interleukin-1β. Our findings reveal that commensal microbes promote a crosstalk between innate myeloid and lymphoid cells that leads to immune homeostasis in the intestine.

Targeting Cardiomyocyte Ca2+ Homeostasis in Heart Failure

Science.gov (United States)

Røe, Åsmund T.; Frisk, Michael; Louch, William E.

2015-01-01

Improved treatments for heart failure patients will require the development of novel therapeutic strategies that target basal disease mechanisms. Disrupted cardiomyocyte Ca2+ homeostasis is recognized as a major contributor to the heart failure phenotype, as it plays a key role in systolic and diastolic dysfunction, arrhythmogenesis, and hypertrophy and apoptosis signaling. In this review, we outline existing knowledge of the involvement of Ca2+ homeostasis in these deficits, and identify four promising targets for therapeutic intervention: the sarcoplasmic reticulum Ca2+ ATPase, the Na+-Ca2+ exchanger, the ryanodine receptor, and t-tubule structure. We discuss experimental data indicating the applicability of these targets that has led to recent and ongoing clinical trials, and suggest future therapeutic approaches. PMID:25483944

Central insulin action in energy and glucose homeostasis.

Science.gov (United States)

Plum, Leona; Belgardt, Bengt F; Brüning, Jens C

2006-07-01

Insulin has pleiotropic biological effects in virtually all tissues. However, the relevance of insulin signaling in peripheral tissues has been studied far more extensively than its role in the brain. An evolving body of evidence indicates that in the brain, insulin is involved in multiple regulatory mechanisms including neuronal survival, learning, and memory, as well as in regulation of energy homeostasis and reproductive endocrinology. Here we review insulin's role as a central homeostatic signal with regard to energy and glucose homeostasis and discuss the mechanisms by which insulin communicates information about the body's energy status to the brain. Particular emphasis is placed on the controversial current debate about the similarities and differences between hypothalamic insulin and leptin signaling at the molecular level.

Redox Homeostasis in Pancreatic beta Cells

Czech Academy of Sciences Publication Activity Database

Ježek, Petr; Dlasková, Andrea; Plecitá-Hlavatá, Lydie

2012-01-01

Roč. 2012, č. 2012 (2012), s. 932838 ISSN 1942-0900 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GPP304/10/P204 Institutional support: RVO:67985823 Keywords : beta cells * reactive oxygen species homeostasis * mitochondria Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.393, year: 2012

Response of normal stem cells to ionizing radiation: A balance between homeostasis and genomic stability

International Nuclear Information System (INIS)

Harfouche, G.; Martin, M.T.

2010-01-01

Stem cells have been described in most adult tissues, where they play a key role in maintaining tissue homeostasis. As they self-renew throughout life, accumulating genetic anomalies can compromise their genomic integrity and potentially give rise to cancer. Stem cells (SCs) may thus be a major target of radiation carcinogenesis. In addition, unrepaired genotoxic damage may cause cell death and stem cell pool depletion, impairing lineage functionality and accelerating aging. Developments in SC biology enabled the characterization of the responses of stem cells to genotoxic stress and their role in tissue damage. We here examine how these cells react to ionizing radiation (IR), and more specifically their radiosensitivity, stress signaling and DNA repair. We first review embryonic SCs, as a paradigm of primitive pluri-potent cells, then three adult tissues, bone marrow, skin and intestine, capable of long-term regeneration and at high risk for acute radiation syndromes and long-term carcinogenesis. We discuss IR disruption of the fine balance between maintenance of tissue homeostasis and genomic stability. We show that stem cell radiosensitivity does not follow a unique model, but differs notably according to the turnover rates of the tissues. (authors)

Transcranial electrical stimulation accelerates human sleep homeostasis.

Directory of Open Access Journals (Sweden)

Davide Reato

Full Text Available The sleeping brain exhibits characteristic slow-wave activity which decays over the course of the night. This decay is thought to result from homeostatic synaptic downscaling. Transcranial electrical stimulation can entrain slow-wave oscillations (SWO in the human electro-encephalogram (EEG. A computational model of the underlying mechanism predicts that firing rates are predominantly increased during stimulation. Assuming that synaptic homeostasis is driven by average firing rates, we expected an acceleration of synaptic downscaling during stimulation, which is compensated by a reduced drive after stimulation. We show that 25 minutes of transcranial electrical stimulation, as predicted, reduced the decay of SWO in the remainder of the night. Anatomically accurate simulations of the field intensities on human cortex precisely matched the effect size in different EEG electrodes. Together these results suggest a mechanistic link between electrical stimulation and accelerated synaptic homeostasis in human sleep.

Dynamic thiol/disulfide homeostasis and effects of smoking on homeostasis parameters in patients with psoriasis.

Science.gov (United States)

Emre, Selma; Demirseren, Duriye Deniz; Alisik, Murat; Aktas, Akin; Neselioglu, Salim; Erel, Ozcan

2017-12-01

Recently, increased reactive oxygen species (ROS), reduced antioxidant capacity, and oxidative stress have been suggested in the pathogenesis of psoriasis. The aim of this study to evaluate the thiol/disulfide homeostasis in patients with psoriasis. Ninety patients with psoriasis who did not receive any systemic treatment in the last six  months were included in the study. Seventy-six age and gender-matched healthy volunteers served as control group. Thiol/disulfide homeostasis was measured in venous blood samples obtained from patient and control groups. Native thiol and total thiol levels were significantly higher in patients than in control group. When thiol/disulfide hemostasis parameters and clinical and demographic characteristics were compared, a negative correlation was detected between native thiol and total thiol with age. The levels of total thiols had also negative correlation with PASI and duration of the disease. When we divided the patients into smokers and non-smokers, native thiol and total thiol levels were significantly higher in smokers than in controls, whereas native thiol and total thiol levels were comparable in non-smoker patients and controls. Thiol/disulfide balance shifted towards thiol in psoriasis patients and this may be responsible for increased keratinocyte proliferation in the pathogenesis of psoriasis.

Time Factor in the Theory of Anthropogenic Risk Prediction in Complex Dynamic Systems

Science.gov (United States)

Ostreikovsky, V. A.; Shevchenko, Ye N.; Yurkov, N. K.; Kochegarov, I. I.; Grishko, A. K.

2018-01-01

The article overviews the anthropogenic risk models that take into consideration the development of different factors in time that influence the complex system. Three classes of mathematical models have been analyzed for the use in assessing the anthropogenic risk of complex dynamic systems. These models take into consideration time factor in determining the prospect of safety change of critical systems. The originality of the study is in the analysis of five time postulates in the theory of anthropogenic risk and the safety of highly important objects. It has to be stressed that the given postulates are still rarely used in practical assessment of equipment service life of critically important systems. That is why, the results of study presented in the article can be used in safety engineering and analysis of critically important complex technical systems.

Competing risk theory and radiation risk assessment

International Nuclear Information System (INIS)

Groer, P.G.

1980-01-01

New statistical procedures are applied to estimate cumulative distribution functions (c.d.f.), force of mortality, and latent period for radiation-induced malignancies. It is demonstrated that correction for competing risks influences the shape of dose response curves, estimates of the latent period, and of the risk from ionizing radiations. The equivalence of the following concepts is demonstrated: force of mortality, hazard rate, and age or time specific incidence. This equivalence makes it possible to use procedures from reliability analysis and demography for radiation risk assessment. Two methods used by reliability analysts - hazard plotting and total time on test plots - are discussed in some detail and applied to characterize the hazard rate in radiation carcinogenesis. C.d.f.'s with increasing, decreasing, or constant hazard rate have different shapes and are shown to yield different dose-response curves for continuous irradiation. Absolute risk is shown to be a sound estimator only if the force of mortality is constant for the exposed and the control group. Dose-response relationships that use the absolute risk as a measure for the effect turn out to be special cases of dose-response relationships that measure the effect with cumulative incidence. (H.K.)

Regulation of intestinal homeostasis by innate and adaptive immunity.

Science.gov (United States)

Kayama, Hisako; Takeda, Kiyoshi

2012-11-01

The intestine is a unique tissue where an elaborate balance is maintained between tolerance and immune responses against a variety of environmental factors such as food and the microflora. In a healthy individual, the microflora stimulates innate and adaptive immune systems to maintain gut homeostasis. However, the interaction of environmental factors with particular genetic backgrounds can lead to dramatic changes in the composition of the microflora (i.e. dysbiosis). Many of the specific commensal-bacterial products and the signaling pathways they trigger have been characterized. The role of T(h)1, T(h)2 and T(h)17 cells in inflammatory bowel disease has been widely investigated, as has the contribution of epithelial cells and subsets of dendritic cells and macrophages. To date, multiple regulatory cells in adaptive immunity, such as regulatory T cells and regulatory B cells, have been shown to maintain gut homeostasis by preventing inappropriate innate and adaptive immune responses to commensal bacteria. Additionally, regulatory myeloid cells have recently been identified that prevent intestinal inflammation by inhibiting T-cell proliferation. An increasing body of evidence has shown that multiple regulatory mechanisms contribute to the maintenance of gut homeostasis.

Taste bud homeostasis in health, disease, and aging.

Science.gov (United States)

Feng, Pu; Huang, Liquan; Wang, Hong

2014-01-01

The mammalian taste bud is an onion-shaped epithelial structure with 50-100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8-12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging.

Taste Bud Homeostasis in Health, Disease, and Aging

Science.gov (United States)

2014-01-01

The mammalian taste bud is an onion-shaped epithelial structure with 50–100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8–12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging. PMID:24287552

Nursing care in patients with cardiovascular risk based on the theory of Nola J. Pender

OpenAIRE

Cadena Estrada, Julio César; Instituto Nacional de Cardiología Ignacio Chávez; González Ortega, Yariela; Universidad de Panamá

2017-01-01

Introduction: chronic degenerative diseases such as coronary heart disease are caused by various risk factors, habits and styles of unhealthy life, so that prevention and health promotion based on theories or models of nursing, play an essential role in solving public health problems. Objective: To develop a proposal for implementation of nursing care to patients with cardiovascular risk supported by the Health Promotion Model (HPM) of Nola J Pender. Proposal: The care of people is proposed b...

A Quick-responsive DNA Nanotechnology Device for Bio-molecular Homeostasis Regulation.

Science.gov (United States)

Wu, Songlin; Wang, Pei; Xiao, Chen; Li, Zheng; Yang, Bing; Fu, Jieyang; Chen, Jing; Wan, Neng; Ma, Cong; Li, Maoteng; Yang, Xiangliang; Zhan, Yi

2016-08-10

Physiological processes such as metabolism, cell apoptosis and immune responses, must be strictly regulated to maintain their homeostasis and achieve their normal physiological functions. The speed with which bio-molecular homeostatic regulation occurs directly determines the ability of an organism to adapt to conditional changes. To produce a quick-responsive regulatory system that can be easily utilized for various types of homeostasis, a device called nano-fingers that facilitates the regulation of physiological processes was constructed using DNA origami nanotechnology. This nano-fingers device functioned in linked open and closed phases using two types of DNA tweezers, which were covalently coupled with aptamers that captured specific molecules when the tweezer arms were sufficiently close. Via this specific interaction mechanism, certain physiological processes could be simultaneously regulated from two directions by capturing one biofactor and releasing the other to enhance the regulatory capacity of the device. To validate the universal application of this device, regulation of the homeostasis of the blood coagulant thrombin was attempted using the nano-fingers device. It was successfully demonstrated that this nano-fingers device achieved coagulation buffering upon the input of fuel DNA. This nano-device could also be utilized to regulate the homeostasis of other types of bio-molecules.

CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis.

Science.gov (United States)

Kim, Hyunbae; Zheng, Ze; Walker, Paul D; Kapatos, Gregory; Zhang, Kezhong

2017-07-15

Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress. Copyright © 2017 American Society for Microbiology.

A Hybrid Approach for Evaluating Faulty Behavior Risk of High-Risk Operations Using ANP and Evidence Theory

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Xia-Zhong Zheng

2017-01-01

Full Text Available Hydropower project construction is a high-risk operation, where accidents occur frequently. Moreover, the factors leading to accidents are often human factors, so safety evaluation of these factors for the hydropower projects’ work system is very significant. The Human Factors Analysis and Classification System (HFACS framework is applied to build evaluation system. In the evaluation process, correlation analysis is used to form the intercriteria analysis matrix that helps the decision makers to build impact relation matrix. Factor weights are calculated by the Analytic Network Process (ANP. In the index value determination step, the evidence theory is used to eliminate the conflicts of three decision makers and the index values are then calculated. The faulty behavior risk (FBR assessment value is finally obtained. The proposed method is practical and its applicability is proved by an example.

Descriptive Modeling of the Dynamical Systems and Determination of Feedback Homeostasis at Different Levels of Life Organization.

Science.gov (United States)

Zholtkevych, G N; Nosov, K V; Bespalov, Yu G; Rak, L I; Abhishek, M; Vysotskaya, E V

2018-05-24

The state-of-art research in the field of life's organization confronts the need to investigate a number of interacting components, their properties and conditions of sustainable behaviour within a natural system. In biology, ecology and life sciences, the performance of such stable system is usually related to homeostasis, a property of the system to actively regulate its state within a certain allowable limits. In our previous work, we proposed a deterministic model for systems' homeostasis. The model was based on dynamical system's theory and pairwise relationships of competition, amensalism and antagonism taken from theoretical biology and ecology. However, the present paper proposes a different dimension to our previous results based on the same model. In this paper, we introduce the influence of inter-component relationships in a system, wherein the impact is characterized by direction (neutral, positive, or negative) as well as its (absolute) value, or strength. This makes the model stochastic which, in our opinion, is more consistent with real-world elements affected by various random factors. The case study includes two examples from areas of hydrobiology and medicine. The models acquired for these cases enabled us to propose a convincing explanation for corresponding phenomena identified by different types of natural systems.

Comfort vs risk: a grounded theory about female adolescent behaviour in the sun.

Science.gov (United States)

Norton, Elizabeth; Holloway, Immy; Galvin, Kathleen

2014-07-01

To generate a grounded theory about female adolescent behaviour in the sun. Nurses have key roles in health promotion and skin cancer prevention. Adolescents' resistance to sun safety messages and their vulnerability to sunburn are of concern internationally. Understanding why young women do as they do in the sun may enhance skin cancer prevention, but their behaviour has not been explained before in the UK. The study incorporated a qualitative grounded theory design using the approach of Glaser. Qualitative data were gleaned from group and one-to-one, semi-structured interviews with 20 female participants aged 14-17, research memos and literature. Sampling was purposive and theoretical. Data collection, analysis and theory generation occurred concurrently. Data were analysed using the constant comparative method. Data collection ended when a substantive theory had been generated. Data analysis revealed five categories of findings: fitting in, being myself, being physically comfortable, slipping up and being comfortable (the core category). The theory generated around the core explains how young women direct their sun-related activities towards meeting their physical and psychosocial comfort needs. A contribution of this research is the grounded theory explaining the behaviour of young women in the sun. Further, the theory challenges assumptions that female adolescents necessarily take risks; it explains their sun-related activities in terms of comfort. The theory extends findings from other researchers' descriptive qualitative studies and also appears to apply to young people in countries other than the UK. Understanding the sun-related activity of young women in terms of physical and psychosocial comfort may help nurses to develop new approaches to skin cancer prevention. These could complement existing messages and humanise health promotion. © 2013 John Wiley & Sons Ltd.

Tissues Use Resident Dendritic Cells and Macrophages to Maintain Homeostasis and to Regain Homeostasis upon Tissue Injury: The Immunoregulatory Role of Changing Tissue Environments

Science.gov (United States)

Lech, Maciej; Gröbmayr, Regina; Weidenbusch, Marc; Anders, Hans-Joachim

2012-01-01

Most tissues harbor resident mononuclear phagocytes, that is, dendritic cells and macrophages. A classification that sufficiently covers their phenotypic heterogeneity and plasticity during homeostasis and disease does not yet exist because cell culture-based phenotypes often do not match those found in vivo. The plasticity of mononuclear phagocytes becomes obvious during dynamic or complex disease processes. Different data interpretation also originates from different conceptual perspectives. An immune-centric view assumes that a particular priming of phagocytes then causes a particular type of pathology in target tissues, conceptually similar to antigen-specific T-cell priming. A tissue-centric view assumes that changing tissue microenvironments shape the phenotypes of their resident and infiltrating mononuclear phagocytes to fulfill the tissue's need to maintain or regain homeostasis. Here we discuss the latter concept, for example, why different organs host different types of mononuclear phagocytes during homeostasis. We further discuss how injuries alter tissue environments and how this primes mononuclear phagocytes to enforce this particular environment, for example, to support host defense and pathogen clearance, to support the resolution of inflammation, to support epithelial and mesenchymal healing, and to support the resolution of fibrosis to the smallest possible scar. Thus, organ- and disease phase-specific microenvironments determine macrophage and dendritic cell heterogeneity in a temporal and spatial manner, which assures their support to maintain and regain homeostasis in whatever condition. Mononuclear phagocytes contributions to tissue pathologies relate to their central roles in orchestrating all stages of host defense and wound healing, which often become maladaptive processes, especially in sterile and/or diffuse tissue injuries. PMID:23251037

Neurohypophyseal hormones: novel actors of striated muscle development and homeostasis

Directory of Open Access Journals (Sweden)

Alessandra Costa

2014-09-01

Full Text Available Since the 1980's, novel functional roles of the neurohypophyseal hormones vasopressin and oxytocin have emerged. Several studies have investigated the effects of these two neurohormones on striated muscle tissues, both in vitro and in vivo. The effects of vasopressin on skeletal myogenic cells, developing muscle and muscle homeostasis have been documented. Oxytocin appears to have a greater influence on cardiomyocite differentiation and heart homeostasis. This review summarizes the studies on these novel roles of the two neurohypophyseal hormones, and open the possibility of new therapeutic approaches for diseases affecting striated muscle.

The liver in regulation of iron homeostasis.

Science.gov (United States)

Rishi, Gautam; Subramaniam, V Nathan

2017-09-01

The liver is one of the largest and most functionally diverse organs in the human body. In addition to roles in detoxification of xenobiotics, digestion, synthesis of important plasma proteins, gluconeogenesis, lipid metabolism, and storage, the liver also plays a significant role in iron homeostasis. Apart from being the storage site for excess body iron, it also plays a vital role in regulating the amount of iron released into the blood by enterocytes and macrophages. Since iron is essential for many important physiological and molecular processes, it increases the importance of liver in the proper functioning of the body's metabolism. This hepatic iron-regulatory function can be attributed to the expression of many liver-specific or liver-enriched proteins, all of which play an important role in the regulation of iron homeostasis. This review focuses on these proteins and their known roles in the regulation of body iron metabolism. Copyright © 2017 the American Physiological Society.

Chatty Mitochondria: Keeping Balance in Cellular Protein Homeostasis.

Science.gov (United States)

Topf, Ulrike; Wrobel, Lidia; Chacinska, Agnieszka

2016-08-01

Mitochondria are multifunctional cellular organelles that host many biochemical pathways including oxidative phosphorylation (OXPHOS). Defective mitochondria pose a threat to cellular homeostasis and compensatory responses exist to curtail the source of stress and/or its consequences. The mitochondrial proteome comprises proteins encoded by the nuclear and mitochondrial genomes. Disturbances in protein homeostasis may originate from mistargeting of nuclear encoded mitochondrial proteins. Defective protein import and accumulation of mistargeted proteins leads to stress that triggers translation alterations and proteasomal activation. These cytosolic pathways are complementary to the mitochondrial unfolded protein response (UPRmt) that aims to increase the capacity of protein quality control mechanisms inside mitochondria. They constitute putative targets for interventions aimed at increasing the fitness, stress resistance, and longevity of cells and organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mga2 transcription factor regulates an oxygen-responsive lipid homeostasis pathway in fission yeast

DEFF Research Database (Denmark)

Burr, Risa; Stewart, Emerson V; Shao, Wei

2016-01-01

-binding protein (SREBP) transcription factors regulate lipid homeostasis. In mammals, SREBP-2 controls cholesterol biosynthesis, whereas SREBP-1 controls triacylglycerol and glycerophospholipid biosynthesis. In the fission yeast Schizosaccharomyces pombe, the SREBP-2 homolog Sre1 regulates sterol homeostasis....... In the absence of mga2, fission yeast exhibited growth defects under both normoxia and low oxygen conditions. Mga2 transcriptional targets were enriched for lipid metabolism genes, and mga2Δ cells showed disrupted triacylglycerol and glycerophospholipid homeostasis, most notably with an increase in fatty acid...

Effectiveness of carnosine on disturbed electrolytes homeostasis ...

African Journals Online (AJOL)

Jane

2011-07-20

Jul 20, 2011 ... of the cells to cisplatin may result from the interaction of specific proteins with ..... respiration, which is similar to uncoupling of oxidative phosphorylation (Binet ... cellular ion homeostasis with decreased cellular K+ content, increased ... of sodium and hydrogen ions will take place passively. Also, magnesium ...

Role of Snf3 in glucose homeostasis of Saccharomyces cerevisiae (review)

DEFF Research Database (Denmark)

Kielland-Brandt, Morten

signal pathways in directions opposite to those caused by extracellular nutrients (6,7), a phenomenon predicted to contribute to intracellular nutrient homeostasis. Although significant, the influence of intracellular leucine on signaling from Ssy1 is relatively modest (6), whereas the conditions...... with enhanced intracellular glucose concentrations (7) caused a strong decrease in signaling from Snf3, suggesting an important role of Snf3 in intracellular glucose homeostasis. Strategies for studies of this role will be discussed....

Dynamic thiol/disulphide homeostasis in patients with basal cell carcinoma.

Science.gov (United States)

Demirseren, Duriye Deniz; Cicek, Cagla; Alisik, Murat; Demirseren, Mustafa Erol; Aktaş, Akın; Erel, Ozcan

2017-09-01

The aim of this study is to measure and compare the dynamic thiol/disulphide homeostasis of patients with basal cell carcinoma and healthy subjects with a newly developed and original method. Thirty four patients attending our outpatient clinic and clinically and histopathologically diagnosed as nodular basal cell carcinoma, and age and gender matched 30 healthy individuals have been involved in the study. Thiol/disulphide homeostasis tests have been measured with a novel automatic spectrophotometric method developed and the results have been compared statistically. Serum native thiol and disulphide levels in the patient and control group show a considerable variance statistically (p = 0.028, 0.039, respectively). Total thiol levels do not reveal a considerable variation (p = 0.094). Disulphide/native thiol ratios and native thiol/total thiol ratios also show a considerable variance statistically (p = 0.012, 0.013, 0.010, respectively). Thiol disulphide homeostasis in patients with basal cell carcinoma alters in the way that disulphide gets lower and thiols get higher. Thiol/disulphide level is likely to have a role in basal cell carcinoma pathogenesis.

Iron Homeostasis in Peripheral Nervous System, Still a Black Box?

Science.gov (United States)

Taveggia, Carla

2014-01-01

Abstract Significance: Iron is the most abundant transition metal in biology and an essential cofactor for many cellular enzymes. Iron homeostasis impairment is also a component of peripheral neuropathies. Recent Advances: During the past years, much effort has been paid to understand the molecular mechanism involved in maintaining systemic iron homeostasis in mammals. This has been stimulated by the evidence that iron dyshomeostasis is an initial cause of several disorders, including genetic and sporadic neurodegenerative disorders. Critical Issues: However, very little has been done to investigate the physiological role of iron in peripheral nervous system (PNS), despite the development of suitable cellular and animal models. Future Directions: To stimulate research on iron metabolism and peripheral neuropathy, we provide a summary of the knowledge on iron homeostasis in the PNS, on its transport across the blood–nerve barrier, its involvement in myelination, and we identify unresolved questions. Furthermore, we comment on the role of iron in iron-related disorder with peripheral component, in demyelinating and metabolic peripheral neuropathies. Antioxid. Redox Signal. 21, 634–648. PMID:24409826

Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

Directory of Open Access Journals (Sweden)

Giovanni Dalmasso

Full Text Available Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis and the removal of damaged mitochondria by selective autophagy (mitophagy. While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1 mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2 restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3 maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4 our model suggests sources of, and stress conditions

The Role of Follicular Fluid Thiol/Disulphide Homeostasis in Polycystic Ovary Syndrome.

Science.gov (United States)

Tola, Esra Nur; Köroğlu, Nadiye; Ergin, Merve; Oral, Hilmi Baha; Turgut, Abdülkadir; Erel, Özcan

2018-04-04

Oxidative stress is suggested as a potential triggering factor in the etiopathogenesis of Polycystic ovary syndrome related infertility. Thiol/disulphide homeostasis, a recently oxidative stress marker, is one of the antioxidant mechanism in human which have critical roles in folliculogenesis and ovulation. The aim of our study is to investigate follicular fluid thiol/disulphide homeostasis in the etiopathogenesis of Polycystic ovary syndrome and to determine its' association with in vitro fertilization outcome. The study procedures were approved by local ethic committee. Cross sectional design Methods: Follicular fluid of twenty-two Polycystic ovary syndrome women and twenty ovulatory controls undergoing in vitro fertilization treatment were recruited. Thiol/disulphide homeostasis was analyzed via a novel spectrophotometric method. Follicular native thiol levels were found to be lower in Polycystic ovary syndrome group than non- Polycystic ovary syndrome group (p=0.041) as well as native thiol/total thiol ratio (pPolycystic ovary syndrome group (pPolycystic ovary syndrome patients was found. A positive predictive effect of native thiol on fertilization rate among Polycystic ovary syndrome group was also found (p=0.03, β=0.45, 95% CI=0.031-0.643). Deterioration in thiol/disulphide homeostasis, especially elevated disulphide levels could be one of the etiopathogenetic mechanism in Polycystic ovary syndrome. Increased native thiol levels is related to fertilization rate among Polycystic ovary syndrome patients and also positive predictor marker of fertilization rate among Polycystic ovary syndrome patients. Improvement of thiol/disulphide homeostasis could be of importance in the treatment of Polycystic ovary syndrome to increase in vitro fertilization success in Polycystic ovary syndrome.

Prospect theory or construal level theory? Diminishing sensitivity vs. psychological distance in risky decisions.

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Trautmann, Stefan T; van de Kuilen, Gijs

2012-01-01

Attitudes toward risks are central to organizational decisions. These attitudes are commonly modeled by prospect theory. Construal level theory has been proposed as an alternative theory of risky choice, accounting for psychological distance deriving from temporal, spatial and social aspects of risk that are typical of agency situations. Unnoticed in the literature, the two theories make contradicting predictions. The current study investigates which theory provides a better description of risky decisions in the presence of temporal, spatial, and social factors. We find that the psychophysical effects modeled by prospect theory dominate the psychological distance effects of construal level theory. Copyright © 2011 Elsevier B.V. All rights reserved.

[Immunological theory of senescence].

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Drela, Nadzieja

2014-01-01

Senescence can result from decreased potential of the immune system to respond to foreign and self antigens. The most common effect is the inhibition to destroy dying and cancer cells and the decrease of the immune response to pathogens. Aging is closely related to inflammatory phenotype, which facilitate the development of age-related diseases. The mammal immune system is highly organized and adapted to react to a wide range of antigens. According to the immunological theory, the causative agents of senescence are multilevel changes of development and functions of immune cells. Some of changes can be beneficial for the maintenance of homeostasis and lifespan in continuously changing endogenous environment and immune history of the organism.

Glucose Homeostasis Variables in Pregnancy versus Maternal and Infant Body Composition

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Pontus Henriksson

2015-07-01

Full Text Available Intrauterine factors influence infant size and body composition but the mechanisms involved are to a large extent unknown. We studied relationships between the body composition of pregnant women and variables related to their glucose homeostasis, i.e., glucose, HOMA-IR (homeostasis model assessment-insulin resistance, hemoglobin A1c and IGFBP-1 (insulin-like growth factor binding protein-1, and related these variables to the body composition of their infants. Body composition of 209 women in gestational week 32 and of their healthy, singleton and full-term one-week-old infants was measured using air displacement plethysmography. Glucose homeostasis variables were assessed in gestational week 32. HOMA-IR was positively related to fat mass index and fat mass (r2 = 0.32, p < 0.001 of the women. Maternal glucose and HOMA-IR values were positively (p ≤ 0.006 associated, while IGFBP-1was negatively (p = 0.001 associated, with infant fat mass. HOMA-IR was positively associated with fat mass of daughters (p < 0.001, but not of sons (p = 0.65 (Sex-interaction: p = 0.042. In conclusion, glucose homeostasis variables of pregnant women are related to their own body composition and to that of their infants. The results suggest that a previously identified relationship between fat mass of mothers and daughters is mediated by maternal insulin resistance.

Environmental metabolomics with data science for investigating ecosystem homeostasis.

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Kikuchi, Jun; Ito, Kengo; Date, Yasuhiro

2018-02-01

A natural ecosystem can be viewed as the interconnections between complex metabolic reactions and environments. Humans, a part of these ecosystems, and their activities strongly affect the environments. To account for human effects within ecosystems, understanding what benefits humans receive by facilitating the maintenance of environmental homeostasis is important. This review describes recent applications of several NMR approaches to the evaluation of environmental homeostasis by metabolic profiling and data science. The basic NMR strategy used to evaluate homeostasis using big data collection is similar to that used in human health studies. Sophisticated metabolomic approaches (metabolic profiling) are widely reported in the literature. Further challenges include the analysis of complex macromolecular structures, and of the compositions and interactions of plant biomass, soil humic substances, and aqueous particulate organic matter. To support the study of these topics, we also discuss sample preparation techniques and solid-state NMR approaches. Because NMR approaches can produce a number of data with high reproducibility and inter-institution compatibility, further analysis of such data using machine learning approaches is often worthwhile. We also describe methods for data pretreatment in solid-state NMR and for environmental feature extraction from heterogeneously-measured spectroscopic data by machine learning approaches. Copyright © 2017. Published by Elsevier B.V.

Perinatal bisphenol A exposure and adult glucose homeostasis: identifying critical windows of exposure.

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Jingli Liu

Full Text Available Bisphenol A (BPA is a widespread endocrine-disrupting chemical used as the building block for polycarbonate plastics. Epidemiological evidence has correlated BPA exposure with higher risk of heart disease and type 2 diabetes. However, it remains unknown whether there are critical windows of susceptibility to BPA exposure on the development of dysglycemia. This study was an attempt to investigate the critical windows and the long-term consequences of perinatal exposure to BPA on glucose homeostasis. Pregnant mice were given either vehicle or BPA (100 µg/kg/day at different time of perinatal stage: 1 on days 1-6 of pregnancy (P1-P6, preimplantation exposure; 2 from day 6 of pregnancy until postnatal day (PND 0 (P6-PND0, fetal exposure; 3 from lactation until weaning (PND0-PND21, neonatal exposure; and 4 from day 6 of gestation until weaning (P6-PND21, fetal and neonatal exposure. At 3, 6 and 8 months of age, offspring in each group were challenged with glucose and insulin tolerance tests. Then islet morphometry and β-cell function were measured. The glucose homeostasis was impaired in P6-PND0 mice from 3 to 6 months of age, and this continued to 8 months in males, but not females. While in PND0-PND21 and P6-PND21 BPA-treated groups, only the 3-month-old male offspring developed glucose intolerance. Moreover, at the age of 3 months, perinatal exposure to BPA resulted in the increase of β-cell mass mainly due to the coordinate changes in cell replication, neogenesis, and apoptosis. The alterations of insulin secretion and insulin sensitivity, rather than β-cell mass, were consistent with the development of glucose intolerance. Our findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and the effects of BPA were dose, sex, and time-dependent. Fetal development stage may be the critical window of susceptibility to BPA exposure.

Association of glucose homeostasis measures with heart rate variability among Hispanic/Latino adults without diabetes: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

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Meyer, Michelle L; Gotman, Nathan M; Soliman, Elsayed Z; Whitsel, Eric A; Arens, Raanan; Cai, Jianwen; Daviglus, Martha L; Denes, Pablo; González, Hector M; Moreiras, Juan; Talavera, Gregory A; Heiss, Gerardo

2016-03-16

Reduced heart rate variability (HRV), a measure of cardiac autonomic function, is associated with an increased risk of cardiovascular disease (CVD) and mortality. Glucose homeostasis measures are associated with reduced cardiac autonomic function among those with diabetes, but inconsistent associations have been reported among those without diabetes. This study aimed to examine the association of glucose homeostasis measures with cardiac autonomic function among diverse Hispanic/Latino adults without diabetes. The Hispanic community Health Study/Study of Latinos (HCHS/SOL; 2008-2011) used two-stage area probability sampling of households to enroll 16,415 self-identified Hispanics/Latinos aged 18-74 years from four USA communities. Resting, standard 12-lead electrocardiogram recordings were used to estimate the following ultrashort-term measures of HRV: RR interval (RR), standard deviation of all normal to normal RR (SDNN) and root mean square of successive differences in RR intervals (RMSSD). Multivariable regression analysis was used to estimate associations between glucose homeostasis measures with HRV using data from 11,994 adults without diabetes (mean age 39 years; 52 % women). Higher fasting glucose was associated with lower RR, SDNN, and RMSSD. Fasting insulin and the homeostasis model assessment of insulin resistance was negatively associated with RR, SDNN, and RMSSD, and the association was stronger among men compared with women. RMSSD was, on average, 26 % lower in men with higher fasting insulin and 29 % lower in men with lower insulin resistance; for women, the corresponding estimates were smaller at 4 and 9 %, respectively. Higher glycated hemoglobin was associated with lower RR, SDNN, and RMSSD in those with abdominal adiposity, defined by sex-specific cut-points for waist circumference, after adjusting for demographics and medication use. There were no associations between glycated hemoglobin and HRV measures among those without abdominal adiposity

[Update views on the theory of phagocytosis].

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Freĭdlin, I S

2008-01-01

Developer of the phagocytosis theory I.I Mechnikov forecasted the most fruitful directions of its development. Macrophages express on the plasma membranes broad spectrum of receptors, which mediate their interaction with altered organism's own components as well as with exogenous agents, including various microorganisms. Recognition leads to changes of expression of surface molecules, enhancement of phagocytic activity as well as production and secretion of cytokines, presentation functions, signaling and genes expression. This reflected on maintenance of homeostasis, as well as on host defense effectiveness, including mechanisms of innate and adaptive immunity.

Mathematical finance theory review and exercises from binomial model to risk measures

CERN Document Server

Gianin, Emanuela Rosazza

2013-01-01

The book collects over 120 exercises on different subjects of Mathematical Finance, including Option Pricing, Risk Theory, and Interest Rate Models. Many of the exercises are solved, while others are only proposed. Every chapter contains an introductory section illustrating the main theoretical results necessary to solve the exercises. The book is intended as an exercise textbook to accompany graduate courses in mathematical finance offered at many universities as part of degree programs in Applied and Industrial Mathematics, Mathematical Engineering, and Quantitative Finance.

Application of Grounded Theory in Determining Required Elements for IPv6 Risk Assessment Equation

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Rosli Athirah

2018-01-01

Full Text Available The deployment of Internet Protocol version 6 (IPv6 has raised security concerns among the network administrators. Thus, in strengthening the network security, administrator requires an appropriate method to assess the possible risks that occur in their networks. Aware of the needs to calculate risk in IPv6 network, it is essential to an organization to have an equation that is flexible and consider the requirements of the network. However, the existing risk assessment equations do not consider the requirement of the network. Therefore, this paper presents the adaptation of grounded theory to search for elements that are needed to develop IPv6 risk assessment (IRA6 equation. The attack scenarios’ experiments; UDP Flooding, TCP Flooding and Multicast attacks were carried out in different network environment to show how the IPv6 risk assessment equation being used. The result shows that the IRA6 equation is more flexible to be used regardless the network sizes and easier to calculate the risk value compared to the existing risk assessment equations. Hence, network administrators can have a proper decision making and strategic planning for a robust network security.

Longitudinal Analysis of the Interaction Between Obesity and Pregnancy on Iron Homeostasis: Role of Hepcidin.

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Flores-Quijano, María Eugenia; Montalvo-Velarde, Irene; Vital-Reyes, Victor Saul; Rodríguez-Cruz, Maricela; Rendón-Macías, Mario Enrique; López-Alarcón, Mardia

2016-10-01

When pregnancy occurs in obese women, two opposite mechanisms for iron homeostasis concur: increased need for available iron to support erythropoiesis and decreased iron mobilization from diets and stores due to obesity-related inflammation linked to overexpressed hepcidin. Few studies have examined the role of hepcidin on maternal iron homeostasis in the context of obese pregnancy. The aim of the study was to evaluate the combined effect of maternal obesity and pregnancy on hepcidin and maternal iron status while accounting for inflammation and iron supplementation. We conducted a secondary analysis of a cohort of pregnant women recruited from a referral obstetric hospital in Mexico City. Circulating biomarkers of iron status (hepcidin, ferritin [SF], transferrin receptor [sTfR], erythropoietin [EPO]), and inflammation (C-reactive protein [CRP], tumor necrosis factor-[TNF]α, and interleukin-[IL]6) were determined monthly throughout pregnancy. Repeated measures ANOVA and logistic regression models were used for statistics. Twenty-three obese (Ob) and 25 lean (Lc) women were studied. SF and hepcidin declined, and EPO and sTfR increased throughout pregnancy in both groups. sTfR increased more in Ob than in Lc (p = 0.024). The smallest hepcidin decline occurred in iron-supplemented Ob women compared to non-supplemented Lc women (p = 0.022). The risk for iron deficiency at the end of pregnancy was higher for Ob than for Lc (OR = 4.45, 95% CI = 2.07-9.58) after adjusting for iron supplementation and hepcidin concentration. Pre-gestational obesity increases the risk of maternal iron deficiency despite iron supplementation. Overexpressed hepcidin appears to be a potential mechanism. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Nutrition and protein energy homeostasis in elderly.

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Boirie, Yves; Morio, Béatrice; Caumon, Elodie; Cano, Noël J

2014-01-01

Protein-energy homeostasis is a major determinant of healthy aging. Inadequate nutritional intakes and physical activity, together with endocrine disturbances are associated with of sarcopenia and frailty. Guidelines from scientific societies mainly address the quantitative aspects of protein and energy nutrition in elderly. Besides these quantitative aspects of protein load, perspective strategies to promote muscle protein synthesis and prevent sarcopenia include pulse feeding, the use of fast proteins and the addition of leucine or citrulline to dietary protein. An integrated management of sarcopenia, taking into account the determinants of muscle wasting, i.e. nutrition, physical activity, anabolic factors such as androgens, vitamin D and n-3 polyunsaturated fatty acids status, needs to be tested in the prevention and treatment of sarcopenia. The importance of physical activity, specifically resistance training, is emphasized, not only in order to facilitate muscle protein anabolism but also to increase appetite and food intake in elderly people at risk of malnutrition. According to present data, healthy nutrition in elderly should respect the guidelines for protein and energy requirement, privilege a Mediterranean way of alimentation, and be associated with a regular physical activity. Further issues relate to the identification of the genetics determinants of protein energy wasting in elderly. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Investigation of manganese homeostasis in dogs with anaemia and ...

African Journals Online (AJOL)

Investigation of manganese homeostasis in dogs with anaemia and chronic enteropathy. Marisa da Fonseca Ferreira, Arielle Elizabeth Ann Aylor, Richard John Mellanby, Susan Mary Campbell, Adam George Gow ...

Reactive Oxygen Species and Mitochondrial Homeostasis as Regulators of Stem Cell Fate and Function.

Science.gov (United States)

Tan, Darren Q; Suda, Toshio

2018-07-10

The precise role and impact of reactive oxygen species (ROS) in stem cells, which are essential for lifelong tissue homeostasis and regeneration, remain of significant interest to the field. The long-term regenerative potential of a stem cell compartment is determined by the delicate balance between quiescence, self-renewal, and differentiation, all of which can be influenced by ROS levels. Recent Advances: The past decade has seen a growing appreciation for the importance of ROS and redox homeostasis in various stem cell compartments, particularly those of hematopoietic, neural, and muscle tissues. In recent years, the importance of proteostasis and mitochondria in relation to stem cell biology and redox homeostasis has garnered considerable interest. Here, we explore the reciprocal relationship between ROS and stem cells, with significant emphasis on mitochondria as a core component of redox homeostasis. We discuss how redox signaling, involving cell-fate determining protein kinases and transcription factors, can control stem cell function and fate. We also address the impact of oxidative stress on stem cells, especially oxidative damage of lipids, proteins, and nucleic acids. We further discuss ROS management in stem cells, and present recent evidence supporting the importance of mitochondrial activity and its modulation (via mitochondrial clearance, biogenesis, dynamics, and distribution [i.e., segregation and transfer]) in stem cell redox homeostasis. Therefore, elucidating the intricate links between mitochondria, cellular metabolism, and redox homeostasis is envisioned to be critical for our understanding of ROS in stem cell biology and its therapeutic relevance in regenerative medicine. Antioxid. Redox Signal. 00, 000-000.

Mechanisms of Cell Polarity-Controlled Epithelial Homeostasis and Immunity in the Intestine.

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Klunder, Leon J; Faber, Klaas Nico; Dijkstra, Gerard; van IJzendoorn, Sven C D

2017-07-05

Intestinal epithelial cell polarity is instrumental to maintain epithelial homeostasis and balance communications between the gut lumen and bodily tissue, thereby controlling the defense against gastrointestinal pathogens and maintenance of immune tolerance to commensal bacteria. In this review, we highlight recent advances with regard to the molecular mechanisms of cell polarity-controlled epithelial homeostasis and immunity in the human intestine. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Treg cell-IgA axis in maintenance of host immune homeostasis with microbiota

OpenAIRE

Feng, Ting; Elson, Charles O.; Cong, Yingzi

2010-01-01

The intestine is the home to a vast diversity of microbiota and a complex of mucosal immune system. Multiple regulatory mechanisms control host immune responses to microbiota and maintain intestinal immune homeostasis. This mini review will provide evidence indicating a Treg cell-IgA axis and such axis playing a major role in maintenance of intestinal homeostasis.

Using Synchrotron X-ray Fluorescence Microprobes in the Study of Metal Homeostasis in Plants

International Nuclear Information System (INIS)

Punshon, T.; Guerinot, M.; Lanzirotti, A.

2009-01-01

Background and Aims: This Botanical Briefing reviews the application of synchrotron X-ray fluorescence (SXRF) microprobes to the plant sciences; how the technique has expanded our knowledge of metal(loid) homeostasis, and how it can be used in the future. Scope: The use of SXRF microspectroscopy and microtomography in research on metal homeostasis in plants is reviewed. The potential use of SXRF as part of the ionomics toolbox, where it is able to provide fundamental information on the way that plants control metal homeostasis, is recommended. Conclusions: SXRF is one of the few techniques capable of providing spatially resolved in-vivo metal abundance data on a sub-micrometre scale, without the need for chemical fixation, coating, drying or even sectioning of samples. This gives researchers the ability to uncover mechanisms of plant metal homeostasis that can potentially be obscured by the artefacts of sample preparation. Further, new generation synchrotrons with smaller beam sizes and more sensitive detection systems will allow for the imaging of metal distribution within single living plant cells. Even greater advances in our understanding of metal homeostasis in plants can be gained by overcoming some of the practical boundaries that exist in the use of SXRF analysis.

Does perceived risk influence the effects of message framing? Revisiting the link between prospect theory and message framing.

Science.gov (United States)

Van 't Riet, Jonathan; Cox, Anthony D; Cox, Dena; Zimet, Gregory D; De Bruijn, Gert-Jan; Van den Putte, Bas; De Vries, Hein; Werrij, Marieke Q; Ruiter, Robert A C

2016-12-01

Health-promoting messages can be framed in terms of the beneficial consequences of healthy behaviour (gain-framed messages) or the detrimental consequences of unhealthy behaviour (loss-framed messages). An influential notion holds that the perceived risk associated with the recommended behaviour determines the relative persuasiveness of gain- and loss-framed messages. This 'risk-framing hypothesis', which was derived from prospect theory, has been central to health message-framing research for the better part of two decades and has enduring appeal to researchers and practitioners. It has found its way into several health communication handbooks and is communicated to the general public. The present article examines the validity of the risk-framing hypothesis anew by providing a review of the health message-framing literature. In spite of its ongoing appeal, we conclude that the hypothesis has severe theoretical flaws. In addition, we find that the empirical evidence in favour of the hypothesis is weak and inconsistent. It seems that, in applying prospect theory's tenets to a health-promotion context, some of the theory's key aspects have been lost in translation. At the close of the article, we offer a research agenda for the future, arguing that, above all, new methodology is needed to bring the message-framing literature further.

Complement: a key system for immune surveillance and homeostasis.

Science.gov (United States)

Ricklin, Daniel; Hajishengallis, George; Yang, Kun; Lambris, John D

2010-09-01

Nearly a century after the significance of the human complement system was recognized, we have come to realize that its functions extend far beyond the elimination of microbes. Complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders. By eliminating cellular debris and infectious microbes, orchestrating immune responses and sending 'danger' signals, complement contributes substantially to homeostasis, but it can also take action against healthy cells if not properly controlled. This review describes our updated view of the function, structure and dynamics of the complement network, highlights its interconnection with immunity at large and with other endogenous pathways, and illustrates its multiple roles in homeostasis and disease.

The total theory about risk management

International Nuclear Information System (INIS)

Furuya, Shunsuke

2003-01-01

A general working procedure of risk management, some example of other countries, topics and problems in the future are described. A definition of risk, risk assessment, risk management process, setting of aim and definite policy are explained. As a fundamental way of thinking, risk is controlled by ALARP (As Low As Reasonably Practicable). The upper and lower limit of risk level is called as Quantitative Safety Goal and Target Level of Safety, respectively. These limits in the atomic power and airplane are decided. Evaluation of risk, countermeasure and practice are explained. For example, a permissible range of risk and practical use in England, U.S.A, Holland and Japan are stated. Recently, accountability risk, missing demand risk and control risk are important. (S.Y.)

Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis

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Arya Bagus Boedi Iswanto

2017-04-01

Full Text Available Abstract: The specialized plasma membrane microdomains known as lipid rafts are enriched by sterols and sphingolipids. Lipid rafts facilitate cellular signal transduction by controlling the assembly of signaling molecules and membrane protein trafficking. Another specialized compartment of plant cells, the plasmodesmata (PD, which regulates the symplasmic intercellular movement of certain molecules between adjacent cells, also contains a phospholipid bilayer membrane. The dynamic permeability of plasmodesmata (PDs is highly controlled by plasmodesmata callose (PDC, which is synthesized by callose synthases (CalS and degraded by β-1,3-glucanases (BGs. In recent studies, remarkable observations regarding the correlation between lipid raft formation and symplasmic intracellular trafficking have been reported, and the PDC has been suggested to be the regulator of the size exclusion limit of PDs. It has been suggested that the alteration of lipid raft substances impairs PDC homeostasis, subsequently affecting PD functions. In this review, we discuss the substantial role of membrane lipid rafts in PDC homeostasis and provide avenues for understanding the fundamental behavior of the lipid raft–processed PDC.

Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis.

Science.gov (United States)

Iswanto, Arya Bagus Boedi; Kim, Jae-Yean

2017-04-03

A bstract: The specialized plasma membrane microdomains known as lipid rafts are enriched by sterols and sphingolipids. Lipid rafts facilitate cellular signal transduction by controlling the assembly of signaling molecules and membrane protein trafficking. Another specialized compartment of plant cells, the plasmodesmata (PD), which regulates the symplasmic intercellular movement of certain molecules between adjacent cells, also contains a phospholipid bilayer membrane. The dynamic permeability of plasmodesmata (PDs) is highly controlled by plasmodesmata callose (PDC), which is synthesized by callose synthases (CalS) and degraded by β-1,3-glucanases (BGs). In recent studies, remarkable observations regarding the correlation between lipid raft formation and symplasmic intracellular trafficking have been reported, and the PDC has been suggested to be the regulator of the size exclusion limit of PDs. It has been suggested that the alteration of lipid raft substances impairs PDC homeostasis, subsequently affecting PD functions. In this review, we discuss the substantial role of membrane lipid rafts in PDC homeostasis and provide avenues for understanding the fundamental behavior of the lipid raft-processed PDC.

The tumor necrosis factor-alpha-induced protein 8 family in immune homeostasis and inflammatory cancer diseases.

Science.gov (United States)

Luan, Y Y; Yao, Y M; Sheng, Z Y

2013-01-01

Within the immune system homeostasis is maintained by a myriad of mechanisms that include the regulation of immune cell activation and programmed cell death. The breakdown of immune homeostasis may lead to fatal inflammatory diseases. We set out to identify genes of tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) family that has a functional role in the process of immune homeostasis. Tumor necrosis factor-alpha-induced protein 8 (TNFAIP8), which functions as an oncogenic molecule, is also associated with enhanced cell survival and inhibition of apoptosis. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) governs immune homeostasis in both the innate and adaptive immune system and prevents hyper-responsiveness by negatively regulating signaling via T cell receptors and Toll-like receptors (TLRs). There also exist two highly homologous but uncharacterized proteins, TIPE1 and TIPE3. This review is an attempt to provide a summary of TNFAIP8 family associated with immune homeostasis and inflammatory cancer diseases.

Disturbance of copper homeostasis is a mechanism for homocysteine-induced vascular endothelial cell injury.

Directory of Open Access Journals (Sweden)

Daoyin Dong

Full Text Available Elevation of serum homocysteine (Hcy levels is a risk factor for cardiovascular diseases. Previous studies suggested that Hcy interferes with copper (Cu metabolism in vascular endothelial cells. The present study was undertaken to test the hypothesis that Hcy-induced disturbance of Cu homeostasis leads to endothelial cell injury. Exposure of human umbilical vein endothelial cells (HUVECs to concentrations of Hcy at 0.01, 0.1 or 1 mM resulted in a concentration-dependent decrease in cell viability and an increase in necrotic cell death. Pretreatment of the cells with a final concentration of 5 µM Cu in cultures prevented the effects of Hcy. Hcy decreased intracellular Cu concentrations. HPLC-ICP-MS analysis revealed that Hcy caused alterations in the distribution of intracellular Cu; more Cu was redistributed to low molecular weight fractions. ESI-Q-TOF detected the formation of Cu-Hcy complexes. Hcy also decreased the protein levels of Cu chaperone COX17, which was accompanied by a decrease in the activity of cytochrome c oxidase (CCO and a collapse of mitochondrial membrane potential. These effects of Hcy were all preventable by Cu pretreatment. The study thus demonstrated that Hcy disturbs Cu homeostasis and limits the availability of Cu to critical molecules such as COX17 and CCO, leading to mitochondrial dysfunction and endothelial cell injury.

A Dual-Sensing Receptor Confers Robust Cellular Homeostasis

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Hannah Schramke

2016-06-01

Full Text Available Cells have evolved diverse mechanisms that maintain intracellular homeostasis in fluctuating environments. In bacteria, control is often exerted by bifunctional receptors acting as both kinase and phosphatase to regulate gene expression, a design known to provide robustness against noise. Yet how such antagonistic enzymatic activities are balanced as a function of environmental change remains poorly understood. We find that the bifunctional receptor that regulates K+ uptake in Escherichia coli is a dual sensor, which modulates its autokinase and phosphatase activities in response to both extracellular and intracellular K+ concentration. Using mathematical modeling, we show that dual sensing is a superior strategy for ensuring homeostasis when both the supply of and demand for a limiting resource fluctuate. By engineering standards, this molecular control system displays a strikingly high degree of functional integration, providing a reference for the vast numbers of receptors for which the sensing strategy remains elusive.

A new vesicle trafficking regulator CTL1 plays a crucial role in ion homeostasis.

Science.gov (United States)

Gao, Yi-Qun; Chen, Jiu-Geng; Chen, Zi-Ru; An, Dong; Lv, Qiao-Yan; Han, Mei-Ling; Wang, Ya-Ling; Salt, David E; Chao, Dai-Yin

2017-12-01

Ion homeostasis is essential for plant growth and environmental adaptation, and maintaining ion homeostasis requires the precise regulation of various ion transporters, as well as correct root patterning. However, the mechanisms underlying these processes remain largely elusive. Here, we reported that a choline transporter gene, CTL1, controls ionome homeostasis by regulating the secretory trafficking of proteins required for plasmodesmata (PD) development, as well as the transport of some ion transporters. Map-based cloning studies revealed that CTL1 mutations alter the ion profile of Arabidopsis thaliana. We found that the phenotypes associated with these mutations are caused by a combination of PD defects and ion transporter misregulation. We also established that CTL1 is involved in regulating vesicle trafficking and is thus required for the trafficking of proteins essential for ion transport and PD development. Characterizing choline transporter-like 1 (CTL1) as a new regulator of protein sorting may enable researchers to understand not only ion homeostasis in plants but also vesicle trafficking in general.

Macrophages in intestinal homeostasis and inflammation

Science.gov (United States)

Bain, Calum C; Mowat, Allan McI

2014-01-01

The intestine contains the largest pool of macrophages in the body which are essential for maintaining mucosal homeostasis in the face of the microbiota and the constant need for epithelial renewal but are also important components of protective immunity and are involved in the pathology of inflammatory bowel disease (IBD). However, defining the biological roles of intestinal macrophages has been impeded by problems in defining the phenotype and origins of different populations of myeloid cells in the mucosa. Here, we discuss how multiple parameters can be used in combination to discriminate between functionally distinct myeloid cells and discuss the roles of macrophages during homeostasis and how these may change when inflammation ensues. We also discuss the evidence that intestinal macrophages do not fit the current paradigm that tissue-resident macrophages are derived from embryonic precursors that self-renew in situ, but require constant replenishment by blood monocytes. We describe our recent work demonstrating that classical monocytes constantly enter the intestinal mucosa and how the environment dictates their subsequent fate. We believe that understanding the factors that drive intestinal macrophage development in the steady state and how these may change in response to pathogens or inflammation could provide important insights into the treatment of IBD. PMID:24942685

Risky Business: An Integrated Institutional Theory for Understanding High-Risk Decision Making in Higher Education

Science.gov (United States)

Turner, Lauren A.; Angulo, A. J.

2018-01-01

Lauren A. Turner and A. J. Angulo explore how institutional theory can be applied to explain variance in higher education organizational strategies. Given strong regulatory, normative, and cultural-cognitive pressures to conform, they ask, why do some colleges engage in high-risk decision making? To answer this, they bring together classic and…

The Greater Phenotypic Homeostasis of the Allopolyploid Coffea arabica Improved the Transcriptional Homeostasis Over that of Both Diploid Parents.

Science.gov (United States)

Bertrand, Benoît; Bardil, Amélie; Baraille, Hélène; Dussert, Stéphane; Doulbeau, Sylvie; Dubois, Emeric; Severac, Dany; Dereeper, Alexis; Etienne, Hervé

2015-10-01

Polyploidy impacts the diversity of plant species, giving rise to novel phenotypes and leading to ecological diversification. In order to observe adaptive and evolutionary capacities of polyploids, we compared the growth, primary metabolism and transcriptomic expression level in the leaves of the newly formed allotetraploid Coffea arabica species compared with its two diploid parental species (Coffea eugenioides and Coffea canephora), exposed to four thermal regimes (TRs; 18-14, 23-19, 28-24 and 33-29°C). The growth rate of the allopolyploid C. arabica was similar to that of C. canephora under the hottest TR and that of C. eugenioides under the coldest TR. For metabolite contents measured at the hottest TR, the allopolyploid showed similar behavior to C. canephora, the parent which tolerates higher growth temperatures in the natural environment. However, at the coldest TR, the allopolyploid displayed higher sucrose, raffinose and ABA contents than those of its two parents and similar linolenic acid leaf composition and Chl content to those of C. eugenioides. At the gene expression level, few differences between the allopolyploid and its parents were observed for studied genes linked to photosynthesis, respiration and the circadian clock, whereas genes linked to redox activity showed a greater capacity of the allopolyploid for homeostasis. Finally, we found that the overall transcriptional response to TRs of the allopolyploid was more homeostatic compared with its parents. This better transcriptional homeostasis of the allopolyploid C. arabica afforded a greater phenotypic homeostasis when faced with environments that are unsuited to the diploid parental species. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Ets transcription factor GABP controls T cell homeostasis and immunity.

Science.gov (United States)

Luo, Chong T; Osmanbeyoglu, Hatice U; Do, Mytrang H; Bivona, Michael R; Toure, Ahmed; Kang, Davina; Xie, Yuchen; Leslie, Christina S; Li, Ming O

2017-10-20

Peripheral T cells are maintained in the absence of vigorous stimuli, and respond to antigenic stimulation by initiating cell cycle progression and functional differentiation. Here we show that depletion of the Ets family transcription factor GA-binding protein (GABP) in T cells impairs T-cell homeostasis. In addition, GABP is critically required for antigen-stimulated T-cell responses in vitro and in vivo. Transcriptome and genome-wide GABP-binding site analyses identify GABP direct targets encoding proteins involved in cellular redox balance and DNA replication, including the Mcm replicative helicases. These findings show that GABP has a nonredundant role in the control of T-cell homeostasis and immunity.

Brain glucose sensing, counterregulation, and energy homeostasis.

Science.gov (United States)

Marty, Nell; Dallaporta, Michel; Thorens, Bernard

2007-08-01

Neuronal circuits in the central nervous system play a critical role in orchestrating the control of glucose and energy homeostasis. Glucose, beside being a nutrient, is also a signal detected by several glucose-sensing units that are located at different anatomical sites and converge to the hypothalamus to cooperate with leptin and insulin in controlling the melanocortin pathway.

ALTERATIONS OF FE HOMEOSTASIS IN RAT CARDIOVASCULAR DISEASE MODELS AND ITS CONTRIBUTION TO CARDIOPULMONARY TOXICITY

Science.gov (United States)

Introduction: Fe homeostasis can be disrupted in human cardiovascular diseases (CVD). We addressed how dysregulation of Fe homeostasis affected the pulmonary inflammation/oxidative stress response and disease progression after exposure to Libby amphibole (LA), an asbestifonn mine...

Hormonal homeostasis in lung cancer patients under combined and radiation treatment

International Nuclear Information System (INIS)

Zotova, I.A.; Firsova, P.P.; Matveenko, E.G.

1984-01-01

Radioimmunoassay of hormonal homeostasis was performed in 200 lung cancer patients before and after combined and radiation treatment and in 25 healthy subjects (controls). The study showed an increase in the basal level of hormones of pituitary - adrenal system matched by a decline in thyroid function. Adequate combined and radiation treatment brought hormone levels to normal. Hormonal disorders accompanying recurrence were identical to those registered at disease onset. In some cases, changes in hormonal homeostasis developed as early as 3-6 months prior to clinically manifest recurrences or dissemination

The Commensal Microbiota Drives Immune Homeostasis

OpenAIRE

Arrieta, Marie-Claire; Finlay, Barton Brett

2012-01-01

For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use t...

MODELLING AND SIMULATING RISKS IN THE TRAINING OF THE HUMAN RESOURCES BY APPLYING THE CHAOS THEORY

OpenAIRE

Eugen ROTARESCU

2012-01-01

The article approaches the modelling and simulation of risks in the training of the human resources, as well as the forecast of the degree of human resources training impacted by risks by applying the mathematical tools offered by the Chaos Theory and mathematical statistics. We will highlight that the level of knowledge, skills and abilities of the human resources from an organization are autocorrelated in time and they depend on the level of a previous moment of the training, as well as on ...

Game theory and risk-based leveed river system planning with noncooperation

Science.gov (United States)

Hui, Rui; Lund, Jay R.; Madani, Kaveh

2016-01-01

Optimal risk-based levee designs are usually developed for economic efficiency. However, in river systems with multiple levees, the planning and maintenance of different levees are controlled by different agencies or groups. For example, along many rivers, levees on opposite riverbanks constitute a simple leveed river system with each levee designed and controlled separately. Collaborative planning of the two levees can be economically optimal for the whole system. Independent and self-interested landholders on opposite riversides often are willing to separately determine their individual optimal levee plans, resulting in a less efficient leveed river system from an overall society-wide perspective (the tragedy of commons). We apply game theory to simple leveed river system planning where landholders on each riverside independently determine their optimal risk-based levee plans. Outcomes from noncooperative games are analyzed and compared with the overall economically optimal outcome, which minimizes net flood cost system-wide. The system-wide economically optimal solution generally transfers residual flood risk to the lower-valued side of the river, but is often impractical without compensating for flood risk transfer to improve outcomes for all individuals involved. Such compensation can be determined and implemented with landholders' agreements on collaboration to develop an economically optimal plan. By examining iterative multiple-shot noncooperative games with reversible and irreversible decisions, the costs of myopia for the future in making levee planning decisions show the significance of considering the externalities and evolution path of dynamic water resource problems to improve decision-making.

Prospect Theory and the Risks Involved in Decision-Making: Content Analysis in ProQuest Articles

Directory of Open Access Journals (Sweden)

Sady Darcy da Silva-Junior

2016-04-01

Full Text Available In this study, the objective is to perform content analysis on articles of a reliable database, dealing with the prospect theory and the risks involved in the decision making process, evaluating some criteria for the theoretical and methodological approaches that allow a joint analysis and comparative. Therefore, a search in ProQuest database was performed which resulted in 15 articles that were submitted to content analysis process, based on the evaluation of nine factors identified by researchers. Among the results highlight the critical attitude to the prospect theory, in contrast to the assertion of his representative capacity of real situations and application in various situations.

Physiological Plausibility and Boundary Conditions of Theories of Risk Sensitivity

DEFF Research Database (Denmark)

Marchiori, Davide; Elqayam, Shira

2012-01-01

dilatation, which in turn positively correlates with a risk aversion behavior. They hypothesize that participants’ attention is increased in decision problems involving losses, which trigger an innate prudent behavior in situations entailing danger and/or hazard. Interestingly, Y&T find that the nature...... of attention is not selective, i.e., when losses are present, participants are shown to devote more attention to the task as a whole rather than to the single negative outcomes, in contrast to Prospect Theory's loss aversion....... and physiological underpinnings of one of the central topics in judgment and decision-making (JDM) research – choice behavior in decisions from experience. Y&T successfully contributes to this goal by demonstrating a novel effect that losses increase experimental participants’ arousal as measured by pupil...

Highly controlled nest homeostasis of honey bees helps deactivate phenolics in nectar

Science.gov (United States)

Liu, Fanglin; He, Jianzhong; Fu, Wenjun

2005-06-01

Honey bees have a highly developed nest homeostasis, for example, maintaining low CO2 levels and stable nest temperatures at 35°C.We investigate the role of nest homeostasis in deactivating phenolic compounds present in the nectar of Aloe littoralis. We show that the phenolic content in nectar was reduced (from 0.65% to 0.49%) after nectar was incubated in a nest of Apis cerana, and that it was reduced still more (from 0.65% to 0.37%) if nectar was mixed with hypopharyngeal gland proteins (HGP) of worker bees before being placed inside a nest. HGP had little effect on samples outside a nest, indicating that nest conditions are necessary for HGP to deactivate phenolics in nectar. Consequently, the highly controlled nest homeostasis of honey bees facilitates direct deactivation of phenolics in nectar, and plays a role in the action of HGP as well.

The influence of bile acids homeostasis by cryptotanshinone ...

African Journals Online (AJOL)

Background: Herbs might affect the homeostasis of bile acids through influence of multiple metabolic pathways of bile acids. Aim: The present study aims to investigate the inhibition of cryptotanshinone towards the glucuronidation of LCA, trying to indicate the possible influence of cryptotanshinone-containing herbs towards ...

Colonic macrophage polarization in homeostasis, inflammation, and cancer

Science.gov (United States)

Appleyard, Caroline B.

2016-01-01

Our review focuses on the colonic macrophage, a monocyte-derived, tissue-resident macrophage, and the role it plays in health and disease, specifically in inflammatory conditions such as inflammatory bowel disease and cancer of the colon and rectum. We give special emphasis to macrophage polarization, or phenotype, in these different states. We focus on macrophages because they are one of the most numerous leukocytes in the colon, and because they normally contribute to homeostasis through an anti-inflammatory phenotype. However, in conditions such as inflammatory bowel disease, proinflammatory macrophages are increased in the colon and have been linked to disease severity and progression. In colorectal cancer, tumor cells may employ anti-inflammatory macrophages to promote tumor growth and dissemination, whereas proinflammatory macrophages may antagonize tumor growth. Given the key roles that this cell type plays in homeostasis, inflammation, and cancer, the colonic macrophage is an intriguing therapeutic target. As such, potential macrophage-targeting strategies are discussed. PMID:27229123

The emerging role of lysosomes in copper homeostasis.

Science.gov (United States)

Polishchuk, Elena V; Polishchuk, Roman S

2016-09-01

The lysosomal system operates as a focal point where a number of important physiological processes such as endocytosis, autophagy and nutrient sensing converge. One of the key functions of lysosomes consists of regulating the metabolism/homeostasis of metals. Metal-containing components are carried to the lysosome through incoming membrane flows, while numerous transporters allow metal ions to move across the lysosome membrane. These properties enable lysosomes to direct metal fluxes to the sites where metal ions are either used by cellular components or sequestered. Copper belongs to a group of metals that are essential for the activity of vitally important enzymes, although it is toxic when in excess. Thus, copper uptake, supply and intracellular compartmentalization have to be tightly regulated. An increasing number of publications have indicated that these processes involve lysosomes. Here we review studies that reveal the expanding role of the lysosomal system as a hub for the control of Cu homeostasis and for the regulation of key Cu-dependent processes in health and disease.

Cellular Links between Neuronal Activity and Energy Homeostasis.

Science.gov (United States)

Shetty, Pavan K; Galeffi, Francesca; Turner, Dennis A

2012-01-01

Neuronal activity, astrocytic responses to this activity, and energy homeostasis are linked together during baseline, conscious conditions, and short-term rapid activation (as occurs with sensory or motor function). Nervous system energy homeostasis also varies during long-term physiological conditions (i.e., development and aging) and with adaptation to pathological conditions, such as ischemia or low glucose. Neuronal activation requires increased metabolism (i.e., ATP generation) which leads initially to substrate depletion, induction of a variety of signals for enhanced astrocytic function, and increased local blood flow and substrate delivery. Energy generation (particularly in mitochondria) and use during ATP hydrolysis also lead to considerable heat generation. The local increases in blood flow noted following neuronal activation can both enhance local substrate delivery but also provides a heat sink to help cool the brain and removal of waste by-products. In this review we highlight the interactions between short-term neuronal activity and energy metabolism with an emphasis on signals and factors regulating astrocyte function and substrate supply.

Comparison of China's oil import risk. Results based on portfolio theory and a diversification index approach

International Nuclear Information System (INIS)

Wu, Gang; Liu, Lan-Cui; Wei, Yi-Ming

2009-01-01

In recent years, the international oil price has fluctuated violently, bringing about huge risk for the international oil trade. In fact, the risk of crude oil and petroleum product imports is different because of the different import origins and prices. Which import risk is lower for China? From the perspective of oil supply security, how should China portfolio crude oil and petroleum product imports to minimize its oil import risk? Using portfolio theory and a diversification index approach, this paper compares and analyzes the supply, price and transport risks of crude oil and petroleum product imports. Our results show that the following: (1) Specific risk (diversification risk) and marine transport risk of China's petroleum product imports are lower than that of crude oil imports. (2) The average rate of return of China's petroleum product imports is higher than that of crude oil imports. Moreover, the average import price variance of petroleum product imports is lower than that of crude oil imports. Thus, the systematic risk (price risk) of petroleum products is lower too. Therefore, from the perspective of oil supply security, China should increase petroleum product imports to decrease its oil import risk. (author)

Regulation of protein homeostasis in neurodegenerative diseases : the role of coding and non-coding genes

NARCIS (Netherlands)

Alvarenga Fernandes Sin, Olga; Nollen, Ellen A. A.

Protein homeostasis is fundamental for cell function and survival, because proteins are involved in all aspects of cellular function, ranging from cell metabolism and cell division to the cell's response to environmental challenges. Protein homeostasis is tightly regulated by the synthesis, folding,

An Evaluation of Financial Institutions: Impact on Consumption and Investment Using Panel Data and the Theory of Risk-Bearing.

Science.gov (United States)

Alem, Mauro; Townsend, Robert M

2014-11-01

The theory of the optimal allocation of risk and the Townsend Thai panel data on financial transactions are used to assess the impact of the major formal and informal financial institutions of an emerging market economy. We link financial institution assessment to the actual impact on clients, rather than ratios and non-performing loans. We derive both consumption and investment equations from a common core theory with both risk and productive activities. The empirical specification follows closely from this theory and allows both OLS and IV estimation. We thus quantify the consumption and investment smoothing impact of financial institutions on households including those running farms and small businesses. A government development bank (BAAC) is shown to be particularly helpful in smoothing consumption and investment, in no small part through credit, consistent with its own operating system, which embeds an implicit insurance operation. Commercial banks are smoothing investment, largely through formal savings accounts. Other institutions seem ineffective by these metrics.

An Evaluation of Financial Institutions: Impact on Consumption and Investment Using Panel Data and the Theory of Risk-Bearing*

Science.gov (United States)

Alem, Mauro; Townsend, Robert M.

2013-01-01

The theory of the optimal allocation of risk and the Townsend Thai panel data on financial transactions are used to assess the impact of the major formal and informal financial institutions of an emerging market economy. We link financial institution assessment to the actual impact on clients, rather than ratios and non-performing loans. We derive both consumption and investment equations from a common core theory with both risk and productive activities. The empirical specification follows closely from this theory and allows both OLS and IV estimation. We thus quantify the consumption and investment smoothing impact of financial institutions on households including those running farms and small businesses. A government development bank (BAAC) is shown to be particularly helpful in smoothing consumption and investment, in no small part through credit, consistent with its own operating system, which embeds an implicit insurance operation. Commercial banks are smoothing investment, largely through formal savings accounts. Other institutions seem ineffective by these metrics. PMID:25400319

Molecular monitoring of equine joint homeostasis

OpenAIRE

de Grauw, J.C.

2010-01-01

Chronic joint disorders are a major cause of impaired mobility and loss of quality of life in both humans and horses. Regardless of the primary insult, any joint disorder is characterized by an upset in normal joint homeostasis, the balance between tissue anabolism and catabolism that is normally maintained by resident articular cells. This upset is often fuelled by a local inflammatory response in the synovial membrane and the articular cartilage. Our current understanding of the pathogenesi...

Orm family proteins mediate sphingolipid homeostasis

DEFF Research Database (Denmark)

Breslow, David K; Collins, Sean R; Bodenmiller, Bernd

2010-01-01

a conserved complex with serine palmitoyltransferase, the first and rate-limiting enzyme in sphingolipid production. We also define a regulatory pathway in which phosphorylation of Orm proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression...... or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma....

Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis

OpenAIRE

Kocalis, Heidi E.; Hagan, Scott L.; George, Leena; Turney, Maxine K.; Siuta, Michael A.; Laryea, Gloria N.; Morris, Lindsey C.; Muglia, Louis J.; Printz, Richard L.; Stanwood, Gregg D.; Niswender, Kevin D.

2014-01-01

Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing...

Exploring the role of glucagon in glucose homeostasis

NARCIS (Netherlands)

Dongen, Maria Gertrud Jobina van

2015-01-01

The aim of this thesis was to gain further insight into the role of glucagon in glucose homeostasis in healthy volunteers and type 2 diabetes mellitus (T2DM) patients, and to explore the novel antisense glucagon receptor antagonist. Chapter 2 showed that the effect of meal replacers containing

Analyzing Test-Taking Behavior: Decision Theory Meets Psychometric Theory.

Science.gov (United States)

Budescu, David V; Bo, Yuanchao

2015-12-01

We investigate the implications of penalizing incorrect answers to multiple-choice tests, from the perspective of both test-takers and test-makers. To do so, we use a model that combines a well-known item response theory model with prospect theory (Kahneman and Tversky, Prospect theory: An analysis of decision under risk, Econometrica 47:263-91, 1979). Our results reveal that when test-takers are fully informed of the scoring rule, the use of any penalty has detrimental effects for both test-takers (they are always penalized in excess, particularly those who are risk averse and loss averse) and test-makers (the bias of the estimated scores, as well as the variance and skewness of their distribution, increase as a function of the severity of the penalty).

The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks

Directory of Open Access Journals (Sweden)

Kim Clarke

2017-11-01

Full Text Available Regular endurance training improves muscle oxidative capacity and reduces the risk of age-related disorders. Understanding the molecular networks underlying this phenomenon is crucial. Here, by exploiting the power of computational modeling, we show that endurance training induces profound changes in gene regulatory networks linking signaling and selective control of translation to energy metabolism and tissue remodeling. We discovered that knockdown of the mTOR-independent factor Eif6, which we predicted to be a key regulator of this process, affects mitochondrial respiration efficiency, ROS production, and exercise performance. Our work demonstrates the validity of a data-driven approach to understanding muscle homeostasis.

Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

Science.gov (United States)

Chen, Xiyue; Eslamfam, Shabnam; Fang, Luoyun; Qiao, Shiyan; Ma, Xi

2017-01-01

Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Zinc signaling : a novel regulatory system on bone homeostasis, and immune and allergic responses].

Science.gov (United States)

Fukada, Toshiyuki; Nishida, Keigo; Yamasaki, Satoru; Hojyo, Shintaro

2012-11-01

Zinc (Zn) is an essential trace element that is required for proliferation, differentiation, and variety of cellular functions, and unbalanced homeostasis of Zn ion (Zn(2 + )) results in health problems such as abnormal bone formation and immunodeficiency. Recent studies have shed light on important roles of Zn(2 + )as a signaling mediator, called Zn signal. Zn(2 + )homeostasis is regulated through Zn transporters and cation channels. Advances of genetic and molecular approaches have revealed that Zn signal regulates mammalian physiology and pathogenesis. We will address that Zn signal undoubtedly contributes to our health, by highlighting it in bone homeostasis and immune regulation, and discuss that the "Zn signal axis" selectively controls intracellular signal transduction to fine-tune cellular functions.

Sustained sleep fragmentation induces sleep homeostasis in mice

KAUST Repository

Baud, Maxime O.; Magistretti, Pierre J.; Petit, Jean Marie

2015-01-01

Study Objectives: Sleep fragmentation (SF) is an integral feature of sleep apnea and other prevalent sleep disorders. Although the effect of repetitive arousals on cognitive performance is well documented, the effects of long-term SF on electroencephalography (EEG) and molecular markers of sleep homeostasis remain poorly investigated. To address this question, we developed a mouse model of chronic SF and characterized its effect on EEG spectral frequencies and the expression of genes previously linked to sleep homeostasis including clock genes, heat shock proteins, and plasticity-related genes. Design: N/A. Setting: Animal sleep research laboratory. Participants : Sixty-six C57BL6/J adult mice. Interventions: Instrumental sleep disruption at a rate of 60/h during 14 days Measurements and Results: Locomotor activity and EEG were recorded during 14 days of SF followed by recovery for 2 days. Despite a dramatic number of arousals and decreased sleep bout duration, SF minimally reduced total quantity of sleep and did not significantly alter its circadian distribution. Spectral analysis during SF revealed a homeostatic drive for slow wave activity (SWA; 1-4 Hz) and other frequencies as well (4-40 Hz). Recordings during recovery revealed slow wave sleep consolidation and a transient rebound in SWA, and paradoxical sleep duration. The expression of selected genes was not induced following chronic SF. Conclusions: Chronic sleep fragmentation (SF) increased sleep pressure confirming that altered quality with preserved quantity triggers core sleep homeostasis mechanisms. However, it did not induce the expression of genes induced by sleep loss, suggesting that these molecular pathways are not sustainably activated in chronic diseases involving SF.

Sustained sleep fragmentation induces sleep homeostasis in mice

KAUST Repository

Baud, Maxime O.

2015-04-01

Study Objectives: Sleep fragmentation (SF) is an integral feature of sleep apnea and other prevalent sleep disorders. Although the effect of repetitive arousals on cognitive performance is well documented, the effects of long-term SF on electroencephalography (EEG) and molecular markers of sleep homeostasis remain poorly investigated. To address this question, we developed a mouse model of chronic SF and characterized its effect on EEG spectral frequencies and the expression of genes previously linked to sleep homeostasis including clock genes, heat shock proteins, and plasticity-related genes. Design: N/A. Setting: Animal sleep research laboratory. Participants : Sixty-six C57BL6/J adult mice. Interventions: Instrumental sleep disruption at a rate of 60/h during 14 days Measurements and Results: Locomotor activity and EEG were recorded during 14 days of SF followed by recovery for 2 days. Despite a dramatic number of arousals and decreased sleep bout duration, SF minimally reduced total quantity of sleep and did not significantly alter its circadian distribution. Spectral analysis during SF revealed a homeostatic drive for slow wave activity (SWA; 1-4 Hz) and other frequencies as well (4-40 Hz). Recordings during recovery revealed slow wave sleep consolidation and a transient rebound in SWA, and paradoxical sleep duration. The expression of selected genes was not induced following chronic SF. Conclusions: Chronic sleep fragmentation (SF) increased sleep pressure confirming that altered quality with preserved quantity triggers core sleep homeostasis mechanisms. However, it did not induce the expression of genes induced by sleep loss, suggesting that these molecular pathways are not sustainably activated in chronic diseases involving SF.

Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis

Science.gov (United States)

Kocalis, Heidi E.; Hagan, Scott L.; George, Leena; Turney, Maxine K.; Siuta, Michael A.; Laryea, Gloria N.; Morris, Lindsey C.; Muglia, Louis J.; Printz, Richard L.; Stanwood, Gregg D.; Niswender, Kevin D.

2014-01-01

Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity, glucose intolerance and behavioral leptin resistance. Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild glucose intolerance. Collectively, we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is important for central regulation of energy and glucose homeostasis. PMID:24944899

Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis.

Science.gov (United States)

Kocalis, Heidi E; Hagan, Scott L; George, Leena; Turney, Maxine K; Siuta, Michael A; Laryea, Gloria N; Morris, Lindsey C; Muglia, Louis J; Printz, Richard L; Stanwood, Gregg D; Niswender, Kevin D

2014-07-01

Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity, glucose intolerance and behavioral leptin resistance. Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild glucose intolerance. Collectively, we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is important for central regulation of energy and glucose homeostasis.

Thiol/disulphide homeostasis in celiac disease

Science.gov (United States)

Kaplan, Mustafa; Ates, Ihsan; Yuksel, Mahmut; Ozderin Ozin, Yasemin; Alisik, Murat; Erel, Ozcan; Kayacetin, Ertugrul

2017-01-01

AIM To determine dynamic thiol/disulphide homeostasis in celiac disease and to examine the associate with celiac autoantibodies and gluten-free diet. METHODS Seventy three patients with celiac disease and 73 healthy volunteers were enrolled in the study. In both groups, thiol/disulphide homeostasis was examined with a new colorimetric method recently developed by Erel and Neselioglu. RESULTS In patients with celiac disease, native thiol (P = 0.027) and total thiol (P = 0.031) levels were lower, while disulphide (P < 0.001) level, disulphide/native thiol (P < 0.001) and disulphide/total thiol (P < 0.001) ratios were higher compared to the control group. In patients who do not comply with a gluten-free diet, disulphide/native thiol ratio was found higher compared to the patients who comply with the diet (P < 0.001). In patients with any autoantibody-positive, disulphide/native thiol ratio was observed higher compared to the patients with autoantibody-negative (P < 0.05). It is found that there is a negative correlation between celiac autoantibodies, and native thiol, total thiol levels and native thiol/total thiol ratio, while a positive correlation is observed between disulphide, disulphide/native thiol and disulphide/total thiol levels. CONCLUSION This study is first in the literature which found that the patients with celiac disease the dynamic thiol/disulphide balance shifts through disulphide form compared to the control group. PMID:28533921

Calcium homeostasis during pregnancy and lactation: role of vitamin ...

African Journals Online (AJOL)

Arun Kumar Agnihotri

skinned but also even Caucasian women tend to go into vitamin D deficiency during ... homeostasis in this phase of life is still controversial. Studies are .... calcium balance in lactating women. .... work on vitamin D. In general these authors.

Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis.

Science.gov (United States)

Bevins, Charles L; Salzman, Nita H

2011-05-01

Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.

Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis

Science.gov (United States)

Hudson, Benjamin H.; Hale, Andrew T.; Irving, Ryan P.; Li, Shenglan; York, John D.

2018-01-01

Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the pathway, bisphosphate 3′-nucleotidase (Bpnt1), in mice, both whole animal and intestine-specific, leads to iron-deficiency anemia. Analysis of mutant enterocytes demonstrates that modulation of their substrate 3′-phosphoadenosine 5′-phosphate (PAP) influences levels of key iron homeostasis factors involved in dietary iron reduction, import and transport, that in part mimic those reported for the loss of hypoxic-induced transcription factor, HIF-2α. Our studies define a genetic basis for iron-deficiency anemia, a molecular approach for rescuing loss of nucleotidase function, and an unanticipated link between nucleotide hydrolysis in the sulfur assimilation pathway and iron homeostasis. PMID:29507250

Origins and Hallmarks of Macrophages: Development, Homeostasis, and Disease

Science.gov (United States)

Wynn, Thomas A.; Chawla, Ajay; Pollard, Jeffrey W.

2013-01-01

Preface Macrophages the most plastic cells of the hematopoietic system are found in all tissues and exhibit great functional diversity. They have roles in development, homeostasis, tissue repair, and immunity. While anatomically distinct, resident tissue macrophages exhibit different transcriptional profiles, and functional capabilities, they are all required for the maintenance of homeostasis. However, these reparative and homeostatic functions can be subverted by chronic insults, resulting in a causal association of macrophages with disease states. In this review, we discuss how macrophages regulate normal physiology and development and provide several examples of their pathophysiologic roles in disease. We define the “hallmarks” of macrophages performing particular functions, taking into account novel insights into the diversity of their lineages, identity, and regulation. This diversity is essential to understand because macrophages have emerged as important therapeutic targets in many important human diseases. PMID:23619691

Salt stress induced ion accumulation, ion homeostasis, membrane ...

African Journals Online (AJOL)

Salt stress induced ion accumulation, ion homeostasis, membrane injury and sugar contents in salt-sensitive rice ( Oryza sativa L. spp. indica ) roots under isoosmotic conditions. ... The accumulation of sugars in PT1 roots may be a primary salt-defense mechanism and may function as an osmotic control. Key words: ...

Regulation of calcium homeostasis in activated human neutrophils ...

African Journals Online (AJOL)

Objectives. The objectives of the current study were to: (i) present an integrated model for the restoration of calcium homeostasis in activated human neutrophils based on current knowledge and recent research; and (ii) identify potential targets for the modulation of calcium fluxes in activated neutrophils based on this model ...

Risk perception and communication in vaccination decisions: a fuzzy-trace theory approach.

Science.gov (United States)

Reyna, Valerie F

2012-05-28

The tenets of fuzzy-trace theory, along with prior research on risk perception and risk communication, are used to develop a process model of vaccination decisions in the era of Web 2.0. The theory characterizes these decisions in terms of background knowledge, dual mental representations (verbatim and gist), retrieval of values, and application of values to representations in context. Lack of knowledge interferes with the ability to extract the essential meaning, or gist, of vaccination messages. Prevention decisions have, by definition, a status quo option of "feeling okay." Psychological evidence from other prevention decisions, such as cancer screening, indicates that many people initially mentally represent their decision options in terms of simple, categorical gist: a choice between (a) a feeling-okay option (e.g., the unvaccinated status quo) versus (b) taking up preventive behavior that can have two potential categorical outcomes: feeling okay or not feeling okay. Hence, applying the same theoretical rules as used to explain framing effects and the Allais paradox, the decision to get a flu shot, for example, boils down to feeling okay (not sick) versus feeling okay (not sick) or not feeling okay (sick, side effects, or death). Because feeling okay is superior to not feeling okay (a retrieved value), this impoverished gist supports choosing not to have the flu vaccine. Anti-vaccination sources provide more coherent accounts of the gist of vaccination than official sources, filling a need to understand rare adverse outcomes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Leptokurtic portfolio theory

Science.gov (United States)

Kitt, R.; Kalda, J.

2006-03-01

The question of optimal portfolio is addressed. The conventional Markowitz portfolio optimisation is discussed and the shortcomings due to non-Gaussian security returns are outlined. A method is proposed to minimise the likelihood of extreme non-Gaussian drawdowns of the portfolio value. The theory is called Leptokurtic, because it minimises the effects from “fat tails” of returns. The leptokurtic portfolio theory provides an optimal portfolio for investors, who define their risk-aversion as unwillingness to experience sharp drawdowns in asset prices. Two types of risks in asset returns are defined: a fluctuation risk, that has Gaussian distribution, and a drawdown risk, that deals with distribution tails. These risks are quantitatively measured by defining the “noise kernel” — an ellipsoidal cloud of points in the space of asset returns. The size of the ellipse is controlled with the threshold parameter: the larger the threshold parameter, the larger return are accepted for investors as normal fluctuations. The return vectors falling into the kernel are used for calculation of fluctuation risk. Analogously, the data points falling outside the kernel are used for the calculation of drawdown risks. As a result the portfolio optimisation problem becomes three-dimensional: in addition to the return, there are two types of risks involved. Optimal portfolio for drawdown-averse investors is the portfolio minimising variance outside the noise kernel. The theory has been tested with MSCI North America, Europe and Pacific total return stock indices.

Ergothioneine Maintains Redox and Bioenergetic Homeostasis Essential for Drug Susceptibility and Virulence of Mycobacterium tuberculosis

Directory of Open Access Journals (Sweden)

Vikram Saini

2016-01-01

Full Text Available The mechanisms by which Mycobacterium tuberculosis (Mtb maintains metabolic equilibrium to survive during infection and upon exposure to antimycobacterial drugs are poorly characterized. Ergothioneine (EGT and mycothiol (MSH are the major redox buffers present in Mtb, but the contribution of EGT to Mtb redox homeostasis and virulence remains unknown. We report that Mtb WhiB3, a 4Fe-4S redox sensor protein, regulates EGT production and maintains bioenergetic homeostasis. We show that central carbon metabolism and lipid precursors regulate EGT production and that EGT modulates drug sensitivity. Notably, EGT and MSH are both essential for redox and bioenergetic homeostasis. Transcriptomic analyses of EGT and MSH mutants indicate overlapping but distinct functions of EGT and MSH. Last, we show that EGT is critical for Mtb survival in both macrophages and mice. This study has uncovered a dynamic balance between Mtb redox and bioenergetic homeostasis, which critically influences Mtb drug susceptibility and pathogenicity.

Cortical delta-opioid receptors potentiate K+ homeostasis during anoxia and oxygen-glucose deprivation.

Science.gov (United States)

Chao, Dongman; Donnelly, David F; Feng, Yin; Bazzy-Asaad, Alia; Xia, Ying

2007-02-01

Central neurons are extremely vulnerable to hypoxic/ischemic insult, which is a major cause of neurologic morbidity and mortality as a consequence of neuronal dysfunction and death. Our recent work has shown that delta-opioid receptor (DOR) is neuroprotective against hypoxic and excitotoxic stress, although the underlying mechanisms remain unclear. Because hypoxia/ischemia disrupts ionic homeostasis with an increase in extracellular K(+), which plays a role in neuronal death, we asked whether DOR activation preserves K(+) homeostasis during hypoxic/ischemic stress. To test this hypothesis, extracellular recordings with K(+)-sensitive microelectrodes were performed in mouse cortical slices under anoxia or oxygen-glucose deprivation (OGD). The main findings in this study are that (1) DOR activation with [D-Ala(2), D-Leu(5)]-enkephalinamide attenuated the anoxia- and OGD-induced increase in extracellular K(+) and decrease in DC potential in cortical slices; (2) DOR inhibition with naltrindole, a DOR antagonist, completely abolished the DOR-mediated prevention of increase in extracellular K(+) and decrease in DC potential; (3) inhibition of protein kinase A (PKA) with N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide dihydrochloride had no effect on the DOR protection; and (4) inhibition of protein kinase C (PKC) with chelerythrine chloride reduced the DOR protection, whereas the PKC activator (phorbol 12-myristate 13-acetate) mimicked the effect of DOR activation on K(+) homeostasis. These data suggest that activation of DOR protects the cortex against anoxia- or ODG-induced derangement of potassium homeostasis, and this protection occurs via a PKC-dependent and PKA-independent pathway. We conclude that an important aspect of DOR-mediated neuroprotection is its early action against derangement of K(+) homeostasis during anoxia or ischemia.

Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis.

Science.gov (United States)

Berglund, Eric D; Liu, Chen; Sohn, Jong-Woo; Liu, Tiemin; Kim, Mi Hwa; Lee, Charlotte E; Vianna, Claudia R; Williams, Kevin W; Xu, Yong; Elmquist, Joel K

2013-12-01

Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high-fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen-inducible POMC-cre system. These data demonstrate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control.

nfluence of antidepressants on glucose homeostasis : effects and mechanisms

NARCIS (Netherlands)

Derijks, H.J.

2009-01-01

Depression has shown to be a common morbidity in patients with diabetes mellitus and comorbid depression in diabetes mellitus patients is frequently treated with antidepressants. It has been postulated that antidepressants may interfere with glucose homeostasis and that the interference of

Asiatic acid influences glucose homeostasis in P. berghei murine ...

African Journals Online (AJOL)

Background: Glucose homeostasis derangement is a common pathophysiology of malaria whose aetiology is still controversial. The Plasmodium parasite, immunological and inflammatory responses, as well as chemotherapeutics currently used cause hypoglycaemia in malaria. Anti-parasitic and anti-disease drugs are ...

Setting sail for glucose homeostasis with the AKAP150-PP2B-anchor.

Science.gov (United States)

Teo, Adrian Kee Keong; Kulkarni, Rohit N

2012-10-17

Glucose-stimulated insulin secretion, controlled by multiple protein phosphorylation events, is critical for the regulation of glucose homeostasis. Protein kinase A (PKA) is known to play a role in β cell physiology, but the role of its anchoring protein is not fully understood. Hinke et al (2012) illustrate the significance of A-kinase anchoring protein 150 in tethering protein phosphatase 2B to mediate nutrient-stimulated insulin secretion and thus modulate glucose homeostasis.

An introduction to decision theory

NARCIS (Netherlands)

Peterson, M.B.

2009-01-01

This up-to-date introduction to decision theory offers comprehensive and accessible discussions of decision making under ignorance and risk, the foundations of utility theory, the debate over subjective and objective probability, Bayesianism, causal decision theory, game theory and social choice

TRPV5, the gateway to Ca2+ homeostasis.

NARCIS (Netherlands)

Mensenkamp, A.R.; Hoenderop, J.G.J.; Bindels, R.J.M.

2007-01-01

Ca2+ homeostasis in the body is tightly controlled, and is a balance between absorption in the intestine, excretion via the urine, and exchange from bone. Recently, the epithelial Ca2+ channel (TRPV5) has been identified as the gene responsible for the Ca2+ influx in epithelial cells of the renal

The influence of bile acids homeostasis by cryptotanshinone ...

African Journals Online (AJOL)

The homeostasis of bile acids can be tightly regulated through feed-back and feed-forward regula- tion pathways. Bile acids exert their toxicity towards cells at high concentrations, and the accumulation of bile acids can induce the severe damage towards liver cells 2. Bile acids have been reported to induce cell injury.

Combination of qualitative and quantitative sources of knowledge for risk assessment in the framework of possibility theory

NARCIS (Netherlands)

Oussalah, M.; Newby, M.J.

2004-01-01

This paper focuses on a representation of system reliability in the framework of possibility theory. Particularly, given a (probabilistic) quantitative knowledge pertaining to the time to failure of a system (risk function) and some qualitative knowledge about the degree of pessimism and optimism of

Disruption of gut homeostasis by opioids accelerates HIV disease progression

Directory of Open Access Journals (Sweden)

Jingjing eMeng

2015-06-01

Full Text Available Cumulative studies during the past 30 years have established the correlation between opioid abuse and human immunodeficiency virus (HIV infection. Further studies also demonstrate that opioid addiction is associated with faster progression to AIDS in patients. Recently, it was revealed that disruption of gut homeostasis and subsequent microbial translocation play important roles in pathological activation of the immune system during HIV infection and contributes to accelerated disease progression. Similarly, opioids have been shown to modulate gut immunity and induce gut bacterial translocation. This review will explore the mechanisms by which opioids accelerate HIV disease progression by disrupting gut homeostasis. Better understanding of these mechanisms will facilitate the search for new therapeutic interventions to treat HIV infection especially in opioid abusing population.

Central insulin and leptin-mediated autonomic control of glucose homeostasis.

Science.gov (United States)

Marino, Joseph S; Xu, Yong; Hill, Jennifer W

2011-07-01

Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular play a crucial role in the development of insulin resistance. This review discusses the neuronal crosstalk between the hypothalamus, autonomic nervous system, and tissues associated with the pathogenesis of type 2 diabetes, and how hypothalamic insulin and leptin signaling are integral to maintaining normal glucose homeostasis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Serum PBDE levels in exposed rats in relation to effects on thyroxine homeostasis

Energy Technology Data Exchange (ETDEWEB)

Darnerud, P.O.; Aune, M.; Larsson, L.; Hallgren, S. [National Food Administration, Uppsala (Sweden)

2004-09-15

Brominated flame retardants (BFRs) is a group of environmental chemicals for which lately both interest and knowledge have increased considerably. Among the BFRs, the polybrominated diphenyl ethers (PBDEs) have attained special interest. Much data on environmental and human levels have been presented and several toxicological reviews are now published. Among interesting results is the difference in human PBDE levels that seem to exist between U.S.A. and Europe, results that suggest differences in exposure but without being able to pin-point the exact sources. In experimental studies PBDEs alter serum thyroxin levels, an effect seen both in rats and in mice. The mechanism(s) are still not completely clarified, but are thought to include alterations in serum transport, induced enzymatic degradation and possibly also direct effects on the thyroid gland. As perinatal alterations in thyroid homeostasis could affect brain development, early effects on thyroid hormones may be of special concern. Indeed, PBDEs have been shown to affect behaviour and learning in mice, when given neonatally. The aim of the present study was to relate the serum levels of PBDEs in rats to effects of these compounds on thyroxine homeostasis in these animals. Specifically, the relation between serum PBDE levels and effects on serum thyroxine levels was investigated, after two weeks of daily oral exposure. The result may have consequences for the future risk assessment activities on PBDE and specifically in finding the critical serum PBDE concentration at which the effect on thyroid hormone levels begin to occur.

Random matrix theory filters in portfolio optimisation: A stability and risk assessment

Science.gov (United States)

Daly, J.; Crane, M.; Ruskin, H. J.

2008-07-01

Random matrix theory (RMT) filters, applied to covariance matrices of financial returns, have recently been shown to offer improvements to the optimisation of stock portfolios. This paper studies the effect of three RMT filters on the realised portfolio risk, and on the stability of the filtered covariance matrix, using bootstrap analysis and out-of-sample testing. We propose an extension to an existing RMT filter, (based on Krzanowski stability), which is observed to reduce risk and increase stability, when compared to other RMT filters tested. We also study a scheme for filtering the covariance matrix directly, as opposed to the standard method of filtering correlation, where the latter is found to lower the realised risk, on average, by up to 6.7%. We consider both equally and exponentially weighted covariance matrices in our analysis, and observe that the overall best method out-of-sample was that of the exponentially weighted covariance, with our Krzanowski stability-based filter applied to the correlation matrix. We also find that the optimal out-of-sample decay factors, for both filtered and unfiltered forecasts, were higher than those suggested by Riskmetrics [J.P. Morgan, Reuters, Riskmetrics technical document, Technical Report, 1996. http://www.riskmetrics.com/techdoc.html], with those for the latter approaching a value of α=1. In conclusion, RMT filtering reduced the realised risk, on average, and in the majority of cases when tested out-of-sample, but increased the realised risk on a marked number of individual days-in some cases more than doubling it.

NATO Advanced Study Institute on Insurance and Risk Theory

CERN Document Server

Vylder, F; Haezendonck, J

1986-01-01

Canadian financial institutions have been in rapid change in the past five years. In response to these changes, the Department of Finance issued a discussion paper: The Regulation of Canadian Financial Institutions, in April 1985, and the government intends to introduce legislation in the fall. This paper studi.es the combinantion of financial institutions from the viewpoint of ruin probability. In risk theory developed to describe insurance companies [1,2,3,4,5J, the ruin probability of a company with initial reserve (capital) u is 6 1 -:;-7;;f3 u 1jJ(u) = H6 e H6 (1) Here,we assume that claims arrive as a Poisson process, and the claim amount is distributed as exponential distribution with expectation liS. 6 is the loading, i.e., premium charged is (1+6) times expected claims. Financial institutions are treated as "insurance companies": the difference between interest charged and interest paid is regarded as premiums, loan defaults are treated as claims.

A discussion of the limitations of the psychometric and cultural theory approaches to risk perception

International Nuclear Information System (INIS)

Sjoeberg, L.

1996-01-01

Risk perception has traditionally been conceived as a cognitive phenomenon, basically a question of information processing. The very term perception suggests that information processing is involved and of crucial importance. Kahneman and Tversky suggested that the use of 'heuristics' in the intuitive estimation of probabilities accounts for biased probability perception, hence claiming to explain risk perception as well. The psychometric approach of Slovic et al, a further step in in the cognitive tradition, conceives of perceived risk as a function of general properties of a hazard. However, the psychometric approach is shown here to explain only about 20% of the variance of perceived risk, even less of risk acceptability. Its claim to explanatory power is based on a statistical illusion: mean values were investigated and accounted for, across hazards. A currently popular alternative to the psychometric tradition, Cultural Theory, is even less successful and explains only about 5% of the variance of perceived risk. The claims of this approach were also based on a statistical illusion: 'significant' results were reported and interpreted as being of substantial importance. The present paper presents a new approach: attitude to the risk generating technology, general sensitivity to risks and specific risk explained well over 60% of the variance of perceived risk of nuclear waste, in a study of extensive data from a representative sample of the Swedish population. The attitude component functioning as an explanatory factor of perceived risk, rather than as a consequence of perceived risk, suggests strongly that perceived risk is something other than cognition. Implications for risk communication are discussed. (author)

Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1

Directory of Open Access Journals (Sweden)

Karla A. Mark

2016-10-01

Full Text Available Vitamin D has multiple roles, including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitamin D, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases, including Alzheimer’s disease, Parkinson’s disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that vitamin-D3-induced lifespan extension requires the stress response pathway genes skn-1, ire-1, and xbp-1. Vitamin D3 (D3 induced expression of SKN-1 target genes but not canonical targets of XBP-1. D3 suppressed an important molecular pathology of aging, that of widespread protein insolubility, and prevented toxicity caused by human β-amyloid. Our observation that D3 improves protein homeostasis and slows aging highlights the importance of maintaining appropriate vitamin D serum levels and may explain why such a wide variety of human age-related diseases are associated with vitamin D deficiency.

Control of Homeostasis and Dendritic Cell Survival by the GTPase RhoA

DEFF Research Database (Denmark)

Li, Shuai; Dislich, Bastian; Brakebusch, Cord H

2015-01-01

11b(-)CD8(+) and CD11b(+)Esam(hi) DC subsets, whereas CD11b(+)Esam(lo) DCs were not affected in conditional RhoA-deficient mice. Proteome analyses revealed a defective prosurvival pathway via PI3K/protein kinase B (Akt1)/Bcl-2-associated death promoter in the absence of RhoA. Taken together, our...... findings identify RhoA as a central regulator of DC homeostasis, and its deletion decreases DC numbers below critical thresholds for immune protection and homeostasis, causing aberrant compensatory DC proliferation....

Bone morphogenetic proteins in inflammation, glucose homeostasis and adipose tissue energy metabolism

DEFF Research Database (Denmark)

Grgurevic, Lovorka; Christensen, Gitte Lund; Schulz, Tim J

2016-01-01

implicated in pancreas development as well as control of adult glucose homeostasis. Lastly, we review the recently recognized role of BMPs in brown adipose tissue formation and their consequences for energy expenditure and adiposity. In summary, BMPs play a pivotal role in metabolism beyond their role...... homeostasis (anaemia, hemochromatosis) and oxidative damage. The second and third parts of this review focus on BMPs in the development of metabolic pathologies such as type-2 diabetes mellitus and obesity. The pancreatic beta cells are the sole source of the hormone insulin and BMPs have recently been...

Postradiation immunoendocrine homeostasis in patients with cancer of the buccal mucosa

International Nuclear Information System (INIS)

Savina, N.P.; Pavlov, A.S.; Lyasko, L.I.

1993-01-01

A follow-up of the immune and endocrine homeostasis was carried out for 1 to 3 years in 80 patients with cancer of the buccal mucose (T 1-2 , N 0 , M 0 ), exposed to intratissue therapy with 252 Cf and 60 Co alone and in combination with longdistance gamma-beam therapy. The status of the postradiation immune and endocrine homeostasis was found to depend on the dose load of the critical organs, the thymus and hypophysis. Complete recovery of the parameters was obsered in the patients administered lower irradiation dose, whereas after higher doses of irradiation no complete recovery was observed in remote periods after radiotherapy

Signalling from the periphery to the brain that regulates energy homeostasis.

Science.gov (United States)

Kim, Ki-Suk; Seeley, Randy J; Sandoval, Darleen A

2018-04-01

The CNS regulates body weight; however, we still lack a clear understanding of what drives decisions about when, how much and what to eat. A vast array of peripheral signals provides information to the CNS regarding fluctuations in energy status. The CNS then integrates this information to influence acute feeding behaviour and long-term energy homeostasis. Previous paradigms have delegated the control of long-term energy homeostasis to the hypothalamus and short-term changes in feeding behaviour to the hindbrain. However, recent studies have identified target hindbrain neurocircuitry that integrates the orchestration of individual bouts of ingestion with the long-term regulation of energy balance.

Challenging homeostasis to define biomarkers for nutrition related health

NARCIS (Netherlands)

Ommen, van B.; Keijer, J.; Heil, S.G.; Kaput, J.

2009-01-01

A primary goal of nutrition research is to optimize health and prevent or delay disease. Biomarkers to quantify health optimization are needed since many if not most biomarkers are developed for diseases. Quantifying normal homeostasis and developing validated biomarkers are formidable tasks because

Renal renin secretion as regulator of body fluid homeostasis

DEFF Research Database (Denmark)

Damkjær, Mads; Isaksson, Gustaf L; Stubbe, Jane

2013-01-01

The renin-angiotensin system is essential for body fluid homeostasis and blood pressure regulation. This review focuses on the homeostatic regulation of the secretion of active renin in the kidney, primarily in humans. Under physiological conditions, renin secretion is determined mainly by sodium...

Activating transcription factor 3 regulates immune and metabolic homeostasis

Czech Academy of Sciences Publication Activity Database

Ryneš, J.; Donohoe, C. D.; Frommolt, P.; Brodesser, S.; Jindra, Marek; Uhlířová, M.

2012-01-01

Roč. 32, č. 19 (2012), s. 3949-3962 ISSN 0270-7306 R&D Projects: GA ČR(CZ) GD204/09/H058 Institutional support: RVO:60077344 Keywords : metabolic homeostasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.372, year: 2012

Multilevel control of glucose homeostasis by adenylyl cyclase 8

NARCIS (Netherlands)

Raoux, Matthieu; Vacher, Pierre; Papin, Julien; Picard, Alexandre; Kostrzewa, Elzbieta; Devin, Anne; Gaitan, Julien; Limon, Isabelle; Kas, Martien J.; Magnan, Christophe; Lang, Jochen

2015-01-01

Aims/hypothesis: Nutrient homeostasis requires integration of signals generated by glucose metabolism and hormones. Expression of the calcium-stimulated adenylyl cyclase ADCY8 is regulated by glucose and the enzyme is capable of integrating signals from multiple pathways. It may thus have an

Integrative studies on cartilage tissue engineering and joint homeostasis

NARCIS (Netherlands)

Rutgers, M.

2014-01-01

The impact of cartilage injury to the joint is often larger than the initial clinical symptoms suggest. Through an alteration in joint homeostasis and biomechanical loading, cartilage lesions may accelerate osteoarthritis onset. Although good clinical results are achieved in patients treated by the

Atmospheric Convective Organization: Self-Organized Criticality or Homeostasis?

Science.gov (United States)

Yano, Jun-Ichi

2015-04-01

Atmospheric convection has a tendency organized on a hierarchy of scales ranging from the mesoscale to the planetary scales, with the latter especially manifested by the Madden-Julian oscillation. The present talk examines two major possible mechanisms of self-organization identified in wider literature from a phenomenological thermodynamic point of view by analysing a planetary-scale cloud-resolving model simulation. The first mechanism is self-organized criticality. A saturation tendency of precipitation rate with the increasing column-integrated water, reminiscence of critical phenomena, indicates self-organized criticality. The second is a self-regulation mechanism that is known as homeostasis in biology. A thermodynamic argument suggests that such self-regulation maintains the column-integrated water below a threshold by increasing the precipitation rate. Previous analyses of both observational data as well as cloud-resolving model (CRM) experiments give mixed results. A satellite data analysis suggests self-organized criticality. Some observational data as well as CRM experiments support homeostasis. Other analyses point to a combination of these two interpretations. In this study, a CRM experiment over a planetary-scale domain with a constant sea-surface temperature is analyzed. This analysis shows that the relation between the column-integrated total water and precipitation suggests self-organized criticality, whereas the one between the column-integrated water vapor and precipitation suggests homeostasis. The concurrent presence of these two mechanisms are further elaborated by detailed statistical and budget analyses. These statistics are scale invariant, reflecting a spatial scaling of precipitation processes. These self-organization mechanisms are most likely be best theoretically understood by the energy cycle of the convective systems consisting of the kinetic energy and the cloud-work function. The author has already investigated the behavior of this

Tuning of redox regulatory mechanisms, reactive oxygen species and redox homeostasis under salinity stress

Directory of Open Access Journals (Sweden)

Hossain eSazzad

2016-05-01

Full Text Available Soil salinity is a crucial environmental constraint which limits biomass production at many sites on a global scale. Saline growth conditions cause osmotic and ionic imbalances, oxidative stress and perturb metabolism, e.g. the photosynthetic electron flow. The plant ability to tolerate salinity is determined by multiple biochemical and physiological mechanisms protecting cell functions, in particular by regulating proper water relations and maintaining ion homeostasis. Redox homeostasis is a fundamental cell property. Its regulation includes control of reactive oxygen species (ROS generation, sensing deviation from and readjustment of the cellular redox state. All these redox related functions have been recognized as decisive factors in salinity acclimation and adaptation. This review focuses on the core response of plants to overcome the challenges of salinity stress through regulation of ROS generation and detoxification systems and to maintain redox homeostasis. Emphasis is given to the role of NADH oxidase (RBOH, alternative oxidase (AOX, the plastid terminal oxidase (PTOX and the malate valve with the malate dehydrogenase isoforms under salt stress. Overwhelming evidence assigns an essential auxiliary function of ROS and redox homeostasis to salinity acclimation of plants.

Neuroimmune interaction and the regulation of intestinal immune homeostasis.

Science.gov (United States)

Verheijden, Simon; Boeckxstaens, Guy E

2018-01-01

Many essential gastrointestinal functions, including motility, secretion, and blood flow, are regulated by the autonomic nervous system (ANS), both through intrinsic enteric neurons and extrinsic (sympathetic and parasympathetic) innervation. Recently identified neuroimmune mechanisms, in particular the interplay between enteric neurons and muscularis macrophages, are now considered to be essential for fine-tuning peristalsis. These findings shed new light on how intestinal immune cells can support enteric nervous function. In addition, both intrinsic and extrinsic neural mechanisms control intestinal immune homeostasis in different layers of the intestine, mainly by affecting macrophage activation through neurotransmitter release. In this mini-review, we discuss recent insights on immunomodulation by intrinsic enteric neurons and extrinsic innervation, with a particular focus on intestinal macrophages. In addition, we discuss the relevance of these novel mechanisms for intestinal immune homeostasis in physiological and pathological conditions, mainly focusing on motility disorders (gastroparesis and postoperative ileus) and inflammatory disorders (colitis).

CNS-targets in control of energy and glucose homeostasis.

Science.gov (United States)

Kleinridders, André; Könner, A Christine; Brüning, Jens C

2009-12-01

The exceeding efforts in understanding the signals initiated by nutrients and hormones in the central nervous system (CNS) to regulate glucose and energy homeostasis have largely revolutionized our understanding of the neurocircuitry in control of peripheral metabolism. The ability of neurons to sense nutrients and hormones and to adopt a coordinated response to these signals is of crucial importance in controlling food intake, energy expenditure, glucose and lipid metabolism. Anatomical lesion experiments, pharmacological inhibition of signaling pathways, and, more recently, the analysis of conditional mouse mutants with modifications of hormone and nutrient signaling in defined neuronal populations have broadened our understanding of these complex neurocircuits. This review summarizes recent findings regarding the role of the CNS in sensing and transmitting nutritional and hormonal signals to control energy and glucose homeostasis and aims to define them as potential novel drug targets for the treatment of obesity and type 2 diabetes mellitus.

Energy homeostasis regulatory peptides in hibernating grizzly bears.

Science.gov (United States)

Gardi, János; Nelson, O Lynne; Robbins, Charles T; Szentirmai, Eva; Kapás, Levente; Krueger, James M

2011-05-15

Grizzly bears (Ursus arctos horribilis) are inactive for up to 6 months during hibernation. They undergo profound seasonal changes in food intake, body mass, and energy expenditure. The circa-annual regulation of metabolism is poorly understood. In this study, we measured plasma ghrelin, leptin, obestatin, and neuropeptide-Y (NPY) levels, hormones known to be involved in the regulation of energy homeostasis, in ten grizzly bears. Blood samples were collected during the active summer period, early hibernation and late hibernation. Plasma levels of leptin, obestatin, and NPY did not change between the active and the hibernation periods. Plasma total ghrelin and desacyl-ghrelin concentrations significantly decreased during the inactive winter period compared to summer levels. The elevated ghrelin levels may help enhance body mass during pre-hibernation, while the low plasma ghrelin concentrations during hibernation season may contribute to the maintenance of hypophagia, low energy utilization and behavioral inactivity. Our results suggest that ghrelin plays a potential role in the regulation of metabolic changes and energy homeostasis during hibernation in grizzly bears. Copyright © 2011 Elsevier Inc. All rights reserved.

Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation.

Science.gov (United States)

Molofsky, Ari B; Savage, Adam K; Locksley, Richard M

2015-06-16

Interleukin-33 (IL-33) is a nuclear-associated cytokine of the IL-1 family originally described as a potent inducer of allergic type 2 immunity. IL-33 signals via the receptor ST2, which is highly expressed on group 2 innate lymphoid cells (ILC2s) and T helper 2 (Th2) cells, thus underpinning its association with helminth infection and allergic pathology. Recent studies have revealed ST2 expression on subsets of regulatory T cells, and for a role for IL-33 in tissue homeostasis and repair that suggests previously unrecognized interactions within these cellular networks. IL-33 can participate in pathologic fibrotic reactions, or, in the setting of microbial invasion, can cooperate with inflammatory cytokines to promote responses by cytotoxic NK cells, Th1 cells, and CD8(+) T cells. Here, we highlight the regulation and function of IL-33 and ST2 and review their roles in homeostasis, damage, and inflammation, suggesting a conceptual framework for future studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Cellular Links Between Neuronal Activity and Energy Homeostasis

Directory of Open Access Journals (Sweden)

Pavan K Shetty

2012-03-01

Full Text Available Neuronal activity, astrocytic responses to this activity, and energy homeostasis are linked together during baseline, conscious conditions, and short-term rapid activation (as occurs with sensory or motor function. Nervous system energy homeostasis also varies during long-term physiological conditions (ie, development and aging and with adaptation to pathological conditions, such as ischemia or low glucose. Neuronal activation requires increased metabolism (i.e., ATP generation which leads initially to substrate depletion, induction of a variety of signals for enhanced astrocytic function, and increased local blood flow and substrate delivery. Energy generation (particularly in mitochondria and use during ATP hydrolysis also lead to considerable heat generation. The local increases in blood flow noted following neuronal activation can both enhance local substrate delivery but also provides a heat sink to help cool the brain and removal of waste byproducts. In this review we highlight the interactions between short-term neuronal activity and energy metabolism with an emphasis on signals and factors regulating astrocyte function and substrate supply.

Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity

OpenAIRE

Xuemei Shi; Shaji Chacko; Feng Li; Depei Li; Douglas Burrin; Lawrence Chan; Xinfu Guan

2017-01-01

Objective: Glucagon-like peptides are co-released from enteroendocrine L cells in the gut and preproglucagon (PPG) neurons in the brainstem. PPG-derived GLP-1/2 are probably key neuroendocrine signals for the control of energy balance and glucose homeostasis. The objective of this study was to determine whether activation of PPG neurons per se modulates glucose homeostasis and insulin sensitivity in vivo. Methods: We generated glucagon (Gcg) promoter-driven Cre transgenic mice and injected...

Cooperation between brain and islet in glucose homeostasis and diabetes

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Schwartz, Michael W.; Seeley, Randy J.; Tschöp, Matthias H.; Woods, Stephen C.; Morton, Gregory J.; Myers, Martin G.; D'Alessio, David

2014-01-01

Although a prominent role for the brain in glucose homeostasis was proposed by scientists in the nineteenth century, research throughout most of the twentieth century focused on evidence that the function of pancreatic islets is both necessary and sufficient to explain glucose homeostasis, and that diabetes results from defects of insulin secretion, action or both. However, insulin-independent mechanisms, referred to as ‘glucose effectiveness’, account for roughly 50% of overall glucose disposal, and reduced glucose effectiveness also contributes importantly to diabetes pathogenesis. Although mechanisms underlying glucose effectiveness are poorly understood, growing evidence suggests that the brain can dynamically regulate this process in ways that improve or even normalize glycaemia in rodent models of diabetes. Here we present evidence of a brain-centred glucoregulatory system (BCGS) that can lower blood glucose levels via both insulin-dependent and -independent mechanisms, and propose a model in which complex and highly coordinated interactions between the BCGS and pancreatic islets promote normal glucose homeostasis. Because activation of either regulatory system can compensate for failure of the other, defects in both may be required for diabetes to develop. Consequently, therapies that target the BCGS in addition to conventional approaches based on enhancing insulin effects may have the potential to induce diabetes remission, whereas targeting just one typically does not. PMID:24201279

Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota.

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Peterson, C T; Sharma, V; Elmén, L; Peterson, S N

2015-03-01

The distal gut harbours ∼10(13) bacteria, representing the most densely populated ecosystem known. The functional diversity expressed by these communities is enormous and relatively unexplored. The past decade of research has unveiled the profound influence that the resident microbial populations bestow to host immunity and metabolism. The evolution of these communities from birth generates a highly adapted and highly personalized microbiota that is stable in healthy individuals. Immune homeostasis is achieved and maintained due in part to the extensive interplay between the gut microbiota and host mucosal immune system. Imbalances of gut microbiota may lead to a number of pathologies such as obesity, type I and type II diabetes, inflammatory bowel disease (IBD), colorectal cancer (CRC) and inflammaging/immunosenscence in the elderly. In-depth understanding of the underlying mechanisms that control homeostasis and dysbiosis of the gut microbiota represents an important step in our ability to reliably modulate the gut microbiota with positive clinical outcomes. The potential of microbiome-based therapeutics to treat epidemic human disease is of great interest. New therapeutic paradigms, including second-generation personalized probiotics, prebiotics, narrow spectrum antibiotic treatment and faecal microbiome transplantation, may provide safer and natural alternatives to traditional clinical interventions for chronic diseases. This review discusses host-microbiota homeostasis, consequences of its perturbation and the associated challenges in therapeutic developments that lie ahead. © 2014 British Society for Immunology.

Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis

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Chen, Jing; Zhang, Xiaolu; Kusumo, Handojo; Costa, Lucio G.; Guizzetti, Marina

2012-01-01

Disruption of cholesterol homeostasis in the central nervous system (CNS) has been associated with neurological, neurodegenerative, and neurodevelopmental disorders. The CNS is a closed system with regard to cholesterol homeostasis, as cholesterol-delivering lipoproteins from the periphery cannot pass the blood-brain-barrier and enter the brain. Different cell types in the brain have different functions in the regulation of cholesterol homeostasis, with astrocytes producing and releasing apolipoprotein E and lipoproteins, and neurons metabolizing cholesterol to 24(S)-hydroxycholesterol. We present evidence that astrocytes and neurons adopt different mechanisms also in regulating cholesterol efflux. We found that in astrocytes cholesterol efflux is induced by both lipid-free apolipoproteins and lipoproteins, while cholesterol removal from neurons is triggered only by lipoproteins. The main pathway by which apolipoproteins induce cholesterol efflux is through ABCA1. By upregulating ABCA1 levels and by inhibiting its activity and silencing its expression, we show that ABCA1 is involved in cholesterol efflux from astrocytes but not from neurons. Furthermore, our results suggest that ABCG1 is involved in cholesterol efflux to apolipoproteins and lipoproteins from astrocytes but not from neurons, while ABCG4, whose expression is much higher in neurons than astrocytes, is involved in cholesterol efflux from neurons but not astrocytes. These results indicate that different mechanisms regulate cholesterol efflux from neurons and astrocytes, reflecting the different roles that these cell types play in brain cholesterol homeostasis. These results are important in understanding cellular targets of therapeutic drugs under development for the treatments of conditions associated with altered cholesterol homeostasis in the CNS. PMID:23010475

Impaired striatal Akt signaling disrupts dopamine homeostasis and increases feeding.

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Nicole Speed

Full Text Available The prevalence of obesity has increased dramatically worldwide. The obesity epidemic begs for novel concepts and therapeutic targets that cohesively address "food-abuse" disorders. We demonstrate a molecular link between impairment of a central kinase (Akt involved in insulin signaling induced by exposure to a high-fat (HF diet and dysregulation of higher order circuitry involved in feeding. Dopamine (DA rich brain structures, such as striatum, provide motivation stimuli for feeding. In these central circuitries, DA dysfunction is posited to contribute to obesity pathogenesis. We identified a mechanistic link between metabolic dysregulation and the maladaptive behaviors that potentiate weight gain. Insulin, a hormone in the periphery, also acts centrally to regulate both homeostatic and reward-based HF feeding. It regulates DA homeostasis, in part, by controlling a key element in DA clearance, the DA transporter (DAT. Upon HF feeding, nigro-striatal neurons rapidly develop insulin signaling deficiencies, causing increased HF calorie intake.We show that consumption of fat-rich food impairs striatal activation of the insulin-activated signaling kinase, Akt. HF-induced Akt impairment, in turn, reduces DAT cell surface expression and function, thereby decreasing DA homeostasis and amphetamine (AMPH-induced DA efflux. In addition, HF-mediated dysregulation of Akt signaling impairs DA-related behaviors such as (AMPH-induced locomotion and increased caloric intake. We restored nigro-striatal Akt phosphorylation using recombinant viral vector expression technology. We observed a rescue of DAT expression in HF fed rats, which was associated with a return of locomotor responses to AMPH and normalization of HF diet-induced hyperphagia.Acquired disruption of brain insulin action may confer risk for and/or underlie "food-abuse" disorders and the recalcitrance of obesity. This molecular model, thus, explains how even short-term exposure to "the fast food

Evaluation of dynamic serum thiol/disulfide homeostasis in locally advanced and metastatic gastric cancer

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Mutlu Hizal

2018-04-01

Full Text Available Background: Gastric cancer is one the most diagnosed cancer and the third leading cause of death from cancer worldwide. As an indicator of antioxidant capacity thiol/disulfide homeostasis regulates detoxification, cell signal mechanisms, apoptosis, transcription and antioxidant defense mechanisms. Disregulation of thiol/disulfide homeostasis identified in other cancer types by recent data. In this study, we aimed to evaluate the thiol/disulfide homeostasis in advanced gastric cancer patients. Methods: The patients who diagnosed with gastric cancer and healthy control subjects were included to study. Serum samples for the thiol-disulphide test were obtained at the time of diagnosis. Thiol-disulphide homeostasis tests were measured by the automated spectrophotometric method. Thiol-disulphide homeostasis was also measured according to clinical and laboratory features. Results: Thirty newly diagnosed advanced gastric adenocarcinoma patients and 28 healthy controls were enrolled in the study. The native thiol (NT and total thiol (TT levels of patients' group were significantly lower compared with controls (p = 0.001 and p < 0.001. In the CEA high (≥5.4 ng/ml group, DS/NT ratio were higher compared with CEA low (<5.4 ng/ml group (p = 0.024. In CA.19-9 high (≥28.3 kU/L group, both DS and DS/NT ratio were significantly higher compared with a CA19-9 low(<28.3 kU/L group (p < 0.05 both. The correlation between CEA and DS levels was also significant (p = 0.02. There was also a positive correlation between CEA levels and DS/NT ratio (p = 0.01. Conclusion: Derangements of thiol/disulfide homeostasis may have a role in gastric cancer pathogenesis and the higher level of oxidative stress may relate to extensive and aggressiveness of the advanced disease. The diagnostic and prognostic values of thiol/disulfide products need to identify with further studies. Keywords: Thiol, Disulfide, Oxidative stress, Gastric cancer, Metastatic

Risk and Rationality in Adolescent Decision Making: Implications for Theory, Practice, and Public Policy.

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Reyna, Valerie F; Farley, Frank

2006-09-01

conditions), adolescents are capable of rational decision making to achieve their goals. In practice, much depends on the particular situation in which a decision is made. In the heat of passion, in the presence of peers, on the spur of the moment, in unfamiliar situations, when trading off risks and benefits favors bad long-term outcomes, and when behavioral inhibition is required for good outcomes, adolescents are likely to reason more poorly than adults do. Brain maturation in adolescence is incomplete. Impulsivity, sensation seeking, thrill seeking, depression, and other individual differences also contribute to risk taking that resists standard risk-reduction interventions, although some conditions such as depression can be effectively treated with other approaches. Major explanatory models of risky decision making can be roughly divided into (a) those, including health-belief models and the theory of planned behavior, that adhere to a "rational" behavioral decision-making framework that stresses deliberate, quantitative trading off of risks and benefits; and (b) those that emphasize nondeliberative reaction to the perceived gists or prototypes in the immediate decision environment. (A gist is a fuzzy mental representation of the general meaning of information or experience; a prototype is a mental representation of a standard or typical example of a category.) Although perceived risks and especially benefits predict behavioral intentions and risk-taking behavior, behavioral willingness is an even better predictor of susceptibility to risk taking-and has unique explanatory power-because adolescents are willing to do riskier things than they either intend or expect to do. Dual-process models, such as the prototype/willingness model and fuzzy-trace theory, identify two divergent paths to risk taking: a reasoned and a reactive route. Such models explain apparent contradictions in the literature, including different causes of risk taking for different individuals

Theory-based approaches to understanding public emergency preparedness: implications for effective health and risk communication.

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Paek, Hye-Jin; Hilyard, Karen; Freimuth, Vicki; Barge, J Kevin; Mindlin, Michele

2010-06-01

Recent natural and human-caused disasters have awakened public health officials to the importance of emergency preparedness. Guided by health behavior and media effects theories, the analysis of a statewide survey in Georgia reveals that self-efficacy, subjective norm, and emergency news exposure are positively associated with the respondents' possession of emergency items and their stages of emergency preparedness. Practical implications suggest less focus on demographics as the sole predictor of emergency preparedness and more comprehensive measures of preparedness, including both a person's cognitive stage of preparedness and checklists of emergency items on hand. We highlight the utility of theory-based approaches for understanding and predicting public emergency preparedness as a way to enable more effective health and risk communication.

The Theory-based Influence of Map Features on Risk Beliefs: Self-reports of What is Seen and Understood for Maps Depicting an Environmental Health Hazard

OpenAIRE

Severtson, Dolores J.; Vatovec, Christine

2012-01-01

Theory-based research is needed to understand how maps of environmental health risk information influence risk beliefs and protective behavior. Using theoretical concepts from multiple fields of study including visual cognition, semiotics, health behavior, and learning and memory supports a comprehensive assessment of this influence. We report results from thirteen cognitive interviews that provide theory-based insights into how visual features influenced what participants saw ...

Chemistry Misconceptions Associated with Understanding Calcium and Phosphate Homeostasis

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Cliff, William H.

2009-01-01

Successful learning of many aspects in physiology depends on a meaningful understanding of fundamental chemistry concepts. Two conceptual diagnostic questions measured student understanding of the chemical equilibrium underlying calcium and phosphate homeostasis. One question assessed the ability to predict the change in phosphate concentration…

Assessing the optimism-pessimism debate: Nuclear proliferation, nuclear risks, and theories of state action

International Nuclear Information System (INIS)

Busch, Nathan Edward

2001-01-01

This dissertation focuses on the current debate in international relations literature over the risks associated with the proliferation of nuclear weapons. On this subject, IR scholars are divided into roughly two schools: proliferation 'optimists,' who argue that proliferation can be beneficial and that its associated hazards are at least surmountable, and proliferation 'pessimists,' who believe the opposite. This debate centers upon a theoretical disagreement about how best to explain and predict the behavior of states. Optimists generally ground their arguments on rational deterrence theory and maintain that nuclear weapons can actually increase stability among states, while pessimists often ground their arguments on 'organization theory,' which contends that organizational, bureaucratic, and other factors prevent states from acting rationally. A major difficulty with the proliferation debate, however, is that both sides tend to advance their respective theoretical positions without adequately supporting them with solid empirical evidence. This dissertation detailed analyses of the nuclear programs in the United States, Russia, China, India, and Pakistan to determine whether countries with nuclear weapons have adequate controls over their nuclear arsenals and tissue material stockpiles (such as highly enriched uranium and plutonium). These case studies identify the strengths and weaknesses of different systems of nuclear controls and help predict what types of controls proliferating states are likely to employ. On the basis of the evidence gathered from these cases, this dissertation concludes that a further spread of nuclear weapons would tend to have seriously negative effects on international stability by increasing risks of accidental, unauthorized, or inadvertent use of nuclear weapons and risks of thefts of fissile materials for use in nuclear or radiological devices by aspiring nuclear states or terrorist groups. (author)

Air pollution particles and iron homeostasis | Science ...

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Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, functional groups at the surface of retained particle complex iron available in the cell. In response to a reduction in concentrations of requisite iron, a functional deficiency can result intracellularly. Superoxide production by the cell exposed to a particle increases ferrireduction which facilitates import of iron with the objective being the reversal of the metal deficiency. Failure to resolve the functional iron deficiency following cell exposure to particles activates kinases and transcription factors resulting in a release of inflammatory mediators and inflammation. Tissue injury is the end product of this disruption in iron homeostasis initiated by the particle exposure. Elevation of available iron to the cell precludes deficiency of the metal and either diminishes or eliminates biological effects.General Significance: Recognition of the pathway for biological effects after particle exposure to involve a functional deficiency of iron suggests novel therapies such as metal supplementation (e.g. inhaled and oral). In addition, the demonstration of a shared mechanism of biological effects allows understanding the common clinical, physiological, and pathological presentation fol

Prospect theory based estimation of drivers' risk attitudes in route choice behaviors.

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Zhou, Lizhen; Zhong, Shiquan; Ma, Shoufeng; Jia, Ning

2014-12-01

This paper applied prospect theory (PT) to describe drivers' route choice behavior under Variable Message Sign (VMS), which presented visual traffic information to assist them to make route choice decisions. A quite rich empirical data from questionnaire and field spot was used to estimate parameters of PT. In order to make the parameters more realistic with drivers' attitudes, they were classified into different types by significant factors influencing their behaviors. Based on the travel time distribution of alternative routes and route choice results from questionnaire, the parameterized value function of each category was figured out, which represented drivers' risk attitudes and choice characteristics. The empirical verification showed that the estimates were acceptable and effective. The result showed drivers' risk attitudes and route choice characteristics could be captured by PT under real-time information shown on VMS. For practical application, once drivers' route choice characteristics and parameters were identified, their route choice behavior under different road conditions could be predicted accurately, which was the basis of traffic guidance measures formulation and implementation for targeted traffic management. Moreover, the heterogeneous risk attitudes among drivers should be considered when releasing traffic information and regulating traffic flow. Copyright © 2014 Elsevier Ltd. All rights reserved.

Energy homeostasis and running wheel activity during pregnancy in the mouse.

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Ladyman, S R; Carter, K M; Grattan, D R

2018-05-05

Pregnancy and lactation are metabolically challenging states, where the mother must supply all the energy requirements for the developing fetus and growing pups respectively. The aim of the current study was to characterize many aspects of energy homeostasis before and during pregnancy in the mouse, and to examine the role of voluntary activity on changes in energy expenditure during pregnancy. In a secondary aim, we evaluate measures of energy homeostasis during pregnancy in mice that successfully reared their litter or in mice that went on to abandon their litter, to determine if an impairment in pregnancy-induced adaptation of energy homeostasis might underlie the abandonment of pups soon after birth. During pregnancy, food intake was increased, characterized by increased meal size and duration but not number of meals per day. The duration of time spent inactive, predicted to indicate sleep behaviour, was increased both early and late in pregnancy compared to pre-pregnancy levels. Increased x + y beam breaks, as a measure of activity increased during pregnancy and this reflected an increase in ambulatory behaviour in mid pregnancy and an increase in non-ambulatory movement in late pregnancy. Energy expenditure, as measured by indirect calorimetry, increased across pregnancy, likely due to the growth and development of fetal tissue. There was also a dramatic reduction in voluntary wheel running as soon as the mice became pregnant. Compared with successful pregnancies and lactations, pregnancies where pups were abandoned soon after birth were associated with reduced body weight gain and an increase in running wheel activity at the end of pregnancy, but no difference in food intake or energy expenditure. Overall, during pregnancy there are multiple adaptations to change energy homeostasis, resulting in partitioning of provisions of energy to the developing fetus and storing energy for future metabolic demands. Copyright © 2018 Elsevier Inc. All rights reserved.

Selenium Homeostasis and Clustering of Cardiovascular Risk Factors: A Systematic Review.

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Gharipour, Mojgan; Sadeghi, Masoumeh; Behmanesh, Mehrdad; Salehi, Mansour; Nezafati, Pouya; Gharpour, Amin

2017-10-23

  Selenium is a trace element required for a range of cellular functions. It is widely used for the biosynthesis of the unique amino acid selenocysteine [Sec], which is a structural element of selenoproteins. This systematic review focused on the possible relation between selenium and metabolic risk factors. The literature was searched via PubMed, Scopus, ISI Web of Science, and Google Scholar. Searches were not restricted by time or language. Relevant studies were selected in three phases. After an initial quality assessment, two reviewers extracted all the relevant data, whereas the third reviewer checked their extracted data. All evidence came from experimental and laboratory studies. Selenoprotein P is the best indicator for selenium nutritional levels. In addition, high levels of selenium may increase the risk of metabolic syndrome while the lack of sufficient selenium may also promote metabolic syndrome. selenium supplementation in subjects with sufficient serum selenium levels has a contrary effect on blood pressure, LDL, and total cholesterol. According to the bioavailability of different types of selenium supplementation such as selenomethionine, selenite and selenium-yeast, it seems that the best nutritional type of selenium is selenium-yeast. Regarding obtained results of longitudinal studies and randomized controlled trials, selenium supplementation should not be recommended for primary or secondary cardio-metabolic risk prevention in populations with adequate selenium status.

IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis

DEFF Research Database (Denmark)

Luda, Katarzyna M.; Joeris, Thorsten; Persson, Emma K.

2016-01-01

The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence...... dependent DCs in the maintenance of intestinal T cell homeostasis....

Coffee Consumption, Newly Diagnosed Diabetes, and Other Alterations in Glucose Homeostasis: A Cross-Sectional Analysis of the Longitudinal Study of Adult Health (ELSA-Brasil)

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Yarmolinsky, James; Mueller, Noel T.; Duncan, Bruce B.; Bisi Molina, Maria del Carmen; Goulart, Alessandra C.; Schmidt, Maria Inês

2015-01-01

Introduction Observational studies have reported fairly consistent inverse associations between coffee consumption and risk of type 2 diabetes, but this association has been little investigated with regard to lesser degrees of hyperglycemia and other alterations in glucose homeostasis. Additionally, the association between coffee consumption and diabetes has been rarely investigated in South American populations. We examined the cross-sectional relationships of coffee intake with newly diagnosed diabetes and measures of glucose homeostasis, insulin sensitivity, and insulin secretion, in a large Brazilian cohort of middle-aged and elderly individuals. Methods We used baseline data from 12,586 participants of the Longitudinal Study of Adult Health (ELSA-Brasil). Logistic regression analyses were performed to examine associations between coffee consumption and newly diagnosed diabetes. Analysis of covariance was used to assess coffee intake in relation to two-hour glucose from an oral glucose tolerance test, fasting glucose, glycated hemoglobin, fasting and –2-hour postload insulin and measures of insulin sensitivity. Results We found an inverse association between coffee consumption and newly diagnosed diabetes, after adjusting for multiple covariates [23% and 26% lower odds of diabetes for those consuming coffee 2–3 and >3 times per day, respectively, compared to those reporting never or almost never consuming coffee, (p = .02)]. An inverse association was also found for 2-hour postload glucose [Never/almost never: 7.57 mmol/L, ≤1 time/day: 7.48 mmol/L, 2-3 times/day: 7.22 mmol/L, >3 times/day: 7.12 mol/L, p3 times/day: 262.2 pmol/L, p = 0.0005) but not with fasting insulin concentrations (p = .58). Conclusion Our present study provides further evidence of a protective effect of coffee on risk of adult-onset diabetes. This effect appears to act primarily, if not exclusively, through postprandial, as opposed to fasting, glucose homeostasis. PMID:25978631

Coffee Consumption, Newly Diagnosed Diabetes, and Other Alterations in Glucose Homeostasis: A Cross-Sectional Analysis of the Longitudinal Study of Adult Health (ELSA-Brasil.

Directory of Open Access Journals (Sweden)

James Yarmolinsky

Full Text Available Observational studies have reported fairly consistent inverse associations between coffee consumption and risk of type 2 diabetes, but this association has been little investigated with regard to lesser degrees of hyperglycemia and other alterations in glucose homeostasis. Additionally, the association between coffee consumption and diabetes has been rarely investigated in South American populations. We examined the cross-sectional relationships of coffee intake with newly diagnosed diabetes and measures of glucose homeostasis, insulin sensitivity, and insulin secretion, in a large Brazilian cohort of middle-aged and elderly individuals.We used baseline data from 12,586 participants of the Longitudinal Study of Adult Health (ELSA-Brasil. Logistic regression analyses were performed to examine associations between coffee consumption and newly diagnosed diabetes. Analysis of covariance was used to assess coffee intake in relation to two-hour glucose from an oral glucose tolerance test, fasting glucose, glycated hemoglobin, fasting and -2-hour postload insulin and measures of insulin sensitivity.We found an inverse association between coffee consumption and newly diagnosed diabetes, after adjusting for multiple covariates [23% and 26% lower odds of diabetes for those consuming coffee 2-3 and >3 times per day, respectively, compared to those reporting never or almost never consuming coffee, (p = .02]. An inverse association was also found for 2-hour postload glucose [Never/almost never: 7.57 mmol/L, ≤1 time/day: 7.48 mmol/L, 2-3 times/day: 7.22 mmol/L, >3 times/day: 7.12 mol/L, p3 times/day: 262.2 pmol/L, p = 0.0005 but not with fasting insulin concentrations (p = .58.Our present study provides further evidence of a protective effect of coffee on risk of adult-onset diabetes. This effect appears to act primarily, if not exclusively, through postprandial, as opposed to fasting, glucose homeostasis.

Work and Risk: Perceptions of Nuclear-Power Personnel. a Study in Grounded Theory.

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Fields, Claire Dewitt

1992-01-01

The utility industry has devoted time and money to assure personnel within nuclear power plants are informed about occupational risks. Radiation-protection training programs are designed to present information to employees about occupational radiation and protective procedures. Work -related concerns are known to create stress, affect the morale of the workforce, influence collective bargaining, and increase compensation claims. This study was designed to determine perceptions of risk among employees of nuclear power plants and identify variables that influence these perceptions. Four power plants were included in the study, one in Canada and three in the United States. Data were generated through participant observations and interviews of 350 participants during a period of 3 weeks at each plant. Data were gathered and analyzed following procedures advanced by Grounded Theory, a naturalistic methodology used in this study. Training content, information, and communication materials were additional sources of data. Findings indicated employees believed health and safety risks existed within the work environment. Perceptions of risk were influenced by training quality, the work environment, nuclear myths and images of the general public, and fears of family members. Among the three groups of workers, administration personnel, security personnel, and radiation workers, the latter identified a larger number of risks. Workers perceived radiation risks, shift work, and steam pipe ruptures as high-level concerns. Experiencing stress, making mistakes, and fear of sabotage were concerns shared among all employee groups at various levels of concern. Strategies developed by employees were used to control risk. Strategies included teamwork, humor, monitoring, avoidance, reframing, and activism. When risks were perceived as uncontrollable, the employee left the plant. A coping strategy of transferring concerns about radiological risks to nonradiological risks were uncovered in

The membrane stress response buffers lethal effects of lipid disequilibrium by reprogramming the protein homeostasis network.

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Thibault, Guillaume; Shui, Guanghou; Kim, Woong; McAlister, Graeme C; Ismail, Nurzian; Gygi, Steven P; Wenk, Markus R; Ng, Davis T W

2012-10-12

Lipid composition can differ widely among organelles and even between leaflets of a membrane. Lipid homeostasis is critical because disequilibrium can have disease outcomes. Despite their importance, mechanisms maintaining lipid homeostasis remain poorly understood. Here, we establish a model system to study the global effects of lipid imbalance. Quantitative lipid profiling was integral to monitor changes to lipid composition and for system validation. Applying global transcriptional and proteomic analyses, a dramatically altered biochemical landscape was revealed from adaptive cells. The resulting composite regulation we term the "membrane stress response" (MSR) confers compensation, not through restoration of lipid composition, but by remodeling the protein homeostasis network. To validate its physiological significance, we analyzed the unfolded protein response (UPR), one facet of the MSR and a key regulator of protein homeostasis. We demonstrate that the UPR maintains protein biogenesis, quality control, and membrane integrity-functions otherwise lethally compromised in lipid dysregulated cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism.

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Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle.

Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis

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Rynes, Jan; Donohoe, Colin D.; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek

2012-01-01

Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins. PMID:22851689

Activating transcription factor 3 regulates immune and metabolic homeostasis.

Science.gov (United States)

Rynes, Jan; Donohoe, Colin D; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek; Uhlirova, Mirka

2012-10-01

Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins.

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

Science.gov (United States)

Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle. PMID:26039160

Integrating physiological regulation with stem cell and tissue homeostasis

Science.gov (United States)

Nakada, Daisuke; Levi, Boaz P.; Morrison, Sean J.

2015-01-01

Summary Stem cells are uniquely able to self-renew, to undergo multilineage differentiation, and to persist throughout life in a number of tissues. Stem cells are regulated by a combination of shared and tissue-specific mechanisms and are distinguished from restricted progenitors by differences in transcriptional and epigenetic regulation. Emerging evidence suggests that other aspects of cellular physiology, including mitosis, signal transduction, and metabolic regulation also differ between stem cells and their progeny. These differences may allow stem cells to be regulated independently of differentiated cells in response to circadian rhythms, changes in metabolism, diet, exercise, mating, aging, infection, and disease. This allows stem cells to sustain homeostasis or to remodel relevant tissues in response to physiological change. Stem cells are therefore not only regulated by short-range signals that maintain homeostasis within their tissue of origin, but also by long-range signals that integrate stem cell function with systemic physiology. PMID:21609826

The nucleolus—guardian of cellular homeostasis and genome integrity.

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Grummt, Ingrid

2013-12-01

All organisms sense and respond to conditions that stress their homeostasis by downregulating the synthesis of rRNA and ribosome biogenesis, thus designating the nucleolus as the central hub in coordinating the cellular stress response. One of the most intriguing roles of the nucleolus, long regarded as a mere ribosome-producing factory, is its participation in monitoring cellular stress signals and transmitting them to the RNA polymerase I (Pol I) transcription machinery. As rRNA synthesis is a most energy-consuming process, switching off transcription of rRNA genes is an effective way of saving the energy required to maintain cellular homeostasis during acute stress. The Pol I transcription machinery is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production which, in turn, guides cell growth and proliferation. This review focuses on the mechanisms that link cell physiology to rDNA silencing, a prerequisite for nucleolar integrity and cell survival.

Analysis of vegetative homeostasis state of elite handball players

Directory of Open Access Journals (Sweden)

Y.N. Prystupa

2015-12-01

Full Text Available Purpose: to study characteristics and dynamic of elite handball players’ physiological indicators. Material: In experiment elite handball players (n=112, age 18-35 years participated. For determination of vegetative homeostasis state we analyzed variability of heart rhythm. The researches were conducted in laboratory conditions in rest state, in lying position during 5 minutes. Results: it was found that organism’s adaptation reactions to training loads go with different tension of regulation systems. At the end of competition period there appears hyper-kinetic syndrome. It witnessed insufficiency of means, which permit to maintain optimal regulation of cardio-vascular system and increase its functional potentials. Conclusions: indicators of cardio-vascular system and their dynamic w3itnessed maintaining of high level of handball players’ organism hemodynamic provisioning. High level of vegetative homeostasis pointed at certain degree of sportsmen’s fitness. Such state is sufficient for preservation of high potential of sympathetic -adrenaline system and overcoming of fatigue processes.

A novel role for Twist-1 in pulp homeostasis.

Science.gov (United States)

Galler, K M; Yasue, A; Cavender, A C; Bialek, P; Karsenty, G; D'Souza, R N

2007-10-01

The molecular mechanisms that maintain the equilibrium of odontoblast progenitor cells in dental pulp are unknown. Here we tested whether homeostasis in dental pulp is modulated by Twist-1, a nuclear protein that partners with Runx2 during osteoblast differentiation. Our analysis of Twist-1(+/-) mice revealed phenotypic changes that involved an earlier onset of dentin matrix formation, increased alkaline phosphatase activity, and pulp stones within the pulp. RT-PCR analyses revealed Twist-1 expression in several adult organs, including pulp. Decreased levels of Twist-1 led to higher levels of type I collagen and Dspp gene expression in perivascular cells associated with the pulp stones. In mice heterozygous for both Twist-1 and Runx2 inactivation, the phenotype of pulp stones appeared completely rescued. These findings suggest that Twist-1 plays a key role in restraining odontoblast differentiation, thus maintaining homeostasis in dental pulp. Furthermore, Twist-1 functions in dental pulp are dependent on its interaction with Runx2.

Peripheral Serotonin: a New Player in Systemic Energy Homeostasis

Science.gov (United States)

Namkung, Jun; Kim, Hail; Park, Sangkyu

2015-01-01

Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. An ancient neurotransmitter, serotonin is among those traditional pharmacological targets for anti-obesity treatment because it exhibits strong anorectic effect in the brain. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Here, we discuss the role of serotonin in the regulation of energy homeostasis and introduce peripheral serotonin as a possible target for anti-obesity treatment. PMID:26628041

THE THEORY OF EFFICIENT MARKETS AND A MODEL OF RATIONAL INVESTOR – FROM CONDITIONS OF RISK TO TERMS OF CONFLICT

Directory of Open Access Journals (Sweden)

Krzysztof Dobrowolski

2014-03-01

Full Text Available The theoretical assumption about the informative effectiveness of financial markets is very important, although the discussion about its compatibility with the reality still re-mains open. The article summarises the key elements of the theory of efficient markets, paying particular attention to the adopted in this theory assumption about a rational inves-tor, which also appears in other models and theories related to the financial markets (such as capital asset pricing model CAPM or Markowitz Portfolio Theory. The views on the way and criteria for decision-making by a rational investor have changed over the centu-ries. Today, the dominant theory in this regard is the theory of expected utility. However, it characterizes the decision-making process under risk conditions, which are not the most common economic environment, particularly in an economy subjected to the process of globalisation. Thus, the problem of using the models of decision making under conditions of uncertainty, ignorance and terms of conflict in the efficient market theory and the theo-ry of expected utility is under consideration in the final part of the article.

Targeting Cellular Calcium Homeostasis to Prevent Cytokine-Mediated Beta Cell Death.

Science.gov (United States)

Clark, Amy L; Kanekura, Kohsuke; Lavagnino, Zeno; Spears, Larry D; Abreu, Damien; Mahadevan, Jana; Yagi, Takuya; Semenkovich, Clay F; Piston, David W; Urano, Fumihiko

2017-07-17

Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.

Effects of Ramadan fasting on glucose homeostasis and adiponectin levels in healthy adult males.

Science.gov (United States)

Gnanou, Justin V; Caszo, Brinnell A; Khalil, Khalifah M; Abdullah, Shahidah L; Knight, Victor F; Bidin, Mohd Z

2015-01-01

Adiponectin is a hormone secreted by adipocytes during the fasting phase of the fast-fed cycle. Ramadan fasting involves prolonged fasting for up to twelve hours and thus could lead to increased secretion of adiponectin by adipocytes. However, studies on the role of adiponectin on glucose and body weight homeostasis during Ramadan fasting is still a matter of controversy. Thus the specific aim of this study was to assess the effect of fasting during Ramadan on the adiponectin levels, body weight and glucose homeostasis in healthy male Malaysian subjects. Twenty healthy male (19-23 years) Muslim subjects were followed up during the fasting month of Ramadan. Anthropometry and blood samples were taken one week before and during the fourth week of fasting. Plasma glucose, insulin and adiponectin were estimated and insulin sensitivity indices were estimated using the Homeostasis Model Assessment. Subjects experienced a significant decrease in body weight (2.4 %, p Ramadan fasting in young healthy individuals has a positive impact on the maintenance of glucose homeostasis. It also shows that adiponectin levels dropped along with significant loss in weight. We feel caloric restriction during the Ramadan fasting is in itself sufficient to improve insulin sensitivity in healthy individuals.

Preoperative octreotide therapy and surgery in acromegaly: associations between glucose homeostasis and treatment response.

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Helseth, R; Carlsen, S M; Bollerslev, J; Svartberg, J; Øksnes, M; Skeie, S; Fougner, S L

2016-02-01

In acromegaly, high GH/IGF-1 levels associate with abnormal glucose metabolism. Somatostatin analogs (SSAs) reduce GH and IGF-1 but inhibit insulin secretion. We studied glucose homeostasis in de novo patients with acromegaly and changes in glucose metabolism after treatment with SSA and surgery. In this post hoc analysis from a randomized controlled trial, 55 de novo patients with acromegaly, not using antidiabetic medication, were included. Before surgery, 26 patients received SSAs for 6 months. HbA1c, fasting glucose, and oral glucose tolerance test were performed at baseline, after SSA pretreatment and at 3 months postoperative. Area under curve of glucose (AUC-G) was calculated. Glucose homeostasis was compared to baseline levels of GH and IGF-1, change after SSA pretreatment, and remission both after SSA pretreatment and 3 months postoperative. In de novo patients, IGF-1/GH levels did not associate with baseline glucose parameters. After SSA pretreatment, changes in GH/IGF-1 correlated positively to change in HbA1c levels (both p acromegaly, disease activity did not correlate with glucose homeostasis. Surgical treatment of acromegaly improved glucose metabolism in both cured and not cured patients, while SSA pretreatment led to deterioration in glucose homeostasis in patients not achieving biochemical control.

Mean-deviation analysis in the theory of choice.

Science.gov (United States)

Grechuk, Bogdan; Molyboha, Anton; Zabarankin, Michael

2012-08-01

Mean-deviation analysis, along with the existing theories of coherent risk measures and dual utility, is examined in the context of the theory of choice under uncertainty, which studies rational preference relations for random outcomes based on different sets of axioms such as transitivity, monotonicity, continuity, etc. An axiomatic foundation of the theory of coherent risk measures is obtained as a relaxation of the axioms of the dual utility theory, and a further relaxation of the axioms are shown to lead to the mean-deviation analysis. Paradoxes arising from the sets of axioms corresponding to these theories and their possible resolutions are discussed, and application of the mean-deviation analysis to optimal risk sharing and portfolio selection in the context of rational choice is considered. © 2012 Society for Risk Analysis.

Intentions to Participate in Counselling among Front-Line, At-Risk Irish Government Employees: An Application of the Theory of Planned Behaviour

Science.gov (United States)

Hyland, Philip E.; McLaughlin, Christopher G.; Boduszek, Daniel; Prentice, Garry R.

2012-01-01

The study set out to examine intentions to engage in counselling among at-risk Irish government employees and the differential utility of two alternative theory of planned behaviour (TPB) models of behaviour to explain intentions to participate in counselling. Individuals (N = 259) employed in a front-line, at-risk occupation for the Irish…

Iron Homeostasis in Yellowstone National Park Hot Spring Microbial Communities

Science.gov (United States)

Brown, I.; Tringe, S. G.; Franklin, H.; Bryant, D. A.; Klatt, C. G.; Sarkisova, S. A.; Guevara, M.

2010-01-01

It has been postulated that life may have originated on Earth, and possibly on Mars, in association with hydrothermal activity and high concentrations of ferrous iron. However, it is not clear how an iron-rich thermal hydrosphere could be hospitable to microbes, since reduced iron appears to stimulate oxidative stress in all domains of life and particularly in oxygenic phototrophs. Therefore, the study of microbial diversity in iron-depositing hot springs (IDHS) and the mechanisms of iron homeostasis and suppression of oxidative stress may help elucidate how Precambrian organisms could withstand the extremely high concentrations of reactive oxygen species (ROS) produced by interaction between environmental Fe(2+) and O2. Proteins and clusters of orthologous groups (COGs) involved in the maintenance of Fe homeostasis found in cyanobacteria (CB) inhabiting environments with high and low [Fe] were main target of this analysis. Preliminary results of the analysis suggest that the Chocolate Pots (CP) microbial community is heavily dominated by phototrophs from the cyanobacteria (CB), Chloroflexi and Chlorobi phyla, while the Mushroom Spring (MS) effluent channel harbors a more diverse community in which Chloroflexi are the dominant phototrophs. It is speculated that CB inhabiting IDHS have an increased tolerance to both high concentrations of Fe(2+) and ROS produced in the Fenton reaction. This hypothesis was explored via a comparative analysis of the diversity of proteins and COGs involved in Fe and redox homeostasis in the CP and MS microbiomes.

Behavioral risk-reduction strategies to prevent HIV infection among homosexual men: a grounded theory approach.

Science.gov (United States)

de Wit, J B; Teunis, N; van Griensven, G J; Sandfort, T G

1994-12-01

To be able to design effective health education interventions for homosexual men, it is necessary to understand determinants of safe and unsafe sex from the perspective of those involved. In this qualitative study, therefore, an open approach was taken to allow for this perspective. Interviews were conducted with 50 randomly selected HIV-antibody negative participants in the Amsterdam Cohort Study. Detailed questions were asked about sexual interactions and behaviors with steady and nonsteady partners. Whether or not homosexual men consciously protected themselves from HIV infection and which strategy they adopted was found to depend on three major factors: 1) motivation and intention, 2) significance of anal sex, and 3) risk perception within specific relationships. From a theoretical perspective results indicate that, next to the centrality of individual motivation as postulated in both the Theory of Reasoned Action and the Theory of Planned Behavior, symbolic meaning inherent in sexual acts, as well as type of relationship are important determinants of protective sexual behaviors that have to be taken into account to understand adequately why homosexual men engage in safe or unsafe sex. Some strategies employed by homosexual men carry uncertainties that continue to put them at increased risk for HIV infection. Health education interventions can be designed to address these issues.

The role of gut microbiota in immune homeostasis and autoimmunity.

Science.gov (United States)

Wu, Hsin-Jung; Wu, Eric

2012-01-01

Keeping a delicate balance in the immune system by eliminating invading pathogens, while still maintaining self-tolerance to avoid autoimmunity, is critical for the body's health. The gut microbiota that resides in the gastrointestinal tract provides essential health benefits to its host, particularly by regulating immune homeostasis. Moreover, it has recently become obvious that alterations of these gut microbial communities can cause immune dysregulation, leading to autoimmune disorders. Here we review the advances in our understanding of how the gut microbiota regulates innate and adaptive immune homeostasis, which in turn can affect the development of not only intestinal but also systemic autoimmune diseases. Exploring the interaction of gut microbes and the host immune system will not only allow us to understand the pathogenesis of autoimmune diseases but will also provide us new foundations for the design of novel immuno- or microbe-based therapies.

The joint power of sex and stress to modulate brain-gut-microbiota axis and intestinal barrier homeostasis: implications for irritable bowel syndrome.

Science.gov (United States)

Pigrau, M; Rodiño-Janeiro, B K; Casado-Bedmar, M; Lobo, B; Vicario, M; Santos, J; Alonso-Cotoner, C

2016-04-01

Intestinal homeostasis is a dynamic process that takes place at the interface between the lumen and the mucosa of the gastrointestinal tract, where a constant scrutiny for antigens and toxins derived from food and microorganisms is carried out by the vast gut-associated immune system. Intestinal homeostasis is preserved by the ability of the mucus layer and the mucosal barrier to keep the passage of small-sized and antigenic molecules across the epithelium highly selective. When combined and preserved, immune surveillance and barrier's selective permeability, the host capacity of preventing the development of intestinal inflammation is optimized, and viceversa. In addition, the brain-gut-microbiome axis, a multidirectional communication system that integrates distant and local regulatory networks through neural, immunological, metabolic, and hormonal signaling pathways, also regulates intestinal function. Dysfunction of the brain-gut-microbiome axis may induce the loss of gut mucosal homeostasis, leading to uncontrolled permeation of toxins and immunogenic particles, increasing the risk of appearance of intestinal inflammation, mucosal damage, and gut disorders. Irritable bowel syndrome is prevalent stress-sensitive gastrointestinal disorder that shows a female predominance. Interestingly, the role of stress, sex and gonadal hormones in the regulation of intestinal mucosal and the brain-gut-microbiome axis functioning is being increasingly recognized. We aim to critically review the evidence linking sex, and stress to intestinal barrier and brain-gut-microbiome axis dysfunction and the implications for irritable bowel syndrome. © 2015 John Wiley & Sons Ltd.

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

Science.gov (United States)

Haldar, Swati; Tripathi, Ajai K.; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K.; Singh, Ajay

2014-01-01

Abstract Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders. Antioxid. Redox Signal. 20, 1324–1363. PMID:23815406

Interference between nanoparticles and metal homeostasis

International Nuclear Information System (INIS)

Petit, A N; Catty, P; Charbonnier, P; Cuillel, M; Mintz, E; Moulis, J M; Niviere, V; Choudens, S Ollagnier de; Garcia, C Aude; Candeias, S; Chevallet, M; Collin-Faure, V; Lelong, C; Luche, S; Rabilloud, T; Casanova, A; Herlin-Boime, N; Douki, T; Ravanat, J L; Sauvaigo, S

2011-01-01

The TiO 2 nanoparticles (NPs) are now produced abundantly and widely used in a variety of consumer products. Due to the important increase in the production of TiO 2 -NPs, potential widespread exposure of humans and environment may occur during both the manufacturing process and final use. Therefore, the potential toxicity of TiO 2 -NPs on human health and environment has attracted particular attention. Unfortunately, the results of the large number of studies on the toxicity of TiO 2 -NPs differ significantly, mainly due to an incomplete characterization of the used nanomaterials in terms of size, shape and crystalline structure and to their unknown state of agglomeration/aggregation. The purpose of our project entitled NanoBioMet is to investigate if interferences between nanoparticles and metal homeostasis could be observed and to study the toxicity mechanisms of TiO 2 -NPs with well-characterized physicochemical parameters, using proteomic and molecular approaches. A perturbation of metal homeostasis will be evaluated upon TiO 2 -NPs exposure which could generate reactive oxygen species (ROS) production. Moreover, oxidative stress consequences such as DNA damage and lipid peroxidation will be studied. The toxicity of TiO 2 -NPs of different sizes and crystalline structures will be evaluated both in prokaryotic (E. coli) and eukaryotic cells (A549 human pneumocytes, macrophages, and hepatocytes). First results of the project will be presented concerning the dispersion of TiO 2 -NPs in bacterial medium, proteomic studies on total extracts of macrophages and genotoxicity on pneumocytes.

Practical homeostasis lighting control system using sensor agent robots for office space

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Tokiwa, Momoko; Mita, Akira

2014-03-01

The comfortable space can be changed by season, age, physical condition and the like. However, the current systems are not able to resolve them absolutely. This research proposes the Homeostasis lighting control system based on the mechanism of biotic homeostasis for making the algorithms of apparatus control. Homeostasis are kept by the interaction of the three systems, endocrine system, immune system, and nervous system[1]. By the gradual reaction in the endocrine system, body's protective response in the immune system, and the electrical reaction in the nerve system, we can keep the environments against variable changes. The new lighting control system utilizes this mechanism. Firstly, we focused on legibility and comfort in the office space to construct the control model learning from the endocrine and immune systems. The mechanism of the endocrine system is used for ambient lights in the space is used considering circadian rhythm for comfort. For the legibility, the immune system is used to control considering devices near the human depending on the distance between the human. Simulations and the demonstration were conducted to show the feasibility. Finally, the nerve system was intruded to enhance the system.

Impaired glucose homeostasis in non-diabetic Greek hypertensives with diabetes family history. Effect of the obesity status.

Science.gov (United States)

Vyssoulis, Gregory P; Liakos, Charalampos I; Karpanou, Eva A; Triantafyllou, Athanasios I; Michaelides, Andreas P; Tzamou, Vanessa E; Markou, Maria I; Stefanadis, Christodoulos I

2013-01-01

Arterial hypertension (AH) and diabetes mellitus (DM) are established cardiovascular risk factors. Impaired glucose homeostasis (IGH; impaired fasting glucose or/and impaired glucose tolerance) or pre-diabetes, obesity, and DM family history identify individuals at risk for type 2 DM in whom preventive interventions are necessary. The aim of this study was to determine the glycemic profile in non-diabetic Greek adult hypertensive men and women according to DM family history and the obesity status. Diabetes family history, obesity markers (waist-to-hip ratio, WHR; body mass index, BMI), glycemic parameters (fasting and 2-hour post-load plasma glucose, if necessary; glycated hemoglobin, HbA1c; fasting insulin), insulin resistance indices (homeostasis model assessment, HOMA; quantitative insulin sensitivity check index, QUICKI; Bennett; McAuley), and IGH prevalence were determined in a large cohort of 11,540 Greek hypertensives referred to our institutions. Positive DM family history was associated with elevated fasting glucose (98.6 ± 13.1 vs 96.5 ± 12.3 mg/dL), HbA1c (5.58% ± 0.49% vs 5.50% ± 0.46%), fasting insulin (9.74 ± 4.20 vs 9.21 ± 3.63 μU/mL) and HOMA (2.43 ± 1.19 vs 2.24 ± 1.01) values, lower QUICKI (0.342 ± 0.025 vs 0.345 ± 0.023), Bennett (0.285 ± 0.081 vs 0.292 ± 0.078) and McAuley (6.73 ± 3.43 vs 6.95 ± 3.44) values, and higher IGH prevalence (45.3% vs 38.7%); P history was significant (P history present with higher IGH prevalence and worse glycemic indices levels compared with those with negative family history, especially in the higher WHR/BMI subgroups. Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Microenvironmental regulation of stem cells in intestinal homeostasis and cancer

NARCIS (Netherlands)

Medema, Jan Paul; Vermeulen, Louis

2011-01-01

The identification of intestinal stem cells as well as their malignant counterparts, colon cancer stem cells, has undergone rapid development in recent years. Under physiological conditions, intestinal homeostasis is a carefully balanced and efficient interplay between stem cells, their progeny and

Development and Validation of the Homeostasis Concept Inventory

Czech Academy of Sciences Publication Activity Database

McFarland, J.L.; Price, R.M.; Wenderoth, M.P.; Martinková, Patrícia; Cliff, W.; Michael, J.; Modell, H.; Wright, A.

2017-01-01

Roč. 16, č. 2 (2017), č. článku ar35. ISSN 1931-7913 R&D Projects: GA ČR GJ15-15856Y Grant - others:NSF(US) DUE-1043443 Institutional support: RVO:67985807 Keywords : homeostasis * physiology * assessment * concept inventory * undergraduate education Subject RIV: AM - Education OBOR OECD: Education, general; including training, pedagogy, didactics [ and education systems] Impact factor: 3.930, year: 2016

Diuretics and disorders of calcium homeostasis.

Science.gov (United States)

Grieff, Marvin; Bushinsky, David A

2011-11-01

Diuretics commonly are administered in disorders of sodium balance. Loop diuretics inhibit the Na-K-2Cl transporter and also increase calcium excretion. They are often used in the treatment of hypercalcemia. Thiazide diuretics block the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and can decrease calcium excretion. They are often used in the treatment of nephrolithiasis. Carbonic anhydrase inhibitors decrease bicarbonate absorption and the resultant metabolic acidosis can increase calcium excretion. Their use can promote nephrocalcinosis and nephrolithiasis. This review will address the use of diuretics on disorders of calcium homeostasis. Copyright © 2011 Elsevier Inc. All rights reserved.

Resilience and disaster risk reduction: an etymological journey

Science.gov (United States)

Alexander, D. E.

2013-11-01

This paper examines the development over historical time of the meaning and uses of the term resilience. The objective is to deepen our understanding of how the term came to be adopted in disaster risk reduction and resolve some of the conflicts and controversies that have arisen when it has been used. The paper traces the development of resilience through the sciences, humanities, and legal and political spheres. It considers how mechanics passed the word to ecology and psychology, and how from there it was adopted by social research and sustainability science. As other authors have noted, as a concept, resilience involves some potentially serious conflicts or contradictions, for example between stability and dynamism, or between dynamic equilibrium (homeostasis) and evolution. Moreover, although the resilience concept works quite well within the confines of general systems theory, in situations in which a systems formulation inhibits rather than fosters explanation, a different interpretation of the term is warranted. This may be the case for disaster risk reduction, which involves transformation rather than preservation of the "state of the system". The article concludes that the modern conception of resilience derives benefit from a rich history of meanings and applications, but that it is dangerous - or at least potentially disappointing - to read to much into the term as a model and a paradigm.

Assessment of urinary concentrations of hepcidin provides novel insight into disturbances in iron homeostasis during malarial infection

NARCIS (Netherlands)

Mast, de Q.; Nadjm, B.; Reyburn, H.; Kemna, E.H.J.M.; Amos, B.; Laarakkers, C.M.M.; Silalye, S.; Verhoef, H.; Sauerwein, R.W.; Swinkels, D.W.; Ven, van der A.J.A.M.

2009-01-01

Disturbances in iron homeostasis are frequently observed in individuals with malaria. To study the effect of malaria and its treatment on iron homeostasis and to provide a mechanistic explanation for observed alterations in iron distribution, we studied the course of the iron regulatory hormone

A comprehensive phylogeny of auxin homeostasis genes involved in adventitious root formation in carnation stem cuttings.

Directory of Open Access Journals (Sweden)

Ana Belén Sánchez-García

Full Text Available Understanding the functional basis of auxin homeostasis requires knowledge about auxin biosynthesis, auxin transport and auxin catabolism genes, which is not always directly available despite the recent whole-genome sequencing of many plant species. Through sequence homology searches and phylogenetic analyses on a selection of 11 plant species with high-quality genome annotation, we identified the putative gene homologs involved in auxin biosynthesis, auxin catabolism and auxin transport pathways in carnation (Dianthus caryophyllus L.. To deepen our knowledge of the regulatory events underlying auxin-mediated adventitious root formation in carnation stem cuttings, we used RNA-sequencing data to confirm the expression profiles of some auxin homeostasis genes during the rooting of two carnation cultivars with different rooting behaviors. We also confirmed the presence of several auxin-related metabolites in the stem cutting tissues. Our findings offer a comprehensive overview of auxin homeostasis genes in carnation and provide a solid foundation for further experiments investigating the role of auxin homeostasis in the regulation of adventitious root formation in carnation.

The Xenobiotic Transporter Mdr1 Enforces T Cell Homeostasis in the Presence of Intestinal Bile Acids.

Science.gov (United States)

Cao, Wei; Kayama, Hisako; Chen, Mei Lan; Delmas, Amber; Sun, Amy; Kim, Sang Yong; Rangarajan, Erumbi S; McKevitt, Kelly; Beck, Amanda P; Jackson, Cody B; Crynen, Gogce; Oikonomopoulos, Angelos; Lacey, Precious N; Martinez, Gustavo J; Izard, Tina; Lorenz, Robin G; Rodriguez-Palacios, Alex; Cominelli, Fabio; Abreu, Maria T; Hommes, Daniel W; Koralov, Sergei B; Takeda, Kiyoshi; Sundrud, Mark S

2017-12-19

CD4 + T cells are tightly regulated by microbiota in the intestine, but whether intestinal T cells interface with host-derived metabolites is less clear. Here, we show that CD4 + T effector (Teff) cells upregulated the xenobiotic transporter, Mdr1, in the ileum to maintain homeostasis in the presence of bile acids. Whereas wild-type Teff cells upregulated Mdr1 in the ileum, those lacking Mdr1 displayed mucosal dysfunction and induced Crohn's disease-like ileitis following transfer into Rag1 -/- hosts. Mdr1 mitigated oxidative stress and enforced homeostasis in Teff cells exposed to conjugated bile acids (CBAs), a class of liver-derived emulsifying agents that actively circulate through the ileal mucosa. Blocking ileal CBA reabsorption in transferred Rag1 -/- mice restored Mdr1-deficient Teff cell homeostasis and attenuated ileitis. Further, a subset of ileal Crohn's disease patients displayed MDR1 loss of function. Together, these results suggest that coordinated interaction between mucosal Teff cells and CBAs in the ileum regulate intestinal immune homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Bim: guardian of tissue homeostasis and critical regulator of the immune system, tumorigenesis and bone biology.

Science.gov (United States)

Akiyama, Toru; Tanaka, Sakae

2011-08-01

One of the most important roles of apoptosis is the maintenance of tissue homeostasis. Impairment of apoptosis leads to a number of pathological conditions. In response to apoptotic signals, various proteins are activated in a pathway and signal-specific manner. Recently, the pro-apoptotic molecule Bim has attracted increasing attention as a pivotal regulator of tissue homeostasis. The Bim expression level is strictly controlled in both transcriptional and post-transcriptional levels. This control is dependent on cell, tissue and apoptotic stimuli. The phenotype of Bim-deficient mice is a systemic lupus erythematosus-like autoimmune disease with an abnormal accumulation of hematopoietic cells. Bim is thus a critical regulator of hematopoietic cells and immune system. Further studies have revealed the critical roles of Bim in various normal and pathological conditions, including bone homeostasis and tumorigenesis. The current understanding of Bim signaling and roles in the maintenance of tissue homeostasis is reviewed in this paper, focusing on the immune system, bone biology and tumorigenesis to illustrate the diversified role of Bim.

A multi-scale model of hepcidin promoter regulation reveals factors controlling systemic iron homeostasis.

Directory of Open Access Journals (Sweden)

Guillem Casanovas

2014-01-01

Full Text Available Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how BMP6 and IL6 control hepcidin expression. Transcription factor (TF phosphorylation and reporter gene expression were measured under co-stimulation conditions, and the promoter was perturbed by mutagenesis. Using mathematical modeling, we systematically analyzed potential mechanisms of cooperative and competitive promoter regulation by the transcription factors, and experimentally validated the model predictions. Our results reveal that hepcidin cross-regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signaling crosstalk is insignificant. We find that the presence of two BMP-responsive elements enhances the steepness of the promoter response towards the iron-sensing BMP signaling axis, which promotes iron homeostasis in vivo. IL6 co-stimulation reduces the promoter sensitivity towards the BMP signal, because the SMAD and STAT transcription factors compete for recruiting RNA polymerase to the transcription start site. This may explain why inflammatory signals disturb iron homeostasis in anemia of inflammation. Taken together, our results reveal why the iron homeostasis circuit is sensitive to perturbations implicated in disease.

Dietary inhibitors of histone deacetylases in intestinal immunity anc homeostasis

NARCIS (Netherlands)

Schilderink, R.; Verseijden, C.; de Jonge, W. J.

2013-01-01

Intestinal epithelial cells (IECs) are integral players in homeostasis of immunity and host defense in the gut and are under influence of the intestinal microbiome. Microbial metabolites and dietary components, including short chain fatty acids (acetate, propionate, and butyrate, SCFAs), have an

Leptin rapidly improves glucose homeostasis in obese mice by increasing hypothalamic insulin sensitivity.

Science.gov (United States)

Koch, Christiane; Augustine, Rachael A; Steger, Juliane; Ganjam, Goutham K; Benzler, Jonas; Pracht, Corinna; Lowe, Chrishanthi; Schwartz, Michael W; Shepherd, Peter R; Anderson, Greg M; Grattan, David R; Tups, Alexander

2010-12-01

Obesity is associated with resistance to the actions of both leptin and insulin via mechanisms that remain incompletely understood. To investigate whether leptin resistance per se contributes to insulin resistance and impaired glucose homeostasis, we investigated the effect of acute leptin administration on glucose homeostasis in normal as well as leptin- or leptin receptor-deficient mice. In hyperglycemic, leptin-deficient Lep(ob/ob) mice, leptin acutely and potently improved glucose metabolism, before any change of body fat mass, via a mechanism involving the p110α and β isoforms of phosphatidylinositol-3-kinase (PI3K). Unlike insulin, however, the anti-diabetic effect of leptin occurred independently of phospho-AKT, a major downstream target of PI3K, and instead involved enhanced sensitivity of the hypothalamus to insulin action upstream of PI3K, through modulation of IRS1 (insulin receptor substrate 1) phosphorylation. These data suggest that leptin resistance, as occurs in obesity, reduces the hypothalamic response to insulin and thereby impairs peripheral glucose homeostasis, contributing to the development of type 2 diabetes.

Research and development modelling in the frame of search - prognosis - risk theory

International Nuclear Information System (INIS)

Valeca, Serban Constantin

2002-01-01

/efficiency descriptors is discussed through the re-engineering concept viewed as a presently optimal means to ensure sustainable development of power systems with nuclear injection. The monograph is structured in the following nine chapters: 1. Conceptual layout; 1.1 Trends in the re-engineering of power systems with nuclear injection; 1.2 The work's goal highlighting the new aspects; 2. Cybernetic principles and models in operational research applied to classic and nonclassical power systems; 2.1 Principles and models of operational research; 2.2 The cybernetics of structure and power fluxes; 3. Management of sustainable development with power systems with nuclear injection; 3.1. Descriptors and objectives of sustainable development; 3.2 Sustainable development of power systems in the frame of operational research; 4. Managing the nuclear risk; 4.1 Descriptors and models of nuclear risks; 4.2 Monitoring systems of risk transforming it in resource savings; 5. Management of catastrophes and power chaos; 5.1 Premises of catastrophe theory and power chaos; 5. 2 Critical issues in dynamical systems; 6. Management of electric energy quality; 6.1 Quality indicators; 6.2 The risk of live cells exposed to electromagnetic field; 7. Informatics of nuclear electric power systems; 7.1 Premises and trends in the field of nuclear informatics; 7.2 Informatics engineering of nuclear systems modelled in game theory; 8. Economic efficiency of power systems with nuclear injection; 8.1 Holistic indicator models within the economic re-engineering concept; 8.2 Logical schemes for computing the indicators and the program product; 9. Conclusions and operational proposals; 9.1 A synthesis of the exposed ideas; 9.2 Novel aspects of the research undertaken

Value-at-risk estimation with wavelet-based extreme value theory: Evidence from emerging markets

Science.gov (United States)

Cifter, Atilla

2011-06-01

This paper introduces wavelet-based extreme value theory (EVT) for univariate value-at-risk estimation. Wavelets and EVT are combined for volatility forecasting to estimate a hybrid model. In the first stage, wavelets are used as a threshold in generalized Pareto distribution, and in the second stage, EVT is applied with a wavelet-based threshold. This new model is applied to two major emerging stock markets: the Istanbul Stock Exchange (ISE) and the Budapest Stock Exchange (BUX). The relative performance of wavelet-based EVT is benchmarked against the Riskmetrics-EWMA, ARMA-GARCH, generalized Pareto distribution, and conditional generalized Pareto distribution models. The empirical results show that the wavelet-based extreme value theory increases predictive performance of financial forecasting according to number of violations and tail-loss tests. The superior forecasting performance of the wavelet-based EVT model is also consistent with Basel II requirements, and this new model can be used by financial institutions as well.

Peculiarities of plasma homeostasis in the patients with rectal cancer according to laser correlation spectroscopy findings

International Nuclear Information System (INIS)

Byilenko, O.A.; Bazhora, Yu.Yi.; Sokolov, V.M.; Andronov, D.Yu.

1997-01-01

Laser correlation spectroscopy was used to investigate plasma homeostasis in 82 patients with rectal cancer. The spectra of the blood plasma from 21 donors of the transfusion station were used as the control. The blood plasma homeostasis changes reheated with laser correlation spectrometry in the patients with rectal cancer allow to use them for diagnosis of this pathology

MicroRNA-orchestrated pathophysiologic control in gut homeostasis and inflammation.

Science.gov (United States)

Lee, Juneyoung; Park, Eun Jeong; Kiyono, Hiroshi

2016-05-01

The intestine represents the largest and most elaborate immune system organ, in which dynamic and reciprocal interplay among numerous immune and epithelial cells, commensal microbiota, and external antigens contributes to establishing both homeostatic and pathologic conditions. The mechanisms that sustain gut homeostasis are pivotal in maintaining gut health in the harsh environment of the gut lumen. Intestinal epithelial cells are critical players in creating the mucosal platform for interplay between host immune cells and luminal stress inducers. Thus, knowledge of the epithelial interface between immune cells and the luminal environment is a prerequisite for a better understanding of gut homeostasis and pathophysiologies such as inflammation. In this review, we explore the importance of the epithelium in limiting or promoting gut inflammation (e.g., inflammatory bowel disease). We also introduce recent findings on how small RNAs such as microRNAs orchestrate pathophysiologic gene regulation. [BMB Reports 2016; 49(5): 263-269].

CHF: circulatory homeostasis gone awry.

Science.gov (United States)

Weber, Karl T; Burlew, Brad S; Davis, Richard C; Newman, Kevin P; D'Cruz, Ivan A; Hawkins, Ralph G; Wall, Barry M; Parker, Robert B

2002-01-01

The role of the renin-angiotensin-aldosterone system (RAAS) is integral to salt and water retention, particularly by the kidneys. Over time, positive sodium balance leads first to intra- and then to extravascular volume expansion, with subsequent symptomatic heart failure. This report examines the role of the RAAS in regulating a less well recognized component essential to circulatory homeostasis--central blood volume. The regulation of central blood volume draws on integrative cardiorenal physiology and a key role played by the RAAS in its regulation. In presenting insights into the role of the RAAS in regulating central blood volume, this review also addresses other sodium-retaining states with a predisposition to edema formation, such as cirrhosis and nephrosis. (c)2002 CHF, Inc

AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

Science.gov (United States)

Chen, Peili; Li, Yan Chun; Toback, F Gary

2015-01-01

Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD). We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP)-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI) mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

Directory of Open Access Journals (Sweden)

Peili Chen

Full Text Available Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD. We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

Homeostasis of metals in the progression of Alzheimer's disease.

Science.gov (United States)

González-Domínguez, Raúl; García-Barrera, Tamara; Gómez-Ariza, José Luis

2014-06-01

In order to study the involvement of metals in the progression of Alzheimer's disease, serum samples from patients with Alzheimer and mild cognitive impairment were investigated. For this purpose, metal content was analyzed after size-fractionation of species and then, inter-element and inter-fraction ratios were computed. In this way, the analysis allowed discovering changes that could be used as markers of disease, but also provided a new insight into the interactions in the homeostasis of elements in neurodegeneration and its progression. Aluminum and labile forms of iron and copper were increased in demented patients, while manganese, zinc and selenium were reduced. Interestingly, levels of different elements, principally iron, aluminum and manganese, were closely inter-related, which could evidence a complex interdependency between the homeostasis of the different metals in this disorder. On the other hand, imbalances in metabolism of copper, zinc and selenium could be associated to abnormal redox status. Therefore, this study may contribute to our understanding of the pathological mechanisms related to metals in Alzheimer's disease.

Quorum sensing in CD4+ T cell homeostasis: a hypothesis and a model.

Directory of Open Access Journals (Sweden)

Afonso R.M. Almeida

2012-05-01

Full Text Available Homeostasis of lymphocyte numbers is believed to be due to competition between cellular populations for a common niche of restricted size, defined by the combination of interactions and trophic factors required for cell survival. Here we propose a new mechanism: homeostasis of lymphocyte numbers could also be achieved by the ability of lymphocytes to perceive the density of their own populations. Such a mechanism would be reminiscent of the primordial quorum sensing systems used by bacteria, in which some bacteria sense the accumulation of bacterial metabolites secreted by other elements of the population, allowing them to count the number of cells present and adapt their growth accordingly. We propose that homeostasis of CD4+ T cell numbers may occur via a quorum-sensing-like mechanism, where IL-2 is produced by activated CD4+ T cells and sensed by a population of CD4+ Treg cells that expresses the high-affinity IL-2Rα-chain and can regulate the number of activated IL-2-producing CD4+ T cells and the total CD4+T cell population. In other words, CD4+ T cell populations can restrain their growth by monitoring the number of activated cells, thus preventing uncontrolled lymphocyte proliferation during immune responses. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled T cell activation and autoimmunity. Finally, we present a mathematical model that describes the role of IL-2 and quorum-sensing mechanisms in CD4+ T cell homeostasis during an immune response.

Method for assessing coal-floor water-inrush risk based on the variable-weight model and unascertained measure theory

Science.gov (United States)

Wu, Qiang; Zhao, Dekang; Wang, Yang; Shen, Jianjun; Mu, Wenping; Liu, Honglei

2017-11-01

Water inrush from coal-seam floors greatly threatens mining safety in North China and is a complex process controlled by multiple factors. This study presents a mathematical assessment system for coal-floor water-inrush risk based on the variable-weight model (VWM) and unascertained measure theory (UMT). In contrast to the traditional constant-weight model (CWM), which assigns a fixed weight to each factor, the VWM varies with the factor-state value. The UMT employs the confidence principle, which is more effective in ordered partition problems than the maximum membership principle adopted in the former mathematical theory. The method is applied to the Datang Tashan Coal Mine in North China. First, eight main controlling factors are selected to construct the comprehensive evaluation index system. Subsequently, an incentive-penalty variable-weight model is built to calculate the variable weights of each factor. Then, the VWM-UMT model is established using the quantitative risk-grade divide of each factor according to the UMT. On this basis, the risk of coal-floor water inrush in Tashan Mine No. 8 is divided into five grades. For comparison, the CWM is also adopted for the risk assessment, and a differences distribution map is obtained between the two methods. Finally, the verification of water-inrush points indicates that the VWM-UMT model is powerful and more feasible and reasonable. The model has great potential and practical significance in future engineering applications.

Essentials of Risk Theory

NARCIS (Netherlands)

Roeser, S.; Hillerbrand, R.; Sandin, P.; Peterson, M.B.

2012-01-01

Risk has become one of the main topics in fields as diverse as engineering, medicine and economics, and it is also studied by social scientists, psychologists and legal scholars. This Springer Essentials version offers an overview of the in-depth handbook and highlights some of the main points

Prospect theory in the valuation of health.

Science.gov (United States)

Moffett, Maurice L; Suarez-Almazor, Maria E

2005-08-01

Prospect theory is the prominent nonexpected utility theory in the estimation of health state preference scores for quality-adjusted life year calculation. Until recently, the theory was not considered to be developed to the point of implementation in economic analysis. This review focuses on the research and evidence that tests the implementation of prospect theory into health state valuation. The typical application of expected utility theory assumes that a decision maker has stable preferences under conditions of risk and uncertainty. Under prospect theory, preferences are dependent on whether the decision maker regards the outcome of a choice as a gain or loss, relative to a reference point. The conceptual preference for standard gamble utilities in the valuation of health states has led to the development of elicitation techniques. Empirical evidence using these techniques indicates that when individual preferences are elicited, a prospect theory consistent framework appears to be necessary for adequate representation of individual health utilities. The relevance of prospect theory to policy making and resource allocation remains to be established. Societal preferences may not need the same attitudes towards risks as individual preferences, and may remain largely risk neutral.

TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis.

Science.gov (United States)

Sun, Honghong; Gong, Shunyou; Carmody, Ruaidhri J; Hilliard, Anja; Li, Li; Sun, Jing; Kong, Li; Xu, Lingyun; Hilliard, Brendan; Hu, Shimin; Shen, Hao; Yang, Xiaolu; Chen, Youhai H

2008-05-02

Immune homeostasis is essential for the normal functioning of the immune system, and its breakdown leads to fatal inflammatory diseases. We report here the identification of a member of the tumor necrosis factor-alpha-induced protein-8 (TNFAIP8) family, designated TIPE2, that is required for maintaining immune homeostasis. TIPE2 is preferentially expressed in lymphoid tissues, and its deletion in mice leads to multiorgan inflammation, splenomegaly, and premature death. TIPE2-deficient animals are hypersensitive to septic shock, and TIPE2-deficient cells are hyper-responsive to Toll-like receptor (TLR) and T cell receptor (TCR) activation. Importantly, TIPE2 binds to caspase-8 and inhibits activating protein-1 and nuclear factor-kappaB activation while promoting Fas-induced apoptosis. Inhibiting caspase-8 significantly blocks the hyper-responsiveness of TIPE2-deficient cells. These results establish that TIPE2 is an essential negative regulator of TLR and TCR function, and its selective expression in the immune system prevents hyperresponsiveness and maintains immune homeostasis.

Chronic Effect of Aspartame on Ionic Homeostasis and Monoamine Neurotransmitters in the Rat Brain.

Science.gov (United States)

Abhilash, M; Alex, Manju; Mathews, Varghese V; Nair, R Harikumaran

2014-07-01

Aspartame is one of the most widely used artificial sweeteners globally. Data concerning acute neurotoxicity of aspartame is controversial, and knowledge on its chronic effect is limited. In the current study, we investigated the chronic effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter concentrations in the brain. Our results showed that aspartame at high dose caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We also investigated the effects of aspartame on brain regional monoamine synthesis, and the results revealed that there was a significant decrease of dopamine in corpus striatum and cerebral cortex and of serotonin in corpus striatum. Moreover, aspartame treatment significantly alters the tyrosine hydroxylase activity and amino acids levels in the brain. Our data suggest that chronic use of aspartame may affect electrolyte homeostasis and monoamine neurotransmitter synthesis dose dependently, and this might have a possible effect on cognitive functions. © The Author(s) 2014.

Deficiency of a alpha-1-antitrypsin influences systemic iron homeostasis

Science.gov (United States)

Abstract Background: There is evidence that proteases and anti-proteases participate in the iron homeostasis of cells and living systems. We tested the postulate that alpha-1 antitrypsin (A1AT) polymorphism and the consequent deficiency of this anti-protease in humans are asso...

Hedgehog Signaling and Maintenance of Homeostasis in the Intestinal Epithelium

NARCIS (Netherlands)

Büller, Nikè V. J. A.; Rosekrans, Sanne L.; Westerlund, Jessica; van den Brink, Gijs R.

2012-01-01

Homeostasis of the rapidly renewing intestinal epithelium depends on a balance between cell proliferation and loss. Indian hedgehog (Ihh) acts as a negative feedback signal in this dynamic equilibrium. We discuss recent evidence that Ihh may be one of the key epithelial signals that indicates

Maintenance of the adult Drosophila intestine: all roads lead to homeostasis.

Science.gov (United States)

Guo, Zheng; Lucchetta, Elena; Rafel, Neus; Ohlstein, Benjamin

2016-10-01

Maintenance of tissue homeostasis is critical in tissues with high turnover such as the intestinal epithelium. The intestinal epithelium is under constant cellular assault due to its digestive functions and its function as a barrier to chemical and bacterial insults. The resulting high rate of cellular turnover necessitates highly controlled mechanisms of regeneration to maintain the integrity of the tissue over the lifetime of the organism. Transient increase in stem cell proliferation is a commonly used and elaborate mechanism to ensure fast and efficient repair of the gut. However, tissue repair is not limited to regulating ISC proliferation, as emerging evidence demonstrates that the Drosophila intestine uses multiple strategies to ensure proper tissue homeostasis that may also extend to other tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of whole-body irradiation on calcium and phosphate homeostasis in the rat

International Nuclear Information System (INIS)

Pento, J.T.; Kenny, A.D.

1975-01-01

Previous irradiation studies have revealed marked alterations in calcium metabolism. Moreover, the maintenance of calcium homeostasis with parathyroid hormone or calcium salts has been reported to reduce radiation lethality. Therefore, the present study was designed to evaluate the influence of irradiation on calcium homeostasis in the rat. Nine hundred rad of whole-body irradiation produced a significant depression of both plasma calcium and phosphate at 4 days postirradiation. This effect of irradiation was observed to be dose-dependent over a range of 600 to 1200 rad, and possibly related to irradiation-induced anorexia. The physiological significance of these observations is discussed

On the mechanism of cytogenetic effect of electromagnetic radiation: role of oxidation homeostasis

International Nuclear Information System (INIS)

Brezitskaya, N.V.; Timchenko, O.I.

2000-01-01

The evaluation of the role of changes in oxidation homeostasis in developing the cytogenetic effects arising by the electromagnetic irradiation impact is carried out. The experiments were performed on white male rats. The animals were subjected to impact of the nonionizing radiations in the microwave range during 40 days by 7 hours a day. It is established that changes in the free-radical oxidation by the impact of nonionizing radiation of the electromagnetic fields have a wave-like character. It is established that changes in the oxidation homeostasis proceed the development of cytogenetic effects and may be the cause thereof [ru

Endogenous ligands for C-type lectin receptors: the true regulators of immune homeostasis.

Science.gov (United States)

García-Vallejo, Juan J; van Kooyk, Yvette

2009-07-01

C-type lectin receptors (CLRs) have long been known as pattern-recognition receptors implicated in the recognition of pathogens by the innate immune system. However, evidence is accumulating that many CLRs are also able to recognize endogenous 'self' ligands and that this recognition event often plays an important role in immune homeostasis. In the present review, we focus on the human and mouse CLRs for which endogenous ligands have been described. Special attention is given to the signaling events initiated upon recognition of the self ligand and the regulation of glycosylation as a switch modulating CLR recognition, and therefore, immune homeostasis.

Influence of oxidative homeostasis on bacterial density and cost of infection in Drosophila-Wolbachia symbioses.

Science.gov (United States)

Monnin, D; Kremer, N; Berny, C; Henri, H; Dumet, A; Voituron, Y; Desouhant, E; Vavre, F

2016-06-01

The evolution of symbioses along the continuum between parasitism and mutualism can be influenced by the oxidative homeostasis, that is the balance between reactive oxygen species (ROS) and antioxidant molecules. Indeed, ROS can contribute to the host immune defence to regulate symbiont populations, but are also toxic. This interplay between ROS and symbiosis is notably exemplified by recent results in arthropod-Wolbachia interactions. Wolbachia are symbiotic bacteria involved in a wide range of interactions with their arthropods hosts, from facultative, parasitic associations to obligatory, mutualistic ones. In this study, we used Drosophila-Wolbachia associations to determine whether the oxidative homeostasis plays a role in explaining the differences between phenotypically distinct arthropod-Wolbachia symbioses. We used Drosophila lines with different Wolbachia infections and measured the effects of pro-oxidant (paraquat) and antioxidant (glutathione) treatments on the Wolbachia density and the host survival. We show that experimental manipulations of the oxidative homeostasis can reduce the cost of the infection through its effect on Wolbachia density. We discuss the implication of this result from an evolutionary perspective and argue that the oxidative homeostasis could underlie the evolution of tolerance and dependence on Wolbachia. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Decision making for animal health and welfare: integrating risk-benefit analysis with prospect theory.

Science.gov (United States)

Hansson, Helena; Lagerkvist, Carl Johan

2014-06-01

This study integrated risk-benefit analysis with prospect theory with the overall objective of identifying the type of management behavior represented by farmers' choices of mastitis control options (MCOs). Two exploratory factor analyses, based on 163 and 175 Swedish farmers, respectively, highlighted attitudes to MCOs related to: (1) grouping cows and applying milking order to prevent spread of existing infection and (2) working in a precautionary way to prevent mastitis occurring. This was interpreted as being based on (1) reactive management behavior on detection of udder-health problems in individual cows and (2) proactive management behavior to prevent mastitis developing. Farmers' assessments of these MCOs were found to be based on asymmetrical evaluations of risks and benefits, suggesting that farmers' management behavior depends on their individual reference point. In particular, attitudes to MCOs related to grouping cows and applying milking order to prevent the spread of mastitis once infected cows were detected were stronger in the risk domain than in the benefit domain, in accordance with loss aversion. In contrast, attitudes to MCOs related to working in a precautionary way to prevent cows from becoming infected in the first place were stronger in the benefit domain than in the risk domain, in accordance with reverse loss aversion. These findings are of practical importance for farmers and agribusiness and in public health protection work to reduce the current extensive use of antibiotics in dairy herds. © 2013 Society for Risk Analysis.

The immune system, natural autoantibodies and general homeostasis in health and disease.

Science.gov (United States)

Poletaev, A; Boura, P

2011-10-01

It is generally accepted that the destination of the immune system is not only to discriminate between self and non-self but also to mount responses against non-self. During the last decades, it became evident that weak self-reactivity is a necessary condition for immune homeostasis. Natural self reactivity and the internal image created by autoantibodies, participate greatly to the maintenance of homeostasis. Under conditions of increased or altered antigenic pressure, the homeostatic status is disrupted and the organism becomes vulnerable to the emergence of diseases. "Immunculus" is the self-reactive and interconnected entity of the immune system, provided by a complicated network of natural autoantibobies of different specificity, as a mosaic picture. Quantitative changes in each part of the image are related to variations of expression of relative antigens. The immune system takes in account image information from the continuous screening of the antigenic status and compares between presented state and the desired (optimal) one. Substantial and prolonged deviations from the optimal state, triggers the induction of compensatory and reparative processes, aiming to restore molecular and functional homeostasis. So, natural autoimmunity through the ability of natural a-Abs to induce mechanisms of natural and acquired immunity, aims to prevent pathogenic processes and maintain or restore health status.

Pain emotion and homeostasis.

Science.gov (United States)

Panerai, Alberto E

2011-05-01

Pain has always been considered as part of a defensive strategy, whose specific role is to signal an immediate, active danger. This definition partially fits acute pain, but certainly not chronic pain, that is maintained also in the absence of an active noxa or danger and that nowadays is considered a disease by itself. Moreover, acute pain is not only an automatic alerting system, but its severity and characteristics can change depending on the surrounding environment. The affective, emotional components of pain have been and are the object of extensive attention and research by psychologists, philosophers, physiologists and also pharmacologists. Pain itself can be considered to share the same genesis as emotions and as a specific emotion in contributing to the maintenance of the homeostasis of each unique subject. Interestingly, this role of pain reaches its maximal development in the human; some even argue that it is specific for the human primate.

Asthma as a disruption in iron homeostasis | Science ...

Science.gov (United States)

Over several decades, asthma has evolved from being recognized as a single disease to include a diverse group of phenotypes with dissimilar natural histories, pathophysiologies, responses to treatment, and distinctive molecular pathways. With the application of Occam’s razor to asthma, it is proposed that there is one cause underlying the numerous phenotypes of this disease and that the responsible molecular pathway is a deficiency of iron in the lung tissues. This deficiency can be either absolute (e.g. asthma in the neonate and during both pregnancy and menstruation) or functional (e.g. asthma associated with infections, smoking, and obesity). Comparable associations between asthma co-morbidity (e.g. eczema, urticaria, restless leg syndrome, and pulmonary hypertension) with iron deficiency support such a shared mechanistic pathway. Therapies directed at asthma demonstrate a capacity to impact iron homeostasis, further strengthening the relationship. Finally, pathophysiologic events producing asthma, including inflammation, increases in Th2 cells, and muscle contraction, can correlate with iron availability. Recognition of a potential association between asthma and an absolute and/or functional iron deficiency suggests specific therapeutic interventions including inhaled iron. Asthma is a public health issue that has environmental triggers. Iron homeostasis is an essential mechanism whereby the body manages the impact of environmental agents on overall

The plasticity of extracellular fluid homeostasis in insects.

Science.gov (United States)

Beyenbach, Klaus W

2016-09-01

In chemistry, the ratio of all dissolved solutes to the solution's volume yields the osmotic concentration. The present Review uses this chemical perspective to examine how insects deal with challenges to extracellular fluid (ECF) volume, solute content and osmotic concentration (pressure). Solute/volume plots of the ECF (hemolymph) reveal that insects tolerate large changes in all three of these ECF variables. Challenges beyond those tolerances may be 'corrected' or 'compensated'. While a correction simply reverses the challenge, compensation accommodates the challenge with changes in the other two variables. Most insects osmoregulate by keeping ECF volume and osmotic concentration within a wide range of tolerance. Other insects osmoconform, allowing the ECF osmotic concentration to match the ambient osmotic concentration. Aphids are unique in handling solute and volume loads largely outside the ECF, in the lumen of the gut. This strategy may be related to the apparent absence of Malpighian tubules in aphids. Other insects can suspend ECF homeostasis altogether in order to survive extreme temperatures. Thus, ECF homeostasis in insects is highly dynamic and plastic, which may partly explain why insects remain the most successful class of animals in terms of both species number and biomass. © 2016. Published by The Company of Biologists Ltd.

Immunology in the liver--from homeostasis to disease.

Science.gov (United States)

Heymann, Felix; Tacke, Frank

2016-02-01

The liver is a central immunological organ with a high exposure to circulating antigens and endotoxins from the gut microbiota, particularly enriched for innate immune cells (macrophages, innate lymphoid cells, mucosal-associated invariant T (MAIT) cells). In homeostasis, many mechanisms ensure suppression of immune responses, resulting in tolerance. Tolerance is also relevant for chronic persistence of hepatotropic viruses or allograft acceptance after liver transplantation. The liver can rapidly activate immunity in response to infections or tissue damage. Depending on the underlying liver disease, such as viral hepatitis, cholestasis or NASH, different triggers mediate immune-cell activation. Conserved mechanisms such as molecular danger patterns (alarmins), Toll-like receptor signalling or inflammasome activation initiate inflammatory responses in the liver. The inflammatory activation of hepatic stellate and Kupffer cells results in the chemokine-mediated infiltration of neutrophils, monocytes, natural killer (NK) and natural killer T (NKT) cells. The ultimate outcome of the intrahepatic immune response (for example, fibrosis or resolution) depends on the functional diversity of macrophages and dendritic cells, but also on the balance between pro-inflammatory and anti-inflammatory T-cell populations. As reviewed here, tremendous progress has helped to understand the fine-tuning of immune responses in the liver from homeostasis to disease, indicating promising targets for future therapies in acute and chronic liver diseases.

The commensal microbiota drives immune homeostasis

Directory of Open Access Journals (Sweden)

Marie-Claire eArrieta

2012-03-01

Full Text Available For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use to keep our immune system healthy, as opposed to trying to correct the immune imbalances caused by dysbiosis, may prove to be a more astute and efficient way of treating immune-mediated disease.

Allergies and Asthma: Do Atopic Disorders Result from Inadequate Immune Homeostasis arising from Infant Gut Dysbiosis?

Science.gov (United States)

Johnson, Christine C; Ownby, Dennis R

2016-01-01

Our global hypothesis is that atopic conditions and asthma develop because an individual's immune system is not able to appropriately resolve inflammation resulting from allergen exposures. We propose that the failure to appropriately down-regulate inflammation and produce a toleragenic state results primarily from less robust immune homeostatic processes rather than from a tendency to over-respond to allergenic stimuli. An individual with lower immune homeostatic capacity is unable to rapidly and completely terminate, on average over time, immune responses to innocuous allergens, increasing risk of allergic disease. A lack of robust homeostasis also increases the risk of other inflammatory conditions, such as prolonged respiratory viral infections and obesity, leading to the common co-occurrence of these conditions. Further, we posit that the development of vigorous immune homeostatic mechanisms is an evolutionary adaptation strongly influenced by both 1) exposure to a diverse maternal microbiota through the prenatal period, labor and delivery, and, 2) an orderly assemblage process of the infant's gut microbiota ecosystem shaped by breastfeeding and early exposure to a wide variety of ingested foods and environmental microbes. This early succession of microbial communities together with early allergen exposures orchestrate the development of an immune system with a robust ability to optimally control inflammatory responses and a lowered risk for atopic disorders.

Uncertainty theory

CERN Document Server

Liu, Baoding

2015-01-01

When no samples are available to estimate a probability distribution, we have to invite some domain experts to evaluate the belief degree that each event will happen. Perhaps some people think that the belief degree should be modeled by subjective probability or fuzzy set theory. However, it is usually inappropriate because both of them may lead to counterintuitive results in this case. In order to rationally deal with belief degrees, uncertainty theory was founded in 2007 and subsequently studied by many researchers. Nowadays, uncertainty theory has become a branch of axiomatic mathematics for modeling belief degrees. This is an introductory textbook on uncertainty theory, uncertain programming, uncertain statistics, uncertain risk analysis, uncertain reliability analysis, uncertain set, uncertain logic, uncertain inference, uncertain process, uncertain calculus, and uncertain differential equation. This textbook also shows applications of uncertainty theory to scheduling, logistics, networks, data mining, c...

Protection motivation theory and adolescent drug trafficking: relationship between health motivation and longitudinal risk involvement.

Science.gov (United States)

Wu, Ying; Stanton, Bonita F; Li, Xiaoming; Galbraith, Jennifer; Cole, Matthew L

2005-03-01

To assess health protection motivation as explained by the constructs of protection motivation theory (PMT) and its association with drug trafficking over 2 years. The sample included 817 African American youth (13-16 years old) participating in an adolescent risk-reduction program. We developed an instrument measuring the level of health protection motivation (LHPM) using factor analysis. Changes in LHPM over time were examined among drug traffickers, abstainers, initiators, and nonrisk youths. In sum, 151 participants reported selling and/or delivering drugs during the study period. The significant inverse correlation between drug-trafficking intention and health protection motivation was consistent with PMT. Changes in LHPM were strongly associated with the dynamics of behavior over 2 years. Adolescent drug trafficking can be predicted by an overall level of health protection motivation. PMT and related theories should be considered in the design of drug-trafficking prevention intervention.

[Bone homeostasis and Mechano biology.

Science.gov (United States)

Nakashima, Tomoki

The weight-bearing exercises help to build bones and to maintain them strength. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication between bone component cells such as osteoclasts, osteoblasts and osteocytes. An imbalance of this process is often linked to various bone diseases. During bone remodeling, resorption by osteoclasts precedes bone formation by osteoblasts. Based on the osteocyte location within the bone matrix and the cellular morphology, it is proposed that osteocytes potentially contribute to the regulation of bone remodeling in response to mechanical and endocrine stimuli.

Galanin-like peptide (GALP) is a hypothalamic regulator of energy homeostasis and reproduction.

Science.gov (United States)

Lawrence, Catherine; Fraley, Gregory S

2011-01-01

Galanin-like peptide (GALP) was discovered in 1999 in the porcine hypothalamus and was found to be a 60 amino acid neuropeptide. GALP shares sequence homology to galanin (1-13) in position 9-21 and can bind to, as well as activate, the three galanin receptor subtypes (GalR1-3). GALP-expressing cells are limited, and are mainly found in the arcuate nucleus of the hypothalamus (ARC) and the posterior pituitary. GALP-positive neurons in the ARC project to several brain regions where they appear to make contact with multiple neuromodulators. These neuromodulators are involved in the regulation of energy homeostasis and reproduction, anatomical evidence that suggests a role for GALP in these physiological functions. In support of this idea, GALP gene expression is regulated by several factors that reflect metabolic state including the metabolic hormones leptin and insulin, thyroid hormones, and blood glucose. Considerable evidence now exists to support the hypothesis that GALP has a role in the regulation of energy homeostasis and reproduction; and, that GALP's role may be independent of the known galanin receptors. In this review, we (1) provide an overview of the distribution of GALP, and discuss the potential relationship between GALP and other neuromodulators of energy homeostasis and reproduction, (2) discuss the metabolic factors that regulate GALP expression, (3) review the evidence for the role of GALP in energy homeostasis and reproduction, (4) discuss the potential downstream mediators and mechanisms underlying GALP's effects, and (5) discuss the possibility that GALP may mediate its effects via an as yet unidentified GALP-specific receptor. Copyright © 2010 Elsevier Inc. All rights reserved.

Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis.

Science.gov (United States)

Klose, Christoph S N; Artis, David

2016-06-21

Research over the last 7 years has led to the formal identification of innate lymphoid cells (ILCs), increased the understanding of their tissue distribution and has established essential functions of ILCs in diverse physiological processes. These include resistance to pathogens, the regulation of autoimmune inflammation, tissue remodeling, cancer and metabolic homeostasis. Notably, many ILC functions appear to be regulated by mechanisms distinct from those of other innate and adaptive immune cells. In this Review, we focus on how group 2 ILC (ILC2) and group 3 ILC (ILC3) responses are regulated and how these cells interact with other immune and non-immune cells to mediate their functions. We highlight experimental evidence from mouse models and patient-based studies that have elucidated the effects of ILCs on the maintenance of tissue homeostasis and the consequences for health and disease.

The quality control theory of aging

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Warren Ladiges

2014-05-01

Full Text Available The quality control (QC theory of aging is based on the concept that aging is the result of a reduction in QC of cellular systems designed to maintain lifelong homeostasis. Four QC systems associated with aging are 1 inadequate protein processing in a distressed endoplasmic reticulum (ER; 2 histone deacetylase (HDAC processing of genomic histones and gene silencing; 3 suppressed AMPK nutrient sensing with inefficient energy utilization and excessive fat accumulation; and 4 beta-adrenergic receptor (BAR signaling and environmental and emotional stress. Reprogramming these systems to maintain efficiency and prevent aging would be a rational strategy for increased lifespan and improved health. The QC theory can be tested with a pharmacological approach using three well-known and safe, FDA-approved drugs: 1 phenyl butyric acid, a chemical chaperone that enhances ER function and is also an HDAC inhibitor, 2 metformin, which activates AMPK and is used to treat type 2 diabetes, and 3 propranolol, a beta blocker which inhibits BAR signaling and is used to treat hypertension and anxiety. A critical aspect of the QC theory, then, is that aging is associated with multiple cellular systems that can be targeted with drug combinations more effectively than with single drugs. But more importantly, these drug combinations will effectively prevent, delay, or reverse chronic diseases of aging that impose such a tremendous health burden on our society.

The quality control theory of aging.

Science.gov (United States)

Ladiges, Warren

2014-01-01

The quality control (QC) theory of aging is based on the concept that aging is the result of a reduction in QC of cellular systems designed to maintain lifelong homeostasis. Four QC systems associated with aging are 1) inadequate protein processing in a distressed endoplasmic reticulum (ER); 2) histone deacetylase (HDAC) processing of genomic histones and gene silencing; 3) suppressed AMPK nutrient sensing with inefficient energy utilization and excessive fat accumulation; and 4) beta-adrenergic receptor (BAR) signaling and environmental and emotional stress. Reprogramming these systems to maintain efficiency and prevent aging would be a rational strategy for increased lifespan and improved health. The QC theory can be tested with a pharmacological approach using three well-known and safe, FDA-approved drugs: 1) phenyl butyric acid, a chemical chaperone that enhances ER function and is also an HDAC inhibitor, 2) metformin, which activates AMPK and is used to treat type 2 diabetes, and 3) propranolol, a beta blocker which inhibits BAR signaling and is used to treat hypertension and anxiety. A critical aspect of the QC theory, then, is that aging is associated with multiple cellular systems that can be targeted with drug combinations more effectively than with single drugs. But more importantly, these drug combinations will effectively prevent, delay, or reverse chronic diseases of aging that impose such a tremendous health burden on our society.

Nuclear terrorism risk analysis using game theory. Case study of sea transportation of MOX fuel

International Nuclear Information System (INIS)

Nakatani, Eri; Tanaka, Satoru; Choi, Jor-Shan

2010-01-01

While considerable attention and resources have been directed towards improving nuclear security in Japan in response to the threat of nuclear terrorism, the transport of nuclear material raises concern by the public as indicated in the recent return of MOX fuel from Europe. This concern cannot be adequately addressed by the government through communications with the public because of the confidential nature of such transport. Also, it remains a challenge for adequately assessing the nuclear terrorism risk because many key parameters associated with such assessment cannot be derived from statistical data and reflect actors' intentions unlike assessment on natural disasters. This study proposes an assessment methodology which introduces game theory to deduce the correlations between those key parameters and can be used to analyze the nuclear terrorism risk, both quantitatively and qualitatively for the civilian use of nuclear power. Risk will be calculated by Monte Carlo methods based on probability distributions set for actors' utilities. A case-study of transporting the MOX fuel by sea is also included. (author)

estimated glomerular filtration rate and risk of survival in acute stroke

African Journals Online (AJOL)

2014-03-03

Mar 3, 2014 ... Design: A prospective observational cross-sectional study. Setting: Medical ... stroke sub-type, blood sugar, serum creatinine, serum urea and ... history of hypertension and diabetes mellitus, history of alcohol ... Declining renal function takes its toll on homeostasis .... risk of stroke: meta-analysis. BMJ 2010 ...

Framing effects and risk-sensitive decision making.

Science.gov (United States)

Mishra, Sandeep; Gregson, Margaux; Lalumière, Martin L

2012-02-01

Prospect theory suggests that people are risk-averse when facing gains, but risk-prone when facing losses, a pattern known as the framing effect. Although framing effects have been widely demonstrated, few studies have investigated framing effects under conditions of need. Risk-sensitivity theory predicts that decision makers should prefer high-risk options in situations of high need, when lower risk options are unlikely to meet those needs. In two experiments, we examined (1) whether framing effects occurred in behavioural tasks involving risky decision making from description and decision making from experience, (2) whether participants' risky decision making conformed to the predictions of risk-sensitivity theory, and (3) whether decision framing interacted with conditions of need to influence decision making under risk. The results suggest that under all circumstances, risky decision making conformed to the predictions of risk-sensitivity theory. Framing effects were at least partially demonstrable under all experimental conditions. Finally, negative frames interacted with situations of high need to produce particularly elevated levels of risky choice. Together, the results suggest that risk-sensitivity theory can augment prospect theory to explain choice under conditions of need. ©2011 The British Psychological Society.

Matriptase zymogen supports epithelial development, homeostasis and regeneration

DEFF Research Database (Denmark)

Friis, Stine; Tadeo, Daniel; Le-Gall, Sylvain M.

2017-01-01

Background Matriptase is a membrane serine protease essential for epithelial development, homeostasis, and regeneration, as well as a central orchestrator of pathogenic pericellular signaling in the context of inflammatory and proliferative diseases. Matriptase is an unusual protease in that its...... previously reported for transgenic mice mis-expressing wildtype epidermal matriptase. Equally surprising, mice engineered to express only zymogen-locked endogenous matriptase, unlike matriptase null mice, were viable, developed epithelial barrier function, and regenerated the injured epithelium. Compatible...

Bone turnover, calcium homeostasis, and vitamin D status in Danish vegans.

Science.gov (United States)

Hansen, Tue H; Madsen, Marie T B; Jørgensen, Niklas R; Cohen, Arieh S; Hansen, Torben; Vestergaard, Henrik; Pedersen, Oluf; Allin, Kristine H

2018-01-23

A vegan diet has been associated with increased bone fracture risk, but the physiology linking nutritional exposure to bone metabolism has only been partially elucidated. This study investigated whether a vegan diet is associated with increased bone turnover and altered calcium homeostasis due to insufficient intake of calcium and vitamin D. Fractionated and total 25-hydroxyvitamin D (25(OH)-D), parathyroid hormone (PTH), calcium, and four bone turnover markers (osteocalcin, N-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BAP), and C-terminal telopeptide of type I collagen (CTX)) were measured in serum from 78 vegans and 77 omnivores. When adjusting for seasonality and constitutional covariates (age, sex, and body fat percentage) vegans had higher concentrations of PINP (32 [95% CI: 7, 64]%, P = 0.01) and BAP (58 [95% CI: 27, 97]%, P Vegans had higher serum PTH concentration (38 [95% CI: 19, 60]%; P Vegans have higher levels of circulating bone turnover markers compared to omnivores, which may in the long-term lead to poorer bone health. Differences in dietary habits including intake of vitamin D and calcium may, at least partly, explain the observed differences.

Nitric oxide and plant iron homeostasis.

Science.gov (United States)

Buet, Agustina; Simontacchi, Marcela

2015-03-01

Like all living organisms, plants demand iron (Fe) for important biochemical and metabolic processes. Internal imbalances, as a consequence of insufficient or excess Fe in the environment, lead to growth restriction and affect crop yield. Knowledge of signals and factors affecting each step in Fe uptake from the soil and distribution (long-distance transport, remobilization from old to young leaves, and storage in seeds) is necessary to improve our understanding of plant mineral nutrition. In this context, the role of nitric oxide (NO) is discussed as a key player in maintaining Fe homeostasis through its cross talk with hormones, ferritin, and frataxin and the ability to form nitrosyl-iron complexes. © 2015 New York Academy of Sciences.

Deletion of Lkb1 in pro-opiomelanocortin neurons impairs peripheral glucose homeostasis in mice.

Science.gov (United States)

Claret, Marc; Smith, Mark A; Knauf, Claude; Al-Qassab, Hind; Woods, Angela; Heslegrave, Amanda; Piipari, Kaisa; Emmanuel, Julian J; Colom, André; Valet, Philippe; Cani, Patrice D; Begum, Ghazala; White, Anne; Mucket, Phillip; Peters, Marco; Mizuno, Keiko; Batterham, Rachel L; Giese, K Peter; Ashworth, Alan; Burcelin, Remy; Ashford, Michael L; Carling, David; Withers, Dominic J

2011-03-01

AMP-activated protein kinase (AMPK) signaling acts as a sensor of nutrients and hormones in the hypothalamus, thereby regulating whole-body energy homeostasis. Deletion of Ampkα2 in pro-opiomelanocortin (POMC) neurons causes obesity and defective neuronal glucose sensing. LKB1, the Peutz-Jeghers syndrome gene product, and Ca(2+)-calmodulin-dependent protein kinase kinase β (CaMKKβ) are key upstream activators of AMPK. This study aimed to determine their role in POMC neurons upon energy and glucose homeostasis regulation. Mice lacking either Camkkβ or Lkb1 in POMC neurons were generated, and physiological, electrophysiological, and molecular biology studies were performed. Deletion of Camkkβ in POMC neurons does not alter energy homeostasis or glucose metabolism. In contrast, female mice lacking Lkb1 in POMC neurons (PomcLkb1KO) display glucose intolerance, insulin resistance, impaired suppression of hepatic glucose production, and altered expression of hepatic metabolic genes. The underlying cellular defect in PomcLkb1KO mice involves a reduction in melanocortin tone caused by decreased α-melanocyte-stimulating hormone secretion. However, Lkb1-deficient POMC neurons showed normal glucose sensing, and body weight was unchanged in PomcLkb1KO mice. Our findings demonstrate that LKB1 in hypothalamic POMC neurons plays a key role in the central regulation of peripheral glucose metabolism but not body-weight control. This phenotype contrasts with that seen in mice lacking AMPK in POMC neurons with defects in body-weight regulation but not glucose homeostasis, which suggests that LKB1 plays additional functions distinct from activating AMPK in POMC neurons.

p300/CBP as a Key Nutritional Sensor for Hepatic Energy Homeostasis and Liver Fibrosis

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Weilei Yao

2018-01-01

Full Text Available The overwhelming frequency of metabolic diseases such as obesity and diabetes are closely related to liver diseases, which might share common pathogenic signaling processes. These metabolic disorders in the presence of inflammatory response seem to be triggered by and to reside in the liver, which is the central metabolic organ that plays primary roles in regulating lipid and glucose homeostasis upon alterations of metabolic conditions. Recently, abundant emerging researches suggested that p300 and CREB binding protein (CBP are crucial regulators of energy homeostasis and liver fibrosis through both their acetyltransferase activities and transcriptional coactivators. Plenty of recent findings demonstrated the potential roles of p300/CBP in mammalian metabolic homeostasis in response to nutrients. This review is focused on the different targets and functions of p300/CBP in physiological and pathological processes, including lipogenesis, lipid export, gluconeogenesis, and liver fibrosis, also provided some nutrients as the regulator of p300/CBP for nutritional therapeutic approaches to treat liver diseases.

Protein Homeostasis Defects of Alanine-Glyoxylate Aminotransferase: New Therapeutic Strategies in Primary Hyperoxaluria Type I

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Angel L. Pey

2013-01-01

Full Text Available Alanine-glyoxylate aminotransferase catalyzes the transamination between L-alanine and glyoxylate to produce pyruvate and glycine using pyridoxal 5′-phosphate (PLP as cofactor. Human alanine-glyoxylate aminotransferase is a peroxisomal enzyme expressed in the hepatocytes, the main site of glyoxylate detoxification. Its deficit causes primary hyperoxaluria type I, a rare but severe inborn error of metabolism. Single amino acid changes are the main type of mutation causing this disease, and considerable effort has been dedicated to the understanding of the molecular consequences of such missense mutations. In this review, we summarize the role of protein homeostasis in the basic mechanisms of primary hyperoxaluria. Intrinsic physicochemical properties of polypeptide chains such as thermodynamic stability, folding, unfolding, and misfolding rates as well as the interaction of different folding states with protein homeostasis networks are essential to understand this disease. The view presented has important implications for the development of new therapeutic strategies based on targeting specific elements of alanine-glyoxylate aminotransferase homeostasis.

Glutathione in Cellular Redox Homeostasis: Association with the Excitatory Amino Acid Carrier 1 (EAAC1

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Koji Aoyama

2015-05-01

Full Text Available Reactive oxygen species (ROS are by-products of the cellular metabolism of oxygen consumption, produced mainly in the mitochondria. ROS are known to be highly reactive ions or free radicals containing oxygen that impair redox homeostasis and cellular functions, leading to cell death. Under physiological conditions, a variety of antioxidant systems scavenge ROS to maintain the intracellular redox homeostasis and normal cellular functions. This review focuses on the antioxidant system’s roles in maintaining redox homeostasis. Especially, glutathione (GSH is the most important thiol-containing molecule, as it functions as a redox buffer, antioxidant, and enzyme cofactor against oxidative stress. In the brain, dysfunction of GSH synthesis leading to GSH depletion exacerbates oxidative stress, which is linked to a pathogenesis of aging-related neurodegenerative diseases. Excitatory amino acid carrier 1 (EAAC1 plays a pivotal role in neuronal GSH synthesis. The regulatory mechanism of EAAC1 is also discussed.

Theory matters for financial advice!

OpenAIRE

Mayer, János; Hens, Thorsten

2013-01-01

We show that the optimal asset allocation for an investor depends crucially on the theory with which the investor is modeled. For the same market data and the same client data different theories lead to different portfolios. The market data we consider is standard asset allocation data. The client data is determined by a standard risk profiling question and the theories we apply are mean-variance analysis, expected utility analysis and cumulative prospect theory.

The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity.

Science.gov (United States)

Sag, Duygu; Cekic, Caglar; Wu, Runpei; Linden, Joel; Hedrick, Catherine C

2015-02-27

ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1(-/-) mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1(-/-) mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1(-/-) macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer.

Deficiency of α-1-antitrypsin influences systemic iron homeostasis

Directory of Open Access Journals (Sweden)

Ghio AJ

2013-01-01

Full Text Available Andrew J Ghio,1 Joleen M Soukup,1 Judy H Richards,1 Bernard M Fischer,2 Judith A Voynow,2 Donald E Schmechel31US Environmental Protection Agency, Chapel Hill, NC, USA; 2Division of Pediatric Pulmonary Medicine, Department of Pediatrics,3Joseph and Kathleen Bryan Alzheimer Disease Research Center, Department of Medicine (Neurology, Duke University Medical Center, Durham, NC, USAAbstract: There is evidence that proteases and antiproteases participate in the iron homeostasis of cells and living systems. We tested the postulate that α-1 antitrypsin (A1AT polymorphism and the consequent deficiency of this antiprotease in humans are associated with a systemic disruption in iron homeostasis. Archived plasma samples from Alpha-1 Foundation (30 MM, 30 MZ, and 30 ZZ individuals were analyzed for A1AT, ferritin, transferrin, and C-reactive protein (CRP. Plasma samples were also assayed for metals using inductively coupled plasma atomic emission spectroscopy (ICPAES. Plasma levels of A1AT in MZ and ZZ individuals were approximately 60% and 20% of those for MM individuals respectively. Plasma ferritin concentrations in those with the ZZ genotype were greater relative to those individuals with either MM or MZ genotype. Plasma transferrin for MM, MZ, and ZZ genotypes showed no significant differences. Linear regression analysis revealed a significant (negative relationship between plasma concentrations of A1AT and ferritin while that between A1AT and transferrin levels was not significant. Plasma CRP concentrations were not significantly different between MM, MZ, and ZZ individuals. ICPAES measurement of metals confirmed elevated plasma concentrations of nonheme iron among ZZ individuals. Nonheme iron concentrations correlated (negatively with levels of A1AT. A1AT deficiency is associated with evidence of a disruption in iron homeostasis with plasma ferritin and nonheme iron concentrations being elevated among those with the ZZ genotype.Keywords: α-1

Risk Assessment in Finland: Theory and Practice

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Hannu Anttonen

2010-09-01

Full Text Available The Finnish risk assessment practice is based on the Occupational Safety and Health Act aiming to improve working conditions in order maintain the employees' work ability, and to prevent occupational accidents and diseases. In practice there are hundreds of risk assessment methods in use. A simple method is used in SME's and more complex risk evaluation methods in larger work places. Does the risk management function in the work places in Finland? According to our experience something more is needed. That is, understanding of common and company related benefits of risk management. The wider conclusion is that commitment for risk assessment in Finland is high enough. However, in those enterprises where OSH management was at an acceptable level or above it, there were also more varied and more successfully accomplished actions to remove or reduce the risks than in enterprises, where OSH management was in lower level. In risk assessment it is important to process active technical prevention and exact communication, increase work place attraction and increase job satisfaction and motivation. Investments in occupational safety and health are also good business. Low absenteeism due to illness or accidents increases directly the production results by improved quality and quantity of the product. In general Finnish studies have consistently shown that the return of an invested euro is three to seven-old. In national level, according to our calculations the savings could be even 20% of our gross national product.

Innate lymphoid cells in tissue homeostasis and diseases.

Science.gov (United States)

Ignacio, Aline; Breda, Cristiane Naffah Souza; Camara, Niels Olsen Saraiva

2017-08-18

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.

Regulatory T Cells in Post-stroke Immune Homeostasis.

Science.gov (United States)

Liesz, Arthur; Kleinschnitz, Christoph

2016-08-01

The secondary neuroinflammatory response has come into focus of experimental stroke research. Immunological mechanisms after acute stroke are being investigated in the hope to identify novel and druggable pathways that contribute to secondary infarct growth after stroke. Among a variety of neuroimmunological events after acute brain ischemia, including microglial activation, brain leukocyte invasion, and secretion of pro-inflammatory factors, lymphocytes have been identified as the key leukocyte subpopulation driving the neuroinflammatory response and contributing to stroke outcome. Several studies have shown that pro-inflammatory lymphocyte subpopulations worsen stroke outcome and that inhibiting their invasion to the injured brain is neuroprotective. In contrast to the effector functions of pro-inflammatory lymphocytes, regulatory T cells (Treg) are critically involved in maintaining immune homeostasis and have been characterized as disease-limiting protective cells in several inflammatory conditions, particularly in primary inflammatory diseases of the central nervous system (CNS). However, due to the complex function of regulatory cells in immune homeostasis and disease, divergent findings have been described for the role of Treg in stroke models. Emerging evidence suggests that this discrepancy arises from potentially differing functions of Treg depending on the predominant site of action within the neurovascular unit and the surrounding inflammatory milieu. This article will provide a comprehensive review of current findings on Treg in brain ischemia models and discuss potential reasons for the observed discrepancies.

MicroRNAs and the regulation of intestinal homeostasis.

Science.gov (United States)

Runtsch, Marah C; Round, June L; O'Connell, Ryan M

2014-01-01

The mammalian intestinal tract is a unique site in which a large portion of our immune system and the 10(14) commensal organisms that make up the microbiota reside in intimate contact with each other. Despite the potential for inflammatory immune responses, this complex interface contains host immune cells and epithelial cells interacting with the microbiota in a manner that promotes symbiosis. Due to the complexity of the cell types and microorganisms involved, this process requires elaborate regulatory mechanisms to ensure mutualism and prevent disease. While many studies have described critical roles for protein regulators of intestinal homeostasis, recent reports indicate that non-coding RNAs are also major contributors to optimal host-commensal interactions. In particular, there is emerging evidence that microRNAs (miRNAs) have evolved to fine tune host gene expression networks and signaling pathways that modulate cellular physiology in the intestinal tract. Here, we review our present knowledge of the influence miRNAs have on both immune and epithelial cell biology in the mammalian intestines and the impact this has on the microbiota. We also discuss a need for further studies to decipher the functions of specific miRNAs within the gut to better understand cellular mechanisms that promote intestinal homeostasis and to identify potential molecular targets underlying diseases such as inflammatory bowel disease and colorectal cancer.

Creatine maintains intestinal homeostasis and protects against colitis.

Science.gov (United States)

Turer, Emre; McAlpine, William; Wang, Kuan-Wen; Lu, Tianshi; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Wang, Tao; Zhan, Xiaowei; Bu, Chun-Hui; Murray, Anne R; Beutler, Bruce

2017-02-14

Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N -ethyl- N -nitrosourea-mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). Among 27 colitis susceptibility phenotypes identified and mapped, one was strongly correlated with a missense mutation in Gatm in a recessive model of inheritance, and causation was confirmed by CRISPR/Cas9 gene targeting. Supplementation of homozygous Gatm mutants with exogenous creatine ameliorated the colitis phenotype. CRISPR/Cas9-targeted ( Gatm c/c ) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatm c/c mice displayed increased cell death and decreased proliferation during DSS treatment. In addition, Gatm c/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin (phospho-mTOR). These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury.

Hypothalamic carnitine metabolism integrates nutrient and hormonal feedback to regulate energy homeostasis.

Science.gov (United States)

Stark, Romana; Reichenbach, Alex; Andrews, Zane B

2015-12-15

The maintenance of energy homeostasis requires the hypothalamic integration of nutrient feedback cues, such as glucose, fatty acids, amino acids, and metabolic hormones such as insulin, leptin and ghrelin. Although hypothalamic neurons are critical to maintain energy homeostasis research efforts have focused on feedback mechanisms in isolation, such as glucose alone, fatty acids alone or single hormones. However this seems rather too simplistic considering the range of nutrient and endocrine changes associated with different metabolic states, such as starvation (negative energy balance) or diet-induced obesity (positive energy balance). In order to understand how neurons integrate multiple nutrient or hormonal signals, we need to identify and examine potential intracellular convergence points or common molecular targets that have the ability to sense glucose, fatty acids, amino acids and hormones. In this review, we focus on the role of carnitine metabolism in neurons regulating energy homeostasis. Hypothalamic carnitine metabolism represents a novel means for neurons to facilitate and control both nutrient and hormonal feedback. In terms of nutrient regulation, carnitine metabolism regulates hypothalamic fatty acid sensing through the actions of CPT1 and has an underappreciated role in glucose sensing since carnitine metabolism also buffers mitochondrial matrix levels of acetyl-CoA, an allosteric inhibitor of pyruvate dehydrogenase and hence glucose metabolism. Studies also show that hypothalamic CPT1 activity also controls hormonal feedback. We hypothesis that hypothalamic carnitine metabolism represents a key molecular target that can concurrently integrate nutrient and hormonal information, which is critical to maintain energy homeostasis. We also suggest this is relevant to broader neuroendocrine research as it predicts that hormonal signaling in the brain varies depending on current nutrient status. Indeed, the metabolic action of ghrelin, leptin or insulin

O-GlcNAcase Expression is Sensitive to Changes in O-GlcNAc Homeostasis.

Science.gov (United States)

Zhang, Zhen; Tan, Ee Phie; VandenHull, Nicole J; Peterson, Kenneth R; Slawson, Chad

2014-01-01

O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. Cellular O-GlcNAc levels are regulated by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove the modification, respectively. The levels of O-GlcNAc can rapidly change in response to fluctuations in the extracellular environment; however, O-GlcNAcylation returns to a baseline level quickly after stimulus removal. This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. Disruptions in O-GlcNAc homeostasis are proposed to lead to the development of diseases, such as cancer, diabetes, and Alzheimer's disease. O-GlcNAc homeostasis is correlated with the expression of OGT and OGA. We reason that alterations in O-GlcNAc levels affect OGA and OGT transcription. We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. OGT transcript levels slightly declined with TMG treatment, but OGA transcript levels were significantly increased. Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. Together, these data suggest that OGA transcription was sensitive to changes in O-GlcNAc homeostasis and was potentially regulated by O-GlcNAc.

NPY modulates PYY function in the regulation of energy balance and glucose homeostasis.

Science.gov (United States)

Zhang, L; Nguyen, A D; Lee, I-C J; Yulyaningsih, E; Riepler, S J; Stehrer, B; Enriquez, R F; Lin, S; Shi, Y-C; Baldock, P A; Sainsbury, A; Herzog, H

2012-08-01

Both the neuronal-derived neuropeptide Y (NPY) and the gut hormone peptide YY (PYY) have been implicated in the regulation of energy balance and glucose homeostasis. However, despite similar affinities for the same Y receptors, the co-ordinated actions of these two peptides in energy and glucose homeostasis remain largely unknown. To investigate the mechanisms and possible interactions between PYY with NPY in the regulation of these processes, we utilized NPY/PYY single and double mutant mouse models and examined parameters of energy balance and glucose homeostasis. PYY(-/-) mice exhibited increased fasting-induced food intake, enhanced fasting and oral glucose-induced serum insulin levels, and an impaired insulin tolerance, - changes not observed in NPY(-/-) mice. Interestingly, whereas PYY deficiency-induced impairment in insulin tolerance remained in NPY(-/-) PYY(-/-) mice, effects of PYY deficiency on fasting-induced food intake and serum insulin concentrations at baseline and after the oral glucose bolus were absent in NPY(-/-) PYY(-/-) mice, suggesting that NPY signalling may be required for PYY's action on insulin secretion and fasting-induced hyperphagia. Moreover, NPY(-/-) PYY(-/-) , but not NPY(-/-) or PYY(-/-) mice had significantly decreased daily food intake, indicating interactive control by NPY and PYY on spontaneous food intake. Furthermore, both NPY(-/-) and PYY(-/-) mice showed significantly reduced respiratory exchange ratio during the light phase, with no additive effects observed in NPY(-/-) PYY(-/-) mice, indicating that NPY and PYY may regulate oxidative fuel selection via partly shared mechanisms. Overall, physical activity and energy expenditure, however, are not significantly altered by NPY and PYY single or double deficiencies. These findings show significant and diverse interactions between NPY and PYY signalling in the regulation of different aspects of energy balance and glucose homeostasis. © 2012 Blackwell Publishing Ltd.

Osteoclasts and CD8 T cells form a negative feedback loop that contributes to homeostasis of both the skeletal and immune systems.

Science.gov (United States)

Buchwald, Zachary S; Aurora, Rajeev

2013-01-01

There are a number of dynamic regulatory loops that maintain homeostasis of the immune and skeletal systems. In this review, we highlight a number of these regulatory interactions that contribute to maintaining homeostasis. In addition, we review data on a negative regulatory feedback loop between osteoclasts and CD8 T cells that contributes to homeostasis of both the skeletal and immune systems.

Thirty Years of Prospect Theory in Economics: A Review and Assessment

OpenAIRE

Nicholas C. Barberis

2013-01-01

In 1979, Daniel Kahneman and Amos Tversky, published a paper in Econometrica titled "Prospect Theory: An Analysis of Decision under Risk." The paper presented a new model of risk attitudes called "prospect theory," which elegantly captured the experimental evidence on risk taking, including the documented violations of expected utility. More than 30 years later, prospect theory is still widely viewed as the best available description of how people evaluate risk in experimental settings. Howev...

Childhood cardiorespiratory fitness, muscular fitness and adult measures of glucose homeostasis.

Science.gov (United States)

Fraser, Brooklyn J; Blizzard, Leigh; Schmidt, Michael D; Juonala, Markus; Dwyer, Terence; Venn, Alison J; Magnussen, Costan G

2018-02-14

To assess whether childhood cardiorespiratory fitness (CRF) and muscular fitness phenotypes (strength, power, endurance) predict adult glucose homeostasis measures. Prospective longitudinal study. Study examining participants who had physical fitness measured in childhood (aged 7-15 years) and who attended follow-up clinics approximately 20 years later and provided a fasting blood sample which was tested for glucose and insulin. Physical fitness measurements included muscular strength (right and left grip, shoulder flexion, shoulder and leg extension), power (standing long jump distance) and endurance (number of push-ups in 30s), and CRF (1.6km run duration). In adulthood, fasting glucose and insulin levels were used to derive glucose homeostasis measures of insulin resistance (HOMA2-IR) and beta cell function (HOMA2-β). A standard deviation increase in childhood CRF or muscular strength (males) was associated with fasting glucose (CRF: β=-0.06mmol/L), fasting insulin (CRF: β=-0.73mU/L; strength: β=-0.40mU/L), HOMA2-IR (CRF: β=-0.06; strength: β=-0.05) and HOMA2-β (CRF: β=-3.06%; strength: β=-2.62%) in adulthood, independent of the alternative fitness phenotype (all p0.06). CRF and muscular fitness in childhood were inversely associated with measures of fasting insulin, insulin resistance and beta cell function in adulthood. Childhood CRF and muscular fitness could both be potential independent targets for strategies to help reduce the development of adverse glucose homeostasis. Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

The influence of jumping risk and volatility risk on TAIEX option return

Science.gov (United States)

Lee, Wei-Long; Hsieh, Ching-Tang; Huang, Jui-Chan; Wu, Tzu-Jung

2017-06-01

Due to the low profits in recent years environmental, as well as the development of financial engineering that promote the derivatives trading Volume increased. Moreover, the fastest-growing of selected right and the lack of research about option risk. This study aim to explore the relationship between the risk and reward of selected right in Taiwan index. This study focus on the pricing the jump risk of selected right in Taiwan index. Using cross-sectional data as a 12-month study period, using the iteration method to research the effects of abnormal returns, the result shows that different risk factors of fluctuations affected the abnormal returns obviously will cause risk premium as well as the jump risk which consistent with the theory of behavioral finance. However, according to traditional finance theory, contrary to the results of this study consider that higher risks should generate higher-paying as well. According this study, the investors in behavioral finance in modern financial theory is not rational, and the trading behavior is non-random, moreover, the financial market is non-efficiency. Instead, the high risk low reward.

Initiation of innate immune responses by surveillance of homeostasis perturbations.

Science.gov (United States)

Colaço, Henrique G; Moita, Luis F

2016-07-01

Pathogen recognition, signaling transduction pathways, and effector mechanisms are necessary steps of innate immune responses that play key roles in the early phase of defense and in the stimulation of the later specific response of adaptive immunity. Here, we argue that in addition to the direct recognition of conserved common structural and functional molecular signatures of microorganisms using pattern recognition receptors, hosts can mount an immune response following the sensing of disruption in homeostasis as proximal reporters for infections. Surveillance of disruption of core cellular activities leading to defense responses is a flexible strategy that requires few additional components and that can effectively detect relevant threats. It is likely to be evolutionarily very conserved and ancient because it is operational in organisms that lack pattern recognition triggered immunity. A homeostasis disruption model of immune response initiation and modulation has broad implications for pathophysiology and treatment of disease and might constitute an often overlooked but central component of a comprehensive conceptual framework for innate immunity. © 2016 Federation of European Biochemical Societies.

NOD-Like Receptors in Intestinal Homeostasis and Epithelial Tissue Repair

Science.gov (United States)

Parlato, Marianna; Yeretssian, Garabet

2014-01-01

The intestinal epithelium constitutes a dynamic physical barrier segregating the luminal content from the underlying mucosal tissue. Following injury, the epithelial integrity is restored by rapid migration of intestinal epithelial cells (IECs) across the denuded area in a process known as wound healing. Hence, through a sequence of events involving restitution, proliferation and differentiation of IECs the gap is resealed and homeostasis reestablished. Relapsing damage followed by healing of the inflamed mucosa is a hallmark of several intestinal disorders including inflammatory bowel diseases (IBD). While several regulatory peptides, growth factors and cytokines stimulate restitution of the epithelial layer after injury, recent evidence in the field underscores the contribution of innate immunity in controlling this process. In particular, nucleotide-binding and oligomerization domain-like receptors (NLRs) play critical roles in sensing the commensal microbiota, maintaining homeostasis, and regulating intestinal inflammation. Here, we review the process of intestinal epithelial tissue repair and we specifically focus on the impact of NLR-mediated signaling mechanisms involved in governing epithelial wound healing during disease. PMID:24886810

Physiological Roles for mafr-1 in Reproduction and Lipid Homeostasis

Directory of Open Access Journals (Sweden)

Akshat Khanna

2014-12-01

Full Text Available Maf1 is a conserved repressor of RNA polymerase (Pol III transcription; however, its physiological role in the context of a multicellular organism is not well understood. Here, we show that C. elegans MAFR-1 is functionally orthologous to human Maf1, represses the expression of both RNA Pol III and Pol II transcripts, and mediates organismal fecundity and lipid homeostasis. MAFR-1 impacts lipid transport by modulating intestinal expression of the vitellogenin family of proteins, resulting in cell-nonautonomous defects in the developing reproductive system. MAFR-1 levels inversely correlate with stored intestinal lipids, in part by influencing the expression of the lipogenesis enzymes fasn-1/FASN and pod-2/ACC1. Animals fed a high carbohydrate diet exhibit reduced mafr-1 expression and mutations in the insulin signaling pathway genes daf-18/PTEN and daf-16/FoxO abrogate the lipid storage defects associated with deregulated mafr-1 expression. Our results reveal physiological roles for mafr-1 in regulating organismal lipid homeostasis, which ensure reproductive success.

Iron homeostasis during pregnancy.

Science.gov (United States)

Fisher, Allison L; Nemeth, Elizabeta

2017-12-01

During pregnancy, iron needs to increase substantially to support fetoplacental development and maternal adaptation to pregnancy. To meet these iron requirements, both dietary iron absorption and the mobilization of iron from stores increase, a mechanism that is in large part dependent on the iron-regulatory hormone hepcidin. In healthy human pregnancies, maternal hepcidin concentrations are suppressed in the second and third trimesters, thereby facilitating an increased supply of iron into the circulation. The mechanism of maternal hepcidin suppression in pregnancy is unknown, but hepcidin regulation by the known stimuli (i.e., iron, erythropoietic activity, and inflammation) appears to be preserved during pregnancy. Inappropriately increased maternal hepcidin during pregnancy can compromise the iron availability for placental transfer and impair the efficacy of iron supplementation. The role of fetal hepcidin in the regulation of placental iron transfer still remains to be characterized. This review summarizes the current understanding and addresses the gaps in knowledge about gestational changes in hematologic and iron variables and regulatory aspects of maternal, fetal, and placental iron homeostasis. © 2017 American Society for Nutrition.

On risks and acceptability

International Nuclear Information System (INIS)

Watson, S.R.

1981-01-01

A very attractive notion is that it should be possible not only to determine how much risk is associated with any particular activity, but also to determine if that risk is acceptable. Stated boldly this seems an entirely unobjectionable and indeed a very acceptable notion. There is, however, underlying this idea, a mistaken view of risk which we might refer to as the ''phlogiston'' theory of risk. In this paper, presented at the SRP meeting on Ethical and Legal Aspects of Radiological Protection, the phlogiston theory of risk is described; secondly, it will be argued that it is too simple a theory to be realistic or useful; and thirdly, the management of risk will be placed in a wider decision framework. Acceptability, it will be argued is highly dependent on context, and it is not possible, therefore, to lay down generally applicable notions of acceptability. (author)

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

OpenAIRE

Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pha...

Human homeostasis in the space environment: A systems synthesis approach

Science.gov (United States)

Economos, A. C.

1982-01-01

The features of homeostatic changes which occur during adaptation to the weightless state are examined and the possible mechanisms underlying the responses are explored. Cardiac output, negative fluid balance, body weight, bone calcium, and muscle atrophy are discussed. Some testable hypotheses concerning possible effects on homeostasis that long-term exposure to weightlessness might cause are proposed.

Prospect Theory for Online Financial Trading

Science.gov (United States)

Liu, Yang-Yu; Nacher, Jose C.; Ochiai, Tomoshiro; Martino, Mauro; Altshuler, Yaniv

2014-03-01

Prospect theory is widely viewed as the best available descriptive model of how people evaluate risk in experimental settings. According to prospect theory, people make decisions based on the potential value of losses and gains rather than the final outcome. People are risk-averse with respect to gains and risk-seeking with respect to losses, a phenomenon called ``loss aversion''. Despite of the fact that prospect theory has been well studied in behavioral economics at the theoretical level, there exist very few empirical research and most of them has been undertaken with micro-panel data. Here we analyze the trading activities of over 1.5 million members of an online financial trading community over 28 months, aiming to explore the large-scale empirical aspect of prospect theory. By analyzing and comparing the behaviour of ``winners'' and ``losers'', i.e., traders with positive or negative final net profit, we find clear evidence of the loss aversion phenomenon, an essence in prospect theory. This work demonstrates an unprecedented large-scale empirical evidence of prospect theory. It has immediate implication in financial trading, e.g., developing new trading strategies by minimizing the effect of loss aversion. It also provides opportunity to augment online social trading, where users are allowed to watch and follow the trading activity of others, by predicting potential winners based on their historical trading behaviour.

Health Risk Perceptions and Exercise in Older Adulthood: An Application of Protection Motivation Theory.

Science.gov (United States)

Ruthig, Joelle C

2016-09-01

Protection Motivation Theory (PMT) was applied to explore the relationship between perceived risk of acute health crises and intent to exercise. Interviews of 351 community-living older adults assessed prior physical activity (PPA), all PMT components, and exercise intent. A multi-group structural equation model revealed gender differences in PMT predictors of exercise intent. PPA, age, self-efficacy, and response efficacy directly predicted men's intent. Women's PPA and age predicted PMT components of self-efficacy and response costs, which predicted intent. Findings have implications for devising interventions to enhance physical activity in later life by targeting different PMT components for older men and women. © The Author(s) 2014.

Exposure to lithium through drinking water and calcium homeostasis during pregnancy: A longitudinal study

International Nuclear Information System (INIS)

Harari, Florencia; Åkesson, Agneta; Casimiro, Esperanza; Lu, Ying; Vahter, Marie

2016-01-01

There is increasing evidence of adverse health effects due to elevated lithium exposure through drinking water but the impact on calcium homeostasis is unknown. This study aimed at elucidating if lithium exposure through drinking water during pregnancy may impair the maternal calcium homeostasis. In a population-based mother-child cohort in the Argentinean Andes (n=178), with elevated lithium concentrations in the drinking water (5–1660 μg/L), blood lithium concentrations (correlating significantly with lithium in water, urine and plasma) were measured repeatedly during pregnancy by inductively coupled plasma mass spectrometry and used as exposure biomarker. Markers of calcium homeostasis included: plasma 25-hydroxyvitamin D 3 , serum parathyroid hormone (PTH), and calcium, phosphorus and magnesium concentrations in serum and urine. The median maternal blood lithium concentration was 25 μg/L (range 1.9–145). In multivariable-adjusted mixed-effects linear regression models, blood lithium was inversely associated with 25-hydroxyvitamin D 3 (−6.1 nmol/L [95%CI −9.5; −2.6] for a 25 μg/L increment in blood lithium). The estimate increased markedly with increasing percentiles of 25-hydroxyvitamin D 3 . In multivariable-adjusted mixed-effects logistic regression models, the odds ratio of having 25-hydroxyvitamin D3<30 nmol/L (19% of the women) was 4.6 (95%CI 1.1; 19.3) for a 25 μg/L increment in blood lithium. Blood lithium was also positively associated with serum magnesium, but not with serum calcium and PTH, and inversely associated with urinary calcium and magnesium. In conclusion, our study suggests that lithium exposure through drinking water during pregnancy may impair the calcium homeostasis, particularly vitamin D. The results reinforce the need for better control of lithium in drinking water, including bottled water. - Highlights: • Elevated drinking water lithium (Li) concentrations are increasingly reported. • We studied a Li

Exposure to lithium through drinking water and calcium homeostasis during pregnancy: A longitudinal study

Energy Technology Data Exchange (ETDEWEB)

Harari, Florencia [Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Åkesson, Agneta [Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Casimiro, Esperanza [Atención Primaria de la Salud, Área Operativa XXIX, Hospital Dr. Nicolás Cayetano Pagano, San Antonio de los Cobres, Salta (Argentina); Lu, Ying [Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Vahter, Marie, E-mail: Marie.Vahter@ki.se [Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden)

2016-05-15

There is increasing evidence of adverse health effects due to elevated lithium exposure through drinking water but the impact on calcium homeostasis is unknown. This study aimed at elucidating if lithium exposure through drinking water during pregnancy may impair the maternal calcium homeostasis. In a population-based mother-child cohort in the Argentinean Andes (n=178), with elevated lithium concentrations in the drinking water (5–1660 μg/L), blood lithium concentrations (correlating significantly with lithium in water, urine and plasma) were measured repeatedly during pregnancy by inductively coupled plasma mass spectrometry and used as exposure biomarker. Markers of calcium homeostasis included: plasma 25-hydroxyvitamin D{sub 3}, serum parathyroid hormone (PTH), and calcium, phosphorus and magnesium concentrations in serum and urine. The median maternal blood lithium concentration was 25 μg/L (range 1.9–145). In multivariable-adjusted mixed-effects linear regression models, blood lithium was inversely associated with 25-hydroxyvitamin D{sub 3} (−6.1 nmol/L [95%CI −9.5; −2.6] for a 25 μg/L increment in blood lithium). The estimate increased markedly with increasing percentiles of 25-hydroxyvitamin D{sub 3}. In multivariable-adjusted mixed-effects logistic regression models, the odds ratio of having 25-hydroxyvitamin D3<30 nmol/L (19% of the women) was 4.6 (95%CI 1.1; 19.3) for a 25 μg/L increment in blood lithium. Blood lithium was also positively associated with serum magnesium, but not with serum calcium and PTH, and inversely associated with urinary calcium and magnesium. In conclusion, our study suggests that lithium exposure through drinking water during pregnancy may impair the calcium homeostasis, particularly vitamin D. The results reinforce the need for better control of lithium in drinking water, including bottled water. - Highlights: • Elevated drinking water lithium (Li) concentrations are increasingly reported. • We studied a Li

The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis

Directory of Open Access Journals (Sweden)

Daisuke Hirayama

2017-12-01

Full Text Available Macrophages are effector cells of the innate immune system that phagocytose bacteria and secrete both pro-inflammatory and antimicrobial mediators. In addition, macrophages play an important role in eliminating diseased and damaged cells through their programmed cell death. Generally, macrophages ingest and degrade dead cells, debris, tumor cells, and foreign materials. They promote homeostasis by responding to internal and external changes within the body, not only as phagocytes, but also through trophic, regulatory, and repair functions. Recent studies demonstrated that macrophages differentiate from hematopoietic stem cell-derived monocytes and embryonic yolk sac macrophages. The latter mainly give rise to tissue macrophages. Macrophages exist in all vertebrate tissues and have dual functions in host protection and tissue injury, which are maintained at a fine balance. Tissue macrophages have heterogeneous phenotypes in different tissue environments. In this review, we focused on the phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis for a better understanding of the role of tissue macrophages in several pathological conditions.

Innate immune signalling at the intestinal epithelium in homeostasis and disease

Science.gov (United States)

Pott, Johanna; Hornef, Mathias

2012-01-01

The intestinal epithelium—which constitutes the interface between the enteric microbiota and host tissues—actively contributes to the maintenance of mucosal homeostasis and defends against pathogenic microbes. The recognition of conserved microbial products by cytosolic or transmembrane pattern recognition receptors in epithelial cells initiates signal transduction and influences effector cell function. However, the signalling pathways, effector molecules and regulatory mechanisms involved are not yet fully understood, and the functional outcome is poorly defined. This review analyses the complex and dynamic role of intestinal epithelial innate immune recognition and signalling, on the basis of results in intestinal epithelial cell-specific transgene or gene-deficient animals. This approach identifies specific epithelial cell functions within the diverse cellular composition of the mucosal tissue, in the presence of the complex and dynamic gut microbiota. These insights have thus provided a more comprehensive understanding of the role of the intestinal epithelium in innate immunity during homeostasis and disease. PMID:22801555

Deletion of Lkb1 in Pro-Opiomelanocortin Neurons Impairs Peripheral Glucose Homeostasis in Mice

Science.gov (United States)

Claret, Marc; Smith, Mark A.; Knauf, Claude; Al-Qassab, Hind; Woods, Angela; Heslegrave, Amanda; Piipari, Kaisa; Emmanuel, Julian J.; Colom, André; Valet, Philippe; Cani, Patrice D.; Begum, Ghazala; White, Anne; Mucket, Phillip; Peters, Marco; Mizuno, Keiko; Batterham, Rachel L.; Giese, K. Peter; Ashworth, Alan; Burcelin, Remy; Ashford, Michael L.; Carling, David; Withers, Dominic J.

2011-01-01

OBJECTIVE AMP-activated protein kinase (AMPK) signaling acts as a sensor of nutrients and hormones in the hypothalamus, thereby regulating whole-body energy homeostasis. Deletion of Ampkα2 in pro-opiomelanocortin (POMC) neurons causes obesity and defective neuronal glucose sensing. LKB1, the Peutz-Jeghers syndrome gene product, and Ca2+-calmodulin–dependent protein kinase kinase β (CaMKKβ) are key upstream activators of AMPK. This study aimed to determine their role in POMC neurons upon energy and glucose homeostasis regulation. RESEARCH DESIGN AND METHODS Mice lacking either Camkkβ or Lkb1 in POMC neurons were generated, and physiological, electrophysiological, and molecular biology studies were performed. RESULTS Deletion of Camkkβ in POMC neurons does not alter energy homeostasis or glucose metabolism. In contrast, female mice lacking Lkb1 in POMC neurons (PomcLkb1KO) display glucose intolerance, insulin resistance, impaired suppression of hepatic glucose production, and altered expression of hepatic metabolic genes. The underlying cellular defect in PomcLkb1KO mice involves a reduction in melanocortin tone caused by decreased α-melanocyte–stimulating hormone secretion. However, Lkb1-deficient POMC neurons showed normal glucose sensing, and body weight was unchanged in PomcLkb1KO mice. CONCLUSIONS Our findings demonstrate that LKB1 in hypothalamic POMC neurons plays a key role in the central regulation of peripheral glucose metabolism but not body-weight control. This phenotype contrasts with that seen in mice lacking AMPK in POMC neurons with defects in body-weight regulation but not glucose homeostasis, which suggests that LKB1 plays additional functions distinct from activating AMPK in POMC neurons. PMID:21266325

Role of orexins in the central and peripheral regulation of glucose homeostasis: Evidences & mechanisms.

Science.gov (United States)

Rani, Monika; Kumar, Raghuvansh; Krishan, Pawan

2018-04-01

Orexins (A & B), neuropeptides of hypothalamic origin, act through G-protein coupled receptors, orexin 1 receptor (OX 1 R) and orexin 2 receptor (OX 2 R). The wide projection of orexin neurons in the hypothalamic region allows them to interact with the other neurons and regulate food intake, emotional status, sleep wake cycle and energy metabolism. The autonomic nervous system plays an important regulatory role in the energy metabolism as well as glucose homeostasis. Orexin neurons are also under the control of GABAergic neurons. Emerging preclinical as well as clinical research has reported the role of orexins in the glucose homeostasis since orexins are involved in hypothalamic metabolism circuitry and also rely on sensing peripheral metabolic signals such as gut, adipose derived and pancreatic peptides. Apart from the hypothalamic origin, integration and control in various physiological functions, peripheral origin in wide organs, raises the possibility of use of orexins as a therapeutic biomarker in the management of metabolic disorders. The present review focuses the central as well as peripheral roles of orexins in the glucose homeostasis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evidence Theory Based Uncertainty Quantification in Radiological Risk due to Accidental Release of Radioactivity from a Nuclear Power Plant

International Nuclear Information System (INIS)

Ingale, S. V.; Datta, D.

2010-01-01

Consequence of the accidental release of radioactivity from a nuclear power plant is assessed in terms of exposure or dose to the members of the public. Assessment of risk is routed through this dose computation. Dose computation basically depends on the basic dose assessment model and exposure pathways. One of the exposure pathways is the ingestion of contaminated food. The aim of the present paper is to compute the uncertainty associated with the risk to the members of the public due to the ingestion of contaminated food. The governing parameters of the ingestion dose assessment model being imprecise, we have approached evidence theory to compute the bound of the risk. The uncertainty is addressed by the belief and plausibility fuzzy measures.

TAM Receptor Signaling in Immune Homeostasis

Science.gov (United States)

Rothlin, Carla V.; Carrera-Silva, Eugenio A.; Bosurgi, Lidia; Ghosh, Sourav

2015-01-01

The TAM receptor tyrosine kinases (RTKs)—TYRO3, AXL, and MERTK—together with their cognate agonists GAS6 and PROS1 play an essential role in the resolution of inflammation. Deficiencies in TAM signaling have been associated with chronic inflammatory and autoimmune diseases. Three processes regulated by TAM signaling may contribute, either independently or collectively, to immune homeostasis: the negative regulation of the innate immune response, the phagocytosis of apoptotic cells, and the restoration of vascular integrity. Recent studies have also revealed the function of TAMs in infectious diseases and cancer. Here, we review the important milestones in the discovery of these RTKs and their ligands and the studies that underscore the functional importance of this signaling pathway in physiological immune settings and disease. PMID:25594431

Negative regulation of Toll-like receptor signaling plays an essential role in homeostasis of the intestine.

Science.gov (United States)

Biswas, Amlan; Wilmanski, Jeanette; Forsman, Huamei; Hrncir, Tomas; Hao, Liming; Tlaskalova-Hogenova, Helena; Kobayashi, Koichi S

2011-01-01

A healthy intestinal tract is characterized by controlled homeostasis due to the balanced interaction between commensal bacteria and the host mucosal immune system. Human and animal model studies have supported the hypothesis that breakdown of this homeostasis may underlie the pathogenesis of inflammatory bowel diseases. However, it is not well understood how intestinal microflora stimulate the intestinal mucosal immune system and how such activation is regulated. Using a spontaneous, commensal bacteria-dependent colitis model in IL-10-deficient mice, we investigated the role of TLR and their negative regulation in intestinal homeostasis. In addition to IL-10(-/-) MyD88(-/-) mice, IL-10(-/-) TLR4(-/-) mice exhibited reduced colitis compared to IL-10(-/-) mice, indicating that TLR4 signaling plays an important role in inducing colitis. Interestingly, the expression of IRAK-M, a negative regulator of TLR signaling, is dependent on intestinal commensal flora, as IRAK-M expression was reduced in mice re-derived into a germ-free environment, and introduction of commensal bacteria into germ-free mice induced IRAK-M expression. IL-10(-/-) IRAK-M(-/-) mice exhibited exacerbated colitis with increased inflammatory cytokine gene expression. Therefore, this study indicates that intestinal microflora stimulate the colitogenic immune system through TLR and negative regulation of TLR signaling is essential in maintaining intestinal homeostasis. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Negative regulation of Toll-like receptor signaling plays an essential role in the homeostasis of the intestine

OpenAIRE

Biswas, Amlan; Wilmanski, Jeanette; Forsman, Huamei; Hrncir, Tomas; Hao, Liming; Tlaskalova-Hogenova, Helena; Kobayashi, Koichi S.

2010-01-01

A healthy intestinal tract is characterized by controlled homeostasis due to the balanced interaction between commensal bacteria and the host mucosal immune system. Human and animal model studies have supported the hypothesis that breakdown of this homeostasis may underlie the pathogenesis of inflammatory bowel diseases (IBDs). However it is not well understood how intestinal microflora stimulate the intestinal mucosal immune system and how such activation is regulated. Using a spontaneous, c...

Homeostasis-altering molecular processes as mechanisms of inflammasome activation.

Science.gov (United States)

Liston, Adrian; Masters, Seth L

2017-03-01

The innate immune system uses a distinct set of germline-encoded pattern recognition receptors (PRRs) to initiate downstream inflammatory cascades. This recognition system is in stark contrast to the adaptive immune system, which relies on highly variable, randomly generated antigen receptors. A key limitation of the innate immune system's reliance on fixed PRRs is its inflexibility in responding to rapidly evolving pathogens. Recent advances in our understanding of inflammasome activation suggest that the innate immune system also has sophisticated mechanisms for responding to pathogens for which there is no fixed PRR. This includes the recognition of debris from dying cells, known as danger-associated molecular patterns (DAMPs), which can directly activate PRRs in a similar manner to pathogen-associated molecular patterns (PAMPs). Distinct from this, emerging data for the inflammasome components NLRP3 (NOD-, LRR- and pyrin domain-containing 3) and pyrin suggest that they do not directly detect molecular patterns, but instead act as signal integrators that are capable of detecting perturbations in cytoplasmic homeostasis, for example, as initiated by infection. Monitoring these perturbations, which we term 'homeostasis-altering molecular processes' (HAMPs), provides potent flexibility in the capacity of the innate immune system to detect evolutionarily novel infections; however, HAMP sensing may also underlie the sterile inflammation that drives chronic inflammatory diseases.

Measuring Value-at-Risk and Expected Shortfall of crude oil portfolio using extreme value theory and vine copula

Science.gov (United States)

Yu, Wenhua; Yang, Kun; Wei, Yu; Lei, Likun

2018-01-01

Volatilities of crude oil price have important impacts on the steady and sustainable development of world real economy. Thus it is of great academic and practical significance to model and measure the volatility and risk of crude oil markets accurately. This paper aims to measure the Value-at-Risk (VaR) and Expected Shortfall (ES) of a portfolio consists of four crude oil assets by using GARCH-type models, extreme value theory (EVT) and vine copulas. The backtesting results show that the combination of GARCH-type-EVT models and vine copula methods can produce accurate risk measures of the oil portfolio. Mixed R-vine copula is more flexible and superior to other vine copulas. Different GARCH-type models, which can depict the long-memory and/or leverage effect of oil price volatilities, however offer similar marginal distributions of the oil returns.

Mechanisms of Cell Polarity-Controlled Epithelial Homeostasis and Immunity in the Intestine

NARCIS (Netherlands)

Klunder, Leon J.; Faber, Klaas Nico; Dijkstra, Gerard; van IJzendoorn, Sven C. D.

Intestinal epithelial cell polarity is instrumental to maintain epithelial homeostasis and balance communications between the gut lumen and bodily tissue, thereby controlling the defense against gastrointestinal pathogens and maintenance of immune tolerance to commensal bacteria. In this review, we

Possibility Theory and the Risk

CERN Document Server

Georgescu, Irina

2012-01-01

The book deals with some of the fundamental issues of risk assessment in grid computing environments. The book describes the development of a hybrid probabilistic and possibilistic model for assessing the success of a computing task in a grid environment

Phloretin Prevents High-Fat Diet-Induced Obesity and Improves Metabolic Homeostasis.

Science.gov (United States)

Alsanea, Sary; Gao, Mingming; Liu, Dexi

2017-05-01

Reactive oxygen species generated as a by-product in metabolism play a central role in the development of obesity and obesity-related metabolic complications. The objective of the current study is to explore the possibility to block obesity and improve metabolic homeostasis via phloretin, a natural antioxidant product from apple tree leaves and Manchurian apricot. Both preventive and therapeutic activities of phloretin were assessed using a high-fat diet-induced obesity mouse model. Phloretin was injected intraperitoneally twice weekly into regular and obese mice fed a high-fat diet. The effects of phloretin treatment on body weight and composition, fat content in the liver, glucose and lipid metabolism, and insulin resistance were monitored and compared to the control animals. Phloretin treatment significantly blocks high-fat diet-induced weight gain but did not induce weight loss in obese animals. Phloretin improved glucose homeostasis and insulin sensitivity and alleviated hepatic lipid accumulation. RT-PCR analysis showed that phloretin treatment suppresses expression of macrophage markers (F4/80 and Cd68) and pro-inflammatory genes (Mcp-1 and Ccr2) and enhances adiponectin gene expression in white adipose tissue. In addition, phloretin treatment elevated the expression of fatty acid oxidation genes such as carnitine palmitoyltransferase 1a and 1b (Cpt1a and Cpt1b) and reduced expression of monocyte chemoattractant protein-1 (Mcp-1), de novo lipogenesis transcriptional factor peroxisome proliferator-activated receptor-γ 2 (Pparγ2), and its target monoacylglycerol O-acyltransferase (Mgat-1) genes. These results provide direct evidence to support a possible use of phloretin for mitigation of obesity and maintenance of metabolic homeostasis.

Immune deficiency vs. immune excess in inflammatory bowel diseases-STAT3 as a rheo-STAT of intestinal homeostasis.

Science.gov (United States)

Leppkes, Moritz; Neurath, Markus F; Herrmann, Martin; Becker, Christoph

2016-01-01

Genome-wide association studies have provided many genetic alterations, conferring susceptibility to multifactorial polygenic diseases, such as inflammatory bowel diseases. Yet, how specific genetic alterations functionally affect intestinal inflammation often remains elusive. It is noteworthy that a large overlap of genes involved in immune deficiencies with those conferring inflammatory bowel disease risk has been noted. This has provided new arguments for the debate on whether inflammatory bowel disease arises from either an excess or a deficiency in the immune system. In this review, we highlight the functional effect of an inflammatory bowel disease-risk allele, which cannot be deduced from genome-wide association studies data alone. As exemplified by the transcription factor signal transducer and activator of transcription 3 (STAT3), we show that a single gene can have a plethora of effects in various cell types of the gut. These effects may individually contribute to the restoration of intestinal homeostasis on the one hand or pave the way for excessive immunopathology on the other, as an inflammatory "rheo-STAT". © Society for Leukocyte Biology.

Testing the incentive-sensitization theory with at-risk drinkers: wanting, liking, and alcohol consumption.