bluuebunny/crossref_metadata_2025 huggingface dataset:
The American Presidency and Environmental Policy
Authors: Vig Norman J.
Published: February 2013

This article begins with a review of research on environmental policy making by different presidents. It classifies presidents into three categories, based primarily on their environmental policy agendas and relative success in achieving them. These are the opportunistic leaders, frustrated underachievers, and rollback advocates. The discussion then turns to the nature of presidential powers.
Environmental Bureaucracies
Authors: Fiorino Daniel J.
Published: February 2013

This article presents a guide to and an analysis of the EPA as possibly the world's foremost environmental bureaucracy. It begins with a brief history of the agency and its evolution over four decades, and then analyzes its organization and decision making. This is followed by an assessment of the EPA and the administrative and policy literature associated with it under three headings: relationships with state agencies; the role of economic and risk analysis in decision making; and the capacity for innovation. The final section considers the extent to which the EPA's past should define its future and that of U.S. environmental policy.
Bureaucracy and Natural Resources Policy
Authors: Thomas Craig W.
Published: February 2013

This article examines the natural resource policies in the United States, the public agencies that have implemented these policies, and the policy subsystems within which they operate. It also considers how agency cultures have changed as new professions and scientific ideas entered the agencies; and new approaches to natural resources management, such as adaptive management and collaborative governance. Policy topics include traditional resource extraction (such as mining, forestry, and water use), recreational and ascetic uses (such as parks and wilderness), and more contemporary issues (such as biodiversity conservation and climate change impacts). Throughout, the article focuses on key directions in theoretical scholarship on natural resource policy and management, while noting potential avenues for future research.
Environmental Federalism and the Role of State and Local Governments
Authors: Scheberle Denise
Published: February 2013

This article begins with an overview of federalism and intergovernmental relations, focusing on the legal structures for federalism and how these structures play out in the environmental field. Subsequent sections highlight the evolving nature of intergovernmental relationships within environmental programs, including discussions of federal-state working relationships, differences in state capacity and willingness to engage in environmental protection, advocacy by state and local governments, and state and local government innovation. A final section offers some conclusions about environmental federalism.
The Promise and Performance of Collaborative Governance
Authors: Gerlak Andrea K. , Heikkila Tanya , Lubell Mark
Published: February 2013

This article analyzes the promises and potential pitfalls of collaborative governance. It first summarizes the origins and evolution of collaborative governance and then compares the claims of the proponents and opponents. It then reviews what is known and what is still uncertain from the growing body of empirical research studying collaborative environmental governance. The conclusion speculates on the future of collaborative governance for both research and practice.
Parties, Campaigns, and Elections
Authors: Below Amy
Published: February 2013

This article reviews existing literature concerning the relationships between parties, campaigns, and elections and environmental politics and policy. It reviews studies conducted on the ability of political parties (the Democratic, Republican, and Green Parties, specifically) to represent environmental interests and win elections, the impact environmental issues have on campaigns and elections, and how well elected representatives carry out their pro- or anti-environmental campaign pledges once in office. It then considers the role of direct democracy and the evolution of environmentally related initiatives and referenda, and their success at the polls. The last section focuses on the role of the media in environmental politics and policy. One of the largest impacts the media have on the electoral process is their ability to craft the agenda for political candidates and policy makers. The article also highlights gaps in knowledge and suggests areas for future research.
The Use of Strategic Planning, Information, and Analysis in Environmental Policy Making and Management
Authors: Cohen Steven
Published: February 2013

This article discusses the use of environmental planning and analysis efforts in the U.S. policy-making system. It begins with an examination of the incremental nature of environmental policy development and describes how the complexity and scientific uncertainty of environmental problems influences policy formulation and implementation. Next, it addresses two important policy-making tools: strategic planning and environmental impact assessment. It then uses a series of case studies to illustrate the factors that condition the success and failure of analysis in environmental policy and administration. In some instances these analytic tools contribute to success, and in other cases they are largely irrelevant. Throughout the article discusses what we know and do not know about environmental planning and analysis. It also identifies potential directions for future research.
Environmental Policy and Science
Authors: Ascher William , Steelman Toddi A.
Published: February 2013

This article considers the intellectual traditions that have shaped how we view science, current controversies related to science and environmental policy, and some alternatives to deal with the complexities of science and environmental policy making. It suggests that science should be seen as one form of knowledge that can inform policy, and that understanding the role of science and these other types of knowledge within the distinct phases of the policy process can provide greater insight into how we might think about and use science more constructively.
Evidence of deterministic assembly according to flowering time in an old‐field plant community
Authors: Dante Sneha K. , Schamp Brandon S. , Aarssen Lonnie W.
Published: February 2013

Theory has produced contrasting predictions related to flowering time overlap among coexisting plant species largely because of the diversity of potential influences on flowering time. In this study, we use a trait‐based null modelling approach to test for evidence of deterministic assembly of species according to flowering time in an old‐field plant community.

Plant species coexisting in one‐metre‐square plots overlapped in flowering time significantly more than expected. This flowering synchrony was more pronounced when analyses focused on bee‐pollinated species. Flowering synchrony was also observed for wind‐pollinated species, although for only one of our two null model tests, highlighting the sensitivity of some results to different randomization methods. In general, these patterns suggest that relationships between pollinators and plants can influence community assembly processes.

Because our study community is composed of approximately 43% native plant species and 57% exotic species, and because the arrival of new species may complicate plant–pollinator interactions, we tested whether flowering time overlap was altered by introduced species. Flowering synchrony was greater in plots with a higher proportion of introduced species. This pattern held for both null model tests, but was slightly stronger when analyses focused on bee‐pollinated species. These results indicate that introduced species alter community flowering distributions and in so doing will inevitably affect pollinator–plant interactions.

Finally, we tested whether our results were influenced by variation among study plots in above‐ground biomass production, which some theory predicts will be related to the importance of competition. Our results were not influenced by this variation, suggesting that resource variation among our plots did not contribute to observed patterns.

Synthesis: Our results provide support for predictions that coexisting species should display flowering synchrony, and provide no support for species coexistence via temporal niche partitioning at this scale in this study community. Our results also indicate that introduced species significantly alter the community assembly process such that flowering synchrony is more pronounced in plots with a greater proportion of introduced plant species.
Cost limitation through constrained oviposition site in a plant‐pollinator/seed predator mutualism
Authors: Labouche Anne‐Marie , Bernasconi Giorgina
Published: February 2013

Mutualism often involves reciprocal exploitation due to individual selection for increased benefits even at the expense of the partner. Therefore, stability and outcomes of such interactions crucially depend on cost limitation mechanisms.

In the plant, pollinator /seed predator interaction betweenSilene latifolia(Caryophyllaceae) andHadena bicruris(Lepidoptera: Noctuidae), moths generate pollination benefits as adults but impose seed predation costs as larvae. We examined whether floral morphology limits over‐exploitation by constraining oviposition site. Oviposition site varies naturally inside vs. outside the corolla tube, but neither its determinants nor its effect on the interaction have been investigated.

In a common garden with plants originating from eight populations, corolla tube length predicted oviposition site, but not egg presence or pollination efficiency, suggesting that long corolla tubes constrain the moth to lay eggs on petals. Egg position was also predicted by the combined effect of corolla tube and moth ovipositor lengths, with shorter ovipositor than corolla tube resulting in higher probability for eggs outside. Egg position on a given plant was repeatable over different exposure nights.

When egg position was experimentally manipulated, eggs placed on the petal resulted in significantly fewer successful fruit attacks compared with eggs placed inside the corolla tube, suggesting differences in egg/larval mortality. Egg position also differently affected larval mass, fruit mass and fruit development.

Our results indicate that constraining oviposition site through a long corolla tube reduces seed predation costs suffered by the plant without negatively affecting pollination efficiency and, hence may act to limit over‐exploitation. However, the net effects of corolla tube depth variation on this interaction may fluctuate with extrinsic factors affecting egg mortality, and with patterns of gene flow affecting trait matching between the interacting species.

The intermediate fitness costs incurred by both plant and insect associated with the different egg positions may reduce selective pressures for this interaction to evolve towards antagonism, favouring instead a mutualistic outcome. While a role for oviposition site variation in cost limitation is a novel finding in this system, it may apply more generally also to other mutualisms involving pollinating seed predators.
Modelling elastic anisotropy of dry rocks as a function of applied stress
Authors: Madadi Mahyar , Pervukhina Marina , Gurevich Boris
Published: February 2013

We propose an analytical model for seismic anisotropy caused by the application of an anisotropic stress to an isotropic dry rock. We first consider an isotropic, linearly elastic medium (porous or non‐porous) permeated by a distribution of discontinuities with random (isotropic) orientation (such as randomly oriented compliant grain contacts or cracks). The geometry of individual discontinuities is not specified. Instead, their behaviour is defined by a ratio B of the normal to tangential excess compliances.

When this isotropic rock is subjected to a compressive stress (isotropic or anisotropic), the specific surface area of cracks aligned parallel to a particular plane is reduced in proportion to the normal stress traction acting on that plane. This effect is modelled using the Sayers‐Kachanov non‐interactive approximation, which expresses the effect of cracks on the elastic compliance tensor as an integral over crack orientations. This integral is evaluated using the Taylor expansion of the stress dependency of the specific surface area of the cracks. This allows the analytical solution previously derived for small anisotropic stresses to be extended to large stresses. Comparison of the model predictions with the results of laboratory measurements shows a reasonable agreement for moderate magnitudes of uniaxial stress (up to 50 MPa).

While the model contains five independent parameters, the variation of the anisotropy pattern (which can be expressed by the ratios of Thomsen’s anisotropy parameters ε, δ and γ) with normalized stress is controlled by only two parameters: Poisson’s ratio ν of the unstressed rock and the compliance ratio B. The model predicts that the ε/γ ratio depends on both ν and B but varies only mildly with stress, while the ε/δ ratio varies between 0.8–1.1 in a wide range of values of ν and B. The latter observation implies that the anisotropy remains close to elliptical even for larger stresses (within the assumptions of the model).

The proposed model of stress‐induced anisotropy may be useful for differentiating stress‐induced anisotropy from that caused by aligned fractures. Conversely, if the cause of seismic anisotropy is known, then the anisotropy pattern allows one to estimate P‐wave anisotropy from S‐wave anisotropy.
Risk‐sensitive allocation in seasonal dynamics of fat and protein reserves in a long‐lived mammal
Authors: Monteith Kevin L. , Stephenson Thomas R. , Bleich Vernon C. , Conner Mary M. , Pierce Becky M. , Bowyer R. Terry
Published: February 2013

Body reserves of numerous taxa follow seasonal rhythms that are a function of temporal patterns in food availability and life‐history events; however, tests of the theory underlying the allocation of somatic reserves for long‐lived organisms are rare, especially for free‐ranging mammals. We evaluated the hypothesis that allocation of somatic reserves to survival (i.e., metabolic processes) and reproduction should be sensitive to current nutritional state relative to seasonal thresholds in those reserves.

Our goal was to reveal the linkages between nutrition and life‐history traits to understand how long‐lived, iteroparous organisms balance the allocation of somatic reserves to reproduction, while retaining reserves as insurance for survival in unpredictable environments. Our evaluation was based on seasonal dynamics in fat (measured as ingesta‐free body fat; IFBFat) and protein reserves (measured as ingesta‐free, fat‐free body mass; IFFFBMass) of 136 female mule deer (Odocoileus hemionus) over 8 years.

Although mean changes in fat and protein reserves were positive over summer and negative over winter, accretion and catabolism of those reserves was not consistent among individuals. Over winter, both lipid and protein stores available in autumn were catabolized in proportion to their availability above a post‐winter threshold (5·8% IFBFat, 33 kg IFFFBMass); however, lean body tissue was spared at the expense of lipid reserves.

Female deer mostly synthesized lean body tissue over summer and committed post‐winter fat reserves to reproduction relative to their availability above an autumn threshold (>8·6% IFBFat), which was lowered by 2·8 percentage points (pp) for each additional young recruited. Mothers reduced their autumn fat threshold to secure current reproductive investment and, thereby, endured a cost of reproduction at the expense of fat accumulation.

Allocation of somatic reserves occurred in a risk‐sensitive framework; females allocated reserves relative to their availability above seasonal thresholds. In contrast to current notions of summer accretion and winter catabolism of body reserves, some individuals deposited reserves over winter and catabolized reserves over summer, mainly because regulation of individual condition was state‐dependent. Consequently, behaviour and life‐history strategies may be as much a function of nutritional contributions of the previous season as of the current one.
Matching observations and reality: using simulation models to improve monitoring under uncertainty in theSerengeti
Authors: Nuno Ana , Bunnefeld Nils , Milner‐Gulland E. J.
Published: February 2013

Planning for conservation success requires identifying effective and efficient monitoring strategies but multiple types of uncertainty affect the accuracy and precision of wildlife abundance estimates. Observation uncertainty, a consequence of sampling effort and design as well as the process of observation, is still understudied, with little attention given to the multiple potential sources of error involved. To establish error minimization priorities and maximize monitoring efficiency, the direction and magnitude of multiple sources of uncertainty must be considered.

Using monitoring of two contrasting ungulate species in theSerengeti ecosystem as a case study, we developed a ‘virtual ecologist’ framework within which we carried out simulated tests of different monitoring strategies for different types of species. We investigated which components of monitoring should be prioritized to increase survey accuracy and precision and explored the robustness of population estimates under different budgetary scenarios.

The relative importance of each process affecting precision and accuracy varied according to the survey technique and biological characteristics of the species. While survey precision was mainly affected by population characteristics and sampling effort, the accuracy of the survey was greatly affected by observer effects, such as juvenile and herd detectability.

Synthesis and applications. Monitoring efficiency is of the utmost importance for conservation, especially in the context of limited budgets and other priorities. We provide insights into the likely effect of different types of observation and process error on population estimates for savanna ungulates, and more generally present a framework for evaluating monitoring programmes in a virtual environment. In highly aggregated species, the main focus should be on survey precision; sampling effort should be defined according to wildlife spatial distribution. For random or slightly aggregated species, accuracy is the key factor; this is most sensitive to observer effects which should be minimized by training and calibration by observer.
Election Inversions, Coalitions and Proportional Representation: Examples of Voting Paradoxes in Danish Government Formations
Authors: Kurrild‐Klitgaard Peter
Published: February 2013

When collective choices are made in more than one round and with different groups of decision makers, so‐called ‘election inversions’ may take place, where each round produces different majority outcomes. In this article, two versions of such compound majority paradoxes are identified that are particularly, but not exclusively, relevant for systems of proportional representation with governing coalitions: the ‘Threshold Paradox’ and the ‘Federal Paradox’. The empirical relevance of the paradoxes is illustrated with examples from two Danish elections (in 1971 and in 1990), where a majority of the voters voted for one bloc of parties, but a majority of the seats fell to another.
Reflexive Habits: Dating and Rationalized Conduct in New York and Berlin
Authors: Krause Monika , Kowalski Alexandra
Published: February 2013

This paper builds on the work of Norbert Elias to examine how conduct varies across cultural contexts. We compare courtship practices in New York and Berlin and ask how people act during the course of ‘getting together’ with a sexual or romantic partner. Drawing on interviews in both contexts, we find that conduct associated with the practice of ‘dating’ among New York respondents is more rationalized as indicated by a greater awareness of timing, a greater degree of intentionality and planning and a greater tendency to psychologize self and others. Berlin respondents report observations of themselves and others in less detail and tend to describe themselves as passive objects of the impersonal forces of love. Whereas conduct associated with dating is more reflexive in some ways, these forms of reflexive conduct are not themselves fully conscious or the object of reflection but have in turn become taken for granted and habitual. These findings challenge us to conceptualize habitus in a manner that does not reproduce the opposition between habit and reflexivity but allows us to use the concept as a tool to capture variations in how self-monitoring and habit are combined in modes of conduct.
In the Shadow of the United States: The International Transmission Effect of Asset Returns
Authors: Chang Kuang‐Liang , Chen Nan‐Kuang , Leung Charles Ka Yui
Published: February 2013

We examine how fluctuations in financial and housing markets in the United States affect asset returns and GDP in Hong Kong. In contrast to studies using linear specifications, which find that the United States and Hong Kong are virtually delinked in terms of the asset markets, our regime‐switching models indicate that an unexpected change in US stock returns, followed by the TED spread, has the most significant effect on Hong Kong asset returns and GDP, typically in a regime of high return and low volatility. For in‐sample one‐step‐ahead forecasting, the US term spread is the best predictor.
Price Scissors and Economic Growth: The Role of Openness
Authors: He Qichun
Published: February 2013

The present paper examines how the reduction in the price scissors impacted economic development during the early stage of China's reform period (i.e. 1981–1998). It is found that an increase in agriculture's terms of trade had a significant complementary effect with exportation on China's economic growth. Moreover, our data supports the results of Sah and Stiglitz (1987), who suggest that a reduction in the price scissors is associated with a decrease in physical capital accumulation in an open economy.
Evidence on the Convergence of Per Capita Income: A Comparison of Founder Members of the Association of South East Asian Nations and the South Asian Association of Regional Cooperation
Authors: Jayanthakumaran Kankesu , Lee Shao‐Wei
Published: February 2013

This paper investigates the per capita income convergence patterns of a set of Association of South East Asian Nations (ASEAN) and South Asian Association of Regional Cooperation (SAARC) countries. We obtained a time‐series analysis for stochastic convergence by applying unit‐root tests in the presence of two endogenously‐determined structural breaks. We then supplemented the results by tests that produced evidence for β convergence. The evidence shows that the relative per capita income series of ASEAN‐5 countries were consistent with stochastic convergence and β convergence, but this was not found for SAARC‐5 countries. For the ASEAN‐5 countries, the structural breaks associated with the world oil crisis and the Asian crisis impacted heavily on the convergence/divergence process.
Adenoma‐like and non‐adenoma‐like dysplasia‐associated lesion or mass in ulcerative colitis
Authors: Chen Ying Xuan , Qiao Liang
Published: February 2013

Ulcerative colitis (UC) patients have an increased risk of colorectal cancer. UC has two general patterns of dysplasia, which are commonly classified as adenoma‐like dysplasia‐associated lesion or mass (DALM) and non‐adenoma‐like DALM. The latter has a high risk of concurrent malignancy and often requires a colectomy. Unfortunately, non‐adenoma‐like DALMs sometimes have endoscopic features similar to those of adenoma‐like DALMs. Therefore, new endoscopic techniques to distinguish between these two kinds of DALM have been proposed.
Characterization of comparative genome‐derived simple sequence repeats for acanthopterygian fishes
Authors: Gotoh Ryo O. , Tamate Satoshi , Yokoyama Jun , Tamate Hidetoshi B. , Hanzawa Naoto
Published: February 2013

Simple sequence repeats (SSRs) have become one of the most popular molecular markers for population genetic studies. The application ofSSRmarkers has often been limited to source species becauseSSRloci are too labile to be maintained in even closely related species. However, a few extremely conservedSSRloci have been reported. Here, we tested for the presence of conservedSSRloci in acanthopterygian fishes, which include over 14 000 species, by comparing the genome sequences of four acanthopterygian fishes. We also examined the comparative genome‐derivedSSRs (CG‐SSRs) for their transferability across acanthopterygian fishes and their applicability to population genetic analysis. Forty‐sixSSRloci with conserved flanking regions were detected and examined for their transferability among seven nonacanthopterygian and 27 acanthopterygian fishes. ThePCRamplification success rate in nonacanthopterygian fishes was low, ranging from 2.2% to 21.7%, except forLophius litulon(Lophiiformes; 80.4%). Conversely, the rate in most acanthopterygian fishes exceeded 70.0%. Sequencing of these 46 loci revealed the presence ofSSRs suitable for scoring while fragment analysis of 20 loci revealed polymorphisms in most of the acanthopterygian fishes. Population genetic analysis ofCottus pollux(Scorpaeniformes) andSphaeramia orbicularis(Perciformes) usingCG‐SSRs showed that these populations did not deviate from linkage equilibrium or Hardy–Weinberg equilibrium. Furthermore, almost no loci showed evidence of null alleles, suggesting thatCG‐SSRs have strong resolving power for population genetic analysis. Our findings will facilitate the use of these markers in species in which markers remain to be identified.
The management of benign salivary disease: a case series
Authors: Jones RHB , Findlay GJ
Published: February 2013

There are many causes for benign salivary gland disease but the most common relate to inflammation and infection. This usually revolves around duct obstruction and a reduction in the normal salivary flow from the gland into the mouth. This leads to retention of saliva, proximal to the obstruction and ascending infection from the mouth, usually because of the decrease in salivary flow. The increase in tension behind the obstruction causes significant pain and swelling, along with the inevitable infection if the obstruction is not relieved. This paper discusses the various treatments available for benign salivary gland disease, the traditional methods of treatment through to the use of endoscopic techniques which are currently available, including a discussion about the use of sialoendoscopy.
Diagnostic value of serum brain natriuretic peptide in syncope in children and adolescents
Authors: Zhang Qingyou , Jin Hongfang , Qi Jianguang , Yan Hui , Du Junbao
Published: February 2013

Aim

This study was designed to evaluate the diagnostic value of B‐type natriuretic peptide (BNP) in syncope in children and adolescents.

Methods

Serum BNP concentration was measured by electrochemiluminescence assay in 62 consecutive children and adolescents hospitalized for syncope.

Results

Of the 62 children and adolescents hospitalized for syncope, 39 had noncardiac syncope, of whom 37 (59.7%) had autonomic‐mediated reflex syncope and two (3.2%) had syncope of unknown cause. Twenty‐three patients (37.1%) had cardiac syncope: 11 of these had cardiac arrhythmias and 12 had structural cardiac/cardiopulmonary disease. Patients with cardiac syncope had significantly higher serum BNP than those with non‐cardiac syncope (958.78 ± 2443.41 pg/mL vs 31.05 ± 22.64 pg/mL, p < 0.05). Logistic multivariate regression analysis revealed that urinary incontinence during syncopal episodes, ECG abnormalities and increased serum BNP levels were independent predictors of cardiac syncope. At a cut‐off value of 40.65 pg/mL, serum BNP was associated with significant risk of a cardiac cause of syncope, with sensitivity of 73.9% and specificity of 70.0% for distinguishing cardiac syncope from noncardiac syncope.

Conclusion

Serum BNP was helpful in differentiating cardiac syncope from noncardiac syncope in children and adolescents.
Neutrophil gelatinase‐associated lipocalin: pathophysiology and clinical applications
Authors: Singer E. , Markó L. , Paragas N. , Barasch J. , Dragun D. , Müller D. N. , Budde K. , Schmidt‐Ott K. M.
Published: February 2013

Neutrophil gelatinase‐associated lipocalin (NGAL), a 25 kDa protein produced by injured nephron epithelia, is one of the most promising new markers of renal epithelial injury. In contrast to serum creatinine and urinary output, which are the measures of kidney function, NGAL is specifically induced in the damaged nephron and then released into blood and urine, where it can be readily measured. Careful proof‐of‐concept studies using defined animal models have uncovered the sources and trafficking of NGAL in acute kidney injury (AKI) and have addressed the contributions of renal and non‐renal sources. Clinical studies indicate that NGAL, unlike creatinine, is a marker responsive to tissue stress and nephron injury, but less so to adaptive hemodynamic responses. In certain clinical settings, NGAL is an earlier marker compared with serum creatinine. In addition, clinical studies have shown that NGAL is a powerful predictor of poor clinical outcomes, which can be used to risk stratify patients when combined with serum creatinine. NGAL has important limitations, including its responsiveness in systemic inflammation, which is partially uncoupled from its response to kidney injury and which needs to be considered when interpreting NGAL results clinically. This review covers the biology and pathophysiology of NGAL and summarizes the results of the growing body of clinical studies that have addressed the utility of NGAL in the early diagnosis of AKI, in the distinction of intrinsic AKI and in the prognostic assessment of broad patient populations.
How I manage patients with acquired haemophilia A
Authors: Sborov Douglas W. , Rodgers George M.
Published: February 2013

Acquired haemophilia A (AHA) is a potentially life‐threatening bleeding disorder occurring in patients without a previous personal or family history of bleeding. Development of immune‐mediated autoantibodies against coagulation factor VIII is associated with a wide range of clinical disorders including pregnancy, autoimmune disorders, malignancy, or with no apparent disease. There exists great potential for morbidity and mortality related to acute and recurrent bleeding episodes, making prompt diagnosis and treatment necessary. The two primary goals of treatment focus on cessation of bleeding and eradication of the acquired factor VIII inhibitor. No randomized clinical trials have been conducted regarding treatment, so expert clinical opinion guides therapeutic intervention. This current report provides a profile of patient characteristics, an algorithm for diagnosis, and outlines treatment recommendations based upon current guidelines and clinical experience. As first‐line interventions for acute bleeding and inhibitor eradication are generally accepted, we will emphasize discussion of second‐line therapeutic options.
The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis
Authors: Romano B , Borrelli F , Fasolino I , Capasso R , Piscitelli F , Cascio MG , Pertwee RG , Coppola D , Vassallo L , Orlando P , Di Marzo V , Izzo AA
Published: February 2013

Background and Purpose

The non‐psychotropic cannabinoid cannabichromene is known to activate the transient receptor potential ankyrin‐type1 (TRPA1) and to inhibit endocannabinoid inactivation, both of which are involved in inflammatory processes. We examined here the effects of this phytocannabinoid on peritoneal macrophages and its efficacy in an experimental model of colitis.

Experimental Approach

Murine peritoneal macrophages were activated in vitro by LPS. Nitrite levels were measured using a fluorescent assay; inducible nitric oxide (iNOS), cyclooxygenase‐2 (COX‐2) and cannabinoid (CB1 and CB2) receptors were analysed by RT‐PCR (and/or Western blot analysis); colitis was induced by dinitrobenzene sulphonic acid (DNBS). Endocannabinoid (anandamide and 2‐arachidonoylglycerol), palmitoylethanolamide and oleoylethanolamide levels were measured by liquid chromatography‐mass spectrometry. Colonic inflammation was assessed by evaluating the myeloperoxidase activity as well as by histology and immunohistochemistry.

Key Results

LPS caused a significant production of nitrites, associated to up‐regulation of anandamide, iNOS, COX‐2, CB1 receptors and down‐regulation of CB2 receptors mRNA expression. Cannabichromene significantly reduced LPS‐stimulated nitrite levels, and its effect was mimicked by cannabinoid receptor and TRPA1 agonists (carvacrol and cinnamaldehyde) and enhanced by CB1 receptor antagonists. LPS‐induced anandamide, iNOS, COX‐2 and cannabinoid receptor changes were not significantly modified by cannabichromene, which, however, increased oleoylethanolamide levels. In vivo, cannabichromene ameliorated DNBS‐induced colonic inflammation, as revealed by histology, immunohistochemistry and myeloperoxidase activity.

Conclusion and Implications

Cannabichromene exerts anti‐inflammatory actions in activated macrophages – with tonic CB1 cannabinoid signalling being negatively coupled to this effect – and ameliorates experimental murine colitis.
Different β‐adrenoceptor subtypes coupling to cAMP or NO/cGMP pathways: implications in the relaxant response of rat conductance and resistance vessels
Authors: Flacco N , Segura V , Perez‐Aso M , Estrada S , Seller JF , Jiménez‐Altayó F , Noguera MA , D'Ocon P , Vila E , Ivorra MD
Published: February 2013

Background and Purpose

To analyse the relative contribution of β1‐, β2‐ and β3‐adrenoceptors (Adrb) to vasodilatation in conductance and resistance vessels, assessing the role of cAMP and/or NO/cGMP signalling pathways.

Experimental Approach

Rat mesenteric resistance artery (MRA) and aorta were used to analyse the Adrb expression by real‐time‐PCR and immunohistochemistry, and for the pharmacological characterization of Adrb‐mediated activity by wire myography and tissue nucleotide accumulation.

Key Results

The mRNAs and protein for all Adrb were identified in endothelium and/or smooth muscle cells (SMCs) in both vessels. In MRA, Adrb1 signalled through cAMP, Adrb3 through both cAMP and cGMP, but Adrb2, did not activate nucleotide formation; isoprenaline relaxation was inhibited by propranolol (β1, β2), CGP20712A (β1), and SQ22536 (adenylyl cyclase inhibitor), but not by ICI118,551 (β2), SR59230A (β3), ODQ (soluble guanylyl cyclase inhibitor), L‐NAME or endothelium removal. In aorta, Adrb1 signalled through cAMP, while β2‐ and β3‐subtypes through cGMP; isoprenaline relaxation was inhibited by propranolol, ICI118,551, ODQ, L‐NAME, and to a lesser extent, by endothelium removal. CL316243 (β3‐agonist) relaxed aorta, but not MRA.

Conclusion and Implication

Despite all three Adrb subtypes being found in both vessels, Adrb1, located in SMCs and acting through the adenylyl cyclase/cAMP pathway, are primarily responsible for vasodilatation in MRA. However, Adrb‐mediated vasodilatation in aorta is driven by endothelial Adrb2 and Adrb3, but also by the Adrb2 present in SMCs, and is coupled to the NO/cGMP pathway. These results could help to understand the different physiological roles played by Adrb signalling in regulating conductance and resistance vessels.
Inhibitory cross‐talk between the AMPK and ERK pathways mediates endoplasmic reticulum stress‐induced insulin resistance in skeletal muscle
Authors: Hwang Seung‐Lark , Jeong Yong‐Tae , Li Xian , Kim Yong Deuk , Lu Yue , Chang Young‐Chae , Lee In‐Kyu , Chang Hyeun Wook
Published: February 2013

Background and Purpose

Endoplasmic reticulum (ER) stress has been implicated in the pathogeneses of insulin resistance and type 2 diabetes, and extracellular signal‐regulated kinase (ERK) antagonist is an insulin sensitizer that can restore muscle insulin responsiveness in both tunicamycin‐treated muscle cells and type 2 diabetic mice. The present study was undertaken to determine whether the chemical or genetic inhibition ER stress pathway targeting by ERK results in metabolic benefits in muscle cells.

Experimental Approach

ER stress was induced in L6 myotubes using tunicamycin (5 μg·mL−1) or thapsigargin (300 nM) and cells were transfected with siRNA ERK or AMPKα2. Changes in ER stress and in the ERK and AMPK signalling pathways were explored by Western blotting. The phosphorylation levels of insulin receptor substrate 1 were analysed by immunoprecipitation and using glucose uptake assay.

Key Results

ER stress dampened insulin‐stimulated signals and glucose uptake, whereas treatment with the specific ERK inhibitor U0126 (25 μM) rescued impaired insulin signalling via AMPK activation. In db/db mice, U0126 administration decreased markers of insulin resistance and increased the phosphorylations of Akt and AMPK in muscle tissues.

Conclusions and Implications

Inhibition of ERK signalling pathways by a chemical inhibitor and knockdown of ERK improved AMPK and Akt signallings and reversed ER stress‐induced insulin resistance in L6 myotubes. These findings suggest that ERK signalling plays an important role in the regulation of insulin signals in muscle cells under ER stress.
Regulation of carboxylesterase‐2 expression by p53 family proteins and enhanced anti‐cancer activities among 5‐fluorouracil, irinotecan and doxazolidine prodrug
Authors: Xiao Da , Yang Dongfang , Guo Liangran , Lu Wei , Charpentier Margaret , Yan Bingfang
Published: February 2013

Background and Purpose

For four decades, 5‐fluorouracil (5‐FU) has been a major anti‐cancer medicine. This drug is increasingly used with other anti‐cancer agents such as irinotecan. Irinotecan and many others such as PPD (pentyl carbamate of p‐aminobenzyl carbamate of doxazolidine) require activation by carboxylesterase‐2 (CES2). 5‐FU, on the other hand, reportedly induces CES2 in colorectal tumour lines. The aims of this study were to determine the molecular basis for the induction and to ascertain interactive cell‐killing activity between 5‐FU and ester prodrugs.

Experimental Approach

Colorectal and non‐colorectal lines and xenografts were treated with 5‐FU and the expression of CES2 was determined. Cell‐killing activity of irinotecan and PPD were determined in the presence or absence of CES2 inhibitor. Several molecular experiments were used to determine the molecular basis for the induction.

Key Results

Without exceptions, robust induction was detected in cell lines expressing functional p53. High‐level induction was also detected in xenografts. 5‐FU pretreatment significantly increased cell‐killing activity of irinotecan and PPD. Molecular experiments established that the induction was achieved by both transactivation and increased mRNA stability through p53. Either p63 or p73, functionally related to p53, did not support the transactivation.

Conclusions and Implications

The results in this study suggest that FOLFIRI, a common regimen combining irinotecan and 5‐FU, should switch the dosing sequence, namely from 5‐FU to irinotecan, to enhance hydrolytic activation of irinotecan. This modified order likely reduces the dose of anti‐cancer agents, thus minimizing overall toxicity. The results also conclude that p53 family members act differently in regulating gene expression.
Do male secondary sexual characters signal ejaculate quality? A meta‐analysis
Authors: Mautz Brian S. , Møller Anders P. , Jennions Michael D.
Published: February 2013

There are two reasons why researchers are interested in the phenotypic relationship between the expression of male secondary sexual characters (SSCs) and ‘ejaculate quality’ (defined as sperm/ejaculate traits that are widely assumed to increase female fertility and/or sperm competitiveness). First, if the relationship is positive then females could gain a direct benefit by choosing more attractive males for fertility assurance reasons (‘the phenotype‐linked fertility’ hypothesis). Second, there is much interest in the direction of the correlation between traits favoured by pre‐copulatory sexual selection (i.e. affecting mating success) and those favoured by post‐copulatory sexual selection (i.e. increasing sperm competitiveness). If the relationship is negative this could lead to the two forms of selection counteracting each other. Theory predicts that the direction of the relationship could be either positive or negative depending on the underlying genetic variance and covariance in each trait, the extent of variation among males in condition (resources available to allocate to reproductive traits), and variation among males in the cost or rate of mating. We conducted a meta‐analysis to determine the average relationship between the expression of behavioural and morphological male secondary sexual characters and four assays of ejaculate quality (sperm number, viability, swimming speed and size). Regardless of how the data were partitioned the mean relationship was consistently positive, but always statistically non‐significant. The only exception was that secondary sexual character expression was weakly but significantly positively correlated with sperm viability (r = 0.07,P < 0.05). There was no significant difference in the strength or direction of the relationship between behavioural and morphologicalSSCs, nor among relationships using the four ejaculate quality assays. The implications of our findings are discussed.
Snails and their trails: the multiple functions of trail‐following in gastropods
Authors: Ng Terence P. T. , Saltin Sara H. , Davies Mark S. , Johannesson Kerstin , Stafford Richard , Williams Gray A.
Published: February 2013

Snails are highly unusual among multicellular animals in that they move on a layer of costly mucus, leaving behind a trail that can be followed and utilized for various purposes by themselves or by other animals. Here we review more than 40 years of experimental and theoretical research to try to understand the ecological and evolutionary rationales for trail‐following in gastropods. Data from over 30 genera are currently available, representing a broad taxonomic range living in both aquatic and terrestrial environments. The emerging picture is that the production of mucus trails, which initially was an adaptation to facilitate locomotion and/or habitat extension, has evolved to facilitate a multitude of additional functions. Trail‐following supports homing behaviours, and provides simple mechanisms for self‐organisation in groups of snails, promoting aggregation and thus relieving desiccation and predation pressures. In gastropods that copulate, trail‐following is an important component in mate‐searching, either as an alternative, or in addition to the release of water‐ or air‐borne pheromones. In some species, this includes a capacity of males not only to identify trails of conspecifics but also to discriminate between trails laid by females and males. Notably, trail discrimination seems important as a pre‐zygotic barrier to mating in some snail species. As production of a mucus trail is the most costly component of snail locomotion, it is also tempting to speculate that evolution has given rise to various ways to compensate for energy losses. Some snails, for example, increase energy intake by eating particles attached to the mucus of trails that they follow, whereas others save energy through reducing the production of their own mucus by moving over previously laid mucus trails. Trail‐following to locate a prey item or a mate is also a way to save energy. While the rationale for trail‐following in many cases appears clear, the basic mechanisms of trail discrimination, including the mechanisms by which many snails determine the polarity of the trail, are yet to be experimentally determined. Given the multiple functions of trail‐following we propose that future studies should adopt an integrated approach, taking into account the possibility of the simultaneous occurrence of many selectively advantageous roles of trail‐following behaviour in gastropods. We also believe that future opportunities to link phenotypic and genotypic traits will make possible a new generation of research projects in which gastropod trail‐following, its multitude of functions and evolutionary trade‐offs can be further elucidated.
Anti-tumour necrosis factor therapy enhances mucosal healing through down-regulation of interleukin-21 expression and T helper type 17 cell infiltration in Crohn's disease
Authors: Liu C , Xia X , Wu W , Wu R , Tang M , Chen T , Xu F , Cong Y , Xu X , Liu Z
Published: February 2013

Anti-tumour necrosis factor (TNF) monoclonal antibody (mAb) (infliximab, IFX) has been shown to be highly effective in the management of Crohn's disease (CD). Herein we investigated the potential role of IFX in inducing clinical remission and regulating interleukin (IL)-21 expression and T helper type 17 (Th17) cell infiltration in the intestinal mucosa of CD patients. Twenty-six CD patients were treated with IFX at weeks 0, 2 and 6. Clinical response, mucosal healing, serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were evaluated at week 10 after IFX administration. Expression of IL-21, IL-17A and retinoic acid-related orphan receptor C (RORC) in intestinal mucosa were analysed by quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. Peripheral blood and lamina propria CD4+ T cells were stimulated with anti-CD3 and anti-CD28 mAbs in the presence of IFX. Cytokine profiles and RORC were determined with enzyme-linked immunosorbent assay (ELISA) and real-time PCR. IL-21 and Th17 cells were found to be expressed highly in inflamed mucosa of active CD patients compared with healthy controls. Ten weeks after IFX infusion, CD activity index, ESR, CRP and intestinal mucosal healing were improved markedly in CD patients, and IL-21 expression and Th17 cell infiltration were decreased significantly compared with those before IFX therapy. In-vitro study demonstrated that IFX treatment could suppress IL-21, IL-17A and RORC expression in cultured CD biopsies. Moreover, IFX was also observed to down-regulate markedly IL-17A, IL-21 and RORC expression by CD CD4+ T cells. IFX is highly effective in inducing clinical remission and promoting intestinal mucosal healing in CD patients through down-regulation of IL-21 expression and Th17 cell infiltration in intestinal mucosa.
Symmetry in 3D Geometry: Extraction and Applications
Authors: Mitra Niloy J. , Pauly Mark , Wand Michael , Ceylan Duygu
Published: February 2013

The concept of symmetry has received significant attention in computer graphics and computer vision research in recent years. Numerous methods have been proposed to find, extract, encode and exploit geometric symmetries and high‐level structural information for a wide variety of geometry processing tasks. This report surveys and classifies recent developments in symmetry detection. We focus on elucidating the key similarities and differences between existing methods to gain a better understanding of a fundamental problem in digital geometry processing and shape understanding in general. We discuss a variety of applications in computer graphics and geometry processing that benefit from symmetry information for more effective processing. An analysis of the strengths and limitations of existing algorithms highlights the plenitude of opportunities for future research both in terms of theory and applications.