G protein-coupled receptor 35: an emerging target in inflammatory and cardiovascular disease

G protein-coupled receptor 35 (GPR35) is an orphan receptor, discovered in 1998, that has garnered interest as a potential therapeutic target through its association with a range of diseases. However, a lack of pharmacological tools and the absence of convincingly defined endogenous ligands have hampered the understanding of function necessary to exploit it therapeutically. Although several endogenous molecules can activate GPR35 none has yet been confirmed as the key endogenous ligand due to reasons that include lack of biological specificity, non-physiologically relevant potency and species ortholog selectivity. Recent advances have identified several highly potent synthetic agonists and antagonists, as well as agonists with equivalent potency at rodent and human orthologs, which will be useful as tool compounds. Homology modeling and mutagenesis studies have provided insight into the mode of ligand binding and possible reasons for the species selectivity of some ligands. Advances have also been made in determining the role of the receptor in disease. In the past, genome-wide association studies have associated GPR35 with diseases such as inflammatory bowel disease, type 2 diabetes, and coronary artery disease. More recent functional studies have implicated it in processes as diverse as heart failure and hypoxia, inflammation, pain transduction and synaptic transmission. In this review, we summarize the progress made in understanding the molecular pharmacology, downstream signaling and physiological function of GPR35, and discuss its emerging potential applications as a therapeutic target

Is innovation always beneficial? A meta-analysis of the relationship between innovation and performance in SMEs

The performance implications of innovation in small and medium-sized enterprises (SMEs) have attracted considerable interest among academics and practitioners. However, empirical research on the innovation–performance relationship in SMEs shows controversial results. This meta-analysis synthesizes empirical findings in order to obtain evidence whether and especially under which circumstances smaller, resource-scarce firms benefit from innovation. We find that innovation–performance relationship is context dependent. Factors such as the age of the firm, the type of innovation, and the cultural context affect the impact of innovation on firm performance to a large extent

Use of Multiple Methods: An Examination of Constraints Effecting Ethnic Minority Visitor Use of National Parks and Management Implications

Understanding outdoor recreation participation and national park visitation by members of ethnic minority groups has been a particular focus of outdoor recreation researchers for the past twenty years. Attracting ethnic minorities, and understanding their recreation needs and interests, demands a multi-faceted approach and sustained commitment not only by the U.S. National Park Service (NPS) but by other resource management agencies as well

Responding to Agency Avoidance of OIRA

Concerns have recently been raised that US federal agencies may sometimes avoid regulatory review by the White House Office of Information and Regulatory Affairs (OIRA). In this article, we assess the seriousness of such potential avoidance, and we recommend a framework for evaluating potential responses. After summarizing the system of presidential regulatory oversight through OIRA review, we analyze the incentives for agencies to cooperate with or avoid OIRA. We identify a wider array of agency avoidance tactics than has past scholarship, and a wider array of corresponding response options available to OIRA, the President, Congress, and the courts. We argue that, because the relationship between agencies and OIRA involves ongoing repeat player interactions, some of these avoidance tactics are less likely to occur (or to succeed) than has previously been alleged, and others are more likely; the difference depends significantly on how easy it is for OIRA to detect avoidance, and for OIRA, the courts, and others to respond. Further, we note that in this repeat player relationship, responses to agency avoidance tactics may induce further strategic moves and countermoves. Thus we further argue that the optimal response may not always be to try to eliminate the avoidance behavior; some avoidance may be worth tolerating where the benefits of trying to reduce agency avoidance would not justify the costs of response options and countermoves. We therefore conclude that responses to agency avoidance should be evaluated in a way similar to what OIRA asks of agencies evaluating proposed regulations: by weighing the pros and cons of alternative response options (including no action)

Phylogenetic signal in amphibian sensitivity to copper sulfate relative to experimental temperature

The release of large quantities of chemicals into the environment represents a major source of environmental disturbance. In recent years, the focus of ecotoxicology has shifted from describing the effects of chemical contaminants on individual species to developing more integrated approaches for predicting and evaluating long term effects of chemicals across species and ecosystems. Traditional ecotoxicology is typically based on data of sensitivity of a few surrogate species to a contaminant and often considers little variability in chemical sensitivity within and among taxonomic groups. This approach assumes that evolutionary history and phylogenetic relatedness among species have little or no impact on species’ sensitivity to chemical compounds. Few studies have tested this assumption. Using phylogenetic comparative methods and published data for amphibians, we show that sensitivity to copper sulfate, a commonly used pesticide, exhibits a strong phylogenetic signal when controlling for experimental temperature. Our results indicate that evolutionary history needs to be accounted for to make accurate predictions of amphibian sensitivity to this contaminant under different temperature scenarios. Since physiological and metabolic traits showing high phylogenetic signal likely underlie variation in species sensitivity to chemical stressors, future studies should evaluate and predict species vulnerability to pollutants using evolutionarily informed approaches

Human capital and entrepreneurial success : a meta-analytical review

The study meta-analytically integrates results from three decades of human capital research in entrepreneurship. Based on 70 independent samples (N = 24,733), we found a significant but small relationship between human capital and success (r(c) = .098). We examined theoretically derived moderators of this relationship referring to conceptualizations of human capital, to context, and to measurement of success. The relationship was higher for outcomes of human capital investments (knowledge/skills) than for human capital investments (education/experience), for human capital with high task-relatedness compared to low task-relatedness, for young businesses compared to old businesses, and for the dependent variable size compared to growth or profitability. Findings are relevant for practitioners (lenders, policy makers, educators) and for future research. Our findings show that future research should pursue moderator approaches to study the effects of human capital on success. Further, human capital is most important if it is task-related and if it consists of outcomes of human capital investments rather than human capital investments; this suggests that research should overcome a static view of human capital and should rather investigate the processes of learning, knowledge acquisition, and the transfer of knowledge to entrepreneurial tasks

Temporal and spatial variations in phytoplankton productivity in surface waters of a warm-temperate, monomictic lake in New Zealand

Surface phytoplankton productivity measurements were carried out in morphologically complex Lake Rotoiti with the objective of defining variations between sites and seasons, and the dominant environmental drivers of these variations. Measurements were carried out monthly at two depths at each of three morphologically diverse stations for 1 year throughout the lake. Productivity at the surface of the shallow embayment was significantly higher in most months of the year compared with the surface of the other two stations but there were no significant differences from September to December 2004. There were no relationships between measured environmental variables and primary productivity or specific production. Inorganic nutrient concentrations at the surface of the shallow station were low throughout the whole year but at the other two stations they showed a typical pattern for monomictic lakes of higher levels during winter mixing and declining concentrations during thermal stratification. The high variability between sites found in this study indicates that it is important to account for local differences in productivity in morphologically diverse lakes, and that whole lake productivity estimates may vary greatly depending on the location and depth of productivity measurements