The many uses of regulatory impact assessment: A meta-analysis of EU and UK cases

Research on regulation has crossed paths with the literature on policy instruments, showing that regulatory policy instruments contain cognitive and normative beliefs about policy. Thus, their usage stacks the deck in favor of one type of actor or one type of regulatory solution. In this article, we challenge the assumption that there is a predetermined relationship between ideas, regulatory policy instruments, and outcomes. We argue that different combinations of conditions lead to different outcomes, depending on how actors use the instrument. Empirically, we analyze 31 EU and UK case studies of regulatory impact assessment (RIA) - a regulatory policy instrument that has been pivotal in the so-called better regulation movement. We distinguish four main usages of RIA, that is, political, instrumental, communicative, and perfunctory. We find that in our sample instrumental usage is not so rare and that the contrast between communicative and political usages is less stark than is commonly thought. In terms of policy recommendations, our analysis suggests that there may be different paths to desirable outcomes. Policymakers should therefore explore different combinations of conditions leading to the usages they deem desirable rather than arguing for a fixed menu of variables.

Tumor cell budding and laminin-5 expression in colorectal carcinoma can be modulated by the tissue micro-environment.

Expression of laminin-5 alpha3, beta3 and gamma2 protein subunits was investigated in colorectal adenocarcinomas using immunostaining and confocal microscopy. The laminin-5 heterotrimer was found in basement membranes and as extracellular deposits in tumor stroma. In contrast to the alpha3 subunit, which was under-expressed, the gamma2 and beta3 subunits were detected in the cytoplasm of carcinoma cells dissociating (budding) from neoplastic tubules, suggestive of focal alterations in laminin-5 assembly and secretion. Laminin-5 gamma2 or beta3 subunit-reactive budding carcinoma cells expressed cytokeratins but not vimentin; they did not proliferate and were not apoptotic. Furthermore, expression of laminin-5 gamma2 and beta3 subunits in budding cells was associated with focal under-expression of the E-cadherin-beta-catenin complex. Results from xenograft experiments showed that budding activity in colorectal adenocarcinomas could be suppressed when these tumors grew at ectopic s.c. sites in nude mice. In vitro, cultured colon carcinoma cells, but not adenoma-derived tumor cells, shared the laminin-5 phenotype expressed by carcinoma cells in vivo. Using colon carcinoma cell lines implanted orthotopically and invading the cecum of nude mice, the laminin-5-associated budding was restored, indicating that this phenotype is not only determined by tumor cell properties but also dependent on the tissue micro-environment. Our results indicate that both laminin-5 alpha3 subunit expression and cell-cell cohesiveness are altered in budding carcinoma cells, which we consider to be actively invading. We propose that the local tissue micro-environment contributes to these events.

The role of microRNAs in the development of type 2 diabets

Pancreatic ß cells are highly specialized endocrine cells located within the islets of Langerhans in the pancreas. Their main role is to produce and secrete insulin, the hormone essential for the regulation of glucose homeostasis and body's metabolism. Diabetes mellitus develops when the amount of insulin released by ß cells is not sufficient to cover the metabolic demand. In type 1 diabetes (5-10% of diagnoses) insulin deficiency is caused by the autoimmune destruction of pancreatic ß cells. Type 2 diabetes (90% of diagnoses) results from a genetic predisposition and from the presence of adverse environmental conditions. The combination of these factors reduces insulin sensitivity of peripheral target tissues, causes impairment in ß-cell function and can lead to partial loss of ß cells. The development of novel therapeutic strategies for the treatment of diabetes necessitates the comprehension of the cellular processes involved in dysfunction and loss of ß cells. My thesis was focused on the involvement in the physiopathological processes leading to the development of diabetes of a class of small regulatory RNA molecules, called microRNAs (miRNAs) that post- transcriptionally regulate gene expression. Global miRNA profiling in pancreatic islets of two animal models of diabetes, the db/db mice and mice that were fed a high fat diet (HFD), characterized by obesity and insulin resistance, led us to identify two groups of miRNAs displaying expression changes under pre-diabetic and diabetic conditions. Among the miRNAs already upregulated in pre-diabetic db/db mice and HFD mice, miR- 132 was found to have beneficial effects on pancreatic ß cell function and survival. Indeed, mimicking the upregulation of miR-132 in primary pancreatic islet cells and ß-cell lines improved glucose- induced insulin secretion and favored survival of the cells upon exposure to pro-apoptotic stimuli such as palmitate and cytokines. MiR-132 was found to exert its action by enhancing the expression of MafA, a transcription factor essential for ß-cell function, survival and identity. On the other hand, up-regulation of miR-199a-5p and miR-199a-3p was detectable only in the islets of diabetic db/db mice and resulted in impaired insulin secretion and sensitization of the cells to apoptosis. MiR-199a- 5p was found to decrease insulin secretion by inducing the expression of granuphilin, a potent inhibitor of ß cell exocytosis. In contrast, miR-199a-3p was demonstrated to directly target and reduce the expression of two key ß-cell genes, mTOR and cMET, resulting in impaired ß-cell adaptation to metabolic demands and loss by apoptosis. Our findings suggest that miRNAs are important players in the onset of type 2 diabetes. MiRNA expression is adjusted in pancreatic ß cells exposed to a diabetogenic environment. These changes initially concern miRNAs responsible for adaptive processes aimed at compensating the onset of insulin resistance, but later such changes can be overlapped by modifications in the level of several additional miRNAs that favor ß-cell failure and the onset of type 2 diabetes.

Humic Haplustox under different land uses in a high altitude environment in the Agreste region of Pernambuco, Brazil

The Garanhuns Plateau in the Agreste region of the State of Pernambuco, Brazil is characterized by humid climatic conditions due to orographic rains, unlike the surrounding semiarid region. These soils are subjected to intense agricultural use and are extremely important for the regional economy. This study was carried out in the municipality of Brejão in the Agreste region with the aim of assessing changes in humic Haplustox soils subjected to different land uses. Four plots with different vegetation covers (native forest, secondary shrubby vegetation (capoeira), traditional cropping system, and planted pasture) were selected, and samples were taken from a soil profile and four small pits surrounding it at each site. Physical and chemical properties were assessed, including aggregate stability, humic organic fractions, and a microbiological evaluation through determination of basal respiration, microbial biomass carbon, and metabolic quotient. The soils under study showed physical and chemical properties typical of a Haplustox, such as low nutrient content, low cation exchange capacity, and high levels of acidity and Al saturation. The total organic carbon (TOC) contents were high regardless of the type of land use. Aggregates < 2 mm were dominant in all the conditions under study. The TOC content was higher in the soil under capoeira, 43.91 g kg-1 on the surface, while 34.36 and 33.43 g kg-1 of TOC were observed in the first layer of forest and pasture soils, respectively. While the microbial biomass C (MBC) was greater than 700 mg kg-1 in the forest and pasture areas (in the 0-5 cm layer), and 588 mg kg-1 in the soil under capoeira, these numbers were not statistically different. In the cultivated soil area, there was a reduction of around 28 % in TOC and MBC contents. Agricultural activity contributed to degradation of the humic horizon, as can be seen from a significant decrease in the TOC and changes in the relative distribution of the humic fractions. In contrast, aggregate stability was not altered as a function of the different land uses; the soil under planted pasture and capoeira were similar to the soil under native forest. Humin was the most important humified fraction for C reserves, contributing over 40 % of the TOC in these soils.

Manipulating the sensitivity of signal-induced repression: quantification and consequences of altered brinker gradients.

Traditionally, the analysis of gene regulatory regions suffered from the caveat that it was restricted to artificial contexts (e.g. reporter constructs of limited size). With the advent of the BAC recombineering technique, genomic constructs can now be generated to test regulatory elements in their endogenous environment. The expression of the transcriptional repressor brinker (brk) is negatively regulated by Dpp signaling. Repression is mediated by small sequence motifs, the silencer elements (SEs), that are present in multiple copies in the regulatory region of brk. In this work, we manipulated the SEs in the brk locus. We precisely quantified the effects of the individual SEs on the Brk gradient in the wing disc by employing a 1D data extraction method, followed by the quantification of the data with reference to an internal control. We found that mutating the SEs results in an expansion of the brk expression domain. However, even after mutating all predicted SEs, repression could still be observed in regions of maximal Dpp levels. Thus, our data point to the presence of additional, low affinity binding sites in the brk locus.

Nanotechnology: balancing benefits and risks to public health and the environment : expert paper

Nanotechnology has been heralded as a "revolution" in science, for two reasons: first, because of its revolutionary view of the way in which chemicals and elements, such as gold and silver, behave, compared to traditional scientific understanding of their properties. Second, the impact of these new discoveries, as applied to commerce, can transform the daily life of consumer products ranging from sun tan lotions and cosmetics, food packaging and paints and coatings for cars, housing and fabrics, medicine and thousands of industrial processes.9 Beneficial consumer use of nanotechnologies, already in the stream of commerce, improves coatings on inks and paints in everything from food packaging to cars. Additionally, "Nanomedicine" offers the promise of diagnosis and treatment at the molecular level in order to detect and treat presymptomatic disease,10 or to rebuild neurons in Alzheimer's and Parkinson's disease. There is a possibility that severe complications such as stroke or heart attack may be avoided by means of prophylactic treatment of people at risk, and bone regeneration may keep many people active who never expected rehabilitation. Miniaturisation of diagnostic equipment can also reduce the amount of sampling materials required for testing and medical surveillance. Miraculous developments, that sound like science fiction to those people who eagerly anticipate these medical products, combined with the emerging commercial impact of nanotechnology applications to consumer products will reshape civil society - permanently. Thus, everyone within the jurisdiction of the Council of Europe is an end-user of nanotechnology, even without realising that nanotechnology has touched daily life.

Self-organized evolution in a socio-economic environment

We propose a general scenario to analyze technological changes in socio-economic environments. We illustrate the ideas with a model that incorporating the main trends is simple enough to extract analytical results and, at the same time, sufficiently complex to display a rich dynamic behavior. Our study shows that there exists a macroscopic observable that is maximized in a regime where the system is critical, in the sense that the distribution of events follow power laws. Computer simulations show that, in addition, the system always self-organizes to achieve the optimal performance in the stationary state.

Calcineurin-Mediated Regulation of Hyphal Growth, Septation, and Virulence in Aspergillus fumigatus.

Calcineurin is a heterodimeric protein phosphatase complex composed of catalytic (CnaA) and regulatory (CnaB) subunits and plays diverse roles in regulating fungal stress responses, morphogenesis, and pathogenesis. Fungal pathogens utilize the calcineurin pathway to survive in the host environment and cause life-threatening infections. The immunosuppressive calcineurin inhibitors (FK506 and cyclosporine A) are active against fungi, making calcineurin a promising antifungal drug target. Here, we review novel findings on calcineurin localization and functions in Aspergillus fumigatus hyphal growth and septum formation through regulation of proteins involved in cell wall biosynthesis. Extensive mutational analysis in the functional domains of A. fumigatus CnaA has led to an understanding of the relevance of these domains for the localization and function of CnaA at the hyphal septum. An evolutionarily conserved novel mode of calcineurin regulation by phosphorylation in filamentous fungi was found to be responsible for virulence in A. fumigatus. This finding of a filamentous fungal-specific mechanism controlling hyphal growth and virulence represents a potential target for antifungal therapy.

Adaptive colour polymorphism of Acrida ungarica H. (Orthoptera: Acrididae) in a spatially heterogeneous environment

Intra-specific colour polymorphism provides a cryptic camouflage from predators in heterogeneous habitats. The orthoptera species, Acrida ungarica (Herbst, 1786) possess two well-distinguished colour morphs: brown and green and displays several disruptive colouration patterns within each morph to improve the crypsis. This study focused on how the features of the background environment relate to the proportion of the two morphs and to the intensity of disruptive colouration patterns in A. ungarica. As the two sexes are very distinct with respect to mass and length, we also distinctively tested the relationship for each sex. In accordance with the background matching hypothesis, we found that, for both sexes, the brown morph was in higher proportion at sites with a brown-dominant environment, and green morphs were in higher proportion in green-dominant environments. Globally, individuals in drier sites and in the drier year also had more intense disruptive colouration patterns, and brown morphs and females were also more striped. Colour patterns differed largely between populations and were significantly correlated with relevant environmental features. Even if A. ungarica is a polymorphic specialist, disruptive colouration still appears to provide strong benefits, particularly in some habitats. Moreover, because females are larger, they are less able to flee, which might explain the difference between sexes

Environment and dispersal paths override life strategies and residence time in determining regional patterns of invasion by alien plants.

We describe a novel dissimilarity framework to analyze spatial patterns of species diversity and illustrate it with alien plant invasions in Northern Portugal. We used this framework to test the hypothesis that patterns of alien invasive plant species richness and composition are differently affected by differences in climate, land use and landscape connectivity (i.e. Geographic distance as a proxy and vectorial objects that facilitate dispersal such as roads and rivers) between pairs of localities at the regional scale. We further evaluated possible effects of plant life strategies (Grime's C-S-R) and residence time. Each locality consisted of a 1 km(2) landscape mosaic in which all alien invasive species were recorded by visiting all habitat types. Multi-model inference revealed that dissimilarity in species richness is more influenced by environmental distance (particularly climate), whereas geographic distance (proxies for dispersal limitations) is more important to explain dissimilarity in species composition, with a prevailing role for ecotones and roads. However, only minor differences were found in the responses of the three C-S-R strategies. Some effect of residence time was found, but only for dissimilarity in species richness. Our results also indicated that environmental conditions (e.g. climate conditions) limit the number of alien species invading a given site, but that the presence of dispersal corridors determines the paths of invasion and therefore the pool of species reaching each site. As geographic distances (e.g. ecotones and roads) tend to explain invasion at our regional scale highlights the need to consider the management of alien invasions in the context of integrated landscape planning. Alien species management should include (but not be limited to) the mitigation of dispersal pathways along linear infrastructures. Our results therefore highlight potentially useful applications of the novel multimodel framework to the anticipation and management of plant invasions. (C) 2013 Elsevier GmbH. All rights reserved.

Iowa Utilities Board Fiscal Year 2013 Regulatory Plan Pursuant to Executive Order Nine

Iowa Utilities Board Fiscal Year 2008 Regulatory Plan Pursuant to Executive Order Nine.

Life-history evolution and the polyphenic regulation of somatic maintenance and survival.

Here we discuss life-history evolution from the perspective of adaptive phenotypic plasticity, with a focus on polyphenisms for somatic maintenance and survival. Polyphenisms are adaptive discrete alternative phenotypes that develop in response to changes in the environment. We suggest that dauer larval diapause and its associated adult phenotypes in the nematode (Caenorhabditis elegans), reproductive dormancy in the fruit fly (Drosophila melanogaster) and other insects, and the worker castes of the honey bee (Apis mellifera) are examples of what may be viewed as the polyphenic regulation of somatic maintenance and survival. In these and other cases, the same genotype can--depending upon its environment--express either of two alternative sets of life-history phenotypes that differ markedly with respect to somatic maintenance, survival ability, and thus life span. This plastic modulation of somatic maintenance and survival has traditionally been underappreciated by researchers working on aging and life history. We review the current evidence for such adaptive life-history switches and their molecular regulation and suggest that they are caused by temporally and/or spatially varying, stressful environments that impose diversifying selection, thereby favoring the evolution of plasticity of somatic maintenance and survival under strong regulatory control. By considering somatic maintenance and survivorship from the perspective of adaptive life-history switches, we may gain novel insights into the mechanisms and evolution of aging.

The rewards of cooperation: The effects of membership in European regulatory networks

Networks famously epitomize the shift from 'government' to 'governance' as governing structures for exercising control and coordination besides hierarchies and markets. Their distinctive features are their horizontality, the interdependence among member actors and an interactive decision-making style. Networks are expected to increase the problem-solving capacity of political systems in a context of growing social complexity, where political authority is increasingly fragmented across territorial and functional levels. However, very little attention has been given so far to another crucial implication of network governance - that is, the effects of networks on their members. To explore this important question, this article examines the effects of membership in European regulatory networks on two crucial attributes of member agencies, which are in charge of regulating finance, energy, telecommunications and competition: organisational growth and their regulatory powers. Panel analysis applied to data on 118 agencies during a ten-year period and semi-structured interviews provide mixed support regarding the expectation of organisational growth while strongly confirming the positive effect of networks on the increase of the regulatory powers attributed to member agencies.

Minimal analytical characterisation of engineered nanomaterials need for hazard assessment in biological matrices

The safe and responsible development of engineered nanomaterials (ENM), nanotechnology-based materials and products, together with the definition of regulatory measures and implementation of "nano"-legislation in Europe require a widely supported scientific basis and sufficient high quality data upon which to base decisions. At the very core of such a scientific basis is a general agreement on key issues related to risk assessment of ENMs which encompass the key parameters to characterise ENMs, appropriate methods of analysis and best approach to express the effect of ENMs in widely accepted dose response toxicity tests. The following major conclusions were drawn: Due to high batch variability of ENMs characteristics of commercially available and to a lesser degree laboratory made ENMs it is not possible to make general statements regarding the toxicity resulting from exposure to ENMs. 1) Concomitant with using the OECD priority list of ENMs, other criteria for selection of ENMs like relevance for mechanistic (scientific) studies or risk assessment-based studies, widespread availability (and thus high expected volumes of use) or consumer concern (route of consumer exposure depending on application) could be helpful. The OECD priority list is focussing on validity of OECD tests. Therefore source material will be first in scope for testing. However for risk assessment it is much more relevant to have toxicity data from material as present in products/matrices to which men and environment are be exposed. 2) For most, if not all characteristics of ENMs, standardized methods analytical methods, though not necessarily validated, are available. Generally these methods are only able to determine one single characteristic and some of them can be rather expensive. Practically, it is currently not feasible to fully characterise ENMs. Many techniques that are available to measure the same nanomaterial characteristic produce contrasting results (e.g. reported sizes of ENMs). It was recommended that at least two complementary techniques should be employed to determine a metric of ENMs. The first great challenge is to prioritise metrics which are relevant in the assessment of biological dose response relations and to develop analytical methods for characterising ENMs in biological matrices. It was generally agreed that one metric is not sufficient to describe fully ENMs. 3) Characterisation of ENMs in biological matrices starts with sample preparation. It was concluded that there currently is no standard approach/protocol for sample preparation to control agglomeration/aggregation and (re)dispersion. It was recommended harmonization should be initiated and that exchange of protocols should take place. The precise methods used to disperse ENMs should be specifically, yet succinctly described within the experimental section of a publication. 4) ENMs need to be characterised in the matrix as it is presented to the test system (in vitro/ in vivo). 5) Alternative approaches (e.g. biological or in silico systems) for the characterisation of ENMS are simply not possible with the current knowledge. Contributors: Iseult Lynch, Hans Marvin, Kenneth Dawson, Markus Berges, Diane Braguer, Hugh J. Byrne, Alan Casey, Gordon Chambers, Martin Clift, Giuliano Elia1, Teresa F. Fernandes, Lise Fjellsbø, Peter Hatto, Lucienne Juillerat, Christoph Klein, Wolfgang Kreyling, Carmen Nickel1, and Vicki Stone.