Identification of an active site in the antisecretory factor protein

AbstractThe antisecretory factor (AF) is a new regulatory protein, produced in the human pituitary gland, which reverses intestinal fluid secretion induced by cholera toxin. We have previously described the cDNA-cloning and characterization of the expressed gene. The aim of this study was to identify the region responsible for the antisecretory activity in the AF-molecule. The recombinant full-length AF has an increased ability to inhibit hypersecretion after treatment with trypsin, indicating that the activity of AF is achieved by smaller peptide fragments. To localize the active region of AF, we expressed truncated forms of the recombinant protein and examined their antisecretory activity against cholera toxin-induced fluid secretion in rat. Nine recombinant AF peptides and four smaller peptides made by solid phase synthesis were tested. Five of the peptides lacked all activity, whereas seven of them were highly active, a dose between 4 and 15pmol causing a half-maximal inhibition. All the active peptides contained amino acid 36–42 of the AF sequence, whereas none of the inactive peptides contained this sequence. Our results suggest that the site of the antisecretory activity resides in a small region (I)VCHSKTR between position 35 and 42 of the AF molecule

Paradigm Shift in Game Theory : Sociological Re-Conceptualization of Human Agency, Social Structure, and Agents’ Cognitive-Normative Frameworks and Action Determination Modalities

This article aims to present some of the initial work of developing a social science grounded game theory—as a clear alternative to classical game theory. Two distinct independent initiatives in Sociology are presented: One, a systems approach, social systems game theory (SGT), and the other, Erving Goffman’s interactionist approach (IGT). These approaches are presented and contrasted with classical theory. They focus on the social rules, norms, roles, role relationships, and institutional arrangements, which structure and regulate human behavior. While strategic judgment and instrumental rationality play an important part in the sociological approaches, they are not a universal or dominant modality of social action determination. Rule following is considered, generally speaking, more characteristic and more general. Sociological approaches, such as those outlined in this article provide a language and conceptual tools to more adequately and effectively than the classical theory describe, model, and analyze the diversity and complexity of human interaction conditions and processes: (1) complex cognitive rule based models of the interaction situation with which actors understand and analyze their situations; (2) value complex(es) with which actors operate, often with multiple values and norms applying in interaction situations; (3) action repertoires (rule complexes) with simple and complex action alternatives—plans, programs, established (sometimes highly elaborated) algorithms, and rituals; (4) a rule complex of action determination modalities for actors to generate and/or select actions in game situations; three action modalities are considered here; each modality consists of one or more procedures or algorithms for action determination: (I) following or implementing a rule or rule complex, norm, role, ritual, or social relation; (II) selecting or choosing among given or institutionalized alternatives according to a rule or principle; and (III) constructing or adopting one or more alternatives according to a value, guideline, or set of criteria. Such determinations are often carried out collectively. The paper identifies and illustrates in a concluding table several of the key differences between classical theory and the sociological approaches on a number of dimensions relating to human agency; social structure, norms, institutions, and cultural forms; patterns of game interaction and outcomes, the conditions of cooperation and conflict, game restructuring and transformation, and empirical relevance. Sociologically based game theory, such as the contributions outlined in this article suggest a language and conceptual tools to more adequately and effectively than the classical theory describe, model, and analyze the diversity, complexity, and dynamics of human interaction conditions and processes and, therefore, promises greater empirical relevance and scientific power. An Appendix provides an elaboration of SGT, concluding that one of SGT’s major contributions is the rule based conceptualization of games as socially embedded with agents in social roles and role relationships and subject to cognitive-normative and agential regulation. SGT rules and rule complexes are based on contemporary developments relating to granular computing and Artificial Intelligence in general.Peer reviewe

En studie om kontaktmännens upplevelser av utslussningsarbetet inne på en klass 1 anstalt i Sverige - "Det är ju inte kriminaliteten man behandlar utan det är människan..."

Authors: Ewa Johansson Sölberg & Vanessa Tuuliainen Title: A Study of the Liaisons’ Experience of the Work Situation Inside A Swedish High Security Penitentiary – “It’s Not the Criminality You Are Treating, It’s the Human…” Supervisor: Johan Cronehed Assessor: Lars B Ohlsson The goal of this study was to identify the liaison’s experience of working with transitioning prisoners from a Swedish high security penitentiary into society. The specific goal was to identify what their observations were and what experience they have gained with regards to this profession. The study is based on five different qualitative semi-structured interviews held with liaison staff at a Swedish high security penitentiary. The interviews were carried out with the aid of a guiding document. Together with each liaison we formed discussions around relevant themes. As a result of the interviews we found two main concepts, these were relationships and profession. We have analyzed these concepts from a point of view of discretion. Our conclusion was that the liaison has a certain amount of discretion in its profession, and mainly in the aspects of creating relationships and in forming its professional role. Key words: Liaison, discretion, relationship creation, penitentiar

Cell wall acetylation in hybrid aspen affects field performance, foliar phenolic composition and resistance to biological stress factors in a construct-dependent fashion

The production of biofuels and “green” chemicals from the lignocellulose of fast-growing hardwood species is hampered by extensive acetylation of xylan. Different strategies have been implemented to reduce xylan acetylation, resulting in transgenic plants that show good growth in the greenhouse, improved saccharification and fermentation, but the field performance of such plants has not yet been reported. The aim of this study was to evaluate the impact of reduced acetylation on field productivity and identify the best strategies for decreasing acetylation. Growth and biological stress data were evaluated for 18 hybrid aspen lines with 10–20% reductions in the cell wall acetyl content from a five year field experiment in Southern Sweden. The reduction in acetyl content was achieved either by suppressing the process of acetylation in the Golgi by reducing expression of REDUCED WALL ACETYLATION(RWA) genes, or by post-syntheticacetyl removal by fungal acetyl xylan esterases (AXEs) from two different families, CE1and CE5, targeting them to cell walls. Transgene expression was regulated by either a constitutive promoter (35S)or a wood-specific promoter (WP). For the majority of transgenic lines, growth was either similar to that in WT and transgenic control (WP:GUS)plants, or slightly reduced. The slight reduction was observed in the AXE-expressing lines regulated by the 35S promoter, not those with the WPpromoter which limits expression to cells developing secondary walls. Expressing AXEs regulated by the 35S promoter resulted in increased foliar arthropod chewing, and altered condensed tannins and salicinoid phenolic glucosides (SPGs) profiles. Greater growth inhibition was observed in the case of CE5 than with CE1 AXE, and it was associated with increased foliar necrosis and distinct SPG profiles, suggesting that CE5 AXE could be recognized by the pathogen-associated molecular pattern system. For each of three different constructs, there was a line with dwarfism and growth abnormalities, suggesting random genetic/epigenetic changes. This high frequency of dwarfism (17%)is suggestive of a link between acetyl metabolism and chromatin function. These data represent the first evaluation of acetyl-reduced plants from the field, indicating some possible pitfalls, and identifying the best strategies, when developing highly productive acetyl-reduced feedstocks

Discontinuation of follow-up care for young people with complex chronic conditions: conceptual definitions and operational components

Background A substantial proportion of young people with Complex Chronic Conditions (CCCs) experience some degree of discontinuation of follow-up care, which is an umbrella term to describe a broken chain of follow-up. Discontinuation of follow-up care is not clearly defined, and the great plethora of terms used within this field cannot go unnoticed. Terms such as “lost to follow-up”, “lapses in care” and “care gaps”, are frequently used in published literature, but differences between terms are unclear. Lack of uniformity greatly affects comparability of study findings. The aims of the present study were to (i) provide a systematic overview of terms and definitions used in literature describing discontinuation of follow-up care in young people with CCC’s; (ii) to clarify operational components of discontinuation of follow-up care (iii); to develop conceptual definitions and suggested terms to be used; and (iv) to perform an expert-based evaluation of terms and conceptual definitions. Methods A systematic literature search performed in PubMed was used to provide an overview of current terms used in literature. Using a modified summative content analysis, operational components were analysed, and conceptual definitions were developed. These conceptual definitions were assessed by an expert panel using a survey. Results In total, 47 terms and definitions were retrieved, and a core set of operational components was identified. Three main types of discontinuation of follow-up care emerged from the analysis and expert evaluation, conceptually defined as follows: Lost to follow-up care: “No visit within a defined time period and within a defined context, and the patient is currently no longer engaged in follow-up care”; Gap in follow-up care: “Exceeded time interval between clinic visits within a defined context, and the patient is currently engaged in follow-up care”; and Untraceability: “Failure to make contact due to lack of contact information”. Conclusion By creating a common vocabulary for discontinuation of follow-up care, the quality of future studies could improve. The conceptual definitions and operational components provide guidance to both researchers and healthcare professionals focusing on discontinuation of follow-up care for young people with CCCs

Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts

<p>Abstract</p> <p>Background</p> <p>The kynurenine pathway (KP) is the main route of tryptophan degradation in the human body and generates several neuroactive and immunomodulatory metabolites. Altered levels of KP-metabolites have been observed in neuropsychiatric and neurodegenerative disorders as well as in patients with affective disorders. The purpose of the present study was to investigate if skin derived human fibroblasts are useful for studies of expression of enzymes in the KP.</p> <p>Methods</p> <p>Fibroblast cultures were established from cutaneous biopsies taken from the arm of consenting volunteers. Such cultures were subsequently treated with interferon (IFN)-γ 200 U/ml and/or tumor necrosis factor (TNF)-α, 100 U/ml for 48 hours in serum-free medium. Levels of transcripts encoding different enzymes were determined by real-time PCR and levels of kynurenic acid (KYNA) were determined by HPLC.</p> <p>Results</p> <p>At base-line all cultures harbored detectable levels of transcripts encoding KP enzymes, albeit with considerable variation across individuals. Following cytokine treatment, considerable changes in many of the transcripts investigated were observed. For example, increases in the abundance of transcripts encoding indoleamine 2,3-dioxygenase, kynureninase or 3-hydroxyanthranilic acid oxygenase and decreases in the levels of transcripts encoding tryptophan 2,3-dioxygenase, kynurenine aminotransferases or quinolinic acid phosphoribosyltransferase were observed following IFN-γ and TNF-α treatment. Finally, the fibroblast cultures released detectable levels of KYNA in the cell culture medium at base-line conditions, which were increased after IFN-γ, but not TNF-α, treatments.</p> <p>Conclusions</p> <p>All of the investigated genes encoding KP enzymes were expressed in human fibroblasts. Expression of many of these appeared to be regulated in response to cytokine treatment as previously reported for other cell types. Fibroblast cultures, thus, appear to be useful for studies of disease-related abnormalities in the kynurenine pathway of tryptophan degradation.</p

Impacts of direct payments – lessons for CAP post-2020 from a quantitative analysis

In this report we aim to analyse the economic and environmental impacts of Pillar I direct payments, and to demonstrate alternative instruments that are better suited to achieve CAP objectives. The instruments—a targeted payment to land at risk of abandonment and a tax on mineral fertilisers—were selected on the basis of the Polluter Pays and Provider Gets Principles. We do this using two state‐of‐the‐art agricultural economic simulation models. The first model, CAPRI, is used to quantify the large‐scale or aggregate impacts for individual countries, the EU and the world. The other model, AgriPoliS, is used to quantify the fine‐scale or farm and field level impacts in a selection of contrasting agricultural regions, to consider the potential influence of the large spatial variability in agricultural and environmental conditions across the EU. The results show that direct payments are keeping more farms in the sector and more land in agricultural use than would otherwise be the case, and thus avoiding land abandonment, principally in marginal regions. Particularly the area of grassland is substantially higher, because it is generally less productive than arable land and hence more dependent on direct payments for keeping it in agricultural use. The magnitudes of the impacts of direct payments on land use therefore vary strongly across regions due to spatial variability in productivity: marginal regions with large areas of less productive land are heavily influenced by direct payments, while regions with large areas of relatively productive land are hardly affected, because this land would be farmed in any case. By keeping more farmers in the sector longer, direct payments are slowing structural change, which can hamper agricultural development. However the potential benefits of faster structural change vary considerably among our study regions. In relatively productive regions direct payments are hindering development, because too many farmers are staying in the sector and preventing the consolidation of land in larger farms, which would improve their competitiveness and increase farm profits. On the contrary, the mass departure of farms that is currently avoided, will not lead to the same general benefits in marginal regions. Instead of freed land being absorbed by remaining farms, large areas of relatively unproductive land are abandoned without payments. This land is unprofitable to maintain in agricultural land use, even if integrated into larger farms, because current market prices are too low to motivate farming it. Consequently direct payments pose a serious goal conflict: the avoidance of land abandonment on the one hand, which can have negative impacts on public goods, and restricting agricultural development on the other hand. Once again this goal conflict is rooted in the spatial variability of agricultural conditions in the EU. Maintaining extensively managed farmland, particularly semi‐natural pastures, is central for conservation of biodiversity and preservation of the cultural landscape. Therefore direct payments are contributing to the provisioning of these public goods, but principally in marginal areas. Further, abandonment of land can reduce its agricultural productivity due to erosion or afforestation. Thus, direct payments are contributing to food security by preserving the productive potential of land for the future, but only marginal land since relatively productive land is farmed in any case. Production of agricultural commodities is affected to a lesser degree by direct payments than land use per se. Nevertheless, food exports from the EU are higher and imports lower as a consequence of direct payments. However, the additional supply generated by direct payments also lowers output prices, which reduces the profitability of commodity production; thereby partially offsetting the additional revenues from direct payments. The higher agricultural output brought about by direct payments causes higher levels of environmentally damaging greenhouse‐gas emissions, nutrient surpluses and pesticide use. The higher greenhouse‐gas emissions for the EU are, to some extent, moderated by lower emissions in the rest of the world. Nevertheless, the net effect of direct payments is higher global emissions of greenhouse gases. The environmental impacts of higher nutrient surpluses and pesticide inputs are less conclusive, since these depend also on spatial factors, i.e., where the emissions occur. Although EU‐scale and regional emissions are higher due to direct payments, agricultural production is less intensive generally, on account of the lower output prices. Analysing the net effects of these two opposing forces requires additional biophysical modelling at relevant spatial scales, such as watersheds or landscapes, which is beyond the scope of this study. Pillar I direct payments generate a significant transfer of income to farmers and land owners who are not necessarily farmers; 40 billion euro annually. Of this transfer a substantial proportion goes to farmers in relatively productive regions and, further, to a minority of farmers that need them least. In relatively productive regions payments are not needed for continued agricultural production and preservation of farmland, but instead rather fuel higher land and rental prices, which hampers structural change. On the contrary, the need for support is greatest in marginal regions, because some form of payment to marginal land is needed to avoid its abandonment and the loss of associated public goods. Finally, the direct payments even come at the cost of lower market returns for farmers due to slower structural change (smaller and less competitive farms) and lower output prices (due to greater EU output). On the other hand the lower output prices lead to somewhat lower food prices, but at the greater cost of financing the direct payments. Our main conclusion is that Pillar I direct payments are generating serious goal conflicts due to spatial variability in conditions across the EU. On the one hand these payments are contributing to the provisioning of public goods by preserving marginal agricultural land. On the other hand they are hampering agricultural development, primarily in relatively productive regions. Payments to relatively productive land that would be farmed any way not only inflate land values (capitalisation) but also slow structural change, which are both likely to hinder agricultural development and hence the competitiveness of the EU on the global market. The direct payments also increase environmental pressure; by subsidising land use generally and the associated production, they are incapable of controlling environmentally damaging emissions, which is also in conflict with broad CAP objectives. The goal conflict arises because direct payments are universal, a payment principal that does not consider spatial variability in the EU and the associated trade‐offs in regard to development and environmental effectiveness. Our analysis considered two alternative policy instruments that have the potential to curb the identified goal conflicts associated with direct payments, by applying the Polluter Pays and Provider (of public goods) Gets Principles at appropriate spatial scales. Replacing direct payments with a payment targeted on marginal land (and associated public goods) prevents land abandonment at a lower cost, by avoiding payments to relatively productive land that is farmed in any case. This also allows surviving farms in regions with relatively productive land to compensate for lost direct payments through expansion and associated scale economies, as well as higher output prices. This instrument therefore finances the provisioning of public goods without adverse effects on development and the efficiency of agricultural production. The EU‐wide tax on mineral fertiliser demonstrates that this instrument has the potential to reduce nutrient surpluses. Since direct payments cause higher levels of polluting emissions, policy instruments targeting emissions at relevant spatial scales are needed to achieve cost‐effective abatement. Overall we find that Pillar I direct payments are not addressing the diversity of challenges facing European agriculture. In fact our quantitative analysis indicates that the potential for the current system to meet these challenges is seriously impaired by goal conflicts and spatial variability across the EU. A better policy requires that instruments are targeted on desired outcomes and designed according to sound principles, specifically the Polluter Pays and Provider Gets Principles. These principles would ensure that farmers are provided with appropriate incentives to i) generate public goods that otherwise would be underprovided; ii) mitigate environmentally damaging emissions at the lowest possible cost to society; and iii) continually strive to improve environmental performance. Such instruments are also fairer and promote a more competitive or viable agricultural sector by not obstructing structural change and hence agricultural development