Mice carrying ubiquitin-specific protease 2 (Usp2) gene inactivation maintain normal sodium balance and blood pressure

Ubiquitylation plays an important role in the control of Na⁺ homeostasis by the kidney. It is well established that the epithelial Na⁺ channel ENaC is regulated by the ubiquitin-protein ligase NEDD4-2, limiting ENaC cell surface expression and activity. Ubiquitylation can be reversed by the action of deubiquitylating enzymes (DUBs). One such DUB, USP2-45, was identified previously as an aldosterone-induced protein in the kidney and is also a circadian output gene. In heterologous expression systems, USP2-45 binds to ENaC, deubiquitylates it, and enhances channel density and activity at the cell surface. Because the role of USP2-45 in renal Na⁺ transport had not been studied in vivo, we investigated here the effect of Usp2 gene inactivation in this process. We demonstrate first that USP2-45 protein has a rhythmic expression with a peak at ZT12. Usp2-KO mice did not show any differences from wild-type littermates with respect to the diurnal control of Na⁺ or K⁺ urinary excretion and plasma levels either on a standard diet or after acute and chronic changes to low- and high-Na⁺ diets, respectively. Moreover, they had similar aldosterone levels on either a low- or high-Na⁺ diet. Blood pressure measurements using telemetry did not reveal variations compared with control mice. Usp2-KO mice did not display alterations in expression of genes involved in sodium homeostasis or the ubiquitin system, as evidenced by transcriptome analysis in the kidney. Our data suggest that USP2 does not play a primary role in the control of Na⁺ balance or blood pressure.

Ecosystem service trade-offs and stakeholder claims - a meso-scale study from a Madagascar biodiversity hotspot

The north-eastern escarpment of Madagascar has been labelled a global biodiversity hotspot due to its extremely high rates of endemic species which are heavily threatened by accelerated deforestation rates and landscape change. The traditional practice of shifting cultivation or "tavy" used by the majority of land users in this area to produce subsistence rice is commonly blamed for these threats. A wide range of stakeholders ranging from conservation to development agencies, and from the private to the public sector has therefore been involved in trying to find solutions to protect the remaining forest fragments and to increase agricultural production. Consequently, provisioning, regulating and socio-cultural services of this forest-mosaic landscape are fundamentally altered leading to trade-offs between them and consequently new winners and losers amongst the stakeholders at different scales. However, despite a growing amount of evidence from case studies analysing local changes, the regional dynamics of the landscape and their contribution to such trade-offs remain poorely understood. This study therefore aims at using generalised landscape units as a base for the assessment of multi-level stakeholder claims on ecosystem services to inform negotiation, planning and decision making at a meso-scale. The presented study applies a mixed-method approach combining remote sensing, GIS and socio-economic methods to reveal current landscape dynamics, their change over time and the corresponding ecosystem service trade-offs induced by diverse stakeholder claims on the regional level. In a first step a new regional land cover classification for three points in time (1995, 2005 and 2011) was conducted including agricultural classes characteristic for shifting cultivation systems. Secondly, a novel GIS approach, termed “landscape mosaics approach” originally developed to assess dynamics of shifting cultivation landscapes in Laos was applied. Through this approach generalised landscape mosaics were generated allowing for a better understanding of changes in land use intensities instead of land cover. As a next step we will try to use these landscape units as proxies to map provisioning and regulating ecosystem services throughout the region. Through the overlay with other regional background data such as accessibility and population density and information from a region-wide stakeholder analysis, multiscale trade-offs between different services will be highlighted. The trade-offs observed on the regional scale will then be validated through a socio-economic ground-truthing within selected sites at the local scale. We propose that such meso-scale knowledge is required by all stakeholders involved in decision making towards sustainable development of north-eastern Madagascar.

The Impact of a Brief Intervention on Medical Students' Readiness to Screen for DV - Changes in Decisional Balance and Self-Efficacy

Introduction: Domestic violence (DV) affects millions of Americans each year. Yet, there is a dearth of theory-based DV curricula, resulting in physicians unprepared to screen for DV. This study utilized a survey based on constructs from the Transtheoretical Model to assess the readiness of first- and second-year medical students to screen for DV. Information from this survey will be used to help institutionalize DV education into the medical curriculum. [See PDF for complete abstract]

EU trade agreements and their impacts on human rights: study commissioned by the German Federal Ministry for Economic Cooperation and Development (BMZ)

The European Union’s (EU) trade policy has a strong influence on economic development and the human rights situation in the EU’s partner countries, particularly in developing countries. The present study was commissioned by the German Federal Ministry for Economic Cooperation and Development (BMZ) as a contribution to further developing appropriate methodologies for assessing human rights risks in development-related policies, an objective set in the BMZ’s 2011 strategy on human rights. The study offers guidance for stakeholders seeking to improve their knowledge of how to assess, both ex ante and ex post, the impact of Economic Partnership Agreements on poverty reduction and the right to food in ACP countries. Currently, human rights impacts are not yet systematically addressed in the trade sustainability impact assessments (trade SIAs) that the European Commission conducts when negotiating trade agreements. Nor do they focus specifically on disadvantaged groups or include other benchmarks relevant to human rights impact assessments (HRIAs). The EU itself has identified a need for action in this regard. In June 2012 it presented an Action Plan on Human Rights and Democracy that calls for the inclusion of human rights in all impact assessments and in this context explicitly refers to trade agreements. Since then, the EU has begun to slightly adapt its SIA methodology and is working to define more adequate human rights–consistent procedures. It is hoped that readers of this study will find inspiration to help contribute to this process and help improve human rights consistency of future trade options.

Mass Balance and Accumulation Rate Across Siple Dome, West Antarctica

Snow-accumulation rates and rates of ice-thickness change (mass balance) are studied at several sites on Siple Dome, West Antarctica. Accumulation rates are derived from analyses of gross beta radioactivity in shallow firn cores located along a 60 km transect spanning both flanks and the crest of the dome. There is a north-south gradient in snow-accumulation rate across the dome that is consistent with earlier radar mapping of internal stratigraphy. Orographic processes probably control this distribution. Mass balance is inferred from the difference between global positioning system (GPS)-derived vertical velocities and snow-accumulation rates for sites close to the firn-core locations. Results indicate that there is virtually no net thickness change at four of the five sites. The exception is at the northernmost site where a small amount of thinning is detected, that appears to be inconsistent with other studies. A possible cause of this anomalous thinning is recent retreat of the grounding line of Ice Stream D.

The European Union, the World Trade Organization and Cultural Diversity

The chapter maps these trade versus culture developments in the WTO and the positions of the European Union (EU or the Union) and its member states, which were not always coherent. It also looks at the actual results of the trade versus culture contestation – that is, the rules on trade in goods and services in the WTO and how they reflect the need for more policy space in matters of cultural policy, which the EU so ardently pressed for. The chapter further analyses the evolution of both the international trade regulation and the discourse on cultural policy. This discourse has in fact undergone a major transformation in the last two decades, as it has moved from the ‘exception culturelle’ rhetoric, which dominated the Uruguay trade talks, towards a more positive but also more pro-active agenda under the slogan of cultural diversity. The EU has been a major driver of this transformation, which has succeeded in mobilising the international community and ultimately led to the adoption of the 2005 UNESCO Convention on the Protection and Promotion of the Diversity of Cultural Expressions. The chapter concludes by appraisal of the current state of the debate situating it into the broader picture of contemporary global governance. It asks how the EU could effectively pursue its cultural policy aspirations and endorse its cultural diversity agenda in a world of complexity and rapid technological change, in particular in view of the affordances of digital media.

Regional Trade Agreements and domestic labour market regulation

This chapter discusses the relationship between labour market regulation and regional trade agreements from both a legal and an economic angle. We examine empirically whether regional trade liberalisation is associated with deterioration (“race to the bottom”) of domestic labour standards beyond those reflected in the 1998 ILO Declaration on the Fundamental Principles and Rights at Work. Using a panel of 90 developed and developing countries, covering the years from 1980 to 2005, we find that after the entry into force of a regional trade agreement (RTA), labour standards applying to employment protection and unemployment benefits are significantly weakened. We show that such a lowering of protection levels tends to occur in high income countries and that this effect mainly stems from RTAs among such countries rather than with low or middle income countries. Concern about competitive pressure to weaken domestic labour regulation is reflected in a variety of undertakings in RTAs not to administer labour laws with a view to improving one’s competitive position in trade or foreign direct investment (FDI). The above-mentioned empirical findings indicate that such provisions could potentially become relevant, and that this is more likely to be the case for high income members of RTAs. Our analysis, from a legal point of view, of relevant institutional and procedural mechanisms indicates however that enforceability of the relevant provisions is weak for most of the existing legal texts.

Glucocorticoid alterations in the human type-1/type-2 cytokine balance and the role of CD28/B7 costimulation

We have recently reported that psychological stress is associated with a shift in the human type-1/type-2 cytokine balance toward a type-2 cytokine response. The mechanisms of these cytokine alterations are unknown, but likely involve glucocorticoid (GC) modulation of cytokine production. Therefore we sought to characterize the effects of GC on the in vitro human type-1/type-2 cytokine balance. We hypothesized that GC induce a type-2 cytokine shift through modulation of critical regulatory cytokines and alterations in the CD28/B7 costimulatory pathway. ^ We first sought to characterize the effect of the GC, dexamethasone (DEX), on type-1 (IFN-γ, IL-12) and type-2 (IL-4, IL-10) cytokine production by human peripheral blood mononuclear blood cells (pBMC) stimulated with a variety of T-lymphocyte and monocyte stimuli. DEX, at concentrations mimicking stress and supraphysiologic levels of cortisol, decreased IFN-γ and IL-12 production and increased IL-4 and IL-10 production, indicating a shift in the type-1/type-2 cytokine balance toward a type-2 response. Furthermore, both CD4+ and CD8+ T-lymphocytes were susceptible to the cytokine modulating effects of DEX. Furthermore, in the absence of the monocyte, the DEX-induced alterations in T-lymphocyte cytokine production were reduced, indicating that the interaction between the monocyte and T-lymphocyte plays a significant role. ^ We next determined the role of regulatory cytokines, known to modulate the type-1/type-2 cytokine balance, in the DEX-induced cytokine alterations. The addition of the recombinant IL-12p70 and IFN-γ, but not the neutralization of IL-4, IL-10 or IL-13 using monoclonal antibodies, attenuated the DEX-induced type-1/type-2 cytokine alterations. These data suggest that the DEX-induced cytokine alterations are mediated, at least in part, through the initial inhibition type-1 cytokines. Lastly, we investigated the role of the CD28/B7 costimulatory pathway in these cytokine alterations. DEX decreased the expression of CD80 and CD86 on THP-1 cells, a monocyte cell line, and the expression of CD28 and CTLA-4 on PHA-stimulated pBMC. The DEX-induced decrease in CD28 and CTLA-4 expression was attenuated by rhIL-12. Finally, CD28 activation attenuated the DEX-induced decrease in IFN-γ production, suggesting that modulation of the CD28/B7 costimulatory pathway may contribute to the DEX-induced type-1/type-2 cytokine alterations. ^

17-beta estradiol and progesterone-induced alterations in human type-1/type-2 cytokine balance and the role of costimulatory and apoptotic mechanisms

Evidence suggests that sex-based differences in immune function may predispose women to numerous hypersensitivity conditions such as Systemic lupus erythematosus (SLE), Hashimoto's thyroiditis and asthma. To date, the exact mechanisms of sexual dimorphism in immunity are not fully characterized but sex hormones such as 17-β estradiol (E2) and progesterone (PR) are believed to be involved. Since E2 and PR may modulate the production of critical regulatory cytokines, we sought to characterize their effects on the in vitro human type-1/type-2 cytokine balance. We hypothesized that E2 and/or PR vary cytokine production and influence costimulatory molecule expression and apoptosis. We first described the effect of E2 and/or PR on type-1 (IFN-γ and IL-12) and type-2 (IL-4 and IL-10) cytokine production by human peripheral blood mononuclear cells (PBMC) treated with various T-lymphocyte and monocyte stimuli. E2 and/or PR were each used at concentrations similar to those found at the maternal-fetal interface during pregnancy. At this dose, E2 increased IFN-γ and IL-12 production and PR decreased IFN-γ production and tended to increase IL-4 production. Furthermore, the combination of E2+PR decreased IL-12 production. This suggests that E2 shifts the type-1/type-2 cytokine balance towards a type-1 response and that PR and E2+PR shift the balance towards a type-2 response. Next, we used intracellular cytokine detection to demonstrate that E2 and/or PR are capable of altering cytokine production of CD3+ T-cells and the CD3+CD4+ and CD3+CD8+ subsets. In addition, we used the H9 T-lymphocyte cell line and the THP-1 monocyte cell line to show that E2 and/or PR can induce cytokine effects in both T-cells and monocytes independent of their interaction. Lastly, we determined the effect of E2 and/or PR on costimulatory molecule expression and apoptosis as potential mechanisms for the cytokine-induced alterations. E2 increased and PR decreased CD80 expression on THP-1 cells and PR and E2+PR decreased CD28 expression in PBMC and Jurkat cells. Furthermore, E2, PR and E2+PR increased Fas-mediated apoptosis in Jurkat cells and E2 increased FasL expression on THP-1 cells. Thus, E2 and/or PR may alter the cytokine balance by modulating the CD28/CD80 costimulatory pathway and apoptosis. ^

The Effects of Trade Orientation and Human Capital on Total Factor Productivity

We study the effects of trade orientation and human capital on total factor productivity for a pooled cross-section, time-series sample of developed and developing countries. We first estimate total factor productivity from a parsimonious specification of the aggregate production function involving output per worker, capital per worker, and the labor force, both with and without the stock of human capital. Then we consider a number of potential determinants of total factor productivity growth including several measures of trade orientation as well as a measure of human capital. We find that a high degree of openness benefits total factor productivity and that human capital contributes to total factor productivity only after our measure of openness passes some threshold level. Before that threshold, increases in human capital actually depress total factor productivity. Finally, we also consider the issue of convergence of real GDP per worker and total factor productivity, finding more evidence of convergence for the latter than for the former.

Assessing residents' readiness to screen for domestic violence: Utilizing the transtheoretical model - stages of change, decisional balance and self-efficacy

Domestic violence is a major public health problem, yet most physicians do not effectively identify patients at risk. Medical students and residents are not routinely educated on this topic and little is known about the factors that influence their decisions to include screening for domestic violence in their subsequent practice. In order to assess the readiness of primary care residents to screen all patients for domestic violence, this study utilized a survey incorporating constructs from the Transtheoretical Model, including Stages of Change, Decisional Balance (Pros and Cons) and Self-Efficacy. The survey was distributed to residents at the University of Texas Health Science Center Medical School in Houston in: Internal Medicine, Medicine/Pediatrics, Pediatrics, Family Medicine, and Obstetrics and Gynecology. Data from the survey was analyzed to test the hypothesis that residents in the earlier Stages of Change report more costs and fewer benefits with regards to screening for domestic violence, and that those in the later stages exhibit higher Self-Efficacy scores. The findings from this study were consistent with the model in that benefits to screening (Pros) and Self-Efficacy were correlated with later Stages of Change, however reporting fewer costs (Cons) was not. Very few residents were ready to screen all of their patients.^

Increased CO2 modifies the carbon balance and the photosynthetic yield of two common Arctic brown seaweeds: Desmarestia aculeata and Alaria esculenta

Ocean acidification affects with special intensity Arctic ecosystems, being marine photosynthetic organisms a primary target, although the consequences of this process in the carbon fluxes of Arctic algae are still unknown. The alteration of the cellular carbon balance due to physiological acclimation to an increased CO2 concentration (1300 ppm) in the common Arctic brown seaweeds Desmarestia aculeata and Alaria esculenta from Kongsfjorden (Svalbard) was analysed. Growth rate of D. aculeata was negatively affected by CO2 enrichment, while A. esculenta was positively affected, as a result of a different reorganization of the cellular carbon budget in both species. Desmarestia aculeata showed increased respiration, enhanced accumulation of storage biomolecules and elevated release of dissolved organic carbon, whereas A. esculenta showed decreased respiration and lower accumulation of storage biomolecules. Gross photosynthesis (measured both as O2 evolution and 14C fixation) was not affected in any of them, suggesting that photosynthesis was already saturated at normal CO2 conditions and did not participate in the acclimation response. However, electron transport rate changed in both species in opposite directions, indicating different energy requirements between treatments and species specificity. High CO2 levels also affected the N-metabolism, and 13C isotopic discrimination values from algal tissue pointed to a deactivation of carbon concentrating mechanisms. Since increased CO2 has the potential to modify physiological mechanisms in different ways in the species studied, it is expected that this may lead to changes in the Arctic seaweed community, which may propagate to the rest of the food web.

Acid-base balance and changes in haemolymph properties of the South African rock lobsters, Jasus lalandii, a palinurid decapod, during chronic hypercapnia

Few studies exist reporting on long-term exposure of crustaceans to hypercapnia. We exposed juvenile South African rock lobsters, Jasus lalandii, to hypercapnic conditions of pH 7.3 for 28 weeks and subsequently analysed changes in the extracellular fluid (haemolymph). Results revealed, for the first time, adjustments in the haemolymph of a palinurid crustacean during chronic hypercapnic exposure: 1) acid-base balance was adjusted and sustained by increased bicarbonate and 2) quantity and oxygen binding properties of haemocyanin changed. Compared with lobsters kept under normocapnic conditions (pH 8.0), during prolonged hypercapnia, juvenile lobsters increased bicarbonate buffering of haemolymph. This is necessary to provide optimum pH conditions for oxygen binding of haemocyanin and functioning of respiration in the presence of a strong Bohr Effect. Furthermore, modification of the intrinsic structure of the haemocyanin molecule, and not the presence of molecular modulators, seems to improve oxygen affinity under conditions of elevated pCO2.