Bio-availability of phosphorus in sediments of the western Dutch Wadden Sea

The purpose of this study was to make a prognosis of the effects of extended purification of terrestrial waste water, reaching the Wadden Sea by the River Rhine and Lake IJssel, on the phosphate concentration in the western Wadden Sea.The quantities of different phosphorus fractions in intertidal and subtidal sediments of the Marsdiep tidal basin (western Dutch Wadden Sea) were measured. Different methods are applied to determine the amount of phosphorus that can be released from these sediments. The direct bioavailability is determined by inoculating sediment suspensions with a natural mixture of precultured micro-organisms from the sampling area. A second approach is the measurement of the phosphate release under different redox conditions. Sequential extraction of sediment samples with different solvents is also applied. Under the present conditions and compared to the nutrient loads from fresh water (Lake IJssel) and from the North Sea, the phosphorus stored in the sediments of the western Dutch Wadden Sea plays a minor role in the total supply to micro-algae and bacteria. The bulk of the biologically available phosphorus in the sediments originates from the metal-associated fraction. Releasable phosphate may contribute to the local annual primary production to an extent of ca 45 to ca 150 g C m^–2 a^–1. The total amount of phosphorus in the sediment (mainly calcite associated) is twice to 6 times the biologically available amount.     

PXR agonism decreases plasma HDL levels in ApoE⁎3-Leiden.CETP mice

Pregnane X receptor (PXR) agonism has been shown to affect multiple steps in both the synthesis and catabolism of HDL, but its integrated effect on HDL metabolism in vivo remains unclear. The aim of this study was to evaluate the net effect of PXR agonism on HDL metabolism in ApoE?3-Leiden (E3L) and E3L.CETP mice, well-established models for human-like lipoprotein metabolism. Female mice were fed a diet with increasing amounts of the potent PXR agonist 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN). In E3L and E3L.CETP mice, PCN increased liver lipids as well as plasma cholesterol and triglycerides. However, whereas PCN increased cholesterol contained in large HDL-1 particles in E3L mice, it dose-dependently decreased HDL-cholesterol in E3L.CETP mice, indicating that CETP expression dominates the effect of PCN on HDL metabolism. Analysis of the hepatic expression of genes involved in HDL metabolism showed that PCN decreased expression of genes involved in HDL synthesis (Abca1, Apoa1), maturation (Lcat, Pltp) and clearance (Sr-b1). The HDL-increasing effect of PCN, observed in E3L mice, is likely caused by a marked decrease in hepatic SR-BI protein expression, and completely reversed by CETP expression. We conclude that chronic PXR agonism dose-dependently reduces plasma HDL-cholesterol in the presence of CETP.     

A RNA interference screen identifies the protein phosphatase 2A subunit PR55gamma as a stress-sensitive inhibitor of c-SRC

Protein Phosphatase type 2A (PP2A) represents a family of holoenzyme complexes with diverse biological activities. Specific holoenzyme complexes are thought to be deregulated during oncogenic transformation and oncogene-induced signaling. Since most studies on the role of this phosphatase family have relied on the use of generic PP2A inhibitors, the contribution of individual PP2A holoenzyme complexes in PP2A-controlled signaling pathways is largely unclear. To gain insight into this, we have constructed a set of shRNA vectors targeting the individual PP2A regulatory subunits for suppression by RNA interference. Here, we identify PR55gamma and PR55delta as inhibitors of c-Jun NH(2)-terminal kinase (JNK) activation by UV irradiation. We show that PR55gamma binds c-SRC and modulates the phosphorylation of serine 12 of c-SRC, a residue we demonstrate to be required for JNK activation by c-SRC. We also find that the physical interaction between PR55gamma and c-SRC is sensitive to UV irradiation. Our data reveal a novel mechanism of c-SRC regulation whereby in response to stress c-SRC activity is regulated, at least in part, through loss of the interaction with its inhibitor, PR55gamma.     

Ten simple rules for establishing a mentorship programme

In recent years, a wide variety of mentorship programmes targeting issues that cannot be addressed through traditional teaching and learning methods alone have been developed. Mentoring plays significant roles in the growth and development of both mentors and mentees, and the positive impacts of mentoring have been well documented. Mentorship programmes are therefore increasingly being implemented in a wide variety of fields by organisations, academic institutes, businesses, and governments. While there is a growing body of literature on mentoring and mentorship programmes, gaining a clear overview of the field is often challenging. In this article, we therefore provide a concise summary of recommendations to consider when designing and establishing mentorship programmes. These recommendations are based on the collective knowledge and experiences of 4 different emerging and established mentorship programmes and can be adapted across various mentorship settings or contexts.     

Morphological parallelism of sympatric cave-dwelling microsnails of the genus Georissa at Mount Silabur,Borneo (Gastropoda,Neritimorpha, Hydrocenidae)

Parallel evolution in phenotype may result when closely related taxa are adapting in the face of similar ecological pressures. Here, we discuss possible parallelism in shell morphology in the context of the microgeographic phylogeography of two conchologically distinct sympatric hydrocenid snails inhabiting a limestone outcrop and its cave system, Georissa pyrrhoderma and Georissa silaburensis, respectively, at Mount Silabur in Sarawak, Malaysian Borneo. Our results show a certain degree of morphological parallelism of a third, possibly new, cryptic Georissa species within the same cave that strongly diverged from its above-ground sister species, G. pyrrhoderma. We found that both sympatric cave species have shifted from a more sculptured, conical shell toward a broader, less sculptured form.     

Philosophy,politics and extralegal action: Native Indian leaders in Canada*

Immigration and asylum are key political issues in Britain and the European Union. Yet the policies of states and supranational bodies seem to have had little success in preventing unwanted flows and effectively managing immigration and integration. This article examines three types of reasons for policy failure: factors arising from the social dynamics of the migratory process; factors linked to globalization and the North-South divide; and factors arising within political systems. Key issues include the role of migrant agency, the way the North-South divide encourages flows, and hidden agendas in national policies. EU efforts attempts to address the root causes of migration in countries of origin are discussed. The article concludes that migration policies might be more successful if they were explicitly linked to long-term political agendas concerned with trade, development and conflict prevention. Reducing North-South inequality is the real key to effective migration management.     

The use of statistical tools in field testing of putative effects of genetically modified plants on nontarget organisms

To fulfill existing guidelines, applicants that aim to place their genetically modified (GM) insect‐resistant crop plants on the market are required to provide data from field experiments that address the potential impacts of the GM plants on nontarget organisms (NTO's). Such data may be based on varied experimental designs. The recent EFSA guidance document for environmental risk assessment (2010) does not provide clear and structured suggestions that address the statistics of field trials on effects on NTO's. This review examines existing practices in GM plant field testing such as the way of randomization, replication, and pseudoreplication. Emphasis is placed on the importance of design features used for the field trials in which effects on NTO's are assessed. The importance of statistical power and the positive and negative aspects of various statistical models are discussed. Equivalence and difference testing are compared, and the importance of checking the distribution of experimental data is stressed to decide on the selection of the proper statistical model. While for continuous data (e.g., pH and temperature) classical statistical approaches – for example, analysis of variance (ANOVA) – are appropriate, for discontinuous data (counts) only generalized linear models (GLM) are shown to be efficient. There is no golden rule as to which statistical test is the most appropriate for any experimental situation. In particular, in experiments in which block designs are used and covariates play a role GLMs should be used. Generic advice is offered that will help in both the setting up of field testing and the interpretation and data analysis of the data obtained in this testing. The combination of decision trees and a checklist for field trials, which are provided, will help in the interpretation of the statistical analyses of field trials and to assess whether such analyses were correctly applied.     

Intestinal Epithelial Cell-Intrinsic Deletion of Setd7 Identifies Role for Developmental Pathways in Immunity to Helminth Infection

The intestine is a common site for a variety of pathogenic infections. Helminth infections continue to be major causes of disease worldwide, and are a significant burden on health care systems. Lysine methyltransferases are part of a family of novel attractive targets for drug discovery. SETD7 is a member of the Suppressor of variegation 3-9-Enhancer of zeste-Trithorax (SET) domain-containing family of lysine methyltransferases, and has been shown to methylate and alter the function of a wide variety of proteins in vitro. A few of these putative methylation targets have been shown to be important in resistance against pathogens. We therefore sought to study the role of SETD7 during parasitic infections. We find that Setd7 ^-/- mice display increased resistance to infection with the helminth Trichuris muris but not Heligmosomoides polygyrus bakeri. Resistance to T. muris relies on an appropriate type 2 immune response that in turn prompts intestinal epithelial cells (IECs) to alter differentiation and proliferation kinetics. Here we show that SETD7 does not affect immune cell responses during infection. Instead, we found that IEC-specific deletion of Setd7 renders mice resistant to T. muris by controlling IEC turnover, an important aspect of anti-helminth immune responses. We further show that SETD7 controls IEC turnover by modulating developmental signaling pathways such as Hippo/YAP and Wnt/β-Catenin. We show that the Hippo pathway specifically is relevant during T. muris infection as verteporfin (a YAP inhibitor) treated mice became susceptible to T. muris. We conclude that SETD7 plays an important role in IEC biology during infection.     

A RNA Interference Screen Identifies the Protein Phosphatase 2A Subunit PR55γ as a Stress-Sensitive Inhibitor of c-SRC

Protein Phosphatase type 2A (PP2A) represents a family of holoenzyme complexes with diverse biological activities. Specific holoenzyme complexes are thought to be deregulated during oncogenic transformation and oncogene-induced signaling. Since most studies on the role of this phosphatase family have relied on the use of generic PP2A inhibitors, the contribution of individual PP2A holoenzyme complexes in PP2A-controlled signaling pathways is largely unclear. To gain insight into this, we have constructed a set of shRNA vectors targeting the individual PP2A regulatory subunits for suppression by RNA interference. Here, we identify PR55γ and PR55δ as inhibitors of c-Jun NH₂-terminal kinase (JNK) activation by UV irradiation. We show that PR55γ binds c-SRC and modulates the phosphorylation of serine 12 of c-SRC, a residue we demonstrate to be required for JNK activation by c-SRC. We also find that the physical interaction between PR55γ and c-SRC is sensitive to UV irradiation. Our data reveal a novel mechanism of c-SRC regulation whereby in response to stress c-SRC activity is regulated, at least in part, through loss of the interaction with its inhibitor, PR55γ.