Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF

Several pathological processes, such as sepsis and inflammatory bowel disease (IBD), are associated with impairment of intestinal epithelial barrier. Here, we investigated the role of matrix metalloproteinase MMP13 in these diseases. We observed that MMP13(-/-) mice display a strong protection in LPS- and caecal ligation and puncture-induced sepsis. We could attribute this protection to reduced LPS-induced goblet cell depletion, endoplasmic reticulum stress, permeability and tight junction destabilization in the gut of MMP13(-/-) mice compared to MMP13(+/+) mice. Both in vitro and in vivo, we found that MMP13 is able to cleave pro-TNF into bioactive TNF. By LC-MS/MS, we identified three MMP13 cleavage sites, which proves that MMP13 is an alternative TNF sheddase next to the TNF converting enzyme TACE. Similarly, we found that the same mechanism was responsible for the observed protection of the MMP13(-/-) mice in a mouse model of DSS-induced colitis. We identified MMP13 as an important mediator in sepsis and IBD via the shedding of TNF. Hence, we propose MMP13 as a novel drug target for diseases in which damage to the gut is essential

Protein processing characterized by a gel-free proteomics approach

We describe a method for the specific isolation of representative N-terminal peptides of proteins and their proteolytic fragments. Their isolation is based on a gel-free, peptidecentric proteomics approach using the principle of diagonal chromatography. We will indicate that the introduction of an altered chemical property to internal peptides holding a free α-N-terminus results in altered column retention of these peptides, thereby enabling the isolation and further characterization by mass spectrometry of N-terminal peptides. Besides pointing to changes in protein expression levels when performing such proteome surveys in a differential modus, protease specificity and substrate repertoires can be allocated since both are specified by neo-N-termini generated after a protease cleavage event. As such, our gel-free proteomics technology is widely applicable and amenable for a variety of proteome-driven protease degradomics research

The Impact of Policy Instruments on Soil Multifunctionality in the European Union

peer-reviewedAgricultural ecosystems provide a range of benefits that are vital to human well-being. These benefits are dependent on several soil functions that are affected in different ways by legislation from the European Union, national, and regional levels. We evaluated current European Union soil-related legislation and examples of regional legislation with regard to direct and indirect impacts on five soil functions: the production of food, fiber, and fuel; water purification and regulation; carbon sequestration and climate regulation; habitat for biodiversity provisioning; and the recycling of nutrients/agro-chemicals. Our results illustrate the diversity of existing policies and the complex interactions present between different spatial and temporal scales. The impact of most policies, positive or negative, on a soil function is usually not established, but depends on how the policy is implemented by local authorities and the farmers. This makes it difficult to estimate the overall state and trends of the different soil functions in agricultural ecosystems. To implement functional management and sustainable use of the different soil functions in agricultural ecosystems, more knowledge is needed on the policy interactions as well as on the impact of management options on the different soil functions

ECOPLAN-SE: Ruimtelijke analyse van ecosysteemdiensten in Vlaanderen, een Q-GIS plugin

ECOPLAN-SE is een ruimtelijk expliciete tool (QGIS) voor het beoordelen van de impact van landgebruikveranderingen op de levering van ecosysteemdiensten. De ontwikkeling van deze tool kadert in het het SBO-project “ECOPLAN” (Planning for Ecosystem Services). ECOPLAN ontwikkelt ruimtelijk expliciete informatie en instrumenten voor de beoordeling van ecosysteemdiensten. Het ontwerpt instrumenten voor de evaluatie van functionele ecosystemen als een kostenefficiënte strategie om de landgebruiksefficiëntie en milieukwaliteit te verbeteren. Het ontwikkelt open source eindproducten voor het identificeren, kwantificeren, waarderen, valideren en monitoren van ecosysteemdiensten. Deze producten kunnen door administraties en consultants worden ingezet in projectontwikkeling, kosten-baten analyses, milieueffecten rapportering, etc

GC content of early metazoan genes and its impact on gene expression levels in mammalian cell lines

With the genomes available for many animal clades, including the early-branching metazoans, one can readily study the functional conservation of genes across a diversity of animal lineages. Ectopic expression of an animal protein in, for instance, a mammalian cell line is a generally used strategy in structure–function analysis. However, this might turn out to be problematic in case of distantly related species. Here we analyzed the GC content of the coding sequences of basal animals and show its impact on gene expression levels in human cell lines, and, importantly, how this expression efficiency can be improved. Optimization of the GC3 content in the coding sequences of cadherin, alpha-catenin, and paracaspase of Trichoplax adhaerens dramatically increased the expression of these basal animal genes in human cell lines

Harvesting European knowledge on soil functions and land management using multi-criteria decision analysis

Soil and its ecosystem functions play a societal role in securing sustainable food production while safeguarding natural resources. A functional land management framework has been proposed to optimize the agro-environmental outputs from the land and specifically the supply and demand of soil functions such as (a) primary productivity, (b) carbon sequestration, (c) water purification and regulation, (d) biodiversity and (e) nutrient cycling, for which soil knowledge is essential. From the outset, the LANDMARK multi-actor research project integrates harvested knowledge from local, national and European stakeholders to develop such guidelines, creating a sense of ownership, trust and reciprocity of the outcomes. About 470 stakeholders from five European countries participated in 32 structured workshops covering multiple land uses in six climatic zones. The harmonized results include stakeholders’ priorities and concerns, perceptions on soil quality and functions, implementation of tools, management techniques, indicators and monitoring, activities and policies, knowledge gaps and ideas. Multi-criteria decision analysis was used for data analysis. Two qualitative models were developed using Decision EXpert methodology to evaluate “knowledge” and “needs”. Soil quality perceptions differed across workshops, depending on the stakeholder level and regionally established terminologies. Stakeholders had good inherent knowledge about soil functioning, but several gaps were identified. In terms of critical requirements, stakeholders defined high technical, activity and policy needs in (a) financial incentives, (b) credible information on improving more sustainable management practices, (c) locally relevant advice, (d) farmers’ discussion groups, (e) training programmes, (f) funding for applied research and monitoring, and (g) strengthening soil science in education.</p

Public Health Emergency Preparedness and Response Communications with Health Care Providers: A Literature Review

<p>Abstract</p> <p>Background</p> <p>Health care providers (HCPs) play an important role in public health emergency preparedness and response (PHEPR) so need to be aware of public health threats and emergencies. To inform HCPs, public health issues PHEPR messages that provide guidelines and updates, and facilitate surveillance so HCPs will recognize and control communicable diseases, prevent excess deaths and mitigate suffering. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. We conducted a literature review to investigate the systems and tools used by public health to generate PHEPR communications to HCPs, and to identify specific characteristics of message delivery mechanisms and formats that may be associated with effective PHEPR communications.</p> <p>Methods</p> <p>A systematic review of peer- and non-peer-reviewed literature focused on the following questions: 1) What public health systems exist for communicating PHEPR messages from public health agencies to HCPs? 2) Have these systems been evaluated and, if yes, what criteria were used to evaluate these systems? 3) What have these evaluations discovered about characterizations of the most effective ways for public health agencies to communicate PHEPR messages to HCPs?</p> <p>Results</p> <p>We identified 25 systems or tools for communicating PHEPR messages from public health agencies to HCPs. Few articles assessed PHEPR communication systems or messaging methods or outcomes. Only one study compared the effectiveness of the delivery format, device or message itself. We also discovered that the potential is high for HCPs to experience "message overload" given redundancy of PHEPR messaging in multiple formats and/or through different delivery systems.</p> <p>Conclusions</p> <p>We found that detailed descriptions of PHEPR messaging from public health to HCPs are scarce in the literature and, even when available are rarely evaluated in any systematic fashion. To meet present-day and future information needs for emergency preparedness, more attention needs to be given to evaluating the effectiveness of these systems in a scientifically rigorous manner.</p

Predicting the start week of respiratory syncytial virus outbreaks using real time weather variables

<p>Abstract</p> <p>Background</p> <p>Respiratory Syncytial Virus (RSV), a major cause of bronchiolitis, has a large impact on the census of pediatric hospitals during outbreak seasons. Reliable prediction of the week these outbreaks will start, based on readily available data, could help pediatric hospitals better prepare for large outbreaks.</p> <p>Methods</p> <p>Naïve Bayes (NB) classifier models were constructed using weather data from 1985-2008 considering only variables that are available in real time and that could be used to forecast the week in which an RSV outbreak will occur in Salt Lake County, Utah. Outbreak start dates were determined by a panel of experts using 32,509 records with ICD-9 coded RSV and bronchiolitis diagnoses from Intermountain Healthcare hospitals and clinics for the RSV seasons from 1985 to 2008.</p> <p>Results</p> <p>NB models predicted RSV outbreaks up to 3 weeks in advance with an estimated sensitivity of up to 67% and estimated specificities as high as 94% to 100%. Temperature and wind speed were the best overall predictors, but other weather variables also showed relevance depending on how far in advance the predictions were made. The weather conditions predictive of an RSV outbreak in our study were similar to those that lead to temperature inversions in the Salt Lake Valley.</p> <p>Conclusions</p> <p>We demonstrate that Naïve Bayes (NB) classifier models based on weather data available in real time have the potential to be used as effective predictive models. These models may be able to predict the week that an RSV outbreak will occur with clinical relevance. Their clinical usefulness will be field tested during the next five years.</p