The effect of climate type on timescales of drought propagation in an ensemble of global hydrological models

Drought is a natural hazard that occurs at many temporal and spatial scales and has severe environmental and socioeconomic impacts across the globe. The impacts of drought change as drought evolves from precipitation deficits to deficits in soil moisture or streamflow. Here, we quantified the time taken for drought to propagate from meteorological drought to soil moisture drought and from meteorological drought to hydrological drought. We did this by cross-correlating the Standardized Precipitation Index (SPI) against standardized indices (SIs) of soil moisture, runoff, and streamflow from an ensemble of global hydrological models (GHMs) forced by a consistent meteorological dataset. Drought propagation is strongly related to climate types, occurring at sub-seasonal timescales in tropical climates and at up to multi-annual timescales in continental and arid climates. Winter droughts are usually related to longer SPI accumulation periods than summer droughts, especially in continental and tropical savanna climates. The difference between the seasons is likely due to winter snow cover in the former and distinct wet and dry seasons in the latter. Model structure appears to play an important role in model variability, as drought propagation to soil moisture drought is slower in land surface models (LSMs) than in global hydrological models, but propagation to hydrological drought is faster in land surface models than in global hydrological models. The propagation time from SPI to hydrological drought in the models was evaluated against observed data at 127 in situ streamflow stations. On average, errors between observed and modeled drought propagation timescales are small and the model ensemble mean is preferred over the use of a single model. Nevertheless, there is ample opportunity for improvement as substantial differences in drought propagation are found at 10% of the study sites. A better understanding and representation of drought propagation in models may help improve seasonal drought forecasting as well as constrain drought variability under future climate scenarios

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

The effect of climate type on timescales of drought propagation in an ensemble of global hydrological models

Drought is a natural hazard that occurs at many temporal and spatial scales and has severe environmental and socioeconomic impacts across the globe. The impacts of drought change as drought evolves from precipitation deficits to deficits in soil moisture or streamflow. Here, we quantified the time taken for drought to propagate from meteorological drought to soil moisture drought and from meteorological drought to hydrological drought. We did this by cross-correlating the Standardized Precipitation Index (SPI) against standardized indices (SIs) of soil moisture, runoff, and streamflow from an ensemble of global hydrological models (GHMs) forced by a consistent meteorological dataset. Drought propagation is strongly related to climate types, occurring at sub-seasonal timescales in tropical climates and at up to multi-annual timescales in continental and arid climates. Winter droughts are usually related to longer SPI accumulation periods than summer droughts, especially in continental and tropical savanna climates. The difference between the seasons is likely due to winter snow cover in the former and distinct wet and dry seasons in the latter. Model structure appears to play an important role in model variability, as drought propagation to soil moisture drought is slower in land surface models (LSMs) than in global hydrological models, but propagation to hydrological drought is faster in land surface models than in global hydrological models. The propagation time from SPI to hydrological drought in the models was evaluated against observed data at 127 in situ streamflow stations. On average, errors between observed and modeled drought propagation timescales are small and the model ensemble mean is preferred over the use of a single model. Nevertheless, there is ample opportunity for improvement as substantial differences in drought propagation are found at 10&thinsp;% of the study sites. A better understanding and representation of drought propagation in models may help improve seasonal drought forecasting as well as constrain drought variability under future climate scenarios.</p

Staphylococcus aureus controls interleukin-5 release in upper airway inflammation

Staphylococcus aureus is a frequent colonizer of the upper airways in chronic rhinosinusitis with nasal polyps, but also resides intramucosally, it has been shown that secreted staphylococcal proteins such as enterotoxins and serine proteases induce the release of cytokines such as IL-5. We have analyzed nasal polyp tissue freshly obtained during routine surgery, which did or did not contain cultivatable S. aureus, to study spontaneous IL-5 production by nasal polyp tissue over 24 and 72 h in tissue culture In S. aureus-positive samples we interfered by killing the bacteria using antibiotics or S. aureus specific intravenous staphylococcal phages (ISP), active or heat-inactivated. Phage-neutralizing antibodies were used to demonstrate the specificity of the phage-mediated effects We monitored S. aureus colony forming units, and identified S. aureus proteins by mass spectrometry We demonstrate that cultivatable S. aureus may be found in type-2 inflamed nasal polyps, the pathogen is replicating within 24 h and secretes proteins, including enterotoxins and serine proteases The presence of S. aureus was associated with a significantly higher release of IL-5 Killing of S. aureus by antibiotics or specific ISP significantly reduced the IL-5 release. The suppressive activity of the bacteriophage on IL-5 be abolished by heat inactivation or anti-phage antibodies. Biological significance In this study, we used high resolution mass spectrometry to identify S. aureus proteins directly in infected nasal polyp tissue and nasal polyp tissue incubated over 24 and 72 h in culture We discovered bacterial proteins including enterotoxins and serine proteases like proteins These experiments indicate a direct role of S. aureus in the regulation of IL-5 production in nasal polyps and may suggest the involvement of bacterial proteins detected in the tissues

Towards a personalised approach in exercise-based cardiovascular rehabilitation: How can translational research help?: A ‘call to action’ from the Section on Secondary Prevention and Cardiac Rehabilitation of the European Association of Preventive Cardiology

The benefit of regular physical activity and exercise training for the prevention of cardiovascular and metabolic diseases is undisputed. Many molecular mechanisms mediating exercise effects have been deciphered. Personalised exercise prescription can help patients in achieving their individual greatest benefit from an exercise-based cardiovascular rehabilitation programme. Yet, we still struggle to provide truly personalised exercise prescriptions to our patients. In this position paper, we address novel basic and translational research concepts that can help us understand the principles underlying the inter-individual differences in the response to exercise, and identify early on who would most likely benefit from which exercise intervention. This includes hereditary, non-hereditary and sex-specific concepts. Recent insights have helped us to take on a more holistic view, integrating exercise-mediated molecular mechanisms with those influenced by metabolism and immunity. Unfortunately, while the outline is recognisable, many details are still lacking to turn the understanding of a concept into a roadmap ready to be used in clinical routine. This position paper therefore also investigates perspectives on how the advent of ‘big data’ and the use of animal models could help unravel interindividual responses to exercise parameters and thus influence hypothesis-building for translational research in exercisebased cardiovascular rehabilitation