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Systemic or localized application of glucocorticoids (GCs) can lead to iatrogenic ocular hypertension, which is a leading cause of secondary open-angle glaucoma and visual impairment. Previous work has shown that dexamethasone increases zonula occludens-1 (ZO-1) protein expression in trabecular meshwork (TM) cells, and that an antisense oligonucleotide inhibitor of ZO-1 can abolish the dexamethasone-induced increase in trans-endothelial flow resistance in cultured Schlemm’s canal (SC) endothelial and TM cells. We have previously shown that intracameral inoculation of small interfering RNA (siRNA) targeting SC endothelial cell tight junction components, ZO-1 and tricellulin, increases aqueous humor outflow facility ex vivo in normotensive mice by reversibly opening SC endothelial paracellular pores. In this study, we show that targeted siRNA downregulation of these SC endothelial tight junctions reduces intraocular pressure (IOP) in vivo, with a concomitant increase in conventional outflow facility in a well-characterized chronic steroid-induced mouse model of ocular hypertension, thus representing a potential focused clinical application for this therapy in a sight-threatening scenario., Graphical Abstract, Cassidy and colleagues show that intracameral inoculation of siRNA targeting Schlemm’s canal endothelial cell tight junction proteins, ZO-1 and tricellulin, can reduce intraocular pressure and increase outflow facility in a murine model of steroid-induced ocular hypertension.

Wildfires have the potential to change the physico-chemical characteristics of soils, and further research is required to establish the nature, extent and duration of these impacts. The extent to which the impacts of wildfires differ from the more frequently studied prescribed burns is an active area of investigation with serious implications for landscape managers and conservation biologists. Here, we take advantage of multiple large wildfires which occurred in vulnerable upland habitats of conservation importance, to measure in-situ differences in soil conditions between burnt and unburnt areas ca. 1.5 years and 3.5 years after fires. There were no detectable differences in pH, total nitrogen, total carbon, potassium or magnesium concentrations between burnt and unburnt locations 15–18 months after wildfires, suggesting that these were either unaffected by the fires, or more likely, as suggested by previous research, had exhibited transient differences immediately after the wildfires which had returned to baseline conditions within 1.5 years. By contrast, burnt and unburnt locations differed with respect to phosphorus and calcium concentrations which remained elevated up to 3.5 years post-fire. Calcium concentrations remained greater in burnt plots across all three habitat types, whilst available phosphorus concentrations remained elevated in blanket bog but returned to the same level as unburnt control plots in wet and dry heath. Taken together, our findings suggest that there is the potential for wildfires to have longer-lasting effects on phosphorus and calcium concentrations in some temperate European Annex I habitats of conservation concern, particularly blanket bog, than previously expected based on results of studies of experimental burning or wildfires in other habitat types. The magnitude and duration of fire impacts on soils depends largely on the environmental and meteorological characteristics of the region. Hence, this study highlights the need for more research across a broader range of sites taking advantage of unexpected wildfires, to assess the extent to which their impacts may differ between habitat types and from those of experimental or controlled burning.

Summary Background Antibacterial resistant infections are rising continuously, resulting in increased morbidity and mortality worldwide. With no new antibiotic classes entering the market and the possibility of returning to the pre-antibiotic era, the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) was established to address this problem. We aimed to quantify the scale and scope of publicly funded antibacterial resistance research across JPIAMR countries and at the European Union (EU) level to identify gaps and future opportunities. Methods We did a systematic observational analysis examining antibacterial resistance research funding. Databases of funding organisations across 19 countries and at EU level were systematically searched for publicly funded antibacterial resistance research from Jan 1, 2007, to Dec 31, 2013. We categorised studies on the basis of the JPIAMR strategic research agenda's six priority topics (therapeutics, diagnostics, surveillance, transmission, environment, and interventions) and did an observational analysis. Only research funded by public funding bodies was collected and no private organisations were contacted for their investments. Projects in basic, applied, and clinical research, including epidemiological, public health, and veterinary research and trials were identified using keyword searches by organisations, and inclusion criteria were based on the JPIAMR strategic research agenda's six priority topics, using project titles and abstracts as filters. Findings We identified 1243 antibacterial resistance research projects, with a total public investment of €1·3 billion across 19 countries and at EU level, including public investment in the Innovative Medicines Initiative. Of the total amount invested in antibacterial resistance research across the time period, €646·6 million (49·5%) was invested at the national level and €659·2 million (50·5%) at the EU level. When projects were classified under the six priority topics we found that 763 (63%) of 1208 projects funded at national level were within the area of therapeutics, versus 185 (15%) in transmission, 131 (11%) in diagnostics, 53 (4%) in interventions, and only 37 (3%) in environment and 39 (3%) in surveillance. Interpretation This was the first systematic analysis of research funding of antibacterial resistance of this scale and scope, which relied on the availability and accuracy of data from organisations included. Large variation was seen between countries both in terms of number of projects and associated investment and across the six priority topics. To determine the future direction of JPIAMR countries a clear picture of the funding landscape across Europe and Canada is needed. Countries should work together to increase the effect of research funding by strengthening national and international coordination and collaborations, harmonising research activities, and collectively pooling resources to fund multidisciplinary projects. The JPIAMR have developed a publicly available database to document the antibacterial resistance research collected and can be used as a baseline to analyse funding from 2014 onwards. Funding JPIAMR and the European Commission.

Exposure to Plant Protection Products, PPPs, (fungicides, herbicides and insecticides) is a significant stressor for bees and other pollinators, and has recently been the focus of intensive debate and research. Specifically, exposure through contaminated pollen and nectar is considered pivotal, as it presents the highest risk of PPP exposure across all bee species. However, the actual risk that multiple PPP residues might pose to non-target species is difficult to assess due to the lack of clear evidence of their actual concentrations. To consolidate the existing knowledge of field-realistic residues detected in pollen and nectar directly collected from plants, we performed a systematic literature review of studies over the past 50 years (1968-2018). We found that pollen was the matrix most frequently evaluated and, of the compounds investigated, the majority were detected in pollen samples. Although the overall most studied category of PPPs were the neonicotinoid insecticides, the compounds with the highest median concentrations of residues in pollen were: the broad spectrum carbamate carbofuran (1,400 ng/g), the fungicide and nematicide iprodione (524 ng/g), and the organophosphate insecticide dimethoate (500 ng/g). In nectar, the highest median concentration of PPP residues detected were dimethoate (1,595 ng/g), chlorothalonil (76 ng/g), and the insecticide phorate (53.5 ng/g). Strong positive correlation was observed between neonicotinoid residues in pollen and nectar of cultivated plant species. The maximum concentrations of several compounds detected in nectar and pollen were estimated to exceed the LD50s for honey bees, bumble bees and four solitary bee species, by several orders of magnitude. However, there is a paucity of information for the biggest part of the world and there is an urgent need to expand the range of compounds evaluated in PPP studies.