ECL Cell Histamine Mobilization Studied byGastric Submucosal Microdialysis in Awake Rats:Methodological Considerations.

The ECL cells are endocrine/paracrine cells in the acid-producing part of the stomach. They secrete histamine in response to circulating gastrin. Gastric submucosal microdialysis has been used to study ECL-cell histamine mobilization in awake rats. In the present study we assess the usefulness and limitations of the technique. Microdialysis probes were implanted in the gastric submucosa. Histological analysis of the stomach wall around the probe revealed a moderate, local inflammatory reaction 1-2 days after implantation; the inflammation persisted for at least 10 days. Experiments were conducted 3 days after the implantation. The "true" submucosal histamine concentration was determined by perfusing at different rates (the zero flow method) or with different concentrations of histamine at a constant rate (the no-net-flux method): in fasted rats it was calculated to be 87±5 (means±S.E.M.) nmol/l and 76±9 nmol/l, respectively. The corresponding histamine concentrations in fed rats were 93±5 and 102±8 nmol/l, respectively. With a perfusion rate of 74 mul/hr the recovery of submucosal histamine was 49%, at 34 mul/hr the recovery increased to 83%. At a perfusion rate below 20 mul/hr the microdialysate histamine concentration was close to the actual concentration in the submucosa. The ECL-cell histamine mobilization was independent of the concentrations of Ca2+ in the perfusion medium (0-3.4 mmol/l Ca2+). In one experiment, histamine mobilization in response to gastrin (10 nmol/kg/hr subcutaneously) was monitored in rats pretreated with prednisolone (60 mg/kg) or indomethacin (15 mg/kg). The two antiinflammatory agents failed to affect the concentration of histamine in the microdialysate either before or during the gastrin challenge, which was in accord with the observation that the inflammatory reaction was modest and that inflammatory cells were relatively few around the probe and in the wall of the probe. In another experiment, rats were given aminoguanidine (10 mg/kg) or metoprine (10 mg/kg) 4 hr before the start of gastrin infusion (5 nmol/kg/hr intravenously). Metoprine (inhibitor of histamine N-methyl transferase) did not affect the microdialysate histamine concentration, while aminoguanidine (inhibitor of diamine oxidase) raised both basal and gastrin-stimulated histamine concentrations. We conclude that microdialysis can be used to monitor changes in the concentration of histamine in the submucosa of the stomach, and that the inflammatory reaction to the probe is moderate and does not affect the submucosal histamine mobilization

Demonstration of reduced efficacy against cyathostomins without change in species composition after pyrantel embonate treatment in Swedish equine establishments

Consisting of approximately 50 different species, the cyathostomin parasites are ubiquitous in grazing horses. Coinfection with several species is common, and large burdens can cause the fatal disease of larval cyathostominosis. Due to intense anthelmintic drug use, cyathostomin resistance has developed to all available anthelmintic drug groups. Resistance to the anthelmintic drug pyrantel (PYR) has been documented in over 90% of studies published over the past two decades. In Sweden, a study performed in the early 2000s only confirmed resistance in 4.5% of farms. Further, prescription-only administration of equine anthelmintic drugs was enforced in Sweden in 2007. However, it is unknown if this conservative drug use has maintained PYR efficacy in cyathostomins. The aim of the present study was to investigate the effect of PYR on cyathostomin infection in Sweden using fecal egg count reduction tests (FECRTs). Further, the effect of PYR treatment on cyathostomin species composition was studied using metabarcoding. Sixteen farms with at least six horses excreting a minimum of 100 eggs per gram feces were included. Using the current World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines, PYR resistance was demonstrated in nine of farms, with seven farms showing full susceptibility. Farms with low biosecurity measures had significantly lower efficacy of PYR treatment. The most common cyathostomin species were Cylicocyclus nassatus, Cyathostomum catinatum, Cylicostephanus longibursatus, Cys. calicatus, Cys. goldi, Cys. minutus, Coronocyclus coronatus and Cya. pateratum, accounting for 97% of all sequence reads prior to treatment. Of these, Cyc. nassatus and Cya. catinatum had the highest occurrence, accounting for 68% of all sequence reads prior to PYR treatment. Treatment did not significantly affect the species composition. The results highlight the importance of drug efficacy testing when using PYR to treat cyathostomin infection, even when selective anthelmintic treatment and thus low treatment intensity, is used on the farm

Using “responsive regulation” to reduce tax base erosion

How can governments get individuals and firms to pay taxes, especially given increasing tax base erosion via tax evasion, tax avoidance, and money laundering? In this paper we discuss the many different perspectives to explain why people pay – and do not pay – their taxes, especially perspectives based on “responsive regulation,” and we use then these perspectives to suggest policies that governments may use to improve tax collections. We first describe an approach that is based on a single individual pursuing a single motivation by choosing a single method (tax evasion) and operating in a single country. This perspective has generated important insights, but it nonetheless has significant limitations. As a result, we then argue that this perspective must be expanded to include additional actors in the field, all pursuing additional motivations. We also expand our discussion to include additional methods of tax base erosion like tax avoidance and money laundering, as well as additional countries. We argue that explaining behavior and then devising appropriate policies requires incorporating all of these additional considerations. We also discuss the likely impact of technological innovations both on the ability of governments to collect taxes and on the ability of private agents to reduce their taxes. An important contribution of our paper is that we simulate the effects of all of these expansions to the basic model using a novel agent‐based model that is fully grounded in theory and calibrated for 33 European economics. We use this model to simulate the impacts over time of various reforms, especially reforms that implement international information‐sharing programs, by comparing tax base erosion in the absence of these reforms to erosion in their presence. Our simulation results demonstrate the importance of using a fully specified theoretical model that goes well beyond the standard economics of crime approach when considering the effects of government policy innovations. We conclude with recommendations that can in principle reduce tax base erosion via evasion, avoidance, and money laundering in the current multi‐dimensional environment as derived from the responsive regulation framework. However, these recommendations require a firm commitment from governments to their tax administrations, and these recommendations also cannot be introduced unilaterally by a single country but require international cooperation, especially via information sharing across borders

Retained efficacy of ivermectin against cyathostomins in Swedish horse establishments practicing selective anthelmintic treatment

Cyathostominae are ubiquitous to grazing horses and regarded the most prevalent internal parasite in the horse. Unfortunately, decades of indiscriminate use of anthelmintic drugs have resulted in the development of resistance in cyathostomins to all currently available drug groups, the most recent being a documented lack of efficacy to the macrocyclic lactones (ML). In vivo determination of anthelmintic resistance in horses most often utilises the faecal egg count reduction test (FECRT). Further, a shortened egg reappearance period (ERP) can indicate a change in response to the applied treatment and suggest an upcoming reduction of efficacy. Although both true resistance as demonstrated by the FECRT and shorter ERPs after ML treatment have now been shown in cyathostomins worldwide, the efficacy of ML as regards to cyathostomins in Sweden is currently unknown. The aim of the present study was therefore to determine FECRTs and ERPs after ivermectin (IVM) treatment in Swedish horses. Sixteen equestrian establishments with a minimum of six horses excreting at least 150 eggs per gram faeces (EPG) at screening were selected. For each establishment, FECRTs and ERPs were determined by collecting faecal samples prior to and 14 days after IVM treatment (200 mu g/kg), and thereafter at weekly intervals for a total of eight weeks. All participants responded to a questionnaire detailing pasture management methods and anthelmintic routines.Questionnaire results showed that the majority of establishments (69%) only treated horses with anthelmintic drugs if indicated by faecal diagnostics and all of the establishments had a mean FECRT exceeding 99.0% and ERPs ranging from six to over eight weeks. The ERP was shown to increase with age as young individuals were shown to excrete cyathostomin eggs earlier after treatment compared with older horses (R = 0.21, p = 0.015). Riding schools, stud farms and those declaring not to use separate summer and winter paddocks had significantly shorter ERPs (p <0.01).In conclusion, retained ERPs and no confirmed resistance to IVM were found in Swedish equine establishments practising selective anthelmintic treatment, and supports the use of selective deworming regimens as a means of reducing the risk of anthelmintic resistance development

The Effect of Cholesterol on the Long-Range Network of Interactions Established among Sea Anemone Sticholysin II Residues at the Water-Membrane Interface

Actinoporins are α-pore forming proteins with therapeutic potential, produced by sea anemones. Sticholysin II (StnII) from Stichodactyla helianthus is one of its most extensively characterized members. These proteins remain stably folded in water, but upon interaction with lipid bilayers, they oligomerize to form a pore. This event is triggered by the presence of sphingomyelin (SM), but cholesterol (Chol) facilitates pore formation. Membrane attachment and pore formation require changes involving long-distance rearrangements of residues located at the protein-membrane interface. The influence of Chol on membrane recognition, oligomerization, and/or pore formation is now studied using StnII variants, which are characterized in terms of their ability to interact with model membranes in the presence or absence of Chol. The results obtained frame Chol not only as an important partner for SM for functional membrane recognition but also as a molecule which significantly reduces the structural requirements for the mentioned conformational rearrangements to occur. However, given that the DOPC:SM:Chol vesicles employed display phase coexistence and have domain boundaries, the observed effects could be also due to the presence of these different phases on the membrane. In addition, it is also shown that the Arg51 guanidinium group is strictly required for membrane recognition, independently of the presence of Chol

Review of existing information on the interrelations between soil and climate change. (ClimSoil). Final report

Carbon stock in EU soils – The soil carbon stocks in the EU27 are around 75 billion tonnes of carbon (C); of this stock around 50% is located in Sweden, Finland and the United Kingdom (because of the vast area of peatlands in these countries) and approximately 20% is in peatlands, mainly in countries in the northern part of Europe. The rest is in mineral soils, again the higher amount being in northern Europe. 2. Soils sink or source for CO2 in the EU – Both uptake of carbon dioxide (CO2) through photosynthesis and plant growth and loss of CO2 through decomposition of organic matter from terrestrial ecosystems are significant fluxes in Europe. Yet, the net terrestrial carbon fluxes are typically 5-10 times smaller relative to the emissions from use of fossil fuel of 4000 Mt CO2 per year. 3. Peat and organic soils - The largest emissions of CO2 from soils are resulting from land use change and especially drainage of organic soils and amount to 20-40 tonnes of CO2 per hectare per year. The most effective option to manage soil carbon in order to mitigate climate change is to preserve existing stocks in soils, and especially the large stocks in peat and other soils with a high content of organic matter. 4. Land use and soil carbon – Land use and land use change significantly affects soil carbon stocks. On average, soils in Europe are most likely to be accumulating carbon on a net basis with a sink for carbon in soils under grassland and forest (from 0 - 100 billion tonnes of carbon per year) and a smaller source for carbon from soils under arable land (from 10 - 40 billion tonnes of carbon per year). Soil carbon losses occur when grasslands, managed forest lands or native ecosystems are converted to croplands and vice versa carbon stocks increase, albeit it slower, following conversion of cropland. 5. Soil management and soil carbon – Soil management has a large impact on soil carbon. Measures directed towards effective management of soil carbon are available and identified, and many of these are feasible and relatively inexpensive to implement. Management for lower nitrogen (N) emissions and lower C emissions is a useful approach to prevent trade off and swapping of emissions between the greenhouse gases CO2, methane (CH4) and nitrous oxide (N2O). 6. Carbon sequestration – Even though effective in reducing or slowing the build up of CO2 in the atmosphere, soil carbon sequestration is surely no ‘golden bullet’ alone to fight climate change due to the limited magnitude of its effect and its potential reversibility; it could, nevertheless, play an important role in climate mitigation alongside other measures, especially because of its immediate availability and relative low cost for 'buying' us time. 7. Effects of climate change on soil carbon pools – Climate change is expected to have an impact on soil carbon in the longer term, but far less an impact than does land use change, land use and land management. We have not found strong and clear evidence for either overall and combined positive of negative impact of climate change (atmospheric CO2, temperature, precipitation) on soil carbon stocks. Due to the relatively large gross exchange of CO2 between atmosphere and soils and the significant stocks of carbon in soils, relatively small changes in these large and opposing fluxes of CO2, i.e. as result of land use (change), land management and climate change, may have significant impact on our climate and on soil quality. 8. Monitoring systems for changes in soil carbon – Currently, monitoring and knowledge on land use and land use change in EU27 is inadequate for accurate calculation of changes in soil carbon contents. Systematic and harmonized monitoring across EU27 and across relevant land uses would allow for adequate representation of changes in soil carbon in reporting emissions from soils and sequestration in soils to the UNFCCC. 9. EU policies and soil carbon – Environmental requirements under the Cross Compliance requirement of CAP is an instrument that may be used to maintain SOC. Neither measures under UNFCCC nor those mentioned in the proposed Soil Framework Directive are expected to adversely impact soil C. EU policy on renewable energy is not necessarily a guarantee for appropriate (soil) carbon management

Microbe-seq : high-throughput, single-microbe genomics with strain resolution, applied to a human gut microbiome

We present Microbe-seq , a high-throughput single-microbe method that yields strain-resolved genomes from complex microbial communities. We encapsulate individual microbes into droplets with microfluidics and liberate their DNA, which we amplify, tag with droplet-specific barcodes, and sequence. We use Microbe-seq to explore the human gut microbiome; we collect stool samples from a single individual, sequence over 20,000 microbes, and reconstruct nearly-complete genomes of almost 100 bacterial species, including several with multiple subspecies strains. We use these genomes to probe genomic signatures of microbial interactions: we reconstruct the horizontal gene transfer (HGT) network within the individual and observe far greater exchange within the same bacterial phylum than between different phyla. We probe bacteria-virus interactions; unexpectedly, we identify a significant in vivo association between crAssphage, an abundant bacteriophage, and a single strain of Bacteroides vulgatus. Microbe-seq contributes high-throughput culture-free capabilities to investigate genomic blueprints of complex microbial communities with single-microbe resolution