Autumn

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Airborne bacterial emission fluxes from manure-fertilized agricultural soil

This is the first study to quantify the dependence on wind velocity of airborne bacterial emission fluxes from soil. It demonstrates that manure bacteria get aerosolized from fertilized soil more easily than soil bacteria, and it applies bacterial genomic sequencing for the first time to trace environmental faecal contamination back to its source in the chicken barn. We report quantitative, airborne emission fluxes of bacteria during and following the fertilization of agricultural soil with manure from broiler chickens. During the fertilization process, the concentration of airborne bacteria culturable on blood agar medium increased more than 600 000-fold, and 1 m3 of air carried 2.9 × 105 viable enterococci, i.e. indicators of faecal contamination which had been undetectable in background air samples. Trajectory modelling suggested that atmospheric residence times and dispersion pathways were dependent on the time of day at which fertilization was performed. Measurements in a wind tunnel indicated that airborne bacterial emission fluxes from freshly fertilized soil under local climatic conditions on average were 100-fold higher than a previous estimate of average emissions from land. Faecal bacteria collected from soil and dust up to seven weeks after fertilization could be traced to their origins in the poultry barn by genomic sequencing. Comparative analyses of 16S rRNA gene sequences from manure, soil and dust showed that manure bacteria got aerosolized preferably, likely due to their attachment to low-density manure particles. Our data show that fertilization with manure may cause substantial increases of bacterial emissions from agricultural land. After mechanical incorporation of manure into soil, however, the associated risk of airborne infection is low

Quasi-spherical ice in convective clouds

Homogeneous freezing of supercooled droplets occurs in convective systems in low and midlatitudes. This droplet-freezing process leads to the formation of a large amount of small ice particles, so-called frozen droplets, that are transported to the upper parts of anvil outflows, where they can influence the cloud radiative properties. However, the detailed microphysics and, thus, the scattering properties of these small ice particles are highly uncertain. Here, the link between the microphysical and optical properties of frozen droplets is investigated in cloud chamber experiments, where the frozen droplets were formed, grown, and sublimated under controlled conditions. It was found that frozen droplets developed a high degree of small-scale complexity after their initial formation and subsequent growth. During sublimation, the small-scale complexity disappeared, releasing a smooth and near-spherical ice particle. Angular light scattering and depolarization measurements confirmed that these sublimating frozen droplets scattered light similar to spherical particles: that is, they had angular light-scattering properties similar to water droplets. The knowledge gained from this laboratory study was applied to two case studies of aircraft measurements in midlatitude and tropical convective systems. The in situ aircraft measurements confirmed that the microphysics of frozen droplets is dependent on the humidity conditions they are exposed to (growth or sublimation). The existence of optically spherical frozen droplets can be important for the radiative properties of detraining convective outflows.Peer reviewe

Deletion of the diabetes candidate gene Slc16a13 in mice attenuates diet-induced ectopic lipid accumulation and insulin resistance

Abstract Genome-wide association studies have identified SLC16A13 as a novel susceptibility gene for type 2 diabetes. The SLC16A13 gene encodes SLC16A13/MCT13, a member of the solute carrier 16 family of monocarboxylate transporters. Despite its potential importance to diabetes development, the physiological function of SLC16A13 is unknown. Here, we validate Slc16a13 as a lactate transporter expressed at the plasma membrane and report on the effect of Slc16a13 deletion in a mouse model. We show that loss of Slc16a13 increases mitochondrial respiration in the liver, leading to reduced hepatic lipid accumulation and increased hepatic insulin sensitivity in high-fat diet fed Slc16a13 knockout mice. We propose a mechanism for improved hepatic insulin sensitivity in the context of Slc16a13 deficiency in which reduced intrahepatocellular lactate availability drives increased AMPK activation and increased mitochondrial respiration, while reducing hepatic lipid content. Slc16a13 deficiency thereby attenuates hepatic diacylglycerol-PKCε mediated insulin resistance in obese mice. Together, these data suggest that SLC16A13 is a potential target for the treatment of type 2 diabetes and non-alcoholic fatty liver disease

A randomized trial of a transglutaminase 2 inhibitor for celiac disease

BACKGROUND In celiac disease, small intestinal transglutaminase 2 causes deamidation of glutamine residues in gluten peptides, which enhances stimulation of T cells and leads to mucosal injury. Inhibition of transglutaminase 2 is a potential treatment for celiac disease. METHODS In a proof-of-concept trial, we assessed the efficacy and safety of a 6-week treatment with ZED1227, a selective oral transglutaminase 2 inhibitor, at three dose levels as compared with placebo, in adults with well-controlled celiac disease who underwent a daily gluten challenge. The primary end point was the attenuation of gluten-induced mucosal damage, as measured by the ratio of villus height to crypt depth. Secondary end points included intraepithelial lymphocyte density, the Celiac Symptom Index score, and the Celiac Disease Questionnaire score (for assessment of health-related quality of life). RESULTS Of the 41 patients assigned to the 10-mg ZED1227 group, the 41 assigned to the 50-mg group, the 41 assigned to the 100-mg group, and the 40 assigned to the placebo group, 35, 39, 38, and 30 patients, respectively, had adequate duodenal-biopsy samples for the assessment of the primary end point. Treatment with ZED1227 at all three dose levels attenuated gluten-induced duodenal mucosal injury. The estimated difference from placebo in the change in the mean ratio of villus height to crypt depth from baseline to week 6 was 0.44 (95% confidence interval [CI], 0.15 to 0.73) in the 10-mg group (P=0.001), 0.49 (95% CI, 0.20 to 0.77) in the 50-mg group (P<0.001), and 0.48 (95% CI, 0.20 to 0.77) in the 100-mg group (P<0.001). The estimated differences from placebo in the change in intraepithelial lymphocyte density were -2.7 cells per 100 epithelial cells (95% CI, -7.6 to 2.2) in the 10-mg group, -4.2 cells per 100 epithelial cells (95% CI, -8.9 to 0.6) in the 50-mg group, and -9.6 cells per 100 epithelial cells (95% CI, -14.4 to -4.8) in the 100-mg group. Use of the 100-mg dose may have improved symptom and quality-of-life scores. The most common adverse events, the incidences of which were similar across all groups, were headache, nausea, diarrhea, vomiting, and abdominal pain. Rash developed in 3 of 40 patients (8%) in the 100-mg group. CONCLUSIONS In this preliminary trial, treatment with ZED1227 attenuated gluten-induced duodenal mucosal damage in patients with celiac disease.publishedVersionPeer reviewe

Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease

The solute carrier (SLC) superfamily comprises more than 400 transport proteins mediating the influx and efflux of substances such as ions, nucleotides, and sugars across biological membranes. Over 80 SLC transporters have been linked to human diseases, including obesity and type 2 diabetes (T2D). This observation highlights the importance of SLCs for human (patho)physiology. Yet, only a small number of SLC proteins are validated drug targets. The most recent drug class approved for the treatment of T2D targets sodium-glucose cotransporter 2, product of the SLC5A2 gene. There is great interest in identifying other SLC transporters as potential targets for the treatment of metabolic diseases. Finding better treatments will prove essential in future years, given the enormous personal and socioeconomic burden posed by more than 500 million patients with T2D by 2040 worldwide. In this review, we summarize the evidence for SLC transporters as target structures in metabolic disease. To this end, we identified SLC13A5/sodium-coupled citrate transporter, and recent proof-of-concept studies confirm its therapeutic potential in T2D and nonalcoholic fatty liver disease. Further SLC transporters were linked in multiple genome-wide association studies to T2D or related metabolic disorders. In addition to presenting better-characterized potential therapeutic targets, we discuss the likely unnoticed link between other SLC transporters and metabolic disease. Recognition of their potential may promote research on these proteins for future medical management of human metabolic diseases such as obesity, fatty liver disease, and T2D. SIGNIFICANCE STATEMENT: Given the fact that the prevalence of human metabolic diseases such as obesity and type 2 diabetes has dramatically risen, pharmacological intervention will be a key future approach to managing their burden and reducing mortality. In this review, we present the evidence for solute carrier (SLC) genes associated with human metabolic diseases and discuss the potential of SLC transporters as therapeutic target structures

Aircraft emissions at cruise and plume processes

The detection of aircraft emissions at cruise altitudes helps to understand and assess the effects of aviation on atmospheric composition and climate. Since the early 1990s, aircraft emissions of carbon dioxide, water vapor, nitrogen and sulfur oxides, aerosol and soot and their processing in the atmosphere as well as contrail formation have been measured in-situ with the instrumented DLR research aircraft Falcon. Scientific results from a series of aircraft missions are summarized and explained, uncertainties are discussed and suggestions are made on how to move forward

Has the aircraft type an impact on the microphysical parameters of young contrails?

Modeling studies suggest an impact of the aircraft type on the microphysical and optical properties of young contrails. However, up to now, a low intercomparability of meteorological conditions has prevented a study on the aircraft effect on contrail properties using in-situ observations. Therefore, we analyze contrail observations from 3 different aircraft, a large A380, a medium sized A340 and a smaller A319, performed during the CONCERT2008 (CONtrail and Cirrus ExpeRimenT) campaign under similar meteorological conditions in terms of relative humidity over ice (RHi) and wind shear. The young contrails were probed on 19 November 2008 over Northern Germany with instruments onboard the DLR research aircraft Falcon. 1-min old contrails were sampled at an altitude of 10.6 km near ice saturation at temperatures of 217 to 218 K above a natural cirrus cloud layer. We find large differences in the 3 observed contrail optical depth distributions, while the aircraft impact is not as pronounced in the detected particle size spectra. In addition, we simulate the contrail properties from the 3 aircraft with two independent models, the Eulerian particle tracking EULAG-LCM model and the contrail and cirrus prediction tool CoCiP. The models generally confirm the observed trend, an increase in contrail optical depth with increasing aircraft size (or weight). However, the models show smaller contrail optical depths for all aircraft types than observations. These discrepancies are reduced assuming higher values for the ambient relative humidity

The longevity gene INDY (I'm Not Dead Yet) in metabolic control: Potential as pharmacological target

The regulation of metabolic processes by the Indy (Fin Not Dead Yet) (SLC13A5/NaCT) gene was revealed through studies in Drosophila melanogaster and Caenorhabditis elegans. Reducing the expression of Indy in these species extended their life span by a mechanism resembling caloric restriction, without reducing food intake. In D. melanogaster, mutating the Indy gene reduced body fat content, insulin-like proteins and reactive oxygen species production. Subsequent studies indicated that Indy encodes a citrate transporter located on the cell plasma membrane. The transporter is highly expressed in the mammalian liver. We generated a mammalian knock out model deleting the mammalian homolog mIndy (SLC13A5). The knock out animals were protected from HFD induced obesity, fatty liver and insulin resistance. Moreover, we have shown that inducible and liver selective knock down of mIndy protects against the development of fatty liver and insulin resistance and that obese humans with type 2 diabetes and non-alcoholic fatty liver disease have increased levels of mIndy. Therefore, the transporter mINDY (NaCT) has been proposed to be an 'ideal target for the treatment of metabolic disease'. A small molecule inhibitor of the mINDY transporter has been generated, normalizing glucose levels and reducing fatty liver in a model of diet induced obese mice. Taken together, studies from lower organisms, mammals and humans suggest that mINDY (NaCT) is an attractive target for the treatment of metabolic disease