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Background Chronic obstructive pulmonary disease (COPD) patients exhibit skeletal muscle atrophy, denervation, and reduced mitochondrial oxidative capacity. Whilst chronic tobacco smoke exposure is implicated in COPD muscle impairment, the mechanisms involved are ambiguous. The aryl hydrocarbon receptor (AHR) is a ligand‐activated transcription factor that activates detoxifying pathways with numerous exogenous ligands, including tobacco smoke. Whereas transient AHR activation is adaptive, chronic activation can be toxic. On this basis, we tested the hypothesis that chronic smoke‐induced AHR activation causes adverse muscle impact. Methods We used clinical patient muscle samples, and in vitro (C2C12 myotubes) and in vivo models (mouse), to perform gene expression, mitochondrial function, muscle and neuromuscular junction morphology, and genetic manipulations (adeno‐associated virus‐mediated gene transfer). Results Sixteen weeks of tobacco smoke exposure in mice caused muscle atrophy, neuromuscular junction degeneration, and reduced oxidative capacity. Similarly, smoke exposure reprogrammed the muscle transcriptome, with down‐regulation of mitochondrial and neuromuscular junction genes. In mouse and human patient specimens, smoke exposure increased muscle AHR signalling. Mechanistically, experiments in cultured myotubes demonstrated that smoke condensate activated the AHR, caused mitochondrial impairments, and induced an AHR‐dependent myotube atrophy. Finally, to isolate the role of AHR activity, expression of a constitutively active AHR mutant without smoke exposure caused atrophy and mitochondrial impairments in cultured myotubes, and muscle atrophy and neuromuscular junction degeneration in mice. Conclusions These results establish that chronic AHR activity, as occurs in smokers, phenocopies the atrophy, mitochondrial impairment, and neuromuscular junction degeneration caused by chronic tobacco smoke exposure.

Members of the verrucomicrobial clade 'Candidatus Udaeobacter' rank among the most dominant bacterial phylotypes in soil. Nevertheless, despite this global prevalence, in-depth analyses with respect to pH preferences of 'Ca. Udaeobacter' representatives are still lacking. Here, we utilized a recently designed primer pair, specifically targeting 'Ca. Udaeobacter', to investigate links between soil pH and the abundance as well as phylotype composition of this largely unexplored verrucomicrobial clade. Based on 150 forest and 150 grassland soils, comprising a broad pH range, we determined the highest total abundance of 'Ca. Udaeobacter' in strongly acidic soil (pH, ~5.1) and, noteworthy, in ultra-acidic soil (pH

Background Biliary cancer, comprising cholangio- and gallbladder carcinomas, is associated with high mortality due to asymptomatic disease onset and resulting late diagnosis. Currently, no robust diagnostic biomarker is clinically available. Therefore, we explored the feasibility of extracellular vesicles (EVs) as a liquid biopsy tool for biliary cancer screening and hepatobiliary cancer differentiation. Methods Serum EVs of biliary cancer, hepatocellular carcinoma, colorectal cancer and non-small cell lung cancer patients, as well as from healthy individuals, were isolated by sequential two-step centrifugation and presence of indicated EVs was evaluated by fluorescence activated cell sorting (FACS) analysis. Results Two directly tumour-related antigen combinations (AnnV+ CD44v6+ and AnnV+ CD44v6+ CD133+ ) and two combinations related to progenitor cells from the tumour microenvironment (AnnV+ CD133+ gp38+ and AnnV+ EpCAM+ CD133+ gp38+ ) were associated with good diagnostic performances that could potentially be used for clinical assessment of biliary cancer and differentiation from other cancer entities. With 91% sensitivity and 69% specificity AnnV+ CD44v6+ EVs showed the most promising results for differentiating biliary cancers from HCC. Moreover using a combined approach of EV levels of the four populations with serum AFP values, we obtained a perfect separation of biliary cancer and HCC with sensitivity, specificity, positive and negative predictive value all reaching 100% respectively. Conclusions EV phenotyping, especially if combined with serum AFP, represents a minimally invasive, accurate liquid biopsy tool that could improve cancer screening and differential diagnosis of hepatobiliary malignancies.

The oxidation of isobutane has been investigated for the first time in a micro reactor for a wide range of process conditions comparing the product ratios obtained with di-tert-butyl peroxide (DTBP) and tert-butyl hydroperoxide (TBHP) as initiator. DTBP led to nearly the double conversion compared to the same concentration of TBHP, but the selectivity of TBHP using TBHP as initiator was higher. Using aqueous TBHP, the conversions reached up to 6 % in case of supercritical conditions but stayed below 2 % in case of two-phase flow experiments. With TBHP in decane as initiator a high conversion was reached but nearly no TBHP was formed. It seems that the silicon layer of the micro reactor was not stable under such experimental conditions. In the present work, for the first time a conversion level near to that of the industrial batch process has been reached in a micro reactor for the isobutane oxidation.

The aerobic oxidative cross-coupling of tetrahydroisoquinolines (THIQs) with diethylzinc catalyzed by CuCl2 has been examined by means of electrospray mass spectrometry (ESI-MS). Substrates, intermediates, and the product were readily detected. Particular emphasis has been placed on the role of CuCl2 . Formation of the intermediate iminium species has been investigated in more detail by ESI-MS, electrochemistry-coupled ESI mass spectrometry (EC-MS), and cyclic voltammetry (CV). Our experiments have consistently revealed strong influences of the N-substituent of the THIQ derivative and its oxidation stability with respect to CuCl2 . The results may help to expand the synthetic scope of the reaction, while also further establishing EC-MS as a valuable technique for linking mass spectrometry with cyclic voltammetry in mechanistic studies of organic redox reactions.

Rotational stocking theoretically enables regrazing of regrowth, but regrowth may be limited in xerophytic vegetation. We tested the hypothesis that regrowth would be slow and fixed in Hesperostipa comata (a caespitose, drought-tolerant grass), while growth would be flexible in Pascopyrum smithii (a rhizomatous, less drought-tolerant grass) under increasing defoliation and moisture, by assessing tiller growth rates, population dynamics and plant yield on marked plants in a Dry Mixed Grass prairie. Plots were clipped in late summer to simulate a deferred control, or intermittently during the growing season (May–August) at high intensity–low frequency (HILF), low intensity–high frequency (LIHF) or high intensity–high frequency and crossed with two water treatments (ambient and addition) in both a xeric upland and a mesic lowland. Growing season defoliation increased tiller growth rates of P. smithii in the upland, whereas HILF and LIHF reduced growth in the lowland. All defoliation regimes increased tiller growth for H. comata. Tiller populations of H. comata increased with frequent defoliation, while tiller populations of P. smithii decreased regardless of defoliation regime. Frequent defoliation, regardless of intensity, reduced yield relative to the deferred control for both grasses. While water addition consistently increased growth rates and reduced differences in tiller number among defoliation treatments, the regrowth of both grasses remained similar under varied defoliation with ambient moisture. High moisture conditions also promoted regrowth more in P. smithii compared to H. comata. In summary, neither grass species displayed an inherently fixed or flexible tiller or plant yield response in response to defoliation or moisture.

Long-term cattle grazing may degrade grassland soils, but how soil CO2, CH4 and N2O fluxes respond to long-term cattle grazing is poorly understood. Therefore, we quantified soil CO2, CH4 and N2O fluxes in response to four levels (none, light, heavy, very heavy) of long-term (>65 yr) cattle grazing on a rough fescue grassland in the foothills of the Rocky Mountains, Canada over three grazing seasons. The grazed grassland soils emitted 37 to 51% more CO2 than non-grazed soils. Grazed grassland soils were small CH4 sinks and small N2O sources each season, and their cumulative emissions were both significantly affected by a cattle stocking rate × year interaction, indicating the grazing effect was a function of environmental conditions. Soil CH4 uptake negatively correlated with soil moisture (r = -0.59). The 2013 grazing season had about 41% greater precipitation than average and grazing significantly decreased CH4 uptake 31 to 38% compared with non-grazed soils. The N2O emissions were 122 to 179% greater with heavy and very heavy grazing than none in the wet year, unaffected by grazing in the normal precipitation year, and 72% lower with light grazing than none in the dry year. Predicting trace gas fluxes from grazed grassland soils across space and time is difficult due to interactions amongst weather conditions, edaphic properties and grazing intensity. However, long-term cattle grazing increased soil CO2 fluxes, while the grazing effect on CH4 uptake depended on precipitation and the soil N2O flux responded as a function of grazing intensity and precipitation.

Cattle trails in grazed pastures close to rivers may adversely affect surface water quality of the adjacent river by directing runoff to it. The objective of this 3-yr study (2013-2015) in southern Alberta, Canada, was to determine if cattle trails significantly increased the risk of runoff and contaminants (sediment, nutrients) compared with the adjacent grazed pasture (control). A portable rainfall simulator was used to generate artificial rainfall (140 mm h) and runoff. The runoff properties measured were time to runoff and initial abstraction (infiltration), total runoff depth and average runoff rates, as well as concentrations and mass loads of sediment, N, and P fractions. Cattle trails significantly ( ≤ 0.10) decreased time to runoff and initial abstraction (26-32%) in the 2 yr measured and increased total runoff depth, runoff coefficients, and average runoff rates (21-51%) in 2 of 3 yr. Concentrations of sediment, N, and P fractions in runoff were not significantly greater for cattle trails than for control areas. However, mass loads of total suspended solids (57-85% increase), NH-N (31-90%), and dissolved reactive P (DRP) (30-92%) were significantly greater because of increased runoff volumes. Overall, runoff quantity and loads of sediment, NH-N, and DRP were greater for cattle trails compared with the adjacent grazed pasture, and hydrologic connection with cattle-access sites on the riverbank suggests that this could adversely affect water quality in the adjacent river. Extrapolation of the study results should be tempered by the specific conditions represented by this rainfall simulation study.

Herbage minerals affect performance of grazing cattle. We investigated the response of herbage P, K, Ca and Mg contents and Ca/P and K/(Ca + Mg) ratios to long-term stocking rate, continuous vs. discontinued grazing practice, and sampling year. Cattle had been stocked at 2·4 and 4·8 animal unit months ha−1 since 1949. Exclosures were installed in April 1998. Herbage samples were collected near peak herbage mass in 2001, 2003, 2008 and 2012 and analysed for mineral content. Mineral contents were similar between the two stocking rates, but were lower (P

OBJECTIVES Patients with Hashimoto thyroiditis show structural changes of the thyroid that can be identified by a variety of sonographic criteria. We conducted this study to investigate whether there is a correlation between sonography and antibody activity and to assess the role of sonography in the diagnosis and follow-up of Hashimoto thyroiditis. In addition, we present a new classification system (termed the VESINC system [volume, echogenicity, sonographic texture, pseudonodular hypoechoic infiltration, nodules, and cysts]), which helps improve the clarity of sonographic findings. METHODS The study included 223 consecutive patients with previously diagnosed Hashimoto autoimmune thyroiditis who attended the thyroid clinic of the German Armed Forces Central Hospital in Koblenz for follow-up examinations between 2006 and 2008. Laboratory tests were performed to measure the levels of free triiodothyronine, free thyroxine, thyrotropin, anti-thyroglobulin antibodies (TgAbs), and antithyroid peroxidase antibodies (TPOAbs). Sonography was performed according to a strict protocol. We then assessed whether a correlation existed between antibody activity and the 6 sonographic variables of the VESINC system. RESULTS Hypoechogenicity, heterogeneity, and pseudonodular hypoechoic infiltration were associated with significantly higher TPOAb activity (P < .001). There were no significant correlations between the other sonographic variables examined (cysts, nodules, and volume) or the biometric data with the TPOAb and TgAb levels. In addition, an assessment of TgAb levels did not show significant differences in correlations with any of the sonographic variables. CONCLUSIONS Sonography is a noninvasive diagnostic imaging modality that provides information about the level of inflammatory activity. Markedly decreased echogenicity, heterogeneity, and multifocal pseudoinodular hypoechoic infiltration are indicative of a high level of inflammatory activity. The sonographic classification system presented here (VESINC system) can be a useful tool for comparing sonographic findings in a rapid and objective manner during follow-up of Hashimoto thyroiditis.

Question: Litter (dead leaves or stems) affects production by conserving soil moisture. However, that role is not clear for grasslands where most precipitation falls during the growing season when the demand for water is high. Our question was: Does litter affect forage production in such an environment? Location: Typical steppe, Inner Mongolia. Methods: We examined the role of plant litter in two experiments where litter was either removed or added in a protected or heavily grazed site, respectively, in autumn and in spring in a split plot design. The treatments (control, moderate and heavy litter application) were applied once in five replications but repeated at new locations in each of 3 years. This was done to examine only the direct effect of litter on annual net primary production and selected plant characteristics and not potential secondary effects. We also measured soil moisture and soil temperature. Results: Removing litter caused a reduction in the amount of grass (Leymus chinensis) that was produced, but litter addition caused an inconsistent effect among years, with moderate applications producing the most positive effects. Litter removal resulted in shorter and less dense plants of L. chinensis and Carex duriuscula, while heavy litter addition in autumn reduced plant height of both Cleistogenes squarrosa and C. duriuscula. Conclusions: Litter was effective for enhancing soil moisture status and reducing soil heat units in the typical steppe of Inner Mongolia. Therefore, litter mass may serve as an index of grassland health in such environments.

Numerous studies have examined the nutritive quality of fodder plants in different seasons but few have related this seasonal response to long-term grazing intensity. Our objective was to examine the effect of long-term grazing on the concentrations of total nitrogen, δ15N, and total phosphorus in selected forage species from the fescue grassland near Stavely, Alberta. Plants were selected from paddocks that had been stocked at 0 (control), 2.4 (moderate grazing), and 4.8 (heavy grazing) animal unit months ha–1 for 58 years. Plant material from ten species was sampled and analyzed at monthly intervals from May to September in 2007. Total N and P concentrations were not (p > 0.05) affected by grazing for most species, but total N and P concentrations in Poa. pratensis L. were higher (p < 0.05) in grazed treatments than in the control. These results reflect an altered plant phenology through defoliation and illustrate delayed phenology in P. pratensis when grazed. The higher δ15N concentration for most species in the grazed treatments than the control is an indication of accelerated nitrogen cycling through dung and urine deposition.

The influence of the length of the linking alkyl spacer and of the presence of either a proton or a methyl group, in four related terdentate N 3 Schiff base ligands, on the structures and properties of the resulting iron(II) and cobalt(II) complexes has been investigated. The four ligands were prepared in situ by condensation of 2-(2-aminoethyl)pyridine or 2-(aminomethyl)pyridine with 2-acetylpyridine (L1 vs. L3) or 2-formylpyridine (L2 vs. L4). Hence they comprised a mixture of a relatively rigid chelate with. a 2-iminopyridyl moiety, comparable to bipyridine coordination, and a more flexible chelate containing the -(CH 2 ) n spacer. Four iron(II) comp lexes , [Fe(L1) 2 ](BF 4 ) 2 ( 1 ), [Fe(L2) 2 ](BF 4 ) 2 (2), [Fe(L3) 2 ](BF 4 ) 2 (3), [Fe(L4) 2 ](BF 4 ) 2 (4), were obtained whereas only in the case of the two ethylene (i.e. not methylene) spaced ligands could pure cobalt(II) complexes, [Co(L1) 2 ](BF 4 ) 2 (5), [Co(L2) 2 ]-(BF 4 ) 2 (6), be obtained. The 1 H NMR spectra confirmed that in MeCN 1-4 are diamagnetic whereas 5 and 6 are paramagnetic. X-ray structure determinations of the ethylene-linked complexes, 1, 5 and 6, revealed distorted octahedral geometries due to chelate ring restrictions. The M-N distances were typical for high-spin cobalt(II) (5 and 6) and for low-spin iron(II) (1). The magnetic data on 5 and 6 are typical of those expected for distorted octahedral high-spin d 7 species; fitting attempts have yielded zero-field splitting and low symmetry ligand field parameters. A metal-centred M 2+/3+ redox wave and ligand-based reduction processes were observed for 1-6 in MeCN. The metal-centred redox potential (Fe: 1 0.59, 2 0.68, 3 0.58, 4 0.70 V; Co: 5 0.03, 6 0.09 V vs. Fc/Fc + ) was influenced much more strongly by the presence of the proton vs. methyl group (Fe: shift of 0.09-0.12 V, Co: shift of 0.06 V) than by the bridging methylene vs. ethylene group (Fe: shift of 0.01-0.02 V).

This study investigated how disturbances from cultivation and haying altered the soil organic C (SOC) at two sites: one (Lethbridge) in a Stipa-Agropyron-Bouteloua community (49°7" N,112°57" W) and a second (Onefour) in a more xeric Stipa-Bouteloua community (49°3" N, 110°27'' W). Seven disturbance treatments were established on previously uncultivated native grassland to assess their effect on SOC 12 or 13 yr after establishment. A randomized complete block design with four replicates was used. Soils were sampled in the fall of 1995, 1997, and 2006 at two increments (0-15 and 15-30 cm) and a third (30-90 cm) was sampled in 2006. The soils were all analyzed for their SOC and, in 2006, also for their light fraction organic C (LF OC) and mineralizable C. Breaking and immediate establishment of perennial grass monocultures had no effect on SOC, LF OC, or mineralizable C. Wheat (Triticum aestivum L.) cropping (either fallow or continuous) resulted in a 19% loss of SOC after 13 yr. The rate of loss varied from an average of about 1.7 Mg ha -1 yr -1 in the first 4 yr to about 0.32 Mg ha -1 yr -1 in the subsequent 9 yr. These results are consistent with a more rapid loss of SOC in the first decade of cropping virgin soils, a slowing rate of loss, and a new steady state within a few decades.

Limited information exists on the effect of streambank fencing on riparian zone pastures. The objective of this study was to test the hypothesis that 4 to 6 yr of streambank fencing would improve the environmental quality of the cattle-excluded pasture compared with the grazed pasture and cause the fenced pasture to act as a buffer or filter strip. Rangeland health, vegetative and soil properties, and rainfall simulation runoff were measured in the cattle-excluded and adjacent grazed native pastures along the fenced reach of the Lower Little Bow River in southern Alberta, Canada, for 3 yr (2005-2007). Rangeland health was improved (health score increase from 55 to 72%); vegetation cover (13-21%) and standing litter (38-742%) were increased; and bare soil (72-93%) and soil bulk density (6-8%) were decreased under cattle exclusion, indicating an improvement in environmental quality from streambank fencing. In contrast, other vegetation (total and live basal area, fallen litter) and soil properties (soil water and soil C, N, and P) were not improved by cattle exclusion. Cattle exclusion significantly (P