Direct recognition of invading pathogens by innate immune cells is a critical driver of the inflammatory response. However, cells of the innate immune system can also sense their local ...microenvironment and respond to physiological fluctuations in temperature, pH, oxygen and nutrient availability, which are altered during inflammation. Although cells of the immune system experience force and pressure throughout their life cycle, little is known about how these mechanical processes regulate the immune response. Here we show that cyclical hydrostatic pressure, similar to that experienced by immune cells in the lung, initiates an inflammatory response via the mechanically activated ion channel PIEZO1. Mice lacking PIEZO1 in innate immune cells showed ablated pulmonary inflammation in the context of bacterial infection or fibrotic autoinflammation. Our results reveal an environmental sensory axis that stimulates innate immune cells to mount an inflammatory response, and demonstrate a physiological role for PIEZO1 and mechanosensation in immunity.
Understanding broiler behaviours provides important implications for animal well-being and farm management. The objectives of this study were to classify specific broiler behaviours by analysing data ...from wearable accelerometers using two machine learning models, K-Nearest Neighbour (KNN) and Support Vector Machine (SVM). Lightweight triaxial accelerometers were used to record accelerations of nine 7-week-old broilers at a sampling frequency of 40 Hz. A total of 261.6-min data were labelled for four behaviours – walking, resting, feeding and drinking. Instantaneous motion features including magnitude area, vector magnitude, movement variation, energy, and entropy were extracted and stored in a dataset which was then segmented by one of the six window lengths (1, 3, 5, 7, 10 and 20 s) with 50% overlap between consecutive windows. The mean, variation, SD, minimum and maximum of each instantaneous motion feature and two-way correlations of acceleration data were calculated within each window, yielding a total of 43 statistic features for training and testing of machine learning models. Performance of the models was evaluated using pure behaviour datasets (single behaviour type per dataset) and continuous behaviour datasets (continuous recording that involved multiple behaviour types per dataset). For pure behaviour datasets, both KNN and SVM models showed high sensitivities in classifying broiler resting (87% and 85%, respectively) and walking (99% and 99%, respectively). The accuracies of SVM were higher than KNN in differentiating feeding (88% and 75%, respectively) and drinking (83% and 62%, respectively) behaviours. Sliding window with 1-s length yielded the best performance for classifying continuous behaviour datasets. The performance of classification model generally improved as more birds were included for training. In conclusion, classification of specific broiler behaviours can be achieved by recording bird triaxial accelerations and analysing acceleration data through machine learning. Performances of different machine learning models differ in classifying specific broiler behaviours.
The emergence of biomass based energy warrants the evaluation of syngas from biomass gasification as a fuel for personal power systems. The objectives of this study were to determine the performance ...and exhaust emissions of a commercial 5.5kW generator modified for operation with 100% syngas at different syngas flows and to compare the results with those obtained for gasoline operation at same electrical power. The maximum electrical power output for syngas operation was 1392W and that for gasoline operation was 2451W. However, the overall efficiency of the generator at maximum electrical power output for both the fuels were found to be the same. The concentrations of CO and NOx in the generator exhaust were lower for the syngas operation, respectively by 30–96% and 54–84% compared to the gasoline operation. However, the concentrations of CO2 in the generator exhaust were significantly higher by 33–167% for the syngas operation.
Recently, it was suggested that β-aminoisobutyric acid (BAIBA) is a myokine involved in browning of fat. However, there is no evidence for an acute effect of exercise supporting this statement and ...the metabolic distinct enantiomers of BAIBA were not taken into account. Concerning these enantiomers, there is at this point no consensus about resting concentrations of plasma R- and S-BAIBA. Additionally, a polymorphism of the alanine - glyoxylate aminotransferase 2 (AGXT2) gene (rs37369) is known to have a high impact on baseline levels of total BAIBA, but the effect on the enantiomers is unknown. Fifteen healthy recreationally active subjects, with different genotypes of rs37369, participated in a randomized crossover trial where they exercised for 1 h at 40% of P
peak
or remained at rest. Plasma samples were analyzed for R- and S-BAIBA using dual column HPLC-fluorescence. The plasma concentration of baseline R-BAIBA was 67 times higher compared to S-BAIBA (1734 ± 821 vs. 29.3 ± 7.8 nM). Exercise induced a 13 and 20% increase in R-BAIBA and S-BAIBA, respectively. The AGXT2 rs37369 genotype strongly affected baseline levels of R-BAIBA, but did not have an impact on baseline S-BAIBA. We demonstrate that BAIBA should not be treated as one molecule, given (1) the markedly uneven distribution of its enantiomers in human plasma favoring R-BAIBA, and (2) their different metabolic source, as evidenced by the AGXT2 polymorphism only affecting R-BAIBA. The proposed function in organ cross talk is supported by the current data and may apply to both enantiomers, but the tissue of origin remains unclear.
Abstract
DNA replication and repair defects or genotoxic treatments trigger interferon (IFN)-mediated inflammatory responses. However, whether and how IFN signaling in turn impacts the DNA ...replication process has remained elusive. Here we show that basal levels of the IFN-stimulated gene 15, ISG15, and its conjugation (ISGylation) are essential to protect nascent DNA from degradation. Moreover, IFNβ treatment restores replication fork stability in BRCA1/2-deficient cells, which strictly depends on topoisomerase-1, and rescues lethality of BRCA2-deficient mouse embryonic stem cells. Although IFNβ activates hundreds of genes, these effects are specifically mediated by ISG15 and ISGylation, as their inactivation suppresses the impact of IFNβ on DNA replication. ISG15 depletion significantly reduces cell proliferation rates in human BRCA1-mutated triple-negative, whereas its upregulation results in increased resistance to the chemotherapeutic drug cisplatin in mouse BRCA2-deficient breast cancer cells, respectively. Accordingly, cells carrying BRCA1/2 defects consistently show increased ISG15 levels, which we propose as an in-built mechanism of drug resistance linked to BRCAness.
The problem of deciding if a given triangulation of a sphere can be realized as the boundary sphere of a simplicial, convex polytope is known as the ‘Simplicial Steinitz problem’. It is known by an ...indirect and non-constructive argument that a vast majority of Bier spheres are non-polytopal. Contrary to that, we demonstrate that the Bier spheres associated to threshold simplicial complexes are all polytopal. Moreover, we show that all Bier spheres are starshaped. We also establish a connection between Bier spheres and Kantorovich–Rubinstein polytopes by showing that the boundary sphere of the KR-polytope associated to a polygonal linkage (weighted cycle) is isomorphic to the Bier sphere of the associated simplicial complex of “short sets”.
We study hidden geometry of Bier spheres Bier(K) = K
∗Δ K° by describing their natural geometric realizations, compute their volume, describe an effective criterion for their polytopality, and ...associate to Bier(K) a natural coarsening Fan(K) of the braid fan. We also establish a connection of Bier spheres of maximal volume with recent generalizations of the classical Van Kampen-Flores theorem and clarify the role of Bier spheres in the theory of generalized permutohedra.
Steam reforming of glycerol for hydrogen production involves complex reactions. As a result, several intermediate byproducts are formed and end up in the product stream affecting final purity of the ...hydrogen produced. Furthermore, the yield of the hydrogen depends on several process variables, such as system pressure, temperature, and ratio of reactants. The first step to understanding the effects of the aforementioned variables is a complete thermodynamic analysis. In this study, a thermodynamic equilibrium analysis has been performed for the steam reforming process of glycerol over the following variable ranges: pressure 1–5
atm, temperature 600–1000
K, and water-to-glycerol feed ratio 1:1–9:1. The equilibrium concentrations of different compounds were calculated by the method of direct minimization of the Gibbs free energy. The study revealed that the best conditions for producing hydrogen is at a temperature
>
900
K
, atmospheric pressure, and a molar ratio of water to glycerol of 9:1. Under these conditions methane production is minimized, and the carbon formation is thermodynamically inhibited.
Purpose
Chronic β-alanine supplementation leads to increased levels of muscle histidine-containing dipeptides. However, the majority of ingested β-alanine is, most likely, degraded by two ...transaminases: GABA-T and AGXT2. In contrast to GABA-T, the in vivo role of AGXT2 with respect to β-alanine metabolism is unknown. The purpose of the present work is to investigate if AGXT2 is functionally involved in β-alanine homeostasis.
Methods
Muscle histidine-containing dipeptides levels were determined in AGXT2 overexpressing or knock-out mice and in human subjects with different rs37369 genotypes which is known to affect AGXT2 activity. Further, plasma β-alanine kinetic was measured and urine was obtained from subjects with different rs37369 genotypes following ingestion of 1400 mg β-alanine.
Result
Overexpression of AGXT2 decreased circulating and muscle histidine-containing dipeptides (> 70% decrease;
p
< 0.05), while AGXT2 KO did not result in altered histidine-containing dipeptides levels. In both models, β-alanine remained unaffected in the circulation and in muscle (
p
> 0.05). In humans, the results support the evidence that decreased AGXT2 activity is not associated with altered histidine-containing dipeptides levels (
p
> 0.05). Additionally, following an acute dose of β-alanine, no differences in pharmacokinetic response were measured between subjects with different rs37369 genotypes (
p
> 0.05). Interestingly, urinary β-alanine excretion was 103% higher in subjects associated with lower AGXT2 activity, compared to subjects associated with normal AGXT2 activity (
p
< 0.05).
Conclusion
The data suggest that in vivo, β-alanine is a substrate of AGXT2; however, its importance in the metabolism of β-alanine and histidine-containing dipeptides seems small.
Background
Through-the-scope (TTS) endoscopic clipping devices are widely used. No benchtop testing or direct comparisons of these endoclips have been performed to show their rotational ability and ...inherent mechanical strengths during closure and after deployment. This study aimed to provide benchtop data that can be used to guide clinical applications and to promote future device research and development.
Methods
Benchtop testing and comparisons were performed for three groups of TTS clips: QuickClip2 long, resolution, and instinct clips. The main outcome measurements were device-in-endoscope retroflection angles (DIERA), opening strength, “snapping” force of acute clip closure, and neoprene pulling strength.
Results
The achievable gastroscope DIERA was 10° for QuickClip2, 3° for the resolution clip, and 10° for the instinct clip. The QuickClip and the Instinct clip rotated almost equally well under all endoscope configurations, including endoscopic retrograde cholangiopancreatography (ERCP). With or without a sheath, the resolution clip lacked the ability to rotate. During clip opening force testing (the amount of force required to force open the jaws of a deployed clip by 3.2 mm; 3.2 mm was chosen due to the standard dimension of the gauge used for the measurement), the Instinct clips were the strongest. For the Instinct clips, an opening force of 404 ± 124 g was needed to open the closed clip, and an additional 386 ± 133 g was required to open the clip jaws to 3.2 mm. In terms of snapping force during acute closure and neoprene pulling strength, the instinct and resolution clips performed almost equally. The limitations of the study were the benchtop testing and the finite sample size for closing and pulling strength comparisons.
Conclusions
The QuickClip2 and the Instinct clip rotate equally well under different endoscope configurations. The resolution clips lack rotational ability. The instinct clips are stronger mechanically than the other two TTS clips. Stronger clips are perhaps associated with higher therapeutic efficacy and retention rates.
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