Cough reflex testing with inhaled capsaicin in the study of chronic cough

AbstractObjectives: To assess the utility of capsaicin test in the differential diagnosis of non-productive causes of chronic cough and to examine the effects of treatment on this reflex. Participants: 86 healthy volunteers and 101 patients with chronic cough: asthma (n: 54), gastroesophageal reflux (n: 35) and post-nasal drip syndrome (n: 12). Design: Prospective intervention trial. Spirometry, bronchoprovocation test with histamine (PC20), and cough challenge with ascending concentrations of capsaicin (0.49–500 μM) were initially performed in all subjects. Patients were treated for 3 months according to the origin of the cough. Concentrations that elicited two (C2) and five or more coughs (C5) were determined before and after treatment.Results: In healthy subjects, cough sensitivity to capsaicin was not influenced by gender or smoking status; however, women with chronic cough were more sensitive to cough challenge than men. C2 and C5 were significantly lower in patients with asthma or gastroesophageal reflux than in post-nasal drip syndrome. No significant correlation was observed between the capsaicin cough threshold and PC20. Cough sensitivity did not improve significantly in most patients with asthma or gastroesophageal reflux despite adequate medical treatment during 3 months. Discriminative value of capsaicin test to differentiate healthy subjects from patients with asthma or reflux was poor. Conclusions: Cough sensitivity to inhaled capsaicin is a safe and reproducible tool in the study of chronic cough. However, its usefulness for the management and differential diagnosis is limited

One Dimensional Hybrid-Vlasov Simulation of a Hall Thruster

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97103/1/AIAA2012-4313.pd

Practical formulas for the refraction coefficient

Knowledge of the actual refraction coefficient is essential in leveling surveys and precise electromagnetic distance measurement reduction. The most common method followed by the surveyor for its determination is based on the use of simultaneous reciprocal zenith observations. The commonly used formula is only an approximation valid for approximately horizontal sightings, whereas the exact geometric solution turns out to be very complicated so that an iterative computation procedure is suggested instead. In the present paper, the goal is to derive a compact formula from the complete solution that is easy to implement and retains the necessary accuracy for horizontal and slanted sightings. In addition, the paper will also focus on the common situation for the surveyor where isolated observations have to be done and no partially compensating procedures—e.g., leap-frog or middle point—are possible. If temperature vertical profiles are unknown then the refraction coefficient cannot be reliably determined. Some surveyors may customarily use then an average value, e.g., k 5 0:13, perhaps being unaware of the risks involved in such simplistic assumption. In the present paper, it is also a goal to present a useful and simple formula for approximately estimating the refraction coefficient in terms of easily accessible parameters to correct the bulk of the refraction effect in single observations, always bearing in mind that determination of the refraction coefficient by means of a model may turn out to be somewhat inaccurate, but still better than the blind use of a universal k.The authors are grateful to the editor and the anonymous reviewers for their valuable suggestions, corrections, and comments that helped improve the original manuscript. This research is funded by the Spanish Ministry of Science and Innovation (Grant No. AYA2011-23232).Baselga Moreno, S.; García-Asenjo Villamayor, L.; Garrigues Talens, P. (2014). Practical formulas for the refraction coefficient. Journal of Surveying Engineering. 140(2):1-5. https://doi.org/10.1061/(ASCE)SU.1943-5428.0000124S15140

GalR, GalX and AraR co-regulate d-galactose and l-arabinose utilization in Aspergillus nidulans

Filamentous fungi produce a wide variety of enzymes in order to efficiently degrade plant cell wall polysaccharides. The production of these enzymes is controlled by transcriptional regulators, which also control the catabolic pathways that convert the released monosaccharides. Two transcriptional regulators, GalX and GalR, control d-galactose utilization in the model filamentous fungus Aspergillus nidulans, while the arabinanolytic regulator AraR regulates l-arabinose catabolism. d-Galactose and l-arabinose are commonly found together in polysaccharides, such as arabinogalactan, xylan and rhamnogalacturonan I. Therefore, the catabolic pathways that convert d-galactose and l-arabinose are often also likely to be active simultaneously. In this study, we investigated the interaction between GalX, GalR and AraR in d-galactose and l-arabinose catabolism. For this, we generated single, double and triple mutants of the three regulators, and analysed their growth and enzyme and gene expression profiles. Our results clearly demonstrated that GalX, GalR and AraR co-regulate d-galactose catabolism in A. nidulans. GalX has a prominent role on the regulation of genes of d-galactose oxido-reductive pathway, while AraR can compensate for the absence of GalR and/or GalX.Peer reviewe

Detailed analysis of the D-galactose catabolic pathways in Aspergillus niger reveals complexity at both metabolic and regulatory level

Funding Information: TC was supported by a grant of the NWO ALWOP.233 to RPdV. RSK and SG were supported by a grant of the Applied Science division (TTW) of NWO and the Technology Program of the Ministry of Infrastructure and Water Management 15807 to RPdV. The work conducted by the U.S. Department of Energy Joint Genome Institute, a DOE Office of Science User Facility, was supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. The Academy of Finland grant no. 308284 to MRM is also acknowledged. Publisher Copyright: © 2022 The Author(s)The current impetus towards a sustainable bio-based economy has accelerated research to better understand the mechanisms through which filamentous fungi convert plant biomass, a valuable feedstock for biotechnological applications. Several transcription factors have been reported to control the polysaccharide degradation and metabolism of the resulting sugars in fungi. However, little is known about their individual contributions, interactions and crosstalk. D-galactose is a hexose sugar present mainly in hemicellulose and pectin in plant biomass. Here, we study D-galactose conversion by Aspergillus niger and describe the involvement of the arabinanolytic and xylanolytic activators AraR and XlnR, in addition to the D-galactose-responsive regulator GalX. Our results deepen the understanding of the complexity of the filamentous fungal regulatory network for plant biomass degradation and sugar catabolism, and facilitate the generation of more efficient plant biomass-degrading strains for biotechnological applications.Peer reviewe

The five dimensions of B cell tolerance

B cell tolerance has been generally understood to be an acquired property of the immune system that governs antibody specificity in ways that avoid auto‐toxicity. As useful as this understanding has proved, it fails to fully explain the existence of auto‐reactive specificities in healthy individuals and contribution these may have to health. Mechanisms underlying B cell tolerance are considered to select a clonal repertoire that generates a collection of antibodies that do not bind self, ie tolerance operates more or less in three dimensions that largely spare autologous cells and antigens. Yet, most B lymphocytes in humans and probably in other vertebrates are auto‐reactive and absence of these auto‐reactive B cells is associated with disease. We suggest that auto‐reactivity can be embodied by extending the concept of tolerance by two further dimensions, one of time and circumstance and one that allows healthy cells to actively resist injury. In this novel concept, macromolecular recognition by the B cell receptor leading to deletion, anergy, receptor editing or B cell activation is extended by taking account of the time of development of normal immune responses (4th dimension) and the accommodation (or tolerance) of normal cells to bound antibody, activation of complement, and interaction with inflammatory cells (fifth dimension). We discuss how these dimensions contribute to understanding B cell biology in health or disease.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153034/1/imr12813.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153034/2/imr12813_am.pd

The transcriptional activator ClrB is crucial for the degradation of soybean hulls and guar gum in Aspergillus niger

Low-cost plant substrates, such as soybean hulls, are used for various industrial applications. Filamentous fungi are important producers of Carbohydrate Active enZymes (CAZymes) required for the degradation of these plant biomass substrates. CAZyme production is tightly regulated by several transcriptional activators and repressors. One such transcriptional activator is CLR-2/ClrB/ManR, which has been identified as a regulator of cellulase and mannanase production in several fungi. However, the regulatory network governing the expression of cellulase and mannanase encoding genes has been reported to differ between fungal species. Previous studies showed that Aspergillus niger ClrB is involved in the regulation of (hemi-)cellulose degradation, although its regulon has not yet been identified. To reveal its regulon, we cultivated an A. niger ΔclrB mutant and control strain on guar gum (a galactomannan-rich substrate) and soybean hulls (containing galactomannan, xylan, xyloglucan, pectin and cellulose) to identify the genes that are regulated by ClrB. Gene expression data and growth profiling showed that ClrB is indispensable for growth on cellulose and galactomannan and highly contributes to growth on xyloglucan in this fungus. Therefore, we show that A. niger ClrB is crucial for the utilization of guar gum and the agricultural substrate, soybean hulls. Moreover, we show that mannobiose is most likely the physiological inducer of ClrB in A. niger and not cellobiose, which is considered to be the inducer of N. crassa CLR-2 and A. nidulans ClrB

The Sugar Metabolic Model of Aspergillus niger Can Only Be Reliably Transferred to Fungi of Its Phylum

Fungi play a critical role in the global carbon cycle by degrading plant polysaccharides to small sugars and metabolizing them as carbon and energy sources. We mapped the well-established sugar metabolic network of Aspergillus niger to five taxonomically distant species (Aspergillus nidulans, Penicillium subrubescens, Trichoderma reesei, Phanerochaete chrysosporium and Dichomitus squalens) using an orthology-based approach. The diversity of sugar metabolism correlates well with the taxonomic distance of the fungi. The pathways are highly conserved between the three studied Eurotiomycetes (A. niger, A. nidulans, P. subrubescens). A higher level of diversity was observed between the T. reesei and A. niger, and even more so for the two Basidiomycetes. These results were confirmed by integrative analysis of transcriptome, proteome and metabolome, as well as growth profiles of the fungi growing on the corresponding sugars. In conclusion, the establishment of sugar pathway models in different fungi revealed the diversity of fungal sugar conversion and provided a valuable resource for the community, which would facilitate rational metabolic engineering of these fungi as microbial cell factories

The Amylolytic Regulator AmyR of Aspergillus niger Is Involved in Sucrose and Inulin Utilization in a Culture-Condition-Dependent Manner

Filamentous fungi degrade complex plant material to its monomeric building blocks, which have many biotechnological applications. Transcription factors play a key role in plant biomass degradation, but little is known about their interactions in the regulation of polysaccharide degradation. Here, we deepened the knowledge about the storage polysaccharide regulators AmyR and InuR in Aspergillus niger. AmyR controls starch degradation, while InuR is involved in sucrose and inulin utilization. In our study, the phenotypes of A. niger parental, ΔamyR, ΔinuR and ΔamyRΔinuR strains were assessed in both solid and liquid media containing sucrose or inulin as carbon source to evaluate the roles of AmyR and InuR and the effect of culture conditions on their functions. In correlation with previous studies, our data showed that AmyR has a minor contribution to sucrose and inulin utilization when InuR is active. In contrast, growth profiles and transcriptomic data showed that the deletion of amyR in the ΔinuR background strain resulted in more pronounced growth reduction on both substrates, mainly evidenced by data originating from solid cultures. Overall, our results show that submerged cultures do not always reflect the role of transcription factors in the natural growth condition, which is better represented on solid substrates. Importance: The type of growth has critical implications in enzyme production by filamentous fungi, a process that is controlled by transcription factors. Submerged cultures are the preferred setups in laboratory and industry and are often used for studying the physiology of fungi. In this study, we showed that the genetic response of A. niger to starch and inulin was highly affected by the culture condition, since the transcriptomic response obtained in a liquid environment did not fully match the behavior of the fungus in a solid environment. These results have direct implications in enzyme production and would help industry choose the best approaches to produce specific CAZymes for industrial purposes

Impact of assimilating NOAA VIIRS aerosol optical depth (AOD) observations on global AOD analysis from the Copernicus Atmosphere Monitoring Service (CAMS)

Global monitoring of aerosols is required to analyse the impacts of aerosols on air quality and to understand their role in modulating the climate variability. The Copernicus Atmosphere Monitoring Service (CAMS) provides near-real-time forecasts and reanalyses of aerosols using the ECMWF Integrated Forecasting System (IFS), constrained by the assimilation of MODIS and Polar Multi-Sensor Aerosol Optical Properties (PMAp) aerosol optical depth (AOD). Given the potential end of lifetime of MODIS AOD, implementing new AOD observations in the CAMS operational suite is a priority to ensure the continuity of the CAMS forecast performances. The objective of this work is to test the assimilation of the NOAA VIIRS AOD product from S-NPP and NOAA20 satellites in the IFS model. Simulation experiments assimilating VIIRS on top or in place of MODIS were carried out from June 2021 to November 2021 to evaluate the impacts on the AOD analysis. For maritime aerosol background, the assimilation of VIIRS and the use of VIIRS from NOAA20 as an anchor reduce the analysis AOD values compared to MODIS-based experiments, in which the analysis values were too high due to the positive bias of MODIS/Terra over ocean. Over land, the assimilation of VIIRS induces a large increase in the analysis over biomass burning regions where VIIRS shows larger AOD than MODIS due to differences in the aerosol models and cloud filtering between MODIS and VIIRS retrieval algorithms. For dust source regions, the analysis is reduced when VIIRS is assimilated on top of or in place of MODIS, particularly over the Sahara, the Arabian Peninsula and a few places in Asia in the July–August period. The assimilation of VIIRS leads to an overall reduction of the bias in AOD analysis evaluated against AERONET measurements, with the largest bias reduction over Europe and desert and maritime sites.</p