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Jérémy Laroche,1 Geneviève Pelletier,1 Marie-Ève Boulay,1 Andréanne Côté,1,2 Krystelle Godbout1,2 1Department of Pulmonology and Thoracic Surgery, Quebec Heart and Lung Institute, Laval University, Quebec City, QC, Canada; 2Department of Medicine, Faculty of Medicine, Laval University, Quebec City, QC, CanadaCorrespondence: Krystelle Godbout, Department of Pulmonology and Thoracic Surgery, Quebec Heart and Lung Institute, 2725 Chemin Sainte-Foy, Quebec, QC, G1V 4G5, Canada, Tel +1 418 656 4747, Fax +1 418 656 4762, Email krystelle.godbout@criucpq.ulaval.caIntroduction: Monoclonal antibodies targeting interleukin 5 (IL5) or its receptor (IL5R) are frequently used in severe asthma, in which they reduce exacerbations rate and oral corticosteroids (OCS) exposure. Anti-IL5/IL5Rs have been studied in patients with chronic obstructive pulmonary disease (COPD) without convincing benefits. However, these therapies have been used in clinical practice in COPD with apparently good results.Purpose: To describe the clinical characteristics and therapeutic response of COPD patients treated with anti-IL5/IL5R in a real-world setting.Patients and Methods: This is a retrospective case series of patients followed at the Quebec Heart and Lung Institute COPD clinic. Men or women, with an established diagnosis of COPD, and treated either with Mepolizumab or Benralizumab were included. Demographics, disease and exacerbation-related data, airway comorbidities, lung function, and inflammatory profile were extracted from patients’ hospital files at baseline visit and 12 months post-treatment. Therapeutic response to biologics was assessed by measuring change in annual exacerbation rate and/or OCS daily dose.Results: Seven COPD patients treated with biologics were identified (5M:2F). All were found to be OCSdependent at baseline. Radiological evidence of emphysema was found in all patients. One case was diagnosed with asthma before age 40. Residual eosinophilic inflammation was found in 5/6 patients (blood eosinophils count 237 ± 225× 106 cells/L) despite chronic OCS use. After 12 months of anti-IL5 treatment, mean OCS dose dropped from 12.0 ± 7.6 to 2.6 ± 4.3 mg/day, representing a 78% decrease. Annual exacerbations rate was reduced by 88%, from 8.2 ± 3.3 to 1.0 ± 1.2 per year.Conclusion: Chronic OCS use is a common characteristic of patients treated with anti-IL5/IL5R biological therapies in this real-world setting. In this population, it may be effective in decreasing OCS exposure and exacerbation.Keywords: COPD, treatment, anti-IL5, monoclonal antibodies, exacerbations, oral corticosteroids

Pertinence of pedological stratification of regional-scale reference systems about metallic trace elements content in soils.Walloon case studies. The natural background levels of metallic trace elements (ETM) in soils should be known in order (i) to understand the processes in which they are involved and (ii) to settle reference systems dedicated to the appraisal of agricultural or forest management practices, to the detection of contaminations, or to the time-course follow-up of regional values. A methodological framework has thus been set up to evaluate the importance of natural driving factors, also-called the pedogeochemical background, of the spatial distribution of ETM in soils. The methodology also aims at defining indicator values of the current degree of ETM contamination in agricultural soils. The spatial distributions of both ETM content and soil forming factors constitute the basement parameters of regional reference soil systems (RSS) about ETM content. The stratification of these regional reference soil systems on a pedological base, which means that soil volumes are clearly identified, appears to be valuable to refine predictions. This is shown through some case studies in the Walloon Region from Belgium. The more the regional reference systems will consider ancillary soil information as well as the geographic specificities of small natural regions, the more they will be relevant to detect local contaminations. For that reason, the digital soil map of Belgium can be considered as a potential powerfull tool for geochemical mapping, after an adaptation of its legend.

Mapping of expression quantitative trait loci (eQTL) is a powerful means for elucidating the genetic architecture of gene regulation. Yet, eQTL mapping has not been applied toward investigating the regulation architecture of genes involved in the process of population divergence, ultimately leading to speciation events. Here, we conducted an eQTL mapping experiment to compare the genetic architecture of transcript regulation in adaptive traits, differentiating the recently evolved limnetic (dwarf) and benthic (normal) species pairs of lake whitefish. The eQTL were mapped in three data sets derived from an [F.sub.1] hybriddwarf backcrossed family: the entire set of 66 genotyped individuals and the two sexes treated separately. We identified strikingly more eQTL in the female data set (174), compared to both male (54) and combined (33) data sets. The majority of these genes were not differentially expressed between male and female progeny of the backcross family, thus providing evidence for a strong pleiotropic sex-linked effect in transcriptomic regulation. The subtelomeric region of a linkage group segregating in females encompassed >50% of all eQTL, which exhibited the most pronounced additive effects. We also conducted a direct comparison of transcriptomic profiles between pure dwarf and normal progeny reared in controlled conditions. We detected 34 differentially expressed transcripts associated with eQTL segregating only in sexspecific data sets and mostly belonging to functional groups that differentiate dwarf and normal whitefish in natural populations. Therefore, these eQTL are not related to interindividual variation, but instead to the adaptive and historical genetic divergence between dwarf and normal whitefish. This study exemplifies how the integration of genetic and transcriptomic data offers a strong means for dissecting the functional genomic response to selection by separating mapping family-specific effects from genetic factors under selection, potentially involved in the phenotypic divergence of natural populations.

Alfalfa has a lower fiber digestibility and a greater concentration of degradable protein than grasses. Dairy cows could benefit from an increased digestibility of alfalfa fibers, or from a better match between nitrogen and energy supplies in the rumen. Alfalfa cultivars with improved fiber digestibility represent an opportunity to increase milk production, but no independent studies have tested these cultivars under the agroclimatic conditions of Canada. Moreover, decreasing metabolizable protein (MP) supply could increase N use efficiency while decreasing environmental impact, but it is often associated with a decrease in milk protein yield, possibly caused by a reduced supply of essential AA. This study evaluated the performance of dairy cows fed diets based on a regular or a reduced-lignin alfalfa cultivar and measured the effect of energy levels at low MP supply when digestible His (dHis), Lys (dLys), and Met (dMet) requirements were met. Eight Holstein cows were used in a double 4 × 4 Latin square design, each square representing an alfalfa cultivar. Within each square, 4 diets were tested: the control diet was formulated for an adequate supply of MP and energy (AMP_AE), whereas the 3 other diets were formulated to be deficient in MP (DMP; formulated to meet 90% of the MP requirement) with deficient (94% of requirement: DMP_DE), adequate (99% of requirement: DMP_AE), or excess energy supply (104% of requirement; DMP_EE). Alfalfa cultivars had no significant effect on all measured parameters. As compared with cows receiving AMP_AE, the dry matter intake of cows fed DMP_AE and DMP_EE was not significantly different but decreased for cows fed DMP_DE. The AMP_AE diet provided 103% of MP and 108% of NE L requirements whereas DMP_DE, DMP_AE, and DMP_EE diets provided 84, 87, and 87% of MP and 94, 101, and 107% of NE L requirements, respectively. In contrast to design, feeding DMP_EE resulted in a similar energy supply compared with AMP_AE, although MP supply has been effectively reduced. This resulted in a maintained milk and milk component yields and improved the efficiency of utilization of N, MP, and essential AA. The DMP diets decreased total N excretion, whereas DMP_AE and DMP_EE diets also decreased milk urea-N concentration. Reducing MP supply without negative effects on dairy cow performance is possible when energy, dHis, dLys, and dMet requirements are met. This could reduce N excretion and decrease the environmental impact of milk production. [ABSTRACT FROM AUTHOR]

The correlation for four marine bacterial isolates grown in chemostats at four or five dilution rates, showed that all measures of RNA content such as RNA cell-1, RNA biovolume ratio, RNA:DNA ratio, RNA:DNA:biovolume ratio were very different among isolates. The RNA:DNA ratio was responsible for 94% of variance. When isolates were considered individually, the regression of (RNA:DNA)/(RNA:DNA) on mu was significant and almost identical for 3 of the 4 isolates, implying a common relationship between RNA content and growth rate. Cellular RNA content is a prospective indicator of growth rate for gradually growing marine bacteria.