ReLA, a local alignment search tool for the identification of distal and proximal gene regulatory regions and their conserved transcription factor binding sites

Motivation: The prediction and annotation of the genomic regions involved in gene expression has been largely explored. Most of the energy has been devoted to the development of approaches that detect transcription start sites, leaving the identification of regulatory regions and their functional transcription factor binding sites (TFBSs) largely unexplored and with important quantitative and qualitative methodological gaps

The economic burden of bronchiectasis - known and unknown:a systematic review

Abstract Background The increasing prevalence and recognition of bronchiectasis in clinical practice necessitates a better understanding of the economic disease burden to improve the management and achieve better clinical and economic outcomes. This study aimed to assess the economic burden of bronchiectasis based on a review of published literature. Methods A systematic literature review was conducted using MEDLINE, Embase, EconLit and Cochrane databases to identify publications (1 January 2001 to 31 December 2016) on the economic burden of bronchiectasis in adults. Results A total of 26 publications were identified that reported resource use and costs associated with management of bronchiectasis. Two US studies reported annual incremental costs of bronchiectasis versus matched controls of US$5681 and US$2319 per patient. Twenty-four studies reported on hospitalization rates or duration of hospitalization for patients with bronchiectasis. Mean annual hospitalization rates per patient, reported in six studies, ranged from 0.3–1.3, while mean annual age-adjusted hospitalization rates, reported in four studies, ranged from 1.8–25.7 per 100,000 population. The average duration of hospitalization, reported in 12 studies, ranged from 2 to 17 days. Eight publications reported management costs of bronchiectasis. Total annual management costs of €3515 and €4672 per patient were reported in two Spanish studies. Two US studies reported total costs of approximately US$26,000 in patients without exacerbations, increasing to US$36,00–37,000 in patients with exacerbations. Similarly, a Spanish study reported higher total annual costs for patients with > 2 exacerbations per year (€7520) compared with those without exacerbations (€3892). P. aeruginosa infection increased management costs by US$31,551 to US$56,499, as reported in two US studies, with hospitalization being the main cost driver. Conclusions The current literature suggests that the economic burden of bronchiectasis in society is significant. Hospitalization costs are the major driver behind these costs, especially in patients with frequent exacerbations. However, the true economic burden of bronchiectasis is likely to be underestimated because most studies were retrospective, used ICD-9-CM coding to identify patients, and often ignored outpatient burden and cost. We present a conceptual framework to facilitate a more comprehensive assessment of the true burden of bronchiectasis for individuals, healthcare systems and society

Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids

We report here the design, development and performance of a novel formulation of liposome- encapsulated glucocorticoids (GCs). A highly efficient (>90%) and stable GC encapsulation was obtained based on a transmembrane calcium acetate gradient driving the active accumulation of an amphipathic weak acid GC pro-drug into the intraliposome aqueous compartment, where it forms a GC-calcium precipitate. We demonstrate fabrication principles that derive from the physicochemical properties of the GC and the liposomal lipids, which play a crucial role in GC release rate and kinetics. These principles allow fabrication of formulations that exhibit either a fast, second-order (t1/2 ∼1 h), or a slow, zero-order release rate (t1/2 ∼ 50 h) kinetics. A high therapeutic efficacy was found in murine models of experimental autoimmune encephalomyelitis (EAE) and hematological malignancies

RADICL-seq identifies general and cell type–specific principles of genome-wide RNA-chromatin interactions

Mammalian genomes encode tens of thousands of noncoding RNAs. Most noncoding transcripts exhibit nuclear localization and several have been shown to play a role in the regulation of gene expression and chromatin remodeling. To investigate the function of such RNAs, methods to massively map the genomic interacting sites of multiple transcripts have been developed; however, these methods have some limitations. Here, we introduce RNA And DNA Interacting Complexes Ligated and sequenced (RADICL-seq), a technology that maps genome-wide RNA-chromatin interactions in intact nuclei. RADICL-seq is a proximity ligation-based methodology that reduces the bias for nascent transcription, while increasing genomic coverage and unique mapping rate efficiency compared with existing methods. RADICL-seq identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type-specific RNA-chromatin interactions, and highlights the role of transcription in the establishment of chromatin structure

The Paleozoic Origin of Enzymatic Lignin Decomposition Reconstructed from 31 Fungal Genomes

Wood is a major pool of organic carbon that is highly resistant to decay, owing largely to the presence of lignin. The only organisms capable of substantial lignin decay are white rot fungi in the Agaricomycetes, which also contains non–lignin-degrading brown rot and ectomycorrhizal species. Comparative analyses of 31 fungal genomes (12 generated for this study) suggest that lignin-degrading peroxidases expanded in the lineage leading to the ancestor of the Agaricomycetes, which is reconstructed as a white rot species, and then contracted in parallel lineages leading to brown rot and mycorrhizal species. Molecular clock analyses suggest that the origin of lignin degradation might have coincided with the sharp decrease in the rate of organic carbon burial around the end of the Carboniferous period

Sensibilité du modèle SNOWPACK à la paramétrisation de la phase de précipitation dans un contexte de stabilité du couvert nival : étude de cas au Col Rogers, Parc national des Glaciers, Colombie-Britannique

La pratique des activités de plein air en hiver dans les régions montagneuses éloignées au Canada prend de plus en plus d’ampleur chez les adeptes du ski hors-piste et motoneigistes. Depuis les années 1990, en moyenne 12 personnes meurent chaque année des suites d’une avalanche au Canada, considérée comme étant le géorisque causant le plus de fatalité en période hivernale au Canada (Stethem, 2003). Il est alors primordial d’optimiser le suivi de la stabilité du couvert nival à grande échelle afin d’améliorer les outils supportant la production de bulletins d’avalanches pour les gestionnaires de parcs. Ce projet est donc motivé par cette problématique de suivi du couvert nival, plus spécifiquement de la stabilité de la neige que nous adressons avec le modèle thermodynamique multicouches SNOWPACK, développé en Suisse par l’institut pour l’étude de la neige et des avalanches (SLF). Ce modèle permet de simuler les propriétés géophysiques du manteau neigeux telles la densité, la température, la taille des grains, la teneur en eau, etc., et à partir desquelles un indice de stabilité est calculé. Puisque le modèle fut développé en prenant en considération l’environnement de la Suisse, il a été démontré qu’il est mal adapté à la réalité des rocheuses canadiennes. Plus particulièrement, une mauvaise paramétrisation de la phase de précipitation pourrait affecter les simulations du couvert nival dans cette région. En effet, le modèle considère que la transition solide à liquide se produit à 1,2 °C, ne représentant pas nécessairement la réalité des rocheuses canadiennes, dont les précipitations mixtes peuvent se produire à des températures beaucoup plus variables que celles qu’offrent les Alpes suisses. Ce projet vise donc l’évaluation et le développement d’une nouvelle paramétrisation empirique de la phase de précipitation à l’aide de données météorologiques in situ. Pour ce faire, les données pour ce projet ont été recueillies, entre autres, par un disdromètre installé depuis 2016 au Mont Fidelity dans le Parc national des Glaciers, en Colombie-Britannique. Celui-ci permet de mesurer les taux et les différents types de précipitations dans l’atmosphère. Aussi, nous travaillons à partir des stations météorologiques de la région, dont celle au Mont Fidelity, qui nous offre des mesures comme la température et taux de précipitations qui sont centrales au développement empirique de notre approche. Les mesures acquises sur le terrain par notre équipe ainsi que celle de Parc Canada permettront de valider nos simulations à la suite du développement de ce nouveau schéma

Variation in Valuation: Open Space and Geography

We estimate hedonic valuation models of local open space separately for 215 cities in the Eastern US, and derive city-specific marginal willingness to pay (MWTP). We then examine variation in MWTP and city-level determinants. Valuation is largely local – relatively large changes in income or existing conservation lead to modest changes in MWTP – suggesting validity of benefit transfer across regions. However, geographic features that naturally limit development do correlate with MWTP. As a result, we examine geographic features as instrumental variables, and find that on average steep slope and water/wetlands yield valuation coefficients of opposite sign, consistent with a LATE interpretation