A patient preference study that evaluated fluticasone furoate and mometasone furoate nasal sprays for allergic rhinitis

Background: Corticosteroid nasal sprays are the mainstay of treatment for allergic rhinitis. These sprays have sensory attributes such as scent and/or odor, taste and aftertaste, and run down the throat and/or the nose, which, when unpleasant, can affect patient preference for, and compliance with, treatment. Objective: This study examined patient preference for fluticasone furoate nasal spray (FFNS) or mometasone furoate nasal spray (MFNS) based on their sensory attributes after administration in patients with allergic rhinitis. Methods: This was a multicenter, randomized, double-blind, cross-over study. Patient preferences were determined by using three questionnaires (Overall Preference, Immediate Attributes, and Delayed Attributes). Results: Overall, 56% of patients stated a preference for FFNS versus 32% for MFNS (p _ 0.001); the remaining 12% stated no preference. More patients stated a preference for FFNS versus MFNS for the attributes of “less drip down the throat” (p _ 0.001), “less run out of the nose” (p _ 0.05), “more soothing” (p _ 0.05), and “less irritating” (p _ 0.001). More patients responded in favor of FFNS versus MFNS for the immediate attributes, “run down the throat” (p _ 0.001), and “run out of the nose” (p _ 0.001), and, in the delayed attributes, “run down the throat” (p _ 0.001), “run out of the nose” (p _ 0.01), “presence of aftertaste” (p _ 0.01), and “no nasal irritation” (p _ 0.001). Conclusion: Patients with allergic rhinitis preferred FFNS versus MFNS overall and based on a number of individual attributes, including “less drip down the throat,” “less run out of the nose,” and “less irritating.” Greater preference may improve patient adherence and thereby improve symptom management of the patient’s allergic rhinitis

Ultraplex- A rapid, flexible, all-in-one fastq demultiplexer [version 1; peer review- 1 approved]

BACKGROUND: The first step of virtually all next generation sequencing analysis involves the splitting of the raw sequencing data into separate files using sample-specific barcodes, a process known as “demultiplexing”. However, we found that existing software for this purpose was either too inflexible or too computationally intensive for fast, streamlined processing of raw, single end fastq files containing combinatorial barcodes. RESULTS: Here, we introduce a fast and uniquely flexible demultiplexer, named Ultraplex, which splits a raw FASTQ file containing barcodes either at a single end or at both 5’ and 3’ ends of reads, trims the sequencing adaptors and low-quality bases, and moves unique molecular identifiers (UMIs) into the read header, allowing subsequent removal of PCR duplicates. Ultraplex is able to perform such single or combinatorial demultiplexing on both single- and paired-end sequencing data, and can process an entire Illumina HiSeq lane, consisting of nearly 500 million reads, in less than 20 minutes. CONCLUSIONS: Ultraplex greatly reduces computational burden and pipeline complexity for the demultiplexing of complex sequencing libraries, such as those produced by various CLIP and ribosome profiling protocols, and is also very user friendly, enabling streamlined, robust data processing. Ultraplex is available on PyPi and Conda and via Github

Mapping landscape-scale peatland degradation using airborne lidar and multispectral data

This is the final version. Available on open access from Springer via the DOI in this recordContext An increased interest in the restoration of peatlands for delivering multiple benefits requires a greater understanding of the extent and location of natural and artificial features that contribute to degradation. Objectives We assessed the utility of multiple, fine-grained remote sensing datasets for mapping peatland features and associated degraded areas at a landscape-scale. Specifically, we developed an integrated approach to identify and quantify multiple types of peatland degradation including: anthropogenic drainage ditches and peat cuttings; erosional gullies and bare peat areas. Methods Airborne LiDAR, CASI and aerial image datasets of the South West UK, were combined to identify features within Dartmoor National Park peatland area that contribute to degradation. These features were digitised and quantified using ArcGIS before appropriate buffers were applied to estimate the wider ecohydrologically affected area. Results Using fine-scale, large-extent remotely sensed data, combined with aerial imagery enabled key features within the wider expanse of peatland to be successfully identified and mapped at a resolution appropriate to future targeted restoration. Combining multiple datasets increased our understanding of spatial distribution and connectivity within the landscape. An area of 29 km2 or 9.2% of the Dartmoor peatland area was identified as significantly and directly ecohydrologically degraded. Conclusions Using a combination of fine-grained remotely sensed datasets has advantages over traditional ground survey methods for identification and mapping of anthropogenic and natural erosion features at a landscape scale. The method is accurate, robust and cost-effective particularly given the remote locations and large extent of these landscapes, facilitating effective and targeted restoration planning, management and monitoring.Dartmoor National Park AuthorityDartmoor Peatland PartnershipDuchy of CornwallEnvironment AgencyForestry CommissionMinistry of DefenceNatural EnglandSouth West partnership for Environmental and Economic Prosperity (SWEEP)South West WaterNatural Environment Research Council (NERC

Finding cell-specific expression patterns in the early Ciona embryo with single-cell RNA-seq

Single-cell RNA-seq has been established as a reliable and accessible technique enabling new types of analyses, such as identifying cell types and studying spatial and temporal gene expression variation and change at single-cell resolution. Recently, single-cell RNA-seq has been applied to developing embryos, which offers great potential for finding and characterising genes controlling the course of development along with their expression patterns. In this study, we applied single-cell RNA-seq to the 16-cell stage of the Ciona embryo, a marine chordate and performed a computational search for cell-specific gene expression patterns. We recovered many known expression patterns from our single-cell RNA-seq data and despite extensive previous screens, we succeeded in finding new cell-specific patterns, which we validated by in situ and single-cell qPCR

The differential absorption of a series of P-glycoprotein substrates in isolated perfused lungs from Mdr1a/1b genetic knockout mice can be attributed to distinct physico-chemical properties: an insight into predicting transporter-mediated, pulmonary specific disposition

Purpose To examine if pulmonary P-glycoprotein (P-gp) is functional in an intact lung; impeding the pulmonary absorption and increasing lung retention of P-gp substrates administered into the airways. Using calculated physico-chemical properties alone build a predictive Quantitative Structure-Activity Relationship (QSAR) model distinguishing whether a substrate’s pulmonary absorption would be limited by P-gp or not. Methods A panel of 18 P-gp substrates were administered into the airways of an isolated perfused mouse lung (IPML) model derived from Mdr1a/Mdr1b knockout mice. Parallel intestinal absorption studies were performed. Substrate physico-chemical profiling was undertaken. Using multivariate analysis a QSAR model was established. Results A subset of P-gp substrates (10/18) displayed pulmonary kinetics influenced by lung P-gp. These substrates possessed distinct physico-chemical properties to those P-gp substrates unaffected by P-gp (8/18). Differential outcomes were not related to different intrinsic P-gp transporter kinetics. In the lung, in contrast to intestine, a higher degree of non-polar character is required of a P-gp substrate before the net effects of efflux become evident. The QSAR predictive model was applied to 129 substrates including eight marketed inhaled drugs, all these inhaled drugs were predicted to display P-gp dependent pulmonary disposition. Conclusions Lung P-gp can affect the pulmonary kinetics of a subset of P-gp substrates. Physico-chemical relationships determining the significance of P-gp to absorption in the lung are different to those operative in the intestine. Our QSAR framework may assist profiling of inhaled drug discovery candidates that are also P-gp substrates. The potential for P-gp mediated pulmonary disposition exists in the clinic

TDP-43 condensation properties specify its RNA binding and regulation

Summary: Mutations causing amyotrophic lateral sclerosis (ALS) often affect the condensation properties of RNA-binding proteins (RBPs). However, the role of RBP condensation in the specificity and function of protein-RNA complexes remains unclear. We created a series of TDP-43 C-terminal domain (CTD) variants that exhibited a gradient of low to high condensation propensity, as observed in vitro and by nuclear mobility and foci formation. Notably, a capacity for condensation was required for efficient TDP-43 assembly on subsets of RNA-binding regions, which contain unusually long clusters of motifs of characteristic types and density. These “binding-region condensates” are promoted by homomeric CTD-driven interactions and required for efficient regulation of a subset of bound transcripts, including autoregulation of TDP-43 mRNA. We establish that RBP condensation can occur in a binding-region-specific manner to selectively modulate transcriptome-wide RNA regulation, which has implications for remodeling RNA networks in the context of signaling, disease, and evolution

Data Science Issues in Understanding Protein-RNA Interactions

An interplay of experimental and computational methods is required to achieve a comprehensive understanding of protein–RNA interactions. UV crosslinking and immunoprecipitation (CLIP) identifies endogenous interactions by sequencing RNA fragments that copurify with a selected RNA-binding protein under stringent conditions. Here we focus on approaches for the analysis of the resulting data and appraise the methods for peak calling, visualization, analysis, and computational modeling of protein–RNA binding sites. We advocate that the sensitivity and specificity of data be assessed in combination for computational quality control. Moreover, we demonstrate the value of analyzing sequence motif enrichment in peaks assigned from CLIP data and of visualizing RNA maps, which examine the positional distribution of peaks around regulated landmarks in transcripts. We use these to assess how variations in CLIP data quality and in different peak calling methods affect the insights into regulatory mechanisms. We conclude by discussing future opportunities for the computational analysis of protein–RNA interaction experiments

Assessing the impact of peat erosion on growing season CO2 fluxes by comparing erosional peat pans and surrounding vegetated haggs (article)

This is the author accepted manuscript. The final version is available from International Mire Conservation Group and International Peat Society via the DOI in this record.The research data supporting this publication are openly available from the University of Exeter's institutional repository at: https://doi.org/10.24378/exe.1143.Peatlands are recognised as an important but vulnerable ecological resource. Understanding the effects of existing damage, in this case erosion, enables more informed land management decisions to be made. Over the growing seasons of 2013 and 2014 photosynthesis and ecosystem respiration were measured using closed chamber techniques within vegetated haggs and erosional peat pans in Dartmoor National Park, southwest England. Below-ground total and heterotrophic respiration were measured and autotrophic respiration estimated from the vegetated haggs. The mean water table was significantly higher in the peat pans than in the vegetated haggs; because of this, and the switching from submerged to dry peat, there were differences in vegetation composition, photosynthesis and ecosystem respiration. In the peat pans photosynthetic CO2 uptake and ecosystem respiration were greater than in the vegetated haggs and strongly dependent on the depth to water table (r2>0.78, p<0.001). Whilst in the vegetated haggs, photosynthesis and ecosystem respiration had the strongest relationships with normalised difference vegetation index (NDVI) (r2=0.82, p<0.001) and soil temperature at 15 cm depth (r2=0.77, p=0.001). Autotrophic and total below-ground respiration in the vegetated haggs varied with soil temperature; heterotrophic respiration increased as water tables fell. An empirically derived net ecosystem model estimated that over the two growing seasons both the vegetated haggs (29 and 20 gC m 2; 95 % confidence intervals of -570 to 762 and -873 to 1105 gC m-2) and the peat pans (7 and 8 gC m 2; 95 % confidence intervals of -147 to 465 and -136 to 436 gC m 2) were most likely net CO2 sources. This study suggests that not only the visibly degraded bare peat pans but also the surrounding vegetated haggs are losing carbon to the atmosphere, particularly during warmer and drier conditions, highlighting a need for ecohydrological restoration.MomentaSouth West Water (SWW)Dartmoor National Park Authorit

Drain blocking has limited short-term effects on greenhouse gas fluxes in a Molinia caerulea dominated shallow peatland (article)

This is the final version. Available on open access from Elsevier via the DOI in this recordThe dataset associated with this article is available in ORE at https://doi.org/10.24378/exe.2723Drained peatlands dominated by purple moor grass (Molinia caerulea) are widespread in the UK and Western Europe. Although substantial carbon stores may be present in these peatlands, in this degraded state they are not currently acting as carbon sinks. Therefore, M.caerulea dominated peatlands have been identified as potential sites for ecohydrological restoration to tackle the current climate emergency. However, at present little is known about whether ditch blocking can raise water tables and promote the recovery of bog plant species, and the subsequent effects on carbon sequestration in these peatlands. To investigate the potential for restoration, we measured changes in water table depth, vegetation composition, photosynthesis at 1000 μmol Photons m−2 s−1 (PG1000), ecosystem respiration (REco) and partitioned below-ground respiration in two M.caerulea dominated peatlands in which drainage ditches had been blocked located in Exmoor National Park, southwest England. Measurements were made in two headwater catchments at ⅛, ¼ and ½ of the distance between adjacent drainage ditches at four control-restored paired sites, during the growing seasons pre- (2012) and post- (2014, 2016 & 2018) restoration. Restoration had a small but significant (p = 0.009) effect on water table depths however, this did not result in a significant change in vegetation composition (p > 0.350). Ecosystem respiration increased in both the control and restored locations following restoration however, this increase was significantly smaller (p = 0.010) at the restored locations, possibly due to a similarly reduced increase in photosynthesis, although this change was not significant (p = 0.116). Below-ground respiration showed no significant changes following restoration. This research illustrates how degraded these shallow peatlands are, and raises concerns that ditch blocking alone may not bring about the high and stable water tables required to perturb the existing Molinia caerulea-dominated ecosystem and substantially alter the carbon balance. Additional restoration measures may be required.South West Water (SWW)University of ExeterTechnology Strategy Board CouncilNatural Environment Research Council (NERC