Linking hydrological connectivity to gully erosion in savanna rangelands tributary to the Great Barrier Reef using structure‐from‐motion photogrammetry

Gully erosion is a major land management challenge globally and a particularly important issue in dry tropical savanna rangelands tributary to the Great Barrier Reef, Australia. This study investigated linkages between hillslope hydrological connectivity pathways and gully geomorphic change in the Burdekin River Basin. High‐resolution (0.1 m) topographic and land cover data derived from low‐cost aerial (via unmanned aircraft system) structure‐from‐motion with multiview stereo photogrammetry (SfM) were used to map fine‐scale connectivity patterns and quantify headcut retreat at the hillslope scale (~150,000 m2). Very high resolution (0.01 m) topographic models derived from ground‐based (via handheld digital camera) SfM were used to quantify the morphology and geomorphic change of several gully arms (300–700 m2) between 2016 and 2018. Median linear, areal, and volumetric headcut (n = 21) retreat rates were 0.2 m, 0.8 m2, and 0.3 m3 yr−1, respectively. At all study sites, the points where modelled hydrological flow lines intersected gullies corresponded to observed geomorphic change, enabling spatially explicit identification of gully extension pathways as a result of overland flow. Application of an index of connectivity demarcated parts of the hillslope most connected to the gully network. Bare areas, roads, and cattle trails were identified as important runoff source areas and hydrological conduits driving gully extension. Ground‐based SfM accurately reconstructed complex morphologic features including undercuts, overhangs, rills, and flutes, providing insights into within‐channel erosion processes. This study contributes to an improved understanding and modelling of hydrogeomorphic drivers of gully erosion in degraded savanna rangelands, ultimately benefiting gully management

A comparison of sequencing platforms and bioinformatics pipelines for compositional analysis of the gut microbiome

Abstract Background Advancements in Next Generation Sequencing (NGS) technologies regarding throughput, read length and accuracy had a major impact on microbiome research by significantly improving 16S rRNA amplicon sequencing. As rapid improvements in sequencing platforms and new data analysis pipelines are introduced, it is essential to evaluate their capabilities in specific applications. The aim of this study was to assess whether the same project-specific biological conclusions regarding microbiome composition could be reached using different sequencing platforms and bioinformatics pipelines. Results Chicken cecum microbiome was analyzed by 16S rRNA amplicon sequencing using Illumina MiSeq, Ion Torrent PGM, and Roche 454 GS FLX Titanium platforms, with standard and modified protocols for library preparation. We labeled the bioinformatics pipelines included in our analysis QIIME1 and QIIME2 (de novo OTU picking [not to be confused with QIIME version 2 commonly referred to as QIIME2]), QIIME3 and QIIME4 (open reference OTU picking), UPARSE1 and UPARSE2 (each pair differs only in the use of chimera depletion methods), and DADA2 (for Illumina data only). GS FLX+ yielded the longest reads and highest quality scores, while MiSeq generated the largest number of reads after quality filtering. Declines in quality scores were observed starting at bases 150–199 for GS FLX+ and bases 90–99 for MiSeq. Scores were stable for PGM-generated data. Overall microbiome compositional profiles were comparable between platforms; however, average relative abundance of specific taxa varied depending on sequencing platform, library preparation method, and bioinformatics analysis. Specifically, QIIME with de novo OTU picking yielded the highest number of unique species and alpha diversity was reduced with UPARSE and DADA2 compared to QIIME. Conclusions The three platforms compared in this study were capable of discriminating samples by treatment, despite differences in diversity and abundance, leading to similar biological conclusions. Our results demonstrate that while there were differences in depth of coverage and phylogenetic diversity, all workflows revealed comparable treatment effects on microbial diversity. To increase reproducibility and reliability and to retain consistency between similar studies, it is important to consider the impact on data quality and relative abundance of taxa when selecting NGS platforms and analysis tools for microbiome studies

Corrigendum to “A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm” [Toxicology and Applied Pharmacology volume 394C (2020) 114961]

© 2020 The Author(s) The authors regret that one affiliation address is mistaken in the published paper. Matthew Bridgland-Taylor's affiliation was incorrectly listed as Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge, United Kingdom. The correct affiliation is Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom. The authors would like to apologise for any inconvenience caused

A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm

© 2020 Introduction: hERG block potency is widely used to calculate a drug's safety margin against its torsadogenic potential. Previous studies are confounded by use of different patch clamp electrophysiology protocols and a lack of statistical quantification of experimental variability. Since the new cardiac safety paradigm being discussed by the International Council for Harmonisation promotes a tighter integration of nonclinical and clinical data for torsadogenic risk assessment, a more systematic approach to estimate the hERG block potency and safety margin is needed. Methods: A cross-industry study was performed to collect hERG data on 28 drugs with known torsadogenic risk using a standardized experimental protocol. A Bayesian hierarchical modeling (BHM) approach was used to assess the hERG block potency of these drugs by quantifying both the inter-site and intra-site variability. A modeling and simulation study was also done to evaluate protocol-dependent changes in hERG potency estimates. Results: A systematic approach to estimate hERG block potency is established. The impact of choosing a safety margin threshold on torsadogenic risk evaluation is explored based on the posterior distributions of hERG potency estimated by this method. The modeling and simulation results suggest any potency estimate is specific to the protocol used. Discussion: This methodology can estimate hERG block potency specific to a given voltage protocol. The relationship between safety margin thresholds and torsadogenic risk predictivity suggests the threshold should be tailored to each specific context of use, and safety margin evaluation may need to be integrated with other information to form a more comprehensive risk assessment

Attenuated Salmonella enterica Serovar Typhimurium, Strain NC983, Is Immunogenic, and Protective against Virulent Typhimurium Challenges in Mice

Non-typhoidal Salmonella (NTS) serovars are significant health burden worldwide. Although much effort has been devoted to developing typhoid-based vaccines for humans, currently there is no NTS vaccine available. Presented here is the efficacy of a live attenuated serovar Typhimurium strain (NC983). Oral delivery of strain NC983 was capable of fully protecting C57BL/6 and BALB/c mice against challenge with virulent Typhimurium. Strain NC983 was found to elicit an anti-Typhimurium IgG response following administration of vaccine and boosting doses. Furthermore, in competition experiments with virulent S. Typhimurium (ATCC 14028), NC983 was highly defective in colonization of the murine liver and spleen. Collectively, these results indicate that strain NC983 is a potential live attenuated vaccine strain that warrants further development

Astrovirus-Induced Synthesis of Nitric Oxide Contributes to Virus Control during Infection

Astrovirus is one of the major causes of infant and childhood diarrhea worldwide. Our understanding of astrovirus pathogenesis trails behind our knowledge of its molecular and epidemiologic properties. Using a recently developed small-animal model, we investigated the mechanisms by which astrovirus induces diarrhea and the role of both the adaptive and innate immune responses to turkey astrovirus type-2 (TAstV-2) infection. Astrovirus-infected animals were analyzed for changes in total lymphocyte populations, alterations in CD4(+)/CD8(+) ratios, production of virus-specific antibodies (Abs), and macrophage activation. There were no changes in the numbers of circulating or splenic lymphocytes or in CD4(+)/CD8(+) ratios compared to controls. Additionally, there was only a modest production of virus-specific Abs. However, adherent spleen cells from infected animals produced more nitric oxide (NO) in response to ex vivo stimulation with lipopolysaccharide. In vitro analysis demonstrated that TAstV-2 induced macrophage production of inducible nitric oxide synthase. Studies using NO donors and inhibitors in vivo demonstrated, for the first time, that NO inhibited astrovirus replication. These studies suggest that NO is important in limiting astrovirus replication and are the first, to our knowledge, to describe the potential role of innate immunity in astrovirus infection