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Biology subjects

Johnson, R. M.

Publications and source records attributed to Johnson, R. M..

3 recordsLinked to original sources

Honey bee pollen foraging ecology across an urbanization gradient

Understanding animal foraging ecology requires large samples sizes spanning broad environmental and temporal gradients. For pollinators, this has been hampered by the laborious nature of morphologically identifying pollen. Metagenetic pollen analysis is a solution to this issue, but the field has struggled with poor quantitative performance. Building upon prior laboratory and bioinformatic methods, we applied quantitative multi-locus metabarcoding to characterize the foraging ecology of honey bee colonies situated along an urban-agricultural gradient in central Ohio, USA. In cross-validating a subset of our metabarcoding results using microscopic palynology, we find strong concordance between the molecular and microscopic methods. Our results show that, relative to the agricultural environment, urban and suburban environments were associated with higher taxonomic diversity and temporal turnover of honey bee pollen forage. This is likely reflective of the fine-grain heterogeneity and high beta diversity of urban floral landscapes at the scale of honey bee foraging. Our work also demonstrates the power of honey bees as environmental samplers of floral community composition at large spatial scales, aiding in the distinction of taxa characteristically associated with urban or agricultural land use from those distributed ubiquitously across our landscape gradient.

ecology

Structure-based identification and characterisation of novel inhibitors of KNa1.1 potassium channels, a stratified target for KCNT1-related epilepsy.

Several types of drug-resistant epileptic encephalopathies of infancy have been associated with mutations in the KCNT1 gene, which encodes the sodium-activated potassium channel subunit KNa1.1. These mutations are commonly gain-of-function, increasing channel activity, therefore inhibition by drugs is proposed as a stratified approach to treat disorders. To date, quinidine therapy has been trialled with several patients, but mostly with unsuccessful outcomes, which has been linked to its low potency and lack of specificity. Here we describe the use of a cryo-electron microscopy-derived KNa1.1 structure and mutational analysis to identify the quinidine biding site and identified novel inhibitors that target this site using computational methods. We describe six compounds that inhibit KNa1.1 channels with low- and sub-micromolar potencies, likely through binding in the intracellular pore vestibule. In preliminary hERG inhibition and cytotoxicity assays, two compounds showed little effect. These compounds may provide starting points for the development of novel pharmacophores for KNa1.1 inhibition, with the view to treating KCNT1-associated epilepsy and, with their potencies higher than quinidine, could become key tool compounds to further study this channel. Furthermore, this study illustrates the potential for utilising cryo-electron microscopy in ion channel drug discovery.

pharmacology and toxicology

Taxonomic identification from metagenomic and metabarcoding data using any genetic marker

Correct taxonomic identification of DNA sequences is central to studies of biodiversity using both shotgun metagenomic and metabarcoding approaches. However, there is no genetic marker that gives sufficient performance across all the biological kingdoms, hampering studies of taxonomic diversity in many groups of organisms. We here present a major update to Metaxa2 (http://microbiology.se/software/metaxa2/) that enables the use of any genetic marker for taxonomic classification of metagenome and amplicon sequence data.

bioinformatics