Biology subjects

Johnson, C. R.

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

9 recordsLinked to original sources

bioRxiv2025

Development of the Early Childhood Duodenum across Ancestry, Geography and Environment

During early childhood, the proximal small intestinal mucosa plays a central role in growth, metabolism, immune priming, and neuronal development. Yet the cellular architecture and environmental responsiveness of the human small intestinal mucosa during this period remain poorly defined. Here, we generate a comprehensive cellular and spatial map of the duodenum from 87 children aged 6 months to 13 years, representing diverse ancestries and geographic contexts. This atlas integrates single-cell transcriptomic and spatial profiling with data on diet, social drivers of health, and environmental exposures. Using these data, we define mucosal cellular composition and chart its developmental trajectory in early childhood. Comparative analyses of children residing in the United States (US) and Pakistan reveal a differentiated enterocyte subset expressing the aquaglyceroporin, AQP10 (AQP10+ enterocyte), that is enriched in children from the US. We show that emergence of this enterocyte state depends on lipid exposure to intestinal stem cells and correlates with dietary fat intake. We also identify a previously-undescribed thyrotropin-releasing hormone (TRH+) enteroendocrine cell and provide evidence for a local endocrine-epithelial-lymphocyte circuit. Our work establishes a detailed framework for pediatric duodenal mucosal development and illuminates how intestinal cellular dynamics are shaped by age and environment.

developmental biology↗

bioRxiv2023

Population genomic analysis reveals genetic structure and thermal-tolerant genotypes in remnant Tasmanian giant kelp populations

Giant kelp, Macrocystis pyrifera, is a foundation species that forms dense forests of complex physical habitat and supports coastal biodiversity, productivity, and other essential ecosystem services. Tasmanian coasts have suffered a massive decline in giant kelp forests due to changes in regional oceanography and environmental conditions, but efforts are being made to restore these disappearing populations using identification and selective breeding for lineages that are more tolerant to warmer temperatures. Here, we used gametophytes that originated from remnant populations collected at three sites in northeastern and three sites in southeastern Tasmania to determine the genetic structure of the giant kelp population via genotyping-by-sequencing (GBS) and assembled a draft genome from a Tasmanian giant kelp sporophyte individual. Previous research identified seven strain lines that were tolerant to warm temperatures, and we used the GBS data to test whether genotypes were associated with warm tolerance. Kelps from the north were genetically distinct from the southern ones, with much lower gene flow between regions than within regions. These results revealed that giant kelp populations from Tasmania are more genetically structured than previously thought. Two loci were significantly associated with warm temperature tolerance. They are population-specific: the alternative allele from one of the loci was found only in the northern populations, while the other was found in the southern populations. This could suggest that thermal tolerance is adapting locally or drifting given large changes in population demography, but further research is needed to confirm this hypothesis. Our research sheds light on genetic patterns in this critical habitat-forming kelp and will help inform conservation management, including selective breeding.

genetics↗

bioRxiv2023

The Antarctic Seafloor Annotated Imagery Database

Marine imagery is a comparatively cost-effective way to collect data on seafloor organisms, biodiversity and habitat morphology. However, annotating these images to extract detailed biological information is time-consuming and expensive, and reference libraries of consistently annotated seafloor images are rarely publicly available. Here, we present the Antarctic Seafloor Annotated Imagery Database (AS-AID), a result of a multinational collaboration to collate and annotate regional seafloor imagery datasets from 19 Antarctic research cruises between 1985 and 2019. AS-AID comprises of 3,599 georeferenced downward facing seafloor images that have been labelled with a total of 615,051 expert annotations. Annotations are based on the CATAMI (Collaborative and Automated Tools for Analysis of Marine Imagery) classification scheme and have been reviewed by experts. In addition, because the pixel location of each annotation within each image is available, annotations can be viewed easily and customised to suit individual research priorities. This dataset can be used to investigate species distributions, community patterns, it provides a reference to assess change through time, and can be used to train algorithms to automatically detect and annotate marine fauna.

ecology↗

bioRxiv2022

Quantifying and Visualizing Uncertainty for Source Localization in Electrocardiographic Imaging

Electrocardiographic imaging (ECGI) presents a clinical opportunity to noninvasively understand the sources of arrhythmias for individual patients. To help increase the effectiveness of ECGI, we provide new ways to visualize associated measurement and modeling errors. In this paper, we study source localization uncertainty in two steps: First, we perform Monte Carlo simulations of a simple inverse ECGI source localization model with error sampling to understand the variations in ECGI solutions. Second, we present multiple visualization techniques, including confidence maps, level-sets, and topology-based visualizations, to better understand uncertainty in source localization. Our approach offers a new way to study uncertainty in the ECGI pipeline.

bioengineering↗

bioRxiv2021

Chemical rescue of mutant proteins in living cells by naturally occurring small molecules

Intracellular proteins function in a complex milieu wherein small molecules influence protein folding and act as essential cofactors for enzymatic reactions. Thus protein function depends not only on amino acid sequence but also on the concentrations of such molecules, which are subject to wide variation between organisms, metabolic states, and environmental conditions. We previously found evidence that exogenous guanidine reverses the phenotypes of specific budding yeast septin mutants by binding to a WT septin at the former site of an Arg side chain that was lost during fungal evolution. Here we used a combination of targeted and unbiased approaches to look for other cases of "chemical rescue" by naturally occurring small molecules. We report in vivo rescue of hundreds of yeast mutants representing a variety of genes, including likely examples of Arg or Lys side chain replacement by the guanidinium ion. Failed rescue of targeted mutants highlight features required for rescue, as well as key differences between the in vitro and in vivo environments. Some non-Arg mutants rescued by guanidine likely result from "off-target" effects on specific cellular processes in WT cells. Molecules isosteric to guanidine and known to influence protein folding had a range of effects, from essentially none for urea, to rescue of a few mutants by DMSO. Strikingly, the osmolyte trimethylamine-N-oxide rescued [~]20% of the mutants we tested, likely reflecting combinations of direct and indirect effects on mutant protein function. Our findings illustrate the potential of natural small molecules as therapeutic interventions and drivers of evolution.

genetics↗

bioRxiv2019

Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast

Septin proteins co-assemble into hetero-oligomers that polymerize into cytoskeletal filaments with a variety of cellular functions. In Saccharomyces cerevisiae, where septins were first discovered, five subunits comprise two species of septin hetero-octamers, Cdc11/Shs1-Cdc12-Cdc3-Cdc10- Cdc10-Cdc3-Cdc12-Cdc11/Shs1. Septins evolved from ancestral GTPases. We previously found evidence that slow GTPase activity by Cdc12 directs the choice of incorporation of Cdc11 vs Shs1 into septin complexes. It was unclear why many septins, including Cdc3, lack GTPase activity. We serendipitously discovered that the small molecule guanidine hydrochloride (GdnHCl) rescues septin function in cdc10 mutants by promoting assembly of non-native Cdc11/Shs1-Cdc12-Cdc3- Cdc3-Cdc12-Cdc11/Shs1 hexamers. We provide evidence that in S. cerevisiae Cdc3 guanidinium ion (Gdm) occupies the site of a "missing" Arg sidechain that is present in other fungal species in which (i) the Cdc3 subunit is an active GTPase and (ii) Cdc10-less hexamers co-exist with octamers in wild-type cells. These findings support a model in which Gdm reactivates a latent septin assembly pathway that was suppressed during fungal evolution in order to restrict assembly to hetero-octamers. Given that septin hexamers made natively in human cells also exclude Cdc10-like central subunits via homodimerization of an active GTPase, our results provide new mechanistic details that likely apply to septin assembly throughout phylogeny.

genetics↗

bioRxiv2019

A High-Resolution Head and Brain Computer Model for Forward and Inverse EEG Simulation

To conduct computational forward and inverse EEG studies of brain electrical activity, researchers must construct realistic head and brain computer models, which is both challenging and time consuming. The availability of realistic head models and corresponding imaging data is limited in terms of imaging modalities and patient diversity. In this paper, we describe a detailed head modeling pipeline and provide a high-resolution, multimodal, open-source, female head and brain model. The modeling pipeline specifically outlines image acquisition, preprocessing, registration, and segmentation; three-dimensional tetrahedral mesh generation; finite element EEG simulations; and visualization of the model and simulation results. The dataset includes both functional and structural images and EEG recordings from two high-resolution electrode configurations. The intermediate results and software components are also included in the dataset to facilitate modifications to the pipeline. This project will contribute to neuroscience research by providing a high-quality dataset that can be used for a variety of applications and a computational pipeline that may help researchers construct new head models more efficiently.

bioengineering↗

bioRxiv2018

Mapping Antarctic suspension feeder abundances and seafloor food-availability, and modelling their change after a major glacier calving

Seafloor communities are a critical part of the unique and diverse Antarctic marine life. Processes at the ocean-surface can strongly influence the diversity and abundance of these communities, even when they live at hundreds of meters water depth. However, even though we understand the importance of this link, there are so far no quantitative spatial predictions on how seafloor communities will respond to changing conditions at the ocean surface.\n\nHere, we map patterns in abundance of important habitat-forming suspension feeders on the seafloor in East Antarctica, and predict how these patterns change after a major disturbance in the icescape, caused by the calving of the Mertz Glacier Tongue. We use a purpose-built ocean model for the time-period before and after the calving of the Mertz-Glacier Tongue in 2010, data from satellites and a validated food-availability model to estimate changes in horizontal flux of food since the glacier calving. We then predict the post-calving distribution of suspension feeder abundances using the established relationships with the environmental variables, and changes in horizontal flux of food.\n\nOur results indicate strong increases in suspension feeder abundances close to the glacier calving site, fueled by increased food supply, while the remainder of the region maintains similar suspension feeder abundances despite a slight decrease in total food supply. The oceanographic setting of the entire region changes, with a shorter ice-free season, altered seafloor currents and changes in food-availability.\n\nOur study provides important insight into the flow-on effects of a changing icescape on seafloor habitat and fauna in polar environments. Understanding these connections is important in the context of current and future effects of climate change, and the mapped predictions of the seafloor fauna as presented for the study region can be used as a decision-tool for planning potential marine protected areas, and for focusing future sampling and monitoring initiatives.

ecology↗

bioRxiv2017

Interactive Visual Exploration And Refinement Of Cluster Assignments

BackgroundWith ever-increasing amounts of data produced in biology research, scientists are in need of efficient data analysis methods. Cluster analysis, combined with visualization of the results, is one such method that can be used to make sense of large data volumes. At the same time, cluster analysis is known to be imperfect and depends on the choice of algorithms, parameters, and distance measures. Most clustering algorithms dont properly account for ambiguity in the source data, as records are often assigned to discrete clusters, even if an assignment is unclear. While there are metrics and visualization techniques that allow analysts to compare clusterings or to judge cluster quality, there is no comprehensive method that allows analysts to evaluate, compare, and refine cluster assignments based on the source data, derived scores, and contextual data.\n\nResultsIn this paper, we introduce a method that explicitly visualizes the quality of cluster assignments, allows comparisons of clustering results and enables analysts to manually curate and refine cluster assignments. Our methods are applicable to matrix data clustered with partitional, hierarchical, and fuzzy clustering algorithms. Furthermore, we enable analysts to explore clustering results in context of other data, for example, to observe whether a clustering of genomic data results in a meaningful differentiation in phenotypes.\n\nConclusionsOur methods are integrated into Caleydo StratomeX, a popular, web-based, disease subtype analysis tool. We show in a usage scenario that our approach can reveal ambiguities in cluster assignments and produce improved clusterings that better differentiate genotypes and phenotypes.

bioinformatics↗