Biology subjects

Kelly, R.

Publications and source records attributed to Kelly, R..

25 records · Page 2Linked to original sources

bioRxiv2020

Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in the murine cardiopharyngeal mesoderm

The poles of the heart and branchiomeric muscles of the face and neck are formed from the cardiopharyngeal mesoderm (CPM) within the pharyngeal apparatus. The formation of the cardiac outflow tract and branchiomeric muscles are disrupted in patients with 22q11.2 deletion syndrome (22q11.2DS), due to haploinsufficiency of TBX1, encoding a T-box transcription factor. Here, using single cell RNA-sequencing, we identified a multilineage primed population (MLP) within the CPM, marked by the Tbx1 lineage, which has bipotent properties to form cardiac and skeletal muscle cells. The MLPs are localized within the nascent mesoderm of the caudal lateral pharyngeal apparatus and provide a continuous source of progenitors that undergo TBX1-dependent progression towards maturation. Tbx1 also regulates the balance between MLP maintenance and maturation while restricting ectopic non-mesodermal gene expression. We further show that TBX1 confers this balance by direct regulation of MLP enriched genes and downstream pathways, partly through altering chromatin accessibility. Our study thus uncovers a new cell population and reveals novel mechanisms by which Tbx1 directs the development of the pharyngeal apparatus, which is profoundly altered in 22q11.2DS.

developmental biology↗

bioRxiv2020

Badger territoriality maintained despite disturbance of major road construction

Road ecology has traditionally focused on the impact of in-situ and functional roads on wildlife. However, road construction also poses a major, yet understudied, threat and any implications for key aspects of animal behaviour are unknown. There are also concerns that environmental disturbances, including major roadworks, can disrupt badger territoriality, promoting the spread of tuberculosis to cattle. To address these knowledge gaps, the ranging behaviour of a medium-density Irish badger population was monitored, using GPS-tracking collars, before, during and after a major road realignment project that bisected the study area. We estimated badgers home range sizes, nightly distances travelled and the distance and frequency of extra-territorial excursions during each phase of the study and quantified any changes to these parameters. We show that roadworks had a very limited effect on ranging behaviour. A small increase in nightly distance during the roadworks did not translate into an increase in home range size, nor an increase in the distance or frequency of extra-territorial excursions during the roadworks. In addition, suitable mitigation measures to prevent badger deaths appeared to ensure that normal patterns of ranging behaviour continued once the new road was in place. Our analysis supports the view that road construction did not cause badgers to change their ranging behaviour in ways likely to increase the spread of tuberculosis.

ecology↗

bioRxiv2020

Nanotrap(R) particles improve detection of SARS-CoV-2 for pooled sample methods, extraction-free saliva methods, and extraction-free medium methods

Here we present a rapid and versatile method for capturing and concentrating SARS-CoV-2 from transport medium and saliva using affinity-capture magnetic hydrogel particles. We demonstrate that the method concentrates virus prior to RNA extraction, thus significantly improving detection of the virus using a real-time RT-PCR assay across a range of viral titers, from 100 to 1,000,000 viral copies/mL; in particular, detection of virus in low viral load samples is enhanced when using the method coupled with the IDT 2019-nCoV CDC EUA Kit. This method is compatible with commercially available nucleic acid extraction kits, as well with a simple heat and detergent method. Using transport medium diagnostic remnant samples that previously had been tested for SARS-CoV-2 using either the Abbott RealTime SARS-CoV-2 EUA Test (n=14) or the Cepheid Xpert Xpress SARS-CoV-2 EUA Test (n=35), we demonstrate that our method not only correctly identifies all positive samples (n = 17) but also significantly improves detection of the virus in low viral load samples. The average improvement in cycle threshold (Ct) value as measured with the IDT 2019-nCoV CDC EUA Kit was 3.1; n = 10. Finally, to demonstrate that the method could potentially be used to enable pooled testing, we spiked infectious virus or a confirmed positive diagnostic remnant sample into 5 mL and 10 mL of negative transport medium and observed significant improvement in the detection of the virus from those larger sample volumes.

microbiology↗

bioRxiv2019

Decentralized multi-site VBM analysis during adolescence shows structural changes linked to age, body mass index, and smoking: A COINSTAC analysis

In the recent past, there has been an upward trend in developing frameworks that enable neuroimaging researchers to address challenging questions by leveraging data across multiple sites all over the world. One such framework, Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation (COINSTAC), provides a platform to analyze neuroimaging data stored locally across multiple organizations without the need for pooling the data at any point during the analysis. In this paper, we perform a decentralized voxel-based morphometry analysis of structural magnetic resonance imaging data across two different sites to understand the structural changes in the brain as linked to age, body mass index and smoking. Results produced by the decentralized analysis are contrasted with similar findings in literature. This work showcases the potential benefits of performing multi-voxel and multivariate analyses of large-scale neuroimaging data located at multiple sites.

neuroscience↗

bioRxiv2019

How indirect interactions shape long-term invasion dynamics in complex ecological communities

Many facets of ecological theory rely on the analysis of invasion processes, and general approaches exist to understand the early stages of an invasion. However, predicting the long-term transformations of communities following an invasion remains a challenging endeavour. We propose an analytical method that uses community structure and invader dynamical features to predict when these impacts can be large, and show it to be applicable across a wide class of dynamical models. Our approach reveals that short-term invasion success and long-term consequences are two distinct axes of variation controlled by different properties of both invader and resident community. Whether a species can invade is controlled by its invasion fitness, which depends on environmental conditions and direct interactions with resident species. But whether this invasion will cause significant transformations, such as extinctions or a regime shift, depends on a specific measure of indirect feedbacks that may involve the entire resident community. Our approach applies to arbitrarily complex communities, from few competing phenotypes in adaptive dynamics to large nonlinear food webs. It hints at new questions to ask as part of any invasion analysis, and suggests that long-term indirect interactions are key determinants of invasion outcomes.

ecology↗

bioRxiv2018

Unique morphogenetic signatures define mammalian neck muscles and associated connective tissues

In vertebrates, head and trunk muscles develop from different mesodermal populations and are regulated by distinct genetic networks. Neck muscles at the head-trunk interface remain poorly defined due to their complex morphogenesis and dual mesodermal origins. Here, we use genetically modified mice to establish a 3D model that integrates regulatory genes, cell populations and morphogenetic events that define this transition zone. We show that the evolutionary conserved cucullaris-derived muscles originate from posterior cardiopharyngeal mesoderm, not lateral plate mesoderm, and we define new boundaries for neural crest and mesodermal contributions to neck connective tissue. Furthermore, lineage studies and functional analysis of Tbx1- and Pax3-null mice reveal a unique genetic program for somitic neck muscles that is distinct from that of somitic trunk muscles. Our findings unveil the embryological and developmental requirements underlying tetrapod neck myogenesis and provide a blueprint to investigate how muscle subsets are selectively affected in some human myopathies.

developmental biology↗

bioRxiv2018

Social licence through citizen science: A tool for marine conservation

1. Introduction 1. Introduction 2. Methods 3. Results Discussion 4. Conclusion References Meaningful public engagement with science and research is essential to improving knowledge about the environment and supporting sustainable use of ecosystems and natural resources. Transparent and culturally-appropriate natural resource management is imperative (Christie et al. 2017) and the publics role in decision-making and data collection is increasingly recognised (Hecker et al. 2018), supported by a rise in the number of citizen science projects in recent years (Chandler et al. 2017;Pocock et al. 2017), including marine-based projects (Cigliano and Ballard 2017). In parallel, social licence has become an important theme for development, pa ...

scientific communication and education↗