Biology subjects

Clark, E.

Publications and source records attributed to Clark, E..

4 recordsLinked to original sources

bioRxiv2018

Simulation of enteric colonisation by and screening for Carbapenemase Producing Enterobacteriaceae using an in-vitro human gut model.

Introduction Introduction Methods Results Discussion Conclusion Appendix 1 Appendix 2 References Carbapenemase Producing Enterobacteriaceae (CPE) are increasing worldwide [1, 2] and pose a significant threat to public health. The burden of CPE infection is multifaceted, encompassing adjustment of treatment regimens [3, 4], increased duration of inpatient stay [5], associated morbidity [6] and mortality [5, 7, 8], in addition to the wider burden it poses on healthcare systems, with financial and societal implications [9]. The rapid spread of CPE within endemic areas [10] and in ...

microbiology↗

bioRxiv2017

The Transcriptional Logic of Mammalian Neuronal Diversity

The mammalian nervous system is constructed of many cell types, but the principles underlying this diversity are poorly understood. To assess brain-wide transcriptional diversity, we sequenced the transcriptomes of the largest collection of genetically and anatomically identified neuronal classes. Using improved expression metrics that distinguish information content from signal-to-noise-ratio, we found that homeobox transcription factors contain the highest information about cell types and have the lowest noise. Genes that contribute the most to neuronal diversity tend to be long and enriched in factors specifically involved in neuronal function. Genome accessibility measurements reveal that long genes have more candidate regulatory elements arrayed in more distinct patterns. These elements frequently overlap interspersed repeats (mobile elements) and the pattern of repeats is predictive of gene expression. New regulatory sites resulting from elongation of neuronal genes by mobile elements may be an evolutionary force enhancing nervous system complexity.

neuroscience↗

bioRxiv2017

Evidence for the temporal regulation of insect segmentation by a conserved set of developmental transcription factors

Long-germ insects, such as the fruit fly Drosophila melanogaster, pattern their segments simultaneously, whereas short germ insects, such as the beetle Tribolium castaneum, pattern their segments sequentially, from anterior to posterior. While the two modes of segmentation at first appear to be very different, many details of segmentation gene expression are surprisingly similar between long-germ and short-germ species. Collectively, these observations hint that insect segmentation may involve fairly conserved patterning mechanisms, which occur within an evolutionarily malleable spatiotemporal framework. Based on genetic and comparative evidence, we now propose that, in both Drosophila and Tribolium embryos, the temporal progression of the segmentation process is regulated by a temporal sequence of Caudal, Dichaete, and Odd-paired expression. These three transcription factors are broadly expressed in segmenting tissues, providing spatiotemporal information that intersects with the information provided by periodically-expressed segmentation genes such as the pair-rule factors. However, they are deployed differently in long-germ versus short-germ insects, acting as simple timers in Drosophila, but as smooth, retracting wavefronts in Tribolium, compatible with either gap gene-based or oscillator-based generation of periodicity, respectively.

developmental biology↗

bioRxiv2017

Dynamic patterning by the Drosophila pair-rule network reconciles long-germ and short-germ segmentation

Drosophila segmentation is a well-established paradigm for developmental pattern formation. However, the later stages of segment patterning, regulated by the \"pair-rule\" genes, are still not well understood at the systems level. Building on established genetic interactions, I construct a logical model of the Drosophila pair-rule system that takes into account the demonstrated stage-specific architecture of the pair-rule gene network. Simulation of this model can accurately recapitulate the observed spatiotemporal expression of the pair-rule genes, but only when the system is provided with dynamic \"gap\" inputs. This result suggests that dynamic shifts of pair-rule stripes are essential for segment patterning in the trunk, and provides a functional role for observed posterior-to-anterior gap domain shifts that occur during cellularisation. The model also suggests revised patterning mechanisms for the parasegment boundaries, and accounts for the even-skipped null mutant phenotype. Strikingly, a slightly modified version of the model is able to pattern segments in either simultaneous or sequential modes, depending only on initial conditions. This suggest that fundamentally similar mechanisms may underlie segmentation in short-germ and long-germ arthropods.

developmental biology↗