'Cant about decorum’:George Thomson’s singular edition of Robert Burns’s ‘The Jolly Beggars’

Robert Burns’s song editor George Thomson (1757–1851) issued the poet’s cantata ‘Love and Liberty’, also known as ‘The Jolly Beggars’, for the first time with music in 1818 (a setting of Burns’s text for narrator, solo singers, choir, and piano trio). The musical score was by London theatre composer Sir Henry Bishop and the text was edited by Thomson in line with his strict policy of decency and politeness. This essay tracks Thomson’s editorial curation of Burns’s text in the context of polite ‘improvement’ and argues that while pursuing apparent ‘decorum’, Thomson’s treatment struggles to negotiate the unruliness at the centre of what is now considered one of Burns’s most important works. The article pays particular attention to the complicated publication history of this work, revealing a chronology of popular print editions in advance of Thomson’s own, as well as the notable influence of Walter Scott’s remarks on the piece in the Quarterly Review. Examining the musical context of Thomson’s ‘Jolly Beggars’ alongside the text reveals a similar aspiration for elevation and the article presents the conversation between Thomson and Bishop, from manuscript correspondence

Making connections between novel transcription factors and their DNA motifs

The key components of a transcriptional regulatory network are the connections between trans-acting transcription factors and cis-acting DNA-binding sites. In spite of several decades of intense research, only a fraction of the estimated ∼300 transcription factors in Escherichia coli have been linked to some of their binding sites in the genome. In this paper, we present a computational method to connect novel transcription factors and DNA motifs in E. coli. Our method uses three types of mutually independent information, two of which are gleaned by comparative analysis of multiple genomes and the third one derived from similarities of transcription-factor-DNA-binding-site interactions. The different types of information are combined to calculate the probability of a given transcription-factor-DNA-motif pair being a true pair. Tested on a study set of transcription factors and their DNA motifs, our method has a prediction accuracy of 59% for the top predictions and 85% for the top three predictions. When applied to 99 novel transcription factors and 70 novel DNA motifs, our method predicted 64 transcription-factor-DNA-motif pairs. Supporting evidence for some of the predicted pairs is presented. Functional annotations are made for 23 novel transcription factors based on the predicted transcription-factor-DNA-motif connections

PhyloScan: identification of transcription factor binding sites using cross-species evidence

BACKGROUND: When transcription factor binding sites are known for a particular transcription factor, it is possible to construct a motif model that can be used to scan sequences for additional sites. However, few statistically significant sites are revealed when a transcription factor binding site motif model is used to scan a genome-scale database. METHODS: We have developed a scanning algorithm, PhyloScan, which combines evidence from matching sites found in orthologous data from several related species with evidence from multiple sites within an intergenic region, to better detect regulons. The orthologous sequence data may be multiply aligned, unaligned, or a combination of aligned and unaligned. In aligned data, PhyloScan statistically accounts for the phylogenetic dependence of the species contributing data to the alignment and, in unaligned data, the evidence for sites is combined assuming phylogenetic independence of the species. The statistical significance of the gene predictions is calculated directly, without employing training sets. RESULTS: In a test of our methodology on synthetic data modeled on seven Enterobacteriales, four Vibrionales, and three Pasteurellales species, PhyloScan produces better sensitivity and specificity than MONKEY, an advanced scanning approach that also searches a genome for transcription factor binding sites using phylogenetic information. The application of the algorithm to real sequence data from seven Enterobacteriales species identifies novel Crp and PurR transcription factor binding sites, thus providing several new potential sites for these transcription factors. These sites enable targeted experimental validation and thus further delineation of the Crp and PurR regulons in E. coli. CONCLUSION: Better sensitivity and specificity can be achieved through a combination of (1) using mixed alignable and non-alignable sequence data and (2) combining evidence from multiple sites within an intergenic region

Determination of the Membrane Topology of the Small EF-Hand Ca2+-Sensing Proteins CaBP7 and CaBP8

The CaBPs represent a subfamily of small EF-hand containing calcium (Ca2+)-sensing proteins related to calmodulin that regulate key ion channels in the mammalian nervous system. In a recent bioinformatic analyses we determined that CaBP7 and CaBP8 form an evolutionarily distinct branch within the CaBPs (also known as the calneurons) a finding that is consistent with earlier observations characterising a putative C-terminal transmembrane (TM) spanning helix in each of these proteins which is essential for their sub-cellular targeting to the Golgi apparatus and constitutive secretory vesicles. The C-terminal position of the predicted TM-helix suggests that CaBP7 and CaBP8 could be processed in a manner analogous to tail-anchored integral membrane proteins which exhibit the ability to insert across membranes post-translationally. In this study we have investigated the topology of CaBP7 and CaBP8 within cellular membranes through a combination of trypsin protection and epitope accessibility analyses. Our results indicate that the TM-helices of CaBP7 and CaBP8 insert fully across membranes such that their extreme C-termini are luminal. The observed type-II membrane topology is consistent with processing of CaBP7 and CaBP8 as true tail-anchored proteins. This targeting mechanism is distinct from any other calmodulin related Ca2+-sensor and conceivably underpins unique physiological functions of these proteins

Evolution and functional diversity of the Calcium Binding Proteins (CaBPs)

The mammalian central nervous system (CNS) exhibits a remarkable ability to process, store, and transfer information. Key to these activities is the use of highly regulated and unique patterns of calcium signals encoded by calcium channels and decoded by families of specific calcium-sensing proteins. The largest family of eukaryotic calcium sensors is those related to the small EF-hand containing protein calmodulin (CaM). In order to maximize the usefulness of calcium as a signaling species and to permit the evolution and fine tuning of the mammalian CNS, families of related proteins have arisen that exhibit characteristic calcium binding properties and tissue-, cellular-, and sub-cellular distribution profiles. The Calcium Binding Proteins (CaBPs) represent one such family of vertebrate specific CaM like proteins that have emerged in recent years as important regulators of essential neuronal target proteins. Bioinformatic analyses indicate that the CaBPs consist of two subfamilies and that the ancestral members of these are CaBP1 and CaBP8. The CaBPs have distinct intracellular localizations based on different targeting mechanisms including a novel type-II transmembrane domain in CaBPs 7 and 8 (otherwise known as calneuron II and calneuron I, respectively). Recent work has led to the identification of new target interactions and possible functions for the CaBPs suggesting that they have multiple physiological roles with relevance for the normal functioning of the CNS

SPOCS User Guide

SPOCS implements a graph-based ortholog prediction method to generate a simple tab-delimited table of orthologs, and in addition, html files that provide a visualization of the ortholog/paralog relationships to which gene/protein expression metadata may be overlaid

Modulation of phosphatidylinositol 4-phosphate levels by CaBP7 controls cytokinesis in mammalian cells

Calcium and phosphoinositide signaling regulate cell division in model systems, but their significance in mammalian cells is unclear. Calcium-binding protein-7 (CaBP7) is a phosphatidylinositol 4-kinaseIIIβ (PI4KIIIβ) inhibitor required during cytokinesis in mammalian cells, hinting at a link between these pathways. Here we characterize a novel association of CaBP7 with lysosomes that cluster at the intercellular bridge during cytokinesis in HeLa cells. We show that CaBP7 regulates lysosome clustering and that PI4KIIIβ is essential for normal cytokinesis. CaBP7 depletion induces lysosome mislocalization, extension of intercellular bridge lifetime, and cytokinesis failure. These data connect phosphoinositide and calcium pathways to lysosome localization and normal cytokinesis in mammalian cells

The tricarboxylic acid cycle in Shewanella oneidensis is independent of Fur and RyhB control

Background: It is well established in E. coli and Vibrio cholerae that strains harboring mutations in the ferric uptake regulator gene (fur) are unable to utilize tricarboxylic acid (TCA) compounds, due to the down-regulation of key TCA cycle enzymes, such as AcnA and SdhABCD. This down-regulation is mediated by a Fur-regulated small regulatory RNA named RyhB. It is unclear in the gamma proteobacterium S. oneidensis whether TCA is also regulated by Fur and RyhB. Results: In the present study, we showed that a fur deletion mutant of S. oneidensis could utilize TCA compounds. Consistently, expression of the TCA cycle genes acnA and sdhA was not down-regulated in the mutant. To explore this observation further, we identified a ryhB gene in Shewanella species and experimentally demonstrated the gene expression. Further experiments suggested that RyhB was up-regulated in fur mutant, but that AcnA and SdhA were not controlled by RyhB. Conclusions: These cumulative results delineate an important difference of the Fur-RyhB regulatory cycle between S. oneidensis and other gamma-proteobacteria. This work represents a step forward for understanding the unique regulation in S. oneidensis

The Gibbs Centroid Sampler

The Gibbs Centroid Sampler is a software package designed for locating conserved elements in biopolymer sequences. The Gibbs Centroid Sampler reports a centroid alignment, i.e. an alignment that has the minimum total distance to the set of samples chosen from the a posteriori probability distribution of transcription factor binding-site alignments. In so doing, it garners information from the full ensemble of solutions, rather than only the single most probable point that is the target of many motif-finding algorithms, including its predecessor, the Gibbs Recursive Sampler. Centroid estimators have been shown to yield substantial improvements, in both sensitivity and positive predictive values, to the prediction of RNA secondary structure and motif finding. The Gibbs Centroid Sampler, along with interactive tutorials, an online user manual, and information on downloading the software, is available at: http://bayesweb.wadsworth.org/gibbs/gibbs.html

A Step-Wise Approach to Managing Post-Operative Pain

Background: Gan et al. (2014) reports in the past 5 years 86% of surgical patients’ experienced immediate post-operative pain, and 75% of those reported pain severities of moderate to extreme in the immediate post-operative pain. Uncontrolled pain leads to multiple health problems such as pneumonia, chronic pain syndrome, and delayed healing. Post-operative pain is best treated with multimodal management. Pain algorithms allow nurses to implement non-pharmacologic techniques and escalate use of medications in a safe manner while improving pain management. Framework: The Comfort Theory (CT) by Katherine Kocalba will be used to guide this project. Kocalba’s CT identifies three types of comfort: 1) relief, 2) ease, and 3) transcendence. Relief of pain allows the patient to relax, rest, and recover. Methods: HCAHPS scores will be collected from January 2018 until three months after the implementation of the algorithm. The 40 registered nurses (RNs) on MS 5 will receive an online evite including the cover/consent letter, demographic survey and “Knowledge and Attitudes Survey Regarding Pain” (KASRP) Ferrell and McCaffery, 2014). Using a semi structured script nurses will be educated regarding implementing an evidence-based algorithm for post-operative pain management, attending brief education classes, and completing three online pain courses. Results: Unfortunately, there was poor response from the nurses and we are unable to analyze data. Out of 41 eligible RNs 10 returned the pre survey, two returned the first post survey, and no responses were recorded from the second post survey. It is unknown if RNs found the algorithm to help them in communication of pain management and treatment with the patient. Implications of Intervention: Implementing a post-operative pain algorithm that involves multimodal pain management will improve patients’ pain. Use of the algorithm assists nurses in communicating effectively with the patients about their pain and pain management