scholarly journals Interplay of a Ligand Sensor and an Enzyme in Controlling Expression of the Saccharomyces cerevisiae GAL Genes

2011 ◽  
Vol 11 (3) ◽  
pp. 334-342 ◽  
Author(s):  
Dariusz Abramczyk ◽  
Stacey Holden ◽  
Christopher J. Page ◽  
Richard J. Reece

ABSTRACT The regulation of the Saccharomyces cerevisiae GAL genes in response to galactose as a source of carbon has served as a paradigm for eukaryotic transcriptional control over the last 50 years. Three proteins—a transcriptional activator (Gal4p), an inhibitor (Gal80p), and a ligand sensor (Gal3p)—control the switch between inert and active gene expression. The molecular mechanism by which the recognition of galactose within the cell is converted into a transcriptional response has been the subject of considerable debate. In this study, using a novel and powerful method of localizing active transcription factors within the nuclei of cells, we show that a short-lived complex between Gal4p, Gal80p, and Gal3p occurs soon after the addition of galactose to cells to activate GAL gene expression. Gal3p is subsequently replaced in this complex by Gal1p, and a Gal4p-Gal80p-Gal1p complex is responsible for the continued expression of the GAL genes. The transient role of the ligand sensor indicates that current models for the induction and continued expression of the yeast GAL genes need to be reevaluated.

2017 ◽  
Vol 16 (2) ◽  
pp. 41-54 ◽  
Author(s):  
Peter Joyce

Purpose The purpose of this paper is to analyse the 2016 elections for Police and Crime Commissioners (PCCs) and to compare them with those that took place in 2012. It seeks to evaluate the background of the candidates who stood for office in 2016, the policies that they put forward, the results of the contests and the implications of the 2016 experience for future PCC elections. Design/methodology/approach This paper is based around several key themes – the profile of candidates who stood for election, preparations conducted prior to the contests taking place, the election campaign and issues raised during the contests, the results and the profile of elected candidates. The paper is based upon documentary research, making particular use of primary source material. Findings The research establishes that affiliation to a political party became the main route for successful candidates in 2016 and that local issues related to low-level criminality will dominate the future policing agenda. It establishes that although turnout was higher than in 2012, it remains low and that further consideration needs to be devoted to initiatives to address this for future PCC election contests. Research limitations/implications The research focusses on the 2016 elections and identifies a number of key issues that emerged during the campaign affecting the conduct of the contests which have a bearing on future PCC elections. It treats these elections as a bespoke topic and does not seek to place them within the broader context of the development of the office of PCC. Practical implications The research suggests that in order to boost voter participation in future PCC election contests, PCCs need to consider further means to advertise the importance of the role they perform and that the government should play a larger financial role in funding publicity for these elections and consider changing the method of election. Social implications The rationale for introducing PCCs was to empower the public in each police force area. However, issues that include the enhanced importance of political affiliation as a criteria for election in 2016 and the social unrepresentative nature of those who stood for election and those who secured election to this office in these contests coupled with shortcomings related to public awareness of both the role of PCCs and the timing of election contests threaten to undermine this objective. Originality/value The extensive use of primary source material ensures that the subject matter is original and its interpretation is informed by an academic perspective.


2016 ◽  
Vol 17 (2) ◽  
pp. 142-149 ◽  
Author(s):  
Kelly Broughton

Purpose – The library’s strategic plan calls for the author to “Transform the role of the subject liaison librarian to better engage the campus community.” This statement specifically focusses on the aspect of the liaison role that builds relationships with the campus partners, “to better engage the campus community.” And like the peers, liaison librarians at this mid-size research institution have been struggling not only with implementing but also determining how to measure this new role. The purpose of this paper is to develop one measure of librarian engagement with the campus community. Design/methodology/approach – The author developed a “campus relationship matrix” that articulates dozens of products that could potentially be the result of liaison work, such as co-authoring a grant proposal, developing a class, co-presenting a workshop on article impact metrics, etc. These relationship products were generated by examining the own work and by scanning liaison responsibility statements from other institutions. These products fall into three relationship status levels: emergent, generative, and productive. Each subject librarian was asked to rate his and her relationship with each department he or she serves. Additionally, in order to achieve consistency across the organization in understanding of three relationship levels, the author engaged in an exercise to calibrate the categorization of these work products. During this exercise and through the discussions, greater nuances were revealed about what the author is hoping to achieve with the strategic goal. A review and summary of the ratings is presented. Findings – Baseline counts of relationship types were completed. The author is working to establish goals for next year’s comparisons. In actuality, the specific goals matters much less than the conversations surrounding these results about what work the author should be doing and why and how is valued. Originality/value – This study presents a tool useful for the exploration and measure of librarian relationships with campus.


mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin G. Sanchez ◽  
Micah J. Ferrell ◽  
Alexandra E. Chirakos ◽  
Kathleen R. Nicholson ◽  
Robert B. Abramovitch ◽  
...  

ABSTRACT Pathogenic mycobacteria encounter multiple environments during macrophage infection. Temporally, the bacteria are engulfed into the phagosome, lyse the phagosomal membrane, and interact with the cytosol before spreading to another cell. Virulence factors secreted by the mycobacterial ESX-1 (ESAT-6-system-1) secretion system mediate the essential transition from the phagosome to the cytosol. It was recently discovered that the ESX-1 system also regulates mycobacterial gene expression in Mycobacterium marinum (R. E. Bosserman, T. T. Nguyen, K. G. Sanchez, A. E. Chirakos, et al., Proc Natl Acad Sci U S A 114:E10772–E10781, 2017, https://doi.org/10.1073/pnas.1710167114), a nontuberculous mycobacterial pathogen, and in the human-pathogenic species M. tuberculosis (A. M. Abdallah, E. M. Weerdenburg, Q. Guan, R. Ummels, et al., PLoS One 14:e0211003, 2019, https://doi.org/10.1371/journal.pone.0211003). It is not known how the ESX-1 system regulates gene expression. Here, we identify the first transcription factor required for the ESX-1-dependent transcriptional response in pathogenic mycobacteria. We demonstrate that the gene divergently transcribed from the whiB6 gene and adjacent to the ESX-1 locus in mycobacterial pathogens encodes a conserved transcription factor (MMAR_5438, Rv3863, now espM). We prove that EspM from both M. marinum and M. tuberculosis directly and specifically binds the whiB6-espM intergenic region. We show that EspM is required for ESX-1-dependent repression of whiB6 expression and for the regulation of ESX-1-associated gene expression. Finally, we demonstrate that EspM functions to fine-tune ESX-1 activity in M. marinum. Taking the data together, this report extends the esx-1 locus, defines a conserved regulator of the ESX-1 virulence pathway, and begins to elucidate how the ESX-1 system regulates gene expression. IMPORTANCE Mycobacterial pathogens use the ESX-1 system to transport protein substrates that mediate essential interactions with the host during infection. We previously demonstrated that in addition to transporting proteins, the ESX-1 secretion system regulates gene expression. Here, we identify a conserved transcription factor that regulates gene expression in response to the ESX-1 system. We demonstrate that this transcription factor is functionally conserved in M. marinum, a pathogen of ectothermic animals; M. tuberculosis, the human-pathogenic species that causes tuberculosis; and M. smegmatis, a nonpathogenic mycobacterial species. These findings provide the first mechanistic insight into how the ESX-1 system elicits a transcriptional response, a function of this protein transport system that was previously unknown.


2014 ◽  
Vol 27 (5) ◽  
pp. 793-806 ◽  
Author(s):  
Eduard Bonet

Purpose – The purpose of this paper is to examine how the boundaries of rhetoric have excluded important theoretical and practical subjects and how these subjects are recuperated and extended since the twentieth century. Its purpose is to foster the awareness on emerging new trends of rhetoric. Design/methodology/approach – The methodology is based on an interpretation of the history of rhetoric and on the construction of a conceptual framework of the rhetoric of judgment, which is introduced in this paper. Findings – On the subject of the extension of rhetoric from public speeches to any kinds of persuasive situations, the paper emphasizes some stimulating relationships between the theory of communication and rhetoric. On the exclusion and recuperation of the subject of rhetorical arguments, it presents the changing relationships between rhetoric and dialectics and emphasizes the role of rhetoric in scientific research. On the introduction of rhetoric of judgment and meanings it creates a conceptual framework based on a re-examination of the concept of judgment and the phenomenological foundations of the interpretative methods of social sciences by Alfred Schutz, relating them to symbolic interactionism and theories of the self. Originality/value – The study on the changing boundaries of rhetoric and the introduction of the rhetoric of judgment offers a new view on the present theoretical and practical development of rhetoric, which opens new subjects of research and new fields of applications.


2014 ◽  
Vol 7 (3) ◽  
pp. 518-535 ◽  
Author(s):  
Mark Mullaly

Purpose – The purpose of this paper is to explore the role of decision rules and agency in supporting project initiation decisions, and the influences of agency on decision-making effectiveness. Design/methodology/approach – The study this paper is based upon used grounded theory methodology, and sought to understand the influences of individual decision makers on project initiation decisions within organizations. Data collection involved 28 participants who were involved in project initiation decisions within their organizations, who discussed the process of project initiation in their organization and their role within that process. Findings – The study demonstrates that the overall effectiveness of project initiation decisions is a product of agency, process effectiveness or rule effectiveness. The employment of agency can have a direct influence on decision-making effectiveness, it can compensate for organizational inadequacies of a process or political nature, and it can be constrained in the evidence of formal and effective organizational practices. Research limitations/implications – While agency was recognized by all participants, there are clearly circumstances where actors perceive the ability to exercise agency to be externally constrained. The study is exploratory, contributing to the development of substantive theory. Theory testing as well as a more in-depth investigation of the underlying drivers of agency would be valuable. Practical implications – The study provides executives and individuals supporting the initiation of projects with insights on how to effectively influence the effectiveness of project initiation decisions, and the degree to which personal characteristics influence organizational dynamics. Originality/value – Most discussions of agency has been framed the subject as an executive- or board-level phenomenon. The current study demonstrates that agency is in fact being perceived and operationalized at all levels. Those demonstrating agency in the majority of instances in this study do so in exercising stewardship behaviours. This has important implications for how agency is perceived by executives, and by how agency is exercised by actors at all levels of the organization.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Maja Dorota Wojciechowska

Purpose The purpose of the paper is to present the latest scholarly trends in the field of social capital in libraries, to review research concepts published by LIS professionals and to suggest further research possibilities in this area. Design/methodology/approach This paper presents a review and critical analysis of literature associated with research on social capital in libraries to highlight its importance for the development of LIS and its impact on the functioning of environments linked with various types of libraries. The goal of literature analysis was to determine the current condition of research on social capital in libraries. The main trends were identified and the need for further qualitative analyses, which are missing at the moment, was confirmed. Findings It was determined that, so far, LIS professionals have focussed mainly on the role of municipal libraries in developing social capital, the problem of building trust, especially in immigrant circles and the impact of libraries on promoting a civil society. Academic libraries, rural libraries, organisational capital in libraries and individual social capital of librarians were a much less frequent subject of research. The role of libraries in developing social capital in educational (primary and secondary education) and professional (non-university professionals) circles is practically non-existent in research, and it will require in-depth studies and analyses in the coming years. Originality/value This paper constitutes a synthetic review of the latest research concepts concerning social capital in libraries. It identifies the most important research trends and areas that so far have not been explored and suggests research methods to help LIS professionals design future research in this area more effectively.


mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Robert W. McKee ◽  
Carissa K. Harvest ◽  
Rita Tamayo

ABSTRACTThe intracellular signaling molecule cyclic diguanylate (c-di-GMP) regulates many processes in bacteria, with a central role in controlling the switch between motile and nonmotile lifestyles. Recent work has shown that inClostridium difficile(also calledClostridioides difficile), c-di-GMP regulates swimming and surface motility, biofilm formation, toxin production, and intestinal colonization. In this study, we determined the transcriptional regulon of c-di-GMP inC. difficile,employing overexpression of a diguanylate cyclase gene to artificially manipulate intracellular c-di-GMP. Consistent with prior work, c-di-GMP regulated the expression of genes involved in swimming and surface motility. c-di-GMP also affected the expression of multiple genes encoding cell envelope proteins, several of which affected biofilm formationin vitro. A substantial proportion of the c-di-GMP regulon appears to be controlled either directly or indirectly via riboswitches. We confirmed the functionality of 11 c-di-GMP riboswitches, demonstrating their effects on downstream gene expression independent of the upstream promoters. The class I riboswitches uniformly functioned as “off” switches in response to c-di-GMP, while class II riboswitches acted as “on” switches. Transcriptional analyses of genes 3′ of c-di-GMP riboswitches over a broad range of c-di-GMP levels showed that relatively modest changes in c-di-GMP levels are capable of altering gene transcription, with concomitant effects on microbial behavior. This work expands the known c-di-GMP signaling network inC. difficileand emphasizes the role of the riboswitches in controlling known and putative virulence factors inC. difficile.IMPORTANCEInClostridium difficile, the signaling molecule c-di-GMP regulates multiple processes affecting its ability to cause disease, including swimming and surface motility, biofilm formation, toxin production, and intestinal colonization. In this study, we used RNA-seq to define the transcriptional regulon of c-di-GMP inC. difficile. Many new targets of c-di-GMP regulation were identified, including multiple putative colonization factors. Transcriptional analyses revealed a prominent role for riboswitches in c-di-GMP signaling. Only a subset of the 16 previously predicted c-di-GMP riboswitches were functionalin vivoand displayed potential variability in their response kinetics to c-di-GMP. This work underscores the importance of studying c-di-GMP riboswitches in a relevant biological context and highlights the role of the riboswitches in controlling gene expression inC. difficile.


2020 ◽  
Author(s):  
Joanna Houghton ◽  
Angela Rodgers ◽  
Graham Rose ◽  
Kristine B. Arnvig

ABSTRACTAlmost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of post-transcriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA, F6, and show it to be dependent on SigF for expression and significantly induced during in vitro starvation and in a mouse model of infection. However, we found no evidence of attenuation of a ΔF6 strain within the first 20 weeks of infection. A further exploration of F6 using in vitro models of infection suggests a role for F6 as a highly specific regulator of the heat shock repressor, HrcA. Our results point towards a role for F6 during periods of low metabolic activity similar to cold shock and associated with nutrient starvation such as that found in human granulomas in later stages of infection.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Fred Cooper ◽  
Charlotte Jones

PurposeThis paper explores the dissonance between co-production and expectations of impact in a research project on student loneliness over the 2019/2020 academic year. Specific characteristics of the project – the subject matter, interpolation of a global respiratory pandemic, informal systems of care that arose among students and role of the university in providing the context and funding for the research – brought co-production into heightened tension with the instrumentalisation of project outputs.Design/methodology/approachThe project consisted of a series of workshops, research meetings and mixed-methods online journalling between 2019 and 2020. This paper is primarily a critical reflection on that research, based on observations by and conversations between the authors, together with discourse analysis of research data.FindingsThe authors argue that co-producing research with students on university contexts elevates existing tensions between co-production and institutional valuations of impact, that co-production with students who had experienced loneliness made necessary space for otherwise absent support and care, that the responsibility to advocate for evidence and co-researchers came into friction with how the university felt the research could be useful and that each of these converging considerations are interconnected symptoms of the ongoing marketisation of HE.Originality/valueThis paper provides a novel analysis of co-production, impact and higher education in the context of an original research project with specific challenges and constraints. It is a valuable contribution to methodological literatures on co-production, multidisciplinary research into student loneliness and reflexive work on the difficult uses of evidence in university contexts.


2014 ◽  
Vol 82 (4) ◽  
pp. 1511-1522 ◽  
Author(s):  
Zhiming Ouyang ◽  
Jianli Zhou ◽  
Michael V. Norgard

ABSTRACTBorrelia burgdorferiencodes a homologue of the bacterial carbon storage regulator A (CsrA). Recently, it was reported that CsrA contributes toB. burgdorferiinfectivity and is required for the activation of the central RpoN-RpoS regulatory pathway. However, many questions concerning the function of CsrA inB. burgdorferigene regulation remain unanswered. In particular, there are conflicting reports concerning the molecular details of how CsrA may modulaterpoSexpression and, thus, how CsrA may influence the RpoN-RpoS pathway inB. burgdorferi. To address these key discrepancies, we examined the role of CsrA in differential gene expression in the Lyme disease spirochete. Upon engineering an induciblecsrAexpression system inB. burgdorferi, controlled hyperexpression of CsrA in a merodiploid strain did not significantly alter the protein and transcript levels ofbosR,rpoS, and RpoS-dependent genes (such asospCanddbpA). In addition, we constructed isogeniccsrAmutants in two widely used infectiousB. burgdorferistrains. When expression ofbosR,rpoS,ospC, anddbpAwas compared between thecsrAmutants and their wild-type counterparts, no detectable differences were observed. Finally, animal studies indicated that thecsrAmutants remained infectious for and virulent in mice. Analyses ofB. burgdorferigene expression in mouse tissues showed comparable levels ofrpoStranscripts by thecsrAmutants and the parental strains. Taken together, these results constitute compelling evidence that CsrA is not involved in activation of the RpoN-RpoS pathway and is dispensable for mammalian infectious processes carried out byB. burgdorferi.


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