scholarly journals The Long Hunt for pssR—Looking for a Phospholipid Synthesis Transcriptional Regulator, Finding the Ribosome

2017 ◽  
Vol 199 (14) ◽  
Author(s):  
J. Bartoli ◽  
L. My ◽  
Lucid Belmudes ◽  
Yohann Couté ◽  
J. P. Viala ◽  
...  

ABSTRACT The phospholipid (PL) composition of bacterial membranes varies as a function of growth rate and in response to changes in the environment. While growth adaptation can be explained by biochemical feedback in the PL synthesis pathway, recent transcriptome studies have revealed that the expression of PL synthesis genes can also be tuned in response to various stresses. We previously showed that the BasRS two-component pathway controls the expression of the diacylglycerol kinase gene, dgkA, in Escherichia coli (A. Wahl, L. My, R. Dumoulin, J. N. Sturgis, and E. Bouveret, Mol Microbiol, 80:1260–1275, 2011, https://doi.org/10.1111/j.1365-2958.2011.07641.x ). In this study, we set up a strategy to identify the mutation responsible for the upregulation of pssA observed in the historical pssR1 mutant and supposedly corresponding to a transcriptional repressor (C. P. Sparrow and J. Raetz, J Biol Chem, 258:9963–9967, 1983). pssA encodes phosphatidylserine synthase, the first step of phosphatidylethanolamine synthesis. We showed that this mutation corresponded to a single nucleotide change in the anti-Shine-Dalgarno sequence of the 16S rRNA encoded by the rrnC operon. We further demonstrated that this mutation enhanced the translation of pssA. Though this effect appeared to be restricted to PssA among phospholipid synthesis enzymes, it was not specific, as evidenced by a global effect on the production of unrelated proteins. IMPORTANCE Bacteria adjust the phospholipid composition of their membranes to the changing environment. In addition to enzymatic regulation, stress response regulators control specific steps of the phospholipid synthesis pathway. We wanted to identify a potential regulator controlling the expression of the phosphatidylserine synthase gene. We showed that it was not the previously suggested hdfR gene and instead that a mutation in the anti-Shine-Dalgarno sequence of 16S RNA was responsible for an increase in pssA translation. This example underlines the fact that gene expression can be modulated by means other than specific regulatory processes.

2005 ◽  
Vol 33 (5) ◽  
pp. 1150-1153 ◽  
Author(s):  
G.M. Carman

The yeast Saccharomyces cerevisiae has the ability to cope with a variety of stress conditions (e.g. zinc deficiency) by regulating the expression of enzyme activities including those involved with phospholipid synthesis. Zinc is an essential mineral required for the growth and metabolism of S. cerevisiae. Depletion of zinc from the growth medium of wild-type cells results in alterations in phospholipid composition including an increase in PI (phosphatidylinositol) and a decrease in phosphatidylethanolamine. These changes can be attributed to an increase in PIS1-encoded PI synthase activity and a decrease in the activities of several CDP-diacylglycerol pathway enzymes including the CHO1-encoded PS (phosphatidylserine) synthase. The reduction in PS synthase in response to zinc depletion is due to a repression mechanism that involves the UASINO (inositol upstream activating sequence) element in the CHO1 promoter and the negative transcription factor Opi1p. These factors are also responsible for the inositol-mediated repression of CHO1. This regulation may play an important role in allowing cells to adapt to zinc deficiency given the essential roles that phospholipids play in the structure and function of cellular membranes.


2017 ◽  
Vol 39 (3) ◽  
pp. 317-334 ◽  
Author(s):  
Johanna Macneil ◽  
Ziheng Liu

Purpose The purpose of this paper is to explain progress, or the lack of it, in achieving workplace gender equality goals prescribed by affirmative action regulation by using concepts from soft regulation and organizational learning. Design/methodology/approach The research design is a longitudinal study (2002-2012) of a critical case, that of a single large organization in the male-dominated steel manufacturing, distribution and mining industries. The case focusses on the evidence about organizational learning to be found in that organization’s reports to government on its activities to promote workplace gender equality. Findings While other factors play a role, the apparent failure of the soft regulation to generate a significant shift in gender equality outcomes may also be attributed to ineffective organizational learning, demonstrated by the absence of systematic reflection within the organization on how to improve workplace gender equality, and the lack of firm targets and external benchmarking. Research limitations/implications Self-reported data may be overstated or incomplete. More research is needed to confirm the nature of the specific learning processes occurring within organizations. Practical implications Absent the advent of hard sanctions in workplace gender equality regulation, the responsible government agencies may find it valuable to focus on ways to encourage target organizations to develop competence in organizational learning. Social implications More effective gender equality regulation may change organizational policy and practice and improve work opportunities for women. Originality/value Rather than concluding that the only alternative, when soft regulation is unsuccessful, is hard regulation, this paper shifts the focus to ways that soft regulatory processes might be improved to strengthen their effect.


2019 ◽  
Vol 28 (2) ◽  
pp. 215-234 ◽  
Author(s):  
Richard Brophy

Purpose The purpose of this paper is to examine the operational and regulatory positions of the employment of Blockchain in the insurance industry. Blockchain technology has attracted wide interest from various stakeholders. Many theorists are predicting that this technology will disrupt financial services, including insurance. As stated that the development of blockchain is dependent on regulatory acceptance of this technology, it is essential to establish the current state of play with regard to the application and use of blockchain from a commercial and regulatory standpoints. Design/methodology/approach This review encompasses a number of approaches to view the current status of Blockchain applications. From a commercial approach, this research lists the current applications of blockchain within the insurance industry. From a regulatory point of view, the current positions of the EU and national regulatory bodies are enquired upon to establish how they are examining FinTech and Blockchain technologies within their regulatory processes. Findings This review illustrates a number of Blockchain applications in situ from a commercial point of view. From a regulatory setting and following a call from international and EU levels, it appears that various regulatory bodies have begun the process of formulating testing processes for FinTech applications. There are two predominant types in operation, while others are forming points of contact for advice for FinTechs and a small amount who have not begun the process at all. Research limitations/implications This review illustrates the current state of play of blockchain in insurance from a commercial and regulatory point of view. While this has been observational, this review pulls together information from various sources to encapsulate the regulatory positioning of evaluating FinTech and Blockchain technologies for academia, regulatory and industry audiences. Originality/value This review offers a central resource of information with regard to the current state of blockchain technologies in operation and regulatory approaches to this and other FinTech developments.


2019 ◽  
Vol 85 (18) ◽  
Author(s):  
Héctor M. Alvarez ◽  
O. Marisa Herrero ◽  
Roxana A. Silva ◽  
Martín A. Hernández ◽  
Mariana P. Lanfranconi ◽  
...  

ABSTRACT Some species belonging to the Rhodococcus genus, such as Rhodococcus opacus, R. jostii, and R. wratislaviensis, are known to be oleaginous microorganisms, since they are able to accumulate triacylglycerols (TAG) at more than 20% of their weight (dry weight). Oleaginous rhodococci are promising microbial cell factories for the production of lipids to be used as fuels and chemicals. Cells could be engineered to create strains capable of producing high quantities of oils from industrial wastes and a variety of high-value lipids. The comprehensive understanding of carbon metabolism and its regulation will contribute to the design of a reliable process for bacterial oil production. Bacterial oleagenicity requires an integral configuration of metabolism and regulatory processes rather than the sole existence of an efficient lipid biosynthesis pathway. In recent years, several studies have been focused on basic aspects of TAG biosynthesis and accumulation using R. opacus PD630 and R. jostii RHA1 strains as models of oleaginous bacteria. The combination of results obtained in these studies allows us to propose a metabolic landscape for oleaginous rhodococci. In this context, this article provides a comprehensive and integrative view of different metabolic and regulatory attributes and innovations that explain the extraordinary ability of these bacteria to synthesize and accumulate TAG. We hope that the accessibility to such information in an integrated way will help researchers to rationally select new targets for further studies in the field.


2019 ◽  
Vol 31 (6) ◽  
pp. 849-869
Author(s):  
Swati Singh ◽  
Ralf Wagner

Purpose This paper aims to focus on how home-grown Indian companies explored the potential of Indian middle class and realized an opportunity to seize the market gap not catered by MNCs in India. Across three distinct business contexts, the authors describe the companies’ procedures of developing segment-specific offerings. Doing so, the authors outline novel strategies implemented by these companies to cater to specific needs of the segments. Design/methodology/approach Seizing Bandura’s (1986) framework that stresses on the role of cognitive, vicarious, self-reflective and self-regulatory processes, the authors develop a four-layered model of the Indian middle class consumers. Building upon this model, they took multiple case (three caselets) approach for illustrating the strategies of home-grown companies. The authors identify their potential to explore the unknown terrains of various market segments and rework with unique local solutions. Findings The study highlights the power of home-grown companies over MNCs in terms of better market understanding and realistic offerings best suited to their needs. Across the divergent business contexts the companies’ strategies have four features in common: customer targeting and developing; localization of business models, particularly services; relating the products to the Indian society; and ethnocentrism and pride. Research limitations/implications This study gives priority to a “thick” description of the proceedings without claiming causality. The authors limit this qualitative investigation to pinpointing congruence and contradictions to previous established results. Practical implications A key implication of this paper is the relevance of linking firm’s strategy to social-psychological development of customers in emerging economies component. This study provides critical insights for both managers and policymakers on the economic and social upswing as socially responsible and ethical practices are likely to gain public awareness. Originality/value The study’s originality springs from understanding the domestic company’s strategies when facing the pressure of (mainly Western) MNCs entering the emerging economies markets. While the latter takes advantage of economies of scale, country of origin effects and the powerful brands, the home-grown businesses are forced to develop divergent advantages and capabilities. Notably, earlier literature focused on changed demand pattern brought by MNCs in emerging economies and not on later part whereby, home-grown companies carve a space for themselves with specially designed improved products and innovative strategies.


2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Julieta Schachter ◽  
Dayane Alvarinho de Oliveira ◽  
Camila Marques da Silva ◽  
Alba Cristina Miranda de Barros Alencar ◽  
Michelle Duarte ◽  
...  

ABSTRACT Infections with Trichuris trichiura are among the most common causes of intestinal parasitism in children worldwide, and the diagnosis is based on microscopic egg identification in the chronic phase of the infection. During parasitism, the adult worm of the trichurid nematode maintains its anterior region inserted in the intestinal mucosa, which causes serious damage and which may open access for gut microorganisms through the intestinal tissue. The immune-regulatory processes taking place during the evolution of the chronic infection are still not completely understood. By use of the Swiss Webster outbred mouse model, mice were infected with 200 eggs, and tolerance to the establishment of a chronic Trichuris muris infection was induced by the administration of a short pulse of dexamethasone during nematode early larval development. The infected mice presented weight loss, anemia, an imbalance of the microbiota, and intense immunological cell infiltration in the large intestine. It was found that mice have a mixed Th1/Th2/Th17 response, with differences being found among the different anatomical locations. After 45 days of infection, the parasitism induced changes in the microbiota composition and bacterial invasion of the large intestine epithelium. In addition, we describe that the excretory-secretory products from the nematode have anti-inflammatory effects on mouse macrophages cultured in vitro, suggesting that T. muris may modulate the immune response at the site of insertion of the worm inside mouse tissue. The data presented in this study suggest that the host immune state at 45 days postinfection with T. muris during the chronic phase of infection is the result of factors derived from the worm as well as alterations to the microbiota and bacterial invasion. Taken together, these results provide new information about the parasite-host-microbiota relationship and open new treatment possibilities.


2015 ◽  
Vol 53 (9) ◽  
pp. 2895-2899 ◽  
Author(s):  
Hazel C. Dobinson ◽  
Trevor P. Anderson ◽  
Stephen T. Chambers ◽  
Matthew P. Doogue ◽  
Lois Seaward ◽  
...  

Corynebacteriumspecies are increasingly recognized as important pathogens in granulomatous mastitis. Currently, there are no published treatment protocols forCorynebacteriumbreast infections. This study describes antimicrobial treatment options in the context of other management strategies used for granulomatous mastitis.Corynebacteriumspp. isolated from breast tissue and aspirate samples stored from 2002 to 2013 were identified and determined to the species level using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), 16S RNA sequencing, andrpoBgene targets. The MICs for 12 antimicrobials were performed using Etest for each isolate. Correlations of these with antimicrobial characteristics, choice of antimicrobial, and disease outcome were evaluated.Corynebacteriumspp. from breast tissue and aspirate samples were confirmed in 17 isolates from 16 patients. Based on EUCAST breakpoints,Corynebacterium kroppenstedtiiisolates (n= 11) were susceptible to seven antibiotic classes but resistant to β-lactam antibiotics.Corynebacterium tuberculostearicumisolates (n= 4) were multidrug resistant. Two nonlipophilic species were isolated,Corynebacterium glucuronolyticumandCorynebacterium freneyi, both of which have various susceptibilities to antimicrobial agents. Short-course antimicrobial therapy was common (median, 6 courses per subject; range, 1 to 9 courses). Patients withC. kroppenstedtiipresented with a hot painful breast mass and underwent multiple surgical procedures (median, 4 procedures; range, 2 to 6 procedures). The management ofCorynebacteriumbreast infections requires a multidisciplinary approach and includes culture and appropriate sensitivity testing to guide antimicrobial therapy. Established infections have a poor outcome, possibly because adequate concentrations of some drugs will be difficult to achieve in lipophilic granulomata. Lipophilic antimicrobial therapy may offer a therapeutic advantage. The role of immunotherapy has not been defined.


2013 ◽  
Vol 57 (5) ◽  
pp. 2095-2102 ◽  
Author(s):  
Christian van Delden ◽  
Malcolm G. P. Page ◽  
Thilo Köhler

ABSTRACTBAL30072 is a monosulfactam conjugated with an iron-chelating dihydroxypyridone moiety. It is active against Gram-negative bacteria, including multidrug-resistantPseudomonas aeruginosa. We selected mutants with decreased susceptibilities to BAL30072 inP. aeruginosaPAO1 under a variety of conditions. Under iron-deficient conditions, mutants with overexpression of AmpC β-lactamase predominated. These mutants were cross-resistant to aztreonam and ceftazidime. Similar mutants were obtained after selection at >16× the MIC in iron-sufficient conditions. At 4× to 8× the MIC, mutants with elevated MIC for BAL30072 but unchanged MICs for aztreonam or ciprofloxacin were selected. The expression ofampCand the major efflux pump genes were also unchanged. These BAL30072-specific mutants were characterized by transcriptome analysis, which revealed upregulation of the Fe-dicitrate operon, FecIRA. Whole-genome sequencing showed that this resulted from a single nucleotide change in the Fur-box of thefecIpromoter. Overexpression of either the FecI ECF sigma factor or the FecA receptor increased BAL30072 MICs 8- to 16-fold. AfecImutant and afecAmutant of PAO1 were hypersusceptible to BAL30072 (MICs < 0.06 μg/ml). The most downregulated gene belonged to the pyochelin synthesis operon, although mutants in pyochelin receptor or synthesis genes had unchanged MICs. ThepiuCgene, coding for a Fe(II)-dependent dioxygenase located next to thepiuAiron receptor gene, was also downregulated. The MICs of BAL30072 forpiuCandpiuAtransposon mutants were increased 8- and 16-fold, respectively. We conclude that the upregulation of the Fe-dicitrate system impacts the expression of other TonB-dependent iron transporters and that PiuA and PiuC contribute to the susceptibility ofP. aeruginosaPAO1 to BAL30072.


2017 ◽  
Vol 19 (6) ◽  
pp. 418-430 ◽  
Author(s):  
Steve Moore

Purpose The purpose of this paper is to present a review of some of the fundamental theoretical and contextual components of commissioning and regulatory processes as applied to care home services, revisiting and examining how they impact on the potential prevention of abuse. Design/methodology/approach By revisiting a number of the theoretical bases of commissioning activity, some of which may also be applied to regulatory functions, the reasons for the apparent limited impact on the prevention of the abuse that occurs in care homes by these agencies are analysed. Findings The paper demonstrates how the application of commissioning and regulatory theory may be applied to the oversight of care homes to inform proposed preventative strategies. Practical implications The paper offers strategies to improve the prevention of abuse in care homes for older people. Originality/value A factual and “back to basics” approach is taken to demonstrate why current strategies that should contribute to tackling abuse in care homes are of limited efficacy.


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