Effects of Surotomycin on Clostridium difficile Viability and Toxin ProductionIn Vitro

ABSTRACTThe increasing incidence and severity of infection byClostridium difficilehave stimulated attempts to develop new antimicrobial therapies. We report here the relative abilities of two antibiotics (metronidazole and vancomycin) in current use for treatingC. difficileinfection and of a third antimicrobial, surotomycin, to killC. difficilecells at various stages of development and to inhibit the production of the toxin proteins that are the major virulence factors. The results indicate that none of the drugs affects the viability of spores at 8× MIC or 80× MIC and that all of the drugs kill exponential-phase cells when provided at 8× MIC. In contrast, none of the drugs killed stationary-phase cells or inhibited toxin production when provided at 8× MIC and neither vancomycin nor metronidazole killed stationary-phase cells when provided at 80× MIC. Surotomycin, on the other hand, did kill stationary-phase cells when provided at 80× MIC but did so without inducing lysis.

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A Nutrient-Regulated Cyclic Diguanylate Phosphodiesterase Controls Clostridium difficile Biofilm and Toxin Production during Stationary Phase

Infection and Immunity ◽

10.1128/iai.00347-17 ◽

2017 ◽

Vol 85 (9) ◽

Cited By ~ 18

Author(s):

Erin B. Purcell ◽

Robert W. McKee ◽

David S. Courson ◽

Elizabeth M. Garrett ◽

Shonna M. McBride ◽

...

Keyword(s):

Clostridium Difficile ◽

Stationary Phase ◽

Nutrient Availability ◽

Biofilm Formation ◽

Biochemical Characterization ◽

Toxin Production ◽

Physiological Adaptation ◽

Cyclic Diguanylate ◽

Content Type ◽

Wide Range

ABSTRACT The signaling molecule cyclic diguanylate (c-di-GMP) mediates physiological adaptation to extracellular stimuli in a wide range of bacteria. The complex metabolic pathways governing c-di-GMP synthesis and degradation are highly regulated, but the specific cues that impact c-di-GMP signaling are largely unknown. In the intestinal pathogen Clostridium difficile, c-di-GMP inhibits flagellar motility and toxin production and promotes pilus-dependent biofilm formation, but no specific biological functions have been ascribed to any of the individual c-di-GMP synthases or phosphodiesterases (PDEs). Here, we report the functional and biochemical characterization of a c-di-GMP PDE, PdcA, 1 of 37 confirmed or putative c-di-GMP metabolism proteins in C. difficile 630. Our studies reveal that pdcA transcription is controlled by the nutrient-regulated transcriptional regulator CodY and accordingly increases during stationary phase. In addition, PdcA PDE activity is allosterically regulated by GTP, further linking c-di-GMP levels to nutrient availability. Mutation of pdcA increased biofilm formation and reduced toxin biosynthesis without affecting swimming motility or global intracellular c-di-GMP. Analysis of the transcriptional response to pdcA mutation indicates that PdcA-dependent phenotypes manifest during stationary phase, consistent with regulation by CodY. These results demonstrate that inactivation of this single PDE gene is sufficient to impact multiple c-di-GMP-dependent phenotypes, including the production of major virulence factors, and suggest a link between c-di-GMP signaling and nutrient availability.

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Islamic hedging for pilgrimage funds: case of Indonesia

Qualitative Research in Financial Markets ◽

10.1108/qrfm-11-2017-0101 ◽

2019 ◽

Vol 11 (3) ◽

pp. 328-341

Author(s):

Rifki Ismal ◽

Nurul Izzati Septiana

Keyword(s):

Exchange Rate ◽

The Other ◽

Exchange Rate Risk ◽

Content Type ◽

Other Hand ◽

Rate Risk ◽

Risk Identify ◽

Hajj Season ◽

The Right ◽

Very High

Purpose The demand for Saudi Arabian real (SAR) is very high in the pilgrimage (hajj) season while the authority, unfortunately, does not hedge the hajj funds. As such, the hajj funds are potentially exposed to exchange rate risk, which can impact the value of hajj funds and generate extra cost to the pilgrims. The purpose of this paper is to conduct simulations of Islamic hedging for pilgrimage funds to: mitigate and minimize exchange rate risk, identify and recommend the ideal time, amount and tenors of Islamic hedging for hajj funds, estimate cost saving by pursuing Islamic hedging and propose technical and general recommendations for the authority. Design/methodology/approach Forward transaction mechanism is adopted to compute Islamic forward between SAR and Rupiah (Indonesian currency) or IDR. Findings – based on simulations, the paper finds that: the longer the Islamic hedging tenors, the better is the result of Islamic hedging, the decreasing of IDR/USD is the right time to hedge the hajj funds and, on the other hand, the IDR/SAR appreciation is not the right time to hedge the hajj funds. Findings Based on simulations, the paper finds that: the longer the Islamic hedging tenors, the better is the result of Islamic hedging, the decreasing of IDR/USD is the right time to hedge the hajj funds and, on the other hand, the IDR/SAR appreciation is not the right time to hedge the hajj funds. Research limitations/implications The research suggests the authority to (and not to) hedge the hajj fund, depending on economic conditions and market indicators. Even though the assessment is for the Indonesian case, other countries maintaining hajj funds might also learn from this paper. Originality/value To the best of author’s knowledge, this is the first paper in Indonesia that attempts to simulate the optimal hedging of hajj funds.

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Comparative leaf development of aerial and aquatic growth forms of Myriophyllum aquaticum

Botany ◽

10.1139/cjb-2012-0190 ◽

2013 ◽

Vol 91 (7) ◽

pp. 421-430 ◽

Cited By ~ 1

Author(s):

M.D. Shafiullah ◽

Christian R. Lacroix

Keyword(s):

Apical Meristem ◽

Epidermal Cells ◽

The Other ◽

Developmental Study ◽

Growth Forms ◽

Myriophyllum Aquaticum ◽

Stages Of Development ◽

Qualitative And Quantitative ◽

Early Stages ◽

Other Hand

Myriophyllum aquaticum (Vell.) Verdc. produces two morphologically different forms of leaves based on whether they are aerial or aquatic. The objective of this study was to determine whether there are any similarities or differences between these two growth forms during their early stages of development. A comparative developmental study of aerial and aquatic growth forms of M. aquaticum was conducted from a qualitative and quantitative perspective using a scanning electron microscope. The pattern of leaf and lobe initiation such as their origin and shape were similar in both growth forms until the fourth plastochron (stage P4). Differences between the two growth forms became evident from stage P5 onward, where a larger shoot apical meristem (SAM), elongated epidermal cells, shorter and slightly more numerous lobes, as well as the presence of appendage-like structures characterized aquatic growth forms. On the other hand, aerial growth forms had smaller SAM, bulb-like epidermal cells, and longer and slightly less numerous leaf lobes. Significant differences between growth forms were noted for parameters such as volume of SAM, length of terminal, first, and middle lobes, as well as the length from first to last lobes. The volume of the SAM of aquatic shoot tips was always greater than aerial forms. On the other hand, lobes of aerial forms were always longer than the aquatic counterpart during early stages of development. This study on the development of M. aquaticum shows that the aerial and aquatic growth forms diverge from their early stages of development.

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Emergence of cultural intelligence and global mindset capital: a multilevel model

Multinational Business Review ◽

10.1108/mbr-12-2015-0062 ◽

2016 ◽

Vol 24 (2) ◽

pp. 106-122 ◽

Cited By ~ 8

Author(s):

Jase R. Ramsey ◽

Amine Abi Aad ◽

Chuandi Jiang ◽

Livia Barakat ◽

Virginia Drummond

Keyword(s):

Multilevel Model ◽

Cultural Intelligence ◽

The Other ◽

Global Mindset ◽

Firm Level ◽

Content Type ◽

Individual Level ◽

Other Hand ◽

Underlying Mechanisms ◽

Conceptual Study

Purpose The purpose of this paper is to establish under which conditions researchers should use the constructs cultural intelligence (CQ) and global mindset (GM). The authors further seek to understand the process through which these constructs emerge to a higher level and link unit-level knowledge, skills and abilities (KSAs) capital to pertinent firm-level outcomes. Design/methodology/approach This paper is a conceptual study with a multilevel model. Findings This paper differentiates two similar lines of research occurring concordantly on the CQ and GM constructs. Next, the authors develop a multilevel model to better understand the process through which CQ and GM emerge at higher levels and their underlying mechanisms. Finally, this paper adds meaning to the firm-level KSAs by linking firm-level KSAs capital to pertinent firm-level outcomes. Research limitations/implications The conclusion implies that researchers should use CQ when the context is focused on interpersonal outcomes and GM when focused on strategic outcomes. The multilevel model is a useful tool for scholars to select which rubric to use in future studies that have international managers as the subjects. The authors argue that if the scholar is interested in an individual’s ability to craft policy and implement strategy, then GM may be more parsimonious than CQ. On the other hand, if the focus is on leadership, human resources or any other relationship dependent outcome, then CQ will provide a more robust measure. Practical implications For practitioners, this study provides a useful tool for managers to improve individual-level commitment by selecting and training individuals high in CQ. On the other hand, if the desired outcome is firm-level sales or performance, the focus should be on targeting individuals high in GM. Originality/value This is the first theoretical paper to examine how CQ and GM emerge to the firm level and describe when to use each measure.

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Little epigraphy

Lampas ◽

10.5117/lam2021.1.007.pitt ◽

2021 ◽

Vol 54 (1) ◽

pp. 119-136

Author(s):

Robert Pitt

Keyword(s):

Metal Surfaces ◽

The Other ◽

Content Type ◽

Weights And Measures ◽

Other Hand ◽

Large Corpus

Abstract Most well-known inscriptions are monumental texts carved on stone. In this contribution, on the other hand, we focus on small, often informal texts scratched or stamped on rocks, metal surfaces and pottery. To this type of so-called ‘little epigraphy’ belong for instance graffiti, ostraca, weights and measures, curse tablets, etcetera. Although the texts themselves are usually very short, together they constitute a large corpus.

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Cyclic Diguanylate Regulates Virulence Factor Genes via Multiple Riboswitches inClostridium difficile

mSphere ◽

10.1128/msphere.00423-18 ◽

2018 ◽

Vol 3 (5) ◽

Cited By ~ 11

Author(s):

Robert W. McKee ◽

Carissa K. Harvest ◽

Rita Tamayo

Keyword(s):

Gene Expression ◽

Clostridium Difficile ◽

Biofilm Formation ◽

Toxin Production ◽

Intestinal Colonization ◽

Cyclic Diguanylate ◽

Signaling Molecule ◽

Content Type ◽

Surface Motility

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.

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Coordinated Hibernation of Transcriptional and Translational Apparatus during Growth Transition ofEscherichia colito Stationary Phase

mSystems ◽

10.1128/msystems.00057-18 ◽

2018 ◽

Vol 3 (5) ◽

Cited By ~ 10

Author(s):

Hideji Yoshida ◽

Tomohiro Shimada ◽

Akira Ishihama

Keyword(s):

Stationary Phase ◽

Sigma Factor ◽

Exponential Phase ◽

Screening System ◽

Content Type ◽

Genome Expression ◽

70S Ribosome ◽

K 12 ◽

Sigma Subunit ◽

Translational Apparatus

ABSTRACTIn the process ofEscherichia coliK-12 growth from exponential phase to stationary, marked alteration takes place in the pattern of overall genome expression through modulation of both parts of the transcriptional and translational apparatus. In transcription, the sigma subunit with promoter recognition properties is replaced from the growth-related factor RpoD by the stationary-phase-specific factor RpoS. The unused RpoD is stored by binding with the anti-sigma factor Rsd. In translation, the functional 70S ribosome is converted to inactive 100S dimers through binding with the ribosome modulation factor (RMF). Up to the present time, the regulatory mechanisms of expression of these two critical proteins, Rsd and RMF, have remained totally unsolved. In this study, attempts were made to identify the whole set of transcription factors involved in transcription regulation of thersdandrmfgenes using the newly developed promoter-specific transcription factor (PS-TF) screening system. In the first screening, 74 candidate TFs with binding activity to both of thersdandrmfpromoters were selected from a total of 194 purified TFs. After 6 cycles of screening, we selected 5 stress response TFs, ArcA, McbR, RcdA, SdiA, and SlyA, for detailed analysisin vitroandin vivoof their regulatory roles. Results indicated that bothrsdandrmfpromoters are repressed by ArcA and activated by McbR, RcdA, SdiA, and SlyA. We propose the involvement of a number of TFs in simultaneous and coordinated regulation of the transcriptional and translational apparatus. By using genomic SELEX (gSELEX) screening, each of the five TFs was found to regulate not only thersdandrmfgenes but also a variety of genes for growth and survival.IMPORTANCEDuring the growth transition ofE. colifrom exponential phase to stationary, the genome expression pattern is altered markedly. For this alteration, the transcription apparatus is altered by binding of anti-sigma factor Rsd to the RpoD sigma factor for sigma factor replacement, while the translation machinery is modulated by binding of RMF to 70S ribosome to form inactive ribosome dimer. Using the PS-TF screening system, a number of TFs were found to bind to both thersdandrmfpromoters, of which the regulatory roles of 5 representative TFs (one repressor ArcA and the four activators McbR, RcdA, SdiA, and SlyA) were analyzed in detail. The results altogether indicated the involvement of a common set of TFs, each sensing a specific environmental condition, in coordinated hibernation of the transcriptional and translational apparatus for adaptation and survival under stress conditions.

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Repression of VvpM Protease Expression by Quorum Sensing and the cAMP-cAMP Receptor Protein Complex inVibrio vulnificus

Journal of Bacteriology ◽

10.1128/jb.00526-17 ◽

2018 ◽

Vol 200 (7) ◽

Cited By ~ 2

Author(s):

Jeong-A Kim ◽

Mi-Ae Lee ◽

You-Chul Jung ◽

Bo-Ram Jang ◽

Kyu-Ho Lee

Keyword(s):

Transcription Factors ◽

Stationary Phase ◽

Cell Density ◽

Transcription Initiation ◽

Vibrio Vulnificus ◽

The Other ◽

Receptor Protein ◽

Camp Receptor Protein ◽

Content Type ◽

Camp Receptor

ABSTRACTSepticemia-causingVibrio vulnificusproduces at least three exoproteases, VvpE, VvpS, and VvpM, all of which participate in interactions with human cells. Expression of VvpE and VvpS is induced in the stationary phase by multiple transcription factors, including sigma factor S, SmcR, and the cAMP-cAMP receptor protein (cAMP-CRP) complex. Distinct roles of VvpM, such as induction of apoptosis, lead us to hypothesize VvpM expression is different from that of the other exoproteases. Its transcription, which was found to be independent of sigma S, is induced at the early exponential phase and then becomes negligible upon entry into the stationary phase. SmcR and CRP were studied regarding the control ofvvpMexpression. Transcription ofvvpMwas repressed by SmcR and cAMP-CRP complex individually, which specifically bound to the regions −2 to +20 and +6 to +27, respectively, relative to thevvpMtranscription initiation site. Derepression ofvvpMgene expression was 10- to 40-fold greater in ansmcR crpdouble mutant than in single-gene mutants. Therefore, these results show that the expression ofV. vulnificusexoproteases is differentially regulated, and in this way, distinct proteases can engage in specific interactions with a host.IMPORTANCEAn opportunistic human pathogen,Vibrio vulnificusproduces multiple extracellular proteases that are involved in diverse interactions with a host. The total exoproteolytic activity is detected mainly in the supernatants of the high-cell-density cultures. However, some proteolytic activity derived from a metalloprotease, VvpM, was present in the supernatants of the low-cell-density cultures sampled at the early growth period. In this study, we present the regulatory mechanism for VvpM expression via repression by at least two transcription factors. This type of transcriptional regulation is the exact opposite of those for expression of the otherV. vulnificusexoproteases. Differential regulation of each exoprotease's production then facilitates the pathogen's participation in the distinct interactions with a host.

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Economic complexity and price competitiveness dependence: empirical evidence using panel models

International Journal of Development Issues ◽

10.1108/ijdi-07-2021-0141 ◽

2021 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Guilherme Magacho ◽

Rafael Ribeiro ◽

Igor Rocha

Keyword(s):

Exchange Rate ◽

Generalized Method Of Moments ◽

Output Growth ◽

The Other ◽

Content Type ◽

Price Competitiveness ◽

Economic Complexity ◽

Other Hand ◽

The Impact

Purpose As economies with high economic complexity and productive capabilities may easily adapt their productive structure due to product differentiation and innovation, the central variable of competitiveness for these countries is the product quality, not price. On the other hand, the price can be an important determinant of less complex countries, and hence, real exchange rate (RER) misalignments may have long-term impacts. This paper aims to empirically assess variations in the magnitude of the impact in RER misalignments on output growth subject to countries’ economic complexity. Design/methodology/approach The estimation technique used is the generalized method of moments-System estimator as this method is robust to reverse causality. Heterogeneous regressions using interaction models are undertaken to analyze to what extend promoting economic complexity can reduce price competitiveness dependence and allow countries to grow faster without relying on cost competitiveness. Findings Estimates show that economic complexity (which measures technological and productive capabilities) determines cross-country differences regarding the effects of RER misalignments on countries’ long-term growth rates. The results suggest that exchange rate devaluations may not be effective for countries at the top end of the technological ladder while an overvalued RER may damage the long-term growth rate of countries with low levels of economic complexity. Originality/value This paper contributes to the literature by empirically investigating the impact of RER misalignments in countries with distinct technological and productive capabilities based on the recent developments of countries’ economic complexity analysis. It investigates whether more diversified and complex economies are less sensitive to RER misalignments as they can adapt their production, undertake other tasks, create new products and increase the quality of products they produce. Less complex economies, on the other hand, are less capable of innovating because it demands productive capabilities they do not have, and hence, they are more dependent on their current export basket.

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Clinical guidelines and patient related outcomes: summary of evidence and recommendations

International Journal of Health Governance ◽

10.1108/ijhg-12-2018-0073 ◽

2019 ◽

Vol 24 (3) ◽

pp. 230-238

Author(s):

Luciana Pereira de Vasconcelos ◽

Luiza de Oliveira Rodrigues ◽

Moacyr Roberto Cuce Nobre

Keyword(s):

Medical Practice ◽

Positive Impact ◽

The Other ◽

Evidence Based ◽

Content Type ◽

Good Medical Practice ◽

Other Hand ◽

Care Improvement ◽

Based Medicine

Purpose Good medical practice, evidence-based medicine (EBM) and clinical practice guidelines (CPG) have been recurring subjects in the scientific literature. EBM advocates argue that good medical practice should be guided by evidence-based CPG. On the other hand, critical authors of EBM methodology argue that various interests undermine the quality of evidence and reliability of CPG recommendations. The purpose of this paper is to evaluate patient related outcomes of CPG implementation, in light of EBM critics. Design/methodology/approach The authors opted for a rapid literature review. Findings There are few studies evaluating the effectiveness of CPG in patient-related outcomes. The systematic reviews found are not conclusive, although they suggest a positive impact of CPGs in relevant outcomes. Research limitations/implications This work was not a systematic review of literature, which is its main limitation. On the other hand, arguments from EBM and CPG critics were considered, and thus it can enlighten health institutions to recognize the caveats and to establish policies toward care improvement. Originality/value The paper is the first of its kind to discuss, based on the published literature, next steps toward better health practice, while acknowledging the caveats of this process.

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