scholarly journals The T788G Mutation in thecyp51CGene Confers Voriconazole Resistance in Aspergillus flavus Causing Aspergillosis

2012 ◽  
Vol 56 (5) ◽  
pp. 2598-2603 ◽  
Author(s):  
Wei Liu ◽  
Yi Sun ◽  
Wei Chen ◽  
Weixia Liu ◽  
Zhe Wan ◽  
...  

ABSTRACTWith voriconazole (VRC) being approved as the first choice in treating invasive aspergillosis (IA) and its increasing use in treatment, a VRC-resistant strain ofAspergillus flavus, the second leading cause of IA afterAspergillus fumigatus, has emerged. The VRC-resistant strain ofA. flavuswas isolated for the first time from the surgical lung specimen of an IA patient with no response to VRC therapy. In order to ascertain the mechanism of VRC resistance, the azole target enzyme genes in this strain ofA. flavuswere cloned and sequenced, and 4 mutations generating amino acid residue substitutions were found in thecyp51Cgene. To further determine the role of this mutated gene for VRC resistance inA. flavus, anAgrobacterium tumefaciens-mediated gene replacement approach was applied. Consequently, the mutatedcyp51Cgene from thisA. flavusstrain was proven to confer the VRC resistance. Finally, to discern the one out of the four mutations in thecyp51Cgene that is responsible for contributing to VRC resistance, a site-directed gene mutagenesis procedure combined with a gene replacement method was performed. As a result, the T788G missense mutation in thecyp51Cgene was identified as responsible for VRC resistance inA. flavus. These findings indicated that the detection of this mutation inA. flavuscould serve as an indicator for physicians to avoid the use of VRC during IA treatment. Further comprehensive surveillance for antifungal susceptibility, as well as intensive study on the mechanism of azole resistance inA. flavuscausing IA, would be required to fully understand this mechanism.

2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Olaf Hoffjann ◽  
Karina Hoffstedde ◽  
Franziska Jaworek

PurposeAlthough the market for communication consultancies has been booming worldwide for many years now, there are still only a handful of theoretical concepts and empirical findings pertaining to communication consulting. This is the fundamental starting point for this paper, which sets out to answer the following research questions: What is the function of communication consulting? What are the differences between consultants' expectations of consulting and those of clients? How do consultants and clients deal with the contradiction between proximity and distance? What are the potential threats to the autonomy of consulting?Design/methodology/approachThe paper combines a theoretical framework of communication consulting with a survey of German communication consultants and clients.FindingsFirst, a theoretical framework is developed in which communication consulting is defined as follows: First, it opens up decision-related contingency and thus produces additional options for managing communicative relationships with internal and external target groups, before helping to close decision-related contingency. The results of the survey show that the expectations of clients and consultants for communication consulting are largely similar. In the closing dimension especially, most clients share the active role of self-conception of most consultants. On the other hand, in some opening activities, clients wish for more critical, independent and courageous consulting.Research limitations/implicationsThe scope of the empirical material is limited to communication consultants and clients in Germany and may therefore not be valid in other cultural contexts.Originality/valueThe paper closes a gap in both theory building and empirical research in communication consulting. The theory presented conceives of communication consulting as a hybrid of management consulting and process consulting and, in addition to the opening dimension, also takes the closing dimension of consulting into consideration for the first time. The study reveals a certain schizophrenia in clients: on the one hand, clients demand more critical consultants and thus call for more distance; on the other hand, clients prefer to be close to their consultants, particularly if they wish to work with them for the long-term.


2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Mojtaba Taghizadeh-Armaki ◽  
Mohammad Taghi Hedayati ◽  
Saham Ansari ◽  
Saeed Mahdavi Omran ◽  
Sasan Saber ◽  
...  

ABSTRACT Aspergillus flavus has been frequently reported as the leading cause of invasive aspergillosis in certain tropical and subtropical countries. Two hundred A. flavus strains originating from clinical and environmental sources and collected between 2008 and 2015 were phylogenetically identified at the species level by analyzing partial β-tubulin and calmodulin genes. In vitro antifungal susceptibility testing was performed against antifungals using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. In addition, genotyping was performed using a short-tandem-repeat (STR) assay of a panel of six microsatellite markers (A. flavus 2A, 2B, 2C, 3A, 3B, and 3C), in order to determine the genetic variation and the potential relationship between clinical and environmental isolates. The geometric means of the minimum inhibitory concentrations/minimum effective concentrations (MICs/MECs) of the antifungals across all isolates were (in increasing order): posaconazole, 0.13 mg/liter; anidulafungin, 0.16 mg/liter; itraconazole, 0.29 mg/liter; caspofungin, 0.42 mg/liter; voriconazole, 0.64 mg/liter; isavuconazole, 1.10 mg/liter; amphotericin B, 3.35 mg/liter; and flucytosine, 62.97 mg/liter. All of the clinical isolates were genetically different. However, an identical microsatellite genotype was found between a clinical isolate and two environmental strains. In conclusion, posaconazole and anidulafungin showed the greatest in vitro activity among systemic azoles and echinocandins, respectively. However, the majority of the A. flavus isolates showed reduced susceptibility to amphotericin B. Antifungal susceptibility of A. flavus was not linked with the clinical or environmental source of isolation. Microsatellite genotyping may suggest an association between clinical and environmental strains, although this requires further investigation.


2016 ◽  
Vol 82 (10) ◽  
pp. 3100-3108 ◽  
Author(s):  
Charlien Clauwers ◽  
Kristof Vanoirbeek ◽  
Laurence Delbrassinne ◽  
Chris W. Michiels

ABSTRACTGroup II nonproteolyticClostridium botulinum(gIICb) strains are an important concern for the safety of minimally processed ready-to-eat foods, because they can grow and produce botulinum neurotoxin during refrigerated storage. The principles of control of gIICb by conventional food processing and preservation methods have been well investigated and translated into guidelines for the food industry; in contrast, the effectiveness of emerging processing and preservation techniques has been poorly documented. The reason is that experimental studies withC. botulinumare cumbersome because of biosafety and biosecurity concerns. In the present work, we report the construction of two nontoxigenic derivatives of the type E gIICb strain NCTC 11219. In the first strain, the botulinum toxin gene (bont/E) was insertionally inactivated with a retargeted intron using the ClosTron system. In the second strain,bont/Ewas exchanged for an erythromycin resistance gene using a new gene replacement strategy that makes use ofpyrEas a bidirectional selection marker. Growth under optimal and stressed conditions, sporulation efficiency, and spore heat resistance of the mutants were unaltered, except for small differences in spore heat resistance at 70°C and in growth at 2.3% NaCl. The mutants described in this work provide a safe alternative for basic research as well as for food challenge and process validation studies with gIICb. In addition, this work expands the clostridial genetic toolbox with a new gene replacement method that can be applied to replace any gene in gIICb and other clostridia.IMPORTANCEThe nontoxigenic mutants described in this work provide a safe alternative for basic research as well as for food challenge and process validation studies with psychrotrophicClostridium botulinum. In addition, this work expands the clostridial genetic toolbox with a new gene replacement method that can be applied to replace any gene in clostridia.


2011 ◽  
Vol 55 (9) ◽  
pp. 4188-4195 ◽  
Author(s):  
Miki Matsuo ◽  
Tomomi Hishinuma ◽  
Yuki Katayama ◽  
Longzhu Cui ◽  
Maria Kapi ◽  
...  

ABSTRACTThe clinical vancomycin-intermediateStaphylococcus aureus(VISA) strain Mu50 carries two mutations in thevraSRandgraRStwo-component regulatory systems (TCRSs), namely,vraS(I5N) andgraR(N197S) (hereinafter designatedgraR*). The clinical heterogeneously vancomycin-intermediateS. aureus(hVISA) strain Mu3 shares with Mu50 the mutation invraSthat encodes the VraS two-component histidine kinase. Previously, we showed that introduction of the plasmid pgraR*, carrying the mutated two-component response regulatorgraR*, converted the hVISA strain Mu3 into VISA (vancomycin MIC = 4 mg/liter). Subsequently, however, we found that the introduction of a single copy ofgraR* into the Mu3 chromosome by a gene replacement method did not confer on Mu3 the VISA phenotype. The gene-replaced strain Mu3graR* thus obtained remained hVISA (MIC ≤ 2 mg/liter), although a small increase in vancomycin MIC was observed compared to that of the parent strain Mu3. Reevaluation of the Mu3 and Mu50 genomes revealed the presence of another mutation responsible for the expression of the VISA phenotype in Mu50. Here, we demonstrate that in addition to the two regulator mutations, a third mutation found in the Mu50rpoBgene, encoding the RNA polymerase β subunit, was required for Mu3 to achieve the level of vancomycin resistance of Mu50. The selection of strain Mu3graR* with rifampin gave rise torpoBmutants with various levels of increased vancomycin resistance. Furthermore, 3 (33%) of 10 independently isolated VISA strains established from the heterogeneous subpopulations of Mu3graR* were found to possessrpoBmutations with or without an accompanying rifampin-resistance phenotype. The data indicate that a sizable proportion of the resistant hVISA cell subpopulations is composed of spontaneousrpoBmutants with various degrees of increased vancomycin resistance.


2017 ◽  
Vol 119 (3) ◽  
pp. 639-657 ◽  
Author(s):  
Gessuir Pigatto ◽  
Joao Guilherme de Camargo Ferraz Machado ◽  
Amanda dos Santos Negreti ◽  
Lucas Miranda Machado

Purpose The purpose of this paper is to characterize the performance of online food delivery companies in Brazil and to analyze the content of the websites of these companies with a view to its use as a site for conducting business transactions. Design/methodology/approach This paper used a qualitative and exploratory approach through the collection and analysis of data from a sample of 30 companies operating in the online delivery sector in Brazil. Reviews of their websites have also been conducted through parameters involving aspects of content, usability and functionality. Findings The Brazilian main platforms received large foreign investment, growing with the acquisition of companies, making them market leaders. There was a greater presence of these companies on social networks, publicizing and interacting with their customers, increasing business visibility and attracting new prospects. The results of the sites analysis showed that the dimension “content” was the one with the highest incidence of attendance, followed by the dimension “functionality” and then the dimension “usability.” The downside was the access security parameter since only 54 percent of websites showed the use of encryption capabilities and secure site. Originality/value The online delivery service is growing rapidly, bringing together innovation and convenience to their customers, coupled with ease of access to mobile phones and internet, that contributed toward the emergence of a large number of platforms that offer this service in Brazil; despite being a relatively new service, its growth was accompanied by a strong sector consolidation process and by the creation of large groups supported by international capital.


2014 ◽  
Vol 53 (2) ◽  
pp. 702-705 ◽  
Author(s):  
Yali Li ◽  
Zhe Wan ◽  
Wei Liu ◽  
Ruoyu Li

Molecular identification andin vitroantifungal susceptibility tests of 43AspergillussectionNigriisolates from China were performed.Aspergillus nigerandAspergillus tubingensiswere present in almost equal numbers. All of the isolates had low MIC/MECs (minimum effective concentrations) for the 7 common antifungals, and a paradoxical effect was observed for the first time in response to caspofungin and micafungin.


2019 ◽  
Vol 36 (2) ◽  
pp. 21-22
Author(s):  
Ray Harper

Purpose The purpose of this paper is to summarise a number of presentations at Day 1 of the Internet Librarian International conference, London, UK (16 October 2018). This was the 20th conference in the series, and the three key themes included were the next-gen library and librarian; understanding users, usage and user experience; and inclusion and inspiration: libraries making a difference. Design/methodology/approach This paper reports from the viewpoint of a first-time attendee of the conference. This summarises the main issues raised by each presentation and draws out the key learning points for practical situations. Findings The conference covered a variety of practical ways in which libraries can use technology to support users and make decisions about services. These include developing interactive physical spaces which include augmented reality; introducing “chat-bots” to support users; using new techniques to analyse data; and piloting new ways to engage users (such as coding clubs). A key theme was how we use and harness data in a way that is ethical, effective and relevant to library services. Originality/value This conference focussed on practical examples of how library and information services across sectors and countries are innovating in a period of huge change. The conference gave delegates numerous useful ideas and examples of best practice and demonstrated the strength of the profession in adapting to new technologies and developments.


2019 ◽  
Vol 37 (1) ◽  
pp. 134-142
Author(s):  
Alberto Bueno-Guerrero

Purpose This paper aims to study the conditions for the hedging portfolio of any contingent claim on bonds to have no bank account part. Design/methodology/approach Hedging and Malliavin calculus techniques recently developed under a stochastic string framework are applied. Findings A necessary and sufficient condition for the hedging portfolio to have no bank account part is found. This condition is applied to a barrier option, and an example of a contingent claim whose hedging portfolio has a bank account part different from zero is provided. Originality/value To the best of the authors’ knowledge, this is the first time that this issue has been addressed in the literature.


2020 ◽  
Vol 36 (8) ◽  
pp. 29-31

Purpose Reviews the latest management developments across the globe and pinpoints practical implications from cutting-edge research and case studies. Design/methodology/approach This briefing is prepared by an independent writer who adds their own impartial comments and places the articles in context. Findings The problem with developing a reputation of being something of an oracle in the business world is that all of a sudden, everyone expects you to pull off the trick of interpreting the future on a daily basis. Like a freak show circus act or one-hit wonder pop singer, people expect you to perform when they see you, and they expect you to perform the thing that made you famous, even if it is the one thing in the world you don’t want to do. And when you fail to deliver on these heightened expectations, you are dismissed as a one trick pony, however good that trick is in the first place. Originality/value The briefing saves busy executives and researchers hours of reading time by selecting only the very best, most pertinent information and presenting it in a condensed and easy-to-digest format.


Kybernetes ◽  
2019 ◽  
Vol 49 (4) ◽  
pp. 1083-1102
Author(s):  
Georgios N. Aretoulis ◽  
Jason Papathanasiou ◽  
Fani Antoniou

Purpose This paper aims to rank and identify the most efficient project managers (PMs) based on personality traits, using Preference Ranking Organization METHod for Enrichment Evaluations (PROMETHEE) methodology. Design/methodology/approach The proposed methodology relies on the five personality traits. These were used as the selection criteria. A questionnaire survey among 82 experienced engineers was used to estimate the required weights per personality trait. A second two-part questionnaire survey aimed at recording the PMs profile and assess the performance of personality traits per PM. PMs with the most years of experience are selected to be ranked through Visual PROMETHEE. Findings The findings suggest that a competent PM is the one that scores low on the “Neuroticism” trait and high especially on the “Conscientiousness” trait. Research limitations/implications The research applied a psychometric test specifically designed for Greek people. Furthermore, the proposed methodology is based on the personality characteristics to rank the PMs and does not consider the technical skills. Furthermore, the type of project is not considered in the process of ranking PMs. Practical implications The findings could contribute in the selection of the best PM that maximizes the project team’s performance. Social implications Improved project team communication and collaboration leading to improved project performance through better communication and collaboration. This is an additional benefit for the society, especially in the delivery of public infrastructure projects. A lot of public infrastructure projects deviate largely as far as cost and schedule is concerned and this is an additional burden for public and society. Proper project management through efficient PMs would save people’s money and time. Originality/value Identification of the best PMbased on a combination of multicriteria decision-making and psychometric tests, which focus on personality traits.


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