scholarly journals Topological analysis of a bacterial DedA protein associated with alkaline tolerance and antimicrobial resistance

Microbiology ◽  
2021 ◽  
Vol 167 (12) ◽  
Author(s):  
Hollie L. Scarsbrook ◽  
Roman Urban ◽  
Bree R. Streather ◽  
Alexandra Moores ◽  
Christopher Mulligan

Maintaining membrane integrity is of paramount importance to the survival of bacteria as the membrane is the site of multiple crucial cellular processes including energy generation, nutrient uptake and antimicrobial efflux. The DedA family of integral membrane proteins are widespread in bacteria and are associated with maintaining the integrity of the membrane. In addition, DedA proteins have been linked to resistance to multiple classes of antimicrobials in various microorganisms. Therefore, the DedA family are attractive targets for the development of new antibiotics. Despite DedA family members playing a key physiological role in many bacteria, their structure, function and physiological role remain unclear. To help illuminate the structure of the bacterial DedA proteins, we performed substituted cysteine accessibility method (SCAM) analysis on the most comprehensively characterized bacterial DedA protein, YqjA from Escherichia coli . By probing the accessibility of 15 cysteine residues across the length of YqjA using thiol reactive reagents, we mapped the topology of the protein. Using these data, we experimentally validated a structural model of YqjA generated using evolutionary covariance, which consists of an α-helical bundle with two re-entrant hairpin loops reminiscent of several secondary active transporters. In addition, our cysteine accessibility data suggest that YqjA forms an oligomer wherein the protomers are arranged in a parallel fashion. This experimentally verified model of YqjA lays the foundation for future work in understanding the function and mechanism of this interesting and important family.

2021 ◽  
Author(s):  
Hollie L Scarsbrook ◽  
Roman Urban ◽  
Bree R Streather ◽  
Alexandra Moores ◽  
Christopher Mulligan

Maintaining membrane integrity is of paramount importance to the survival of bacteria as the membrane is the site of multiple crucial cellular processes including energy generation, nutrient uptake, and antimicrobial efflux. The DedA family of integral membrane proteins are widespread in bacteria and are associated with maintaining the integrity of the membrane. In addition, DedA proteins have been linked to resistance to multiple classes of antimicrobials in various microorganisms. Therefore, the DedA family are attractive targets for the development of new antibiotics. Despite DedA family members playing a key physiological role in many bacteria, their structure, function and physiological role remain unclear. To help illuminate the structure of the bacterial DedA proteins, we have performed substituted cysteine accessibility method (SCAM) analysis on the most comprehensively characterized bacterial DedA protein, YqjA from Escherichia coli. By probing the accessibility of 15 cysteine residues across the length of YqjA using thiol reactive reagents, we have mapped the topology of the protein. Using these data, we have experimentally validated a structural model of YqjA generated using evolutionary co-variance, which consists of an a-helical bundle with two re-entrant hairpin loops reminiscent of several secondary active transporters. In addition, our cysteine accessibility data suggests that YqjA forms an oligomer wherein the protomers are arranged in a parallel fashion. This experimentally verified model of YqjA lays the foundation for future work in understanding the function and mechanism of this interesting and important family.


2019 ◽  
Vol 19 (1) ◽  
pp. 10-14
Author(s):  
Ryan Scott ◽  
Malcolm Le Lievre

Purpose The purpose of this paper is to explore insights methodology and technology by using behavioral to create a mind-set change in the way people work, especially in the age of artificial intelligence (AI). Design/methodology/approach The approach is to examine how AI is driving workplace change, introduce the idea that most organizations have untapped analytics, add the idea of what we know future work will look like and look at how greater, data-driven human behavioral insights will help prepare future human-to-human work and inform people’s work with and alongside AI. Findings Human (behavioral) intelligence will be an increasingly crucial part of behaviorally smart organizations, from hiring to placement to adaptation to team building, compliance and more. These human capability insights will, among other things, better prepare people and organizations for changing work roles, including working with and alongside AI and similar tech innovation. Research limitations/implications No doubt researchers across the private, public and nonprofit sectors will want to further study the nexus of human capability, behavioral insights technology and AI, but it is clear that such work is already underway and can prove even more valuable if adopted on a broader, deeper level. Practical implications Much “people data” inside organizations is currently not being harvested. Validated, scalable processes exist to mine that data and leverage it to help organizations of all types and sizes be ready for the future, particularly in regard to the marriage of human capability and AI. Social implications In terms of human capability and AI, individuals, teams, organizations, customers and other stakeholders will all benefit. The investment of time and other resources is minimal, but must include C-suite buy in. Originality/value Much exists on the softer aspects of the marriage of human capability and AI and other workplace advancements. What has been lacking – until now – is a 1) practical, 2) validated and 3) scalable behavioral insights tech form that quantifiably informs how people and AI will work in the future, especially side by side.


2020 ◽  
Vol 31 (3) ◽  
pp. 465-487 ◽  
Author(s):  
Carla Ruiz-Mafe ◽  
Enrique Bigné-Alcañiz ◽  
Rafael Currás-Pérez

PurposeThis paper analyses the interrelationships between emotions, the cognitive information cues of online reviews and intention to follow the advice obtained from digital platforms, paying special attention to the moderating effect of the sequencing of review valence.Design/methodology/approachThe data were collected from 830 Spanish Tripadvisor users. In a two-step approach, a measurement model was estimated and a structural model analysed to test the proposed hypotheses. SmartPLS 3.0 software was used. The moderating effect of sequencing of reviews is tested.FindingsThe data analysis showed a bias effect of review sequence on the impact of online information cues and emotions on intention to follow advice obtained from Tripadvisor. When the online reviews of a restaurant begin with positive commentaries, their perceived persuasiveness is a stronger driver of the pleasure and arousal elicited by online reviews than when they begin with negative reviews. On the other hand, the perceived helpfulness of online reviews only triggers arousal when the user reads negative, followed by positive, comments. The impact of pleasure on intention to follow the advice provided in an online travel community is higher with positive-negative than with negative-positive sequences.Originality/valueWhile researchers have demonstrated the benefits of customer reviews on company sales, a largely uninvestigated issue is the interplay between emotions and cognitive information cues in the processing of online reviews. This is one of the first studies to examine the moderating effect of conflicting reviews on the impact of emotions and cognitive information cues on consumer intention to follow the advice obtained from digital services.


Author(s):  
Lorenzo Cangiano ◽  
Sabrina Asteriti

AbstractIn the vertebrate retina, signals generated by cones of different spectral preference and by highly sensitive rod photoreceptors interact at various levels to extract salient visual information. The first opportunity for such interaction is offered by electrical coupling of the photoreceptors themselves, which is mediated by gap junctions located at the contact points of specialised cellular processes: synaptic terminals, telodendria and radial fins. Here, we examine the evolutionary pressures for and against interphotoreceptor coupling, which are likely to have shaped how coupling is deployed in different species. The impact of coupling on signal to noise ratio, spatial acuity, contrast sensitivity, absolute and increment threshold, retinal signal flow and colour discrimination is discussed while emphasising available data from a variety of vertebrate models spanning from lampreys to primates. We highlight the many gaps in our knowledge, persisting discrepancies in the literature, as well as some major unanswered questions on the actual extent and physiological role of cone-cone, rod-cone and rod-rod communication. Lastly, we point toward limited but intriguing evidence suggestive of the ancestral form of coupling among ciliary photoreceptors.


2017 ◽  
Vol 24 (5) ◽  
pp. 1309-1336 ◽  
Author(s):  
Sarang Joshi ◽  
Manoj Kharat ◽  
Rakesh Raut ◽  
Sachin Kamble ◽  
Sheetal Kamble

Purpose The purpose of this paper is to examine the relationships between supplier development practices (SDPs) and supplier-buyer relationship practices from the supplier’s perspective (SBRSP), and seek to understand how specific SDPs may impact a buyer’s operational performance as well as supplier-buyer relationship practices. Design/methodology/approach The authors conducted a survey of 512 respondents from the different manufacturing firms in India and applied structural equation modelling to test a structural model that proposes the impacts of various efforts of SDPs on a buyer’s performance as well as SBRSP. Findings The study concludes that SDPs and SBRSP together improve the relationship between a buyer and supplier, and this improved relationship leads to competitive advantages (CAs) followed by profitability. Results indicate that supplier perspective of buyer-supplier relationship can be improved under the condition of SDPs and SBRSP together. SDPs are driven by productive measure and competitive pressure, whereas customer uncertainty is found to be statistically insignificant. Research limitations/implications The study was carried out in North Maharashtra Industrial Zone of India, where the auto sector and machine/components manufacturing firms have been established for a considerable period of time. Results of the study are limited to manufacturing organizations predominantly focussing on the automobile sector and machine/components manufacturing firms. Practical implications This study provides significant insights into the specific impact of various SDPs and SBRSP for both academics and practitioners. SDPs along with SBRSP practices lead to improvement in the relationship leading to CAs. SBRSP suggests that trust, long-term commitments and the supplier’s perspective are important practices for relationship improvement. Originality/value The current study attempts to identify what are the success factors for the supplier-buyer relationship from the supplier’s perspective and SDPs and how the supplier-buyer relationship can be improved under the condition of SDPs and SBRSP. Hence, the aim is to develop a more thorough understanding of the outcomes of a supplier-buyer relationship improvement from both buyer’s and supplier’s perspective, under the conditions of supplier development to achieve CAs leading to profitability. Furthermore, the study analyses the effect of the improved supplier-buyer relationship for achieving CAs leading to profitability.


2020 ◽  
Vol 24 (6) ◽  
pp. 1369-1392 ◽  
Author(s):  
Elena-Mădălina Vătămănescu ◽  
Juan-Gabriel Cegarra-Navarro ◽  
Andreia Gabriela Andrei ◽  
Violeta-Mihaela Dincă ◽  
Vlad-Andrei Alexandru

Purpose In the context of resource scarcity, the affiliation of small and medium-sized enterprises (SMEs) to strategic networks has emerged as a fruitful path towards knowledge sharing as a reaction to fierce competition and with a view to enhance their innovative performance. In this framework, this paper aims to investigate the influence exerted by a specific relational design (i.e. types of strategic networks) and methodology (i.e. channels and content) of knowledge sharing on SMEs innovative performance. Design/methodology/approach A questionnaire-based survey with 102 top managers of European SMEs in the industrial field was conducted from June to August 2019 and a partial least squares structural equation modelling technique was used. The database was initially filtered to ensure the adequacy of the sample and data was analysed using the statistics software package SmartPLS 3.0. Findings The results concluded that the structural model explains 38.5% of the variance in SMEs innovative performance, indicating the positive effects exerted by offline and online and by competitive knowledge sharing on the dependent variable. Research implications The study has both theoretical and practical implications in that it sets out a reference point for the key performance indicators for strategic networks structure, formation and development and, implicitly, for the selection of the most efficient relational design and methodology. Originality/value The pivotal originality elements reside in the advancement of a more comprehensive conceptual and structural model combining a two-fold operationalization of SMEs strategic networks (founded on business abilities or on the personality of the partner) and in the investigation of knowledge transfer processes at the inter-organizational levels within a context-centric approach.


2017 ◽  
Vol 13 (4) ◽  
pp. 403-418
Author(s):  
Kate Thompson ◽  
Pippa Brown ◽  
Stephanie Vieira

Purpose The purpose of this paper is to describe an intervention with a group of homeless men from the Horn of Africa, service users of the Horn of Africa Health and Wellbeing Project in London. The group was conceived by the second author who noted the presence of significant psychosocial issues for her clients, but equally their reluctance to access mainstream mental health or social care services. Design/methodology/approach Designing the group and introducing it to the men involved threw up some challenges which are explored, and the impact of the group on participants is evaluated. Findings Overall both the participants and the facilitators evaluated the group positively and it appeared to have led to lasting change for some of the group members, and this is described. The authors argue that this sort of group may be a more acceptable way to work on psychosocial issues than something more directly focused on mental health intervention. The group protocol is outlined along with suggestions for future work in this area. Originality/value This intervention represents a creative alternative to more mainstream psychological interventions for homeless or exiled men.


2015 ◽  
Vol 67 (2) ◽  
pp. 172-180 ◽  
Author(s):  
Mumin Sahin ◽  
Cenk Misirli ◽  
Dervis Özkan

Purpose – The purpose of this paper is to examine mechanical and metallurgical properties of AlTiN- and TiN-coates high-speed steel (HSS) materials in detail. Design/methodology/approach – In this study, HSS steel parts have been processed through machining and have been coated with AlTiN and TiN on physical vapour deposition workbench at approximately 6,500°C for 4 hours. Tensile strength, fatigue strength, hardness tests for AlTiN- and TiN-coated HSS samples have been performed; moreover, energy dispersive X-ray spectroscopy and X-ray diffraction analysis and microstructure analysis have been made by scanning electron microscopy. The obtained results have been compared with uncoated HSS components. Findings – It was found that tensile strength of TiAlN- and TiN-coated HSS parts is higher than that of uncoated HSS parts. Highest tensile strength has been obtained from TiN-coated HSS parts. Number of cycles for failure of TiAlN- and TiN-coated HSS parts is higher than that for HSS parts. Particularly TiN-coated HSS parts have the most valuable fatigue results. However, surface roughness of fatigue samples may cause notch effect. For this reason, surface roughness of coated HSS parts is compared with that of uncoated ones. While the average surface roughness (Ra) of the uncoated samples was in the range of 0.40 μm, that of the AlTiN- and TiN-coated samples was in the range of 0.60 and 0.80 μm, respectively. Research limitations/implications – It would be interesting to search different coatings for cutting tools. It could be the good idea for future work to concentrate on wear properties of tool materials. Practical implications – The detailed mechanical and metallurgical results can be used to assess the AlTiN and TiN coating applications in HSS materials. Originality/value – This paper provides information on mechanical and metallurgical behaviour of AlTiN- and TiN-coated HSS materials and offers practical help for researchers and scientists working in the coating area.


2018 ◽  
Vol 25 (1) ◽  
pp. 5-21 ◽  
Author(s):  
Ylenia Cau ◽  
Daniela Valensin ◽  
Mattia Mori ◽  
Sara Draghi ◽  
Maurizio Botta

14-3-3 is a class of proteins able to interact with a multitude of targets by establishing protein-protein interactions (PPIs). They are usually found in all eukaryotes with a conserved secondary structure and high sequence homology among species. 14-3-3 proteins are involved in many physiological and pathological cellular processes either by triggering or interfering with the activity of specific protein partners. In the last years, the scientific community has collected many evidences on the role played by seven human 14-3-3 isoforms in cancer or neurodegenerative diseases. Indeed, these proteins regulate the molecular mechanisms associated to these diseases by interacting with (i) oncogenic and (ii) pro-apoptotic proteins and (iii) with proteins involved in Parkinson and Alzheimer diseases. The discovery of small molecule modulators of 14-3-3 PPIs could facilitate complete understanding of the physiological role of these proteins, and might offer valuable therapeutic approaches for these critical pathological states.


2014 ◽  
Vol 197 (2) ◽  
pp. 354-361 ◽  
Author(s):  
Kerry A. Sokol ◽  
Neil E. Olszewski

The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. The enzyme responsible for this modification,O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. Although OGTs with domain structures similar to those of eukaryotic OGTs are predicted for many bacterial species, the cellular roles of these OGTs are unknown. We have identified a putative OGT in the cyanobacteriumSynechococcus elongatusPCC 7942 that shows active-site homology and similar domain structure to eukaryotic OGTs. An OGT deletion mutant was created and found to exhibit several phenotypes. Without agitation, mutant cells aggregate and settle out of the medium. The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. These phenotypes are rescued by reintroduction of the wild-type OGT but are not fully rescued by OGTs with single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity.S. elongatusOGT purified fromEscherichia colihydrolyzed the sugar donor, UDP-GlcNAc, while the mutant OGTs that did not fully rescue the deletion mutant phenotypes had reduced or no activity. These results suggest that bacterial eukaryote-like OGTs, like their eukaryotic counterparts, influence multiple processes.


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