bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering the rules underlying xenogeneic silencing and counter-silencing of Lsr2-like proteins
Authors: Wiechert Johanna , Filipchyk Andrei , Hünnefeld Max , Gätgens Cornelia , Heermann Ralf , Frunzke Julia 
Published: August 2019

ABSTRACTLsr2-like nucleoid-associated proteins play an important role as xenogeneic silencers (XS) of horizontally acquired genomic regions in actinobacteria. In this study, we systematically analyzed the in vivo constraints underlying silencing and counter-silencing of the Lsr2-like protein CgpS inCorynebacterium glutamicum. Genome-wide analysis revealed binding of CgpS to regions featuring a distinct drop in GC-profile close to the transcription start site (TSS), but also identified an overrepresented motif with multiple A/T steps at the nucleation site of the nucleoprotein complex. Binding of specific transcription factors (TFs) may oppose XS activity leading to counter-silencing. Following a synthetic counter-silencing approach, target gene activation was realized by inserting operator sites of an effector-responsive TF within various CgpS target promoters resulting in an increased promoter activity upon TF binding. Analysis of reporter constructs revealed maximal counter-silencing when the TF operator site was inserted at the position of maximal CgpS coverage. This principle was implemented in a synthetic toggle switch, which features a robust and reversible response to effector availability highlighting the potential for biotechnological applications. Altogether, our results provide comprehensive insights into how Lsr2 silencing and counter-silencing shapes evolutionary network expansion in this medically- and biotechnologically-relevant bacterial phylum.IMPORTANCEIn actinobacteria, Lsr2-like nucleoid-associated proteins function as xenogeneic silencers (XS) of horizontally acquired genomic regions, including viral elements, virulence gene clusters inMycobacterium tuberculosis, and genes involved in cryptic specialized metabolism inStreptomycesspecies. Consequently, a detailed mechanistic understanding of Lsr2 binding in vivo is relevant as a potential drug target and for the identification novel bioactive compounds. Here, we followed an in vivo approach to investigate the rules underlying xenogeneic silencing and counter-silencing of the Lsr2-like XS CgpS fromCorynebacterium glutamicum. Our results demonstrated that CgpS distinguishes between self and foreign by recognizing a distinct drop in GC-profile in combination with a short, sequence specific motif at the nucleation site. Following a synthetic counter-silencer approach, we studied the potential and constraints of transcription factors to counteract CgpS silencing thereby facilitating the integration of new genetic traits into host regulatory networks.
AMPK regulates ESCRT-dependent microautophagy of proteasomes concomitant with proteasome storage granule assembly during glucose starvation
Authors: Li Jianhui , Breker Michal , Graham Morven , Schuldiner Maya , Hochstrasser Mark 
Published: August 2019

AbstractThe ubiquitin-proteasome system regulates numerous cellular processes and is central to protein homeostasis. In proliferating yeast and many mammalian cells, proteasomes are highly enriched in the nucleus. In carbon-starved yeast, proteasomes migrate to the cytoplasm and collect in phase-separated proteasome storage granules (PSGs). PSGs dissolve and proteasomes return to the nucleus within minutes of glucose refeeding. The mechanisms by which cells regulate proteasome homeostasis under these conditions remain largely unknown. Here we show that AMP-activated protein kinase (AMPK) together with endosomal sorting complexes required for transport (ESCRTs) drive a glucose starvation-dependent microautophagy pathway that preferentially sorts aberrant proteasomes into the vacuole, thereby biasing accumulation of functional proteasomes in PSGs. The proteasome core particle (CP) and regulatory particle (RP) are regulated differently. Without AMPK, the insoluble protein deposit (IPOD) serves as an alternative site that specifically sequesters CP aggregates. Our findings reveal a novel AMPK-controlled ESCRT-mediated microautophagy mechanism in the regulation of proteasome trafficking and homeostasis under carbon starvation.
The burden of cutaneous and mucocutaneous leishmaniasis in Ecuador (2014-2018), a national registry-based study
Authors: Henríquez-Trujillo Aquiles R. , Coral-Almeida Marco , Calvopiña Hinojosa Manuel 
Published: August 2019

AbstractBackgroundCutaneous (CL) and mucocutaneous (MCL) leishmaniasis remain as endemic tropical diseases in several Latin American countries. This study aimed to estimate the burden of CL and MCL in Ecuador for the period 2014-2018, in order to inform decision-making and resource allocation to tackle this neglected disease.MethodsAmbulatory consultations, hospitalizations, and reported cases of Leishmaniasis registered by the Ecuadorian National Institute of Statistics and Census and the Ministry of Public Health were used to estimate the burden of CL and MCL during a five-year period. Case estimations were stratified by prevalence of acute and long-term sequelae, to calculate Years Lived with Disability (YLD) by sex and age group using the DALY package in R. Spatial analysis was conducted to identify statistically significant spatial clusters of leishmaniasis.ResultsBetween years 2014 and 2018, a total 6,937 cases of leishmaniasis were registered, with an average of 1,395 cases reported per year, 97.5% of them were CL and 2.5% MCL. The average cumulative incidence for the study period corrected for underreporting was estimated in 21.98 to 36.10 per 100 thousand inhabitants. Health losses due to leishmaniasis reach 0.32 DALY per 100,000 people per year (95% CI 0.15 – 0.49). The most affected by the disease were men between 15 to 64 years old living below 1,500 m.a.s.l. in sub-tropical and tropical rural communities on both slopes of the Andes mountains. Cantons with the highest cumulative incidence of CL and MCL were Pedro Vicente Maldonado, San Miguel de Los Bancos, and Puerto Quito, in the Pichincha Province; Taisha and Aguarico in the Morona Santiago and Orellana provinces respectively.ConclusionCompared to previous reports, in the past five years CL and MCL persist as a public health problem in Ecuador. There is a need for more comprehensive and robust data sources to track leishmania cases in Ecuador.Author summaryCutaneous (CL) and mucocutaneous (MCL) leishmaniasis remains as an endemic neglected tropical disease in several Latin American countries, including Ecuador. Both CL and MCL can produce disfiguring lesions on exposed parts of the body like face and extremities, and permanent scars, contributing to the burden of the disease due to stigma. In order to inform health authorities in their efforts to improve the control of the transmission of the Leishmaniases in the Ecuadorian population, we estimate the burden of CL and MCL for Ecuador in the period 2014-2018, calculating the years lived with disability due to acute and chronic sequelae. We also look for geographical regions within Ecuador with significant clusters of people with the disease, and we found 17 spatial clusters in sub-tropical and tropical rural communities below 1,500 m.a.s.l. on both slopes of the Andes mountains.
Prognostics for pain in osteoarthritis: Can clinical measures predict pain after total joint replacement?
Authors: Barroso Joana , Wakaizumi Kenta , Reckziegel Diane , Pinto-Ramos João , Schnitzer Thomas , Galhardo Vasco , Apkarian A. Vania 
Published: August 2019

AbstractA significant proportion of osteoarthritis (OA) patients continues to experience moderate to severe pain after total joint replacement (TJR). So far, preoperative factors related to pain persistence have been mainly studied using individual predictor variables and distinct pain outcomes, thus leading to lack of consensus in the field. In this prospective observational study, we evaluated knee and hip OA patients before, 3 and 6 months post-TJR searching for clinical predictors of pain persistence. We assessed multiple measures of quality, mood, affect, health and quality of life, together with radiographic evaluation and performance-based tasks, modeling four distinct pain outcomes. Multivariate regression models were built, and a network analysis was applied to pain related biopsychosocial measures and their change with surgery. A total of 106 patients completed the study. Pre-surgical pain levels were not related to post-surgical residual pain. Distinct pain scales were associated with different aspects of the pain experience. Multi-factorial models did not reliably predict post-surgical pain in knee OA across four distinct pain scales and did not generalize to hip OA; however, network analysis of pain related biopsychosocial measures showed significant changes post-surgery in both groups. Our results show that although tested clinical and biopsychosocial variables are reorganizing after TJR in OA, they do not present as a robust markers for post-surgery pain outcomes. A better understanding of mechanisms underlying pain persistence after TJR is necessary to derive clinical prognostic factors.
Olfactory Landmarks and Path Integration Converge to Form a Cognitive Spatial Map
Authors: Fischler Walter M. , Joshi Narendra R. , Devi-Chou Virginia , Kitch Lacey J. , Schnitzer Mark J. , Abbott Larry F. , Axel Richard 
Published: August 2019

AbstractThe convergence of internal path integration with sensory information from external landmarks generates a cognitive spatial map in the hippocampus. We have recorded the activity of cells in CA1 during a virtual navigation task to examine how mice represent, recognize and employ sparse olfactory landmarks to estimate their location. We observe that the presence of odor landmarks at multiple locations in a virtual environment greatly enriches the place cell representation and dramatically improves navigation. Presentation of the same odor at different locations generates distinct place cell representations, indicating that path integration can disambiguate two identical cues on the basis of location. The enhanced place cell representation at one cue location led to the formation of place cells at locations beyond that cue and, ultimately recognition of a second odor cue as a distinct landmark. This suggests an iterative mechanism for extending place cell representations into unknown territory. These results reveal how odor cues can serve as landmarks to guide navigation and suggest a model to explain how the convergence of landmarks and path integration participates in an iterative process that generates a cognitive spatial map.
Fast and robust detection of colistin resistance in Escherichia coli using the MALDI Biotyper Sirius mass spectrometry system
Authors: Furniss R. Christopher D. , Dortet Laurent , Bolland William , Drews Oliver , Sparbier Katrin , Bonnin Rémy A. , Filloux Alain , Kostrzewa Markus , Mavridou Despoina A.I. , Larrouy-Maumus Gerald 
Published: August 2019

ABSTRACTPolymyxin antibiotics are a last-line treatment for multidrug-resistant Gram-negative bacteria. However, the emergence of colistin resistance, including the spread of mobile mcr genes, necessitates the development of improved diagnostics for the detection of colistin-resistant organisms in hospital settings. The recently developed MALDIxin test enables detection of colistin resistance by MALDI-TOF mass spectrometry in less than 15 minutes but is not optimized for the mass spectrometers commonly found in clinical microbiology laboratories. In this study, we adapted the MALDIxin test for the MALDI Biotyper Sirius MALDI-TOF mass spectrometry system (Bruker Daltonics). We optimized the sample preparation protocol using a set of 6 MCR-expressing Escherichia coli clones and validated the assay with a collection of 40 E. coli clinical isolates, including 19 MCR producers, 12 chromosomally-resistant isolates and 9 polymyxin-susceptible isolates. We calculated Polymyxin resistance ratio (PRR) values from the acquired spectra; a PRR value of zero, indicating polymyxin susceptibility, was obtained for all colistin-susceptible E. coli isolates, whereas positive PRR values, indicating resistance to polymyxins, were obtained for all resistant strains independent of the genetic basis of resistance. Thus, we report a preliminary feasibility study showing that an optimized version of the MALDIxin test, adapted for the routine MALDI Biotyper Sirius, provides an unbiased, fast, reliable, cost-effective and high-throughput way of detecting colistin resistance in clinical E. coli isolates.
Structural Studies of Overlapping Dinucleosomes in Solution
Authors: Matsumoto A. , Sugiyama M. , Li Z. , Martel A. , Porcar L. , Inoue R. , Kato D. , Osakabe A. , Kurumizaka H. , Kono H. 
Published: August 2019

AbstractAn overlapping dinucleosome (OLDN) is a structure composed of one hexasome and one octasome and appears to be formed through nucleosome collision promoted by nucleosome remodeling factor(s). In the present study, the solution structure of the OLDN was investigated through integration of small-angle X-ray and neutron scattering (SAXS and SANS, respectively), computer modeling, and molecular dynamics simulations. Starting from the crystal structure, we generated a conformational ensemble based on normal mode analysis, and searched for the conformations that well reproduced the SAXS and SANS scattering curves. We found that inclusion of histone tails, which are not observed in the crystal structure, greatly improved model quality. The obtained structural models suggest that OLDNs adopt a variety of conformations stabilized by histone tails situated at the interface between the hexasome and octasome, simultaneously binding to both the hexasomal and octasomal DNA. In addition, our models define a possible direction for the conformational changes or dynamics, which may provide important information that furthers our understanding of the role of chromatin dynamics in gene regulation.Statement of SignificanceOverlapping dinucleosomes (OLDNs) are intermediate structures formed through nucleosome collision promoted by nucleosome remodeling factor(s). To study the solution structure of OLDNs, a structural library containing a wide variety of conformations was prepared though simulations, and the structures that well reproduced the small angle X-ray and neutron scattering data were selected from the library. Simultaneous evaluation of the conformational variation in the global OLDN structures and in the histone tails is difficult using conventional MD simulations. We overcame this problem by combining multiple simulation techniques, and showed the importance of the histone tails for stabilizing the structures of OLDNs in solution.
The positioning and competitive strategies of higher education institutions in the United Arab Emirates
Authors: Wilkins Stephen 
Published: August 2019

Purpose
The purpose of this paper is to discover how higher education institutions may segment the market in a competitive higher education hub and to assess the usefulness of strategic group analysis as an analytical technique for market and competitor analysis. As a case example of a competitive higher education market, this research investigates how higher education institutions in the United Arab Emirates (UAE) position themselves and compete with one another.

Design/methodology/approach
The research relied mainly on secondary data, which were obtained from the websites of institutions and regulatory bodies. Then, hierarchical cluster analysis was used to identify strategic groups and institutional competitive strategies in the UAE higher education market. A panel of experts helped interpret and explain the cluster results.

Findings
Eight distinct institutional clusters were identified, which include public- and privately-owned institutions, as well as elite and specialist institutions. Institution and programme accreditation were found to be particularly important in the UAE market. The institutions in each group appear to operate in a particular market segment, targeting students who have similar needs and wants, and who often share similar demographic features.

Practical implications
It is concluded that strategic group analysis may help institutions to evaluate potential markets, select target segments and develop competitive strategies. In the UAE market context, the results demonstrate how institutions may position themselves to create strong and distinctive identities. The results of the research may be of interest to higher education institutions that operate in competitive markets, and particularly those that want to evaluate foreign markets.

Originality/value
This is believed to be the first study to use a strategic group approach for analysing competitors in a higher education hub.
A study of the mobility of mainland students
Authors: Wong Ping Man , Cheung Alan , Yuen Wai Wa 
Published: August 2019

PurposeThe purpose of this paper is to contribute to a better understanding of the international mobility of mainland students in special administrative regions of China and in places outside China.Design/methodology/approachThere have been studies using the framework of push–pull and reverse push–pull factors to explore the movement of mainland students to North America, Australia, Singapore and Hong Kong. This study follows up by exploring such research directions in Macau, which is another special administrative region of China. Different from previous studies, the sample of this study came specifically from 130 students enrolling in teacher education undergraduate programs in Macau.FindingsIn this study, using data collected from questionnaires and interviews, the factors affecting mainland student teachers’ choice of Macau as a place for their undergraduate studies are examined. Other related issues such as the challenges these students face and their intentions after their graduation are also studied.Originality/valueThe data collected for this study were primary and original, drawing specifically from students enrolling teacher education programs. Following the various studies on the global movement of mainland students, this study aimed at understanding mainland students’ mobility pattern in one of China’s special administration regions, Macau. In this regard, cultural identity and cultural factors were considered on top of other factors.
Developing gender-specific evidence-based standards to improve the health and wellbeing of women in prison in England: a literature review and modified eDelphi survey
Authors: McCann Lucy J. , Peden Jo , Phipps Emily , Plugge Emma , O’Moore Eamonn J. 
Published: August 2019

PurposeThere are significant health inequalities experienced by women in prison. They face distinct challenges and have particular and complex needs, specifically with regard to their physical and mental health. The purpose of this paper is to describe the approach taken to develop a set of health and wellbeing standards for the women’s prison estate in England, which can be applied elsewhere.Design/methodology/approachA structured literature review of standard healthcare databases and grey literature was used to inform development of suggested standards. A multidisciplinary expert panel provided consensus on the standards through an online survey and women with a history of contact with the criminal justice system were consulted through consensus groups.FindingsA total of 549 papers were included in the final review. From this, 127 standards were identified for inclusion in the Delphi process. Consensus was achieved on all standards; this, combined with the analysis of qualitative feedback provided by both the survey and the consensus groups, resulted in the development of 6 overarching principles and 122 standards, across ten topic areas.Originality/valueThese standards are the most extensive that are known to exist for health and wellbeing of women in prison and the first to be developed in England. The process used ensures the standards have high validity, acceptability and feasibility and can be used to support those developing similar methodologies. There are few papers which document the development of standards to improve health and to the authors knowledge, only one other paper has been published detailing the development of health standards in prison settings specifically.
A study on the promotional mix of pre-service in the view of service design
Authors: Qian Chenxiang , Wu Chih-Fu , Zhang Zhenbo , Huang Hsin-Yu 
Published: August 2019

Purpose
The purpose of this paper is to explore current marketing communication mixes (MCMs) in two industries, electronics home appliance stores (face-to-face interaction) and remote care (interface-mediated interaction), to propose marketing strategies from the perspective of service design and determine the relationships between service interaction patterns and MCMs in the pre-service phase.

Design/methodology/approach
Six industry experts in marketing were interviewed through semi-structured interviews, the topic of which focused on the details of five MCMs and their correlations were analyzed using a customer journey maps. Finally, the MCMs were further explored to verify differences in attractiveness to customers, respectively.

Findings
The result showed that the most attractive activity for the electronics home appliance stores customer is the promotion. And the four face-to-face service interaction patterns and MCMs exhibited a low correlation. In addition, the customers of remote care service argued that the personnel selling was the most attractive MCMs to them. For customers who utilize smart devices to communicate with advertisement exhibited the highest correlation coefficient.

Research limitations/implications
The limitation of this study is that the research only conducts interview research on two service industries.

Practical implications
This study was expected to develop improved marketing communication strategies to remedy the sales predicament induced by virtual channels and to increase people’s acceptance of remote care service.

Originality/value
The value of this paper is to analyze the correlation and difference of MCMs and service interaction patterns between electronics home appliance stores and remote care, and propose a structural model of MCMs for two different industries.
From power to punishment: consumer empowerment and online complaining behaviors
Authors: Li Zongchao 
Published: August 2019

Purpose
The purpose of this paper is to examine how psychological empowerment affects individuals’ likelihood of publicly punishing a company with whom they had unsatisfactory experiences through online complaining behaviors.

Design/methodology/approach
A 3 (intrapersonal empowerment: high/low/control) by 3 (interactional empowerment: high/low/control) online experiment was designed using the priming technique. Following the priming tasks, participants were given a scenario in which a restaurant failed their expectations followed by dependent and control measures.

Findings
Results revealed a significant main effect of interactional empowerment: participants in the low interactional empowerment condition reported being less likely to engage in the revenge-motivated online public complaining behaviors than participants in the control condition. The study also found a significant interaction effect between interactional and intrapersonal empowerment.

Practical implications
The study findings yield practical application for crisis management and relationship management. Understanding the linkage between power and online complaining behaviors should help corporate communication professionals to better perform risk assessment, environmental scanning and crisis communication and management.

Originality/value
Limited empirical studies have investigated the linkage between empowerment and online complaining behaviors in the consumer context. The present study fills this gap by conceptualizing online public complaining as a revenge-motivated behavior. The study yields both theoretical and practical implications.