bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncover the Mechanism of Nucleotide Import by HIV-1 Capsid
Authors: Song Guang 
Published: July 2019

AbstractIn this work, we carry out a series of Brownian diffusion simulations to elucidate the nucleotide importing process through the hexamer pores of HIV-1 capsid. Our simulations reveal the mechanism by which deoxynucleoside triphosphates (dNTPs) diffuse through the arginine ring, the role of electrostatic potential within the pore in the importing process, and surprisingly, how IP6s and ATPs, though competing with dNTPs for binding at the arginine ring, end up accelerating the nucleotide import rate by thousands of folds so that it is sufficiently high to fuel the encapsidated DNA synthesis.IMPORTANCEEfficient nucleotide import is critical to fuel the reverse DNA synthesis that takes place within the capsid. However, the mechanism by which capsid imports the nucleotides is presently unclear. The current study through Brownian simulations shed insights into the process. A clear understanding of the mechanism of nucleotide import can be informative in developing drugs that target the process.
Ionpair-π interactions favor cell penetration of arginine/tryptophan-rich cell-penetrating peptides
Authors: Walrant Astrid , Bauzá Antonio , Girardet Claudia , Alves Isabel D. , Lecomte Sophie , Illien Françoise , Cardon Sébastien , Chaianantakul Natpasit , Pallerla Manjula , Burlina Fabienne , Frontera Antonio , Sagan Sandrine 
Published: July 2019

AbstractCell-penetrating peptides (CPPs) internalization can occur both by endocytosis and direct translocation through the cell membrane. These different entry routes suggest that molecular partners at the plasma membrane, phospholipids or glycosaminoglycans (GAGs), bind CPPs with different affinity or selectivity. The analysis of sequence-dependent interactions of CPPs with lipids and GAGs should lead to a better understanding of the molecular mechanisms underlying their internalization. CPPs are short sequences generally containing a high number of basic arginines and lysines and sometimes aromatic residues, in particular tryptophans. Tryptophans are crucial residues in membrane-active peptides, because they are important for membrane interaction. Membrane-active peptides often present facial amphiphilicity, which also promote the interaction with lipid bilayers. To study the role of Trp and facial amphiphilicity in cell interaction and penetration of CPPs, a nonapeptide series containing only Arg, Trp or D-Trp residues at different positions was designed. Our quantitative study indicates that to maintain/increase the uptake efficiency, Arg can be advantageously replaced by Trp in the nonapeptides. The presence of Trp in oligoarginines increases the uptake in cells expressing GAGs at their surface, when it only compensates for the loss of Arg and maintains similar peptide uptake in GAG-deficient cells. In addition, we show that facial amphiphilicity is not required for efficient uptake of these nonapeptides. Thermodynamic analyses point towards a key role of Trp that highly contributes to the binding enthalpy of complexes formation. Density functional theory (DFT) analysis highlights that salt bridge-π interactions play a crucial role for the GAG-dependent entry mechanisms.
Detecting changes in the Caenorhabditis elegans intestinal environment using an engineered bacterial biosensor
Authors: Rutter Jack W. , Ozdemir Tanel , Quintaneiro Leonor M. , Thomas Geraint , Cabreiro Filipe , Barnes Chris P. 
Published: July 2019

AbstractCaenorhabditis elegans has become a key model organism within biology. In particular, the transparent gut, rapid growing time and ability to create a defined gut microbiota make it an ideal candidate organism for understanding and engineering the host microbiota. Here we present the development of an experimental model which can be used to characterise whole-cell bacterial biosensors in vivo. A dual-plasmid sensor system responding to isopropyl β-D-1-thiogalactopyranoside was developed and fully characterised in vitro. Subsequently, we show the sensor was capable of detecting and reporting on changes in the intestinal environment of C. elegans after introducing exogenous inducer into the environment. The protocols presented here may be used for aiding the rational design of engineered bacterial circuits, primarily for diagnostic applications. In addition, the model system may serve to reduce the use of current animal models and aid in the exploration of complex questions within general nematode and host-microbe biology.
Multiple probabilistic models extract features from protein sequence data and resolve functional diversity of very different protein families
Authors: Vicedomini R. , Bouly J.P. , Laine E. , Falciatore A. , Carbone A. 
Published: July 2019

AbstractSequence functional classification has become a critical bottleneck in understanding the myriad of protein sequences that accumulate in our databases. The great diversity of homologous sequences hides, in many cases, a variety of functional activities that cannot be anticipated. Their identification appears critical for a fundamental understanding of living organisms and for biotechnological applications.ProfileView is a sequence-based computational method, designed to functionally classify sets of homologous sequences. It relies on two main ideas: the use of multiple probabilistic models whose construction explores evolutionary information in available databases, and a new definition of a representation space where to look at sequences from the point of view of probabilistic models combined together. ProfileView classifies families of proteins for which functions should be discovered or characterised within known groups.We validate ProfileView on seven classes of widespread proteins, involved in the interaction with nucleic acids, amino acids and small molecules, and in a large variety of functions and enzymatic reactions. ProfileView agrees with the large set of functional data collected for these proteins from the literature regarding the organisation into functional subgroups and residues that characterize the functions. Furthermore, ProfileView resolves undefined functional classifications and extracts the molecular determinants underlying protein functional diversity, showing its potential to select sequences towards accurate experimental design and discovery of new biological functions.ProfileView proves to outperform three functional classification approaches, CUPP, PANTHER, and a recently developed neural network approach based on Restricted Boltzmann Machines. It overcomes time complexity limitations of the latter.
GARDEN-NET and ChAseR: a suite of tools for the analysis of chromatin networks
Authors: Madrid-Mencía Miguel , Raineri Emanuele , Pancaldi Vera 
Published: July 2019

AbstractWe introduce an R package and a web-based visualization tool for the representation, analysis and integration of epigenomic data in the context of 3D chromatin interaction networks. GARDEN-NET allows for the projection of user-submitted genomic features on pre-loaded chromatin interaction networks exploiting the functionalities of the ChAseR package to explore the features in combination with chromatin network topology. We demonstrate the approach on epigenomic and chromatin structure datasets in haematopoietic cells.
Influence of human population density on spatial distribution patterns of environmental suitability for triatomine vectors of Chagas disease
Authors: Eduardo Anderson A. , Santos Lucas A. B. O. , Rebouças Mônica C. , Martinez Pablo A. 
Published: July 2019

AbstractPrevious work on Chagas Disease disease at large spatial scales has not explored how interaction with humans can affect projections for geographical distribution of environmental suitability of vector species. Here, we compare niche-based species distribution models with climatic variables as predictors (SDMclim) and with climatic variables + human population density (SDMHuman). Our results show that accounting for human population density helps refine the models to finer geographical scales. Also, different spatial patterns of accumulated environmental suitability were obtained by SDMclim and SDMHuman. Moreover, projections were more accurate for SDMHuman than for SDMclim. Our results show that considering human populations in SDMs for epidemiologically relevant triatomiane species can improve our understanding of macroecology and biogeography of environmental suitability for vectors of Chagas disease.
Serine-arginine protein kinase 1 regulates Ebola virus transcription
Authors: Takamatsu Yuki , Krähling Verena , Kolesnikova Larissa , Halwe Sandro , Lier Clemens , Baumeister Stefan , Noda Takeshi , Biedenkopf Nadine , Becker Stephan 
Published: July 2019

AbstractEbola virus (EBOV) causes a severe and often fatal disease for which no approved vaccines or antivirals are currently available. EBOV transcription requires the sequential phosphorylation and dephosphorylation of the viral transcription factor VP30. While dephosphorylation is carried out by phosphatases PP2A and PP1, the VP30-specific kinase is unknown. Here, we report that serine-arginine protein kinase 1 and 2 (SRPK1 and SRPK2) phosphorylate serine-29 of VP30, which is located in an N-terminal R26xxS29motif. Interaction with VP30 via the R26xxS29motif recruits SRPK1 into EBOV-induced inclusion bodies, the sites of viral RNA synthesis and an inhibitor of SRPK1/SRPK2 downregulates primary viral transcription. When the SRPK1 recognition motif of VP30 was mutated in a recombinant EBOV, virus replication was severely impaired. It is presumed that the interplay between SRPK1 and PP2A in the EBOV inclusions provides a comprehensive regulatory circuit to ensure the activity of VP30 in EBOV transcription.
Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion
Authors: Frausto Ricardo F. , Swamy Vinay S. , Peh Gary S. L. , Boere Payton M. , Hanser E. Maryam , Chung Doug. D. , George Benjamin L. , Morselli Marco , Kao Liyo , Azimov Rustam , Wu Jessica , Pellegrini Matteo , Kurtz Ira , Mehta Jodhbir S. , Aldave Anthony J. 
Published: July 2019

SUMMARYThe advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured CEnC across serial passages has not been performed. To this end, we compared two established CEnC culture methods by assessing the transcriptomic changes that occur during in vitro expansion. In confluent monolayers, low mitogenic culture conditions preserved corneal endothelial cell state identity better than culture in high mitogenic conditions. Expansion by continuous passaging induced replicative cell senescence. Transcriptomic analysis of the senescent phenotype identified a cell senescence signature distinct for CEnC. We identified activation of both classic and new cell signaling pathways that may be targeted to prevent senescence, a significant barrier to realizing the potential clinical utility of in vitro expansion.
Resolving heterogeneous high-mass macromolecular machineries by Orbitrap-based single particle charge detection mass spectrometry
Authors: Wörner Tobias P. , Snijder Joost , Bennett Antonette , Agbandje-McKenna Mavis , Makarov Alexander A. , Heck Albert J.R. 
Published: July 2019

AbstractHere we show that single particle charge-detection mass spectrometry (CD-MS) can be performed on a ubiquitous Orbitrap mass analyser and applied to the analysis of high-mass (megadalton) heterogeneous biomolecular assemblies. We demonstrate that single particle high-mass ions can survive in the Orbitrap for seconds, whereby their measured signal amplitudes scale linearly with charge state over the entire m/z range. Orbitrap based single particle CD-MS can be used to resolve mixed ion populations, accurately predict charge states, and consequently also the mass of the ions. We successfully applied CD-MS to challenging natural and biotherapeutic protein assemblies, such as IgM oligomers, designed protein nano-cages, ribosome particles and intact, empty- and genome-loaded Adeno-associated virus particles. Single particle CD-MS combined with native MS on existing Orbitrap platforms will greatly expand its application, especially in the mass analysis of megadalton heterogeneous biomolecular assemblies.
At what spatial scales are alternative stable states relevant in highly interconnected ecosystems?
Authors: Karatayev Vadim A. , Baskett Marissa L. 
Published: July 2019

AbstractWhether ecosystems recover from disturbance depends on the presence of alternative stable states, which are theoretically possible in simple models of many systems. However, definitive empirical evidence for this phenomenon remains limited to demographically closed ecosystems such as lakes. In more interconnected systems such as temperate rocky reefs, the local relevance of alternative stable states might erode as immigration overwhelms local feedbacks and produces a single stable state. At larger spatial scales, dispersal might counter localized disturbance and feedbacks to synchronize states throughout a region. Here, we quantify how interconnectedness affects the relevance of alternative stable states using dynamical models of California rocky reef communities that incorporate observed environmental stochasticity and feedback loops in kelp-urchin-predator interactions. Our models demonstrate the potential for localized alternative states despite high interconnectedness likely due to feedbacks affecting dispersers as they settle into local communities. Regionally, such feedbacks affecting settlement can produce a mosaic of alternative stable states that span local (10-20km) scales despite the synchronizing effect of long-distance dispersal. The specific spatial scale and duration of each state predominantly depend on the scales of environmental variation and on local dynamics (here, fishing). Model predictions reflect observed scales of community states in California rocky reefs and suggest how alternative states co-occur in the wide array of marine and terrestrial systems with settlement feedbacks.
Combinatorial use of communication technologies in organizations
Authors: Zhu Yaguang 
Published: August 2019

PurposeThe purpose of this paper is to critique and extend contemporary scholarship on information and communication technologies (ICTs). This paper argues that the focus on the selection and use of a single communication medium limits the understanding of current ICT use in organizations. A combinatorial perspective is needed to capture the complexities of multiple ICTs use for achieving communication goals and completing tasks.Design/methodology/approachThis paper addresses the trending phenomenon of combinatorial use of ICTs by offering a critical review of the theoretical studies and empirical research in scholarly books and journals and deriving novel theoretical research questions that set the stage for future studies.FindingsThis paper identifies how combinatorial ICT use as a perspective that uniquely elucidates ICT use in organizations, clarifies key terms used in previous research and proposes theoretical and operational recommendations for researchers and corporate practitioners who are interested in studying the combinatorial use of ICTs.Originality/valueThis paper highlights that understanding the combinatorial use ICTs in complex work environments could have significant implications for productivity and efficiency of individuals and corporations. This paper serves as a catalyst for on-going research conversations regarding combinatorial ICT use, while assisting organizational communication researchers and practitioners in describing, theorizing and advancing ICT implementation, use and outcomes.
Resistance toward dominant US work practices in emerging markets
Authors: Sinha Paresha N. , Bathini Dharma Raju 
Published: August 2019

Purpose
The purpose of this study is to apply the dominance effect theory and postcolonial notions of “otherness” to critically study the enactment of mimicry at IndianBread, an Indian fast-food chain that has adopted work practices typically found in US fast-food multinational enterprises (MNEs).

Design/methodology/approach
The authors used an interpretive sensemaking case study approach and collected qualitative data drawing on observations, notes from the company policy manual and in-depth interviews with eight staff at an IndianBread outlet. Data were also collected during informal interactions with staff at three other IndianBread outlets. The analysis focused on the enactment of mimicry and studied the postcolonial dynamics between managers and migrant workers to explain their resistance to the adoption of US work practices.

Findings
Work practices of US fast-food MNEs such as the standardization of workers’ appearance and basic “Englishization” such as greeting customers in English had been adopted at the IndianBread outlet. However, migrant workers resisted enforcement by contesting the superiority and relevance of these US work practices. The workers’ resistance was accommodated by local managers to pacify and retain them.

Research limitations/implications
The analysis contributes to a deeper understanding of the dynamics of resistance to the dominant influence of US work practices in emerging market firms. It expands current notions of “otherness” by presenting the perspective of “local” managers and migrant workers. The authors show how worker resistance embedded in their “identity work” involves contesting notions of “inferiority” of local work practices and selves. In the case of managers, accommodating resistance maintains their “legitimacy of dominance”. To that end, the study explains how the need to mimic US work practices is enforced, contested and ultimately diluted in competitive local firms in rising India.

Practical implications
The organizationally grounded data show how managerial accommodation of workers’ resistance to US practices creates a more flexible working environment that dilutes migrant workers’ sensitivity to their exploitation at the fast-food outlet.

Social implications
The findings identify the link between mimicry and resistance by the “other,” the ambivalence of the colonizing agent and the ongoing material exploitation within emerging economies.

Originality/value
To that end, the study explains how the need to mimic the US work practices is enforced, contested and ultimately diluted in the context of the competitive local firms in India.
Pre‐hospital outcomes of adult out‐of‐hospital cardiac arrest of presumed cardiac aetiology in Queensland, Australia (2002–2014): Trends over time
Authors: Pemberton Katherine , Bosley Emma , C Franklin Richard , Watt Kerrianne 
Published: July 2019

AbstractObjectiveTo describe temporal trends in incidence of pre‐hospital outcomes from adult out‐of‐hospital cardiac arrest (OHCA) of presumed cardiac aetiology attended by Queensland Ambulance Service (QAS) paramedics between 2002 and 2014, by age, gender, geographical remoteness and socio‐economic status.MethodsCases included in this retrospective cohort study were identified from the QAS OHCA Registry. Included cases were linked with Queensland Hospital Admitted Patient Data Collection and Queensland Death Registry. Population data were obtained from the Australian Bureau of Statistics to calculate incidence rates for each year. Analyses were undertaken by four mutually exclusive pre‐hospital outcomes: (i) no resuscitation (No‐Resus); (ii) resuscitation, no pre‐hospital return of spontaneous circulation (No‐ROSC); (iii) resuscitation, pre‐hospital return of spontaneous circulation not sustained to hospital (Unsustained‐ROSC); and (iv) resuscitation, pre‐hospital return of spontaneous circulation sustained to hospital (Sustained‐ROSC). Trends over time were analysed for crude and specific rates for total OHCA events and for each outcome.ResultsBetween 2002 and 2014, there were 30 560 OHCA cases. Crude incidence significantly increased over time for No‐Resus and Sustained‐ROSC, and significantly decreased for No‐ROSC. These trends were reflected in major cities, inner and outer regional areas. There was a significant increase in Sustained‐ROSC in remote areas, and no significant trends in very remote areas.ConclusionIncidence of withholding resuscitation and ROSC sustained to hospital have independently increased over time. Factors of middle age, more rural location and lower socio‐economic status should all be targeted in the development and implementation of future strategies.
Epidemiology of pre‐hospital outcomes of out‐of‐hospital cardiac arrest in Queensland, Australia
Authors: Pemberton Katherine , Bosley Emma , Franklin Richard C , Watt Kerrianne 
Published: July 2019

AbstractObjectiveTo describe incidence in pre‐hospital outcomes of adult out‐of‐hospital cardiac arrest (OHCA) of presumed cardiac aetiology, attended by Queensland Ambulance Service (QAS) paramedics between 2002 and 2014, by age, gender, geographical remoteness and socio‐economic status.MethodsThe QAS OHCA Registry was used to identify cases, which was then linked with Queensland Hospital Admitted Patient Data Collection and Queensland Death Registry. Population data were obtained for each calendar year by age and gender from the Australian Bureau of Statistics in order to calculate incidence rates. Four mutually exclusive pre‐hospital outcomes were analysed: (i) no resuscitation (No‐Resus); (ii) resuscitation, no pre‐hospital return of spontaneous circulation (No‐ROSC); (iii) resuscitation, pre‐hospital return of spontaneous circulation not sustained to hospital (Unsustained‐ROSC); and (iv) resuscitation, pre‐hospital return of spontaneous circulation sustained to hospital (Sustained‐ROSC).ResultsOver the 13 years, there were 30 560 OHCA cases for analyses. Incidence was significantly greater in males than females and incrementally increased with age, for each outcome. Incidence of total OHCA events generally increased as remoteness increased (major cities: 72.39 per 100 000 [95% CI 71.35–73.45]; very remote: 87.01 per 100 000 [95% CI 78.03–95.98]). There was an inverse association between incidence of OHCA events and socio‐economic status (SEIFA 1 and 2: 81.34 per 100 000 [95% CI 79.28–83.40]; SEIFA 9 and 10: 61.57 per 100 000 [95% CI 59.67–63.46]).ConclusionRural‐specific strategies should be continued. Prevention and management strategies for OHCA targeting lower socio‐economic groups require focus.
Daring to be wise: We are black boxes, and artificial intelligence will be the solution
Authors: Gutenstein Marc 
Published: July 2019

AbstractEmergency physicians seek wisdom through personal resilience, deliberate reasoning, clinical consensus and reflective practice. However, there is a limit to how useful psychological training, clinical guidelines and audit initiatives can be in the face of inherent human fallibility, increasing system complexity and escalating demand. Wisdom may be more easily attained through the careful design of new technology and this should be a priority for the emergency medicine community.