bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent Chikungunya Virus Replication in Human Cells is Associated with Presence of Stable Cytoplasmic Granules Containing Non-structural Protein 3
Authors: Remenyi Roland , Gao Yanni , Hughes Ruth E , Curd Alistair , Zothner Carsten , Peckham Michelle , Merits Andres , Harris Mark 
Published: February 2018

AbstractChikungunya virus (CHIKV), a mosquito-borne human pathogen, causes a disabling disease characterized by severe joint pain that can persist for weeks, months or even years in patients. The non-structural protein 3 (nsP3) plays essential roles during acute infection, but little is known about the function of nsP3 during chronic disease. Here, we used sub-diffraction multi-color microscopy for a spatial and temporal analysis of CHIKV nsP3 within human cells that persistently replicate viral RNA. Round cytoplasmic granules of various sizes (i) contained nsP3 and G3BP Stress Granule Assembly factor; (ii) were next to double-stranded RNA foci, and nsP1-positive structures; and (iii) made contact with markers of the cytoskeleton and cellular structures, such as early endosomes and nucleopores. Analysis of protein turnover and mobility by live-cell microscopy revealed that granules could persist for hours to days, can accumulate newly synthesized protein, and move at differently through the cytoplasm. Granules also had a static internal architecture and were stable in cell lysates. Whereas cells with active replication and stable nsP3-granules did not respond to oxidative stress, refractory cells that had cleared the non-cytotoxic replicon could. In summary, nsP3 can form uniquely stable granular structures that persist long-term within the host cell. This continued presence of viral and cellular protein-complexes has implications for the study of the pathogenic consequences of lingering CHIKV infection and the development of strategies to mitigate the burden of chronic musculoskeletal disease brought about by a medically important arthropod-borne virus (arbovirus).ImportanceChikungunya virus (CHIKV) is a re-emerging alphavirus transmitted by mosquitos and causes widespread transient sickness but also chronic disease affecting muscles and joints. Although no approved vaccines or antivirals are available, a better understanding of the viral life cycle and the role of individual viral proteins can aid in identifying new therapeutic targets. Advances in microscopy and persistent CHIKV model systems now allow researchers to study viral proteins within controlled laboratory environments. Here we established human cells that stably replicate viral RNA and express a tagged version of non-structural protein 3. The ability to track this viral protein within the host cell and during persistent replication can benefit fundamental research efforts to better understand long-term consequences of the persistence of viral protein complexes and thereby provide the foundation for new therapeutic targets to control CHIKV infection and treat chronic disease symptoms.
PAGE4 and Conformational Switching: Insights from Molecular Dynamics Simulations and Implications for Prostate Cancer
Authors: Lin Xingcheng , Roy Susmita , Jolly Mohit Kumar , Bocci Federico , Schafer Nicholas , Tsai Min-Yeh , Chen Yihong , He Yanan , Grishaev Alexander , Weninger Keith , Orban John , Kulkarni Prakash , Rangarajan Govindan , Levine Herbert , Onuchic José N. 
Published: February 2018

AbstractProstate-Associated Gene 4 (PAGE4) is a disordered protein implicated in the progression of prostate cancer. PAGE4 can be phosphorylated at two residue sites by Homeodomain-Interacting Protein Kinase 1 (HIPK1) to facilitate its binding to the Activator Protein-1 (AP-1) transcription factor. In contrast, a further hyperphosphorylation of PAGE4 by CDC-Like Kinase 2 (CLK2) reduces its binding affinity to AP-1, thus affecting the androgen receptor (AR) activity. Both SAXS and smFRET experiments have shown a structural expansion of PAGE4 upon hyperphosphorylation and a significant increase in size at its N-terminal half than that at its C-terminus. To understand the molecular mechanism underlying this structural transition, we performed a series of constant temperature molecular dynamics simulations using Atomistic AWSEM — a multi-scale molecular model combining detailed atomistic and coarse-grained simulation approaches. Our simulations show that electrostatic interaction drives a transient formation of an N-terminal loop, which causes the change in size for different phosphorylated forms of PAGE4. Phosphorylation also changes the preference of secondary structure formation of PAGE4, which signifies a transition between states that display different degree of disorder. Finally, we construct a mechanism-based mathematical model that allows us to capture the interactions of different forms of PAGE4 with AP-1 and AR, a key therapeutic target in prostate cancer. Our model predicts intracellular oscillatory dynamics of HIPK1-PAGE4, CLK2-PAGE4 and AR activity, indicating phenotypic heterogeneity in an isogenic cell population. Thus, conformational switching among different forms of PAGE4 may potentially affect the efficiency of therapeutic targeting of AR.
Size-dependent movement explains why bigger is better in fragmented landscapes
Authors: Hillaert Jasmijn , Hovestadt Thomas , Vandegehuchte Martijn L. , Bonte Dries 
Published: February 2018

AbstractBody size is a fundamental trait known to allometrically scale with metabolic rate, and therefore a key determinant of individual development, life history and consequently fitness. In spatially structured environments, movement is an equally important driver of fitness. Because movement is tightly coupled with body size, we expect habitat fragmentation to induce a strong selection pressure on size variation across and within species. Changes in body size distributions are then, in turn, expected to alter food web dynamics. However, no consensus has been reached on how spatial isolation and resource growth affect body size distributions.Our aim was to investigate how these two factors shape the body size distribution of consumers under scenarios of size-dependent and -independent consumer movement by applying a mechanistic, individual-based resource-consumer model. The outcome was then linked to important ecosystem traits such as resource abundance and stability. Finally, we determined those factors that explain most variation in size distributions.We demonstrate that decreasing connectivity and resource growth select for communities (or populations) consisting of larger species (or individuals) due to strong selection for the ability to move over longer distances. When including size-dependent movement, moderate levels of connectivity result in increases in local size diversity. Due to this elevated functional diversity, resource uptake is optimized at the metapopulation or metacommunity level. At these intermediate levels of connectivity, size-dependent movement explains most of the observed variation in size distributions. Interestingly, local and spatial stability of consumer biomass are lowest when isolation and resource productivity are high. Finally, we highlight that size-dependent movement is of vital importance for the survival of populations within highly fragmented landscapes. Our results demonstrate that considering size-dependent movement and resource growth is essential to understand patterns of size distributions at the population or community level and the resulting metapopulation or metacommunity dynamics.
Edge fires drive the shape and stability of tropical forests
Authors: Hébert-Dufresne Laurent , Pellegrini Adam F. A. , Bhat Uttam , Redner Sidney , Pacala Stephen W. , Berdahl Andrew M. 
Published: February 2018

AbstractIn tropical regions, fires propagate readily in grasslands but typically consume only edges of forest patches. Thus forest patches grow due to tree propagation and shrink by fires in surrounding grasslands. The interplay between these competing edge effects is unknown, but critical in determining the shape and stability of individual forest patches, as well the landscape-level spatial distribution and stability of forests. We analyze high-resolution remote-sensing data from protected areas of the Brazilian Cerrado and find that forest shapes obey a robust perimeter-area scaling relation across climatic zones. We explain this scaling by introducing a heterogeneous fire propagation model for tropical forest-grassland ecotones. Deviations from this perimeter-area relation determine the stability of individual forest patches. At a larger scale, our model predicts that the relative rates of tree growth due to propagative expansion and long-distance seed dispersal determine whether collapse of regional-scale tree cover is continuous or discontinuous as fire frequency changes.
Modelling cell-cell interactions from spatial molecular data with spatial variance component analysis
Authors: Arnol Damien , Schapiro Denis , Bodenmiller Bernd , Saez-Rodriguez Julio , Stegle Oliver 
Published: February 2018

AbstractTechnological advances allow for assaying multiplexed spatially resolved RNA and protein expression profiling of individual cells, thereby capturing physiological tissue contexts of single cell variation. While methods for the high-throughput generation of spatial expression profiles are increasingly accessible, computational methods for studying the relevance of the spatial organization of tissues on cell-cell heterogeneity are only beginning to emerge. Here, we presentspatial variance component analysis (SVCA),a computational framework for the analysis of spatial molecular data. SVCA enables quantifying the effect of cell-cell interactions, as well as environmental and intrinsic cell features on the expression levels of individual genes or proteins. In application to a breast cancer Imaging Mass Cytometry dataset, our model allows for robustly estimating spatial variance signatures, identifying cell-cell interactions as a major driver of expression heterogeneity. Finally, we apply SVCA to high-dimensional imaging-derived RNA data, where we identify molecular pathways that are linked to cell-cell interactions.
Cluster expansion ofapolipoprotein D (ApoD)genes in teleost fishes
Authors: Gu Langyu , Xia Canwei 
Published: February 2018

AbstractBackgroundGene and genome duplication play important roles in the evolution of gene function. Compared to individual duplicated genes, gene clusters attract particular attentions considering their frequent associations with innovation and adaptation. Here, we report for the first time the expansion of the ligand (e.g., pheromone and hormone)-transporter genes,apolipoprotein D(ApoD) genes in a cluster, specific to teleost fishes.ResultsThe singleApoDgene in the ancestor expands in two clusters with a dynamic evolutionary pattern in teleost fishes. Based on comparative genomic and transcriptomic analyses, protein 3D structure comparison, evolutionary rate detection and breakpoint detection, orthologous genes show conserved expression patterns. Lineage-specific duplicated genes that are under positive selection evolved specific and even new expression profiles. Different duplicates show high tissue-specific expression patterns (e.g., skin, eye, anal fin pigmentation patterns, gonads, gills, spleen and lower pharyngeal jaw). Cluster analyses based on protein 3D structure comparisons, especially the four loops at the opening side, show segregation patterns with different duplicates. DuplicatedApoDgenes are predicted to be associated with forkhead transcription factors and MAPK genes, and they are located next to the breakpoints of genome rearrangements.ConclusionsHere, we report the expansion ofApoDgenes specific to teleost fishes in a cluster manner for the first time. Neofunctionalization and subfunctionalization were observed at both protein and expression levels after duplication. Evidence from different aspects, i.e. abnormal expression induced disease in human, fish-specific expansion, predicted associations with forkhead transcription factors and MAPK genes, highly specific expression patterns in tissues related to sexual selection and adaptation, duplicated genes that are under positive selection, and their locations next to breakpoints of genome rearrangement, suggests the potential advantageous roles ofApoDgenes in teleost fishes. Cluster expansion ofApoDgenes specific to teleost fishes thus provides an ideal evo-devo model for studying gene duplication, cluster maintenance and new gene function emergence.
Uncoupling of sgRNAs from their associated barcodes during PCR amplification of combinatorial CRISPR screens
Authors: Hegde Mudra , Strand Christine , Hanna Ruth E. , Doench John G. 
Published: February 2018

ABSTRACTMany implementations of pooled screens in mammalian cells rely on linking an element of interest to a barcode, with the latter subsequently quantitated by next generation sequencing. However, substantial uncoupling between these paired elements during lentiviral production has been reported, especially as the distance between elements increases. We detail that PCR amplification is another major source of uncoupling, and becomes more pronounced with increased amounts of DNA template molecules and PCR cycles. To lessen uncoupling in systems that use paired elements for detection, we recommend minimizing the distance between elements, using low and equal template DNA inputs for plasmid and genomic DNA during PCR, and minimizing the number of PCR cycles. We also present a vector design for conducting combinatorial CRISPR screens that enables accurate barcode-based detection with a single short sequencing read and minimal uncoupling.
Relationships between advanced manufacturing technologies, absorptive capacity, mass customization, time to market and financial and market performance
Authors: Deshpande Anant 
Published: February 2018

Purpose
The purpose of the paper is to empirically investigate the relationships between advanced manufacturing technology (AMT), absorptive capacity, mass customization (MC) capability, competitive advantage, and organizational performance measures.

Design/methodology/approach
Based on a literature review, a theoretical framework is derived. Structural equation modeling was chosen for the empirical analysis based on the focus of the research. Data collection was conducted from 232 Indian manufacturing managers.

Findings
The findings indicate that absorptive capacity has a positive impact on MC capability. Also, MC capability mediated the relationship between AMT and the financial and market performance. Furthermore, AMT positively impacted MC capability, and MC capability positively impacted both time to market and financial and market performance. AMT was not found to have a significant impact on financial and market performance.

Originality/value
The current study is meaningful and unique in that no study has investigated the linkages between AMT, absorptive capacity, MC capability and organization performance and competitive advantage measures in a unified context. Such investigations are important because the results will encourage managers to invest in developing these mechanisms, which in turn will influence firm’s ability to implement MC practices and yield benefits such as improved performance and competitive advantage.
Emotional intelligence as a moderator in abusive supervision-intention to quit relationship among Indian healthcare professionals
Authors: Pradhan Sajeet , Jena Lalatendu Kesari 
Published: February 2018

PurposeDespite knowledge of the destructive effect of abusive supervision on several individual and organizational outcomes, the construct remains scarcely investigated, especially in Indian organizations. Drawing upon the conservation of resources theory, the purpose of this paper is to explore the linkage between abusive supervision (an interpersonal stressor) and subordinate’s intention to quit and to focuss on the moderating role of subordinate’s emotional intelligence as a neutralizer in curbing the pernicious effect of abusive supervision on subordinate’s intention to quit.Design/methodology/approachThe participants of this study were 353 healthcare professionals working in a large Indian hospital chain having all India presence. The authors have collected data on our predictor and criterion variables at two time points with a separation of three to four weeks for reducing common method bias (Podsakoffet al., 2012). At Time 1, participants rated the perception of their supervisor’s abusiveness and answered few demographic questions. At Time 2, participants completed measures of intention to quit and their emotional intelligence.FindingsThe finding of this study corroborates the assertion that subordinates who perceive their supervisors to be abusive have higher intension to quit organization. But surprisingly, this study reports that the moderating effect of emotional intelligence showed stronger relationship between abusive supervision and intention to quit when emotional intelligence is high than low.Practical implicationsOrganization should take serious note of supervisors or managers that are abusive or are perceived to be abusive by their subordinates. As it is impossible to completely eradicate abusive and deviant supervisory behaviors at workplace, these toxic behaviors can be checked at several levels like hiring people high on emotional intelligence and through imparting emotional intelligence training and counseling to both the accused and the victim.Originality/valueThe study finds support to the relationship between abusive supervision and intention to quit in Indian context. The finding of this study fails to empirically corroborate the assumption that emotional intelligence will act as a neutralizer in mitigating the pernicious effect of abusive supervision on subordinates’ intention to quit.
Providing a sustainable living environment in not-for-profit retirement villages
Authors: Hu Xin , Xia Bo , Skitmore Martin , Buys Laurie 
Published: February 2018

Purpose
As a viable housing option for older people, retirement villages need to provide a sustainable living environment that satisfies their residents’ needs in terms of affordability, lifestyle and environmental friendliness. This is, however, a significant challenge for not-for-profit developers because of the high upfront costs involved in using sustainable practices. The purpose of this paper is to identify the sustainable features and practices adopted in not-for-profit retirement villages.

Design/methodology/approach
Because of the lack of quantitative historical data, a case study approach was adopted to identify the sustainable features and practices used in a not-for-profit retirement village in Sunshine Coast, Queensland, Australia. Data were collected based on interviews, direct observation and documentation, and collected data were analysed by using content analysis.

Findings
The research findings indicate that similar to private developers, not-for-profit developers also have the capability to make their village environment sustainable. In this case, the sustainable practices cover various aspects including the selection of village location, site planning, provision of facilities and services, social life and living costs. Although the associated costs of adopting sustainable features is a concern for both developers and residents, some of the identified sustainable practices in this case do not result in significant cost increase but can improve the residents’ quality of life substantially.

Practical implications
The research findings provide a number of practical implications on how to deliver sustainable retirement villages in a not-for-profit village setting.

Originality/value
This paper provides a first look at sustainable features and practices adopted in both the development and operation stages of a not-for-profit retirement village.
Comparison study on the nonlinear parameter optimization of nonlinear grey Bernoulli model (NGBM(1,1)) between intelligent optimizers
Authors: Kong Lingcun , Ma Xin 
Published: February 2018

PurposeThe purpose of this paper is to find out which algorithm, among Genetic Algorithm (GA), Particle Swarm Optimizer (PSO), the novel Grey Wolf Optimizer (GWO) and the novel Ant Lion Optimizer (ALO), is the best to obtain the optimal value of the nonlinear parameterγof nonlinear grey Bernoulli model (NGBM(1,1)) under different situations.Design/methodology/approachThe optimization ofγhas been attributed to a nonlinear programming problem at first. The convergence, convergence rate, time consuming and stability of GA, PSO, GWO and ALO are compared in the numerical experiments, and in each subcase the criteria are set to be the same. Over 10,000 iterations have been run on the same environment in order to guarantee the reliability of the results.FindingsAll the selected algorithms can converge to the same optimal value with sufficient iterations. But the best algorithm should be chose under different situations.Practical implicationsThe optimal value ofγseems to exist uniquely due to the empirical results. And there does not exist a best algorithm for all the cases. The researchers and commercial software developers should choose a proper algorithm due to different cases.Originality/valueThe performance of GA, PSO, GWO and ALO to compute the optimalγof NGBM(1,1) has been compared for the first time. And it is the original work which uses the GWO and ALO to optimize the NGBM(1,1).
Examining the effects of source selection method on procurement outcomes
Authors: Landale Karen A.F. , Rendon Rene G. , Hawkins Timothy G. 
Published: February 2018

PurposeThe purpose of this research is to explore the effects of supplier selection method on key procurement outcomes such as procurement lead time (PLT), supplier performance and buyer team size.Design/methodology/approachData were collected from a sample of 124 archival contract records from the US Department of Defense. A multiple regression model and multivariate analysis of covariance/analysis of covariance models were used to test the effects of source selection method on pertinent procurement outcomes.FindingsThe trade-off (TO) source selection method increases PLT, as does the number of evaluation factors and the number of proposals received. Substantially larger sourcing teams are also associated with the TO source selection method. Nonetheless, the TO method results in better supplier performance.Practical implicationsTO source selections yield superior supplier performance than low-bidder methods. However, they are costly in terms of time and personnel. Any assessment of supplier value should consider not only the price premium for higher performance but also the transaction costs associated with the TO method.Originality/valueVery little research addresses a buying team’s evaluation of supplier-offered value ex ante and whether that value assessment materializes into actual value-added supplier performance. Low bidder tactics are pervasive, but price (i.e. sacrifice) is only one component of value. Benefits from superior supplier performance may yield greater overall value. If value is critical to the buyer, a TO source selection method – versus a low-bidder approach – is the appropriate tool because of higher supplier performance ex post.