bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atomic structure of Hsp90:Cdc37:Cdk4 reveals Hsp90 regulates kinase via dramatic unfolding
Authors: Verba Kliment A. , Wang Ray Yu-Ruei , Arakawa Akihiko , Liu Yanxin , Shirouzu Mikako , Yokoyama Shigeyuki , Agard David A. 
Published: February 2016

AbstractThe Hsp90 molecular chaperone and its Cdc37 co-chaperone help stabilize and activate over half of the human kinome. However, neither the mechanism by which these chaperones assist their client kinases nor why some kinases are addicted to Hsp90 while closely related family members are independent is known. Missing has been any structural understanding of these interactions, with no full-length structures of human Hsp90, Cdc37 or either of these proteins with a kinase. Here we report a 3.9Å cryoEM structure of the Hsp90:Cdc37:Cdk4 kinase complex. Cdk4 is in a novel conformation, with its two lobes completely separated. Cdc37 mimics part of the kinase N-lobe, stabilizing an open kinase conformation by wedging itself between the two lobes. Finally, Hsp90 clamps around the unfolded kinase β5 strand and interacts with exposed N-and C-lobe interfaces, safely trapping the kinase in an unfolded state. Based on this novel structure and extensive previous data, we propose unifying conceptual and mechanistic models of chaperone-kinase interactions.One Sentence SummaryThe first structure of a chaperone:kinase complex reveals that the Hsp90 system modulates and stabilizes kinases via a functionally relevant, unfolded open state.
Genetic redundancies enhance information transfer in noisy regulatory circuits
Authors: Rodrigo Guillermo , Poyatos Juan F. 
Published: February 2016

AbstractCellular decision making is based on regulatory circuits that associate signal thresholds to specific physiological actions. This transmission of information is subjected to molecular noise what can decrease its fidelity. Here, we show instead how such intrinsic noise enhances information transfer in the presence of multiple circuit copies. The result is due to the contribution of noise to the generation of autonomous responses by each copy, which are altogether associated with a common decision. Moreover, factors that correlate the responses of the redundant units (extrinsic noise or regulatory cross-talk) contribute to reduce fidelity, while those that further uncouple them (heterogeneity within the copies) can lead to stronger information gain. Overall, our study emphasizes how the interplay of signal thresholding, redundancy, and noise influences the accuracy of cellular decision making. Understanding this interplay provides a basis to explain collective cell signaling mechanisms, and to engineer robust decisions with noisy genetic circuits.
Exploitation by cheaters facilitates the preservation of essential public goods in microbial communities
Authors: Moreno-Fenoll Clara , Cavaliere Matteo , Martínez-García Esteban , Poyatos Juan F. 
Published: February 2016

SummaryHow are public goods1-4maintained in bacterial cooperative populations? The presence of these compounds is usually threatened by the rise of cheaters that do not contribute but just exploit the common resource5,6. Minimizing cheater invasions appears then as a necessary maintenance mechanism7,8. However, that invasions can instead add to the persistence of cooperation is a prospect that has yet remained largely unexplored6. Here, we show that the detrimental consequences of cheaters can actually preserve public goods, at the cost of recurrent collapses and revivals of the population. The result is made possible by the interplay between spatial constraints and the essentiality of the shared resource. We validate this counter-intuitive effect by carefully combining theory and experiment, with the engineering of an explicit synthetic community in which the public compound allows survival to a bactericidal stress. Notably, the characterization of the experimental system identifies additional factors that can matter, like the impact of the lag phase on the tolerance to stress, or the appearance of spontaneous mutants. Our work emphasizes the unanticipated consequences of the eco-evolutionary feedbacks that emerge in microbial communities relying on essential public goods to function, feedbacks that reveal fundamental for the adaptive change of ecosystems at all scales.
Bayesian Inference of the Evolution of a Phenotype Distribution on a Phylogenetic Tree
Authors: Ansari M. Azim , Didelot Xavier 
Published: February 2016

AbstractThe distribution of a phenotype on a phylogenetic tree is often a quantity of interest. Many phenotypes have imperfect heritability, so that a measurement of the phenotype for an individual can be thought of as a single realisation from the phenotype distribution of that individual. If all individuals in a phylogeny had the same phenotype distribution, measured phenotypes would be randomly distributed on the tree leaves. This is however often not the case, implying that the phenotype distribution evolves over time. Here we propose a new model based on this principle of evolving phenotype distribution on the branches of a phylogeny, which is different from ancestral state reconstruction where the phenotype itself is assumed to evolve. We develop an efficient Bayesian inference method to estimate the parameters of our model and to test the evidence for changes in the phenotype distribution. We use multiple simulated datasets to show that our algorithm has good sensitivity and specificity properties. Since our method identifies branches on the tree on which the phenotype distribution has changed, it is able to break down a tree into components for which this distribution is unique and constant. We present two applications of our method, one investigating the association between HIV genetic variation and human leukocyte antigen, and the other studying host range distribution in a lineage ofSalmonella enterica, and we discuss many other potential applications. All the methods described in this paper are implemented in a software package called TreeBreaker which is freely available for download athttps://github.com/ansariazim/TreeBreaker
Pooled enrichment sequencing identifies diversity and evolutionary pressures at NLR resistance genes within a wild tomato population
Authors: Stam Remco , Scheikl Daniela , Tellier Aurélien 
Published: February 2016

AbstractNod-like Receptors (NLRs) are Nucleotide-binding domain and Leucine rich Repeats (NB-LRR)-containing proteins that are important in plant resistance signaling. Many of the known pathogen Resistance (R)-genes in plants are NLRs and they can recognise directly or indirectly pathogen molecules. As such, divergence and copy number variants at these genes is found to be high between species. Within populations, positive and balancing selection are to be expected if plants coevolve with their pathogens. In order to understand the complexity of R-gene coevolution in wild non-model species, it is necessary to identify the full range of NLRs and infer their evolutionary history.Here we investigate and reveal polymorphism occurring at 220 NLR genes within one population of the partially selfing wild tomato speciesS. pennellii. We use a combination of enrichment sequencing and pooling of ten individuals, to specifically sequence NLR genes in a resource and cost-effective manner. We focus on the effects which different of mapping and SNP calling software and settings have on calling polymorphisms in customized pooled samples. Our results are accurately verified using Sanger sequencing of polymorphic gene fragments. Our results indicate that some NLRs, namely 13 out of 220, have maintained polymorphism within ourS. pennelliipopulation. These genes show a wide range of πN/πsratios and differing site frequency spectra. We compare our observed rate of heterozygosity to expectations for this selfing and bottlenecked population. We conclude that our method enables us to pinpoint NLR genes which have experienced natural selection in their habitat.
On the Regulator of Spike Activity in Cortical Neurons Under Hypothermic Conditions
Authors: Mednikova Yu. S. , Zakharova N. M. , Pasikova N. V. , Averina I. V. 
Published: February 2016

AbstractIn sensorimotor cortical slices of guinea pig in the course of cooling incubating fluid from 34 to 21-22°C it was shown that hypothermia exerted both increase and decrease of spontaneous activity in different neurons. On hypothermic increase of firing level spike responses of soma to iontophoretic application of glutamate to dendritic locus appeared with shorter latencies and with longer latencies – on hypothermic decrease of spontaneous activity. At the same time hypothermia did not influence on the evoked spike reactions to iontophoretic application of glutamate straight to the soma. It means that hypothermic disorders of neuronal activity are not connected with changes in sensitivity to glutamate but determined by changes of amplitude of glutamatergic excitation while propagating along dendritic branches. The changes in spontaneous activity began at 30°C along with the decreased spike reactions to iontophoretic applications of acetylcholine and efficacy of dendro-somatic propagation. At the same temperature the fall of spike amplitude was initiated and increased with further hypothermia. It is proposed that the basis for hypothermic changes of neuronal activity is the decreased rate of M-cholinergic process at 27-29°C which leads both to attenuation of conductive function of dendrites and imbalance of K+ion homeostasis. Peculiarities of hypothermic regulation of neuronal spike activity depend on individual functional properties of cortical neurons.
foxc1agenetically interacts withripply1to regulatemesp-baexpression and somitogenesis in the zebrafish embryo
Authors: Lavy Rotem , Allison W. Ted , Berry Fred B. 
Published: February 2016

AbstractSomitogenesis is a fundamental segmentation process that forms the vertebrate body plan. A network of transcription factors is essential in establishing the spatial temporal order of this process. One such transcription factor is mesp-bawhich has an important role in determining somite boundary formation. Its expression in somitogenesis is tightly regulated by the transcriptional activator Tbx6 and the repressor Ripply1 via a feedback regulatory network. Loss offoxc1afunction in zebrafish leads to lack of anterior somite formation and reducedmesp-baexpression. Here we examine howfoxc1ainteracts with thetbx6-ripply1network to regulatemesp-baexpression. Infoxc1amorphants, anterior somites did not form at 12.5 hours post fertilization (hpf). At 22 hpf posterior somites formed, whereas anterior somites remained absent. Inripply1morphants, no somites were observed at any time point. The expression ofmesp-bawas reduced in thefoxc1amorphants and expanded anteriorly inripply1morphants. Thetbx6expression domain was smaller and shifted anteriorly in thefoxc1amorphants. Double knockdown offoxc1aandripply1resulted in absence of anterior somite formation while posterior somites did form, suggesting a partial rescue of theripply1phenotype. However, unlike the singlefoxc1amorphants, expression ofmesp-bawas restored in the anterior PSM. Expression oftbx6was expanded anteriorly in the double morphants. In conclusion, bothfoxc1aandripply1morphants displayed defects in somitogenesis, but their individual loss of function had opposing effects onmesp-baexpression. Loss ofripply1appears to have rescued themesp-ba expression in thefoxc1amorphant, suggesting that intersection of these parallel regulatory mechanisms is required for normalmesp-baexpression and somite formation.
Accurate promoter and enhancer identification in 127 ENCODE and Roadmap Epigenomics cell types and tissues by GenoSTAN
Authors: Zacher Benedikt , Michel Margaux , Schwalb Björn , Cramer Patrick , Tresch Achim , Gagneur Julien 
Published: February 2016

AbstractAccurate maps of promoters and enhancers are required for understanding transcriptional regulation. Promoters and enhancers are usually mapped by integration of chromatin assays charting histone modifications, DNA accessibility, and transcription factor binding. However, current algorithms are limited by unrealistic data distribution assumptions. Here we propose GenoSTAN (Genomic STate ANnotation), a hidden Markov model overcoming these limitations. We map promoters and enhancers for 127 cell types and tissues from the ENCODE and Roadmap Epigenomics projects, today’s largest compendium of chromatin assays. Extensive benchmarks demonstrate that GenoSTAN consistently identifies promoters and enhancers with significantly higher accuracy than previous methods. Moreover, GenoSTAN-derived promoters and enhancers showed significantly higher enrichment of complex trait-associated genetic variants than current annotations. Altogether, GenoSTAN provides an easy-to-use tool to define promoters and enhancers in any system, and our annotation of human transcriptional cis-regulatory elements constitutes a rich resource for future research in biology and medicine.
Effectors and potential targets selectively upregulated in human KRAS-mutant lung adenocarcinomas
Authors: Li Jinyu , Sordella Raffaella , Powers Scott 
Published: February 2016

AbstractGenetic and proteomic analysis of human tumor samples can provide an important compliment to information obtained from model systems. Here we examined protein and gene expression from the Cancer Genome and Proteome Atlases (TCGA and TCPA) to characterize proteins and protein-coding genes that are selectively upregulated inKRAS-mutant lung adenocarcinomas. Phosphoprotein activation of several MAPK signaling components was considerably stronger inKRAS-mutants than any other group of tumors, even those with activating mutations in receptor tyrosine kinases (RTKs) and BRAF. Co-occurring mutations inKRAS-mutants were associated with differential activation of PDK1 and PKC-alpha. Genes showing strong activation in RNA-seq data included negative regulators of RTK/RAF/MAPK signaling along with potential oncogenic effectors including activators of Rac and Rho proteins and the receptor protein-tyrosine phosphatase genes PTPRM and PTPRE. These results corroborate RAF/MAPK signaling as an important therapeutic target inKRAS-mutant lung adenocarcinomas and pinpoint new potential targets.
Natural selection driven by DNA binding proteins shapes genome-wide motif statistics
Authors: Qian Long , Kussell Edo 
Published: February 2016

AbstractEctopic DNA binding by transcription factors and other DNA binding proteins can be detrimental to cellular functions and ultimately to organismal fitness. The frequency of protein-DNA binding at non-functional sites depends on the global composition of a genome with respect to all possible short motifs, ork-mer words. To determine whether weak yet ubiquitous protein-DNA interactions could exert significant evolutionary pressures on genomes, we correlatein vitromeasurements of binding strengths on all 8-mer words from a large collection of transcription factors, in several different species, against their relative genomic frequencies. Our analysis reveals a clear signal of purifying selection to reduce the large number of weak binding sites genome-wide. This evolutionary process, which we callglobal selection, has a detectable hallmark in that similar words experience similar evolutionary pressure, a consequence of the biophysics of protein-DNA binding. By analyzing a large collection of genomes, we show that global selection exists in all domains of life, and operates through tiny selective steps, maintaining genomic binding landscapes over long evolutionary timescales.
A new arc-length control method based on the rates of the internal and the dissipated energy
Authors: May Stefan , Vignollet Julien , de Borst René 
Published: February 2016

Purpose
– The purpose of this paper is to introduce a new arc-length control method for physically non-linear problems based on the rates of the internal and the dissipated energy.

Design/methodology/approach
– In this paper, the authors derive from the second law of thermodynamics the arc-length method based on the rate of the dissipated energy and from the time derivative of the energy density the arc-length method based on the rate of the internal energy.

Findings
– The method requires only two parameters and can automatically trace equilibrium paths which display multiple snap-through and/or snap-back phenomena.

Originality/value
– A fully energy-based control procedure is developed, which facilitates switching between dissipative and non-dissipative arc-length control equations in a natural way. The method is applied to a plate with an eccentric hole using the phase field model for brittle fracture and to a perforated beam using interface elements with decohesion.
Strategies for computationally feasible multi-objective simulation-driven design of compact RF/microwave components
Authors: Koziel Slawomir , Bekasiewicz Adrian 
Published: February 2016

Purpose– Strategies for accelerated multi-objective optimization of compact microwave and RF structures are investigated, including the possibility of exploiting surrogate modeling techniques for electromagnetic (EM)-driven design speedup for such components. The paper aims to discuss these issues.Design/methodology/approach– Two algorithmic frameworks are described that are based on fast response surface approximation models, structure decomposition, and Pareto front refinement. Numerical case studies are provided demonstrating feasibility of solving real-world problems involving multi-objective optimization of miniaturized microwave passives and expensive EM-simulation models of such structures.Findings– It is possible, through appropriate combination of the surrogate modeling techniques and response correction methods, to identify the set of alternative designs representing the best possible trade-offs between conflicting design objectives in a realistic time frame corresponding to a few dozen of high-fidelity EM simulations of the respective structures.Research limitations/implications– The present study sets a direction for further studied on expedited optimization of computationally expensive simulation models for miniaturized microwave components.Originality/value– The proposed algorithmic framework proved useful for fast design of microwave structures, which is extremely challenging when using conventional methods. To the authors’ knowledge, this is one of the first attempts to surrogate-assisted multi-objective optimization of compact components at the EM-simulation level.
Effects of economic and social satisfaction on partner trust
Authors: Ha Hong-Youl , Lee Myung-Soo , Janda Swinder 
Published: February 2016

Purpose– It has previously been noted that channel relationships are more richly understood when viewed over time. Moreover, there is a lack of research on how two types of satisfaction (economic and social satisfaction) have differential effects on partner trust over time. The purpose of this study is to investigate whether (and if so how) these two types of satisfaction have differential effects on partner trust from the initial stage of channel relationship to the subsequent relationship period.Design/methodology/approach– Longitudinal data are used in an effort to understand the dynamic process of channel relationships over time.Findings– It is found that over time, the strength of the relationship between economic satisfaction and partner trust decreases, while the effect of social satisfaction on partner trust increases. Interestingly, the direct effect of perceived value on partner trust dramatically decreases from time point T to T + 1, indicating that these relationships exhibit significant temporal effects.Research limitations/implications– The most relevant theoretical implication is that social satisfaction has a desirable role of bridging the relationship between perceived value and partner trust at time points T and T + 1. Thus, social satisfaction is a key factor in sustaining a channel partnership over time even after initial perceived value has been enhanced via the route of economic satisfaction. The main limitation is that data were collected in South Korea – further validation would require data from multiple cultural contexts.Practical implications– Results provide important implications for channel members aiming to enhance trust with partners. In initial stages of a relationship, channel members should concentrate their marketing resources on enhancing economic satisfaction, as it plays a key role in enhancing trust. As channel relationships evolve, the role of social satisfaction between perceived value and partner trust becomes more important. Thus, in the latter stages of a relationship, it would be prudent to focus more on activities which enhance social satisfaction.Originality/value– To the best of the authors’ knowledge, there is very little research focusing on temporal carryover effects. The authors thus contribute to the establishment and testing of temporal carryover effects of various business-to-business (B2B) relationship-related constructs, such as perceived value, economic and social satisfaction and partner trust.
Exploring the impact of employees’ self-concept, brand identification and brand pride on brand citizenship behaviors
Authors: Helm Sabrina Verena , Renk Uwe , Mishra Anubha 
Published: February 2016

Purpose
– The purpose of this paper is to identify how employees’ perceived congruity of their employers’ corporate brand with their own actual and ideal self may affect their brand identification (BI), brand pride (BP) and brand citizenship behavior (BCB).

Design/methodology/approach
– This cross-sectional paper involved 283 employees in Germany who completed an online survey.

Findings
– Congruity of the brand with employees’ actual self and with their ideal self has similar effects on employees’ BI. However, effects differ with respect to the other outcome variables. BP is only affected by congruity of the brand with the ideal self, whereas BCB is only affected by congruity of the brand with the actual self. Brand identity is positively related to BP and BCB; BP also affects BCB.

Research limitations/implications
– Future studies could include different sources for evaluation of BI, BP and BCB; for temporally separate measurement of identification, pride and BCB; and for use of fictitious brands or experimental manipulations of pride to increase internal validity. The discrepant impacts of congruity of the brand with the actual self and the ideal self as detected in the paper could spark research interest in addressing motivations to increase self-esteem and self-consistency in a work context or in investigating specific mediators or moderators in the relationship between self-concept, (brand) identification and pride, as well as behaviors. Finally, research could address different kinds of pride, such as individual and collective forms of pride, as well as their interplay.

Practical implications
– Managers should be aware of the different effects of a corporate brand’s fit with employees’ actual and ideal self, and also should note that BI seems essential in augmenting BP and brand-related behaviors. The paper develops implications for internal branding and HRM strategies regarding employee selection, promotion and retention. Findings also indicate that BP motivates BCB in line with current assumptions in research and practice on individual forms of pride.

Originality/value
– This paper investigates employees’ perceptions of “their” brand’s fit with their actual and ideal self separately, and determines the differences in impact on BP and BCB, extending existing knowledge on drivers of brand-building behaviors. It also develops the concept of BP in the context of social identity theory and the need for distinction; it further provides initial empirical insights into the role of employees’ BP, including the development of a measure.