bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of quercetin with transcriptional regulator LasR of Pseudomonas aeruginosa: Mechanistic insights of the inhibition of virulence through quorum sensing
Authors: Grabski Hovakim , Hunanyan Lernik , Tiratsuyan Susanna , Vardapetyan Hrachik 
Published: December 2017

ABSTRACTBackgroundPseudomonas aeruginosais one of the most dangerous superbugs in the list of bacteria for which new antibiotics are urgently needed, which was published by World Health Organization.P. aeruginosais an antibiotic-resistant opportunistic human pathogen. It affects patients with AIDS, cystic fibrosis, cancer, burn victims and people with prosthetics and implants.P. aeruginosaalso forms biofilms. Biofilms increase resistance to antibiotics and host immune responses. Because of biofilms, current therapies are not effective. It is important to find new antibacterial treatment strategies againstP. aeruginosa. Biofilm formation is regulated through a system called quorum sensing. Thus disrupting this system is considered a promising strategy to combat bacterial pathogenicity. It is known that quercetin inhibitsPseudomonas aeruginosabiofilm formation, but the mechanism of action is unknown. In the present study, we tried to analyse the mode of interactions of LasR with quercetin.ResultsWe used a combination of molecular docking, molecular dynamics (MD) simulations and machine learning techniques for the study of the interaction of the LasR protein ofP. aeruginosawith quercetin. We assessed the conformational changes of the interaction and analysed the molecular details of the binding of quercetin with LasR. We show that quercetin has two binding modes. One binding mode is the interaction with ligand binding domain, this interaction is not competitive and it has also been shown experimentally. The second binding mode is the interaction with the bridge, it involves conservative amino acid interactions from LBD, SLR, and DBD and it is also not competitive. Experimental studies show hydroxyl group of ring A is necessary for inhibitory activity, in our model the hydroxyl group interacts with Leu177 during the second binding mode. This could explain the molecular mechanism of how quercetin inhibits LasR protein.ConclusionsThis study may offer insights on how quercetin inhibits quorum sensing circuitry by interacting with transcriptional regulator LasR. The capability of having two binding modes may explain why quercetin is effective at inhibiting biofilm formation and virulence gene expression.List of abbreviationsPDBProtein data bankMDMolecular DynamicsPCAPrincipal Component AnalysisPCPrincipal ComponentSLRShort Linker RegionBLASTBasic local alignment search toolDBIDavid-Bouldin IndexpsFpseudo-F statistic
Neural computations combine low- and high-order motion cues similarly, in dragonfly and monkey
Authors: Nitzany Eyal I. , Menda Gil , Shamble Paul S. , Golden James R. , Hu Qin , Hoy Ron R. , Victor Jonathan D. 
Published: December 2017

AbstractVisual motion analysis is fundamental to survival across the animal kingdom. In insects, our understanding of the underlying computations has centered on the Hassenstein-Reichardt motion detector, which computes two-point cross-correlation via multiplication; in mammalian cortex, it is postulated that a similar signal is computed by comparing matched squaring operations. Both of these operations are difficult to implement biophysically in a precise fashion; moreover, they fail to detect the more complex multipoint local motion cues present in the visual environment. Here, via single-unit recordings in two visual specialists, dragonfly "(Odonata)" and macaque, and via model simulations, we show that neuronal computations are not simply approximations to idealized behaviors forced by biological constraints, but rather, are signatures of a common computational strategy to capture multiple local motion cues. The similarity of motion computations at the neuronal level in the brains of two extremely dissimilar animals, with evolutionary divergence of over 700 Myr1, suggests convergence on a common computational scheme for detecting visual motion.
Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation
Authors: Frei Oleksandr , Holland Dominic , Smeland Olav B. , Shadrin Alexey A. , Fan Chun Chieh , Maeland Steffen , O’Connell Kevin S. , Wang Yunpeng , Djurovic Srdjan , Thompson Wesley K. , Andreassen Ole A. , Dale Anders M. 
Published: December 2017

ABSTRACTAccumulating evidence from genome wide association studies (GWAS) suggests an abundance of shared genetic influences among complex human traits and disorders, such as mental disorders. While current cross-trait analytical methods focus on genetic correlation between traits, we developed a novel statistical tool (MiXeR), which quantifies polygenic overlap independent of genetic correlation, using summary statistics from GWAS. MiXeR results can be presented as a Venn diagram of unique and shared polygenic components across traits. At 90% of SNP-heritability explained for each phenotype, MiXeR estimates that more than 9K variants causally influence schizophrenia, 7K influence bipolar disorder, and out of those variants 6.9K are shared between these two disorders, which have high genetic correlation. Further, MiXeR uncovers extensive polygenic overlap between schizophrenia and educational attainment. Despite a genetic correlation close to zero, these traits share more than 9K causal variants, while 3K additional variants only influence educational attainment. By considering the polygenicity, heritability and discoverability of complex phenotypes, MiXeR provides a more complete quantification of shared genetic architecture than offered by other available tools.
Deep image reconstruction from human brain activity
Authors: Shen Guohua , Horikawa Tomoyasu , Majima Kei , Kamitani Yukiyasu 
Published: December 2017

AbstractMachine learning-based analysis of human functional magnetic resonance imaging (fMRI) patterns has enabled the visualization of perceptual content. However, it has been limited to the reconstruction with low-level image bases (Miyawaki et al., 2008; Wen et al., 2016) or to the matching to exemplars (Naselaris et al., 2009; Nishimoto et al., 2011). Recent work showed that visual cortical activity can be decoded (translated) into hierarchical features of a deep neural network (DNN) for the same input image, providing a way to make use of the information from hierarchical visual features (Horikawa & Kamitani, 2017). Here, we present a novel image reconstruction method, in which the pixel values of an image are optimized to make its DNN features similar to those decoded from human brain activity at multiple layers. We found that the generated images resembled the stimulus images (both natural images and artificial shapes) and the subjective visual content during imagery. While our model was solely trained with natural images, our method successfully generalized the reconstruction to artificial shapes, indicating that our model indeed ‘reconstructs’ or ‘generates’ images from brain activity, not simply matches to exemplars. A natural image prior introduced by another deep neural network effectively rendered semantically meaningful details to reconstructions by constraining reconstructed images to be similar to natural images. Furthermore, human judgment of reconstructions suggests the effectiveness of combining multiple DNN layers to enhance visual quality of generated images. The results suggest that hierarchical visual information in the brain can be effectively combined to reconstruct perceptual and subjective images.
Isoxanthopterin: An Optically Functional Biogenic Crystal in the Eyes of Decapod Crustaceans
Authors: Palmer Benjamin A. , Hirsch Anna , Brumfeld Vlad , Aflalo Eliahu D. , Pinkas Iddo , Sagi Amir , Rozenne S. , Oron Dan , Leiserowitz Leslie , Kronik Leeor , Weiner Steve , Addadi Lia 
Published: December 2017

AbstractThe eyes of some aquatic animals form images through reflective optics. Shrimp, lobsters, crayfish and prawns possess reflecting superposition compound eyes, composed of thousands of square-faceted eye-units (ommatidia). Mirrors in the upper part of the eye (the distal mirror) reflect light collected from many ommatidia onto the underlying photosensitive elements of the retina, the rhabdoms. A second reflector, the tapetum, underlying the retina, back-scatters dispersed light onto the rhabdoms. Using microCT and cryo-SEM imaging accompanied byin situmicro-X-ray diffraction and micro-Raman spectroscopy, we investigated the hierarchical organization and materials properties of the reflective systems at high resolution and under close to physiological conditions. We show that the distal mirror consists of three or four layers of sparse plate-like nano-crystals. The tapetum is a diffuse reflector composed of hollow nanoparticles constructed from concentric lamellae of crystals. Isoxanthopterin, a pteridine analog of guanine, forms both the reflectors in the distal mirror and in the tapetum. The crystal structure of isoxanthopterin was determined from crystal structure prediction calculations and verified by comparison with experimental X-ray diffraction. The extended hydrogen bonded layers of the molecules results in an extremely high calculated refractive index in the H-bonded plane,n= 1.96, which makes isoxanthopterin crystals an ideal reflecting material. The crystal structure of isoxanthopterin, together with a detailed knowledge of the reflector superstructures, provide a rationalization of the reflective optics of the crustacean eye.SignificanceAquatic animals use reflectors in their eyes either to form images or to increase photon capture. Guanine is the most widespread molecular component of these reflectors. Here we show that crystals of isoxanthopterin, a pteridine analogue of guanine, form both the image-forming ‘distal’ mirror and the intensity-enhancing tapetum reflector in the compound eyes of some decapod crustaceans. The crystal structure of isoxanthopterin was determined, providing an explanation for why these crystals are so well suited for efficient reflection. Pteridines were previously known only as pigments and our discovery raises the question of which other organic molecules may be used to form crystals with superior reflective properties either in organisms or in artificial optical devices.
An ordered pattern of Ana2 phosphorylation by Plk4 is required for centriole assembly
Authors: McLamarrah Tiffany A. , Buster Daniel W. , Galletta Brian J. , Boese Cody J. , Ryniawec John M. , Hollingsworth Natalie A. , Byrnes Amy E. , Brownlee Christopher W. , Slep Kevin C. , Rusan Nasser M. , Rogers Gregory C. 
Published: December 2017

AbstractPolo-like kinase 4 (Plk4) initiates an early step in centriole assembly by phosphorylating Ana2/STIL, a structural component of the procentriole. Here, we show that Plk4 binding to the central coiled-coil (CC) of Ana2 is a conserved event, involving Polo-box 3 and a previously unidentified putative CC located adjacent to the kinase domain. Ana2 binding stimulates Plk4 kinase activity in vitro, and, in turn, is phosphorylated along its length. Previous studies showed that Plk4 phosphorylates the C-terminal STAN domain of Ana2/STIL, triggering binding and recruitment of the cartwheel protein Sas6 to the procentriole assembly site. However, the physiological relevance of N-terminal phosphorylation was unknown. We found that Plk4 first phosphorylates the extreme N–terminus of Ana2 which is critical for subsequent STAN domain modification. Phosphorylation of the central region then breaks the Plk4-Ana2 interaction. This phosphorylation pattern is important for centriole assembly and integrity because replacement of endogenous Ana2 with phospho-Ana2 mutants disrupts distinct steps in Ana2 function and inhibits centriole duplication.
Boosting ATM Activity Promotes Longevity in Nematodes and Mice
Authors: Qian Minxian , Liu Zuojun , Peng Linyuan , Meng Fanbiao , Tang Xiaolong , Ao Ying , Shi Lei , Zhou Mingyan , Wang Ming , Qin Baoming , Cao Xinyue , Wang Zimei , Zhou Zhongjun , Liu Baohua 
Published: December 2017

AbstractDNA damage accumulates with age1. However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that activation of ataxia-telangiectasia mutated (ATM) via low dose of chloroquine (CQ) promotes DNA damage clearance, rescues age-related metabolic shift, and extends lifespan in nematodes and mice. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies ofSirt6inAtm-/- mice extend lifespan, accompanied with restored metabolic homeostasis. In a progeria mouse model with low ATM protein level and DNA repair capacity, the treatment with CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases.
Multiple Determinants and Consequences of Cohesion Fatigue in Mammalian Cells
Authors: Sapkota Hem , Wasiak Emilia , Gorbsky Gary J. 
Published: December 2017

AbstractCells delayed in metaphase with intact mitotic spindles undergo cohesion fatigue, where sister chromatids separate asynchronously, while cells remain in M phase. Cohesion fatigue requires release of sister chromatid cohesion. However, the pathways necessary to breach sister chromatid cohesion during cohesion fatigue remain unknown. Using a regulated protein heterodimerization system to lock different cohesin interfaces at specific times in mitosis, we show that the prophase pathway of Cohesin release is not required for cohesion fatigue. By manipulating microtubule stability and Cohesin complex integrity in cell lines with varying sensitivity to cohesion fatigue, we show that rates of cohesion fatigue reflect a dynamic balance between spindle pulling forces and resistance to separation by interchromatid cohesion. Cohesion fatigue that results in complete chromatid separation may be an unrecognized but common source of chromosome instability. Here, we extend the significance of cohesion fatigue by showing that even limited delays at metaphase lead to partial centromere separation and predispose cells to chromosome missegregation.
Patterns in protein flexibility: a comparison of NMR “ensembles”, MD trajectories and crystallographic B-factors
Authors: Riga Anthony , Rivera Jasmin , Snyder David A. 
Published: December 2017

AbstractProteins are molecular machines requiring flexibility to function. Crystallographic B-factors and Molecular Dynamics (MD) simulations both provide insights into protein flexibility on an atomic scale. Nuclear Magnetic Resonance (NMR) lacks a universally accepted analog of the B-factor, however, a lack of convergence in atomic coordinates in an NMR-based structure calculation also suggests atomic mobility. This paper describes a pattern in the coordinate uncertainties of backbone heavy atoms in NMR-derived structural “ensembles” first noted in the development of FindCore2 (previously called Expanded FindCore: DA Snyder, J Grullon, YJ Huang, R Tejero, GT Montelione,Proteins: Structure, Function, and Bioinformatics82 (S2), 219–230) and demonstrates that this pattern exists in coordinate variances across MD trajectories but not in crystallographic B-factors. This either suggests that MD trajectories and NMR “ensembles” capture motional behavior of peptide bond units not captured by B-factors or indicates a deficiency common to force fields used in both NMR and MD calculations. Additionally, a comparison of Cα B-factors with Cα coordinate variability in NMR “ensembles” and MD trajectories shows that NMR-derived coordinate uncertainties measure variability in atomic positions as well as crystallographic B-factors and superimpositions of MD trajectories do.
Retrofitting heritage office buildings in the UK: a case study
Authors: Tokede Olubukola , Udawatta Nilupa , Luther Mark 
Published: December 2017

Purpose
Heritage buildings are a crucial part of the UK built sector. They perpetuate a sense of identity, prestige and community. Many heritage buildings however tend to be energy inefficient and the scope for retrofitting such buildings is paramount. Heritage buildings require ratification from planning bodies in order to undertake any alteration on the building. This tends to create a bottleneck in the retrofitting of heritage office buildings. The paper aims to discuss this issue.

Design/methodology/approach
This study utilises a case study building in Scotland to evaluate the potential for retrofitting in a UK heritage office building. Building energy simulation software is used to generate the energy data in different retrofit options. A scenario analysis on the heritage status of the building is also undertaken.

Findings
The costs, energy consumption and carbon emission levels are evaluated and compared. It was found that the differential in annual energy savings achieved, based on the proportion of capital cost to operational cost, is 14.6 per cent in the heritage building, compared to 24.6 per cent in the non-heritage building.

Originality/value
The study suggests that government and other stakeholders should seek for ways of incentivising retrofit investments in heritage buildings. This will provide an effective way of minimising the contributions of the built environment to global warming and climate change.
Operations capability, productivity and business performance
Authors: Yu Wantao , Ramanathan Ramakrishnan , Wang Xingyu , Yang Jiehui 
Published: December 2017

PurposeThe purpose of this paper is to investigate the relationships between operations capability, productivity, and business performance in the context of environmental dynamism.Design/methodology/approachA proposed conceptual framework grounded in the resource-based view (RBV) and dynamic capability view (DCV) is analyzed using archival data from 193 automakers in the UK.FindingsThe results show that operations capability, as an important dynamic capability, has a significant positive effect on productivity, which in turn leads to improved business performance. The results also suggest that productivity fully mediates the relationship between operations capability and business performance, and that environmental dynamism significantly moderates the relationship between operations capability and productivity.Practical implicationsThe research findings provide practical insights that will help managers develop operations capability to gain greater productivity and business performance in a dynamic environment.Originality/valueAddressing the two important issues of moderation (i.e. environmental dynamism) and mediation (i.e. productivity), this study makes important contributions to the field of operations management by applying the RBV and DCV.
Supply chain quality and pricing decisions under multi-manufacturer competition
Authors: Pang Jiangang , Tan Kim Hua 
Published: December 2017

PurposeIn today’s global competition, supply chain quality management is the key to a firms’ competitiveness. However, managers find that making sound quality and pricing decisions under a complex multi-echelon in the current competitive electronic commerce environment is daunting and challenging. The purpose of this paper is to examine the optimum quality strategies under different cooperative mechanisms and investigate its effects on channel members’ profits.Design/methodology/approachThis paper is a result of a China-UK collaborative research effort, involving researchers with expertise in information systems, quality management, supply chain management, pricing, and game theory models. The authors consider the quality decisions of a single product in a supply chain system that consists of a supplier and two competing manufacturers. The authors examine the optimum quality strategies under different cooperative mechanisms and investigate its effects on channel members’ profits. A modified Nerlove-Arrow model is employed to investigate the quality levels on goodwill and product sales.FindingsThe results reveal that the traditional cooperative program is not very effective in the horizontal competitive market; and each channel member may have a profit improvement when the supplier integrates with a manufacturer.Originality/valueThe authors believe that this paper will contribute to the existing body of knowledge. Moreover, the paper provides insights for managers to better manage their supply chain quality management in an information-centric context.
A comparison between structural equation modelling (SEM) and Bayesian SEM approaches on in-store behaviour
Authors: Ong Fon Sim , Khong Kok Wei , Yeoh Ken Kyid , Syuhaily Osman , Nor Othman Mohd. 
Published: December 2017

Purpose
The purpose of this paper is to examine the effects of atmospherics and affective state on shoppers’ in-store behaviour using the two approaches in structural equation modelling (SEM), i.e. Frequentist and Bayesian approaches. Shoppers’ affective state was tested for its mediating effect on in-store shopping behaviour.

Design/methodology/approach
The final sample consists of 382 respondents who were drawn from shoppers at selected apparel stores in six of the most popular shopping malls around Kuala Lumpur (Malaysia). A frequentist approach to SEM is common among researchers and offers generally an analysis of the relationships between multiple latent variables and constructs. Alternatively, the Bayesian SEM (BSEM) approach stems from the diffusion of the model’s posterior distributions using the Markov Chain Monte Carlo technique. More specifically, this technique is inherently more flexible and substantive in determining parameter estimates as compared to the more conventional, the frequentist approach to SEM.

Findings
The results show the mixed effects of atmospheric cues in retail setting on shoppers’ affective state. More specifically, the positive direct effect of atmospheric cues (music) on in-store behaviour was confirmed while other atmospheric cues (colour and store layout) were found to be fully mediated by affective state. The Bayesian approach was able to offer more distinctive results complementing the frequentist approach.

Research limitations/implications
Although the current sample size is adequate, it will be interesting to examine how a bigger sample size and different antecedents of in-store behaviour in retailing can affect the comparison between the frequentist approach in SEM and BSEM.

Practical implications
The authors found that a combination of well-designed store atmospherics and layout store can produce pleasurable effects on shoppers resulting in positive affective state. This study found that results from both frequentist and Bayesian approaches complement each other and it may be beneficial for future studies to utilise both approaches in SEM.

Originality/value
This paper met the aim to compare the approaches in SEM and the need to consider both approaches on in-store shopping environment. Overall, the authors contend that the Bayesian approach to SEM is a potentially viable alternative to frequentist SEM, especially when studies are conducted under dynamic conditions such as apparel retailing.