bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iso-propyl stilbene: A life-cycle signal?
Authors: Hapeshi Alexia , Benarroch Jonatan Mimon , Clarke David James , Waterfield Nicholas Robin 
Published: December 2018

ABSTRACTMembers of the Gram-negative bacterial genusPhotorhabdusare all highly insect pathogenic and exist in an obligate symbiosis with the entomopathogenic nematode wormHeterorhabditis. All members of the genus produce the small molecule 3,5-dihydroxy-4-isopropyl-trans-stilbene (IPS) as part of their secondary metabolism. IPS is a multi-potent compound that has antimicrobial, antifungal and anticancer activities and also plays an important role in symbiosis with the nematode. In this study we have examined the response ofPhotorhabdusitself to exogenous ectopic addition of IPS at physiologically relevant concentrations. We observed that the bacteria had a measureable phenotypic response, which included a decrease in bioluminescence and pigment production. This was reflected in changes in its transcriptomic response, in which we reveal a reduction in transcript levels of genes relating to many fundamental cellular processes, such as translation and oxidative phosphorylation. Our observations suggest that IPS plays an important role in the biology ofPhotorhabdusbacteria, fulfilling roles in quorum sensing, antibiotic-competition advantage and maintenance of the symbiotic developmental cycle.
Pandoravirus celtis illustrates the microevolution processes at work in the giant Pandoraviridae genomes
Authors: Legendre Matthieu , Alempic Jean-Marie , Philippe Nadège , Lartigue Audrey , Jeudy Sandra , Poirot Olivier , Ta Ngan Thi , Nin Sébastien , Couté Yohann , Abergel Chantal , Claverie Jean-Michel 
Published: December 2018

AbstractWith genomes of up to 2.7 Mb propagated in µm-long oblong particles and initially predicted to encode more than 2000 proteins, members of the Pandoraviridae family display the most extreme features of the known viral world. The mere existence of such giant viruses raises fundamental questions about their origin and the processes governing their evolution. A previous analysis of six newly available isolates, independently confirmed by a study including 3 others, established that the Pandoraviridae pan-genome is open, meaning that each new strain exhibits protein-coding genes not previously identified in other family members. With an average increment of about 60 proteins, the gene repertoire shows no sign of reaching a limit and remains largely coding for proteins without recognizable homologs in other viruses or cells (ORFans). To explain these results, we proposed that most new protein-coding genes were created de novo, from pre-existing non-coding regions of the G+C rich pandoravirus genomes. The comparison of the gene content of a new isolate, P. celtis, closely related (96% identical genome) to the previously described P. quercus is now used to test this hypothesis by studying genomic changes in a microevolution range. Our results confirm that the differences between these two similar gene contents mostly consist of protein-coding genes without known homologs (ORFans), with statistical signatures close to that of intergenic regions. These newborn proteins are under slight negative selection, perhaps to maintain stable folds and prevent protein aggregation pending the eventual emergence of fitness-increasing functions. Our study also unraveled several insertion events mediated by a transposase of the hAT family, 3 copies of which are found in P. celtis and are presumably active. Members of the Pandoraviridae are presently the first viruses known to encode this type of transposase.
Nanobody Detection of Standard Fluorescent Proteins Enables Multi-Target DNA-PAINT with High Resolution and Minimal Displacement Errors
Authors: Sograte-Idrissi Shama , Oleksiievets Nazar , Isbaner Sebastian , Eggert-Martinez Mariana , Enderlein Jörg , Tsukanov Roman , Opazo Felipe 
Published: December 2018

AbstractDNA-PAINT is a rapidly developing fluorescence super-resolution technique which allows for reaching spatial resolutions below 10 nm. It also enables the imaging of multiple targets in the same sample. However, using DNA-PAINT to observe cellular structures at such resolution remains challenging. Antibodies, which are commonly used for this purpose, lead to a displacement between the target protein and the reporting fluorophore of 20-25 nm, thus limiting the resolving power. Here, we used nanobodies to minimize this linkage error to ~4 nm. We demonstrate multiplexed imaging by using 3 nanobodies, each able to bind to a different family of fluorescent proteins. We couple the nanobodies with single DNA strands via a straight forward and stoichiometric chemical conjugation. Additionally, we built a versatile computer-controlled microfluidic setup to enable multiplexed DNA-PAINT in an efficient manner. As a proof of principle, we labeled and imaged proteins on mitochondria, the Golgi apparatus, and chromatin. We obtained super-resolved images of the 3 targets with 20 nm resolution, and within only 35 minutes acquisition time.
Antibody-mediated immobilization of virions in mucus
Authors: Jensen Melanie A. , Wang Ying-Ying , Lai Samuel K. , Forest M. Gregory , McKinley Scott A. 
Published: December 2018

AbstractAntibodies have been shown to hinder the movement of Herpes Simplex Virus (HSV) virions in cervicovaginal mucus (CVM), as well as other viruses in other mucus secretions. However, it has not been possible to directly observe the mechanisms underlying this phenomenon, so the nature of virion-antibody-mucin interactions remain poorly understood. In this work, we analyzed thousands of virion traces from single particle tracking experiments to explicate how antibodies must cooperate to immobilize virions for relatively long time periods. First, using a clustering analysis, we observed a clear separation between two classes of virion behavior: Freely Diffusing and Immobilized. While the proportion of Freely Diffusing virions decreased with antibody concentration, the magnitude of their diffusivity did not, implying an all-or-nothing dichotomy in the pathwise effect of the antibodies. Proceeding under the assumption that all binding events are reversible, we used a novel switch-point detection method to conclude that there are very few, if any, state-switches on the experimental time scale of twenty seconds. To understand this slow state-switching, we analyzed a recently proposed continuous-time Markov chain model for binding kinetics and virion movement. Model analysis implied that virion immobilization requires cooperation by multiple antibodies that are simultaneously bound to the virion and mucin matrix, and that there is an entanglement phenomenon that accelerates antibody-mucin binding when a virion is immobilized. In addition to developing a widely-applicable framework for analyzing multi-state particle behavior, this work substantially enhances our mechanistic understanding of how antibodies can reinforce a mucus barrier against passive invasive species.
Functional characterization of Arabidopsis ARGONAUTE 3 in reproductive tissue
Authors: Jullien Pauline E. , Grob Stefan , Marchais Antonin , Pumplin Nathan , Chevalier Clement , Otto Caroline , Schott Gregory , Voinnet Olivier 
Published: December 2018

SUMMARYArabidopsis encodes ten ARGONAUTE (AGO) effectors of RNA silencing, canonically loaded with either 21-22nt small RNAs (sRNA) to mediate post-transcriptional-gene-silencing (PTGS) or 24nt sRNAs to promote RNA-directed-DNA-methylation. Using full-locus constructs, we characterized the expression, biochemical properties, and possible modes of action of AGO3. Although AGO3 arose from a recent duplication at the AGO2 locus, their expression differs drastically, with AGO2 being expressed in both male and female gametes whereas AGO3 accumulates in aerial vascular terminations and specifically in chalazal seed integuments. Accordingly, AGO3 down-regulation alters gene expression in siliques. Similar to AGO2, AGO3 binds sRNAs with a strong 5’-adenosine bias, but unlike most Arabidopsis AGOs - AGO2 included - it binds efficiently both 24nt and 21nt sRNAs. AGO3 immunoprecipitation experiments in siliques revealed that these sRNAs mostly correspond to genes and intergenic regions. in a manner reflecting their respective accumulation from their loci-of-origin. AGO3 localizes to the cytoplasm and co-fractionates with polysomes to possibly mediate PTGS via translation inhibition.Significance statementThe regulation of gene expression by small RNAs is key for proper plant development and defense. Here, we characterize Arabidopsis AGO3 expression pattern, microRNA regulation and biochemical properties during sexual reproduction.
Human Gene Expression Variability and its Dependence on Methylation and Aging
Authors: Bashkeel Nasser , Perkins Theodore J. , Kærn Mads , Lee Jonathan M. 
Published: December 2018

AbstractBackgroundPhenotypic variability of human populations is partly the result of gene polymorphism and differential gene expression. As such, understanding the molecular basis for diversity requires identifying genes with both high and low population expression variance and identifying the mechanisms underlying their expression control. Key issues remain unanswered with respect to expression variability in human populations. The role of gene methylation as well as the contribution that age, sex and tissue-specific factors have on expression variability are not well understood.ResultsHere we used a novel method that accounts for sampling error to classify human genes based on their expression variability in normal human breast and brain tissues. We find that high expression variability is almost exclusively unimodal, indicating that variance is not the result of segregation into distinct expression states. Genes with high expression variability differ markedly between tissues and we find that genes with high population expression variability are likely to have age-, but not sex-dependent expression. Lastly, we find that methylation likely has a key role in controlling expression variability insofar as genes with low expression variability are likely to be non-methylated.ConclusionsWe conclude that gene expression variability in the human population is likely to be important in tissue development and identity, methylation, and in natural biological aging. The expression variability of a gene is an important functional characteristic of the gene itself and the classification of a gene as one with Hyper-Variability or Hypo-Variability in a human population or in a specific tissue should be useful in the identification of important genes that functionally regulate development or disease.
Neuronal Mechanisms of Strategic Cooperation
Authors: Song Ong Wei , Madlon-Kay Seth , Platt Michael L. 
Published: December 2018

SummaryHere we demonstrate that during strategic gameplay monkeys behave as if they reason recursively about other individuals’ beliefs and desires in order to predict their choices and to guide their own actions, especially the decision to cooperate. Neurons in mid superior temporal sulcus (mSTS), the putative homolog of the human temporo-parietal junction (TPJ), signal abstract non-perceptual social information, including payoffs, intentions, and outcomes, and further distinguish between social and nonsocial agents while monkeys play the game. We demonstrate for the first time that a subpopulation of these neurons selectively signals cooperatively obtained rewards. Neurons in the anterior cingulate gyrus (ACCg), an area implicated in vicarious reinforcement and empathy, do not distinguish agency and as a population carry less information about strategic variables. These findings suggest the capacity to mentalize has deep roots in the strategic social behavior of primates, and endorse mSTS as the evolutionary wellspring of these functions.
Sustaining attention for a prolonged period of time increases temporal variability in cortical responses
Authors: Reteig Leon C. , van den Brink Ruud L. , Prinssen Sam , Cohen Michael X , Slagter Heleen A. 
Published: December 2018

AbstractOur ability to stay focused is limited: prolonged performance of a task typically results in mental fatigue and decrements in performance over time. This so-called vigilance decrement has been attributed to depletion of attentional resources, though other factors such as reductions in motivation likely also play a role. In this study, we examined three EEG markers of attentional control, to elucidate which stage of attentional processing is most affected by time-on-task and motivation. To elicit the vigilance decrement, participants performed a sustained attention task for 80 minutes without breaks. After 60 minutes, participants were motivated by an unexpected monetary incentive to increase performance in the final 20 minutes. We found that task performance and self-reported motivation declined rapidly, reaching a stable levels well before the motivation manipulation was introduced. Thereafter, motivation increased back up to the initial level, and remained there for the final 20 minutes. While task performance also increased, it did not return to the initial level, and fell to the lowest level overall during the final 10 minutes. This pattern of performance changes was mirrored by the trial-to-trial consistency of the phase of theta (3–7 Hz) oscillations, an index of the variability in timing of the neural response to the stimulus. As task performance decreased, temporal variability increased, suggesting that attentional stability is crucial for sustained attention performance. The effects of attention on our two other EEG measures—early P1/N1 event-related potentials and pre-stimulus alpha (9–14 Hz) power—did not change with time-on-task or motivation. In sum, these findings show that the vigilance decrement is accompanied by a decline in only some facets of attentional control, which cannot be fully brought back online by increases in motivation. The vigilance decrement might thus not occur due to a single cause, but is likely multifactorial in origin.
Diversification of retinoblastoma protein function associated with cis and trans adaptations
Authors: Mouawad Rima , Prasad Jaideep , Thorley Dominic , Himadewi Pamela , Kadiyala Dhruva , Wilson Nathan , Kapranov Philipp , Arnosti David N. 
Published: December 2018

AbstractRetinoblastoma proteins are eukaryotic transcriptional co-repressors that play central roles in cell cycle control, among other functions. Although most metazoan genomes encode a single retinoblastoma protein, gene duplications have occurred at least twice: in the vertebrate lineage, leading to three genes encoding Rb, p107, and p130, while separately in the Drosophila lineage an ancestral Rbf1 gene and a derived Rbf2 gene. Structurally, Rbf1 resembles p107 and p130 most closely, and mutation of the gene is lethal, while Rbf2 is more divergent, and is not essential for development. Rbf1 has been demonstrated to be a potent repressor of canonical cell-cycle promoters, unlike Rbf2. The retention of Rbf2 over 60 million years in the entire Drosophila lineage points to essential functions, however. We show here that Rbf2 regulates a broad set of cell growth control related genes, and can antagonize Rbf1 on specific sets of promoters. Rbf2 null mutants exhibit abnormal development of the female reproductive tract, with reduced egg laying, while heterozygous null mutants exhibit an increased rate of egg deposition, suggesting that the normal function of this protein is critical for optimal control of fertility. The structural alterations found in conserved regions of the Rbf2 gene suggest that this gene was sub- or neofunctionalized to develop specific regulatory specificity and activity. We define cis regulatory features of Rbf2 target genes that allow preferential repression by this protein, indicating that it is not merely a weaker version of the ancestral protein. The specialization of retinoblastoma function in Drosophila may reflect a parallel evolution found in vertebrates, and raises the possibility that cell growth control is equally important to cell cycle function for this conserved family of transcriptional corepressors.
Does Big N matter for audit quality? Evidence from Japan
Authors: Semba Hu Dan , Kato Ryo 
Published: December 2018

PurposeThere has been growing concern worldwide regarding audit quality in Japan after the Kanebo and Olympus accounting scandals. The purpose of this paper is to examine the Japanese audit market from 2001 to 2011 to determine whether audit quality differs between Big N and Non-Big N audit firms and whether this difference, if existed, changed during 2007 when the number of big audit firms declined from four to three and the requirements of audit quality became more rigorous.Design/methodology/approachThis study employs a sample of Japanese listed firms from fiscal year 2001 to 2011. Five proxy variables for audit quality are used and the data are analyzed using the propensity score matching method.FindingsThe authors show that irrespective of their size, all audit firms in Japan provide the same quality of service, when controlling for client characteristics including keiretsu, foreign sales ratio and bankruptcy risk measured in Japan. Additionally, the results suggest that although only three major audit firms remain in the Japanese audit market after the dissolution of PricewaterhouseCooper’s Chuo-Aoyama firm in 2007, the audit quality difference between Big N and Non-Big N remained unchanged before and after 2007.Originality/valueThe study contributes to the lack of existing empirical evidence on audit quality in Japan, a country characterized with low audit litigation risk and more emphasis on auditor reputation, given the influence of the notable change in Japanese audit market competition from Big 4 to Big 3. The study’s research design contributes to the extant literature by using multiple proxies of audit quality.
Numerical simulation of EWOD on a printed circuit board for cleanroom-less digital fluidic manufacturing applications
Authors: Vafaie Reza Hadjiaghaie , Dehganpour Hossein , Moradpour Abolfazl 
Published: December 2018

Purpose
Digital microfluidic devices have been demonstrated to have great potential for a wide range of applications. These devices need expensive photolithography process and clean room facilities, while printed circuit board (PCB) technology provides high configurability and at low cost. This study aims to investigate the mechanism of electrowetting-on-a-dielectric (EWOD) on PCB by solving the multiphysics interaction between fluid droplet and electric field. The performance of system will be improved by inducing an efficient electric field inside the droplet.

Design/methodology/approach
To induce an electric field inside the droplet on a PCB and change the initial contact angle, the mechanism of EWOD is studied based on energy minimization method and a set of simulations are carried out by considering multiphysics interaction between the fluid droplet and external electric field. The performance of EWOD on a PCB system is investigated using different electrode structures.

Findings
Surface tension plays an efficient role in smaller sizes and can be used to move and control a fluid droplet on a surface by changing the interfacial surface tension. EWOD on a PCB system is studied. and it revealed that any change in electric field affects the droplet contact angle and as a result droplet deformation and movement. The electrode pattern is an important parameter which could change the electric potential distribution inside the droplet. Array of electrodes with square, zigzag interdigitated and crescent shapes are studied to enhance the EWOD force on a PCB substrate. Based on the results, the radial shape of the crescent electrodes keeps almost the same actuated contact line, applies uniform force on the droplet periphery and prevents the droplet from large deformation. A droplet velocity of 0.6 mm/s is achieved by exciting the crescent electrodes at 315 V. Furthermore, the behavior of system is characterized for process parameters such as actuation voltage, dielectric constant of insulator layer, fluidic material properties and the resultant velocity and contact angle. The study of contact angle distribution and droplet motion revealed that it is helpful to generate EWOD mechanism on a PCB which does not need more complicated fabrication processes.

Originality/value
The ability to handle and manipulate the droplets is very important for chemistry on-chip analysis such as immunoassay chips. Furthermore, a PCB-based electrowetting-on-dielectric device is of high interest because it does not need cleanroom facilities and avoids additional high-cost fabrication processes. In the present research, the EWOD mechanism is studied on a PCB by using different electrode patterns.
Numerical study of Carreau nanofluid flow past vertical plate with the Cattaneo–Christov heat flux model
Authors: B. Vasu , Ray Atul Kumar 
Published: December 2018

PurposeTo achieve material-invariant formulation for heat transfer of Carreau nanofluid, the effect of Cattaneo–Christov heat flux is studied on a natural convective flow of Carreau nanofluid past a vertical plate with the periodic variations of surface temperature and the concentration of species. Buongiorno model is considered for nanofluid transport, which includes the relative slip mechanisms, Brownian motion and thermophoresis.Design/methodology/approachThe governing equations are non-dimensionalized using suitable transformations, further reduced to non-similar form using stream function formulation and solved by local non-similarity method with homotopy analysis method. The numerical computations are validated and verified by comparing with earlier published results and are found to be in good agreement.FindingsThe effects of varying the physical parameters such as Prandtl number, Schmidt number, Weissenberg number, thermophoresis parameter, Brownian motion parameter and buoyancy ratio parameter on velocity, temperature and species concentration are discussed and presented through graphs. The results explored that the velocity of shear thinning fluid is raised by increasing the Weissenberg number, while contrary response is seen for the shear thickening fluid. It is also found that heat transfer in Cattaneo–Christov heat conduction model is less than that in Fourier’s heat conduction model. Furthermore, the temperature and thermal boundary layer thickness expand with the increase in thermophoresis and Brownian motion parameter, whereas nanoparticle volume fraction increases with increase in thermophoresis parameter, but reverse trend is observed with increase in Brownian motion parameter.Originality/valueThe present investigation is relatively original as very little research has been reported on Carreau nanofluids under the effect of Cattaneo–Christov heat flux model.