bluuebunny/crossref_metadata_2025 huggingface dataset:
Functions of heat shock transcription factors involved in response to photooxidative stresses inArabidopsis
Authors: Yabuta Yukinori
Published: April 2016

Because plants are continually exposed to various environmental stresses, they possess numerous transcription factors that regulate metabolism to adapt and acclimate to those conditions. To clarify the gene regulation systems activated in response to photooxidative stress, we isolated 76 high light and heat shock stress-inducible genes, including heat shock transcription factor (Hsf) A2 from Arabidopsis. Unlike yeast or animals, more than 20 genes encoding putative Hsfs are present in the genomes of higher plants, and they are categorized into three classes based on their structural characterization. However, the multiplicity of Hsfs in plants remains unknown. Furthermore, the individual functions of Hsfs are also largely unknown because of their genetic redundancy. Recently, the developments of T-DNA insertion knockout mutant lines and chimeric repressor gene-silencing technology have provided effective tools for exploring the individual functions of Hsfs. This review describes the current knowledge on the individual functions and activation mechanisms of Hsfs.
Community–environment interactions explain octopus-catshark spatial overlap
Authors: Puerta Patricia , Hunsicker Mary E. , Hidalgo Manuel , Reglero Patricia , Ciannelli Lorenzo , Esteban Antonio , González María , Quetglas Antoni
Published: April 2016

The octopus Eledone cirrhosa and the catshark Scyliorhinus canicula present the same feeding habits and distributional preferences in the Mediterranean Sea. We explore patterns of spatial overlap between these species to address coexistence and infer possible competition from spatial patterns in the western Mediterranean Sea. A spatially explicit modelling approach revealed that spatial overlap mainly responded to the distribution of shared resources, where coexistence is allowed by different ecological processes. Catshark (k-strategy) was highly abundant and widely distributed. However, the fluctuating population dynamics of octopus (r-strategy) explained the variations in spatial patterns of overlap. Spatial structuring across the study area was observed both in population distributions and in species interactions (coexistence or exclusion). Areas with high resources in terms of specific prey items (Catalan Sea) or alternative supplies, such as niche opportunities and ecosystem functions defined by community diversity (Balearic Islands), favoured species coexistence. Sea surface temperature showed opposite effects on overlap in northern and southern regions of the study area, which were not related to differences in species sensitivity. We suggest a surface trophic link, where different phytoplankton communities at each region might have opposite responses to temperature. This triggers contrasting mechanisms of food transfer to deeper benthic communities that subsequently facilitates species overlap. Characterizing how benthic and pelagic seascape properties shape species interactions across space and time is pivotal to properly address community spatial dynamics and move towards ecosystem-based management for sustainable fisheries and conservation planning.
Effect of Mechanical Ventilation Mode Type on Intra- and Postoperative Blood Loss in Patients Undergoing Posterior Lumbar Interbody Fusion Surgery
Authors: Kang Woon-Seok , Oh Chung-Sik , Kwon Won-Kyoung , Rhee Ka Young , Lee Yun Gu , Kim Tae-Hoon , Lee Suk Ha , Kim Seong-Hyop
Published: April 2016

AbstractAbstract

Fifty-six patients having spine surgery were randomized. Intraoperative blood loss was 130 ml less with pressure- than with volume-controlled ventilation.

Background

The aim of study was to evaluate the effect of mechanical ventilation mode type, pressure-controlled ventilation (PCV), or volume-controlled ventilation (VCV) on intra- and postoperative surgical bleeding in patients undergoing posterior lumbar interbody fusion (PLIF) surgery.

Methods

This was a prospective, randomized, single-blinded, and parallel study that included 56 patients undergoing PLIF and who were mechanically ventilated using PCV or VCV. A permuted block randomization was used with a computer-generated list. The hemodynamic and respiratory parameters were measured after anesthesia induction in supine position, 5 min after patients were changed from supine to prone position, at the time of skin closure, and 5 min after the patients were changed from prone to supine position. The amount of intraoperative surgical bleeding, fluid administration, urine output, and transfusion requirement were measured at the end of surgery. The amount of postoperative bleeding and transfusion requirement were recorded every 24 h for 72 h.

Results

The primary outcome was the amount of intraoperative surgical bleeding, and 56 patients were analyzed. The amount of intraoperative surgical bleeding was significantly less in the PCV group than that in the VCV group (median, 253.0 [interquartile range, 179.0 to 316.5] ml in PCV group vs. 382.5 [328.0 to 489.5] ml in VCV group; P < 0.001). Comparing other parameters between groups, only peak inspiratory pressure at each measurement point in PCV group was significantly lower than that in VCV group. No harmful events were recorded.

Conclusion

Intraoperative PCV decreased intraoperative surgical bleeding in patients undergoing PLIF, which may be related to lower intraoperative peak inspiratory pressure.
Tips and nodes are complementary not competing approaches to the calibration of molecular clocks
Authors: O'Reilly Joseph E. , Donoghue Philip C. J.
Published: April 2016

Molecular clock methodology provides the best means of establishing evolutionary timescales, the accuracy and precision of which remain reliant on calibration, traditionally based on fossil constraints on clade (node) ages. Tip calibration has been developed to obviate undesirable aspects of node calibration, including the need for maximum age constraints that are invariably very difficult to justify. Instead, tip calibration incorporates fossil species as dated tips alongside living relatives, potentially improving the accuracy and precision of divergence time estimates. We demonstrate that tip calibration yields node calibrations that violate fossil evidence, contributing to unjustifiably young and ancient age estimates, less precise and (presumably) accurate than conventional node calibration. However, we go on to show that node and tip calibrations are complementary, producing meaningful age estimates, with node minima enforcing realistic ages and fossil tips interacting with node calibrations to objectively define maximum age constraints on clade ages. Together, tip and node calibrations may yield evolutionary timescales that are better justified, more precise and accurate than either calibration strategy can achieve alone.
Energy scaling and reduction in controlling complex networks
Authors: Chen Yu-Zhong , Wang Le-Zhi , Wang Wen-Xu , Lai Ying-Cheng
Published: April 2016

Recent works revealed that the energy required to control a complex network depends on the number of driving signals and the energy distribution follows an algebraic scaling law. If one implements control using a small number of drivers, e.g. as determined by the structural controllability theory, there is a high probability that the energy will diverge. We develop a physical theory to explain the scaling behaviour through identification of the fundamental structural elements, the longest control chains (LCCs), that dominate the control energy. Based on the LCCs, we articulate a strategy to drastically reduce the control energy (e.g. in a large number of real-world networks). Owing to their
structural
nature, the LCCs may shed light on energy issues associated with control of nonlinear dynamical networks.
The detection of flaws in austenitic welds using the decomposition of the time-reversal operator
Authors: Cunningham Laura J. , Mulholland Anthony J. , Tant Katherine M. M. , Gachagan Anthony , Harvey Gerry , Bird Colin
Published: April 2016

The non-destructive testing of austenitic welds using ultrasound plays an important role in the assessment of the structural integrity of safety critical structures. The internal microstructure of these welds is highly scattering and can lead to the obscuration of defects when investigated by traditional imaging algorithms. This paper proposes an alternative objective method for the detection of flaws embedded in austenitic welds based on the singular value decomposition of the time-frequency domain response matrices. The distribution of the singular values is examined in the cases where a flaw exists and where there is no flaw present. A lower threshold on the singular values, specific to austenitic welds, is derived which, when exceeded, indicates the presence of a flaw. The detection criterion is successfully implemented on both synthetic and experimental data. The datasets arising from welds containing a flaw are further interrogated using the decomposition of the time-reversal operator (DORT) method and the total focusing method (TFM), and it is shown that images constructed via the DORT algorithm typically exhibit a higher signal-to-noise ratio than those constructed by the TFM algorithm.
Ten Simple Rules for Taking Advantage of git and GitHub
Authors: Perez-Riverol Yasset , Gatto Laurent , Wang Rui , Sachsenberg Timo , Uszkoreit Julian , Veiga Leprevost Felipe da , Fufezan Christian , Ternent Tobias , Eglen Stephen J. , Katz Daniel S. , Pollard Tom J , Konovalov Alexander , Flight Robert M. , Blin Kai , Vizcaino Juan Antonio
Published: April 2016

A ‘Ten Simple Rules’ guide to git and GitHub. We describe and provide examples on how to use these software to track projects, as users, teams and organizations. We document collaborative development using branching and forking, interaction between collaborators using issues and continuous integration and automation using, for example, Travis CI and codevoc. We also describe dissemination and social aspects of GitHub such as GitHub pages, following and watching repositories, and give advice on how to make code citable.
On the (un-)predictability of a large intragenic fitness landscape
Authors: Bank Claudia , Matuszewski Sebastian , Hietpas Ryan T. , Jensen Jeffrey D.
Published: April 2016

The study of fitness landscapes, which aims at mapping genotypes to fitness, is receiving ever-increasing attention. Novel experimental approaches combined with NGS methods enable accurate and extensive studies of the fitness effects of mutations – allowing us to test theoretical predictions and improve our understanding of the shape of the true underlying fitness landscape, and its implications for the predictability and repeatability of evolution.

Here, we present a uniquely large multi-allelic fitness landscape comprised of 640 engineered mutants that represent all possible combinations of 13 amino-acid changing mutations at six sites in the heat-shock protein Hsp90 inSaccharomyces cerevisiaeunder elevated salinity. Despite a prevalent pattern of negative epistasis in the landscape, we find that the global fitness peak is reached via four positively epistatic mutations. Combining traditional and extending recently proposed theoretical and statistical approaches, we quantify features of the global multi-allelic fitness landscape. Using subsets of the data, we demonstrate that extrapolation beyond a known part of the landscape is difficult owing to both local ruggedness and amino-acid specific epistatic hotspots, and that inference is additionally confounded by the non-random choice of mutations for experimental fitness landscapes.

Author Summary

The study of fitness landscapes is fundamentally concerned with understanding the relative roles of stochastic and deterministic processes in adaptive evolution. Here, the authors present a uniquely large and complete multi-allelic intragenic fitness landscape of 640 systematically engineered mutations in yeast Hsp90. Using a combination of traditional and recently proposed theoretical approaches, they study the accessibility of the global fitness peak, and the potential for predictability of the fitness landscape topography. They report local ruggedness of the landscape and the existence of epistatic hotspot mutations, which together make extrapolation and hence predictability inherently difficult, if mutation-specific information is not considered.
Salt Effects on the Thermodynamics of a Frameshifting RNA Pseudoknot under Tension
Authors: Hori Naoto , Denesyuk Natalia A. , Thirumalai D.
Published: April 2016

Because of the potential link between -1 programmed ribosomal frameshifting and response of a pseudoknot (PK) RNA to force, a number of single molecule pulling experiments have been performed on PKs to decipher the mechanism of programmed ribosomal frameshifting. Motivated in part by these experiments, we performed simulations using a coarse-grained model of RNA to describe the response of a PK over a range of mechanical forces (fs) and monovalent salt concentrations (Cs). The coarse-grained simulations quantitatively reproduce the multistep thermal melting observed in experiments, thus validating our model. The free energy changes obtained in simulations are in excellent agreement with experiments. By varyingfandC, we calculated the phase diagram that shows a sequence of structural transitions, populating distinct intermediate states. AsfandCare changed, the stem-loop tertiary interactions rupture first, followed by unfolding of the 3’-end hairpin (I⇌F). Finally, the 5’-end hairpin unravels, producing an extended state (E⇌I). A theoretical analysis of the phase boundaries shows that the critical force for rupture scales as (logCm)αwithα= 1 (0.5) for E⇌I (I⇌F) transition. This relation is used to obtain the preferential ion-RNA interaction coefficient, which can be quantitatively measured in single-molecule experiments, as done previously for DNA hairpins. A by-product of our work is the suggestion that the frameshift efficiency is likely determined by the stability of the 5’ end hairpin that the ribosome first encounters during translation.
A model of compound heterozygous, loss-of-function alleles is broadly consistent with observations from complex-disease GWAS datasets
Authors: Sanjak Jaleal S. , Long Anthony D. , Thornton Kevin R.
Published: April 2016

The genetic component of complex disease risk in humans remains largely unexplained. A corollary is that the allelic spectrum of genetic variants contributing to complex disease risk is unknown. Theoretical models that relate population genetic processes to the maintenance of genetic variation for quantitative traits may suggest profitable avenues for future experimental design. Here we use forward simulation to model a genomic region evolving under a balance between recurrent deleterious mutation and Gaussian stabilizing selection. We consider multiple genetic and demographic models, and several different methods for identifying genomic regions harboring variants associated with complex disease risk. We demonstrate that the model of gene action, relating genotype to phenotype, has a qualitative effect on several relevant aspects of the population genetic architecture of a complex trait. In particular, the genetic model impacts genetic variance component partitioning across the allele frequency spectrum and the power of statistical tests. Models with partial recessivity closely match the minor allele frequency distribution of significant hits from empirical genome-wide association studies without requiring homozygous effect-sizes to be small. We highlight a particular gene-based model of incomplete recessivity that is appealing from first principles. Under that model, deleterious mutations in a genomic region partially fail to complement one another. This model of gene-based recessivity predicts the empirically observed inconsistency between twin and SNP based estimated of dominance heritability. Furthermore, this model predicts considerable levels of unexplained variance associated with intralocus epistasis. Our results suggest a need for improved statistical tools for region based genetic association and heritability estimation.

Author Summary

Gene action determines how mutations affect phenotype. When placed in an evolutionary context, the details of the genotype-to-phenotype model can impact the maintenance of genetic variation for complex traits. Likewise, non-equilibrium demographic history may affect patterns of genetic variation. Here, we explore the impact of genetic model and population growth on distribution of genetic variance across the allele frequency spectrum underlying risk for a complex disease. Using forward-in-time population genetic simulations, we show that the genetic model has important impacts on the composition of variation for complex disease risk in a population. We explicitly simulate genome-wide association studies (GWAS) and perform heritability estimation on population samples. A particular model of gene-based partial recessivity, based on allelic non-complementation, aligns well with empirical results. This model is congruent with the dominance variance estimates from both SNPs and twins, and the minor allele frequency distribution of GWAS hits.
Evidence of a recombination rate valley in human regulatory domains
Authors: Liu Yaping , Sarkar Abhishek , Kellis Manolis
Published: April 2016

Human recombination rate varies greatly, but the forces shaping it remain incompletely understood. Here, we study the relationship between recombination rate and gene-regulatory domains defined by a gene and its linked control elements. We define these links using methylation quantitative trait loci (meQTLs), expression quantitative trait loci (eQTLs), chromatin conformation, and correlated activity across cell types. Each link type shows a “recombination valley” of significantly-reduced recombination rate compared to control regions, indicating preferential co-inheritance of genes and linked regulatory elements as a single unit. This recombination valley is most pronounced for gene-regulatory domains of early embryonic developmental genes, housekeeping genes, and constitutive regulatory elements, which are known to show increased evolutionary constraint across species. Recombination valleys show increased DNA methylation, reduced double-stranded break initiation, and increased repair efficiency, specifically in the lineage leading to the germ line, providing a potential molecular mechanism facilitating their maintenance by exclusion of recombination events.
A simple offspring-to-mother size ratio predicts post-reproductive lifespan
Authors: Maliha George , Murphy Coleen T.
Published: April 2016

Why do many animals live well beyond their reproductive period? This seems counter to the theory that the fraction of life spent reproducing should be maximized in order to maximize the number of offspring produced in each generation. To resolve this paradox, hypotheses have been developed that evoke parental or grandparental care as reasons for post-reproductive life (e.g., the Mother and Grandmother Hypotheses). However, these hypotheses fail to explain the presence of post-reproductive life in organisms that do not care for their young, such asCaenorhabditis elegans. Here we show that a candidate proxy of the stress of childbirth explains a large portion of the variance in post-reproductive lifespans across many species. A remarkably simple metric, the “offspring ratio” (ratio of the size or weight of offspring to that of the mother) explained 77% of the variance of the post-reproductive lifespan in a sample drawn from widely dispersed taxa. Our results suggest that the stress of childbirth is an important and conserved determinant of post-reproductive lifespan. Thus, long post-reproductive lifespan may simply be a byproduct of the somatic health required for reproduction of large progeny, regardless of parental care.
k-BOOM: A Bayesian approach to ontology structure inference, with applications in disease ontology construction
Authors: Mungall Christopher J. , Koehler Sebastian , Robinson Peter , Holmes Ian , Haendel Melissa
Published: April 2016

One strategy for building ontologies covering domains such as disease or anatomy is to weave together existing knowledge sources (databases, vocabularies and ontologies) into single cohesive whole. A first step in this process is to generatemappingsbetween the elements of these different sources. There are a number of well-known techniques for generating mappings (also known asontology alignemnt), both manual and automatic[7]. Sometimes mappings are seen as an end in themselves, with the sources remaining in a loosely connected state. However, if we want to take the next step and use the mappings to integrate the different sources into a cohesive reference ontology, then we need to translate the mappings into precise logical relationships. This will allow us to safely merge equivalent concepts, creating a unified ontology. This translation is a non-trivial step, as each mapping can be interpreted as multiple different logical relationships, with each interpretation affecting the likelihood of the others. There is a lack of automated methods to assist with this last step; this resolution is typically performed by expert ontologists.

Here we describe an ontology construction technique that takes two or more ontologies linked by hypothetical axioms, and estimates the most likely unified logical ontology. Hypothetical axioms can themselves be derived from semantically loose mappings. The method combines deductive reasoning and probabilistic inference and is called Bayesian OWL Ontology Merging (BOOM). We describe a special form k-BOOM that works by factorizing the probabilistic ontology intoksubmodules. We also briefly describe a supplemental lexical and knowledge-based technique for generating a set of hypothetical axioms from loose mappings.

We are currently using this technique to build a merged disease ontology (Monarch Disease Ontology; MonDO) that unifies a broad range of vocabularies into a consistent and coherent whole.
Enrichment of long DNA fragments from mixed samples for Nanopore sequencing
Authors: Eckert SE , Chan JZ-M , Houniet Darren ,   the PATHSEEK consortium, Breuer J , Speight G
Published: April 2016

Whole-genome sequencing of pathogenic organisms directly from clinical samples combines detection and genotyping in one step. This can speed up diagnosis, especially for slow-growing organisms likeMycobacterium tuberculosis (Mtb), which need considerable time to grow in subculture, and can provide vital information for effective personalised treatment. Within the PATHSEEK project, we have developed a bait-capture approach to selectively enrich DNA/RNA from specific bacterial and viral pathogens present in clinical samples. Here, we present a variation of the method that allows enrichment of large fragments of target DNA for sequencing on an Oxford Nanopore MinIONTMsequencer. We enriched and sequenced cDNA from Influenza A (FluA), genomic DNA (gDNA) from human cytomegalovirus (CMV) and from two strains ofMtb, and present an evaluation of the method together with analysis of the sequencing results from a MinIONTMand an Illumina MiSeq sequencer. While unenriched FluA and CMV samples had no reads matching the target organism due to the high background of DNA from host cell lines, enriched samples had 56.7% and 90.9% on-target reads respectively for the best quality Nanopore reads.
Emergence of increased frequency and severity of multiple infections by viruses due to spatial clustering of hosts
Authors: Taylor Bradford P , Penington Catherine J , Weitz Joshua S.
Published: April 2016

Multiple virus particles can infect a target host cell. Such multiple infections (MIs) have significant and varied ecological and evolutionary consequences for both virus and host populations. Yet, the in situ rates and drivers of MIs in virusmicrobe systems remain largely unknown. Here, we develop an individual-based model (IBM) of virus-microbe dynamics to probe how spatial interactions drive the frequency and nature of MIs. In our IBMs, we identify increasingly spatially correlated clusters of viruses given sufficient decreases viral movement. We also identify increasingly spatially correlated clusters of viruses and clusters of hosts given sufficient increases in viral infectivity. The emergence of clusters is associated with an increase in multiply infected hosts as compared to expectations from an analogous mean-field model. We also observe longtails in the distribution of the multiplicity of infection (MOI) in contrast to mean-field expectations that such events are exponentially rare. We show that increases in both the frequency and severity of MIs occur when viruses invade a cluster of uninfected microbes. We contend that population-scale enhancement of MI arises from an aggregate of invasion dynamics over a distribution of microbe cluster sizes. Our work highlights the need to consider spatially explicit interactions as a potentially key driver underlying the ecology and evolution of virus-microbe communities.
A comparative analysis of 5-azacytidine and zebularine induced DNA demethylation
Authors: Griffin Patrick T. , Niederhuth Chad E. , Schmitz Robert J.
Published: April 2016

The non-methylable cytosine analogs, 5-azacytidine and zebularine, are widely used to inhibit DNA methyltransferase activity and reduce genomic DNA methylation. In this study, whole-genome bisulfite sequencing is used to construct maps of DNA methylation with single base pair resolution inArabidopsis thalianaseedlings treated with each demethylating agent. We find that both inhibitor treatments result in nearly indistinguishable patterns of genome-wide DNA methylation and that 5-azacytidine had a slightly greater demethylating effect across the genome at higher concentrations. Transcriptome analyses revealed a substantial number of up-regulated genes, with an overrepresentation of transposable element genes, in particular CACTA-like elements. This demonstrates that chemical demethylating agents have a disproportionately large effect on loci that are otherwise silenced by DNA methylation.
C4photosynthesis and climate through the lens of optimality
Authors: Zhou Haoran , Helliker Brent R. , Akçay Erol
Published: April 2016

CO2, temperature, water availability and light intensity were all potential selective pressures to propel the initial evolution and global expansion of C4photosynthesis over the last 30 million years. To tease apart how the primary selective pressures varied along this evolutionary trajectory, we coupled photosynthesis and hydraulics models while optimizing photosynthesis over stomatal resistance and leaf/fine-root allocation. We further examined the importance of resource (e.g. nitrogen) reallocation from the dark to the light reactions during and after the initial formation of C4syndrome. We show here that the primary selective pressures—all acting upon photorespiration in C3progenitors—changed through the course of C4evolution. The higher stomatal resistance and leaf-to-root allocation ratio enabled by the C4carbon-concentrating mechanism led to a C4advantage without any change in hydraulic properties, but selection on nitrogen reallocation varied. Water limitation was the primary driver for the initial evolution of C425-32 million years ago, and could positively select for C4evolution with atmospheric CO2as high as 600 ppm. Under these high CO2conditions, nitrogen reallocation was necessary. Low CO2and light intensity, but not nitrogen reallocation, were the primary drivers during the global radiation of C45-10 MYA. Finally, our results suggest that identifying the predominate selective pressures at the time C4first evolved within a lineage should help explain current biogeographical distributions.

Statement of authorship:

HZ, BH and EA conceptualized the study. HZ and EA built the model, HZ and BH put the idea in a general evolutionary context, HZ performed the modeling work and analyzed output data. HZ wrote the first draft, BH and EA contributed substantially to revisions.

Significance Statement

C4photosynthesis pathway had evolved more than 60 times independently across the terrestrial plants through mid-Oligocene (~30 MYA) and diversified at late Miocene (5 to 10 MYA). We use an optimal physiology model to examine the primary selective pressures along the evolutionary history. Water limitation was the primary driver for C4evolution from the initial evolutionary events 25-32 MYA until CO2became low enough to, along with light intensity, drive the global radiation of C45-10 MYA. This modeling framework can be used to investigate evolution of other physiological traits (e.g. N reallocation, hydraulics) after the initial formation of C4syndrome, which contributed to further increasing productivity of C4in historical and current environmental conditions.
plasmidSPAdes: Assembling Plasmids from Whole Genome Sequencing Data
Authors: Antipov Dmitry , Hartwick Nolan , Shen Max , Raiko Mikhail , Lapidus Alla , Pevzner Pavel A.
Published: April 2016

Motivation

Plasmids are stably maintained extra-chromosomal genetic elements that replicate independently from the host cell’s chromosomes. Although plasmids harbor biomedically important genes, (such as genes involved in virulence and antibiotics resistance), there is a shortage of specialized software tools for extracting and assembling plasmid data from whole genome sequencing projects.

Results

We present the plasmidSPAdes algorithm and software tool for assembling plasmids from whole genome sequencing data and benchmark its performance on a diverse set of bacterial genomes.

Availability and implementation

PLASMIDSPADESis publicly available athttp://spades.bioinf.spbau.ru/plasmidSPAdes/

Contact

d.antipov@spbu.ru
Time-resolved dual RNA-Seq reveals extensive rewiring of lung epithelial and pneumococcal transcriptomes during early infection
Authors: Aprianto Rieza , Slager Jelle , Holsappel Siger , Veening Jan-Willem
Published: April 2016

Streptococcus pneumoniae(pneumococcus) is the main etiological agent of pneumonia. Pneumococcal pneumonia is initiated by bacterial adherence to lung epithelial cells. Infection to the epithelium is a disruptive interspecies interaction involving numerous transcription-mediated processes. Revealing transcriptional changes may provide valuable insights into pneumococcal disease. Dual RNA-Seq allows simultaneous monitoring of the transcriptomes of both host and pathogen. Here, we developed a time-resolved infection model of human lung alveolar epithelial cells byS. pneumoniaeand assessed transcriptome changes by dual RNA-Seq. Our data provide new insights into host-microbe interactions and show that the epithelial glutathione-detoxification pathway is activated by bacterial presence. We observed that adherent pneumococci, not free-floating bacteria, access host-associated carbohydrates and repress innate immune responses. In conclusion, we provide a dynamic dual-transcriptomics overview of early pneumococcal infection with easy online access (http://dualrnaseq.molgenrug.nl). Further database exploration may expand our understanding of epithelial-pneumococcal interaction, leading to novel antimicrobial strategies.

Graphical Abstract
Allele Surfing Promotes Microbial Adaptation from Standing Variation
Authors: Gralka Matti , Stiewe Fabian , Farrell Fred , Möebius Wolfram , Waclaw Bartek , Hallatschek Oskar
Published: April 2016

The coupling of ecology and evolution during range expansions enables mutations to establish at expanding range margins and reach high frequencies. This phenomenon, called allele surfing, is thought to have caused revolutions in the gene pool of many species, most evidently in microbial communities. It has remained unclear, however, under which conditions allele surfing promotes or hinders adaptation. Here, using microbial experiments and simulations, we show that, starting with standing adaptive variation, range expansions generate a larger increase in mean fitness than spatially uniform population expansions. The adaptation gain results from ‘soft’ selective sweeps emerging from surfing beneficial mutations. The rate of these surfing events is shown to sensitively depend on the strength of genetic drift, which varies among strains and environmental conditions. More generally, allele surfing promotes the rate of adaptation per biomass produced, which could help developing biofilms and other resource-limited populations to cope with environmental challenges.
Interactions between pluripotency factors specifycis-regulation in embryonic stem cells
Authors: Fiore Chris , Cohen Barak A.
Published: April 2016

We investigated how interactions between pluripotency transcription factors (TFs) affectcis-regulation. We created hundreds of syntheticcis-regulatory elements (CREs) comprised of combinations of binding sites for pluripotency TFs and measured their expression in mouse embryonic stem (ES) cells. A thermodynamic model that incorporates interactions between TFs explains a large portion (72%) of the variance in expression of these CREs. These interactions include three favorable heterotypic interactions between TFs. The model also predicts an unfavorable homotypic interaction between TFs, helping to explain the observation that homotypic chains of binding sites express at low levels. We further investigated the expression driven by CREs comprised of homotypic chains of KLF4 binding sites. Our results suggest that KLF homologs make unique contributions to regulation by these CREs. We conclude that a specific set of interactions between pluripotency TFs plays a large role in setting the levels of expression driven by CREs in ES cells.
Preexposure to salty and sour taste enhances conditioned taste aversion to novel sucrose
Authors: Flores Veronica L. , Moran Anan , Bernstein Max , Katz Donald B.
Published: April 2016

Conditioned taste aversion (CTA) is an intensively studied single-trial learning paradigm whereby animals are trained to avoid a taste that has been paired with malaise. Many factors influence the strength of aversion learning; prominently studied among these is taste novelty—the fact that preexposure to the taste conditioned stimulus (CS) reduces its associability. The effect of exposure to tastes other than the CS has, in contrast, received little investigation. Here, we exposed rats to sodium chloride (N) and citric acid (C), either before or within a conditioning session involving novel sucrose (S). Presentation of this taste array within the conditioning session weakened the resultant S aversion, as expected. The opposite effect, however, was observed when exposure to the taste array was provided in sessions that preceded conditioning: such experience enhanced the eventual S aversion—a result that was robust to differences in CS delivery method and number of tastes presented in conditioning sessions. This “non-CS preexposure effect” scaled with the number of tastes in the exposure array (experience with more stimuli was more effective than experience with fewer) and with the amount of exposure sessions (three preexposure sessions were more effective than two). Together, our results provide evidence that exposure and experience with the realm of tastes changes an animal's future handling of even novel tastes.
Transforming growth factor β recruits persistent MAPK signaling to regulate long-term memory consolidation in Aplysia californica
Authors: Shobe Justin , Philips Gary T. , Carew Thomas J.
Published: April 2016

In this study, we explore the mechanistic relationship between growth factor signaling and kinase activity that supports the protein synthesis-dependent phase of long-term memory (LTM) consolidation for sensitization of Aplysia. Specifically, we examine LTM for tail shock-induced sensitization of the tail-elicited siphon withdrawal (T-SW) reflex, a form of memory that requires both (i) extracellular signal-regulated kinase (ERK1/2; MAPK) activity within identified sensory neurons (SNs) that mediate the T-SW and (ii) the activation of transforming growth factor β (TGFβ) signaling. We now report that repeated tail shocks that induce intermediate-term (ITM) and LTM for sensitization, also induce a sustained post-training phase of MAPK activity in SNs (lasting at least 1 h). We identified two mechanistically distinct phases of post-training MAPK: (i) an immediate phase that does not require ongoing protein synthesis or TGFβ signaling, and (ii) a sustained phase that requires both protein synthesis and extracellular TGFβ signaling. We find that LTM consolidation requires sustained MAPK, and is disrupted by inhibitors of protein synthesis and TGFβ signaling during the consolidation window. These results provide strong evidence that TGFβ signaling sustains MAPK activity as an essential mechanistic step for LTM consolidation.
Ripple-triggered stimulation of the locus coeruleus during post-learning sleep disrupts ripple/spindle coupling and impairs memory consolidation
Authors: Novitskaya Yulia , Sara Susan J. , Logothetis Nikos K. , Eschenko Oxana
Published: April 2016

Experience-induced replay of neuronal ensembles occurs during hippocampal high-frequency oscillations, or ripples. Post-learning increase in ripple rate is predictive of memory recall, while ripple disruption impairs learning. Ripples may thus present a fundamental component of a neurophysiological mechanism of memory consolidation. In addition to system-level local and cross-regional interactions, a consolidation mechanism involves stabilization of memory representations at the synaptic level. Synaptic plasticity within experience-activated neuronal networks is facilitated by noradrenaline release from the axon terminals of the locus coeruleus (LC). Here, to better understand interactions between the system and synaptic mechanisms underlying “off-line” consolidation, we examined the effects of ripple-associated LC activation on hippocampal and cortical activity and on spatial memory. Rats were trained on a radial maze; after each daily learning session neural activity was monitored for 1 h via implanted electrode arrays. Immediately following “on-line” detection of ripple, a brief train of electrical pulses (0.05 mA) was applied to LC. Low-frequency (20 Hz) stimulation had no effect on spatial learning, while higher-frequency (100 Hz) trains transiently blocked generation of ripple-associated cortical spindles and caused a reference memory deficit. Suppression of synchronous ripple/spindle events appears to interfere with hippocampal-cortical communication, thereby reducing the efficiency of “off-line” memory consolidation.
Prior activation of inositol 1,4,5-trisphosphate receptors suppresses the subsequent induction of long-term potentiation in hippocampal CA1 neurons
Authors: Fujii Satoshi , Yamazaki Yoshihiko , Goto Jun-Ichi , Fujiwara Hiroki , Mikoshiba Katsuhiko
Published: April 2016

We investigated the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) activated by preconditioning low-frequency afferent stimulation (LFS) in the subsequent induction of long-term potentiation (LTP) in CA1 neurons in hippocampal slices from mature guinea pigs. Induction of LTP in the field excitatory postsynaptic potential or the population spike by the delivery of high-frequency stimulation (HFS, a tetanus of 100 pulses at 100 Hz) to the Schaffer collateral–commissural pathway to CA1 neuron synapses was suppressed when group I metabotropic glutamate receptors (mGluRs) were activated prior to the delivery of HFS. LTP induction was also suppressed when CA1 synapses were preconditioned 60 min before HFS by LFS of 1000 pulses at 1 Hz and this effect was inhibited when the test stimulation delivered at 0.05 Hz was either halted or applied in the presence of an antagonist of N-methyl-d-aspartate receptors, group I mGluRs, or IP3Rs during a 20-min period from 20 to 40 min after the end of LFS. Furthermore, blockade of group I mGluRs or IP3Rs immediately before the delivery of HFS overcame the effects of the preconditioning LFS on LTP induction. These results suggest that, in CA1 neurons, after a preconditioning LFS, activation of group I mGluRs caused by the test stimulation results in IP3Rs activation that leads to a failure of LTP induction.
Random vibration analysis for coupled vehicle-track systems with uncertain parameters
Authors: Xiang Pan , Zhao Yan , Lin Jiahao , Kennedy D , Williams Fred W
Published: April 2016

Purpose

The purpose of this paper is to present a new random vibration-based assessment method for coupled vehicle-track systems with uncertain parameters when subjected to random track irregularity.

Design/methodology/approach

The uncertain parameters of vehicle are described as bounded random variables. The track is regarded as an infinite periodic structure, and the dynamic equations of the coupled vehicle-track system, under mixed physical coordinates and symplectic dual coordinates, are established through wheel-rail coupling relationships. The random track irregularities at the wheel-rail contact points are converted to a series of deterministic harmonic excitations with phase lag by using the pseudo excitation method. Based on the polynomial chaos expansion of the pseudo response, a chaos expanded pseudo equation is derived, leading to the combined hybrid pseudo excitation method - polynomial chaos expansion method

Findings

The impact of uncertainty propagation on the random vibration analysis is assessed efficiently. According to GB5599-85, the reliability analysis for the stability index is implemented, which can grade the comfort level by the probability. Comparing to the deterministic analysis, it turns out that neglect of the parameter uncertainty will lead to potentially risky analysis results.

Originality/value

The proposed method is compared with Monte Carlo simulations, achieving good agreement. It is an effective means for random vibration analysis of uncertain coupled vehicle-track systems and has good engineering practicality
Squeeze film behavior in porous transversely circular stepped plates with a couple stress fluid
Authors: Narayanan Santhana Krishnan , Chamkha A , Kesavan Sundarammal
Published: April 2016

Purpose

The purpose of this work is to carry our a study of the effect of surface roughness on squeeze film behavior between two transversely circular stepped plates with couple stress lubricant when the upper circular stepped plate has porous facing which approaches the lower plate with uniform velocity.

Design/methodology/approach

The modified Stochastic Reynolds equation is derived for Christensen Stochastic theory for the rough surfaces. Closed form solution of the Stochastic Reynolds equation is obtained in terms of Fourier-Bessel series.

Findings

It is found that the effect of couple stress fluid and surface roughness is more pronounced compared to classical case.

Originality/value

The problem is original that it consider a couple stress fluid in this type of applications.
Exchange rate volatility and exports: a panel data analysis
Authors: Vieira Flavio Vilela , MacDonald Ronald
Published: April 2016

Purpose

– The purpose of this paper is to empirically investigate the role of real effective exchange rate (REER) volatility on export volume and also to address the impact of the international financial crisis of 2008.

Design/methodology/approach

– The empirical methodology is based on System GMM estimation for a set of 106 countries for the period of 2000-2011.

Findings

– For the complete sample of countries and for a set of developing/emerging economies, there is evidence that an increase (decrease) in REER volatility reduces (increases) export volume. The results are not robust once the oil export countries are removed from the sample. The estimated coefficients for the financial crisis dummy are positive and statistically significant, indicating that export volume were 0.14 percent higher after the financial crisis of 2008 compared to the previous period (2000-2007). There is also evidence that the export volume is price (REER) and income (trade weighted) inelastic.

Research limitations/implications

– The empirical results are valid for the complete set of countries and for developing and emerging economies when including the oil export countries, suggesting that countries should reduce exchange rate volatility in order to foster their export volume and that oil export countries have an important role on these results.

Practical implications

– The paper suggests that policymakers should adopt different policies to minimize exchange rate volatility if they seek to increase export volume. The international financial crisis had a significant impact on export volume in all estimated models regardless of the set of countries used.

Originality/value

– One of the main novelties of this work is that it deals with possible endogeneity using GMM estimators and addresses the issue of instrument proliferation, which is not a common feature of previous empirical studies on exchange rate volatility and trade flows. Another original aspect of the research is the construction of trade weighted variables for foreign income and REER based on the major 20 export partners for each country used in the panel data estimation. The work also incorporates the years following the international financial crisis of 2008, which is an additional empirical novelty, in order to address the impact of the international financial crisis on the export volume.
Real exchange rate and investment in the Brazilian manufacturing industry
Authors: Baltar Carolina Troncoso , Hiratuka Celio , Lima Gilberto Tadeu
Published: April 2016

Purpose

– The purpose of this paper is to study the impact of the real exchange rate on investment in the Brazilian manufacturing industry.

Design/methodology/approach

– The authors develop an investment model that considers the effect of changes in the real exchange rate, taking into account that the effect of the real exchange rate on the Brazilian manufacturing investment operates through demand and cost channels. The composition of these effects varies across manufacturing sectors, with different repercussions on investment decisions, depending on sectoral characteristics. A panel data analysis is applied to estimate the model for the Brazilian manufacturing sectors from 1996 to 2010.

Findings

– One main result is that the responsiveness of the Brazilian manufacturing investment to real exchange rate varies considerably across manufacturing sectors. Overall, the results contribute to a better understanding of the relationship between exchange rate dynamics, manufacturing investment and industrial development, thus unveiling important empirical elements for the debate on industrial policies to stimulate manufacturing investment and production.

Originality/value

– As the (scant) empirical literature on real exchange rate and investment in Brazil has invariably been using aggregate data, this paper contributes to the literature by obtaining sectoral estimates of the responsiveness of manufacturing investment to exchange rate fluctuations that further the understanding of the complex relationship between these economic variables.