bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rational design of hidden thermodynamic driving through DNA mismatch repair
Authors: Haley Natalie E. C. , Ouldridge Thomas E. , Geraldini Alessandro , Louis Ard A. , Bath Jonathan , Turberfield Andrew J. 
Published: September 2018

AbstractRecent years have seen great advances in the development of synthetic self-assembling molecular systems. Designing out-of-equilibrium architectures, however, requires a more subtle control over the thermodynamics and kinetics of reactions. We propose a new mechanism for enhancing thermodynamic drive of DNA strand displacement reactions whilst barely perturbing forward reaction rates - introducing mismatches in an internal location within the initial duplex. Through a combination of experiment and simulation, we demonstrate that displacement rates are strongly sensitive to mismatch location and can be tuned by rational design. By placing mismatches away from duplex ends, the thermodynamic drive for a strand-displacement reaction can be varied without significantly affecting the forward reaction rate. This hidden thermodynamic driving motif is ideal for the engineering of nonequilibrium systems that rely on catalytic control and must be robust to leak reactions.
Chemosensory structure and function in the filarial nematode, Brugia malayi
Authors: Fraser Lisa M. , Madriz R. Isai , Srinivasan Divyaa , Zamanian Mostafa , Bartholomay Lyric C. , Kimber Michael J. 
Published: September 2018

AbstractNematode chemosensory behaviors underlie fundamental processes and activities in development, reproduction, tropisms and taxes. For parasitic species, chemosensation is essential for host seeking and host and tissue invasion behaviors. Such fundamental biology presents an attractive target for developing behavior-blocking anthelminthic drugs, but the anatomy and functional relevance of parasitic nematode chemosensory machinery are poorly understood. The goals of this study were to better understand the chemosensory apparatus and behaviors of infectious stage Brugia malayi (Spirurida: Onchocercidae), a mosquito-borne nematode and etiological agent of Lymphatic Filariasis. Scanning electron microscopy revealed that amphids, the major chemosensory organs, are present on adult B. malayi and arranged in a conserved manner. Internal sensory neuroanatomy display structural differences between life stages, and a simpler chemosensory architecture as compared to free-living nematodes. Positive and negative chemotactic behaviors were identified for a repertoire of chemicals with known chemostimulatory activity for the mosquito host that may facilitate host-selectivity and invasion. This is the first description of chemosensory anatomy and chemotactic behaviors in B. malayi that reveal the involvement of chemosensation in parasite transmission and host invasion.Key findings•Amphidial arrangement in B. malayi is less complex than free-living nematodes.•Chemosensory neuroanatomy is stage-specific and simpler than free-living nematodes.•B. malayi responses to stimuli can be measured using a plate-based assay.•Chemostimulants associated with mosquito host-seeking induce negative and positive tropisms for L3 stage B. malayi.
Molecular Nearest Neighbors Determine Generalization of Odorant Mixtures
Authors: Brackney Ryan J. , Dai Kael , Der-Ghazarian Taleen , Smith Brian H. , Gerkin Richard C. 
Published: September 2018

ABSTRACTMost natural odors arise from mixtures of multiple odorants. Some such mixtures are perceived “elementally”, with each odorant component clearly identifiable, while others are perceived “configurally”, with the mixture adopting a perceptual quality distinct from any of the components. While the perceptual similarity of two mixtures is presumably related in some way to the similarity of the corresponding components, given the elemental/configural dichotomy it is unclear if any formal principle can be used to predict mixture similarity. To investigate this problem, we trained mice to respond to a binary reference mixture of structurally similar odorants (S+) and then tested generalization of this response to other structurally related binary test mixtures. Across 5 experiments, we parametrically varied these mixtures in distinct ways to test candidate models for the perceptual similarity of mixtures. The best-performing model predicted behavioral responses by considering, for each component of theS+, only the similarity of the most structurally similar (”nearest neighbor”) component of each test mixture. We conclude that for mixture generalization tasks the olfactory system may deemphasize or discard information about mixture components not perceptually “near” enough to any of those in theS+, consistent with a sparse and elemental rule for perception of structurally-related binary mixtures.
Non-canonicalDrosophilaX chromosome dosage compensation and repressive topologically-associated domains
Authors: Lee Hangnoh , Oliver Brian 
Published: September 2018

AbstractBackgroundIn animals withXYsex chromosomes,X-linked genes from a singleXchromosome in males are imbalanced relative to autosomal genes. To minimize the impact of genic imbalance in maleDrosophila, there is a dosage compensation complex (MSL), that equilibratesX-linked gene expression with the autosomes. There are other potential contributions to dosage compensation. Hemizygous autosomal genes located in repressive chromatin domains are often de-repressed. If this homolog-dependent repression occurs on theX, which has no pairing partner, then de-repression could contribute to male dosage compensation.ResultsWe asked whether different chromatin states or topological associations correlate withXchromosome dosage compensation, especially in regions with little MSL occupancy. Our analyses demonstrated that maleXchromosome genes that are located in repressive chromatin states are depleted of MSL occupancy, however they show dosage compensation. The genes in these repressive regions were also less sensitive to knockdown of MSL components.ConclusionsOur results suggest that this non-canonical dosage compensation is due to the same trans-acting de-repression that occurs on autosomes. This mechanism would facilitate immediate compensation during the evolution of sex chromosomes from autosomes. This mechanism is similar to that ofC. elegans, where enhanced recruitment ofXchromosomes to the nuclear lamina dampensXchromosome expression as part of the dosage compensation response inXXindividuals.
Mitochondrial DNA Repair in anArabidopsis thalianaUracil N-Glycosylase Mutant
Authors: Wynn Emily , Purfeerst Emma , Christensen Alan 
Published: September 2018

AbstractSubstitution rates in plant mitochondrial genes are extremely low, indicating strong selective pressure as well as efficient repair. Plant mitochondria possess base excision repair pathways, however, many repair pathways such as nucleotide excision repair and mismatch repair appear to be absent. In the absence of these pathways, many DNA lesions must be repaired by a different mechanism. To test the hypothesis that double-strand break repair (DSBR) is that mechanism, we maintained independent self-crossing lineages of plants deficient in uracil-N-glycosylase (UNG) for 11 generations to determine the repair outcomes when that pathway is missing. Surprisingly, no single nucleotide polymorphisms (SNPs) were fixed in any line in generation 11. The pattern of heteroplasmic SNPs was also unaltered through 11 generations. When the rate of cytosine deamination was increased by mitochondrial expression of the cytosine deaminase APOBEC3G, there was an increase in heteroplasmic SNPs, but only in mature leaves. Clearly DNA maintenance in reproductive meristem mitochondria is very effective in the absence of UNG, while mitochondrial genomes in differentiated tissue are maintained through a different mechanism, or not at all. Several genes involved in DSBR are upregulated in the absence of UNG, indicating that double strand break repair is a general system of repair in plant mitochondria. It is important to note that the developmental stage of tissues is critically important for these types of experiments.
Untangling the dynamics of persistence and colonization in microbial communities
Authors: Ranjeva Sylvia L. , Mihaljevic Joseph R. , Joseph Maxwell B. , Giuliano Anna R. , Dwyer Greg 
Published: September 2018

AbstractA central goal of community ecology is to infer biotic interactions from observed distributions of co-occurring species. Evidence for biotic interactions, however, can be obscured by shared environmental requirements, posing a challenge for statistical inference. Here we introduce a dynamic statistical model that quantifies the effects of spatial and temporal covariance in longitudinal co-occurrence data. We separate the fixed pairwise effects of species occurrences on persistence and colonization rates, a potential signal of direct interactions, from latent pairwise correlations in occurrence, a potential signal of shared environmental responses. We apply our modeling approach to a pressing epidemiological question by examining how human papillomavirus (HPV) types coexist. Our results suggest that while HPV types respond similarly to common host traits, direct interactions are sparse and weak, so that HPV type diversity depends largely on shared environmental drivers. Our modeling approach is widely applicable to microbial communities and provides valuable insights that should lead to more directed hypothesis testing and mechanistic modeling.
Rapid CD4 cell loss is caused by specific CRF01_AE cluster with V3 signatures favoring CXCR4 usage
Authors: Song Hongshuo , Ou Weidong , Feng Yi , Zhang Junli , Li Fan , Hu Jing , Peng Hong , Xing Hui , Ma Liying , Tan Qiuxiang , Wu Beili , Shao Yiming 
Published: September 2018

AbstractHIV-1 evolved into various genetic subtypes and circulating recombinant forms (CRFs) in the global epidemic, with the same subtype or CRF usually having similar phenotype. Being one of the world’s major CRFs, CRF01_AE infection was reported to associate with higher prevalence of CXCR4 (X4) viruses and faster CD4 decline. However, the underlying mechanisms remain unclear. We identified eight phylogenetic clusters of CRF01_AE in China and hypothesized that they may have different phenotypes. In the national HIV molecular epidemiology survey, we discovered that people infected by CRF01_AE cluster 4 had significantly lower CD4 count (391 vs. 470,p< 0.0001) and higher prevalence of predicted X4-using viruses (17.1% vs. 4.4%,p< 0.0001) compared to those infected by cluster 5. In a MSM cohort, X4-using viruses were only isolated from sero-convertors infected by cluster 4, which associated with rapid CD4 loss within the first year of infection (141 vs. 440,p= 0.01). Using co-receptor binding model, we identified unique V3 signatures in cluster 4 that favor CXCR4 usage. We demonstrate for the first time that HIV-1 phenotype and pathogenicity can be determined at the phylogenetic cluster level in a single subtype. Since its initial spread to human from chimpanzee in 1930s, HIV-1 remains undergoing rapid evolution in larger and more diverse population. The divergent phenotype evolution of two major CRF01_AE clusters highlights the importance in monitoring the genetic evolution and phenotypic shift of HIV-1 to provide early warning for the appearance of more pathogenic strains such as CRF01_AE cluster 4.Significance StatementPast studies on HIV-1 evolution were mainly at the genetic level. This study provides well-matched genotype and phenotype data and demonstrates disparate pathogenicity of two major CRF01_AE clusters. While both CRF01_AE cluster 4 and cluster 5 are mainly spread through the MSM route, cluster 4 but not cluster 5 causes fast CD4 loss, which is associated with the higher prevalence CXCR4 viruses in cluster 4. The higher CXCR4 use tendency in cluster 4 is derived from its unique V3 loop favoring CXCR4 binding. This study for the first time demonstrates disparate HIV-1 phenotype between different phylogenetic clusters. It is important to monitor HIV-1 evolution at both the genotype and phenotype level to identify and control more pathogenic HIV-1 strains.
pavo 2: new tools for the spectral and spatial analysis of colour in R
Authors: Maia Rafael , Gruson Hugo , Endler John A. , White Thomas E. 
Published: September 2018

AbstractBiological colouration presents a canvas for the study of ecological and evolutionary processes. Enduring interest in colour-based phenotypes has driven, and been driven by, improved techniques for quantifying colour patterns in ever-more relevant ways, yet the need for flexible, open frameworks for data processing and analysis persists.Here we introduce pavo 2, the latest iteration of the R package pavo. This release represents the extensive refinement and expansion of existing methods, as well as a suite of new tools for the cohesive analysis of the spectral and (now) spatial structure of colour patterns and perception. At its core, the package retains a broad focus on (a) the organisation and processing of spectral and spatial data, and tools for the alternating (b) visualisation, and (c) analysis of data. Significantly, pavo 2 introduces image-analysis capabilities, providing a cohesive workflow for the comprehensive analysis of colour patterns.We demonstrate the utility of pavo with a brief example centred on mimicry in Heliconius butterflies. Drawing on visual modelling, adjacency, and boundary strength analyses, we show that the combined spectral (colour and luminance) and spatial (pattern element distribution and boundary salience) features of putative models and mimics are closely aligned.pavo 2 offers a flexible and reproducible environment for the analysis of colour, with renewed potential to assist researchers in answering fundamental questions in sensory ecology and evolution.
Leveraging the effects of chloroquine on resistant malaria parasites for combination therapies
Authors: Untaroiu Ana M. , Carey Maureen A. , Guler Jennifer L. , Papin Jason A. 
Published: September 2018

AbstractMalaria is a major global health problem, with thePlasmodium falciparumprotozoan parasite causing the most severe form of the disease. Prevalence of drug-resistantP. falciparumhighlights the need to understand the biology of resistance and to identify novel combination therapies that are effective against resistant parasites. Resistance has compromised the therapeutic use of many antimalarial drugs, including chloroquine, and limited our ability to treat malaria across the world. Fortunately, chloroquine resistance comes at a fitness cost to the parasite; this can be leveraged in developing combination therapies or to reinstate use of chloroquine. To understand biological changes induced by chloroquine treatment, we compared transcriptomics data from chloroquine-resistant parasites in the presence or absence of the drug. Using both linear models and a genome-scale metabolic network reconstruction of the parasite to interpret the expression data, we identified targetable pathways in resistant parasites. This study identified an increased importance of lipid synthesis, glutathione production/cycling, isoprenoids biosynthesis, and folate metabolism in response to chloroquine. We identified potential drug targets for chloroquine combination therapies. Significantly, our analysis suggests that the combination of chloroquine and sulfadoxine-pyrimethamine or fosmidomycin may be more effective against chloroquine-resistant parasites than either drug alone; further studies will explore the use of these drugs as chloroquine resistance blockers. Additional metabolic weaknesses were found in glutathione generation and lipid synthesis during chloroquine treatment. These processes could be targeted with novel inhibitors to reduce parasite growth and reduce the burden of malaria infections. Thus, we identified metabolic weaknesses of chloroquine-resistant parasites and propose targeted chloroquine combination therapies.
Modelling of a permanent magnet synchronous machine using isogeometric analysis
Authors: Bhat Prithvi , Bontinck Zeger , Corno Jacopo , Schöps Sebastian , DeGersem Herbert 
Published: September 2018

Purpose
This paper aims to propose the use of isogeometric analysis (IGA) for the simulation of electrical machines to represent their geometries exactly and obtain numerical solutions of high accuracy and regularity.

Design/methodology/approach
IGA makes use of non-uniform rational b-splines to parametrise the domain and approximate the solution spaces. Dealing with the different stator and rotor topologies, the computational domain is split into two non-overlapping parts on which Maxwell’s equations are solved independently and are interconnected by a classical Schwarz domain decomposition scheme. The results are compared with the conventional polynomial finite element method (FEM).

Findings
The new methodology is reliable and efficient. The obtained solutions of the fields are in good agreement with the ones obtained by the FEM approach. IGA offers a better accuracy than FEM.

Originality/value
The application of IGA combined with domain decomposition to the model of an electric machine is a new and original contribution.
3D harmonic modeling of eddy currents in segmented conducting structures
Authors: Custers C.H.H.M. , Jansen J.W. , van Beurden M.C. , Lomonova E.A. 
Published: September 2018

PurposeThe purpose of this paper is to describe a semi-analytical modeling technique to predict eddy currents in three-dimensional (3D) conducting structures with finite dimensions. Using the developed method, power losses and parasitic forces that result from eddy current distributions can be computed.Design/methodology/approachIn conducting regions, the Fourier-based solutions are developed to include a spatially dependent conductivity in the expressions of electromagnetic quantities. To validate the method, it is applied to an electromagnetic configuration and the results are compared to finite element results.FindingsThe method shows good agreement with the finite element method for a large range of frequencies. The convergence of the presented model is analyzed.Research limitations/implicationsBecause of the Fourier series basis of the solution, the results depend on the considered number of harmonics. When conducting structures are small with respect to the spatial period, the number of harmonics has to be relatively large.Practical implicationsBecause of the general form of the solutions, the technique can be applied to a wide range of electromagnetic configurations to predict, e.g. eddy current losses in magnets or wireless energy transfer systems. By adaptation of the conductivity function in conducting regions, eddy current distributions in structures containing holes or slit patterns can be obtained.Originality/valueWith the presented technique, eddy currents in conducting structures of finite dimensions can be modeled. The semi-analytical model is for a relatively low number of harmonics computationally faster than 3D finite element methods. The method has been validated and shown to be computationally accurate.
Teaching marketing to non-marketers: some experiences from New Zealand and the UK
Authors: Crick James M. 
Published: September 2018

Purpose
The purpose of this paper is to explore how marketing can be taught to students originating from non-marketing or non-business backgrounds (non-marketers), so that academics can engage such students in lectures and tutorials.

Design/methodology/approach
The research design involved a qualitative methodology using data from two undergraduate marketing courses (one in New Zealand and one in the UK) that contained a large proportion of non-marketing students. Data were collected from a combination of empirical and archival sources and were analysed using self-reflection techniques, alongside other checks for methodological credibility.

Findings
When teaching marketing to non-marketing students, it is important to integrate theory with practice to help their learning (e.g. through practical case studies). Marketing educators must also maximise their interactivity with their students and have in-class discussions to engage the cohort. Further, lecturers and tutors should relate marketing theories and concepts with non-business subjects to demonstrate the subject’s relevance to students with limited commercial knowledge. These teaching and learning strategies were important for students intending to become entrepreneurs after graduating from university, as well as those planning to enter paid employment.

Originality/value
Prior studies have focussed on teaching marketing to specialist marketing students; however, they have scarcely considered how educators can teach non-specialist marketing to students with non-marketing and non-business backgrounds. This viewpoint solves this research problem, by discussing the best ways that academics can maximise such students’ engagement. It is proposed that the main way that non-marketers can be engaged is through linking marketing with their subjects-of-origin, to demonstrate how marketing activities apply to all organisations and should not be overlooked. A framework is presented, based on the empirical data, to help academics teach marketing to non-marketers. This paper ends with some directions for future research.
Research on 3D reconstruction of late Victorian riding skirts
Authors: Kuzmichev Victor , Moskvin Aleksei , Moskvina Mariia , Pryor Jane 
Published: September 2018

Purpose
Virtual design of contemporary and historical clothes is a very intensive and developing area of science that can be considered as a bridge between costume heritage and modern way of its presentation by means of CAD. The purpose of this paper is to apply 2D and 3D existing CAD for virtual reconstruction of the very specific kind of women’s clothes such as a side-saddle riding habit (RH) used in 1875–1915.

Design/methodology/approach
The construction of RH was adapted to the aesthetic rules of the mentioned time, ergonomic posture of a woman sitting on a horse, surface of the horse’s body which the woman is sitting on. For the new method, the huge databases were obtained after analyzing the historical pattern manuals and features of pattern blocks used, possible postures of riding, construction of RH and converting it into virtual system “avatar – RH.” To reconstruct the side-saddle RH in virtual reality, the images dated 1887 and authentic pattern blocks were used. Special attention has been given to the topology of contacting areas existing between the sitting woman and “shaped” riding skirt and to the method of presenting it by means of special points combination.

Findings
The authors have developed a new method of virtual reconstruction of an RH that is based on automatic consideration of all joining elements such as “shaped” riding skirt, avatar and its ergonomic posture. The new approach allows reconstruction of the clothes in virtual reality in three ways: by using the real skirts, the historical pattern blocks or pictures.

Originality/value
The results obtained allow increased possibilities of virtual reconstruction and include in the list new objects of engineering achievements of the nineteenth century such as the side-saddle RH. This study should help researchers and practical specialists to recreate and save the historical treasure in a digital way.