bluuebunny/crossref_metadata_2025_split huggingface dataset:
TAS2R38 predisposition to bitter taste associated with differential changes in vegetable intake in response to a community-based dietary intervention
Authors: Calancie Larissa , Keyserling Thomas C. , Smith-Taillie Lindsey , Robasky Kimberly , Patterson Cam , Ammerman Alice S. , Schisler Jonathan C. 
Published: January 2018

AbstractBackgroundAlthough vegetable consumption is associated with decreased risk for a variety of chronic diseases, few Americans meet the CDC recommendations for vegetable intake. The TAS2R38 gene encodes a taste receptor that confers bitter taste sensing from chemicals found in some vegetables. Common polymorphisms in TAS2R38, including rs713598, rs1726866, and rs10246939, lead to coding substitutions that alter receptor function and result in the loss of bitter taste perception.ObjectiveOur study examines whether bitter taste perception TAS2R38 diplotypes were associated with vegetable consumption in participants enrolled in either an enhanced or a minimal nutrition counseling intervention within a community-based dietary intervention.MethodsDNA was isolated from the peripheral blood cells of study participants (N = 497) and analyzed for polymorphisms using genotyping arrays. The Block Fruit and Vegetable screener was used to determine frequency of vegetable consumption. Mixed effects models were used to test differences in frequency of vegetable consumption between intervention and genotype groups over time.ResultsThere was no association between baseline vegetable consumption frequency and the bitter taste diplotype (p = 0.937), however after six months of the intervention, we observed an interaction between bitter taste diplotypes and time (p = 0.046). Participants in the enhanced intervention increased their vegetable consumption frequency (p = 0.020) and within this intervention group, the non-bitter and intermediate-bitter tasting participants had the largest increase in vegetable consumption. In contrast, in the minimal intervention group, the bitter tasting participants reported a decrease in vegetable consumption.ConclusionsNon‐ and intermediate-bitter taste blind participants increased vegetable consumption in either intervention group more than those who perceive bitterness. Future applications of precision medicine could consider genetic variation in bitter taste perception genes when designing dietary interventions.Author summaryMost Americans under consume vegetables, despite clear associations between vegetable consumption and health benefits. Vegetables, such as broccoli, kale, and Brussels sprouts, contain bitter-tasting compounds, leading to taste aversion. Common polymorphisms on the TAS2R38 taste receptor gene (rs713598, rs1726866, and rs10246939) influence the perception of bitter taste. We tested whether genetic predisposition to bitter taste influenced vegetable intake in a dietary intervention and found that TAS2R38 diplotypes were related to vegetable consumption. Combining precision medicine approaches that identify taste profiles and personalizing dietary advice could help engage intervention participants and improve the impact of dietary interventions.
A Toolbox for Discrete Modelling of Cell Signalling Dynamics
Authors: Paterson Yasmin Z. , Shorthouse David , Pleijzier Markus W. , Piterman Nir , Bendtsen Claus , Hall Benjamin A. , Fisher Jasmin 
Published: January 2018

ABSTRACTIn an age where the volume of data regarding biological systems exceeds our ability to analyse it, many researchers are looking towards systems biology and computational modelling to help unravel the complexities of gene and protein regulatory networks. In particular, the use of discrete modelling allows generation of signalling networks in the absence of full quantitative descriptions of systems, which are necessary for ordinary differential equation (ODE) models. In order to make such techniques more accessible to mainstream researchers, tools such as the BioModelAnalyzer (BMA) have been developed to provide a user-friendly graphical interface for discrete modelling of biological systems. Here we use the BMA to build a library of discrete target functions of known canonical molecular interactions, translated from ordinary differential equations (ODEs). We then show that these BMA target functions can be used to reconstruct complex networks, which can correctly predict many known genetic perturbations. This new library supports the accessibility ethos behind the creation of BMA, providing a toolbox for the construction of complex cell signalling models without the need for extensive experience in computer programming or mathematical modelling, and allows for construction and simulation of complex biological systems with only small amounts of quantitative data.AUTHOR SUMMARYOrdinary differential equation (ODE) based models are a popular approach for modelling biological networks. A limitation of ODE models is that they require complete networks and detailed kinetic parameterisation. An alternative is the use of discrete, executable models, in which nodes are assigned discrete value ranges, and the relationship between them defined with simple mathematical operations. One tool for constructing such models is the BioModelAnalyzer (BMA), an open source and publicly available (https://www.biomodelanalyzer.org) software, aimed to be fully usable by researchers without extensive computational or mathematical experience. A fundamental question for executable models is whether the high level of abstraction substantially reduces expressivity relative to continuous approaches. Here, we present a canonical library of biological signalling motifs, initially defined by Tyson et al (2003), translated for the first time into the BMA. We show that; 1) these motifs are easily and fully translatable from continuous to discrete models, 2) Combining these motifs in a computationally naïve way generates a fully functional and predictive model of the yeast cell cycle.
Experimental Directory Structure (Exdir): An alternative to HDF5 without introducing a new file format
Authors: Dragly Svenn-Arne , Mobarhan Milad Hobbi , Lepperød Mikkel , Tennøe Simen , Fyhn Marianne , Hafting Torkel , Malthe-Sørenssen Anders 
Published: January 2018

ABSTRACTNatural sciences generate an increasing amount of data in a wide range of formats developed by different research groups and commercial companies. At the same time there is a growing desire to share data along with publications in order to enable reproducible research. Open formats have publicly available specifications which facilitate data sharing and reproducible research. Hierarchical Data Format 5 (HDF5) is a popular open format widely used in neuroscience, often as a foundation for other, more specialized formats. However, drawbacks related to HDF5’s complex specification have initiated a discussion for an improved replacement. We propose a novel alternative, the Experimental Directory Structure (Exdir), an open standard for data storage in experimental pipelines which amends drawbacks associated with HDF5 while retaining its advantages. HDF5 stores data and metadata in a hierarchy within a complex binary file which, among other things, is not human-readable, not optimal for version control systems, and lacks support for storing raw data. Exdir, one the other hand, uses file system directories to represent the hierarchy, with metadata stored in human-readable YAML files, datasets stored in binary NumPy files, and raw data stored directly in subdirectories. Furthermore, storing data in multiple files makes it easier to track for version control systems. Exdir is not a file format in itself, but a standard for organizing files in a directory structure. Exdir uses the same abstractions as HDF5 and is compatible with the HDF5 Abstract Data Model. Several research groups are already using data stored in a directory hierarchy as an alternative to HDF5, but no common standard exists in the field. This complicates and limits the opportunity for data sharing and development of common tools for reading, writing, and analyzing data. Exdir facilitates improved data storage, data sharing, reproducible research, and novel insight from interdisciplinary collaboration. With the publication of Exdir, we invite the scientific community to join the development to create an open standard that will serve as many needs as possible and that will serve as a foundation for open access to and exchange of data.SIGNIFICANCE STATEMENTExperimental Directory Structure (Exdir) is a proposal to standardize a storage solution that has become an increasingly popular alternative to Hierarchical Data Format 5 (HDF5), namely to use directories to define a hierarchy, store data in binary files, and metadata in text files. While this strategy is deployed locally by several research groups, no common standard exists. We envision the establishment of such a standard and present Exdir to the community as a starting point.
The molecular recognition of phosphatidic acid by an amphipathic helix in Opi1
Authors: Hofbauer Harald F. , Gecht Michael , Fischer Sabine C. , Seybert Anja , Frangakis Achilleas S. , Stelzer Ernst H. K. , Covino Roberto , Hummer Gerhard , Ernst Robert 
Published: January 2018

AbstractA key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important lipid intermediate and signaling lipid at the branch point of these pathways and constantly monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. Here, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for the selective binding to membranes containing PA over phosphatidylserine (PS). The insertion of the AH into the hydrophobic core of the membrane renders Opi1 sensitive to the lipid acyl chain composition as an important factor contributing to the regulation of membrane biogenesis. Based on these findings, we rationally designed the membrane binding properties of Opi1 to control its responsiveness in the physiological context. Using extensive molecular dynamics (MD) simulations, we identified two PA-selective three-finger grips that tightly bind the phosphate headgroup, while interacting less intimately and more transiently with PS. This work establishes lipid headgroup selectivity as a new feature in the family of AH-containing membrane property sensors.
A Hidden Markov Model to Estimate the Time Dairy Cows Spend in Feeder Based on Indoor Positioning Data
Authors: Pastell Matti , Lilli Frondelius 
Published: January 2018

The feeding time of dairy cows is linked with the health status of the animal and can be used to estimate daily feed intake together with other measurements. The aim of this study was to develop a model to measure the time a dairy cow spends at a feed bunk using an Ultra wide-band indoor positioning system.We measured the feeding behavior of 50 dairy cows during 7 days using Ubisense indoor positioning system and Insentec roughage feeders. We calculated the feeding (presence at the feeder) probability of the cow using logistic regression model with the distance to feed barrier as input and used the Viterbi algorithm to calculate the most likely state (feeding or not feeding) given state transition probabilities. The model was able to predict whether the cow was at the feeding trough or not with the accuracy of 97.6%, sensitivity 95.3% and specificity 97.9%. The model was also able to estimate the mean bout duration and the number of feeding bouts.
Parallels between experimental and natural evolution of legume symbionts
Authors: Clerissi Camille , Touchon Marie , Capela Delphine , Tang Mingxing , Cruveiller Stephane , Parker Matthew A. , Moulin Lionel , Masson-Boivin Catherine , Rocha Eduardo P.C. 
Published: January 2018

AbstractThe emergence of symbiotic interactions has been studied using population genomics in nature and experimental evolution in the laboratory, but the parallels between these processes remain unknown. We compared the emergence of rhizobia after the horizontal transfer of a symbiotic plasmid in natural populations ofCupriavidus taiwanensis, over 10 MY ago, with the experimental evolution of symbioticRalstonia solanacearumfor a few hundred generations. In spite of major differences in terms of time-span, environment, genetic background and phenotypic achievement, both processes resulted in rapid diversification dominated by purifying selection concomitant with acquisition of positively selected mutations. The latter were lacking in the plasmid carrying the genes responsible for the ecological transition. Instead, adaptation targeted the same set of genes leading to the cooption of the same quorum-sensing system. Our results provide evidence for similarities in experimental and natural evolutionary transitions and highlight the potential of comparisons between both processes to understand symbiogenesis.
Therapeutic ICOS blockade reduces T follicular helper cells and improves allergic airway disease
Authors: Uwadiae F. I. , Pyle C.J. , Walker S.A. , Lloyd C.M. , Harker J.A. 
Published: January 2018

ABSTRACTAllergic asthma is a disease of chronic airway inflammation and remodelling, characterised by a dysregulated type 2 response and allergen-specific IgE. T follicular helper cells (TFH) are critical to antibody production and have recently been implicated in allergic airway disease (AAD) pathogenesis. The role of TFHin established disease and the therapeutic potential of targeting them are however not fully understood. Using two aeroallergen driven murine models of chronic AAD, TFHwere first identified in the lung draining lymph nodes but with prolonged exposure were present in the lung itself. Sustained allergen exposure led to the accumulation of TFH, and concomitant development of germinal centre B cells. Blockade of Inducible T cell co-stimulator (ICOS) signalling during established AAD depleted TFHwithout adversely affecting the differentiation of other CD4+T cell subsets. This resulted in impaired germinal centre responses, reduced allergen specific IgE and ameliorated inflammation and airway hyper-responsiveness, including reduced pulmonary IL-13. TFHdid not however appear to produce IL-13 directly, suggesting they indirectly promote type-2 inflammation in the lungs. These data show that TFHplay a pivotal role in the regulation of AAD and that targeting the ICOS-L pathway could represent a novel therapeutic approach in this disease.
Exploiting regulatory heterogeneity to systematically identify enhancers with high accuracy
Authors: Arbel Hamutal , Fisher William W. , Hammonds Ann S. , Wan Kenneth H. , Park Soo , Weiszmann Richard , Keränen Soile , Henriquez Clara , Solari Omid Shams , Bickel Peter , Biggin Mark D. , Celniker Susan E. , Brown James B. 
Published: January 2018

AbstractIdentifying functional enhancers elements in metazoan systems is a major challenge. For example, large-scale validation of enhancers predicted by ENCODE reveal false positive rates of at least 70%. Here we use the pregrastrula patterning network ofDrosophila melanogasterto demonstrate that loss in accuracy in held out data results from heterogeneity of functional signatures in enhancer elements. We show that two classes of enhancer are active during earlyDrosophilaembryogenesis and that by focusing on a single, relatively homogeneous class of elements, over 98% prediction accuracy can be achieved in a balanced, completely held-out test set. The class of well predicted elements is composed predominantly of enhancers driving multi-stage, segmentation patterns, which we designate segmentation driving enhancers (SDE). Prediction is driven by the DNA occupancy of early developmental transcription factors, with almost no additional power derived from histone modifications. We further show that improved accuracy is not a property of a particular prediction method: after conditioning on the SDE set, naïve Bayes and logistic regression perform as well as more sophisticated tools. Applying this method to a genome-wide scan, we predict 1,640 SDEs that cover 1.6% of the genome, 916 of which are novel. An analysis of 32 novel SDEs using wholemount embryonic imaging of stably integrated reporter constructs chosen throughout our prediction rank-list showed >90% drove expression patterns. We achieved 86.7% precision on a genome-wide scan, with an estimated recall of at least 98%, indicating high accuracy and completeness in annotating this class of functional elements.Significance StatementWe demonstrate a high accuracy method for predicting enhancers genome wide with > 85% precision as validated by transgenic reporter assays inDrosophilaembryos. This is the first time such accuracy has been achieved in a metazoan system, allowing us to predict with high-confidence 1640 enhancers, 916 of which are novel. The predicted enhancers are demarcated by heterogeneous collections of epigenetic marks; many strong enhancers are free from classical indicators of activity, including H3K27ac, but are bound by key transcription factors. H3K27ac, often used as a one-dimensional predictor of enhancer activity, is an uninformative parameter in our data.
Host range and genetic plasticity explain the co-existence of integrative and extrachromosomal mobile genetic elements
Authors: Cury Jean , Oliveira Pedro H. , de la Cruz Fernando , Rocha Eduardo P.C. 
Published: January 2018

AbstractSelf-transmissible mobile genetic elements drive horizontal gene transfer between prokaryotes. Some of these elements integrate in the chromosome, whereas others replicate autonomously as plasmids. Recent works showed the existence of few differences, and occasional interconversion, between the two types of elements. Here, we enquired on why evolutionary processes have maintained the two types of mobile genetic elements by comparing integrative and conjugative elements (ICE) with extrachromosomal ones (conjugative plasmids) of the highly abundant MPFT conjugative type. We observed that plasmids encode more replicases, partition systems, and antibiotic resistance genes, whereas ICEs encode more integrases and metabolism-associated genes. ICEs and plasmids have similar average sizes, but plasmids are much more variable, have more DNA repeats, and exchange genes more frequently. On the other hand, we found that ICEs are more frequently transferred between distant taxa. We propose a model where differential plasticity and transmissibility range explain the co-occurrence of integrative and extra-chromosomal elements in microbial populations. In particular, the conversion from ICE to plasmid allows ICE to be more plastic, while the conversion from plasmid to ICE allows the expansion of the element‘s host range.
New hybrid-Trefftz Mindlin–Reissner plate elements for efficiently modeling the edge zones near free/SS1 edges
Authors: Shang Yan , Cen Song , Ouyan Wengen 
Published: January 2018

Purpose
The purpose of this paper is to propose a new finite element method (FEM) solving strategy for efficient analysis of the challenging edge effect problem in plate structures. Its main ideas are to develop special-purpose plate element models to effectively simulate the behaviors in the plate’s edge zones near free/SS1 edges.

Design/methodology/approach
These new elements are developed based on the hybrid-Trefftz element method. During their construction procedures, the analytical solutions of the edge effect problem, which are in exponential forms, are used to enhance the interior displacement fields. Besides, the Lagrangian multipliers are introduced into the modified hybrid-Trefftz functional for considering the stress resultant constraints at free/SS1 edges. Thus, these elements theoretically possess the abilities to correctly capture the very steep gradients of the resultant distributions in the boundary layers.

Findings
These new specialized hybrid-Trefftz plate elements can very efficiently solve the edge effect problem with high accuracy, even when distorted meshes are used. Moreover, because these elements’ construction procedures contain only boundary integrals, the computation expense for accurately integrating the exponential trial functions can be considerably saved.

Originality/value
This work presents an alternative novel idea for using the FEM to more effectively handle the local stress problems by incorporating the use of the analytical trial functions.
Development and validation of a new finite element human head model
Authors: Fernandes Fábio A.O. , Tchepel Dmitri , Alves de Sousa Ricardo J. , Ptak Mariusz 
Published: January 2018

Purpose
Currently, there are some finite element head models developed by research groups all around the world. Nevertheless, the majority are not geometrically accurate. One of the problems is the brain geometry, which usually resembles a sphere. This may raise problems when reconstructing any event that involves brain kinematics, such as accidents, affecting the correct evaluation of resulting injuries. Thus, the purpose of this study is to develop a new finite element head model more accurate than the existing ones.

Design/methodology/approach
In this work, a new and geometrically detailed finite element brain model is proposed. Special attention was given to sulci and gyri modelling, making this model more geometrically accurate than currently available ones. In addition, these brain features are important to predict specific injuries such as brain contusions, which usually involve the crowns of gyri.

Findings
The model was validated against experimental data from impact tests on cadavers, comparing the intracranial pressure at frontal, parietal, occipital and posterior fossa regions.

Originality/value
As this model is validated, it can be now used in accident reconstruction and injury evaluation and even as a design tool for protective head gear.
Bending and vibration analyses of plate and shell using an element decomposition method
Authors: Li She , Cui Xiangyang , Wang Gang 
Published: January 2018

Purpose
The purpose of this paper is to apply the element decomposition method (EDM) in the study of the bending and vibration properties of plate and shell.

Design/methodology/approach
In the present method, each quadrilateral element is first divided into four sub-triangular cells, and the local strains are obtained in those sub-triangles based on linear interpolation. The whole strain filed is formulated through a weighted averaging operation of local strains, implying that only one integration point is adopted to construct the stiffness matrix. To reduce the instability of one-point integration and increase the accuracy of the present method, a stabilization item of the stiffness matrix is formulated by variance of the local strains. A mixed interpolated tensorial components (MITC) method is used in eliminating the shear locking phenomenon.

Findings
The novel EDM based on linear interpolation is effective in bending and vibration analyses of plate and shell, and the present method used in practical problems is reliable for static and free vibration analysis.

Originality/value
This method eliminated the instability of one-point integration and increased the accuracy by a stabilization item and performed stably in engineering analysis including large-scale problems of vehicle components.