bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hip circumduction is not a compensation for reduced knee flexion angle during gait
Authors: Akbas Tunc , Prajapati Sunil , Ziemnicki David , Tamma Poornima , Gross Sarah , Sulzer James 
Published: January 2019

AbstractIt has long been held that hip abduction compensates for reduced swing-phase knee flexion angle, especially in those after stroke. However, there are other compensatory motions such as pelvic obliquity (hip hiking) that could also be used to facilitate foot clearance with greater energy efficiency. Our previous work suggested that hip abduction may not be a compensation for reduced knee flexion after stroke. Previous study applied robotic knee flexion assistance in people with post-stroke Stiff-Knee Gait (SKG) during pre-swing, finding increased abduction despite improved knee flexion and toe clearance. Thus, our hypothesis was that hip abduction is not a compensation for reduced knee flexion. We simulated the kinematics of post-stroke SKG on unimpaired individuals with three factors: a knee orthosis to reduce knee flexion, an ankle-foot orthosis commonly worn by those post-stroke, and matching gait speeds. We compared spatiotemporal measures and kinematics between experimental factors within healthy controls and with a previously recorded cohort of people with post-stroke SKG. We focused on frontal plane motions of hip and pelvis as possible compensatory mechanisms. We observed that regardless of gait speed, knee flexion restriction significantly increased pelvic obliquity (2.79°, p<0.01) compared to unrestricted walking (1.5°, p<0.01), but similar to post-stroke SKG (3.4°). However, those with post-stroke SKG had significantly greater hip abduction (8.2°) compared to unimpaired individuals with restricted knee flexion (4.2°, p<0.05). These results show that pelvic obliquity, not hip abduction, compensates for reduced knee flexion angle. Thus, other factors, possibly neural, facilitate exaggerated hip abduction observed in post-stroke SKG.
Nucleus accumbens cholinergic interneurons oppose cue-motivated behavior
Authors: Collins Anne L. , Aitken Tara J. , Huang I-Wen , Shieh Christine , Greenfield Venuz Y. , Monbouquette Harold G. , Ostlund Sean B. , Wassum Kate. M. 
Published: January 2019

ABSTRACTBackgroundEnvironmental reward-predictive stimuli provide a major source of motivation for adaptive reward pursuit behavior. This cue-motivated behavior is known to be mediated by the nucleus accumbens core (NAc). The cholinergic interneurons in the NAc are tonically active and densely arborized and, thus, well-suited to modulate NAc function. But their causal contribution to adaptive behavior remains unknown. Here we investigated the function of NAc cholinergic interneurons in cue-motivated behavior.MethodsTo do this, we used chemogenetics, optogenetics, pharmacology, and a translationally analogous Pavlovian-to-instrumental transfer behavioral task designed to assess the motivating influence of a reward-predictive cue over reward-seeking actions in male and female rats.ResultsThe data show that NAc cholinergic interneuron activity is necessary and sufficient to oppose the motivating influence of appetitive cues. Chemogenetic inhibition of NAc cholinergic interneurons augmented cue-motivated behavior. Optical stimulation of acetylcholine release from NAc cholinergic interneurons prevented cues from invigorating reward-seeking behavior, an effect that was mediated by activation of β2-containing nicotinic acetylcholine receptors.ConclusionsThus, NAc cholinergic interneurons provide a critical regulatory influence over adaptive cue-motivated behavior and, therefore, are a potential therapeutic target for the maladaptive cue-motivated behavior that marks many psychiatric conditions, including addiction and depression.
Quantitatively Partitioning Microbial Genomic Traits among Taxonomic Ranks across the Microbial Tree of Life
Authors: Royalty Taylor M. , Steen Andrew D. 
Published: January 2019

AbstractWidely used microbial taxonomies, such as the NCBI taxonomy, are based on a combination of sequence homology among conserved genes and historically accepted taxonomies, which were developed based on observable traits such as morphology and physiology. A recently-proposed alternative taxonomy, the Genome Taxonomy Database (GTDB), incorporates only sequence homology of conserved genes and attempts to partition taxonomic ranks such that each rank implies the same amount of evolutionary distance, regardless of its position on the phylogenetic tree. This provides the first opportunity to completely separate taxonomy from traits, and therefore to quantify how taxonomic rank corresponds to traits across the microbial tree of life. We quantified the enrichment of clusters of orthologous gene functional categories (COG-FCs) as a proxy for traits within the lineages of 13,735 cultured and uncultured microbial lineages from a custom-curated genome database. On average, 41.4% of the variation in COG-FC enrichment is explained by taxonomic rank, with domain, phylum, class, order, family, and genus explaining, on average, 3.2%, 14.6%, 4.1%, 9.2%, 4.8%, and 5.5% of the variance, respectively (p<0.001 for all). To our knowledge, this is the first work to quantify the variance in metabolic potential contributed by individual taxonomic ranks. A qualitative comparison between the COG-FC enrichments and genus-level phylogenies, generated from published concatenated protein sequence alignments, further supports the idea that metabolic potential is taxonomically coherent at higher taxonomic ranks. The quantitative analyses presented here constrain the integral relationship between diversification of microbial lineages and the metabolisms which they host.ImportanceRecently there has been great progress in defining a complete taxonomy of bacteria and archaea, which has been enabled by improvements in DNA sequencing technology and new bioinformatic techniques. A new, algorithmically-defined microbial tree of life describes those linkages relying solely on genetic data, which raises the question of how microbial traits relate to taxonomy. Here, we adopted cluster of orthologous group functional categories as a scheme to describe the genomic contents of microbes, which can be applied to any microbial lineage for which genomes are available. This simple approach allows quantitative comparisons between microbial genomes with different gene composition from across the microbial tree of life. Our observations demonstrate statistically significant patterns in cluster of orthologous group functional categories at the taxonomic levels spanning from domain to genus.
Circular inference in bistable perception
Authors: Leptourgos Pantelis , Notredame Charles-Edouard , Eck Marion , Jardri Renaud , Denève Sophie 
Published: January 2019

AbstractWhen facing fully ambiguous images, the brain cannot commit to a single percept and instead switches between mutually exclusive interpretations every few seconds, a phenomenon known as bistable perception. Despite years of research, there is still no consensus on whether bistability, and perception in general, is driven primarily by bottom-up or top-down mechanisms. Here, we adopted a Bayesian approach in an effort to reconcile these two theories. Fifty-five healthy participants were exposed to an adaptation of the Necker cube paradigm, in which we manipulated sensory evidence (by shadowing the cube) and prior knowledge (e.g., by varying instructions about what participants should expect to see). We found that manipulations of both sensory evidence and priors significantly affected the way participants perceived the Necker cube. However, we observed an interaction between the effect of the cue and the effect of the instructions, a finding incompatible with Bayes-optimal integration. In contrast, the data were well predicted by a circular inference model. In this model, ambiguous sensory evidence is systematically biased in the direction of current expectations, ultimately resulting in a bistable percept.
Why does the zebrafishclochemutant develop lens cataract?
Authors: Posner Mason , McDonald Matthew S. , Murray Kelly L. , Kiss Andor J. 
Published: January 2019

AbstractThe zebrafish has become a valuable model for examining ocular lens development, physiology and disease. The zebrafishclochemutant, first described for its loss of hematopoiesis, also shows reduced eye and lens size, interruption in lens cell differentiation and a cataract likely caused by abnormal protein aggregation. To facilitate the use of theclochemutant for studies on cataract development and prevention we characterized variation in the lens phenotype, quantified changes in gene expression by qRT-PCR and RNA-Seq and compared the ability of two promoters to drive expression of introduced proteins into theclochelens. We found that the severity ofclocheembryo lens cataract varied, while the decrease in lens diameter and retention of nuclei in differentiating lens fiber cells was constant. We found very low expression of both αB-crystallin genes (cryabaandcryabb) at 4 days post fertilization (dpf) by both qRT-PCR and RNA-Seq incloche, clochesibling and wildtype embryos and no significant difference in αA-crystallin (cryaa) expression. RNA-Seq analysis of 4 dpf embryos identified transcripts from 25,281 genes, with 1,329 showing statistically significantly different expression betweenclocheand wildtype samples. Downregulation of eight lens β- and γM-crystallin genes and 22 retinal related genes may reflect a general reduction in eye development and growth. Six stress response genes were upregulated. We did not find misregulation of any known components of lens development gene regulatory networks. These results suggest that theclochelens cataract is not caused by loss of αA-crystallin or changes to lens gene regulatory networks. Instead, we propose that the cataract results from general physiological stress related to loss of hematopoiesis. Our finding that the zebrafish αA-crystallin promoter drove strong GFP expression in theclochelens demonstrates its use as a tool for examining the effects of introduced proteins on lens crystallin aggregation and cataract prevention.
Use of FFPE-Derived DNA in Next Generation Sequencing: DNA extraction methods
Authors: McDonough Samantha J. , Bhagwate Aditya , Sun Zhifu , Wang Chen , Zschunke Michael , Gorman Joshua A. , Kopp Karla J. , Cunningham Julie M. 
Published: January 2019

AbstractArchival tissues represent a rich resource for clinical genomic studies, particularly when coupled with comprehensive medical records. Use of these in NGS is a priority. Nine formalin-fixed paraffin-embedded (FFPE) DNA extraction methods were evaluated using twelve FFPE samples of varying tissue types. Quality assessment included total yield, percent ds DNA, fragment analysis and multiplex PCR. After assessment, three tissue types from four FFPE DNA methods were selected for NGS downstream evaluation, whole exome (WES) and targeted sequencing. In addition, two low input library protocols were evaluated for WES. Analysis revealed average coverage across the target regions for WES was ~20-30X for all four FFPE DNA methods. For the targeted panels, the highest molecular tag coverage was obtained with the Kingfisher FFPE extraction method. The genotype concordance was 99% for the commonly called variant positions between all four extraction methods with the targeted PCR NGS panel and 96% with WES.
Binding of Filamentous Actin to CaMKII as a Potential Mechanism for the Regulation of Bidirectional Synaptic Plasticity by βCaMKII in Cerebellar Purkinje Cells
Authors: Pinto Thiago M. , Schilstra Maria J. , Roque Antonio C. , Steuber Volker 
Published: January 2019

AbstractCalcium-calmodulin dependent protein kinase II (CaMKII) regulates many forms of synaptic plasticity, but little is known about its functional role during plasticity induction in the cerebellum. Experiments have indicated that the β isoform of CaMKII controls the bidirectional inversion of plasticity at parallel fibre (PF)-Purkinje cell (PC) synapses in cerebellar cortex. Because the cellular events that underlie these experimental findings are still poorly understood, we developed a simple computational model to investigate how βCaMKII regulates the direction of plasticity in cerebellar PCs. We present the first model of AMPA receptor phosphorylation that simulates the induction of long-term depression (LTD) and potentiation (LTP) at the PF-PC synapse. Our simulation results suggest that the balance of CaMKII-mediated phosphorylation and protein phosphatase 2B (PP2B)-mediated dephosphorylation of AMPA receptors can determine whether LTD or LTP occurs in cerebellar PCs. The model replicates experimental observations that indicate that βCaMKII controls the direction of plasticity at PF-PC synapses, and demonstrates that the binding of filamentous actin to CaMKII can enable the β isoform of the kinase to regulate bidirectional plasticity at these synapses.Author SummaryMany molecules and the complex interactions between them are involved in synaptic plasticity in the cerebellum. However, the exact relationship between cerebellar plasticity and the different signalling cascades remains unclear. Calcium-calmodulin dependent protein kinase II (CaMKII) is an important component of the signalling network that is responsible for plasticity in cerebellar Purkinje cells (PCs). The CaMKII holoenzyme contains different isoforms such as αCaMKII and βCaMKII. Experiments with Camk2b knockout mice that lack the β isoform of CaMKII demonstrated that βCaMKII regulates the direction of plasticity at parallel fibre (PF)-PC synapses. Stimulation protocols that induce long-term depression in wild-type mice, which contain both α and βCaMKII, lead to long-term potentiation in knockout mice without βCaMKII, and vice versa. We developed a kinetic simulation of the phosphorylation and dephosphorylation of AMPA receptors by CaMKII and protein phosphatase 2B to investigate how βCaMKII can control bidirectional synaptic plasticity in cerebellar PCs. Our simulation results demonstrate that the binding of filamentous actin to βCaMKII can contribute to the regulation of bidirectional plasticity at PF-PC synapses. Our computational model of intracellular signalling significantly advances the understanding of the mechanisms of synaptic plasticity induction in the cerebellum.
Regulation of Parent-of-Origin Allelic Expression inArabidopsis thalianaendosperm
Authors: Hornslien Karina S. , Miller Jason R. , Grini Paul E. 
Published: January 2019

AbstractGenomic imprinting is an epigenetic phenomenon set in the gametes prior to fertilization that causes differential expression of parental alleles mainly in the endosperm of flowering plants. The overlap between previously identified panels of imprinted genes is limited. In order to achieve high resolution sequencing data we have used sequence capture technology to investigate imprinting. Here, we present a bioinformatics pipeline to assay parent-of-origin allele specific expression and report more than 300 loci with parental expression bias. We find that the level of expression from maternal and paternal alleles in most cases is not binary, instead favouring a differential dosage hypothesis for the evolution of imprinting in plants. To address imprinting regulation, we systematically employed mutations in regulative epigenetic pathways suggested to be major players in the process. We establish the mechanistic mode of imprinting for more than 50 loci regulated by DNA methylation and Polycomb-dependent histone methylation. However, the imprinting patterns of the majority of genes were not affected by these mechanisms. To this end we also demonstrate that the RNA-directed DNA methylation pathway alone does not influence imprinting patterns in a substantial manner, suggesting more complex epigenetic regulation pathways for the majority of identified imprinted genes.Author summaryExpression of gene copies only from the mother or the father’s genome, also termed imprinting, is a specialized epigenetic phenomenon that is found to be enriched at some genes expressed in the mammalian placenta and in the endosperm of the plant seed. Although several studies have reported on imprinted genes in plants, the identified loci are at large non-overlapping between reports. This motivated us to investigate in detail the expression pattern of imprinted genes in the endosperm and to determine how imprinting patterns are established at various imprinted loci. Although several underlying epigenetic regulation mechanisms have been demonstrated to establish imprinting patterns at certain genes, the majority of imprinted genes have not been linked to such mechanisms. In the present study we systematically investigated the mechanisms that are involved in establishing imprinting, by employing mutants of epigenetic regulators and high-throughput sequencing. In our high resolution study, we report more than 300 imprinted genes and demonstrate that the biological phenomenon imprinting involves gradual expression of parental gene copies rather than switching gene copies on or off. Notably, for the majority of imprinted genes, the mechanisms previously believed to be major to establish their imprinting patterns, are not responsible for mediating imprinting.
100 PhD rules of the game to successfully complete a doctoral dissertation
Authors: Brennan Niamh M. 
Published: January 2019

Purpose
A doctoral dissertation is a challenging undertaking requiring determination, persistence and resilience over a long time: four to six years’ study or more. These PhD “rules of the game” are intended to help students successfully navigate this challenge.

Design/methodology/approach
The author has assembled 100 PhD rules of the game from the author’s work over many years with masters and doctoral students. Each rule is accompanied by some further short guidance. Additional citations are included directing readers to resources embellishing the 100 PhD rules of the game.

Findings
The paper documents 100 PhD rules of the game.

Research limitations/implications
There are many other PhD rules of the game not included in the author’s list of 100 PhD rules of the game.

Originality/value
This paper is a one-stop-shop brief introduction to the author’s 100 PhD rules of the game.
The evolving nature of the marketing–supply chain management interface in contemporary markets
Authors: Noci Giuliano 
Published: January 2019

Purpose
The purpose of this paper is to reshape and interpret the essence of marketing–supply chain management (M–SCM) interface in the glance of the dramatic changes occurring in competition and market relationships.

Design/methodology/approach
By reviewing relevant literature and analyzing evolutions in the different phases of the marketing funnel, the author develops an evolutionary pattern for M–SCM interface.

Findings
As the markets evolve to an always-on, service-dominant logic, being market-driving becomes a necessary condition, and as such marketing strategies must be capable of reconfiguring supply chains to reshape the value for customers. This implies a dramatic organizational change, even beyond mere technological issues.

Originality/value
The paper aims at setting some research directions for business process management and organizational patterns to govern M–SCM interface.
Measuring construction for social, economic and environmental assessment
Authors: Ilhan Bahriye , Yobas Banu 
Published: January 2019

Purpose
The purpose of this paper is to examine the issues that should be considered for a better gauge of the construction industry and built environment and to propose a set of indicators for measuring the social, economic and environmental value of construction.

Design/methodology/approach
The indicators proposed in this study use Pearce’s schema, which presents a framework to evaluate the socio-economic value of construction and its contribution to sustainable development. After analysing the problems faced by the industry, solutions are raised and finally indicators for each pillar of Pearce’s schema are established through a literature review. Since the proposed indicators can be used for cross-country analysis, these comparisons are also presented as graphs including only those countries for which valid national data could be sourced from OECD databases.

Findings
The issues, suggestions and indicators related to each concern about the main domains of the schema are addressed through the related literature and supported by available statistical data.

Originality/value
Although previous studies have drawn attention to measures for better evaluation of the construction industry and the built environment, this study, distinctively, presents an integrated approach in order to gauge the true value and impacts of construction in a more comprehensive way. The work’s contribution to the body of knowledge is in revealing the hidden input and impact of construction on sustainable development by determining the barriers to this and their solutions, in addition to the proposal of relevant indicators.
Genome‐wide variation in nucleotides and retrotransposons in alpine populations of Arabis alpina (Brassicaceae)
Authors: Rogivue Aude , Choudhury Rimjhim R. , Zoller Stefan , Joost Stéphane , Felber François , Kasser Michel , Parisod Christian , Gugerli Felix 
Published: January 2019

AbstractAdvances in high‐throughput sequencing have promoted the collection of reference genomes and genome‐wide diversity. However, the assessment of genomic variation among populations has hitherto mainly been surveyed through single‐nucleotide polymorphisms (SNPs) and largely ignored the often major fraction of genomes represented by transposable elements (TEs). Despite accumulating evidence supporting the evolutionary significance of TEs, comprehensive surveys remain scarce. Here, we sequenced the full genomes of 304 individuals of Arabis alpina sampled from four nearby natural populations to genotype SNPs as well as polymorphic long terminal repeat retrotransposons (polymorphic TEs; i.e., presence/absence of TE insertions at specific loci). We identified 291,396 SNPs and 20,548 polymorphic TEs, comparing their contributions to genomic diversity and divergence across populations. Few SNPs were shared among populations and overall showed high population‐specific variation, whereas most polymorphic TEs segregated among populations. The genomic context of these two classes of variants further highlighted candidate adaptive loci having a putative impact on functional genes. In particular, 4.96% of the SNPs were identified as nonsynonymous or affecting start/stop codons. In contrast, 43% of the polymorphic TEs were present next to Arabis genes enriched in functional categories related to the regulation of reproduction and responses to biotic as well as abiotic stresses. This unprecedented data set, mapping variation gained from SNPs and complementary polymorphic TEs within and among populations, will serve as a rich resource for addressing microevolutionary processes shaping genome variation.