bluuebunny/crossref_metadata_2025_split huggingface dataset:
A microcalorimetric approach for investigating stoichiometric constraints on the standard metabolic rate of a small invertebrate
Authors: Thomas Ruiz , Alexandre Bec , Michael Danger , Apostolos-Manuel Koussoroplis , Jean-Pierre Aguer , Jean-Pierre Morel , Nicole Morel-Desrosiers 
Published: March 2018

Abstract1: Understanding the determinant of metabolism is a core ecological topic since it permits to link individuals energetic requirements to the ecology of communities and ecosystems. Yet, besides temperature, the effects of environmental factors on metabolism remain poorly understood. For example, dietary stoichiometric constraints have been hypothesized to increase maintenance metabolism of small invertebrates, yet experimental support remains scarce.2: Here, we used microcalorimetric heat flow measurements to determine the standard metabolic rate (SMR) ofDaphnia magnathroughout its ontogeny when fed stoichiometrically balanced (C/P ratio:166) or imbalanced (C/P ratio:1439) diets.3: When fed a stoichiometrically imbalanced diet,daphnidswere able to maintain the stoichiometric homeostasis within narrow boundaries. However, they consistently increased their SMR while decreasing their somatic growth rate. Our measurements unequivocally demonstrate that homeostatic regulation implies higher metabolic costs and thereby reduces the portion of energy that can be allocated to growth.4: Our study demonstrates that microcalorimetry is a powerful and precise tool for measuring the metabolic rate of small-sized organisms and opens promising perspectives for understanding how environmental factors, such as nutritional constraints, affect organismal metabolism.
Automation of citation screening in pre-clinical systematic reviews
Authors: Liao J. , Ananiadou S. , Currie L. G. , Howard B. E. , Rice A. , Sena S. E. , Thomas J. , Varghese A. , Macleod M.R. 
Published: March 2018

AbstractBackgroundThe amount of published in vivo studies and the speed researchers are publishing them make it virtually impossible to follow the recent development in the field. Systematic review emerged as a method to summarise and analyse the studies quantitatively and critically but it is often out-of-date due to its lengthy process.MethodWe invited five machine learning and text-mining groups to build classifiers for identifying publications relevant to neuropathic pain (33814 training publications). We kept 1188 publications for the assessment of the performance of different classifiers. Two groups participated in the next stage: testing their algorithm on datasets labeled for psychosis (11777/2944) and datasets labeled for Vitamin D in multiple sclerosis (train/text: 2038/510).ResultThe performances (sensitive/specificity) of the most promising classifier built for neuropathic pain are: 95%/84%. The performance for psychosis and Vitamin D in multiple sclerosis datasets are 95%/73% and 100%/45%.ConclusionsMachine learning can significantly reduce the irrelevant publications in a systematic review, and save the scientists’ time and money. Classifier algorithms built for one dataset can be reapplied on another dataset in different field. We are building a machine learning service at the back of Systematic Review & Meta-analysis Facility (SyRF).
A homing CRISPR mouse resource for barcoding and lineage tracing
Authors: Kalhor Reza , Kalhor Kian , Leeper Kathleen , Graveline Amanda , Mali Prashant , Church George M. 
Published: March 2018

AbstractCellular barcoding using nuclease-induced genetic mutations is an effective approach that is emerging for recording biological information, including developmental lineages. We have previously introduced the homing CRISPR system as a promising methodology for generating such barcodes with scalable diversity and without crosstalk. Here, we present a mouse line (MARC1) with multiple genomically-integrated and heritable homing guide RNAs (hgRNAs). We determine the genomic locations of these hgRNAs, their activity profiles during gestation, and the diversity of their mutants. We apply the line for unique barcoding of mouse embryos and differential barcoding of embryonic tissues. We conclude that this mouse line can address the unique challenges associated with in vivo barcoding in mammalian model organisms and is thus an enabling platform for recording and lineage tracing applications in a mammalian model system.
Automated Adherent Cell Elimination by a High-Speed Laser Mediated by a Light-Responsive Polymer
Authors: Hayashi Yohei , Matsumoto Junichi , Kumagai Shohei , Morishita Kana , Xiang Long , Kobori Yohei , Hori Seiji , Suzuki Masami , Kanamori Toshiyuki , Hotta Kazuhiro , Sumaru Kimio 
Published: March 2018

AbstractConventional cell handling and sorting methods require manual dissociation, which decreases cell quality and quantity and is not well suited for monitoring applications. To purify adherent cultured cells, in situ cell purification technologies that are high throughput and can be utilized in an on-demand manner are expected. Previous demonstrations using direct laser-mediated cell elimination revealed only limited success in terms of their usability and throughput. Here, we developed a Laser-Induced, Light-responsive-polymer-Activated, Cell Killing (LILACK) system that enables high-speed and on-demand adherent cell sectioning and purification. This system employs a visible laser beam, which does not kill cells directly, but induces local heat production through the trans-cis-trans photo-isomerization of azobenzene moieties in only the irradiated area of a light-responsive thin layer. Using this system in each passage for sectioning, human induced pluripotent stem cells (hiPSCs) were maintained their pluripotency and self-renewal during long-term culture. Furthermore, combined with deep machine-learning analysis on fluorescent and phase contrast images, a label-free and automatic cell processing system was developed by eliminating unwanted spontaneously differentiated cells in undifferentiated hiPSC culture conditions.
A generalizable experimental framework for automated cell growth and laboratory evolution
Authors: Wong Brandon G. , Mancuso Christopher P. , Kiriakov Szilvia , Bashor Caleb J. , Khalil Ahmad S. 
Published: March 2018

ABSTRACTIn the post-genomics era, exploration of phenotypic adaptation is limited by our ability to experimentally control selection conditions, including multi-variable and dynamic pressure regimes. While automated cell culture systems offer real-time monitoring and fine control over liquid cultures, they are difficult to scale to high-throughput, or require cumbersome redesign to meet diverse experimental requirements. Here we describe eVOLVER, a multipurpose, scalable DIY framework that can be easily configured to conduct a wide variety of growth fitness experiments at scale and cost. We demonstrate eVOLVER’s versatility by configuring it for diverse growth and selection experiments that would be otherwise challenging for other systems. We conduct high-throughput evolution of yeast across different population density niches. We perform growth selection on a yeast knockout library under temporally varying temperature regimes. Finally, inspired by large-scale integration in electronics and microfluidics, we develop novel millifluidic multiplexing modules that enable complex fluidic routines including multiplexed media routing, cleaning, vial-to-vial transfers, and automated yeast mating. We propose eVOLVER to be a versatile design framework in which to study, characterize, and evolve biological systems.
Wheat shovelomics I: A field phenotyping approach for characterising the structure and function of root systems in tillering species
Authors: York Larry M. , Slack Shaunagh , Bennett Malcolm J , Foulkes M John 
Published: March 2018

AbstractWheat represents a major crop, yet the current rate of yield improvement is insufficient to meet its projected global food demand. Breeding root systems more efficient for water and nitrogen capture represents a promising avenue for accelerating yield gains. Root crown phenotyping, or shovelomics, relies on excavation of the upper portions of root systems in the field and measuring root properties such as numbers, angles, densities and lengths. We report a new shovelomics method that images the whole wheat root crown, then partitions it into the main shoot and tillers for more intensive phenotyping. Root crowns were phenotyped using the new method from the Rialto × Savannah population consisting of both parents and 94 doubled-haploid lines. For the whole root crown, the main shoot, and tillers, root phenes including nodal root number, growth angle, length, and diameter were measured. Substantial variation and heritability were observed for all phenes. Principal component analysis revealed latent constructs that imply pleiotropic genetic control of several related root phenes. Correlational analysis revealed that nodal root number and growth angle correlate among the whole crown, main shoot, and tillers, indicating shared genetic control among those organs. We conclude that this phenomics approach will be useful for breeding ideotype root systems in tillering species.
GABA promotes survival and axonal regeneration in identifiable descending neurons after spinal cord injury in larval lampreys
Authors: Romaus-Sanjurjo D , Ledo-García R , Fernández-López B , Hanslik K , Morgan JR , Barreiro-Iglesias A , Rodicio MC 
Published: March 2018

AbstractIn mammals, spinal cord injury (SCI) causes permanent disability. The poor regenerative capacity of descending neurons is one of the main causes of the lack of recovery after SCI. In addition, the prevention of retrograde degeneration leading to the atrophy or death of descending neurons is an obvious prerequisite for the activation of axonal regeneration. Lampreys show an amazing regenerative capacity after SCI. Recent histological work in lampreys suggested that GABA, which is massively released after a SCI, could promote the survival of descending neurons. Here, we aimed to study if GABA, acting through GABAB receptors, promotes the survival and axonal regeneration of descending neurons of larval sea lampreys after a complete SCI. First, we used in situ hybridization to confirm that identifiable descending neurons of late stage larvae express the gabab1 subunit of the sea lamprey GABAB receptor. We also observed an acute increase in the expression of this subunit in descending neurons after a complete SCI, which further supported the possible role of GABA and GABAB receptors in promoting the survival and regeneration of these neurons. So, we performed gain and loss of function experiments to confirm this hypothesis. Treatments with GABA and baclofen (GABAB agonist) significantly reduced caspase activation in descending neurons 2 weeks after a complete SCI. Long-term treatments with GABOB (a GABA analogue) and baclofen significantly promoted axonal regeneration of descending neurons after SCI. These data indicate that GABAergic signalling through GABAB receptors promotes the survival and regeneration of descending neurons after SCI. Finally, we used morpholinos against the gabab1 subunit to specifically knockdown the expression of the GABAB receptor in descending neurons. Long-term morpholino treatments caused a significant inhibition of axonal regeneration, which shows that endogenous GABA promotes axonal regeneration after a complete SCI in lampreys by activating GABAB receptors expressed in descending neurons. These data implicate GABAB receptors in spinal cord regeneration in lampreys and further provide a new target of interest for SCI.
BART: a transcription factor prediction tool with query gene sets or epigenomic profiles
Authors: Wang Zhenjia , Civelek Mete , Miller Clint L. , Sheffield Nathan C. , Guertin Michael J. , Zang Chongzhi 
Published: March 2018

AbstractSummaryIdentification of functional transcription factors that regulate a given gene set is an important problem in gene regulation studies. Conventional approaches for identifying transcription factors, such as DNA sequence motif analysis, are unable to predict functional binding of specific factors and not sensitive to detect factors binding at distal enhancers. Here we present Binding Analysis for Regulation of Transcription (BART), a novel computational method and software package for predicting functional transcription factors that regulate a query gene set or associate with a query genomic profile, based on more than 6,000 existing ChIP-seq datasets for over 400 factors in human or mouse. This method demonstrates the advantage of utilizing publicly available data for functional genomics research.AvailabilityBART is implemented in Python and available at http://faculty.virginia.edu/zanglab/bartContact: zang@virginia.edu
Progressive impairment of directional and spatially precise trajectories by TgF344-AD Rats in the Morris Water Task
Authors: Berkowitz Laura E. , Harvey Ryan E. , Drake Emma , Thompson Shannon M. , Clark Benjamin J. 
Published: March 2018

AbstractSpatial navigation is impaired in early stages of Alzheimer’s disease (AD), and may be a defining behavioral marker of preclinical AD. Nevertheless, limitations of diagnostic criteria for AD and within animal models of AD make characterization of preclinical AD difficult. A new rat model (TgF344-AD) of AD overcomes many of these limitations, though spatial navigation has not been comprehensively assessed. Using the hidden and cued platform variants of the Morris water task, a longitudinal assessment of spatial navigation was conducted on TgF344-AD (n=16) and Fischer 344 (n=12) male and female rats at three age ranges: 4 to 5 months, 7 to 8, and 10 to 11 months of age. TgF344-AD rats exhibited largely intact navigation at 4-5 and 7-8 months of age, with deficits in the hidden platform task emerging at 10-11 months of age. In general, TgF344-AD rats displayed less accurate swim trajectories to the platform and a wider search area around the platform region compared to wildtype rats. Impaired navigation occurred in the absence of deficits in acquiring the procedural task demands or navigation to the cued platform location. Together, the results indicate that TgF344-AD rats exhibit comparable deficits to those found in individuals in the early stages of AD.
Putative rapid-acting antidepressant nitrous oxide (“laughing gas”) evokes rebound emergence of slow EEG oscillations during which TrkB signaling is induced
Authors: Kohtala Samuel , Theilmann Wiebke , Rosenholm Marko , Kiuru Paula , Uusitalo Salla , Järventausta Kaija , Yli-Hankala Arvi , Yli-Kauhaluoma Jari , Wigren Henna-Kaisa , Rantamäki Tomi 
Published: March 2018

AbstractElectroconvulsive therapy (ECT) remains among the most efficient antidepressants but it seldom brings immediate remedy. However, a subanesthetic dose of NMDA-R (N-methyl-D-aspartate receptor) blocker ketamine ameliorates symptoms of depression already within hours. Glutamatergic excitability and regulation of TrkB neurotrophin receptor and GSK3β (glycogen synthase kinase 3β) signaling are considered as molecular-level determinants for ketamine’s antidepressant effects. Recent clinical observations suggests that nitrous oxide (N2O, “laughing gas”), another NMDA-R blocking dissociative anesthestic, also produces rapid antidepressant effects but the underlying mechanisms remain essentially unstudied. In this animal study we show that N2O, with a clinically relevant dosing regimen, evokes an emergence of rebound slow EEG (electroencephalogram) oscillations, a phenomenon considered to predict the efficacy and onset-of-action ECT. Very similar rebound slow oscillations are induced by subanesthetic ketamine and flurothyl (a treatment analogous to ECT). These responses become best evident upon drug withdrawal, i.e. after the peak of acute pharmacological actions, when their most prominent effects on cortical excitability have subsided. Most importantly, TrkB and GSK3β signaling remain unchanged during N2O administration (ongoing NMDA-R blockade) but emerge gradually upon gas withdrawal along with increased slow EEG oscillations. Collectively these findings reveal that rapid-acting antidepressants produce cortical excitability that triggers “a brain state” dominated by ongoing slow oscillations, sedation and drowsiness during which TrkB and GSK3β signaling alterations are induced.
Variability and compensation of cardiomycoyte ionic conductances at the population level
Authors: Rees Colin , Yang Jun-Hai , Santolini Marc , Lusis Aldons J. , Weiss James N. , Karma Alain 
Published: March 2018

AbstractConductances of ion channels and transporters controlling cardiac excitation may vary in a population of subjects with different cardiac gene expression patterns. However, the amount of variability and its origin are not quantitatively known. We propose a new computational method to predict this variability that consists of finding combinations of conductances generating a normal intracellular Ca2+transient without any constraint on the action potential. Furthermore, we validate experimentally its predictions using the Hybrid Mouse Diversity Panel, a model system of genetically diverse mouse strains that allows us to quantify inter-subject versus intra-subject variability. The method predicts that conductances of inward Ca2+and outward K+currents compensate each other to generate a normal Ca2+transient in good quantitative agreement with current measurements in ventricular myocytes from hearts of different isogenic strains. Our results suggest that a feedback mechanism sensing the aggregate Ca2+transient of the heart suffices to regulate ionic conductances.
Response surface approach to robust design of assembly cells through simulation
Authors: Aydin Cem Savas , Ozgurler Senim , Durmusoglu Mehmet Bulent , Ozgurler Mesut 
Published: March 2018

PurposeThis paper aims to present a multi-response robust design (RD) optimization approach for U-shaped assembly cells (ACs) with multi-functional walking-workers by using operational design (OD) factors in a simulation setting. The proposed methodology incorporated the design factors related to the operation of ACs into an RD framework. Utilization of OD factors provided a practical design approach for ACs addressing system robustness without modifying the cell structure.Design/methodology/approachTaguchi’s design philosophy and response surface meta-models have been combined for robust simulation optimization (SO). Multiple performance measures have been considered for the study and concurrently optimized by using a multi-response optimization (MRO) approach. Simulation setting provided flexibility in experimental design selection and facilitated experiments by avoiding cost and time constraints in real-world experiments.FindingsThe present approach is illustrated through RD of an AC for performance measures: average throughput time, average WIP inventory and cycle time. Findings are in line with expectations that a significant reduction in performance variability is attainable by trading-off optimality for robustness. Reductions in expected performance (optimality) values are negligible in comparison to reductions in performance variability (robustness).Practical implicationsACs designed for robustness are more likely to meet design objectives once they are implemented, preventing changes or roll-backs. Successful implementations serve as examples to shop-floor personnel alleviating issues such as operator/supervisor resistance and scepticism, encouraging participation and facilitating teamwork.Originality/valueACs include many activities related to cell operation which can be used for performance optimization. The proposed framework is a realistic design approach using OD factors and considering system stochasticity in terms of noise factors for RD optimization through simulation. To the best of the authors’ knowledge, it is the first time a multi-response RD optimization approach for U-shaped manual ACs with multi-functional walking-workers using factors related to AC operation is proposed.
Examining the linkage among open innovation, customer knowledge management and radical innovation
Authors: Wang Xin , Xu Ming 
Published: March 2018

PurposeThe purpose of this paper is to propose a research model exploring the link between open innovation, customer knowledge management and radical innovation. It seeks to answer these research questions: is there any difference among the effects of different types of open innovation activities on radical innovation? How does the organizational learning ability influence the impact of customer knowledge management on radical innovation?Design/methodology/approachThe paper is based on the data collected from a sample of 165 modern service enterprises located in the Yangtze River Delta region. The authors conducted a structural equation modeling analysis using SPSS and MPLUS to test the proposed hypotheses.FindingsThe results showed that different kinds of open innovation activities had different impacts on the path to radical innovation. Inbound open innovation activities directly influenced radical innovation while the effect of outbound open innovation activities on radical innovation combined with the organizational exploitative learning ability is indirect. Similarly, the empirical results also proved that customer knowledge management had an indirect effect on radical innovation through the organizational learning ability, and the influence of the exploratory learning ability was more prominent.Originality/valueUnder the background of the national innovation driven by the development strategy, this paper studies the impact mechanism of radical innovation from the perspectives of open innovation and customer knowledge management. Therefore, it is suggested that the enterprise should adopt open innovation activities to foster innovation performance, formulate a customer-oriented innovation strategy and invest information and communication technologies to enhance the organizational learning ability of the enterprise.