bluuebunny/crossref_metadata_2025 huggingface dataset:
Ducks in space: from nonlinear absolute instability to noise-sustained structures in a pattern-forming system
Authors: Avitabile D. , Desroches M. , Knobloch E. , Krupa M.
Published: March 2018

A subcritical pattern-forming system with nonlinear advection in a bounded domain is recast as a slow–fast system in space and studied using a combination of geometric singular perturbation theory and numerical continuation. Two types of solutions describing the possible location of stationary fronts are identified, whose origin is traced to the onset of convective and absolute instability when the system is unbounded. The former are present only for non-zero upstream boundary conditions and provide a quantitative understanding of noise-sustained structures in systems of this type. The latter correspond to the onset of a global mode and are present even with zero upstream boundary conditions. The role of canard trajectories in the nonlinear transition between these states is clarified and the stability properties of the resulting spatial structures are determined. Front location in the convective regime is highly sensitive to the upstream boundary condition, and its dependence on this boundary condition is studied using a combination of numerical continuation and Monte Carlo simulations of the partial differential equation. Statistical properties of the system subjected to random or stochastic boundary conditions at the inlet are interpreted using the deterministic slow–fast spatial dynamical system.
Force direction patterns promote whole body stability even in hip-flexed walking, but not upper body stability in human upright walking
Authors: Müller Roy , Rode Christian , Aminiaghdam Soran , Vielemeyer Johanna , Blickhan Reinhard
Published: March 2018

Directing the ground reaction forces to a focal point above the centre of mass of the whole body promotes whole body stability in human and animal gaits similar to a physical pendulum. Here we show that this is the case in human hip-flexed walking as well. For all upper body orientations (upright, 25°, 50°, maximum), the focal point was well above the centre of mass of the whole body, suggesting its general relevance for walking. Deviations of the forces' lines of action from the focal point increased with upper body inclination from 25 to 43 mm root mean square deviation (RMSD). With respect to the upper body in upright gait, the resulting force also passed near a focal point (17 mm RMSD between the net forces' lines of action and focal point), but this point was 18 cm below its centre of mass. While this behaviour mimics an unstable inverted pendulum, it leads to resulting torques of alternating sign in accordance with periodic upper body motion and probably provides for low metabolic cost of upright gait by keeping hip torques small. Stabilization of the upper body is a consequence of other mechanisms, e.g. hip reflexes or muscle preflexes.
Symmetric rearrangement of groundwater-fed streams
Authors: Yi Robert , Cohen Yossi , Devauchelle Olivier , Gibbins Goodwin , Seybold Hansjörg , Rothman Daniel H.
Published: March 2018

Streams shape landscapes through headward growth and lateral migration. When these streams are primarily fed by groundwater, recent work suggests that their tips advance to maximize the symmetry of the local Laplacian field associated with groundwater flow. We explore the extent to which such forcing is responsible for the lateral migration of streams by studying two features of groundwater-fed streams in Bristol, Florida: their confluence angle near junctions and their curvature. First, we find that, while streams asymptotically form a 72° angle near their tips, they simultaneously exhibit a wide 120° confluence angle within approximately 10 m of their junctions. We show that this wide angle maximizes the symmetry of the groundwater field near the junction. Second, we argue that streams migrate laterally within valleys and present a new spectral analysis method to relate planform curvature to the surrounding groundwater field. Our results suggest that streams migrate laterally in response to fluxes from the surrounding groundwater table, providing evidence of a new mechanism that complements Laplacian growth at their tips.
Neuropharmacology of compulsive eating
Authors: Moore Catherine F. , Panciera Julia I. , Sabino Valentina , Cottone Pietro
Published: March 2018

Compulsive eating behaviour is a transdiagnostic construct observed in certain forms of obesity and eating disorders, as well as in the proposed construct of ‘food addiction'. Compulsive eating can be conceptualized as comprising three elements: (i) habitual overeating, (ii) overeating to relieve a negative emotional state, and (iii) overeating despite adverse consequences. Neurobiological processes that include maladaptive habit formation, the emergence of a negative affect, and dysfunctions in inhibitory control are thought to drive the development and persistence of compulsive eating behaviour. These complex psychobehavioural processes are under the control of various neuropharmacological systems. Here, we describe the current evidence implicating these systems in compulsive eating behaviour, and contextualize them within the three elements. A better understanding of the neuropharmacological substrates of compulsive eating behaviour has the potential to significantly advance the pharmacotherapy for feeding-related pathologies.

This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.
Translational new approaches for investigating mood disorders in rodents and what they may reveal about the underlying neurobiology of major depressive disorder
Authors: Robinson Emma S. J.
Published: March 2018

Mood disorders represent one of society's most costly and challenging health burdens. The drug treatments used today were initially discovered serendipitously in the 1950s. Animal models were then developed based on the ability of these drugs to alter specific behaviours. These models have played a major role in the development of the second generation of antidepressants. However, their use has been heavily criticized, particularly in relation to whether they recapitulate similar underlying biology to the psychiatric disorder they are proposed to represent. This article considers our work in the field of affective bias and the development of a translational research programme to try to develop and validate better animal models. We discuss whether the new data that have arisen from these studies support an alternative perspective on the underlying neurobiological processes that lead to major depressive disorder (MDD). Specifically, this article will consider whether a neuropsychological mechanism involving affective biases plays a causal role in the development of MDD and its associated emotional and behavioural symptoms. These animal studies also raise the possibility that neuropsychological mechanisms involving affective biases are a precursor to, rather than a consequence of, the neurotrophic changes linked to MDD.

This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.
Responses of migratory species and their pathogens to supplemental feeding
Authors: Satterfield Dara A. , Marra Peter P. , Sillett T. Scott , Altizer Sonia
Published: March 2018

Migratory animals undergo seasonal and often spectacular movements and perform crucial ecosystem services. In response to anthropogenic changes, including food subsidies, some migratory animals are now migrating shorter distances or halting migration altogether and forming resident populations. Recent studies suggest that shifts in migratory behaviour can alter the risk of infection for wildlife. Although migration is commonly assumed to enhance pathogen spread, for many species, migration has the opposite effect of lowering infection risk, if animals escape from habitats where pathogen stages have accumulated or if strenuous journeys cull infected hosts. Here, we summarize responses of migratory species to supplemental feeding and review modelling and empirical work that provides support for mechanisms through which resource-induced changes in migration can alter pathogen transmission. In particular, we focus on the well-studied example of monarch butterflies and their protozoan parasites in North America. We also identify areas for future research, including combining new technologies for tracking animal movements with pathogen surveillance and exploring potential evolutionary responses of hosts and pathogens to changing movement patterns. Given that many migratory animals harbour pathogens of conservation concern and zoonotic potential, studies that document ongoing shifts in migratory behaviour and infection risk are vitally needed.

This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’.
Food for contagion: synthesis and future directions for studying host–parasite responses to resource shifts in anthropogenic environments
Authors: Altizer Sonia , Becker Daniel J. , Epstein Jonathan H. , Forbes Kristian M. , Gillespie Thomas R. , Hall Richard J. , Hawley Dana M. , Hernandez Sonia M. , Martin Lynn B. , Plowright Raina K. , Satterfield Dara A. , Streicker Daniel G.
Published: March 2018

Human-provided resource subsidies for wildlife are diverse, common and have profound consequences for wildlife–pathogen interactions, as demonstrated by papers in this themed issue spanning empirical, theoretical and management perspectives from a range of study systems. Contributions cut across scales of organization, from the within-host dynamics of immune function, to population-level impacts on parasite transmission, to landscape- and regional-scale patterns of infection. In this concluding paper, we identify common threads and key findings from author contributions, including the consequences of resource subsidies for (i) host immunity; (ii) animal aggregation and contact rates; (iii) host movement and landscape-level infection patterns; and (iv) interspecific contacts and cross-species transmission. Exciting avenues for future work include studies that integrate mechanistic modelling and empirical approaches to better explore cross-scale processes, and experimental manipulations of food resources to quantify host and pathogen responses. Work is also needed to examine evolutionary responses to provisioning, and ask how diet-altered changes to the host microbiome influence infection processes. Given the massive public health and conservation implications of anthropogenic resource shifts, we end by underscoring the need for practical recommendations to manage supplemental feeding practices, limit human–wildlife conflicts over shared food resources and reduce cross-species transmission risks, including to humans.

This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’.
Estimating mechanical properties of cloth from videos using dense motion trajectories: human psychophysics and machine learning
Authors: Bi Wenyan , Jin Peiran , Nienborg Hendrikje , Xiao Bei
Published: March 2018

Humans can visually estimate the mechanical properties of deformable objects (e.g. cloth stiffness). While much of the recent work on material perception has focused on static image cues (e.g., textures and shape), little is known whether humans can integrate information over time to make a judgment. Here, we investigate the effect of spatiotemporal information across multiple frames (multi-frame motion) on estimating the bending stiffness of cloth. Using high-fidelity cloth animations, we first examined how the perceived bending stiffness changed as a function of the physical bending stiffness defined in the simulation model. Using maximum likelihood difference scaling methods (MLDS) we found that the perceived stiffness and the physical bending stiffness were highly correlated. A second experiment in which we scrambled the frame sequences diminished this correlation. This suggests that multi-frame motion plays an important role. To provide further evidence for this finding, we extracted dense motion trajectories from the videos across 15 consecutive frames and used the trajectory descriptors to train a machine-learning model with the measured perceptual scales. The model can predict human perceptual scales in new videos with varied winds, optical properties of cloth, and scene setups. When the correct multi-frame was removed (using either scrambled videos or 2-frame optical flow to train the model), the predictions significantly worsened. Our findings demonstrate that multi-frame motion information is important for both humans and machines to estimate the mechanical properties. In addition, we show that dense motion trajectories are effective features to build a successful automatic cloth estimation system.
Patterns of genetic differentiation and the footprints of historical migrations in the Iberian Peninsula
Authors: Bycroft Clare , Fernandez-Rozadilla Ceres , Ruiz-Ponte Clara , Quintela-García Inés , Carracedo Ángel , Donnelly Peter , Myers Simon
Published: March 2018

Genetic differences within or between human populations (population structure) has been studied using a variety of approaches over many years. Recently there has been an increasing focus on studying genetic differentiation at fine geographic scales, such as within countries. Identifying such structure allows the study of recent population history, and identifies the potential for confounding in association studies, particularly when testing rare, often recently arisen variants. The Iberian Peninsula is linguistically diverse, has a complex demographic history, and is unique among European regions in having a centuries-long period of Muslim rule. Previous genetic studies of Spain have examined either a small fraction of the genome or only a few Spanish regions. Thus, the overall pattern of fine-scale population structure within Spain remains uncharacterised. Here we analyse genome-wide genotyping array data for 1,413 Spanish individuals sampled from all regions of Spain. We identify extensive fine-scale structure, down to unprecedented scales, smaller than 10 Km in some places. We observe a major axis of genetic differentiation that runs from east to west of the peninsula. In contrast, we observe remarkable genetic similarity in the north-south direction, and evidence of historical north-south population movement. Finally, without making particular prior assumptions about source populations, we show that modern Spanish people have regionally varying fractions of ancestry from a group most similar to modern north Moroccans. The north African ancestry results from an admixture event, which we date to 860 - 1120 CE, corresponding to the early half of Muslim rule. Our results indicate that it is possible to discern clear genetic impacts of the Muslim conquest and population movements associated with the subsequent Reconquista.
FASTGenomics: An analytical ecosystem for single-cell RNA sequencing data
Authors: Scholz Claus J. , Biernat Paweł , Becker Matthias , Baßler Kevin , Günther Patrick , Balfer Jenny , Dickten Henning , Flöer Lars , Heikamp Kathrin , Angerer Philipp , Heilig Mathias , Karle Ralf , Köhler Meike , Mazurkiewicz Thomas , Mönnighoff Martin , Sauer Christian , Schick Albrecht , Schlemm Gerhard , Weigelt Roland , Winkler Martin , Ulas Thomas , Theis Fabian , Huthmacher Stephan , Kratsch Christina , Schultze Joachim L.
Published: March 2018

Recent technological advances enable genomics of individual cells, the building blocks of all living organisms. Single cell data characteristics differ from those of bulk data, which led to a plethora of new analytical strategies. However, solutions are only useful for experts and currently, there are no widely accepted gold standards for single cell data analysis. To meet the requirements of analytical flexibility, ease of use and data security, we developed FASTGenomics (https://fastgenomics.org) as a powerful, efficient, versatile, robust, safe and intuitive analytical ecosystem for single-cell transcriptomics.
A genome-wide assessment of the ancestral neural crest gene regulatory network
Authors: Hockman Dorit , Chong-Morrison Vanessa , Gavriouchkina Daria , Green Stephen , Amemiya Chris T. , Smith Jeramiah J. , Bronner Marianne E. , Sauka-Spengler Tatjana
Published: March 2018

The neural crest is an embryonic cell population that contributes to key vertebrate-specific features including the craniofacial skeleton and peripheral nervous system. Here we examine the transcriptional profiles and chromatin accessibility of neural crest cells in the basal sea lamprey, in order to gain insight into the ancestral state of the neural crest gene regulatory network (GRN) at the dawn of vertebrates. Transcriptome analyses reveal clusters of co-regulated genes during neural crest specification and migration that show high conservation across vertebrates for dynamic programmes like Wnt modulation during the epithelial to mesenchymal transition, but also reveal novel transcription factors and cell-adhesion molecules not previously implicated in neural crest migration. ATAC-seq analysis refines the location of knowncis-regulatory elements at theHox-α2locus and uncovers novelcis-regulatory elements forTfap2BandSoxE1. Moreover, cross-species deployment of lamprey elements in zebrafish reveals that the lampreySoxE1enhancer activity is deeply conserved, mediating homologous expression in jawed vertebrates. Together, our data provide new insight into the core elements of the GRN that are conserved to the base of the vertebrates, as well as expose elements that are unique to lampreys.
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

1: 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

Background

The 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.

Method

We 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).

Result

The 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%.

Conclusions

Machine 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

Cellular 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.
Embryonic gene transcription in the spiny mouse (Acomys cahirinus): an investigtion into the embryonic genome activation
Authors: Mamrot Jared , Gardner David K. , Temple-Smith Peter , Dickinson Hayley
Published: March 2018

Our understanding of genetic mechanisms driving early embryonic development is primarily based on experiments conducted on mice, however translation of findings can be limited by physiological differences between mice and humans. To address this, we investigated whether the spiny mouse (Acomys cahirinus) is a closer model of early human embryonic development due to their more human-like endocrine profile. We therefore characterised the initiation of gene transcription in the spiny mouse embryo and compared the pattern of gene expression during the embryonic genome activation (EGA) with common mouse and human embryos. Naturally-mated spiny mouse embryos were obtained at the 2-cell, 4-cell and 8-cell stages of development (n=4 biological replicates per stage). RNA-Seq of these samples produced 709.1M paired-end reads in total.De novoassembly of reads was conducted using Trinity. Embryo-specific transcripts were extracted from thede novoassembly and added to the reference spiny mouse transcriptome. Transcription was first detected between the 2-cell and 4-cell stages for the majority of genes (n=3,428), with fewer genes first transcribed between the 4-cell and 8-cell stages (n=1,150). The pattern of gene expression in spiny mouse embryos during this period of development is more human-like than common mouse embryos. This is the first evidence the spiny mouse may provide a more suitable model of human embryonic development. The improved referenceAcomys cahirinustranscriptome is publically accessible, further increasing the value of this tool for ongoing research. Further investigation into early development in the spiny mouse is warranted.
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

Conventional 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

In 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

Wheat 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

In 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

Identification 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.

Availability

BART is implemented in Python and available at http://faculty.virginia.edu/zanglab/bart

Contact: 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

Spatial 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

Electroconvulsive 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.
Implications for human odor sensing revealed from the statistics of the odorant-receptor interactions
Authors: Bak Ji Hyun , Jang Seogjoo , Hyeon Changbong
Published: March 2018

Binding of odorants to olfactory receptors (ORs) elicits downstream chemical and neural signals, which are further processed to odor perception in the brain. Recently, Mainland et al. [Sci. data, (2015) 2:sdata20152] have measured ≳ 500 pairs of odorant-OR interaction by a high-throughput screening assay method, opening a new avenue to understanding the principles of human odor coding. Here, using a recently developed minimal model for OR activation kinetics [J. Phys. Chem. B (2017) 121, 1304–1311], we characterize the statistics of OR activation by odorants in terms of three empirical parameters: the half-maximum effective concentration EC50, the efficacy, and the basal activity. While the data size of odorants is still limited, the statistics offer meaningful information on the breadth and optimality of the tuning of human ORs to odorants, and allow us to relate the three parameters with the microscopic rate constants and binding affinities that define the OR activation kinetics. Despite the stochastic nature of the response expected at individual OR-odorant level, we assess that the confluence of signals in a neuron released from the multitude of ORs is effectively free of noise and deterministic with respect to changes in odorant concentration. Thus, setting a threshold to the fraction of activated OR copy number for neural spiking binarizes the electrophysiological signal of olfactory sensory neuron, thereby making an information theoretic approach a viable tool in studying the principles of odor perception.
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

Conductances 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.
Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d
Authors: Knuckles Philip , Lence Tina , Haussmann Irmgard U. , Jacob Dominik , Kreim Nastasja , Carl Sarah H. , Masiello Irene , Hares Tina , Villaseñor Rodrigo , Hess Daniel , Andrade-Navarro Miguel A. , Biggiogera Marco , Helm Mark , Soller Matthias , Bühler Marc , Roignant Jean-Yves
Published: March 2018

N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotes, playing crucial roles in multiple biological processes. m6A is catalyzed by the activity of methyltransferase-like 3 (Mettl3), which depends on additional proteins whose precise functions remain poorly understood. Here we identified Zc3h13 (zinc finger CCCH domain-containing protein 13)/Flacc [Fl(2)d-associated complex component] as a novel interactor of m6A methyltransferase complex components in Drosophila and mice. Like other components of this complex, Flacc controls m6A levels and is involved in sex determination in Drosophila. We demonstrate that Flacc promotes m6A deposition by bridging Fl(2)d to the mRNA-binding factor Nito. Altogether, our work advances the molecular understanding of conservation and regulation of the m6A machinery.
Elongator complex is required for long-term olfactory memory formation in Drosophila
Authors: Yu Dinghui , Tan Ying , Chakraborty Molee , Tomchik Seth , Davis Ronald L.
Published: March 2018

The evolutionarily conserved Elongator Complex associates with RNA polymerase II for transcriptional elongation. Elp3 is the catalytic subunit, contains histone acetyltransferase activity, and is associated with neurodegeneration in humans. Elp1 is a scaffolding subunit and when mutated causes familial dysautonomia. Here, we show that elp3 and elp1 are required for aversive long-term olfactory memory in Drosophila. RNAi knockdown of elp3 in adult mushroom bodies impairs long-term memory (LTM) without affecting earlier forms of memory. RNAi knockdown with coexpression of elp3 cDNA reverses the impairment. Similarly, RNAi knockdown of elp1 impairs LTM and coexpression of elp1 cDNA reverses this phenotype. The LTM deficit in elp3 and elp1 knockdown flies is accompanied by the abolishment of a LTM trace, which is registered as increased calcium influx in response to the CS+ odor in the α-branch of mushroom body neurons. Coexpression of elp1 or elp3 cDNA rescues the memory trace in parallel with LTM. These data show that the Elongator complex is required in adult mushroom body neurons for long-term behavioral memory and the associated long-term memory trace.
tert-Butyl 4-{3-[6-(4-methoxyphenyl)-2-methylpyrimidin-4-yl]quinolin-2-yl}piperazine-1-carboxylate
Authors: Anthal Sumati , Singh Vikram. D. , Desai N. R. , Arunakumar D. B. , Sreenivasa S. , Kamni  , Kant Rajni
Published: March 2018

The asymmetric unit of the title compound, C30H33N5O3, contains two independent molecules,AandB. In moleculeA, thetert-butyl 4-methylpiperazine-1-carboxylate group was refined as disordered over two sets of sites with an occupancy ratio of 0.821 (4):0.179 (4). The piperazine ring adopts a chair conformation in both molecules. The dihedral angles between the pyrimidine ring and methoxyphenyl ring are 20.27 (14) and 8.72 (11)° for moleculesAandB, respectively. The quinoline ring system makes dihedral angles of 30.68 (11) and 37.76 (10)° with the pyrimidine ring in moleculesAandB, respectively. In the crystal, C—H...O hydrogen bonds link the molecules into chains along [100].
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

Purpose

This 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/approach

Taguchi’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.

Findings

The 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 implications

ACs 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/value

ACs 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

Purpose

The 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/approach

The 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.

Findings

The 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/value

Under 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.