bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of solvents used for fabrication of microphysiological systems
Authors: Wen Xiaopeng , Takahashi Seiichiro , Hatakeyama Kenji , Kamei Ken-ichiro 
Published: March 2021

AbstractMicrophysiological systems (MPSs) have shown great promise for the advancement of drug discovery and toxicological tests, and as an alternative to animal models. However, although several chips and systems have been reported, some important issues are yet to be addressed, such as the use of polydimethylsiloxane (PDMS). Cyclo olefin polymers (COPs) have advantages over other thermoplastic materials, but most COP-based MPSs use solvent bonding during fabrication, which can affect any cells they are used to culture. This study uses a photobonding process with vacuum ultraviolet (UVU) to produce MPSs without the need for solvents such as cyclohexane, dichloromethane, and toluene. This is then used for comparison to investigate the effects of solvents on cell cultures. Quantitative immunofluorescent assays show that the coating efficiencies of extracellular matrix proteins, such as Matrigel and collagen I, are reduced on solvent-treated COP surfaces, compared with those prepared using VUV photobonding. Furthermore, SH-SY5Y neuroblastoma cells are used to evaluate cytotoxicity. This shows that solvent-MPSs induce apoptosis, but VUV-MPSs do not. These results provide insights into solvent bonding for MPS fabrication so that undesirable reactions can be avoided. Moreover, this work may be used to standardize MPS protocols and establish good manufacturing practices.
Spikebench: an open benchmark for spike train time-series classification
Authors: Lazarevich Ivan , Prokin Ilya , Gutkin Boris , Kazantsev Victor 
Published: March 2021

AbstractModern well-performing approaches to neural decoding are based on machine learning models such as decision tree ensembles and deep neural networks. The wide range of algorithms that can be utilized to learn from neural spike trains, which are essentially time-series data, results in the need for diverse and challenging benchmarks for neural decoding, similar to the ones in the fields of computer vision and natural language processing. In this work, we propose a spike train classification benchmark, based on open-access neural activity datasets and consisting of several learning tasks such as stimulus type classification, animal’s behavioral state prediction and neuron type identification. We demonstrate that an approach based on hand-crafted time-series feature engineering establishes a strong baseline performing on par with state-of-the-art deep learning based models for neural decoding. We release thecode allowing to reproduce the reported results.Author summaryMachine learning-based neural decoding has been shown to outperform the traditional approaches like Wiener and Kalman filters on certain key tasks [1]. To further the advancement of neural decoding models, such as improvements in deep neural network architectures and better feature engineering for classical ML models, there need to exist common evaluation benchmarks similar to the ones in the fields of computer vision or natural language processing. In this work, we propose a benchmark consisting of severalindividual neuronspike train classification tasks based on open-access data from a range of animals and brain regions. We demonstrate that it is possible to achieve meaningful results in such a challenging benchmark using the massive time-series feature extraction approach, which is found to perform similarly to state-of-the-art deep learning approaches.
Anisotropy Measure from Three Diffusion-Encoding Gradient Directions
Authors: Aja-Fernández Santiago , París Guillem , Tristán-Vega Antonio 
Published: March 2021

PurposeWe propose a method that can provide information about the anisotropy and orientation of diffusion in the brain from only 3 orthogonal gradient directions without imposing additional assumptions.MethodsThe method is based on the Diffusion Anisotropy (DiA) that measures the distance from a diffusion signal to its isotropic equivalent. The original formulation based on a Spherical Harmonics basis allows to go down to only 3 orthogonal directions in order to estimate the measure. In addition, an alternative simplification and a color-coding representation are also proposed.ResultsAcquisitions from a publicly available database are used to test the viability of the proposal. The DiA succeeded in providing anisotropy information from the white matter using only 3 diffusion-encoding directions. The price to pay for such reduced acquisition is an increment in the variability of the data and a subestimation of the metric.ConclusionsThe calculation of anisotropy information from DMRI is feasible using fewer than 6 gradient directions by using DiA. The method is totally compatible with existing acquisition protocols and it may provide complementary information about orientation in fast diffusion acquisitions.
Role of ventral subiculum neuronal ensembles in incubation of oxycodone craving after electric barrier-induced voluntary abstinence
Authors: Fredriksson Ida , Shekara Aniruddha , Applebey Sarah V. , Minier-Toribio Angelica , Altidor Lindsay , Cifani Carlo , Hope Bruce T. , Bossert Jennifer M. , Shaham Yavin 
Published: March 2021

AbstractWe recently developed a rat model of incubation of oxycodone craving where opioid seeking progressively increases after voluntary suppression of drug self-administration by adverse consequences of drug seeking. Here, we studied the role of ventral subiculum (vSub) neuronal ensembles in this incubation, using the activity marker Fos, muscimol-baclofen (GABAergic agonists) inactivation, and Daun02 chemogenetic inactivation.We trained Sprague-Dawley orFos-lacZtransgenic male and female rats to self-administer oxycodone (0.1 mg/kg/infusion, 6-h/d) for 14 days. The rats were then exposed for 14 days to an electric barrier of increasing intensity (0.1 to 0.4 mA) near the drug-paired lever that caused voluntary abstinence or were exposed to 14 days of forced abstinence. We tested Sprague-Dawley rats for relapse to oxycodone seeking without shock and drug on abstinence day 15 and extracted their brains for Fos-immunohistochemistry, or tested them after vSub vehicle or muscimol-baclofen injections on abstinence days 1 and 15. We performed Daun02 inactivation of relapse-activated vSub Fos neurons in Fos-lacZ transgenic rats on abstinence day 15 and then tested them for relapse on abstinence day 18.Relapse after electric barrier-induced abstinence increased Fos expression in vSub. Muscimol-baclofen inactivation or Daun02 selective inactivation of vSub Fos-expressing neuronal ensembles decreased “incubated” oxycodone seeking after voluntary abstinence. Muscimol-baclofen vSub inactivation had no effect on non-incubated opioid seeking on abstinence day 1 or incubation after forced abstinence.Our results demonstrate a selective role of vSub neuronal ensembles in incubation of opioid craving after cessation of drug self-administration by adverse consequences of drug seeking.Significance statementHigh relapse rate is a cardinal feature of opioid addiction and a major impediment for successful treatment. In humans, abstinence is often self-imposed, and relapse typically involves a conflict situation between the desire to experience the drug’s rewarding effects and negative consequences of drug seeking. To mimic this human condition, we recently introduced a rat model of incubation of oxycodone craving after electric barrier-induced voluntary abstinence. Here, we used the activity marker Fos, muscimol-baclofen (GABAergic agonists) inactivation, and Daun02 chemogenetic inactivation to demonstrate a selective role of vSub neuronal ensembles in incubation of oxycodone craving after electric barrier-induced voluntary abstinence, but not in incubation of opioid craving after forced abstinence or non-incubated opioid seeking during early abstinence.
Extracellular Matrix Hydrogels Promote Expression of Muscle-Tendon Junction Proteins
Authors: Gaffney Lewis S. , Davis Zachary G. , Mora-Navarro Camilo , Fisher Matthew B. , Freytes Donald O. 
Published: March 2021

AbstractMuscle and tendon injuries are prevalent and range from minor sprains and strains to traumatic, debilitating injuries. However, the interactions between these tissues during injury and recovery remain unclear. Three-dimensional tissue models that incorporate both tissues and a physiologically relevant junction between muscle and tendon may help understand how the two tissues interact. Here, we use tissue specific extracellular matrix (ECM) derived from muscle and tendon to determine how cells of each tissue interact with the microenvironment of the opposite tissue resulting in junction specific features. ECM materials were derived from the Achilles tendon and gastrocnemius muscle, decellularized, and processed to form tissue specific pre-hydrogel digests. ECM materials were unique in respect to protein composition and included many types of ECM proteins, not just collagens. After digestion and gelation, ECM hydrogels had similar complex viscosities which were less than type I collagen hydrogels at the same concentration. C2C12 myoblasts and tendon fibroblasts were cultured in tissuespecific ECM conditioned media or encapsulated in tissue-specific ECM hydrogels to determine cell-matrix interactions and the effects on a muscle-tendon junction marker, paxillin. ECM conditioned media had only a minor effect on upregulation of paxillin in cells cultured in monolayer. However, cells cultured within ECM hydrogels had 50-70% higher paxillin expression than cells cultured in type I collagen hydrogels. Contraction of the ECM hydrogels varied by the type of ECM used. Subsequent experiments with varying density of type I collagen (and thus contraction) showed no correlation between paxillin expression and the amount of gel contraction, suggesting that a constituent of the ECM was the driver of paxillin expression in the ECM hydrogels. In addition, the extracellular matrix protein type XXII collagen had similar expression patterns as paxillin, with smaller effect sizes. Using tissue specific ECM allowed for the de-construction of the cell-matrix interactions similar to muscletendon junctions to study the expression of MTJ specific proteins.Impact StatementThe muscle-tendon junction is an important feature of muscle-tendon units; however, despite crosstalk between the two tissue types, it is overlooked in current research. Deconstructing the cell-matrix interactions will provide the opportunity to study significant junction specific features and markers that should be included in tissue models of the muscletendon unit, while gaining a deeper understanding of the natural junction. This research aims to inform future methods to engineer a more relevant multi-tissue platform to study the muscletendon unit.
Stress is basic: ABA alkalinizes both the xylem sap and the cytosol of Arabidopsis vascular bundle sheath cells by inhibiting their P-type H+-ATPase and stimulating their V-type H+-ATPase
Authors: Torne Tanmayee , Grunwald Yael , Dalal Ahan , Yaaran Adi , Moshelion Menachem , Moran Nava 
Published: March 2021

ABSTRACTBACKGROUND AND HYPOTHESIS•Under water deprivation, in many perennial species, the stress hormone, ABA, appears in the xylem sap in the shoot (including leaf) veins and the xylem sap pH (pHEXT) increases. This study aimed to test the hypothesis that ABA is the signal for an altered proton balance of the leaf-vein-enwrapping bundle sheath cells (BSCs).METHODS•Plant Material.We used a fewArabidopsis thaliana(L.) Heynh. genotypes: wildtype (WT) of two accessions, Landsbergerecta(Ler) and Columbia (Col), and a few mutants and transformants in these backgrounds.•H+-Pumps activities.We monitored ABA effects on the H+-pump activities in the BSCs cytosol-delimiting membranes (plasma membrane and tonoplast) by monitoring the cytosol and the xylem pH, and the membrane potential (EM), by imaging the fluorescence of pH- and membrane potential (EM)-reporting probes: (a) the BSCs’ pHEXT– with the ratiometric fluorescent dye FITC-dextran petiole-fed into detached leaves in unbuffered xylem perfusion solution (XPS), (b) the BSCs’ pHCYT– with the ratiometric dye SNARF1 loaded into BSCs isolated protoplasts, and (c) the BSCs’ EM– with the ratiometric dye di- 8-ANEPPS.RESULTS•ABA increased the pHEXT; this response was abolished in anabi1-1mutant with impaired signaling via a PP2C (ABI1) and in anaha2-4mutant with knocked-down AHA2;•ABA depolarized the WT BSCs;•ABA increased pHCYTirrespective of AHA2 activity (i.e., whether or not AHA was inhibited by vanadate, or in theaha2-4mutant);•The ABA-induced cytosol alkalinization was abolished in the absence of VHA activity (i.e., when VHA was inhibited by bafilomycin A1, or in thevha-a2 vha-a3double mutant with inactive VHA);•All these results resemble the ABA effect on GCs;•In contrast to GCs, AHA2 and not AHA1 is the ABA major target in BSCs;•Blue light (BL) enabled the response of the BSCs’ VHA to ABA;•The ABA- and BL-signaling pathways acting on both BSCs’ pumps, AHA2 and VHA, are likely to be BSCs autonomous, based on (a) the presence in the BSCs of many genes of the ABA- and BL-signaling pathways and (b) ABA responses (depolarization and pHCYTelevation) demonstrated under BL in isolated protoplasts.SIGNIFICANCE STATEMENTWe reveal here an alkalinizing effect of the plant drought-stress hormone ABA on the pH on both sides of the plasmalemma of the vein-enwrapping bundle sheath cells (BSCs), due to ABA inhibition of the BSCs’ AHA2, the plasmalemma H+- ATPase and stimulation of VHA, their vacuolar H+-ATPase. Since pH affects the BSCs’ selective regulation of solute and water fluxes into the leaf, these H+- pumps may be attractive targets for manipulations aiming to improve plant drought response.
Negative effects of agricultural intensification on the food provisioning rate of a declining aerial insectivore
Authors: Garrett Daniel R. , Pelletier Fanie , Garant Dany , Bélisle Marc 
Published: March 2021

AbstractThe historical rise of intensive agricultural practices is hypothesized to be related to declines of grassland and aerial insectivorous birds. Drivers of declines may also influence the overall abundance and spatial distribution of insects within agricultural landscapes. Subsequently, the food provisioning rate of birds breeding within more agro-intensive landscapes may be impacted. Lower provisioning rates in agro-intensive landscapes may lead to reduced growth rate, body condition or fledging success of nestlings but also to diminished body condition of food provisioning adults. Results from a previous study supported this hypothesis as the fledging success and proxies of nestling body condition were lowest for an aerial insectivore breeding in more agro intensive landscapes. Of the multiple hypotheses put forward to explain these correlations, one mechanism may act through variation in food provisioning rates. In this study, we expounded on this hypothesis using data derived from the aforementioned study system and assessed if provisioning rates to nestlings and food provisioning behavior of adults varied across a gradient of agricultural intensification in a declining aerial insectivore, the Tree Swallow (Tachycineta bicolor). We found that the hourly provisioning rate was lower in agro-intensive landscapes, and yet travel distances were longest within less agro-intensive landscapes. Our results highlight that, in order to maximize long term average gain rates, Tree Swallows breeding within agro-intensive landscapes must forage with greater intensity, perhaps at a cost to themselves, or else costs will transfer to growing broods. Our work provides further evidence that agricultural intensification on the breeding grounds can contribute to the declines of aerial insectivores in part through a trophic pathway.
Interhemispheric Connectivity Supports Load-Dependent Working Memory Maintenance for Complex Visual Stimuli
Authors: Plaska Chelsea Reichert , Ortega Jefferson , Gomes Bernard A. , Ellmore Timothy M. 
Published: March 2021

AbstractA critical manipulation used to study the neural basis of working memory (WM) is to vary the information load at encoding followed by measurements of activity and connectivity during maintenance in the subsequent delay period. The hallmark finding is that delay period activity and connectivity increases between frontal and parietal brain regions as load is increased. Most WM studies, however, employ simple stimuli (e.g., simple shapes or letters) during encoding and utilize unfilled intervals (e.g., a blank screen or fixation cross) during the delays. In the present study, we asked how delay period activity and connectivity change during low and high load maintenance of complex stimuli. Twenty-two participants completed a modified Sternberg WM task with two or five naturalistic scenes as stimuli while scalp EEG was recorded. In each trial, the delay interval was filled with phase scrambled scenes to provide a visual perceptual control with color and spatial frequency similar to the non-scrambled scenes presented during encoding. The results showed that theta and alpha delay activity amplitude was reduced during high compared to low WM load across frontal, central, and parietal sources. Functional connectivity during the delay was assessed by phase-locking value (PLV) and revealed a network with higher connectivity during low WM load consisting of increased PLV between 1) left frontal and right posterior temporal sources in the theta and alpha bands, 2) right anterior temporal and left central sources in the alpha and lower beta bands, and 3) left anterior temporal and posterior temporal sources in the theta, alpha, and lower beta bands. These findings demonstrate a role for interhemispheric connectivity during WM maintenance of complex stimuli. We discuss significance with respect to allocation of limited attentional resources and the filtering of interference.
A folder mechanism ensures size uniformity amongC. elegansindividuals by coupling growth and development
Authors: Towbin Benjamin D. , Grosshans Helge 
Published: March 2021

AbstractAnimals increase by orders of magnitude in their volume during development. Hence, even small differences in the growth rates between individuals could generate large differences in their adult body size. Yet, such volume divergence among individuals is usually not observed in nature.We combined theory and experiment to understand the mechanisms of body size uniformity. Using live imaging, we measured the volume growth of hundreds of individuals ofC. elegansover the entire span of their postembryonic development. We find thatC. elegansgrows exponentially in volume with a coefficient of variation of the growth rate of ∼7%, but that individuals diverge much less in volume than expected from this heterogeneity. The mechanism counteracting size divergence does not involve size thresholds for developmental milestones. Instead, an inverse coupling of the growth rate and the duration of development produces a constant volume fold change per larval stage.The duration of larval stages ofC. elegansis determined by the period of a developmental oscillator. Using mathematical modelling, we show that an anti-correlation between the growth rate and the oscillatory period emerges as an intrinsic property of a genetic oscillator. We propose that the robustness of body volume fold change is a hard-wired characteristic of the oscillatory circuit and does not require elaborate mechanisms of size control by cellular signalling. Indeed, the coupling of growth and development was unaltered by mutation of canonical pathways of growth control. This novel concept of size homeostasis may broadly apply to other multicellular systems controlled by genetic oscillators.
minicore: Fast scRNA-seq clustering with various distances
Authors: Baker Daniel N. , Dyjack Nathan , Braverman Vladimir , Hicks Stephanie C. , Langmead Ben 
Published: March 2021

AbstractSingle-cell RNA-sequencing (scRNA-seq) analyses typically begin by clustering a gene-by-cell expression matrix to empirically define groups of cells with similar expression profiles. We describe new methods and a new open source library,minicore, for efficientk-means++ center finding andk-means clustering of scRNA-seq data.Minicoreworks with sparse count data, as it emerges from typical scRNA-seq experiments, as well as with dense data from after dimensionality reduction.Minicore’s novel vectorized weighted reservoir sampling algorithm allows it to find initialk-means++ centers for a 4-million cell dataset in 1.5 minutes using 20 threads.Minicorecan cluster using Euclidean distance, but also supports a wider class of measures like Jensen-Shannon Divergence, Kullback-Leibler Divergence, and the Bhattacharyya distance, which can be directly applied to count data and probability distributions.Further,minicoreproduces lower-cost centerings more efficiently than scikit-learn for scRNA-seq datasets with millions of cells. With careful handling of priors,minicoreimplements these distance measures with only minor (<2-fold) speed differences among all distances. We show that aminicorepipeline consisting ofk-means++, localsearch++ and minibatchk-means can cluster a 4-million cell dataset in minutes, using less than 10GiB of RAM. This memory-efficiency enables atlas-scale clustering on laptops and other commodity hardware. Finally, we report findings on which distance measures give clusterings that are most consistent with known cell type labels.AvailabilityThe open source library is athttps://github.com/dnbaker/minicore. Code used for experiments is athttps://github.com/dnbaker/minicore-experiments.
A viral toolbox for conditional and transneuronal gene expression in zebrafish
Authors: Satou Chie , Neve Rachael L. , Oyibo Hassana K. , Zmarz Pawel , Huang Kuo-Hua , Bouldoires Estelle Arn , Mori Takuma , Higashijima Shin-ichi , Keller Georg B. , Friedrich Rainer W. 
Published: March 2021

AbstractThe zebrafish is an important model in systems neuroscience but a key limitation is the lack of viral tools to dissect the structure and function of neuronal circuitry. We developed methods for efficient gene transfer and retrograde tracing in adult and larval zebrafish by herpes simplex viruses (HSV1). HSV1 can be combined with the Gal4/UAS system to target cell types with high spatial, temporal and molecular specificity. We also established methods for efficient transneuronal tracing by modified rabies viruses in zebrafish. We demonstrate that HSV1 and rabies viruses can be used to visualize and manipulate genetically or anatomically identified neurons within and across different brain areas of adult and larval zebrafish. An expandable library of viruses is provided to express fluorescent proteins, calcium indicators, optogenetic probes, toxins and other molecular tools. This toolbox creates new opportunities to interrogate neuronal circuits in zebrafish through combinations of genetic and viral approaches.