bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medusa: software to build and analyze ensembles of genome-scale metabolic network reconstructions
Authors: Medlock Gregory L. , Papin Jason A. 
Published: February 2019

AbstractUncertainty in the structure and parameters of networks is ubiquitous across computational biology. In constraint-based reconstruction and analysis of metabolic networks, this uncertainty is present both during the reconstruction of networks and in simulations performed with them. Here, we present Medusa, a Python package for the generation and analysis of ensembles of genome-scale metabolic network reconstructions. Medusa builds on the COBRApy package for constraint-based reconstruction and analysis by compressing a set of models into a compact ensemble object, providing functions for the generation of ensembles using experimental data, and extending constraint-based analyses to ensemble scale. We demonstrate how Medusa can be used to generate ensembles, perform ensemble simulations, and how machine learning can be used in conjunction with Medusa to guide the curation of genome-scale metabolic network reconstructions. Medusa is available under the permissive MIT license from the Python Packaging Index (https://pypi.org/) and from github (https://github.com/gregmedlock/Medusa/), and comprehensive documentation is available at https://medusa.readthedocs.io/en/latest/.
Glia-derived exosomal miR-274 targets Sprouty in trachea and synaptic boutons to modulate growth and responses to hypoxia
Authors: Tsai Yi-Wei , Sung Hsin-Ho , Li Jian-Chiuan , Yeh Chun-Yen , Chen Pei-Yi , Cheng Ying-Ju , Chen Chun-Hong , Tsai Yu-Chen , Chien Cheng-Ting 
Published: February 2019

AbstractSecreted exosomal miRNAs mediate inter-organ/tissue communication by downregulating gene expression, thereby modulating developmental and physiological functions. However, the source, route, and function have not been formally established for specific miRNAs. Here, we show that glial miR-274 non-cell autonomously modulates the growth of synaptic boutons and tracheal branches. Whereas precursor miR-274 was expressed in glia, mature miR-274 was secreted. miR-274 secretion to circulating hemolymph was detected in exosomes, a process requiring ESCRT components in exosome biogenesis and Rab11 and Syx1A in exosome release. miR-274 downregulated Sprouty to activate MAPK in synaptic boutons and tracheal branches, thereby promoting their growth. Expression of miR-274 solely in glia of amir-274null mutant reset normal levels of Sprouty and MAPK, and hemolymphatic exosomal miR-274.mir-274mutant larvae were hypersensitive to hypoxia, which was suppressed by increasing tracheal branches. Thus, glia-derived miR-274 coordinates growth of synaptic boutons and tracheal branches to modulate larval hypoxia responses.
rhizoTrak: A flexible open source Fiji plugin for user-friendly manual annotation of time-series images from minirhizotrons
Authors: Möller Birgit , Chen Hongmei , Schmidt Tino , Zieschank Axel , Patzak Roman , Türke Manfred , Weigelt Alexandra , Posch Stefan 
Published: February 2019

AbstractBackground and aimsMinirhizotrons are commonly used to study root turnover which is essential for understanding ecosystem carbon and nutrient cycling. Yet, extracting data from minirhizotron images requires intensive annotation effort. Existing annotation tools often lack flexibility and provide only a subset of the required functionality. To facilitate efficient root annotation in minirhizotrons, we present the user-friendly open source tool rhizoTrak.Methods and resultsrhizoTrak builds on TrakEM2 and is publically available as Fiji plugin. It uses treelines to represent branching structures in roots and assigns customizable status labels per root segment. rhizoTrak offers configuration options for visualization and various functions for root annotation mostly accessible via keyboard shortcuts. rhizoTrak allows time-series data import and particularly supports easy handling and annotation of time series images. This is facilitated via explicit temporal links (connectors) between roots which are automatically generated when copying annotations from one image to the next. rhizoTrak includes automatic consistency checks and guided procedures for resolving conflicts. It facilitates easy data exchange with other software by supporting open data formats.ConclusionsrhizoTrak covers the full range of functions required for user-friendly and efficient annotation of time-series images. Its flexibility and open source nature will foster efficient data acquisition procedures in root studies using minirhizotrons.
Genuine cross-frequency coupling networks in human resting-state electrophysiological recordings
Authors: Siebenhühner Felix , Wang Sheng H , Arnulfo Gabriele , Lampinen Anna , Nobili Lino , Palva J. Matias , Palva Satu 
Published: February 2019

AbstractPhase synchronization of neuronal oscillations in specific frequency bands coordinates anatomically distributed neuronal processing and communication. Typically, oscillations and synchronization take place concurrently in many distinct frequencies, which serve separate computational roles in cognitive functions. While within-frequency phase synchronization has been studied extensively, less is known about the mechanisms that govern neuronal processing distributed across frequencies and brain regions. Such integration of processing between frequencies could be achieved via cross-frequency coupling (CFC), either by phase-amplitude coupling (PAC) or byn:m-cross-frequency phase synchrony (CFS). So far, studies have mostly focused on local CFC in individual brain regions, whereas the presence and functional organization of CFC between brain areas have remained largely unknown. We posit that inter-areal CFC may be essential for large-scale coordination of neuronal activity and investigate here whether genuine CFC networks are present in human resting-state brain activity.To assess the functional organization of CFC networks, we identified brain-wide CFC networks at meso-scale resolution from stereo-electroencephalography (SEEG) and at macro-scale resolution from source-reconstructed magnetoencephalography (MEG) data. We developed a novel graph-theoretical method to distinguish genuine CFC from spurious CFC that may arise from non-sinusoidal signals ubiquitous in neuronal activity. We show that genuine inter-areal CFC is present in human resting-state activity in both MEG and SEEG data. Both CFS and PAC networks coupled theta and alpha oscillations with higher frequencies in large-scale networks connecting anterior and posterior brain regions. CFS and PAC networks had distinct spectral patterns and opposing distribution of low- and high frequency network hubs, implying that they constitute distinct CFC mechanisms. The strength of CFS networks was also predictive of cognitive performance in a separate neuropsychological assessment. In conclusion, these results provide evidence for inter-areal CFS and PAC being two distinct mechanisms for coupling oscillations across frequencies in large-scale brain networks.
Generating High Density, Low Cost Genotype Data in Soybean [Glycine max (L.) Merr.]
Authors: Happ Mary M. , Wang Haichuan , Graef George L. , Hyten David L. 
Published: February 2019

AbstractObtaining genome-wide genotype information for millions of SNPs in soybean [Glycine max (L.) Merr.] often involves completely resequencing a line at 5X or greater coverage. Currently, hundreds of soybean lines have been resequenced at high depth levels with their data deposited in the NCBI short read achieve. This publicly available dataset may be leveraged as an imputation reference panel in combination with skim (low coverage) sequencing of new soybean genotypes to economically obtain high-density SNP information. Ninety-nine soybean lines resequenced at an average of 17.1X were used to generate a reference panel, with over 10 million SNPs called using GATK’s Haplotype Caller tool. Whole genome resequencing at approximately 1X depth was performed on 114 previously ungenotyped experimental soybean lines. Coverages down to 0.1X were analyzed by randomly subsetting raw reads from the original 1X sequence data. SNPs discovered in the reference panel were genotyped in the experimental lines after aligning to the soybean reference genome, and missing markers imputed using Beagle 4.1. Sequencing depth of the experimental lines could be reduced to 0.3X while still retaining an accuracy of 97.8%. Accuracy was inversely related to minor allele frequency, and highly correlated with marker linkage disequilibrium. The high accuracy of skim sequencing combined with imputation provides a low cost method for obtaining dense genotypic information that can be used for various genomics applications in soybean.
EPI distortion correction for simultaneous human brain stimulation and imaging at 3T
Authors: Oh Hyuntaek , Kim Jung Hwan , Yau Jeffrey M. 
Published: February 2019

AbstractTranscranial magnetic stimulation (TMS) can be paired with functional magnetic resonance imaging (fMRI) in simultaneous TMS-fMRI experiments. These multimodal experiments enable causal probing of network architecture in the human brain which can complement alternative network mapping approaches. Critically, merely introducing the TMS coil into the scanner environment can sometimes produce substantial magnetic field inhomogeneities and spatial distortions which limit the utility of simultaneous TMS-fMRI. We assessed the efficacy of point spread function corrected echo planar imaging (PSF-EPI) in correcting for the field inhomogeneities associated with a TMS coil at 3T. In phantom and brain scans, we quantitatively compared the coil-induced distortion artifacts measured in PSF-EPI scans to artifacts measured in conventional echo-planar imaging (EPI) and a simultaneous multi-slice sequence (SMS)-EPI. While we observed substantial coil-related artifacts in the data produced by the conventional EPI and SMS sequences, PSF-EPI produced data that had significantly greater signal-to-noise and less distortions. In phantom scans with the PSF-EPI sequence, we also characterized the temporal profile of dynamic artifacts associated with TMS delivery and found that image quality remained high as long as the TMS pulse preceded the RF excitation pulses by at least 50ms. Lastly, we validated the PSF-EPI sequence in human brain scans involving TMS and motor behavior as well as resting state fMRI scans. Our collective results demonstrate the superiority of PSF-EPI over conventional EPI and SMS sequences for simultaneous TMS-fMRI when coil-related artifacts are a concern. The ability to collect high quality resting state fMRI data in the same session as the simultaneous TMS-fMRI experiment offers a unique opportunity to interrogate network architecture in the human brain.
Tracking the emergence of location-based spatial representations in human scene-selective cortex
Authors: Berens Sam C. , Joensen Bárður H , Horner Aidan J. 
Published: February 2019

AbstractScene-selective regions of the human brain form allocentric representations of locations in our environment. These representations are independent of heading direction and allow us to know where we are regardless of our direction of travel. However, we know little about how these location-based representations are formed. Using fMRI representational similarity analysis and linear mixed-models, we tracked the emergence of location-based representations in scene-selective brain regions. We estimated patterns of activity for two distinct scenes, taken before and after participants learnt they were from the same location. During a learning phase, we presented participants with two types of panoramic videos: (1) an overlap video condition displaying two distinct scenes (0° and 180°) from the same location, and (2) a no-overlap video displaying two distinct scenes from different locations (that served as a control condition). In the parahippocampal cortex (PHC) and retrosplenial cortex (RSC), representations of scenes from the same location became more similar to each other only after they had been shown in the overlap condition, suggesting the emergence of viewpoint-independent location-based representations. Whereas these representations emerged in the PHC regardless of task performance, RSC representations only emerged for locations where participants could behaviourally identify the two scenes as belonging to the same location. The results suggest that we can track the emergence of location-based representations in the PHC and RSC in a single fMRI experiment. Further, they support computational models that propose the RSC plays a key role in transforming viewpoint-independent representations into behaviourally-relevant representations of specific viewpoints.
A Gelatin Hydrogel to Study Endometrial Angiogenesis and Trophoblast Invasion
Authors: Zambuto Samantha G. , Clancy Kathryn B.H. , Harley Brendan A.C. 
Published: February 2019

ABSTRACTAs the lining of the uterus and site of blastocyst implantation, the endometrium is a dynamic tissue that undergoes rapid cycles of growth, breakdown, and remodeling each menstrual cycle. Significant vascular remodeling is also driven by trophoblast cells that form the outer layer of the blastocyst. Trophoblast invasion and remodeling enhance blood flow to the embryo ahead of placentation. Insight into endometrial vascular remodeling and trophoblast invasion would provide key insights into endometrial physiology and cellular interactions critical for establishment of pregnancy. The objective for this study was to develop a tissue engineering platform to investigate processes of endometrial angiogenesis and trophoblast invasion in a 3D environment. We report adaptation of a methacrylamide-functionalized gelatin hydrogel that presents matrix stiffness in the range of the native tissue. Further, the hydrogel supports the formation of stable endometrial endothelial cell networks and attachment of a stratified endometrial epithelial cell layer, enables culture of a hormone-responsive stromal compartment, and provides the capacity to monitor the kinetics of trophoblast invasion. With these studies, we provide a series of techniques that will instruct researchers in the development of endometrial models of increasing complexity.
Repressive gene regulation synchronizes development with cellular metabolism
Authors: Cassidy Justin J. , Bernasek Sebastian , Bakker Rachael , Giri Ritika , Peláez Nicolás , Eder Bryan , Bobrowska Anna , Bagheri Neda , Amaral Luis A. Nunes , Carthew Richard W. 
Published: February 2019

ABSTRACTMetabolic conditions affect the developmental tempo of most animal species. Consequently, developmental gene regulatory networks (GRNs) must faithfully adjust their dynamics to a variable time scale. We find evidence that layered weak repression of genes provides the necessary coupling between GRN output and cellular metabolism. Using a mathematical model that replicates such a scenario, we find that lowering metabolism corrects developmental errors that otherwise occur when different layers of repression are lost. Through mutant analysis, we show that gene expression dynamics are unaffected by loss of repressors, but only when cellular metabolism is reduced. We further show that when metabolism is lowered, formation of a variety of sensory organs inDrosophilais normal despite loss of individual repressors of transcription, mRNA stability, and protein stability. We demonstrate the universality of this phenomenon by experimentally eliminating the entire microRNA family of repressors, and find that all microRNAs are rendered unnecessary when metabolism is reduced. Thus, layered weak repression provides robustness through error frequency suppression, and may provide an evolutionary route to a shorter reproductive cycle.
Single-cell RNA sequencing of a European and an African lymphoblastoid cell line
Authors: Osorio Daniel , Yu Xue , Yu Peng , Serpedin Erchin , Cai James J. 
Published: February 2019

AbstractIn biomedical research, lymphoblastoid cell lines (LCLs), often established byin vitroinfection of resting B cells with Epstein Barr Virus, are commonly used as surrogates for peripheral blood lymphocytes. Genomic and transcriptomic information on LCLs has been used to study the impact of genetic variation on gene expression in humans. Here we present single-cell RNA sequencing (scRNA-seq) data on GM12878 and GM18502—two LCLs derived from the blood of female donors of European and African ancestry, respectively. Cells from three samples (the two LCLs and a 1:1 mixture of the two) were prepared separately using a 10X Genomics Chromium Controller and deeply sequenced. The final dataset contained 7,045 cells from GM12878, 5,189 from GM18502, and 5,820 from the mixture, offering valuable information on single-cell gene expression in highly homogenous cell populations. This dataset is a suitable reference of population differentiation in gene expression at the single-cell level. Data from the mixture provides additional valuable information facilitating the development of statistical methods for data normalization and batch effect correction.
MicroRNA-143 plays a protective role in ischemia-induced retinal neovascularization
Authors: Wang Jiang-Hui , Chen Jinying , Ling Damien , Tu Leilei , Singh Vikrant , Riaz Moeen , Li Fan , Prea Selwyn M. , He Zheng , Bui Bang V. , Hewitt Alex W. , van Wijngaarden Peter , Dusting Gregory J. , Liu Guei-Sheung 
Published: February 2019

AbstractRetinal neovascularization is a severe complication of proliferative diabetic retinopathy. MicroRNAs (miRNAs) are master regulators of gene expression that play important roles in retinal neovascularization. Here, we investigated the retinal miRNA expression profile in a rat model of oxygen-induced retinopathy (OIR) through miRNA-Seq. We found that miR-143-3p, miR-126-3p, miR-150-5p and miR-145-5p were significantly down-regulated in the retina of OIR rats, and directly involved in the development of retinal neovascularization. Of these identified miRNAs, miR-143 is enriched in retina and was first reported being associated with pathological retinal angiogenesis. Our RNA-Seq data further suggested that miR-143 alleviates retinal neovascularization by mediating the inflammation/stress pathways via Fos. Moreover, the computational analysis indicated that Transforming Growth Factor-beta Activated Kinase 1 (TAK1) is involved in several key pathways associated with the dysregulated miRNAs. The pharmacological inhibition of TAK1 suppressed angiogenesis in vitro and retinal neovascularization in vivo. Our data highlight the utility of next-generation sequencing in the development of therapeutics for ocular neovascularization and further suggest that therapeutic targeting the dysregulated miRNAs or TAK1 may be a feasible adjunct therapeutic approach in patients with retinal neovascularization.
Structure of the Ebola virus nucleoprotein – RNA complex
Authors: Kirchdoerfer Robert N. , Saphire Erica Ollmann , Ward Andrew B. 
Published: February 2019

AbstractEbola virus is an emerging virus capable of causing a deadly disease in humans. Replication, transcription and packaging of the viral genome is carried out by the viral nucleocapsid. The nucleocapsid is a complex of the viral nucleoprotein, RNA and several other viral proteins. The nucleoprotein NP forms large, RNA-bound, helical filaments and acts as a scaffold for additional viral proteins. The 3.1 Å single-particle cryo-electron microscopy structure of the nucleoprotein-RNA helical filament presented here resembles previous structures determined at lower resolution while providing improved molecular details of protein-protein and protein-RNA interactions. The higher resolution of the structure presented here will facilitate the design and characterization of novel and specific Ebola virus therapeutics targeting the nucleocapsid.SynopsisThe 3.1 Å single-particle cryo-electron microscopy structure of the RNA-bound, Ebola virus nucleoprotein helical filament provides molecular details of protein-protein and protein-RNA interactions.
Repeated treatment with cocaine or methamphetamine increases CRF2 and decreases astrocytic markers in the ventral tegmental area and substantia nigra
Authors: Sharpe Amanda L. , Trzeciak Marta , Douglas Phillip , Beckstead Michael J. 
Published: February 2019

AbstractDopamine neurons in the substantia nigra (SN) and ventral tegmental area (VTA) play a crucial role in the reinforcing properties of abused drugs including methamphetamine and cocaine. Evidence also suggests the involvement of non-dopaminergic transmitters, including glutamate and the stress-related peptide corticotropin-releasing factor (CRF), on the chronic effects of psychostimulants in the SN/VTA. Astrocytes express a variety of membrane-bound neurotransmitter receptors and transporters which influence neurotransmission in the SN/VTA. CRF2 activity in the VTA is important for stress-induced relapse and drug-seeking behavior, but the localization of its effects are not completely understood. Here we used immunofluorescence to identify the effect of methamphetamine and cocaine administration on astrocytes, the glial glutamate transporter GLAST, and CRF2 in the SN/VTA. We treated adult male mice with i.p. injections of methamphetamine (3 mg/kg), cocaine (10 mg/kg), or saline for 12 days. Coronal brain sections were processed for immunofluorescence using S100β (marker for astrocytes), glial-specific glutamate/aspartate transporters (GLAST), and CRF2. The results showed a significant decrease in GLAST immunofluorescence in brains of mice treated with cocaine or methamphetamine compared to saline. In addition, we observed increased labelling of CRF2 in drug treated groups, a decrease in the number of S100β positive cells, and an increase in co-staining of these two markers. Our results suggest that administration of either methamphetamine or cocaine decreases astrocytic markers and increases immunoreactivity for CRF2 in the VTA, an effect that is most pronounced in S100β positive cells.
A null model of the mouse whole-neocortex micro-connectome
Authors: Reimann Michael W , Gevaert Michael , Shi Ying , Lu Huanxiang , Markram Henry , Muller Eilif 
Published: February 2019

1AbstractConnectomics, the study of the structure of networks of synaptically connected neurons, is one of the most important frontiers of neuroscience. Great advances are being made on the level of macro- and meso-scale connectomics, that is the study of how and which populations of neurons are wired together by tracing axons of anatomically and genetically defined neurons throughout the brain. Similarly, the use of electron-microscopy and statistical connectome models has improved our understanding of micro-connectomics, that is the study of connectivity patterns between individual neurons. We have combined these two complementary views of connectomics to build a first draft statistical model of the neuron-to-neuron micro-connectome of a whole mouse neocortex. We combined available data on region-to-region connectivity and individual whole-brain axon reconstructions to model in addition to the meso-scale trends also the innervation of individual neurons by individual axons, within and across regions. This process revealed a novel targeting principle that allowed us to predict the innervation logic of individual axons from meso-scale data. The resulting micro-connectome of 10 million neurons and 88 billion synapses recreates biological trends of targeting on the macro-meso- and micro-scale, i.e. targeting of brain regions, domains and layers within a brain region down to individual neurons. This openly accessible connectome can serve as a powerful null model to compare experimental findings to and as a substrate for whole-brain simulations of detailed neural networks.