bluuebunny/crossref_metadata_2025_split huggingface dataset:
A semi-automated organoid screening method demonstrates epigenetic control of intestinal epithelial differentiation
Authors: Ostrop Jenny , Zwiggelaar Rosalie , Pedersen Marianne Terndrup , Gerbe François , Bösl Korbinian , Lindholm Håvard T. , Díez-Sánchez Alberto , Parmar Naveen , Radetzki Silke , von Kries Jens Peter , Jay Philippe , Jensen Kim B. , Arrowsmith Cheryl , Oudhoff Menno J. 
Published: July 2020

AbstractIntestinal organoids are an excellent model to study epithelial biology. Yet, the selection of analytical tools to accurately quantify heterogeneous organoid cultures remains limited. Here, we developed a semi-automated organoid screening method, which we applied to a library of highly specific chemical probes to identify epigenetic regulators of intestinal epithelial biology. The role of epigenetic modifiers in adult stem cell systems, such as the intestinal epithelium, is still undefined. Based on this resource data, we identified several targets that affected epithelial cell differentiation, including HDACs, EP300/CREBBP, LSD1, and type I PRMTs, which were verified by complementary methods. For example, we show that inhibiting type I PRMTs, which leads enhanced epithelial differentiation, blocks the growth of adenoma but not normal organoid cultures. Thus, epigenetic probes are powerful tools to study intestinal epithelial biology and may have therapeutic potential.
Network and synaptic mechanisms underlying high frequency oscillations in the rat and cat olfactory bulb under ketamine-xylazine anesthesia
Authors: Średniawa Władysław , Wróbel Jacek , Kublik Ewa , Wójcik Daniel Krzysztof , Whittington Miles Adrian , Hunt Mark Jeremy 
Published: July 2020

AbstractHigh frequency oscillations (HFO) are receiving increased attention for their role in health and disease. Ketamine-dependent HFO have been identified in cortical and subcortical regions in rodents, however, the mechanisms underlying their generation and whether they occur in higher mammals is unclear. Here, we show under ketamine-xylazine anesthesia, classical gamma oscillations diminish and a prominent > 80 Hz oscillation emerges in the olfactory bulb of rats and cats. In cats negligible HFO was observed in the thamalus and visual cortex indicating the OB was a suitable site for further investigation. Simultaneous local field potential and thermocouple recordings demonstrated HFO was dependent on nasal airflow. Silicon probe mapping studies spanning almost the entire dorsal ventral aspect of the OB revealed this rhythm was strongest in ventral areas of the bulb and associated with microcurrent sources about the mitral layer. Pharmacological microinfusion studies revealed HFO was dependent on excitatory-inhibitory synaptic activity, but not gap junctions. Finally, we showed HFO was preserved despite surgical removal of the piriform cortex. We conclude that ketamine-dependent HFO in the OB are driven by nasal airflow and local dendrodendritic interactions. The relevance of our findings to ketamine’s model of psychosis in awake state are also discussed.
Data-guided Multi-Map variables for ensemble refinement of molecular movies
Authors: Vant John W. , Sarkar Daipayan , Streitwieser Ellen , Fiorin Giacomo , Skeel Robert , Vermaas Josh V. , Singharoy Abhishek 
Published: July 2020

AbstractDriving molecular dynamics simulations with data-guided collective variables offer a promising strategy to recover thermodynamic information from structure-centric experiments. Here, the 3-dimensional electron density of a protein, as it would be determined by cryo-EM or X-ray crystallography, is used to achieve simultaneously free-energy costs of conformational transitions and refined atomic structures. Unlike previous density-driven molecular dynamics methodologies that determine only the best map-model fits, our work uses the recently developedMulti-Mapmethodology to monitor concerted movements within equilibrium, non-equilibrium, and enhanced sampling simulations. Construction of all-atom ensembles along chosen values of the Multi-Map variable enables simultaneous estimation of average properties, as well as real-space refinement of the structures contributing to such averages. Using three proteins of increasing size, we demonstrate that biased simulation along reaction coordinates derived from electron densities can serve to induce conformational transitions between known intermediates. The simulated pathways appear reversible, with minimal hysteresis and require only low-resolution density information to guide the transition. The induced transitions also produce estimates for free energy differences that can be directly compared to experimental observables and population distributions. The refined model quality is superior compared to those found in the Protein DataBank. We find that the best quantitative agreement with experimental free-energy differences is obtained using medium resolution (~5 Å) density information coupled to comparatively large structural transitions. Practical considerations for generating transitions with multiple intermediate atomic density distributions are also discussed.
Retinal optic flow during natural locomotion
Authors: Matthis Jonathan Samir , Muller Karl S , Bonnen Kathryn , Hayhoe Mary M 
Published: July 2020

AbstractWe examine the structure of visual motion on the retina during natural locomotion in real world environments. Natural locomotion generates a rhythmic translation and rotation profile of the head in space, which means that visually specified heading varies throughout the gait cycle. This presents a challenge if optic flow is to be used to control heading towards a goal. The complex, phasic head movements that occur through the gait cycle create a highly unstable pattern of flow relative to the head. In contrast, vestibular-ocular-reflex mediated fixation simplifies patterns of optic flow on the retinae, resulting in regular features that may be valuable for the control of locomotion. In particular, the sign and magnitude of foveal curl in retinal flow fields specifies the body’s trajectory relative to the fixation point. In addition, the peak in the divergence of the retinal flow field specifies the walker’s instantaneous overground velocity/momentum vector in retinotopic coordinates. Assuming that walkers can determine the body position relative to fixation, this time-varying retinotopic cue for the body’s momentum could provide a visual control signal for foot placement over complex terrain. In contrast, the temporal variation of heading is large enough to be problematic for use in steering towards a goal. Consideration of optic flow in the context of natural locomotion therefore suggests a re-evaluation of the role of optic flow in the visual control of locomotion.
Microbial drama in four acts - Extreme rain events cause cyclic succession in plankton communities
Authors: Shabarova Tanja , Salcher Michaela M. , Porcal Petr , Znachor Petr , Nedoma Jiří , Grossart Hans-Peter , Seďa Jaromír , Hejzlar Josef , Šimek Karel 
Published: July 2020

AbstractHighly abundant, small waterbodies contribute substantially to global freshwater shoreline and surface area. They are strongly interlinked with the terrestrial surrounding, thus controlling the flow of energy, nutrients and organisms through the landscape. Disturbance events can have severe consequences for these ecosystems and the entire downstream freshwater network and require more attention in the context of global change-induced increases in weather extremes. Here we show that extreme rain events (floods) cause cyclic successions in microbial communities and the planktonic food web of a small forest pond. We analyzed the dynamics of nutrients and the entire plankton community during two flood events and subsequent quasi-stable conditions. Floods induced a repeated washout of resident organisms and hundred-fold increases in nutrient load. However, within two weeks, the microbial community recovered to a pre-disturbance state through four well-defined succession phases. Reassembly of phyto- and especially zooplankton took considerably longer and displayed both repetitive and adaptive patterns. Release of dissolved nutrients from the pond was associated with inflow rates and state of community recovery, and it returned to pre-disturbance levels earlier than microbial composition. Our study exemplifies extraordinary compositional and functional resilience of small waterbodies and presents the detailed mechanism of the underlying processes.
Detection of homozygous and hemizygous partial exon deletions by whole-exome sequencing
Authors: Bigio Benedetta , Seeleuthner Yoann , Kerner Gaspard , Migaud Melanie , Rosain Jérémie , Boisson Bertrand , Nasca Carla , Puel Anne , Bustamante Jacinta , Casanova Jean-Laurent , Abel Laurent , Cobat Aurelie 
Published: July 2020

ABSTRACTThe detection of copy number variations (CNVs) in whole-exome sequencing (WES) data is important, as CNVs may underlie a number of human genetic disorders. The recently developed HMZDelFinder algorithm can detect rare homozygous and hemizygous (HMZ) deletions in WES data more effectively than other widely used tools. Here, we present HMZDelFinder_opt, an approach that outperforms HMZDelFinder for the detection of HMZ deletions, including partial exon deletions in particular, in typical laboratory cohorts that are generated over time under different experimental conditions. We show that using an optimized reference control set of WES data, based on a PCA-derived Euclidean distance for coverage, strongly improves the detection of HMZ deletions both in real patients carrying validated disease-causing deletions and in simulated data. Furthermore, we develop a sliding window approach enabling HMZDelFinder-opt to identify HMZ partial deletions of exons that are otherwise undiscovered by HMZDelFinder. HMZDelFinder_opt is a timely and powerful approach for detecting HMZ deletions, particularly partial exon deletions, in laboratory cohorts, which are typically heterogeneous.
Identifying signal and noise structure in neural population activity with Gaussian process factor models
Authors: Keeley Stephen L. , Aoi Mikio C. , Yu Yiyi , Smith Spencer L. , Pillow Jonathan W. 
Published: July 2020

AbstractNeural datasets often contain measurements of neural activity across multiple trials of a repeated stimulus or behavior. An important problem in the analysis of such datasets is to characterize systematic aspects of neural activity that carry information about the repeated stimulus or behavior of interest, which can be considered “signal”, and to separate them from the trial-to-trial fluctuations in activity that are not time-locked to the stimulus, which for purposes of such analyses can be considered “noise”. Gaussian Process factor models provide a powerful tool for identifying shared structure in high-dimensional neural data. However, they have not yet been adapted to the problem of characterizing signal and noise in multi-trial datasets. Here we address this shortcoming by proposing “signal-noise” Poisson-spiking Gaussian Process Factor Analysis (SNP-GPFA), a flexible latent variable model that resolves signal and noise latent structure in neural population spiking activity. To learn the parameters of our model, we introduce a Fourier-domain black box variational inference method that quickly identifies smooth latent structure. The resulting model reliably uncovers latent signal and trial-to-trial noise-related fluctuations in large-scale recordings. We use this model to show that predominantly, noise fluctuations perturb neural activity within a subspace orthogonal to signal activity, suggesting that trial-by-trial noise does not interfere with signal representations. Finally, we extend the model to capture statistical dependencies across brain regions in multi-region data. We show that in mouse visual cortex, models with shared noise across brain regions out-perform models with independent per-region noise.
The global and promoter-centric 3D genome organization temporally resolved during a circadian cycle
Authors: Ando-Kuri Masami , Arzate-Mejía Rodrigo G. , Morf Jorg , Cairns Jonathan , Poot-Hernández Cesar A. , Andrews Simon , Várnai Csilla , Virk Boo , Wingett Steven W. , Fraser Peter , Furlan-Magaril Mayra 
Published: July 2020

SummaryCircadian gene expression is essential for organisms to adjust cellular responses and anticipate daily changes in the environment. In addition to its physiological importance, the clock circuit represents an ideal, temporally resolved, system to study transcription regulation. Here, we analysed changes in spatial mouse liver chromatin conformation using genome-wide and promoter-capture Hi-C alongside daily oscillations in gene transcription in mouse liver. We found circadian topologically associated domains switched assignments to the transcriptionally active, open chromatin compartment and the inactive compartment at different hours of the day while their boundaries stably maintain their structure over time. Individual circadian gene promoters displayed maximal chromatin contacts at times of peak transcriptional output and the expression of circadian genes and contacted transcribed regulatory elements, or other circadian genes, was phase-coherent. Anchor sites of promoter chromatin loops were enriched in binding sites for liver nuclear receptors and transcription factors, some exclusively present in either rhythmic or stable contacts. The circadian 3D chromatin maps provided here identify the scales of chromatin conformation that parallel oscillatory gene expression and protein factors specifically associated with circadian or stable chromatin configurations.
PKA-mediated phosphorylation of Neuroligin-2 regulates its cell surface expression and synaptic stabilisation
Authors: Halff Els F. , Hannan Saad , Smart Trevor G. , Kittler Josef T. 
Published: July 2020

AbstractThe trans-synaptic adhesion molecule Neuroligin-2 (NL2) is essential for the development and function of inhibitory synapses. NL2 recruits the postsynaptic scaffold protein gephyrin, which in turn stabilises GABAAreceptors (GABAARs) in the postsynaptic domain. Dynamic regulation of synaptic GABAAR concentration is crucial for inhibitory neurotransmission efficacy. Changes in synaptic levels of NL2 contribute to regulating GABAAR synaptic concentration, however the mechanisms that control NL2 synaptic stabilisation are mostly unknown. Here, by combining biochemistry, imaging, single particle tracking and electrophysiology, we identify a key role for cAMP-dependent protein kinase (PKA) in synaptic stabilisation of NL2. We show that PKA-mediated phosphorylation of NL2 at S714 causes its dispersal from the synapse and reduces NL2 surface levels, leading to a loss of synaptic GABAARs. Conversely, enhanced stability of NL2 at synapses through abolishing phosphorylation leads to increased inhibitory signalling. Thus, PKA plays a key role in regulating NL2 function and synaptic inhibition.
Identification of a meiosis-specific chromosome movement pattern induced by persistent DNA damage
Authors: León-Periñán Daniel , Fernández-Álvarez Alfonso 
Published: July 2020

ABSTRACTAs one of the main events occurring during meiotic prophase, the dynamics of meiotic chromosome movement is not yet well understood. Currently, although it is well-established that chromosome movement takes an important role during meiotic recombination promoting the pairing between homologous chromosomes and avoiding excessive chromosome associations, it is mostly unclear whether those movements follow a particular fixed pattern, or are stochastically distributed. UsingSchizosaccharomyces pombeas a model organism, which exhibits dramatic meiotic nuclear oscillations, we have developed a computationally automatized statistical analysis of three-dimensional time-lapse fluorescence information in order to characterize nuclear trajectories and morphological patterns during meiotic prophase. This approach allowed us to identify a patterned oscillatory microvariation during the meiotic nuclear motion. Additionally, we showed evidence suggesting that this unexpected oscillatory motif might be due to the detection of persistent DNA damage during the nuclear movement, supporting how the nucleus also regulates its oscillations. Our computationally automatized tool will be useful for the identification of new patterns of nuclear oscillations during gametogenesis.
Respiratory bacteria stabilize and promote airborne transmission of influenza A virus
Authors: Rowe Hannah M. , Livingston Brandi , Margolis Elisa , Davis Amy , Meliopoulos Victoria A. , Echlin Haley , Schultz-Cherry Stacey , Rosch Jason W 
Published: July 2020

ABSTRACTInfluenza A virus (IAV) is a major pathogen of the human respiratory tract where the virus co-exists and interacts with bacterial populations comprising the respiratory microbiome. Synergies between IAV and respiratory bacterial pathogens promote enhanced inflammation and disease burden that exacerbate morbidity and mortality. We demonstrate that direct interactions between IAV and encapsulated bacteria commonly found in the respiratory tract promote environmental stability and infectivity of IAV. Antibiotic-mediated depletion of the respiratory bacterial flora abrogated IAV transmission in ferret models, indicating that these viral-bacterial interactions are operative for airborne transmission of IAV. Restoring IAV airborne transmission in antibiotic treated ferrets by co-infection withStreptococcus pneumoniaeconfirmed a role for specific members of the bacterial respiratory community in promoting IAV transmission. These results implicate a role for the bacterial respiratory flora in promoting airborne transmission of IAV.
Expression of the type III secretion system genes in epiphyticErwinia amylovoracells on apple stigmas benefits endophytic infection at the hypanthium
Authors: Cui Zhouqi , Huntley Regan B. , Schultes Neil P , Kakar Kaleem U. , Zeng Quan 
Published: July 2020

AbstractErwinia amylovoracauses fire blight on rosaceous plants. Flower surfaces are the primary location in the fire blight infection pathway. Here E. amylovora proliferates on stigmatic and hypanthium surfaces as epiphytic growth, followed by subsequent endophytic (intercellular) infection in the hypanthium. The type III secretion system (T3SS) is an important virulence factor inE. amylovora. Although the role of T3SS during the endophytic infection is well characterized, its expression during the epiphytic colonization and role in the subsequent infection is less understood. Here, we investigated the T3SS expression in epiphyticE. amylovoraon stigma and hypanthium of apple flowers, under different relative humidities (RH). On stigma surfaces, T3SS was expressed in a high percentage of E. amylovora cells, and its expression promotes epiphytic growth. On hypanthium surfaces however, T3SS was expressed in fewerE. amylovoracells than on the stigma, and displayed no correlation with epiphytic growth, even though T3SS expression is essential for infection.E. amylovoracells grown on stigmatic surfaces and then flushed down to the hypanthium displayed a higher level of T3SS expression than cells grown on the hypanthium surface alone. Furthermore, cells pre-cultured on stigma before inoculation on hypanthium caused more infections than cells pre-cultured in a T3SS-repressive medium then used as inoculum, suggesting that the T3SS induction during the stigmatic epiphytic colonization may be beneficial for the subsequent infection. Finally, the epiphytic expression of T3SS is influenced by RH. Higher percentage of stigmaticE. amylovoracells expressed T3SS under high RH than under low RH.
Ethoflow: computer vision and artificial intelligence-based software for automatic behavior analysis
Authors: Bernardes Rodrigo Cupertino , Lima Maria Augusta Pereira , Guedes Raul Narciso C. , Martins Gustavo Ferreira 
Published: July 2020

AbstractManual monitoring of animal behavior is time-consuming and prone to bias. An alternative to such limitations is the use of computational resources in behavioral assessments, such as a tracking system, to facilitate accurate and long-term evaluations. There is a demand for robust software that addresses analysis in heterogeneous environments (such as in field conditions) and evaluates multiple individuals in groups while maintaining their identities.The Ethoflow software was developed using computer vision and artificial intelligence (AI) tools to automatically monitor various behavioral parameters. A state-of-the-art object detection algorithm based on instance segmentation was implemented, allowing behavior monitoring in the field under heterogeneous environments. Moreover, a convolutional neural network was implemented to assess complex behaviors, thus expanding the possibilities of animal behavior analyses.The heuristics used to automatically generate training data for the AI models are described, and the models trained with these datasets exhibited high accuracy in detecting individuals in heterogeneous environments and assessing complex behavior. Ethoflow was employed for kinematic assessments and to detect trophallaxis in social bees. The software runs on the Linux, Microsoft Windows, and IOS operating systems with an intuitive graphical interface.In the Ethoflow algorithm, the processing with AI is separate from the other modules, which facilitates kinematic measurements on an ordinary computer and the assessment of complex behavior on machines with graphics processing units (GPUs). Thus, Ethoflow is a useful support tool for applications in biology and related fields.
Synergid calcium ion oscillations define a new feature of pollen tube reception critical for blocking interspecific hybridization
Authors: Ponvert Nathaniel , Johnson Mark A. 
Published: July 2020

AbstractReproductive isolation leads to the evolution of distinct new species, however, the molecular mechanisms that promote and maintain reproductive barriers are elusive. In flowering plants sperm cells are immotile and are delivered to female gametes by the pollen grain which germinates a polarized extension, the pollen tube, into floral tissue. After growing via polar extension to the female gametophyte, the pollen tube signals with receptive female cells flanking the egg in two distinct steps. If signaling is successful, the pollen tube releases sperm cells for fusion with female gametes. To better understand cell-cell recognition during reproduction, we investigated calcium ion dynamics associated with interspecific cell signaling between mating partners. We observed that interspecific pollen tubes successfully complete initial cell-cell signaling, but fail during later phases of pollen tube reception. Our work refines our understanding of pollen tube reception as a critical block to interspecific hybridization. Our results also shed light on the functional significance of the two phases of pollen tube reception, and implicate the second step as being the stage during which the pollen tube presents its genetic identity.