bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forward and backward blocking in statistical learning
Authors: Nazlı İlayda , Ferrari Ambra , Huber-Huber Christoph , de Lange Floris P. 
Published: February 2022

AbstractPrediction errors have a prominent role in many forms of learning. For example, in reinforcement learning, agents learn by updating the association between states and outcomes as a function of the prediction error elicited by the event. One paradigm often used to study error-driven learning is blocking. In forward blocking, participants are first presented with stimulus A, followed by outcome X (A→X). In the second phase, A and B are presented together, followed by X (AB→X). Here, A→X blocks the formation of B→X, given that X is already fully predicted by A. In backward blocking, the order of phases is reversed. Here, the association between B and X that is formed during the first learning phase of AB→X is weakened when participants learn exclusively A→X in the second phase. The present study asked the question whether forward and backward blocking occur during visual statistical learning, the largely automatic and incidental learning of the statistical structure of the environment. In a series of studies, using both forward and backward blocking, we observed robust statistical learning of temporal associations among pairs of images. While we found no compelling evidence for forward blocking, we observed reliable backward blocking in visual statistical learning.
Looming stimuli reliably drive innate, but not learned, defensive responses in rats
Authors: Heinemans Mirjam , Moita Marta A. 
Published: February 2022

AbstractSurvival relies on an organism’s intrinsic ability to instinctively react to stimuli such as food, water, and threats, ensuring the fundamental ability to feed, drink, and avoid danger even in the absence of prior experience. These natural, unconditioned stimuli can also facilitate associative learning, where pairing them consistently with neutral cues will elicit responses to those cue. Threat conditioning, a well-explored form of associative learning, commonly employs painful electric shocks, mimicking injury, as unconditioned stimuli. It remains elusive whether actual injury or pain is necessary for effective learning, or whether the threat of harm is sufficient. Approaching predators create looming shadows and sounds, triggering strong innate defensive responses like escape and freezing. This study investigates whether visual looming stimuli can induce learned freezing or learned escape responses to a conditioned stimulus in rats. Surprisingly, pairing a neutral tone with a looming stimulus only weakly evokes learned defensive responses, in contrast to the strong responses observed when the looming stimulus is replaced by a shock. This dissociation sheds light on the boundaries for learned defensive responses thereby impacting our comprehension of learning processes and defensive strategies.
Locomotor strategies inside the blind walks: freely moving previsual rat pups in the open field test
Authors: Midzyanovskaya I.S. , Strelkov V. V. 
Published: February 2022

ABSTRACTBlind walks of previsual rat pups in the open field test were considered as a supposedly random process. At this age, immature rats should rely only on non-visual modalities for sampling a novel space and constructing putative cognitive maps. Spontaneous locomotion of outbred Wistar rat infants (n=51) on their 13th postnatal day was tracked for 2 minutes and analyzed offline for the presence of random components and/or strategies of locomotion. Three distinct patterns were observed. A large portion of the pups (n=22) performed sub-diffusive localized walks in the center. A smaller cohort (n=9) undertook almost immediate quasi-linear raids in a random direction, thus succeeded in reaching a shelter (i.e., walls’ vicinity). The rest (n=20) demonstrated a mixed strategy: localized walks interspersed with quasi-linear raids. An algorithm for automated segmentation of the open field trajectories into the localized walks and quasi-linear fragments was developed; the fragments were analyzed separately.Statistical analysis shows the localized walks to be diffusive (i.e., Brownian) only within 2-3 seconds, but essentially sub-diffusive for longer time scales. The autocorrelation function shows that sub-diffusion was caused by the trajectories’ re-attraction. Self-odor traces can be a physical cue ensuring the effect.Gender or body weights were not significant predictors for any locomotor parameters. The localized walks can be considered as a primary level of idiothetically-cued path integration in previsual pups, whereas the run trials can be a form of an active escape response. The applied method of space potentials avails the automated functional segmentation of locomotor tracks and thus brings advantages of big data analysis for studying non-visual navigation in animals.
Continuous two-phase in vitro co-culture model of the enthesis
Authors: Park Hyeree , Cooke Megan E. , Lacombe Jean-Gabriel , Weber Michael H. , Martineau Paul A. , Nazhat Showan N. , Rosenzweig Derek H. 
Published: February 2022

AbstractThe enthesis is the interfacial tissue between ligament or tendon, and bone, which connects tissues of distinctly different mechanical properties. Although ligament and enthesis injury is commonplace, the development and healing mechanisms of these tissues are yet unclear. Current models for investigating these mechanisms are primarily in vivo animal models as in vitro models have been limited. In this study, an in vitro enthesis model was developed using a modified gel aspiration-ejection (GAE) method. Continuous two-phase aligned dense collagen (ADC) hydrogels with an overlapping interface were fabricated within 2 hours. The mechanical properties of acellular two-phase ADC confirmed the continuous nature of this model, as the mechanical properties showed no significant difference compared to single-phase ADC and maintained comparable structural and mechanical characteristics of immature ligaments and unmineralized bone. Human anterior cruciate ligament (ACL) fibroblasts and human spine vertebral osteoblasts were isolated from donor tissues and were seeded to form the enthesis model. These were cultured for 14 days, at which the viability and proliferation was observed to be 85 ± 7.5% and 230 ± 52%, respectively. Histological and immunofluorescence analyses at day 14 revealed extensive cell-driven matrix remodelling, and the seeded fibroblasts and osteoblasts maintained their phenotype within their compartments of the layered co-culture model. These results demonstrate the rapid fabrication of a two-phase co-culture system that can be utilized as an in vitro model to further understand the degenerative and regenerative mechanisms within the enthesis.
Correlative imaging of spatio-angular dynamics of molecular assemblies and cells with multimodal instant polarization microscope
Authors: Ivanov Ivan E. , Yeh Li-Hao , Perez-Bermejo Juan A. , Byrum Janie R. , Kim James Y.S. , Leonetti Manuel D. , Mehta Shalin B. 
Published: February 2022

AbstractBiological function depends on the spatio-angular architecture of macromolecules - for example, functions of lipid membrane and cytoskeletal polymers arise from both the spatial and the angular organization of the constituent molecules. Correlative imaging of cellular and molecular architecture is valuable across cell biology and pathology. However, current live imaging methods primarily focus on spatial component of the architecture. Imaging the dynamic angular architecture of cells and organelles requires fast polarization-, depth-, and wavelength-diverse measurement of intrinsic optical properties and fluorophore concentration, but remains challenging with current designs. We report a multimodal instant polarization microscope (miPolScope) that combines a broadband polarization-resolved detector, automation, and reconstruction algorithms to enable label-free imaging of phase, retardance, and orientation, multiplexed with fluorescence imaging of concentration, anisotropy, and orientation of molecules at diffraction-limited resolution and high speed. miPolScope enabled multimodal imaging of myofibril architecture and contractile activity of beating cardiomyocytes, cell and organelle architecture of live HEK293T and U2OS cells, and density and anisotropy of white and grey matter of mouse brain tissue across the visible spectrum. We anticipate these developments in joint quantitative imaging of density and anisotropy to enable new studies in tissue pathology, mechanobiology, and imaging-based screens.
Machine learning algorithm to characterize antimicrobial resistance associated with the International Space Station surface microbiome
Authors: Madrigal Pedro , Singh Nitin K. , Wood Jason M. , Gaudioso Elena , Hernández-del-Olmo Félix , Mason Christopher E. , Venkateswaran Kasthuri , Beheshti Afshin 
Published: February 2022

ABSTRACTBackgroundAntimicrobial Resistance (AMR) has a detrimental impact on human health on Earth and it is equally concerning in other environments such as space due to microgravity, radiation and confinement, especially for long-distance space travel. The International Space Station (ISS) is ideal for investigating microbial diversity and virulence. The shotgun metagenomics data of the ISS generated during the Microbial Tracking – 1 (MT-1) project and resulting metagenome-assembled genomes (MAGs) across three flights in eight different locations during 12 months were used in this study. The objective of this study was to identify the AMR genes associated with whole genomes of 227 cultivable strains, 21 shotgun metagenome sequences, and 24 MAGs retrieved from the ISS environmental samples that were treated with propidium monoazide (PMA; viable microbes).ResultsWe have analyzed the data using a deep learning model, allowing us to go beyond traditional cut-offs based only on high DNA sequence similarity and extending the catalog of AMR genes. Our results in PMA treated samples revealed AMR dominance in the last flight for Kalamiella piersonii, a bacteria related to urinary tract infection in humans. The analysis of 227 pure strains isolated from the MT-1 project revealed hundreds of antibiotic resistance genes from many isolates, including two top-ranking species that corresponded to strains of Enterobacter bugandensis and Bacillus cereus. Computational predictions were experimentally validated by antibiotic resistance profiles in these two species, showing a high degree of concordance. Specifically, disc assay data confirmed the high resistance of these two pathogens to various beta-lactam antibiotics.ConclusionOverall, our computational predictions and validation analyses demonstrate the advantages of machine learning to uncover concealed AMR determinants in metagenomics datasets, expanding the understanding of the ISS environmental microbiomes and their pathogenic potential in humans.
A Sulfonated Thermoresponsive Injectable Gel for Sequential Release of Therapeutic Proteins to Protect Cardiac Function After a Myocardial Infarction
Authors: Rocker Adam J. , Cavasin Maria , Johnson Noah , Shandas Robin , Park Daewon 
Published: February 2022

ABSTRACTMyocardial infarction causes cardiomyocyte death and persistent inflammatory responses, which generates adverse pathological remodeling. Delivering therapeutic proteins from injectable materials in a controlled release manner may present an effective biomedical approach for treating this disease. A thermoresponsive injectable gel composed of chitosan, conjugated with poly(N-isopropylacrylamide) and sulfonate groups, was developed for spatiotemporal protein delivery to protect cardiac function after a myocardial infarction. The thermoresponsive gel delivered VEGF, IL-10 and PDGF in a sequential and sustained manner in vitro. An acute myocardial infarction mouse model was used to evaluate polymer biocompatibility and to determine therapeutic effects from the delivery system on cardiac function. Immunohistochemistry showed biocompatibility of the hydrogel, while the controlled delivery of the proteins reduced macrophage infiltration and increased vascularization. Echocardiography showed an improvement in ejection fraction and fractional shortening after injecting the thermal gel and proteins. A factorial design of experiments study was implemented to optimize the delivery system for the best combination and doses of proteins for further increasing stable vascularization and reducing inflammation using a subcutaneous injection mouse model. The results showed that VEGF, IL-10, and FGF-2 demonstrated significant contributions towards promoting long-term vascularization, while PDGF’s effect was minimal.
The direction and timing of theta and alpha traveling waves modulate human memory processing
Authors: Mohan Uma R. , Zhang Honghui , Jacobs Joshua 
Published: February 2022

AbstractTo support a range of behaviors, the brain must flexibly coordinate neural activity across widespread brain regions. One potential mechanism for this coordination is a traveling wave, in which a neural oscillation propagates across the brain while organizing the order and timing of activity across regions1,2. Although traveling waves are present across the brain in various species3–5, their potential functional relevance remained unknown. Here, using rare direct human brain recordings, we demonstrate two novel functional roles for traveling waves of theta- and alpha-band (2–13 Hz) oscillations in the cortex. First, traveling waves propagate in different directions during separate cognitive processes. In episodic memory, traveling waves tended to propagate in posterior-to-anterior and anterior-to-posterior directions, respectively, during encoding and retrieval. Second, traveling waves are informative about the timing of behavior, with the phase of ongoing traveling waves indicating when subjects would retrieve memories. Because traveling waves of oscillations correspond to local neuronal spiking, these patterns indicate that rhythmic pulses of activity move across the brain with different directions and timing for separate behaviors. More broadly, our results suggest a fundamental role for traveling waves and oscillations in dynamically coordinating neural connectivity, by flexibly organizing the timing and directionality of network interactions across the cortex to support cognition and behavior.
Building an atlas of transposable elements reveals the extensive roles of young SINE in gene regulation, genetic diversity, and complex traits in pigs
Authors: Zhao Pengju , Gu Lihong , Gao Yahui , Pan Zhangyuan , Liu Lei , Li Xingzheng , Zhou Huaijun , Yu Dongyou , Han Xinyan , Qian Lichun , Liu George E. , Fang Lingzhao , Wang Zhengguang 
Published: February 2022

AbstractTransposable elements (TEs) are an extensive source of genetic polymorphisms and play an indispensable role in chromatin architecture, transcriptional regulatory networks, and genomic evolution. The pig is an important source of animal protein and serves as a biomedical model for humans, yet the functional role of TEs in pigs and their contributions to complex traits are largely unknown. Here, we built a comprehensive catalog of TEs (n = 3,087,929) in pigs by a newly developed pipeline. Through integrating multi-omics data from 21 tissues, we found that SINEs with different ages were significantly associated with genomic regions with distinct functions across tissues. The majority of young SINEs were predominantly silenced by histone modifications, DNA methylation, and decreased accessibility. However, the expression of transcripts that were derived from the remaining active young SINEs exhibited strong tissue specificity through cross-examining 3,570 RNA-seq from 79 tissues and cell types. Furthermore, we detected 211,067 polymorphic SINEs (polySINEs) in 374 individuals genome-wide and found that they clearly recapitulated known patterns of population admixture in pigs. Out of them, 340 population-specific polySINEs were associated with local adaptation. Mapping these polySINEs to genome-wide associations of 97 complex traits in pigs, we found 54 candidate genes (e.g., ANK2 and VRTN) that might be mediated by TEs. Our findings highlight the important roles of young SINEs in functional genomics and provide a supplement for genotype-to-phenotype associations and modern breeding in pigs.
Genome-wide profiling of histone H3K4me3 and H3K27me3 modifications in individual blastocysts by CUT&Tag without a solid support (NON-TiE-UP CUT&Tag)
Authors: Susami Kazuki , Ikeda Shuntaro , Hoshino Yoichiro , Honda Shinnosuke , Minami Naojiro 
Published: February 2022

AbstractIndividual analysis of the epigenome of preimplantation embryos is useful for characterizing each embryo and for investigating the effects of environmental factors on their epigenome. However, it is difficult to analyze genome-wide epigenetic modifications, especially histone modifications, in a large number of single embryos due to the small number of cells and the complexity of the analysis methods. To solve this problem, we further modified the CUT&Tag method, which can analyze histone modifications in a small number of cells, such that the embryo is handled as a cell mass in the reaction solutions in the absence of the solid-phase magnetic beads that are used for antibody and enzyme reactions in the original method (NON-TiE-UP CUT&Tag; NTU-CAT). By using bovine blastocysts as a model, we showed that genome-wide profiles of representative histone modifications, H3K4me3 and H3K27me3, could be obtained by NTU-CAT that are in overall agreement with the conventional chromatin immunoprecipitation-sequencing (ChIP-seq) method, even from single embryos. However, this new approach has limitations that require attention, including false positive peaks and lower resolution for broad modifications. Despite these limitations, we conclude that NTU-CAT is a promising replacement for ChIP-seq with the great advantage of being able to analyze individual embryos.
SAI: Fast and automated quantification of stomatal parameters on microscope images
Authors: Sai Na , Bockman James Paul , Chen Hao , Watson-Haigh Nathan , Xu Bo , Feng Xueying , Piechatzek Adriane , Shen Chunhua , Gilliham Matthew 
Published: February 2022

AbstractUsing microscopy to investigate stomatal behaviour is a common technique in plant physiology research. Manual inspection and measurement of stomatal features is a low throughput process in terms of time and human effort, which relies on expert knowledge to identify and measure stomata accurately. This process represents a significant bottleneck in research pipelines, adding significant researcher time to any project that requires it. To alleviate this, we introduce StomaAI (SAI): a reliable and user-friendly tool that measures stomata of the model plant Arabidopsis (dicot) and the crop plant barley (monocot grass) via the application of deep computer vision. We evaluated the reliability of predicted measurements: SAI is capable of producing measurements consistent with human experts and successfully reproduced conclusions of published datasets. Hence, SAI boosts the number of images that biologists can evaluate in a fraction of the time so is capable of obtaining more accurate and representative results.
Highly perturbed genes and hub genes associated with type 2 diabetes in different tissues of adult humans: A bioinformatics analytic workflow
Authors: Silva Kushan De , Demmer Ryan T. , Jönsson Daniel , Mousa Aya , Forbes Andrew , Enticott Joanne 
Published: February 2022

ABSTRACTIntroductionType 2 diabetes (T2D) has a complex etiology which is not fully elucidated. Identification of gene perturbations and hub genes of T2D may assist in personalizing care.ObjectivesWe aimed to identify highly perturbed genes and hub genes associated with T2D in different tissues of adult humans via an extensive workflow.MethodsWorkflow comprised five sequential steps: systematic review of NCBI GEO database; identification and classification of differentially expressed genes (DEG); identification of highly perturbed genes via meta-analysis; identification of hub genes via network analysis; downstream analyses. Three meta-analytic strategies: random effects model (REM); vote counting approach (VC);p-value combining approach (CA), were applied. Nodes having above average betweenness, closeness, and degree in the network were defined as hub genes. Downstream analyses included gene ontologies, Kyoto Encyclopedia of Genes and Genomes pathways, metabolomics, COVID-19 related genes, and Genotype-Tissue Expression profiles.ResultsAnalysis of 27 eligible microarrays identified 6284 DEG (4592 down-regulated and 1692 up-regulated) within four tissue types. Tissue-specific gene expression was significantly greater than tissue non-specific (shared) gene expression. Meta-analysis of DEG identified 49, 27, and 8 highly perturbed genes via REM, VC, and CA, respectively, producing a compiled set of 79 highly perturbed (41 down-regulated and 38 up-regulated) genes. The 28 hub genes comprised 13 up-regulated, 9 down-regulated, and 6 predicted genes. Downstream analyses identified enrichments of: shared genes with other diabetes phenotypes; insulin synthesis and action related pathways and metabolomics; mechanistic associations with apoptosis and immunity-related pathways, COVID-19 related gene sets; and cell types demonstrating over- and under-expression of marker genes of T2D.ConclusionsWe identified highly perturbed genes and hub genes of T2D and revealed their associations with other diabetes phenotypes and COVID-19 as well as pathophysiological manifestations such as those related to insulin, immunity, and apoptosis. Broader utility of the proposed pipeline is envisaged.
Food Insecurity Among Older Adults with a History of Incarceration
Authors: Jordan Tamara , Sneed Rodlescia 
Published: February 2022

AbstractObjectivesTo examine the association between history of incarceration (HOI) and food insecurity (FI) among older adults.MethodsThis is a secondary analysis utilizing data from 12,702 respondents aged 51+ who participated in the 2012 and 2014 waves of The Health and Retirement Study. Multiple logistic regression was used to estimate the association between HOI and FI, adjusting for demographic variables using odds ratios (OR) and 95% confidence intervals (CI).ResultsIn our sample, 12.8% of participants reported FI. Having a HOI increased odds of FI (OR 1.83; 95% CI 1.52-2.21), especially among Blacks (OR 1.78; 95% CI 1.29-2.46) and Whites (OR 2.27; 95% CI 1.74-2.97), but not Hispanics (OR 1.11; 95% CI 0.69-1.77) or other racial/ethnic groups (OR 1.79; 95% CI 0.71-4.52).DiscussionFI is an important issue among older adults with a HOI. Stronger linkages between formerly incarcerated older adults and existing food assistance programs are needed.