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116 results for “developmental model”
Text-fig. 2. Developmental morphospace of molariform ratios in Lestodon armatus compared to the IC model. Dash-dot line (-.-), show OLS line; dash double-dot line (-..-) shows RMA line. in Unexpected Inhibitory Cascade In The Molariforms Of Sloths (Folivora, Xenarthra): A Case Study In Xenarthrans Honouring Gerhard Storch'S Open-Mindedness
Text-fig. 2. Developmental morphospace of molariform ratios in Lestodon armatus compared to the IC model. Dash-dot line (-.-), show OLS line; dash double-dot line (-..-) shows RMA line.
isoTWAS models for developmental brain cortex (06/2023)
<p>This folder contains isoTWAS and TWAS models for developmental brain cortex using data from Walker et al 2019, <em>Cell</em> (June 2023). The folder contains two subfolders with .RDS files for isoTWAS and TWAS models and a third subfolder that contains .RDS files for in-sample LD matrices corresponding to each model. Models were trained using R package isotwas (github.com/bhattacharya-a-bt/isotwas). <strong>Please note that updated TWAS models are available at <a href="../records/10642128">https://zenodo.org/records/10642128</a>; isoTWAS models remain equivalent across these two releases.</strong></p>
Comparison of physiologically based pharmacokinetic modeling platforms for developmental neurotoxicity in vitro to in vivo extrapolation
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Developmental stress elicits preference for methamphetamine in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder
<p>The raw data of the manuscript, "Developmental stress elicits preference for methamphetamine in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder".</p>
Movements during sleep reveal the developmental emergence of a cerebellar-dependent internal model in motor thalamus
<p>With our eyes closed, we can track a limb's moment-to-moment location in space. If this capacity relied on sensory feedback from the limb, we would always be a step behind because sensory feedback takes time: For the execution of rapid and precise movements, such lags are not tolerable. Nervous systems solve this problem by computing representations—or internal models—that mimic movements as they are happening, with the associated neural activity occurring after the motor command but before the sensory feedback. Research in adults indicates that the cerebellum is necessary to compute internal models. What is not known, however, is when—and under what conditions—this computational capacity develops. Here, taking advantage of the unique kinematic features of the discrete, spontaneous limb twitches that characterize active sleep, we captured the developmental emergence of a cerebellar-dependent internal model. Using rats at postnatal days (P) 12, P16, and P20, we compared neural activity in the ventral posterior (VP) and ventral lateral (VL) thalamic nuclei, both of which receive somatosensory input but only the latter of which receives cerebellar input. At all ages, twitch-related activity in VP lagged behind the movement, consistent with sensory processing; similar activity was observed in VL through P16. At P20, however, VL activity no longer lagged behind movement, but instead precisely mimicked the movement itself; this activity depended on cerebellar input. In addition to demonstrating the emergence of internal models of movement, these findings implicate twitches in their development and calibration through, at least, the preweanling period.</p>
Transcriptomic characterization of 2D and 3D human induced pluripotent stem cell-based in vitro models as New Approach Methodologies for developmental neurotoxicity testing
<p><strong>Abstract:</strong> The safety and developmental neurotoxicity (DNT) potential of chemicals remain critically understudied due to limitations of current in vivo testing guidelines, which are low throughput, resource-intensive, and hindered by species differences that limit their relevance to human health. To address these issues, robust new approach methodologies (NAMs) using deeply characterized cell models are essential. This study presents the comprehensive transcriptomic characterization of two advanced human-induced pluripotent stem cell (hiPSC)-derived models: a 2D adherent and a 3D neurosphere model of human neural progenitor cells (hiNPCs) differentiated up to 21 days. Using high-throughput RNA sequencing, we compared gene expression profiles of 2D and 3D models at three developmental stages (3, 14, and 21 days of differentiation). Both models exhibit maturation towards post-mitotic neurons, with the 3D model maturing faster and showing a higher prevalence of GABAergic neurons, while the 2D model is enriched with glutamatergic neurons. Both models demonstrate broad applicability domains, including excitatory and inhibitory neurons, astrocytes, and key endocrine and especially the understudied cholinergic receptors. Comparison with human fetal brain samples confirms their physiological relevance. This study provides novel in-depth applicability insights into the temporal and dimensional aspects of hiPSC-derived neural models for DNT testing. The complementary use of these two models is highlighted: the 2D model excels in synaptogenesis assessment, while the 3D model is particularly suited for neural network formation as observed as well in previous functional studies with these models. This research marks a significant advancement in developing human-relevant, high-throughput DNT assays for regulatory purposes.</p> <p><strong>This data sets contains:</strong></p> <p><strong>Tab. S1</strong> - Significant genes results</p> <p><strong>Tab. S2</strong> - Enriched pathways_GO_Biological Processes</p> <p><strong>Tab. S3</strong> - Enriched pathways_GO_Cellular Components</p> <p><strong>Tab. S4</strong> - Enriched pathways_GO_Molecular Function</p> <p><strong>Tab. S5</strong> - Enriched pathways_KEGG</p> <p><strong>Tab. S6</strong> - EnrichEnriched pathways_Panther</p> <p><strong>Tab. S7</strong> - Enriched pathways_Reactome</p> <p><strong>Tab. S8</strong> - Gene counts</p> <p><strong>Tab. S9</strong> - Gene selection for targeted analysis</p>
Transcriptional patterns of sexual dimorphism and in host developmental programs in the model parasitic nematode Heligmosomoides bakeri
<p><strong>Background</strong></p> <p><em>Heligmosomoides bakeri </em>(often mistaken for <em>Heligmosomoides</em> <em>polygyrus</em>) is a promising model for parasitic nematodes with the key advantage of being amenable to study and manipulation within a controlled laboratory environment. While draft genome sequences are available for this worm, which allow for comparative genomic analyses between nematodes, there is a notable lack of information on its gene expression.</p> <p><strong>Methods </strong></p> <p>We generated biologically replicated RNA-seq datasets from samples taken throughout the parasitic life of <em>H. bakeri</em>. RNA from tissue-dwelling and lumen-dwelling worms, collected under a dissection microscope, was sequenced on an Illumina platform. <strong> </strong></p> <p><strong>Results</strong></p> <p>We find extensive transcriptional sexual dimorphism throughout the fourth larval and adult stages of this parasite and identify alternative splicing, glycosylation, and ubiquitination as particularly important processes for establishing and/or maintaining sex-specific gene expression in this species. We find sex-linked differences in transcription related to aging and oxidative and osmotic stress responses. We observe a starvation-like signature among transcripts whose expression is consistently upregulated in males, which may reflect a higher energy expenditure by male worms. We detect evidence of increased importance for anaerobic respiration among the adult worms, which coincides with the parasite's migration into the physiologically hypoxic environment of the intestinal lumen. Furthermore, we hypothesize that oxygen concentration may be an important driver of the worms encysting in the intestinal mucosa as larvae, which not only fully exposes the worms to their host's immune system but also shapes many of the interactions between the host and parasite. We find stage- and sex-specific variation in the expression of immunomodulatory genes and in anthelmintic targets. <strong> </strong></p> <p><strong>Conclusions</strong></p> <p>We examine how different the male and female worms are at the molecular level and describe major developmental events that occur in the worm, which extend our understanding of the interactions between this parasite and its host. In addition to generating new hypotheses for follow-up experiments into the worm's behavior, physiology, and metabolism, our datasets enable future more in-depth comparisons between nematodes to better define the utility of <em>H. bakeri</em> as a model for parasitic nematodes in general. </p>
Movements during sleep reveal the developmental emergence of a cerebellar-dependent internal model in motor thalamus
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Abnormal cytoskeletal remodeling but normal neuronal excitability in a mouse model of the recurrent developmental and epileptic encephalopathy-susceptibility KCNB1-p.R312H variant
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Data from: Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model
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Transcriptional patterns of sexual dimorphism and in host developmental programs in the model parasitic nematode Heligmosomoides bakeri
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Data from: Life stage hypothesis modeling determines insect vulnerability during developmental life stages to climate extremes
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Data from: A model of developmental canalization, applied to human cranial form
<p>Developmental mechanisms that canalize or compensate perturbations of organismal development (targeted or compensatory growth) are widely considered a prerequisite of individual health and the evolution of complex life, but little is known about the nature of these mechanisms. It is even unclear if and how a "target trajectory" of individual development is encoded in the organism's genetic-developmental system or, instead, emerges as an epiphenomenon. Here we develop a statistical model of developmental canalization based on an extended autoregressive model. We show that under certain assumptions the strength of canalization and the amount of canalized variance in a population can be estimated, or at least approximated, from longitudinal phenotypic measurements, even if the target trajectories are unobserved. We extend this model to multivariate measures and discuss reifications of the ensuing parameter matrix. We apply these approaches to longitudinal geometric morphometric data on human postnatal craniofacial size and shape as well as to the size of the frontal sinuses. Craniofacial size showed strong developmental canalization during the first 5 years of life, leading to a 50% reduction of cross-sectional size variance, followed by a continual increase in variance during puberty. Frontal sinus size, by contrast, did not show any signs of canalization. Total variance of craniofacial shape decreased slightly until about 5 years of age and increased thereafter. However, different features of craniofacial shape showed very different developmental dynamics. Whereas the relative dimensions of the nasopharynx showed strong canalization and a reduction of variance throughout postnatal development, facial orientation continually increased in variance. Some of the signals of canalization may owe to independent variation in developmental timing of cranial components, but our results indicate evolved, partly mechanically induced mechanisms of canalization that ensure properly sized upper airways and facial dimensions.</p>
Data and results from: "De novo spatiotemporal modelling of cell-type signatures in the developmental human heart"
<p>This repository contains data used and results produced in the manuscript:</p> <p>Sergio Marco Salas, Xiao Yuan, Christer Sylven, Mats Nilsson, Carolina Wählby, Gabriele Partel. "De novo spatiotemporal modelling of cell-type signatures in the developmental human heart"</p> <p>In situ sequencing [1] and scRNA-seq data [2] generated by Asp et al. [3] were downloaded and redistributed under CC BY 4.0 license.</p> <p>[1] Wu, Chenglin; Qian, Xiaoyan; Nilsson, Mats (2019): ISS data in "A spatiotemporal organ-wide gene expression and cell atlas of the developing human heart". figshare. Dataset. https://doi.org/10.6084/m9.figshare.10058048.v1 </p> <p>[2] Asp, Michaela (2021), “Developmental heart - filtered and unfiltered count matrices and meta tables”, Mendeley Data, V2, doi: 10.17632/mbvhhf8m62.2</p> <p>[3] Asp, M., Giacomello, S., Larsson, L., Wu, C., Fürth, D., Qian, X., ... & Lundeberg, J. (2019). A spatiotemporal organ-wide gene expression and cell atlas of the developing human heart. <em>Cell</em>, <em>179</em>(7), 1647-1660.</p>
The developmental and evolutionary characteristics of transcription factor binding site clustered regions based on an explainable machine learning model
<p>## Identification of transcription factor binding sites clustered regions</p> <p>First, the TFBSs were identified from ATAC-seq peaks by FIMO. The position-specific weight matrices (PWMs) of transcription factors were downloaded from CIS-BP databases. The genomic sequences under the open chromatin regions were used as inputs for FIMO with a custom library of all motifs for each species to scan for motif instances at a p-value threshold of 1e-5. </p> <p>Then, an established method was used to identify TFCRs by performing the Gaussian kernel density estimations across the genome (with a bandwidth of 300bp centered on each TFBS). Each peak in density profile was considered a TFCR. To determine the complexity of each TFCR, the Gaussian kernelized distances from each peak that contributed at least 0.1 to its strength were determined. The complexity of each TFCR was determined by the quantity and proximity of the contributing TFBS. We combined motif instances based on the TF family information from CIS-BP to calculate the complexity of TFCR. The window for each TFCR was determined by finding the maximum distance (in bp) from the TFCR to a contributing TF and then adding 150 bp (one-half of the bandwidth). Each window was centered on the TFCR. The identified TFCR was grouped into 10 groups based on their complexity from low to high. </p> <p>usage: <br>indir="Human_fimo" # the directory where you put the output files of FIMO <br>motifMap="Homo_sapiens_2020_0920/TF_Information_all_motifs_plus.txt" # the mapping relationship of TF and its TF family from CIS-BP <br>cd Codes/TFCR_embryo <br>perl d-motif_combine.pl $indir TFfamily $motifMap <br>perl e-tfpos_combine.pl TFfamily <br>perl f1-tf_bed-new-c.pl TFfamily <br>perl 0-merge-TFCR.pl $indir TFfamily </p>
Natural history of model organisms: the secret (group) life of Drosophila melanogaster larvae and why it matters to developmental ecology
<ol> <li>Model organisms such as <i>Drosophila melanogaster</i> have been key tools for advancing our fundamental and applied knowledge in biological and biomedical sciences. However, model organisms have become intertwined with the idea of controlled and stable laboratory environments, and their natural history has been overlooked.</li> <li>In holometabolous insects, lack of natural history information on larval ecology has precluded major advances in the field of developmental ecology, especially in terms of manipulations of population density early in life (i.e., larval density). This is because of relativistic and to some extent, arbitrary methodologies employed to manipulate larval densities in laboratory studies. As a result, these methodologies render comparisons between species impossible, precluding our understanding of macroevolutionary responses to population densities during development that can be derived from comparative studies.</li> <li>We recently proposed a new conceptual framework to address this issue and here, we provide the first natural history investigation of <i>Drosophila melanogaster </i>larval density under such framework. First, we characterised the distribution of larval densities in wild population of <i>D. melanogaster </i>using rotting apples as breeding substrate in a suburban area in Sweden.</li> <li>Next, we compiled the commonly used methodologies for manipulating larval densities in laboratory studies from the literature and found that the majority of laboratory studies did not manipulate larval densities below or above the densities observed in nature, suggesting that we have yet to study true life-history and physiological responses to low and high population densities during <i>D. melanogaster</i> development.</li> <li>This is, to our knowledge, the first direct natural history account of larval density in nature for this model organism. Our study paves the way for a more integrated view of organismal biology which re-incorporates natural history of model organisms into hypothesis-driven research in developmental ecology.</li> </ol>
Predictive modeling reveals that higher-order cooperativity drives transcriptional repression in a synthetic developmental enhancer
<p>A challenge in quantitative biology is to predict output patterns of gene expression from knowledge of input transcription factor patterns and from the arrangement of binding sites for these transcription factors on regulatory DNA. We tested whether widespread thermodynamic models could be used to infer parameters describing simple regulatory architectures that inform parameter-free predictions of more complex enhancers in the context of transcriptional repression by Runt in the early fruit fly embryo. By modulating the number and placement of Runt binding sites within an enhancer, and quantifying the resulting transcriptional activity using live imaging, we discovered that thermodynamic models call for higher-order cooperativity between multiple molecular players. This higher-order cooperativity capture the combinatorial complexity underlying eukaryotic transcriptional regulation and cannot be determined from simpler regulatory architectures, highlighting the challenges in reaching a predictive understanding of transcriptional regulation in eukaryotes and calling for approaches that quantitatively dissect their molecular nature.</p>
Data from: A model of developmental canalization, applied to human cranial form
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Predictive modeling reveals that higher-order cooperativity drives transcriptional repression in a synthetic developmental enhancer
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Data from: Modeling winter moth Operophtera brumata egg phenology: nonlinear effects of temperature and developmental stage on developmental rate
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.