Embryo-scale epithelial buckling forms a propagating furrow that initiates gastrulation

2021 ◽  
Author(s):  
Julien Fierling ◽  
Alphy John ◽  
Barthélémy Delorme ◽  
Alexandre Torzynski ◽  
Guy B Blanchard ◽  
...  
Keyword(s):  
Computational Models ◽  
Molecular Mechanisms ◽  
Computational Modelling ◽  
Ventral Side ◽  
Force Balance ◽  
Drosophila Embryo ◽  
Epithelial Surface ◽  
Apical Constriction ◽  
Necessary And Sufficient ◽  
Actomyosin Contraction

Cell apical constriction driven by actomyosin contraction forces is a conserved mechanism during tissue folding in embryo development. While much effort has been made to better understand the molecular mechanisms responsible for apical constriction, it is still not clear if apical actomyosin contraction forces are necessary or sufficient per se to drive tissue folding. To tackle this question, we use the Drosophila embryo model system that forms a furrow on the ventral side, initiating mesoderm internalization. Past computational models support the idea that cell apical contraction forces may not be sufficient and that active or passive cell apico-basal forces may be necessary to drive cell wedging and tissue furrowing. By using 3D computational modelling and in toto embryo image analysis and manipulation, we now challenge this idea and show that embryo-scale force balance of the tissue surface, rather than cell-autonomous shape changes, is necessary and sufficient to drive a buckling of the epithelial surface forming a furrow which propagates and initiates embryo gastrulation.

scholarly journals Integrative Modelling of Gene Expression and Digital Phenotypes to Describe Senescence in Wheat

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 909
Author(s):  
Anyela Valentina Camargo Rodriguez
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Computational Modelling ◽  
Plant Morphology ◽  
Reproductive Organs ◽  
Biological Trait ◽  
Cereal Grain ◽  
Plant Level

Senescence is the final stage of leaf development and is critical for plants’ fitness as nutrient relocation from leaves to reproductive organs takes place. Although senescence is key in nutrient relocation and yield determination in cereal grain production, there is limited understanding of the genetic and molecular mechanisms that control it in major staple crops such as wheat. Senescence is a highly orchestrated continuum of interacting pathways throughout the lifecycle of a plant. Levels of gene expression, morphogenesis, and phenotypic development all play key roles. Yet, most studies focus on a short window immediately after anthesis. This approach clearly leaves out key components controlling the activation, development, and modulation of the senescence pathway before anthesis, as well as during the later developmental stages, during which grain development continues. Here, a computational multiscale modelling approach integrates multi-omics developmental data to attempt to simulate senescence at the molecular and plant level. To recreate the senescence process in wheat, core principles were borrowed from Arabidopsis Thaliana, a more widely researched plant model. The resulted model describes temporal gene regulatory networks and their effect on plant morphology leading to senescence. Digital phenotypes generated from images using a phenomics platform were used to capture the dynamics of plant development. This work provides the basis for the application of computational modelling to advance understanding of the complex biological trait senescence. This supports the development of a predictive framework enabling its prediction in changing or extreme environmental conditions, with a view to targeted selection for optimal lifecycle duration for improving resilience to climate change.

scholarly journals The AF-6 Homolog Canoe Acts as a Rap1 Effector During Dorsal Closure of the Drosophila Embryo

Genetics ◽  
2003 ◽  
Vol 165 (1) ◽  
pp. 159-169
Author(s):  
Benjamin Boettner ◽  
Phoebe Harjes ◽  
Satoshi Ishimaru ◽  
Michael Heke ◽  
Hong Qing Fan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Genetic Interaction ◽  
Critical Role ◽  
Adherens Junction ◽  
Small Gtpases ◽  
Drosophila Embryo ◽  
Dorsal Closure ◽  
Cell Sheets ◽  
Jnk Pathway

Abstract Rap1 belongs to the highly conserved Ras subfamily of small GTPases. In Drosophila, Rap1 plays a critical role in many different morphogenetic processes, but the molecular mechanisms executing its function are unknown. Here, we demonstrate that Canoe (Cno), the Drosophila homolog of mammalian junctional protein AF-6, acts as an effector of Rap1 in vivo. Cno binds to the activated form of Rap1 in a yeast two-hybrid assay, the two molecules colocalize to the adherens junction, and they display very similar phenotypes in embryonic dorsal closure (DC), a process that relies on the elongation and migration of epithelial cell sheets. Genetic interaction experiments show that Rap1 and Cno act in the same molecular pathway during DC and that the function of both molecules in DC depends on their ability to interact. We further show that Rap1 acts upstream of Cno, but that Rap1, unlike Cno, is not involved in the stimulation of JNK pathway activity, indicating that Cno has both a Rap1-dependent and a Rap1-independent function in the DC process.

scholarly journals Error Propagation in the Simulation of Atherosclerotic Plaque Growth and the Prediction of Atherosclerotic Disease Progression

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2306
Author(s):  
Antonis I. Sakellarios ◽  
Panagiotis Siogkas ◽  
Vassiliki Kigka ◽  
Panagiota Tsompou ◽  
Dimitrios Pleouras ◽  
...  
Keyword(s):  
Error Propagation ◽  
Computational Models ◽  
Computational Modelling ◽  
Predictive Modelling ◽  
Prognostic Models ◽  
Current Analysis ◽  
Non Invasive ◽  
Plaque Growth ◽  
Artery Disease ◽  
Diagnostic Index

Assessments of coronary artery disease can be achieved using non-invasive computed tomography coronary angiography (CTCA). CTCA can be further used for the 3D reconstruction of the coronary arteries and the development of computational models. However, image acquisition and arterial reconstruction introduce an error which can be propagated, affecting the computational results and the accuracy of diagnostic and prognostic models. In this work, we investigate the effect of an imaging error, propagated to a diagnostic index calculated using computational modelling of blood flow and then to prognostic models based on plaque growth modelling or binary logistic predictive modelling. The analysis was performed utilizing data from 20 patients collected at two time points with interscan period of six years. The collected data includes clinical and risk factors, biological and biohumoral data, and CTCA imaging. The results demonstrated that the error propagated and may have significantly affected some of the final outcomes. The calculated propagated error seemed to be minor for shear stress, but was major for some variables of the plaque growth model. In parallel, in the current analysis SmartFFR was not considerably affected, with the limitation of only one case located into the gray zone.

scholarly journals Neuronal and Astrocytic Regulations in Schizophrenia: A Computational Modelling Study

2021 ◽  
Vol 15 ◽  
Author(s):  
Lea Fritschi ◽  
Johanna Hedlund Lindmar ◽  
Florian Scheidl ◽  
Kerstin Lenk
Keyword(s):  
Computational Models ◽  
Glutamate Release ◽  
Signal Transmission ◽  
Computational Modelling ◽  
Atp Release ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Neuronal Network Activity ◽  
Cell Densities ◽  
Synapse Model

According to the tripartite synapse model, astrocytes have a modulatory effect on neuronal signal transmission. More recently, astrocyte malfunction has been associated with psychiatric diseases such as schizophrenia. Several hypotheses have been proposed on the pathological mechanisms of astrocytes in schizophrenia. For example, post-mortem examinations have revealed a reduced astrocytic density in patients with schizophrenia. Another hypothesis suggests that disease symptoms are linked to an abnormality of glutamate transmission, which is also regulated by astrocytes (glutamate hypothesis of schizophrenia). Electrophysiological findings indicate a dispute over whether the disorder causes an increase or a decrease in neuronal and astrocytic activity. Moreover, there is no consensus as to which molecular pathways and network mechanisms are altered in schizophrenia. Computational models can aid the process in finding the underlying pathological malfunctions. The effect of astrocytes on the activity of neuron-astrocyte networks has been analysed with computational models. These can reproduce experimentally observed phenomena, such as astrocytic modulation of spike and burst signalling in neuron-astrocyte networks. Using an established computational neuron-astrocyte network model, we simulate experimental data of healthy and pathological networks by using different neuronal and astrocytic parameter configurations. In our simulations, the reduction of neuronal or astrocytic cell densities yields decreased glutamate levels and a statistically significant reduction in the network activity. Amplifications of the astrocytic ATP release toward postsynaptic terminals also reduced the network activity and resulted in temporarily increased glutamate levels. In contrast, reducing either the glutamate release or re-uptake in astrocytes resulted in higher network activities. Similarly, an increase in synaptic weights of excitatory or inhibitory neurons raises the excitability of individual cells and elevates the activation level of the network. To conclude, our simulations suggest that the impairment of both neurons and astrocytes disturbs the neuronal network activity in schizophrenia.

scholarly journals What is the role of computational models in Cognitive Science? A quantitative and qualitative analysis of the history of the TRACE model of speech segmentation

2019 ◽  
Author(s):  
Manisha Chawla ◽  
Richard Shillcock
Keyword(s):  
Qualitative Analysis ◽  
Cognitive Science ◽  
Computational Models ◽  
Computational Modelling ◽  
Speech Segmentation ◽  
Cognitive Modelling ◽  
Trace Model ◽  
History Of ◽  
Central Paradigm

Implemented computational models are a central paradigm of Cognitive Science. How do cognitive scientists really use such models? We take the example of one of the most successful and influential cognitive models, TRACE (McClelland & Elman, 1986), and we map its impact on the field in terms of published, electronically available documents that cite the original TRACE paper over a period of 25 years since its publication. We draw conclusions about the general status of computational cognitive modelling and make critical suggestions regarding the nature of abstraction in computational modelling.

Posterior stripe expression of hunchback is driven from two promoters by a common enhancer element

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 3067-3077 ◽  
Author(s):  
J.S. Margolis ◽  
M.L. Borowsky ◽  
E. Steingrimsson ◽  
C.W. Shim ◽  
J.A. Lengyel ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Initiation Site ◽  
Drosophila Embryo ◽  
Upstream Region ◽  
Enhancer Element ◽  
Gap Gene ◽  
Gap Genes ◽  
Two Phases ◽  
Necessary And Sufficient

The gap gene hunchback (hb) is required for the formation and segmentation of two regions of the Drosophila embryo, a broad anterior domain and a narrow posterior domain. Accumulation of hb transcript in the posterior of the embryo occurs in two phases, an initial cap covering the terminal 15% of the embryo followed by a stripe at the anterior edge of this region. By in situ hybridization with transcript-specific probes, we show that the cap is composed only of mRNA from the distal transcription initiation site (P1), while the later posterior stripe is composed of mRNA from both the distal and proximal (P2) transcription initiation sites. Using a series of genomic rescue constructs and promoter-lacZ fusion genes, we define a 1.4 kb fragment of the hb upstream region that is both necessary and sufficient for posterior expression. Sequences within this fragment mediate regulation by the terminal gap genes tailless (tll) and a huckebein, which direct the formation of the posterior hb stripe. We show that the tll protein binds in vitro to specific sites within the 1.4 kb posterior enhancer region, providing the first direct evidence for activation of gene expression by tll. We propose a model in which the anterior border of the posterior hb stripe is determined by tll concentration in a manner analogous to the activation of anterior hb expression by bicoid.

A processed form of the Spatzle protein defines dorsal-ventral polarity in the Drosophila embryo

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1243-1250 ◽  
Author(s):  
D.S. Schneider ◽  
Y. Jin ◽  
D. Morisato ◽  
K.V. Anderson
Keyword(s):  
Extracellular Space ◽  
Active Form ◽  
Ventral Side ◽  
Proteolytic Processing ◽  
Drosophila Embryo ◽  
Translation Product ◽  
Primary Translation Product ◽  
Early Drosophila Embryo ◽  
Extracellular Factor ◽  
Processed Form

Stein et al. (1991) identified a soluble, extracellular factor that induces ventral structures at the site where it is injected in the extracellular space of the early Drosophila embryo. This factor, called polarizing activity, has the properties predicted for a ligand for the transmembrane receptor encoded by the Toll gene. Using a bioassay to follow activity, we purified a 24 × 10(3) M(r) protein that has polarizing activity. The purified protein is recognized by antibodies to the C-terminal half of the Spatzle protein, indicating that this polarizing activity is a product of the spatzle gene. The purified protein is smaller than the primary translation product of spatzle, suggesting that proteolytic processing of Spatzle on the ventral side of the embryo is required to generate the localized, active form of the protein.

The use of ‘normal’ and ‘transformed’ gynandromorphs in mapping the primordial germ cells and the gonadal mesoderm in Drosophila

Development ◽  
1976 ◽  
Vol 35 (3) ◽  
pp. 607-616
Author(s):  
W. J. Gehring ◽  
E. Wieschaus ◽  
M. Holliger
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells ◽  
Cell Lineage ◽  
Ventral Side ◽  
Drosophila Embryo ◽  
The Real ◽  
Genital Disc ◽  
Stage Of Development ◽  
Data Support ◽  
Blastoderm Stage

The primordial germ cells and the gonadal mesoderm were mapped in the Drosophila embryo by analyzing the patterns of mosaicism in ‘normal’ and ‘transformed’ gynandromorphs. Relative to the adult cuticular markers the germ cells map as the posterior moststructure, which coincides with their known location in the blastoderm embryo. These data support the hypothesis that the gynandromorph map reflects the real position of the pri-mordia in the embryo. Since after the blastoderm stage the primordial germ cells migrateanteriorly these data also indicate that the map in fact corresponds to the blastoderm stageand not to a later stage of development. The genital disc maps as a single median primordium anterior and ventral to the germ cells, the gonadal mesoderm is located anterior to the genital disc and also forms a single median primordium on the ventral side of the embryo. The primordia for the genital disc and the gonadal mesoderm are unusually large in size, which presumably reflects some indeterminacy of the cell lineage leading to an ‘expansion’ of the map.

scholarly journals Shadow enhancers enable Hunchback bifunctionality in the Drosophila embryo

2015 ◽  
Vol 112 (3) ◽  
pp. 785-790 ◽  
Author(s):  
Max V. Staller ◽  
Ben J. Vincent ◽  
Meghan D. J. Bragdon ◽  
Tara Lydiard-Martin ◽  
Zeba Wunderlich ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Computational Models ◽  
Drosophila Embryo ◽  
Cellular Resolution ◽  
Genetic Perturbations ◽  
Regulatory Dna

Hunchback (Hb) is a bifunctional transcription factor that activates and represses distinct enhancers. Here, we investigate the hypothesis that Hb can activate and repress the same enhancer. Computational models predicted that Hb bifunctionally regulates the even-skipped (eve) stripe 3+7 enhancer (eve3+7) in Drosophila blastoderm embryos. We measured and modeled eve expression at cellular resolution under multiple genetic perturbations and found that the eve3+7 enhancer could not explain endogenous eve stripe 7 behavior. Instead, we found that eve stripe 7 is controlled by two enhancers: the canonical eve3+7 and a sequence encompassing the minimal eve stripe 2 enhancer (eve2+7). Hb bifunctionally regulates eve stripe 7, but it executes these two activities on different pieces of regulatory DNA—it activates the eve2+7 enhancer and represses the eve3+7 enhancer. These two “shadow enhancers” use different regulatory logic to create the same pattern.

High-performance computing for computational modelling in built environment-related studies – a scientometric review

2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Emmanuel Imuetinyan Aghimien ◽  
Lerato Millicent Aghimien ◽  
Olutomilayo Olayemi Petinrin ◽  
Douglas Omoregie Aghimien
Keyword(s):  
High Performance Computing ◽  
Graphics Processing Units ◽  
High Performance ◽  
Large Scale ◽  
Computational Models ◽  
Computational Modelling ◽  
Scientometric Analysis ◽  
Content Type ◽  
Performance Computing ◽  
Aec Industry

Purpose This paper aims to present the result of a scientometric analysis conducted using studies on high-performance computing in computational modelling. This was done with a view to showcasing the need for high-performance computers (HPC) within the architecture, engineering and construction (AEC) industry in developing countries, particularly in Africa, where the use of HPC in developing computational models (CMs) for effective problem solving is still low. Design/methodology/approach An interpretivism philosophical stance was adopted for the study which informed a scientometric review of existing studies gathered from the Scopus database. Keywords such as high-performance computing, and computational modelling were used to extract papers from the database. Visualisation of Similarities viewer (VOSviewer) was used to prepare co-occurrence maps based on the bibliographic data gathered. Findings Findings revealed the scarcity of research emanating from Africa in this area of study. Furthermore, past studies had placed focus on high-performance computing in the development of computational modelling and theory, parallel computing and improved visualisation, large-scale application software, computer simulations and computational mathematical modelling. Future studies can also explore areas such as cloud computing, optimisation, high-level programming language, natural science computing, computer graphics equipment and Graphics Processing Units as they relate to the AEC industry. Research limitations/implications The study assessed a single database for the search of related studies. Originality/value The findings of this study serve as an excellent theoretical background for AEC researchers seeking to explore the use of HPC for CMs development in the quest for solving complex problems in the industry.

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