Modular Organization of Dynamic Camouflage Body Patterning in Cuttlefish

DTIC Science & Technology

2014-11-28

Final 3. DATES COVERED (From - To) 28 Feb 13 – 19 Sept 14 4. TITLE AND SUBTITLE Modular organization of dynamic camouflage body...responsive areas are positively correlated with increasing voltages and depths of the electrode in the medulla of the optic lobe, and (2) the island- like...aim of using the dynamically changing visual background to study the spatiotemporal expression of body patterns was not successful, we discovered

Modeling the Underlying Dynamics of the Spread of Crime

PubMed Central

McMillon, David; Simon, Carl P.; Morenoff, Jeffrey

2014-01-01

The spread of crime is a complex, dynamic process that calls for a systems level approach. Here, we build and analyze a series of dynamical systems models of the spread of crime, imprisonment and recidivism, using only abstract transition parameters. To find the general patterns among these parameters—patterns that are independent of the underlying particulars—we compute analytic expressions for the equilibria and for the tipping points between high-crime and low-crime equilibria in these models. We use these expressions to examine, in particular, the effects of longer prison terms and of increased incarceration rates on the prevalence of crime, with a follow-up analysis on the effects of a Three-Strike Policy. PMID:24694545

Regulatory analysis of the mouse Hoxb3 gene: multiple elements work in concert to direct temporal and spatial patterns of expression.

PubMed

Kwan, C T; Tsang, S L; Krumlauf, R; Sham, M H

2001-04-01

The expression pattern of the mouse Hoxb3 gene is exceptionally complex and dynamic compared with that of other members of the Hoxb cluster. There are multiple types of transcripts for Hoxb3 gene, and the anterior boundaries of its expression vary at different stages of development. Two enhancers flanking Hoxb3 on the 3' and 5' sides regulate Hoxb2 and Hoxb4, respectively, and these control regions define the two ends of a 28-kb interval in and around the Hoxb3 locus. To assay the regulatory potential of DNA fragments in this interval we have used transgenic analysis with a lacZ reporter gene to locate cis-elements for directing the dynamic patterns of Hoxb3 expression. Our detailed analysis has identified four new and widely spaced cis-acting regulatory regions that can together account for major aspects of the Hoxb3 expression pattern. Elements Ib, IIIa, and IVb control gene expression in neural and mesodermal tissues; element Va controls mesoderm-specific gene expression. The most anterior neural expression domain of Hoxb3 is controlled by an r5 enhancer (element IVa); element IIIa directs reporter expression in the anterior spinal cord and hindbrain up to r6, and the region A enhancer (in element I) mediates posterior neural expression. Hence, the regulation of segmental expression of Hoxb3 in the hindbrain is different from that of Hoxa3, as two separate enhancer elements contribute to expression in r5 and r6. The mesoderm-specific element (Va) directs reporter expression to prevertebra C1 at 12.5 dpc, which is the anterior limit of paraxial mesoderm expression for Hoxb3. When tested in combinations, these cis-elements appear to work as modules in an additive manner to recapitulate the major endogenous expression patterns of Hoxb3 during embryogenesis. Together our study shows that multiple control elements direct reporter gene expression in diverse tissue-, temporal-, and spatially restricted subset of the endogenous Hoxb3 expression domains and work in concert to control the neural and mesodermal patterns of expression. Copyright 2001 Academic Press.

Unique patterns of organization and migration of FGF-expressing cells during Drosophila morphogenesis.

PubMed

Du, Lijuan; Zhou, Amy; Patel, Akshay; Rao, Mishal; Anderson, Kelsey; Roy, Sougata

2017-07-01

Fibroblast growth factors (FGF) are essential signaling proteins that regulate diverse cellular functions in developmental and metabolic processes. In Drosophila, the FGF homolog, branchless (bnl) is expressed in a dynamic and spatiotemporally restricted pattern to induce branching morphogenesis of the trachea, which expresses the Bnl-receptor, breathless (btl). Here we have developed a new strategy to determine bnl- expressing cells and study their interactions with the btl-expressing cells in the range of tissue patterning during Drosophila development. To enable targeted gene expression specifically in the bnl expressing cells, a new LexA based bnl enhancer trap line was generated using CRISPR/Cas9 based genome editing. Analyses of the spatiotemporal expression of the reporter in various embryonic stages, larval or adult tissues and in metabolic hypoxia, confirmed its target specificity and versatility. With this tool, new bnl expressing cells, their unique organization and functional interactions with the btl-expressing cells were uncovered in a larval tracheoblast niche in the leg imaginal discs, in larval photoreceptors of the developing retina, and in the embryonic central nervous system. The targeted expression system also facilitated live imaging of simultaneously labeled Bnl sources and tracheal cells, which revealed a unique morphogenetic movement of the embryonic bnl- source. Migration of bnl- expressing cells may create a dynamic spatiotemporal pattern of the signal source necessary for the directional growth of the tracheal branch. The genetic tool and the comprehensive profile of expression, organization, and activity of various types of bnl-expressing cells described in this study provided us with an important foundation for future research investigating the mechanisms underlying Bnl signaling in tissue morphogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamic expression patterns of ECM molecules in the developing mouse olfactory pathway

PubMed Central

Shay, Elaine L.; Greer, Charles A.; Treloar, Helen B.

2009-01-01

Olfactory sensory neuron (OSN) axons follow stereotypic spatio-temporal paths in the establishment of the olfactory pathway. Extracellular matrix (ECM) molecules are expressed early in the developing pathway and are proposed to have a role in its initial establishment. During later embryonic development, OSNs sort out and target specific glomeruli to form precise, complex topographic projections. We hypothesized that ECM cues may help to establish this complex topography. The aim of this study was to characterize expression of ECM molecules during the period of glomerulogenesis, when synaptic contacts are forming. We examined expression of laminin-1, perlecan, tenascin-C and CSPGs and found a coordinated pattern of expression of these cues in the pathway. These appear to restrict axons to the pathway while promoting axon outgrowth within. Thus, ECM molecules are present in dynamic spatio-temporal positions to affect OSN axons as they navigate to the olfactory bulb and establish synapses. PMID:18570250

Dynamic expression of a Hydra FGF at boundaries and termini.

PubMed

Lange, Ellen; Bertrand, Stephanie; Holz, Oliver; Rebscher, Nicole; Hassel, Monika

2014-12-01

Guidance of cells and tissue sheets is an essential function in developing and differentiating animal tissues. In Hydra, where cells and tissue move dynamically due to constant cell proliferation towards the termini or into lateral, vegetative buds, factors essential for guidance are still unknown. Good candidates to take over this function are fibroblast growth factors (FGFs). We present the phylogeny of several Hydra FGFs and analysis of their expression patterns. One of the FGFs is expressed in all terminal regions targeted by tissue movement and at boundaries crossed by moving tissue and cells with an expression pattern slightly differing in two Hydra strains. A model addressing an involvement of this FGF in cell movement and morphogenesis is proposed: Hydra FGFf-expressing cells might serve as sources to attract tissue and cells towards the termini of the body column and across morphological boundaries. Moreover, a function in morphogenesis and/or differentiation of cells and tissue is suggested.

Medium-throughput processing of whole mount in situ hybridisation experiments into gene expression domains.

PubMed

Crombach, Anton; Cicin-Sain, Damjan; Wotton, Karl R; Jaeger, Johannes

2012-01-01

Understanding the function and evolution of developmental regulatory networks requires the characterisation and quantification of spatio-temporal gene expression patterns across a range of systems and species. However, most high-throughput methods to measure the dynamics of gene expression do not preserve the detailed spatial information needed in this context. For this reason, quantification methods based on image bioinformatics have become increasingly important over the past few years. Most available approaches in this field either focus on the detailed and accurate quantification of a small set of gene expression patterns, or attempt high-throughput analysis of spatial expression through binary pattern extraction and large-scale analysis of the resulting datasets. Here we present a robust, "medium-throughput" pipeline to process in situ hybridisation patterns from embryos of different species of flies. It bridges the gap between high-resolution, and high-throughput image processing methods, enabling us to quantify graded expression patterns along the antero-posterior axis of the embryo in an efficient and straightforward manner. Our method is based on a robust enzymatic (colorimetric) in situ hybridisation protocol and rapid data acquisition through wide-field microscopy. Data processing consists of image segmentation, profile extraction, and determination of expression domain boundary positions using a spline approximation. It results in sets of measured boundaries sorted by gene and developmental time point, which are analysed in terms of expression variability or spatio-temporal dynamics. Our method yields integrated time series of spatial gene expression, which can be used to reverse-engineer developmental gene regulatory networks across species. It is easily adaptable to other processes and species, enabling the in silico reconstitution of gene regulatory networks in a wide range of developmental contexts.

Protein-DNA binding dynamics predict transcriptional response to nutrients in archaea.

PubMed

Todor, Horia; Sharma, Kriti; Pittman, Adrianne M C; Schmid, Amy K

2013-10-01

Organisms across all three domains of life use gene regulatory networks (GRNs) to integrate varied stimuli into coherent transcriptional responses to environmental pressures. However, inferring GRN topology and regulatory causality remains a central challenge in systems biology. Previous work characterized TrmB as a global metabolic transcription factor in archaeal extremophiles. However, it remains unclear how TrmB dynamically regulates its ∼100 metabolic enzyme-coding gene targets. Using a dynamic perturbation approach, we elucidate the topology of the TrmB metabolic GRN in the model archaeon Halobacterium salinarum. Clustering of dynamic gene expression patterns reveals that TrmB functions alone to regulate central metabolic enzyme-coding genes but cooperates with various regulators to control peripheral metabolic pathways. Using a dynamical model, we predict gene expression patterns for some TrmB-dependent promoters and infer secondary regulators for others. Our data suggest feed-forward gene regulatory topology for cobalamin biosynthesis. In contrast, purine biosynthesis appears to require TrmB-independent regulators. We conclude that TrmB is an important component for mediating metabolic modularity, integrating nutrient status and regulating gene expression dynamics alone and in concert with secondary regulators.

Investigating pianists' individuality in the performance of five timbral nuances through patterns of articulation, touch, dynamics, and pedaling

PubMed Central

Bernays, Michel; Traube, Caroline

2014-01-01

Timbre is an essential expressive feature in piano performance. Concert pianists use a vast palette of timbral nuances to color their performances at the microstructural level. Although timbre is generally envisioned in the pianistic community as an abstract concept carried through an imaged vocabulary, performers may share some common strategies of timbral expression in piano performance. Yet there may remain further leeway for idiosyncratic processes in the production of piano timbre nuances. In this study, we examined the patterns of timbral expression in performances by four expert pianists. Each pianist performed four short pieces, each with five different timbral intentions (bright, dark, dry, round, and velvety). The performances were recorded with the high-accuracy Bösendorfer CEUS system. Fine-grained performance features of dynamics, touch, articulation and pedaling were extracted. Reduced PCA performance spaces and descriptive performance portraits confirmed that pianists exhibited unique, specific profiles for different timbral intentions, derived from underlying traits of general individuality, while sharing some broad commonalities of dynamics and articulation for each timbral intention. These results confirm that pianists' abstract notions of timbre correspond to reliable patterns of performance technique. Furthermore, these effects suggest that pianists can express individual styles while complying with specific timbral intentions. PMID:24624099

Unstable genomes elevate transcriptome dynamics

PubMed Central

Stevens, Joshua B.; Liu, Guo; Abdallah, Batoul Y.; Horne, Steven D.; Ye, Karen J.; Bremer, Steven W.; Ye, Christine J.; Krawetz, Stephen A.; Heng, Henry H.

2015-01-01

The challenge of identifying common expression signatures in cancer is well known, however the reason behind this is largely unclear. Traditionally variation in expression signatures has been attributed to technological problems, however recent evidence suggests that chromosome instability (CIN) and resultant karyotypic heterogeneity may be a large contributing factor. Using a well-defined model of immortalization, we systematically compared the pattern of genome alteration and expression dynamics during somatic evolution. Co-measurement of global gene expression and karyotypic alteration throughout the immortalization process reveals that karyotype changes influence gene expression as major structural and numerical karyotypic alterations result in large gene expression deviation. Replicate samples from stages with stable genomes are more similar to each other than are replicate samples with karyotypic heterogeneity. Karyotypic and gene expression change during immortalization is dynamic as each stage of progression has a unique expression pattern. This was further verified by comparing global expression in two replicates grown in one flask with known karyotypes. Replicates with higher karyotypic instability were found to be less similar than replicates with stable karyotypes. This data illustrates the karyotype, transcriptome, and transcriptome determined pathways are in constant flux during somatic cellular evolution (particularly during the macroevolutionary phase) and this flux is an inextricable feature of CIN and essential for cancer formation. The findings presented here underscore the importance of understanding the evolutionary process of cancer in order to design improved treatment modalities. PMID:24122714

Detection of changes in gene regulatory patterns, elicited by perturbations of the Hsp90 molecular chaperone complex, by visualizing multiple experiments with an animation

PubMed Central

2011-01-01

Background To make sense out of gene expression profiles, such analyses must be pushed beyond the mere listing of affected genes. For example, if a group of genes persistently display similar changes in expression levels under particular experimental conditions, and the proteins encoded by these genes interact and function in the same cellular compartments, this could be taken as very strong indicators for co-regulated protein complexes. One of the key requirements is having appropriate tools to detect such regulatory patterns. Results We have analyzed the global adaptations in gene expression patterns in the budding yeast when the Hsp90 molecular chaperone complex is perturbed either pharmacologically or genetically. We integrated these results with publicly accessible expression, protein-protein interaction and intracellular localization data. But most importantly, all experimental conditions were simultaneously and dynamically visualized with an animation. This critically facilitated the detection of patterns of gene expression changes that suggested underlying regulatory networks that a standard analysis by pairwise comparison and clustering could not have revealed. Conclusions The results of the animation-assisted detection of changes in gene regulatory patterns make predictions about the potential roles of Hsp90 and its co-chaperone p23 in regulating whole sets of genes. The simultaneous dynamic visualization of microarray experiments, represented in networks built by integrating one's own experimental with publicly accessible data, represents a powerful discovery tool that allows the generation of new interpretations and hypotheses. PMID:21672238

Dynamic texture recognition using local binary patterns with an application to facial expressions.

PubMed

Zhao, Guoying; Pietikäinen, Matti

2007-06-01

Dynamic texture (DT) is an extension of texture to the temporal domain. Description and recognition of DTs have attracted growing attention. In this paper, a novel approach for recognizing DTs is proposed and its simplifications and extensions to facial image analysis are also considered. First, the textures are modeled with volume local binary patterns (VLBP), which are an extension of the LBP operator widely used in ordinary texture analysis, combining motion and appearance. To make the approach computationally simple and easy to extend, only the co-occurrences of the local binary patterns on three orthogonal planes (LBP-TOP) are then considered. A block-based method is also proposed to deal with specific dynamic events such as facial expressions in which local information and its spatial locations should also be taken into account. In experiments with two DT databases, DynTex and Massachusetts Institute of Technology (MIT), both the VLBP and LBP-TOP clearly outperformed the earlier approaches. The proposed block-based method was evaluated with the Cohn-Kanade facial expression database with excellent results. The advantages of our approach include local processing, robustness to monotonic gray-scale changes, and simple computation.

Geometric Morphometrics on Gene Expression Patterns Within Phenotypes: A Case Example on Limb Development

PubMed Central

Martínez-Abadías, Neus; Mateu, Roger; Niksic, Martina; Russo, Lucia; Sharpe, James

2016-01-01

How the genotype translates into the phenotype through development is critical to fully understand the evolution of phenotypes. We propose a novel approach to directly assess how changes in gene expression patterns are associated with changes in morphology using the limb as a case example. Our method combines molecular biology techniques, such as whole-mount in situ hybridization, with image and shape analysis, extending the use of Geometric Morphometrics to the analysis of nonanatomical shapes, such as gene expression domains. Elliptical Fourier and Procrustes-based semilandmark analyses were used to analyze the variation and covariation patterns of the limb bud shape with the expression patterns of two relevant genes for limb morphogenesis, Hoxa11 and Hoxa13. We devised a multiple thresholding method to semiautomatically segment gene domains at several expression levels in large samples of limb buds from C57Bl6 mouse embryos between 10 and 12 postfertilization days. Besides providing an accurate phenotyping tool to quantify the spatiotemporal dynamics of gene expression patterns within developing structures, our morphometric analyses revealed high, non-random, and gene-specific variation undergoing canalization during limb development. Our results demonstrate that Hoxa11 and Hoxa13, despite being paralogs with analogous functions in limb patterning, show clearly distinct dynamic patterns, both in shape and size, and are associated differently with the limb bud shape. The correspondence between our results and already well-established molecular processes underlying limb development confirms that this morphometric approach is a powerful tool to extract features of development regulating morphogenesis. Such multilevel analyses are promising in systems where not so much molecular information is available and will advance our understanding of the genotype–phenotype map. In systematics, this knowledge will increase our ability to infer how evolution modified a common developmental pattern to generate a wide diversity of morphologies, as in the vertebrate limb. PMID:26377442

Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression

PubMed Central

Verd, Berta; Crombach, Anton

2017-01-01

Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory processes in development. PMID:28158178

Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression.

PubMed

Verd, Berta; Crombach, Anton; Jaeger, Johannes

2017-02-01

Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory processes in development.

Dynamic patterns of expression for genes regulating cytokinin metabolism and signaling during rice inflorescence development.

PubMed

Yamburenko, Maria V; Kieber, Joseph J; Schaller, G Eric

2017-01-01

Inflorescence development in cereals, including such important crops as rice, maize, and wheat, directly affects grain number and size and is a key determinant of yield. Cytokinin regulates meristem size and activity and, as a result, has profound effects on inflorescence development and architecture. To clarify the role of cytokinin action in inflorescence development, we used the NanoString nCounter system to analyze gene expression in the early stages of rice panicle development, focusing on 67 genes involved in cytokinin biosynthesis, degradation, and signaling. Results point toward key members of these gene families involved in panicle development and indicate that the expression of many genes involved in cytokinin action differs between the panicle and vegetative tissues. Dynamic patterns of gene expression suggest that subnetworks mediate cytokinin action during different stages of panicle development. The variation of expression during panicle development is greater among genes encoding proteins involved in cytokinin metabolism and negative regulators of the pathway than for the genes in the primary response pathway. These results provide insight into the expression patterns of genes involved in cytokinin action during inflorescence development in a crop of agricultural importance, with relevance to similar processes in other monocots. The identification of subnetworks of genes expressed at different stages of early panicle development suggests that manipulation of their expression could have substantial effects on inflorescence architecture.

Intraindividual dynamics of transcriptome and genome-wide stability of DNA methylation

PubMed Central

Furukawa, Ryohei; Hachiya, Tsuyoshi; Ohmomo, Hideki; Shiwa, Yuh; Ono, Kanako; Suzuki, Sadafumi; Satoh, Mamoru; Hitomi, Jiro; Sobue, Kenji; Shimizu, Atsushi

2016-01-01

Cytosine methylation at CpG dinucleotides is an epigenetic mechanism that affects the gene expression profiles responsible for the functional differences in various cells and tissues. Although gene expression patterns are dynamically altered in response to various stimuli, the intraindividual dynamics of DNA methylation in human cells are yet to be fully understood. Here, we investigated the extent to which DNA methylation contributes to the dynamics of gene expression by collecting 24 blood samples from two individuals over a period of 3 months. Transcriptome and methylome association analyses revealed that only ~2% of dynamic changes in gene expression could be explained by the intraindividual variation of DNA methylation levels in peripheral blood mononuclear cells and purified monocytes. These results showed that DNA methylation levels remain stable for at least several months, suggesting that disease-associated DNA methylation markers are useful for estimating the risk of disease manifestation. PMID:27192970

Lateralization for dynamic facial expressions in human superior temporal sulcus.

PubMed

De Winter, François-Laurent; Zhu, Qi; Van den Stock, Jan; Nelissen, Koen; Peeters, Ronald; de Gelder, Beatrice; Vanduffel, Wim; Vandenbulcke, Mathieu

2015-02-01

Most face processing studies in humans show stronger activation in the right compared to the left hemisphere. Evidence is largely based on studies with static stimuli focusing on the fusiform face area (FFA). Hence, the pattern of lateralization for dynamic faces is less clear. Furthermore, it is unclear whether this property is common to human and non-human primates due to predisposing processing strategies in the right hemisphere or that alternatively left sided specialization for language in humans could be the driving force behind this phenomenon. We aimed to address both issues by studying lateralization for dynamic facial expressions in monkeys and humans. Therefore, we conducted an event-related fMRI experiment in three macaques and twenty right handed humans. We presented human and monkey dynamic facial expressions (chewing and fear) as well as scrambled versions to both species. We studied lateralization in independently defined face-responsive and face-selective regions by calculating a weighted lateralization index (LIwm) using a bootstrapping method. In order to examine if lateralization in humans is related to language, we performed a separate fMRI experiment in ten human volunteers including a 'speech' expression (one syllable non-word) and its scrambled version. Both within face-responsive and selective regions, we found consistent lateralization for dynamic faces (chewing and fear) versus scrambled versions in the right human posterior superior temporal sulcus (pSTS), but not in FFA nor in ventral temporal cortex. Conversely, in monkeys no consistent pattern of lateralization for dynamic facial expressions was observed. Finally, LIwms based on the contrast between different types of dynamic facial expressions (relative to scrambled versions) revealed left-sided lateralization in human pSTS for speech-related expressions compared to chewing and emotional expressions. To conclude, we found consistent laterality effects in human posterior STS but not in visual cortex of monkeys. Based on our results, it is tempting to speculate that lateralization for dynamic face processing in humans may be driven by left-hemispheric language specialization which may not have been present yet in the common ancestor of human and macaque monkeys. Copyright © 2014 Elsevier Inc. All rights reserved.

Combined lineage mapping and gene expression profiling of embryonic brain patterning using ultrashort pulse microscopy and image registration

NASA Astrophysics Data System (ADS)

Gibbs, Holly C.; Dodson, Colin R.; Bai, Yuqiang; Lekven, Arne C.; Yeh, Alvin T.

2014-12-01

During embryogenesis, presumptive brain compartments are patterned by dynamic networks of gene expression. The spatiotemporal dynamics of these networks, however, have not been characterized with sufficient resolution for us to understand the regulatory logic resulting in morphogenetic cellular behaviors that give the brain its shape. We have developed a new, integrated approach using ultrashort pulse microscopy [a high-resolution, two-photon fluorescence (2PF)-optical coherence microscopy (OCM) platform using 10-fs pulses] and image registration to study brain patterning and morphogenesis in zebrafish embryos. As a demonstration, we used time-lapse 2PF to capture midbrain-hindbrain boundary morphogenesis and a wnt1 lineage map from embryos during brain segmentation. We then performed in situ hybridization to deposit NBT/BCIP, where wnt1 remained actively expressed, and reimaged the embryos with combined 2PF-OCM. When we merged these datasets using morphological landmark registration, we found that the mechanism of boundary formation differs along the dorsoventral axis. Dorsally, boundary sharpening is dominated by changes in gene expression, while ventrally, sharpening may be accomplished by lineage sorting. We conclude that the integrated visualization of lineage reporter and gene expression domains simultaneously with brain morphology will be useful for understanding how changes in gene expression give rise to proper brain compartmentalization and structure.

Combined lineage mapping and gene expression profiling of embryonic brain patterning using ultrashort pulse microscopy and image registration.

PubMed

Gibbs, Holly C; Dodson, Colin R; Bai, Yuqiang; Lekven, Arne C; Yeh, Alvin T

2014-12-01

During embryogenesis, presumptive brain compartments are patterned by dynamic networks of gene expression. The spatiotemporal dynamics of these networks, however, have not been characterized with sufficient resolution for us to understand the regulatory logic resulting in morphogenetic cellular behaviors that give the brain its shape. We have developed a new, integrated approach using ultrashort pulse microscopy [a high-resolution, two-photon fluorescence (2PF)-optical coherence microscopy (OCM) platform using 10-fs pulses] and image registration to study brain patterning and morphogenesis in zebrafish embryos. As a demonstration, we used time-lapse 2PF to capture midbrain-hindbrain boundary morphogenesis and a wnt1 lineage map from embryos during brain segmentation. We then performed in situ hybridization to deposit NBT/BCIP, where wnt1 remained actively expressed, and reimaged the embryos with combined 2PF-OCM. When we merged these datasets using morphological landmark registration, we found that the mechanism of boundary formation differs along the dorsoventral axis. Dorsally, boundary sharpening is dominated by changes in gene expression, while ventrally, sharpening may be accomplished by lineage sorting. We conclude that the integrated visualization of lineage reporter and gene expression domains simultaneously with brain morphology will be useful for understanding how changes in gene expression give rise to proper brain compartmentalization and structure.

Gene Expression Dynamics Inspector (GEDI): for integrative analysis of expression profiles

NASA Technical Reports Server (NTRS)

Eichler, Gabriel S.; Huang, Sui; Ingber, Donald E.

2003-01-01

Genome-wide expression profiles contain global patterns that evade visual detection in current gene clustering analysis. Here, a Gene Expression Dynamics Inspector (GEDI) is described that uses self-organizing maps to translate high-dimensional expression profiles of time courses or sample classes into animated, coherent and robust mosaics images. GEDI facilitates identification of interesting patterns of molecular activity simultaneously across gene, time and sample space without prior assumption of any structure in the data, and then permits the user to retrieve genes of interest. Important changes in genome-wide activities may be quickly identified based on 'Gestalt' recognition and hence, GEDI may be especially useful for non-specialist end users, such as physicians. AVAILABILITY: GEDI v1.0 is written in Matlab, and binary Matlab.dll files which require Matlab to run can be downloaded for free by academic institutions at http://www.chip.org/ge/gedihome.html Supplementary information: http://www.chip.org/ge/gedihome.html.

Four not six: Revealing culturally common facial expressions of emotion.

PubMed

Jack, Rachael E; Sun, Wei; Delis, Ioannis; Garrod, Oliver G B; Schyns, Philippe G

2016-06-01

As a highly social species, humans generate complex facial expressions to communicate a diverse range of emotions. Since Darwin's work, identifying among these complex patterns which are common across cultures and which are culture-specific has remained a central question in psychology, anthropology, philosophy, and more recently machine vision and social robotics. Classic approaches to addressing this question typically tested the cross-cultural recognition of theoretically motivated facial expressions representing 6 emotions, and reported universality. Yet, variable recognition accuracy across cultures suggests a narrower cross-cultural communication supported by sets of simpler expressive patterns embedded in more complex facial expressions. We explore this hypothesis by modeling the facial expressions of over 60 emotions across 2 cultures, and segregating out the latent expressive patterns. Using a multidisciplinary approach, we first map the conceptual organization of a broad spectrum of emotion words by building semantic networks in 2 cultures. For each emotion word in each culture, we then model and validate its corresponding dynamic facial expression, producing over 60 culturally valid facial expression models. We then apply to the pooled models a multivariate data reduction technique, revealing 4 latent and culturally common facial expression patterns that each communicates specific combinations of valence, arousal, and dominance. We then reveal the face movements that accentuate each latent expressive pattern to create complex facial expressions. Our data questions the widely held view that 6 facial expression patterns are universal, instead suggesting 4 latent expressive patterns with direct implications for emotion communication, social psychology, cognitive neuroscience, and social robotics. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Epigenetic regulation of serotype expression antagonizes transcriptome dynamics in Paramecium tetraurelia

PubMed Central

Cheaib, Miriam; Dehghani Amirabad, Azim; Nordström, Karl J. V.; Schulz, Marcel H.; Simon, Martin

2015-01-01

Phenotypic variation of a single genotype is achieved by alterations in gene expression patterns. Regulation of such alterations depends on their time scale, where short-time adaptations differ from permanently established gene expression patterns maintained by epigenetic mechanisms. In the ciliate Paramecium, serotypes were described for an epigenetically controlled gene expression pattern of an individual multigene family. Paradoxically, individual serotypes can be triggered in Paramecium by alternating environments but are then stabilized by epigenetic mechanisms, thus raising the question to which extend their expression follows environmental stimuli. To characterize environmental adaptation in the context of epigenetically controlled serotype expression, we used RNA-seq to characterize transcriptomes of serotype pure cultures. The resulting vegetative transcriptome resource is first analysed for genes involved in the adaptive response to the altered environment. Secondly, we identified groups of genes that do not follow the adaptive response but show co-regulation with the epigenetically controlled serotype system, suggesting that their gene expression pattern becomes manifested by similar mechanisms. In our experimental set-up, serotype expression and the entire group of co-regulated genes were stable among environmental changes and only heat-shock genes altered expression of these gene groups. The data suggest that the maintenance of these gene expression patterns in a lineage represents epigenetically controlled robustness counteracting short-time adaptation processes. PMID:26231545

Cortical responses to dynamic emotional facial expressions generalize across stimuli, and are sensitive to task-relevance, in adults with and without Autism.

PubMed

Kliemann, Dorit; Richardson, Hilary; Anzellotti, Stefano; Ayyash, Dima; Haskins, Amanda J; Gabrieli, John D E; Saxe, Rebecca R

2018-06-01

Individuals with Autism Spectrum Disorders (ASD) report difficulties extracting meaningful information from dynamic and complex social cues, like facial expressions. The nature and mechanisms of these difficulties remain unclear. Here we tested whether that difficulty can be traced to the pattern of activity in "social brain" regions, when viewing dynamic facial expressions. In two studies, adult participants (male and female) watched brief videos of a range of positive and negative facial expressions, while undergoing functional magnetic resonance imaging (Study 1: ASD n = 16, control n = 21; Study 2: ASD n = 22, control n = 30). Patterns of hemodynamic activity differentiated among facial emotional expressions in left and right superior temporal sulcus, fusiform gyrus, and parts of medial prefrontal cortex. In both control participants and high-functioning individuals with ASD, we observed (i) similar responses to emotional valence that generalized across facial expressions and animated social events; (ii) similar flexibility of responses to emotional valence, when manipulating the task-relevance of perceived emotions; and (iii) similar responses to a range of emotions within valence. Altogether, the data indicate that there was little or no group difference in cortical responses to isolated dynamic emotional facial expressions, as measured with fMRI. Difficulties with real-world social communication and social interaction in ASD may instead reflect differences in initiating and maintaining contingent interactions, or in integrating social information over time or context. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Java tool for dynamic web-based 3D visualization of anatomy and overlapping gene or protein expression patterns.

PubMed

Gerth, Victor E; Vize, Peter D

2005-04-01

The Gene Expression Viewer is a web-launched three-dimensional visualization tool, tailored to compare surface reconstructions of multi-channel image volumes generated by confocal microscopy or micro-CT.

Impaired Overt Facial Mimicry in Response to Dynamic Facial Expressions in High-Functioning Autism Spectrum Disorders

ERIC Educational Resources Information Center

Yoshimura, Sayaka; Sato, Wataru; Uono, Shota; Toichi, Motomi

2015-01-01

Previous electromyographic studies have reported that individuals with autism spectrum disorders (ASD) exhibited atypical patterns of facial muscle activity in response to facial expression stimuli. However, whether such activity is expressed in visible facial mimicry remains unknown. To investigate this issue, we videotaped facial responses in…

Gap Gene Regulatory Dynamics Evolve along a Genotype Network

PubMed Central

Crombach, Anton; Wotton, Karl R.; Jiménez-Guri, Eva; Jaeger, Johannes

2016-01-01

Developmental gene networks implement the dynamic regulatory mechanisms that pattern and shape the organism. Over evolutionary time, the wiring of these networks changes, yet the patterning outcome is often preserved, a phenomenon known as “system drift.” System drift is illustrated by the gap gene network—involved in segmental patterning—in dipteran insects. In the classic model organism Drosophila melanogaster and the nonmodel scuttle fly Megaselia abdita, early activation and placement of gap gene expression domains show significant quantitative differences, yet the final patterning output of the system is essentially identical in both species. In this detailed modeling analysis of system drift, we use gene circuits which are fit to quantitative gap gene expression data in M. abdita and compare them with an equivalent set of models from D. melanogaster. The results of this comparative analysis show precisely how compensatory regulatory mechanisms achieve equivalent final patterns in both species. We discuss the larger implications of the work in terms of “genotype networks” and the ways in which the structure of regulatory networks can influence patterns of evolutionary change (evolvability). PMID:26796549

Epigenetic regulation of serotype expression antagonizes transcriptome dynamics in Paramecium tetraurelia.

PubMed

Cheaib, Miriam; Dehghani Amirabad, Azim; Nordström, Karl J V; Schulz, Marcel H; Simon, Martin

2015-08-01

Phenotypic variation of a single genotype is achieved by alterations in gene expression patterns. Regulation of such alterations depends on their time scale, where short-time adaptations differ from permanently established gene expression patterns maintained by epigenetic mechanisms. In the ciliate Paramecium, serotypes were described for an epigenetically controlled gene expression pattern of an individual multigene family. Paradoxically, individual serotypes can be triggered in Paramecium by alternating environments but are then stabilized by epigenetic mechanisms, thus raising the question to which extend their expression follows environmental stimuli. To characterize environmental adaptation in the context of epigenetically controlled serotype expression, we used RNA-seq to characterize transcriptomes of serotype pure cultures. The resulting vegetative transcriptome resource is first analysed for genes involved in the adaptive response to the altered environment. Secondly, we identified groups of genes that do not follow the adaptive response but show co-regulation with the epigenetically controlled serotype system, suggesting that their gene expression pattern becomes manifested by similar mechanisms. In our experimental set-up, serotype expression and the entire group of co-regulated genes were stable among environmental changes and only heat-shock genes altered expression of these gene groups. The data suggest that the maintenance of these gene expression patterns in a lineage represents epigenetically controlled robustness counteracting short-time adaptation processes. © The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Population-Level Transcriptomic Responses of the Southern Ocean Salp Salpa thompsoni to Environment Variability of the Western Antarctic Peninsula Region

NASA Astrophysics Data System (ADS)

Bucklin, A. C.; Batta Lona, P. G.; Maas, A. E.; O'Neill, R. J.; Wiebe, P. H.

2015-12-01

In response to the changing Antarctic climate, the Southern Ocean salp Salpa thompsoni has shown altered patterns of distribution and abundance that are anticipated to have profound impacts on pelagic food webs and ecosystem dynamics. The physiological and molecular processes that underlay ecological function and biogeographical distribution are key to understanding present-day dynamics and predicting future trajectories. This study examined transcriptome-wide patterns of gene expression in relation to biological and physical oceanographic conditions in coastal, shelf and offshore waters of the Western Antarctic Peninsula (WAP) region during austral spring and summer 2011. Based on field observations and collections, seasonal changes in the distribution and abundance of salps of different life stages were associated with differences in water mass structure of the WAP. Our observations are consistent with previous suggestions that bathymetry and currents in Bransfield Strait could generate a retentive cell for an overwintering population of S. thompsoni, which may generate the characteristic salp blooms found throughout the region later in summer. The statistical analysis of transcriptome-wide patterns of gene expression revealed differences among salps collected in different seasons and from different habitats (i.e., coastal versus offshore) in the WAP. Gene expression patterns also clustered by station in austral spring - but not summer - collections, suggesting stronger heterogeneity of environmental conditions. During the summer, differentially expressed genes covered a wider range of functions, including those associated with stress responses. Future research using novel molecular transcriptomic / genomic characterization of S. thompsoni will allow more complete understanding of individual-, population-, and species-level responses to environmental variability and prediction of future dynamics of Southern Ocean food webs and ecosystems.

Differential expression pattern of UBX family genes in Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamauchi, Seiji; Sasagawa, Yohei; Ogura, Teru

2007-06-29

UBX (ubiquitin regulatory X)-containing proteins belong to an evolutionary conserved protein family and determine the specificity of p97/VCP/Cdc48p function by binding as its adaptors. Caenorhabditis elegans was found to possess six UBX-containing proteins, named UBXN-1 to -6. However, no general or specific function of them has been revealed. During the course of understanding not only their function but also specified function of p97, we investigated spatial and temporal expression patterns of six ubxn genes in this study. Transcript analyses showed that the expression pattern of each ubxn gene was different throughout worm's development and may show potential developmental dynamics inmore » their function, especially ubxn-5 was expressed specifically in the spermatogenic germline, suggesting a crucial role in spermatogenesis. In addition, as ubxn-4 expression was induced by ER stress, it would function as an ERAD factor in C. elegans. In vivo expression analysis by using GFP translational fusion constructs revealed that six ubxn genes show distinct expression patterns. These results altogether demonstrate that the expression of all six ubxn genes of C. elegans is differently regulated.« less

Global transgenerational gene expression dynamics in two newly synthesized allohexaploid wheat (Triticum aestivum) lines

PubMed Central

2012-01-01

Background Alteration in gene expression resulting from allopolyploidization is a prominent feature in plants, but its spectrum and extent are not fully known. Common wheat (Triticum aestivum) was formed via allohexaploidization about 10,000 years ago, and became the most important crop plant. To gain further insights into the genome-wide transcriptional dynamics associated with the onset of common wheat formation, we conducted microarray-based genome-wide gene expression analysis on two newly synthesized allohexaploid wheat lines with chromosomal stability and a genome constitution analogous to that of the present-day common wheat. Results Multi-color GISH (genomic in situ hybridization) was used to identify individual plants from two nascent allohexaploid wheat lines between Triticum turgidum (2n = 4x = 28; genome BBAA) and Aegilops tauschii (2n = 2x = 14; genome DD), which had a stable chromosomal constitution analogous to that of common wheat (2n = 6x = 42; genome BBAADD). Genome-wide analysis of gene expression was performed for these allohexaploid lines along with their parental plants from T. turgidum and Ae. tauschii, using the Affymetrix Gene Chip Wheat Genome-Array. Comparison with the parental plants coupled with inclusion of empirical mid-parent values (MPVs) revealed that whereas the great majority of genes showed the expected parental additivity, two major patterns of alteration in gene expression in the allohexaploid lines were identified: parental dominance expression and non-additive expression. Genes involved in each of the two altered expression patterns could be classified into three distinct groups, stochastic, heritable and persistent, based on their transgenerational heritability and inter-line conservation. Strikingly, whereas both altered patterns of gene expression showed a propensity of inheritance, identity of the involved genes was highly stochastic, consistent with the involvement of diverse Gene Ontology (GO) terms. Nonetheless, those genes showing non-additive expression exhibited a significant enrichment for vesicle-function. Conclusions Our results show that two patterns of global alteration in gene expression are conditioned by allohexaploidization in wheat, that is, parental dominance expression and non-additive expression. Both altered patterns of gene expression but not the identity of the genes involved are likely to play functional roles in stabilization and establishment of the newly formed allohexaploid plants, and hence, relevant to speciation and evolution of T. aestivum. PMID:22277161

Principal network analysis: identification of subnetworks representing major dynamics using gene expression data

PubMed Central

Kim, Yongsoo; Kim, Taek-Kyun; Kim, Yungu; Yoo, Jiho; You, Sungyong; Lee, Inyoul; Carlson, George; Hood, Leroy; Choi, Seungjin; Hwang, Daehee

2011-01-01

Motivation: Systems biology attempts to describe complex systems behaviors in terms of dynamic operations of biological networks. However, there is lack of tools that can effectively decode complex network dynamics over multiple conditions. Results: We present principal network analysis (PNA) that can automatically capture major dynamic activation patterns over multiple conditions and then generate protein and metabolic subnetworks for the captured patterns. We first demonstrated the utility of this method by applying it to a synthetic dataset. The results showed that PNA correctly captured the subnetworks representing dynamics in the data. We further applied PNA to two time-course gene expression profiles collected from (i) MCF7 cells after treatments of HRG at multiple doses and (ii) brain samples of four strains of mice infected with two prion strains. The resulting subnetworks and their interactions revealed network dynamics associated with HRG dose-dependent regulation of cell proliferation and differentiation and early PrPSc accumulation during prion infection. Availability: The web-based software is available at: http://sbm.postech.ac.kr/pna. Contact: dhhwang@postech.ac.kr; seungjin@postech.ac.kr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21193522

Differential Gene Expression (DEX) and Alternative Splicing Events (ASE) for Temporal Dynamic Processes Using HMMs and Hierarchical Bayesian Modeling Approaches.

PubMed

Oh, Sunghee; Song, Seongho

2017-01-01

In gene expression profile, data analysis pipeline is categorized into four levels, major downstream tasks, i.e., (1) identification of differential expression; (2) clustering co-expression patterns; (3) classification of subtypes of samples; and (4) detection of genetic regulatory networks, are performed posterior to preprocessing procedure such as normalization techniques. To be more specific, temporal dynamic gene expression data has its inherent feature, namely, two neighboring time points (previous and current state) are highly correlated with each other, compared to static expression data which samples are assumed as independent individuals. In this chapter, we demonstrate how HMMs and hierarchical Bayesian modeling methods capture the horizontal time dependency structures in time series expression profiles by focusing on the identification of differential expression. In addition, those differential expression genes and transcript variant isoforms over time detected in core prerequisite steps can be generally further applied in detection of genetic regulatory networks to comprehensively uncover dynamic repertoires in the aspects of system biology as the coupled framework.

Developmental expression of Drosophila Wiskott-Aldrich Syndrome family proteins

PubMed Central

Rodriguez-Mesa, Evelyn; Abreu-Blanco, Maria Teresa; Rosales-Nieves, Alicia E.; Parkhurst, Susan M.

2012-01-01

Background Wiskott-Aldrich Syndrome (WASP) family proteins participate in many cellular processes involving rearrangements of the actin cytoskeleton. To the date, four WASP subfamily members have been described in Drosophila: Wash, WASp, SCAR, and Whamy. Wash, WASp, and SCAR are essential during early Drosophila development where they function in orchestrating cytoplasmic events including membrane-cytoskeleton interactions. A mutant for Whamy has not yet been reported. Results We generated monoclonal antibodies that are specific to Drosophila Wash, WASp, SCAR, and Whamy, and use these to describe their spatial and temporal localization patterns. Consistent with the importance of WASP family proteins in flies, we find that Wash, WASp, SCAR, and Whamy are dynamically expressed throughout oogenesis and embryogenesis. For example, we find that Wash accumulates at the oocyte cortex. WASp is highly expressed in the PNS, while SCAR is the most abundantly expressed in the CNS. Whamy exhibits an asymmetric subcellular localization that overlaps with mitochondria and is highly expressed in muscle. Conclusion All four WASP family members show specific expression patterns, some of which reflect their previously known roles and others revealing new potential functions. The monoclonal antibodies developed offer valuable new tools to investigate how WASP family proteins regulate actin cytoskeleton dynamics. PMID:22275148

Embryonic expression of the transforming growth factor beta ligand and receptor genes in chicken.

PubMed

Cooley, James R; Yatskievych, Tatiana A; Antin, Parker B

2014-03-01

Transforming growth factor-beta (TGFβ) signaling regulates a myriad of biological processes during embryogenesis, in the adult, and during the manifestation of disease. TGFβ signaling is propagated through one of three TGFβ ligands interacting with Type I and Type II receptors, and Type III co-receptors. Although TGFβ signaling is regulated partly by the combinatorial expression patterns of TGFβ receptors and ligands, a comprehensive gene expression analysis has not been published. Here we report the embryonic mRNA expression patterns in chicken embryos of the canonical TGFβ ligands (TGFB1, TGFB2, and TGFB3) and receptors (TGFBR1, TGFBR2, TGFBR3), plus the Activin A receptor, type 1 (ACVR1) and co receptor Endoglin (ENG) that also transduce TGFβ signaling. TGFB ligands and receptors show dynamic and frequently overlapping expression patterns in numerous embryonic cell layers and structures. Integrating expression information identifies combinations of ligands and receptors that are involved in specific developmental processes including somitogenesis, cardiogenesis and vasculogenesis. Copyright © 2013 Wiley Periodicals, Inc.

Predictive computation of genomic logic processing functions in embryonic development

PubMed Central

Peter, Isabelle S.; Faure, Emmanuel; Davidson, Eric H.

2012-01-01

Gene regulatory networks (GRNs) control the dynamic spatial patterns of regulatory gene expression in development. Thus, in principle, GRN models may provide system-level, causal explanations of developmental process. To test this assertion, we have transformed a relatively well-established GRN model into a predictive, dynamic Boolean computational model. This Boolean model computes spatial and temporal gene expression according to the regulatory logic and gene interactions specified in a GRN model for embryonic development in the sea urchin. Additional information input into the model included the progressive embryonic geometry and gene expression kinetics. The resulting model predicted gene expression patterns for a large number of individual regulatory genes each hour up to gastrulation (30 h) in four different spatial domains of the embryo. Direct comparison with experimental observations showed that the model predictively computed these patterns with remarkable spatial and temporal accuracy. In addition, we used this model to carry out in silico perturbations of regulatory functions and of embryonic spatial organization. The model computationally reproduced the altered developmental functions observed experimentally. Two major conclusions are that the starting GRN model contains sufficiently complete regulatory information to permit explanation of a complex developmental process of gene expression solely in terms of genomic regulatory code, and that the Boolean model provides a tool with which to test in silico regulatory circuitry and developmental perturbations. PMID:22927416

RNA-Seq reveals the dynamic and diverse features of digestive enzymes during early development of Pacific white shrimp Litopenaeus vannamei.

PubMed

Wei, Jiankai; Zhang, Xiaojun; Yu, Yang; Li, Fuhua; Xiang, Jianhai

2014-09-01

The Pacific white shrimp (Litopenaeus vannamei), with high commercial value, has a typical metamorphosis pattern by going through embryo, nauplius, zoea, mysis and postlarvae during early development. Its diets change continually in this period, and a high mortality of larvae also occurs in this period. Since there is a close relationship between diets and digestive enzymes, a comprehensive investigation about the types and expression patterns of all digestive enzyme genes during early development of L. vannamei is of considerable significance for shrimp diets and larvae culture. Using RNA-Seq data, the types and expression characteristics of the digestive enzyme genes were analyzed during five different development stages (embryo, nauplius, zoea, mysis and postlarvae) in L. vannamei. Among the obtained 66,815 unigenes, 296 were annotated as 16 different digestive enzymes including five types of carbohydrase, seven types of peptidase and four types of lipase. Such a diverse suite of enzymes illustrated the capacity of L. vannamei to exploit varied diets to fit their nutritional requirements. The analysis of their dynamic expression patterns during development also indicated the importance of transcriptional regulation to adapt to the diet transition. Our study revealed the diverse and dynamic features of digestive enzymes during early development of L. vannamei. These results would provide support to better understand the physiological changes during diet transition. Copyright © 2014 Elsevier Inc. All rights reserved.

Isolation of a transcription factor expressed in neural crest from the region of 22q11 deleted in DiGeorge syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wadey, R.; Roberts, C.; Daw, S.

1994-09-01

Deletions within chromosome 22q11 cause a wide variety of birth defects including DiGeorge syndrome and Shprintzen syndrome. We have defined a commonly deleted region of over 2 Mb, and a critical region of 300 kb. A gene, TUPLE1, has been isolated from this critical region encoding a transcriptional regulator similar to the yeast HIR1 histone regulator gene. Since it has been suggested that DGS results from a defective neural crest, the expression of Tuple1 was examined in whole mouse and chick embryos, tissue sections and neural tube explants: Tuple1 is expressed in a dynamic pattern with high levels in regionsmore » containing migrating crest. Prior to crest migration Tuple1 is expressed in a rhombomere-specific expression pattern. Later Tuple1 is expressed in discrete domains within the developing neural tube. A remarkable feature of the experiments was the detection of a similar dynamic pattern with sense probe; i.e., there is an antisense Tuple1 transcript. This was confirmed using RPA. Tuple1 is being screened for mutations in non-deletion patients and constructs assembled for homologous recombination in ES cells. Tuple1 maps to MMU16 extending the homology of linkage with human chromosome 22. From these data we predict that the human homologue of the murine scid mutation maps to 22q11.« less

Characterization of basal gene expression trends over a diurnal cycle in Xiphophorus maculatus skin, brain and liver.

PubMed

Lu, Yuan; Reyes, Jose; Walter, Sean; Gonzalez, Trevor; Medrano, Geraldo; Boswell, Mikki; Boswell, William; Savage, Markita; Walter, Ronald

2018-06-01

Evolutionarily conserved diurnal circadian mechanisms maintain oscillating patterns of gene expression based on the day-night cycle. Xiphophorus fish have been used to evaluate transcriptional responses after exposure to various light sources and it was determined that each source incites distinct genetic responses in skin tissue. However, basal expression levels of genes that show oscillating expression patterns in day-night cycle, may affect the outcomes of such experiments, since basal gene expression levels at each point in the circadian path may influence the profile of identified light responsive genes. Lack of knowledge regarding diurnal fluctuations in basal gene expression patterns may confound the understanding of genetic responses to external stimuli (e.g., light) since the dynamic nature of gene expression implies animals subjected to stimuli at different times may be at very different stages within the continuum of genetic homeostasis. We assessed basal gene expression changes over a 24-hour period in 200 select Xiphophorus gene targets known to transcriptionally respond to various types of light exposure. We identified 22 genes in skin, 36 genes in brain and 28 genes in liver that exhibit basal oscillation of expression patterns. These genes, including known circadian regulators, produced the expected expression patterns over a 24-hour cycle when compared to circadian regulatory genes identified in other species, especially human and other vertebrate animal models. Our results suggest the regulatory network governing diurnal oscillating gene expression is similar between Xiphophorus and other vertebrates for the three Xiphophorus organs tested. In addition, we were able to categorize light responsive gene sets in Xiphophorus that do, and do not, exhibit circadian based oscillating expression patterns. Copyright © 2017 Elsevier Inc. All rights reserved.

Gene expression patterns and dynamics of the colonization of common bean (Phaseolus vulgaris L.) by highly virulent and weakly virulent strains of Fusarium oxysporum

PubMed Central

Niño-Sánchez, Jonathan; Tello, Vega; Casado-del Castillo, Virginia; Thon, Michael R.; Benito, Ernesto P.; Díaz-Mínguez, José María

2015-01-01

The dynamics of root and hypocotyl colonization, and the gene expression patterns of several fungal virulence factors and plant defense factors have been analyzed and compared in the interaction of two Fusarium oxysporum f. sp. phaseoli strains displaying clear differences in virulence, with a susceptible common bean cultivar. The growth of the two strains on the root surface and the colonization of the root was quantitatively similar although the highly virulent (HV) strain was more efficient reaching the central root cylinder. The main differences between both strains were found in the temporal and spatial dynamics of crown root and hypocotyl colonization. The increase of fungal biomass in the crown root was considerably larger for the HV strain, which, after an initial stage of global colonization of both the vascular cylinder and the parenchymal cells, restricted its growth to the newly differentiated xylem vessels. The weakly virulent (WV) strain was a much slower and less efficient colonizer of the xylem vessels, showing also growth in the intercellular spaces of the parenchyma. Most of the virulence genes analyzed showed similar expression patterns in both strains, except SIX1, SIX6 and the gene encoding the transcription factor FTF1, which were highly upregulated in root crown and hypocotyl. The response induced in the infected plant showed interesting differences for both strains. The WV strain induced an early and strong transcription of the PR1 gene, involved in SAR response, while the HV strain preferentially induced the early expression of the ethylene responsive factor ERF2. PMID:25883592

Gene expression in spider appendages reveals reversal of exd/hth spatial specificity, altered leg gap gene dynamics, and suggests divergent distal morphogen signaling.

PubMed

Prpic, Nikola-Michael; Janssen, Ralf; Wigand, Barbara; Klingler, Martin; Damen, Wim G M

2003-12-01

Leg development in Drosophila has been studied in much detail. However, Drosophila limbs form in the larva as imaginal discs and not during embryogenesis as in most other arthropods. Here, we analyze appendage genes in the spider Cupiennius salei and the beetle Tribolium castaneum. Differences in decapentaplegic (dpp) expression suggest a different mode of distal morphogen signaling suitable for the specific geometry of growing limb buds. Also, expression of the proximal genes homothorax (hth) and extradenticle (exd) is significantly altered: in the spider, exd is restricted to the proximal leg and hth expression extends distally, while in insects, exd is expressed in the entire leg and hth is restricted to proximal parts. This reversal of spatial specificity demonstrates an evolutionary shift, which is nevertheless compatible with a conserved role of this gene pair as instructor of proximal fate. Different expression dynamics of dachshund and Distal-less point to modifications in the regulation of the leg gap gene system. We comment on the significance of this finding for attempts to homologize leg segments in different arthropod classes. Comparison of the expression profiles of H15 and optomotor-blind to the Drosophila patterns suggests modifications also in the dorsal-ventral patterning system of the legs. Together, our results suggest alterations in many components of the leg developmental system, namely proximal-distal and dorsal-ventral patterning, and leg segmentation. Thus, the leg developmental system exhibits a propensity to evolutionary change, which probably forms the basis for the impressive diversity of arthropod leg morphologies.

A Model-Based Analysis of Chemical and Temporal Patterns of Cuticular Hydrocarbons in Male Drosophila melanogaster

PubMed Central

Kent, Clement; Azanchi, Reza; Smith, Ben; Chu, Adrienne; Levine, Joel

2007-01-01

Drosophila Cuticular Hydrocarbons (CH) influence courtship behaviour, mating, aggregation, oviposition, and resistance to desiccation. We measured levels of 24 different CH compounds of individual male D. melanogaster hourly under a variety of environmental (LD/DD) conditions. Using a model-based analysis of CH variation, we developed an improved normalization method for CH data, and show that CH compounds have reproducible cyclic within-day temporal patterns of expression which differ between LD and DD conditions. Multivariate clustering of expression patterns identified 5 clusters of co-expressed compounds with common chemical characteristics. Turnover rate estimates suggest CH production may be a significant metabolic cost. Male cuticular hydrocarbon expression is a dynamic trait influenced by light and time of day; since abundant hydrocarbons affect male sexual behavior, males may present different pheromonal profiles at different times and under different conditions. PMID:17896002

Continuum theory of gene expression waves during vertebrate segmentation.

PubMed

Jörg, David J; Morelli, Luis G; Soroldoni, Daniele; Oates, Andrew C; Jülicher, Frank

2015-09-01

The segmentation of the vertebrate body plan during embryonic development is a rhythmic and sequential process governed by genetic oscillations. These genetic oscillations give rise to traveling waves of gene expression in the segmenting tissue. Here we present a minimal continuum theory of vertebrate segmentation that captures the key principles governing the dynamic patterns of gene expression including the effects of shortening of the oscillating tissue. We show that our theory can quantitatively account for the key features of segmentation observed in zebrafish, in particular the shape of the wave patterns, the period of segmentation and the segment length as a function of time.

Continuum theory of gene expression waves during vertebrate segmentation

PubMed Central

Jörg, David J; Morelli, Luis G; Soroldoni, Daniele; Oates, Andrew C; Jülicher, Frank

2015-01-01

Abstract The segmentation of the vertebrate body plan during embryonic development is a rhythmic and sequential process governed by genetic oscillations. These genetic oscillations give rise to traveling waves of gene expression in the segmenting tissue. Here we present a minimal continuum theory of vertebrate segmentation that captures the key principles governing the dynamic patterns of gene expression including the effects of shortening of the oscillating tissue. We show that our theory can quantitatively account for the key features of segmentation observed in zebrafish, in particular the shape of the wave patterns, the period of segmentation and the segment length as a function of time. PMID:28725158

Neuronal expression of fibroblast growth factor receptors in zebrafish.

PubMed

Rohs, Patricia; Ebert, Alicia M; Zuba, Ania; McFarlane, Sarah

2013-12-01

Fibroblast growth factor (FGF) signaling is important for a host of developmental processes such as proliferation, differentiation, tissue patterning, and morphogenesis. In vertebrates, FGFs signal through a family of four fibroblast growth factor receptors (FGFR 1-4), one of which is duplicated in zebrafish (FGFR1). Here we report the mRNA expression of the five known zebrafish fibroblast growth factor receptors at five developmental time points (24, 36, 48, 60, and 72h postfertilization), focusing on expression within the central nervous system. We show that the receptors have distinct and dynamic expression in the developing zebrafish brain, eye, inner ear, lateral line, and pharynx. In many cases, the expression patterns are similar to those of homologous FGFRs in mouse, chicken, amphibians, and other teleosts. Copyright © 2013 Elsevier B.V. All rights reserved.

Tissue specific characterisation of Lim-kinase 1 expression during mouse embryogenesis

PubMed Central

Lindström, Nils O.; Neves, Carlos; McIntosh, Rebecca; Miedzybrodzka, Zosia; Vargesson, Neil; Collinson, J. Martin

2012-01-01

The Lim-kinase (LIMK) proteins are important for the regulation of the actin cytoskeleton, in particular the control of actin nucleation and depolymerisation via regulation of cofilin, and hence may control a large number of processes during development, including cell tensegrity, migration, cell cycling, and axon guidance. LIMK1/LIMK2 knockouts disrupt spinal cord morphogenesis and synapse formation but other tissues and developmental processes that require LIMK are yet to be fully determined. To identify tissues and cell-types that may require LIMK, we characterised the pattern of LIMK1 protein during mouse embryogenesis. We showed that LIMK1 displays an expression pattern that is temporally dynamic and tissue-specific. In several tissues LIMK1 is detected in cell-types that also express Wilms’ tumour protein 1 and that undergo transitions between epithelial and mesenchymal states, including the pleura, epicardium, kidney nephrons, and gonads. LIMK1 was also found in a subset of cells in the dorsal retina, and in mesenchymal cells surrounding the peripheral nerves. This detailed study of the spatial and temporal expression of LIMK1 shows that LIMK1 expression is more dynamic than previously reported, in particular at sites of tissue–tissue interactions guiding multiple developmental processes. PMID:21167960

Dynamic Changes in Nucleosome Occupancy Are Not Predictive of Gene Expression Dynamics but Are Linked to Transcription and Chromatin Regulators

PubMed Central

Huebert, Dana J.; Kuan, Pei-Fen; Keleş, Sündüz

2012-01-01

The response to stressful stimuli requires rapid, precise, and dynamic gene expression changes that must be coordinated across the genome. To gain insight into the temporal ordering of genome reorganization, we investigated dynamic relationships between changing nucleosome occupancy, transcription factor binding, and gene expression in Saccharomyces cerevisiae yeast responding to oxidative stress. We applied deep sequencing to nucleosomal DNA at six time points before and after hydrogen peroxide treatment and revealed many distinct dynamic patterns of nucleosome gain and loss. The timing of nucleosome repositioning was not predictive of the dynamics of downstream gene expression change but instead was linked to nucleosome position relative to transcription start sites and specific cis-regulatory elements. We measured genome-wide binding of the stress-activated transcription factor Msn2p over time and found that Msn2p binds different loci with different dynamics. Nucleosome eviction from Msn2p binding sites was common across the genome; however, we show that, contrary to expectation, nucleosome loss occurred after Msn2p binding and in fact required Msn2p. This negates the prevailing model that nucleosomes obscuring Msn2p sites regulate DNA access and must be lost before Msn2p can bind DNA. Together, these results highlight the complexities of stress-dependent chromatin changes and their effects on gene expression. PMID:22354995

Proteomics analysis reveals a dynamic diurnal pattern of photosynthesis-related pathways in maize leaves.

PubMed

Feng, Dan; Wang, Yanwei; Lu, Tiegang; Zhang, Zhiguo; Han, Xiao

2017-01-01

Plant leaves exhibit differentiated patterns of photosynthesis rates under diurnal light regulation. Maize leaves show a single-peak pattern without photoinhibition at midday when the light intensity is maximized. This mechanism contributes to highly efficient photosynthesis in maize leaves. To understand the molecular basis of this process, an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics analysis was performed to reveal the dynamic pattern of proteins related to photosynthetic reactions. Steady, single-peak and double-peak protein expression patterns were discovered in maize leaves, and antenna proteins in these leaves displayed a steady pattern. In contrast, the photosystem, carbon fixation and citrate pathways were highly controlled by diurnal light intensity. Most enzymes in the limiting steps of these pathways were major sites of regulation. Thus, maize leaves optimize photosynthesis and carbon fixation outside of light harvesting to adapt to the changes in diurnal light intensity at the protein level.

Spatial and temporal expression patterns of auxin response transcription factors in the syncytium induced by the beet cyst nematode Heterodera schachtii in Arabidopsis.

PubMed

Hewezi, Tarek; Piya, Sarbottam; Richard, Geoffrey; Rice, J Hollis

2014-09-01

Plant-parasitic cyst nematodes induce the formation of a multinucleated feeding site in the infected root, termed the syncytium. Recent studies point to key roles of the phytohormone auxin in the regulation of gene expression and establishment of the syncytium. Nevertheless, information about the spatiotemporal expression patterns of the transcription factors that mediate auxin transcriptional responses during syncytium formation is limited. Here, we provide a gene expression map of 22 auxin response factors (ARFs) during the initiation, formation and maintenance stages of the syncytium induced by the cyst nematode Heterodera schachtii in Arabidopsis. We observed distinct and overlapping expression patterns of ARFs throughout syncytium development phases. We identified a set of ARFs whose expression is predominantly located inside the developing syncytium, whereas others are expressed in the neighbouring cells, presumably to initiate specific transcriptional programmes required for their incorporation within the developing syncytium. Our analyses also point to a role of certain ARFs in determining the maximum size of the syncytium. In addition, several ARFs were found to be highly expressed in fully developed syncytia, suggesting a role in maintaining the functional phenotype of mature syncytia. The dynamic distribution and overlapping expression patterns of various ARFs seem to be essential characteristics of ARF activity during syncytium development. © 2014 BSPP AND JOHN WILEY & SONS LTD.

Dynamic Organization of lncRNA and Circular RNA Regulators Collectively Controlled Cardiac Differentiation in Humans.

PubMed

Li, Yongsheng; Zhang, Jinwen; Huo, Caiqin; Ding, Na; Li, Junyi; Xiao, Jun; Lin, Xiaoyu; Cai, Benzhi; Zhang, Yunpeng; Xu, Juan

2017-10-01

Advances in developmental cardiology have increased our understanding of the early aspects of heart differentiation. However, understanding noncoding RNA (ncRNA) transcription and regulation during this process remains elusive. Here, we constructed transcriptomes for both long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in four important developmental stages ranging from early embryonic to cardiomyocyte based on high-throughput sequencing datasets, which indicate the high stage-specific expression patterns of two ncRNA types. Additionally, higher similarities of samples within each stage were found, highlighting the divergence of samples collected from distinct cardiac developmental stages. Next, we developed a method to identify numerous lncRNA and circRNA regulators whose expression was significantly stage-specific and shifted gradually and continuously during heart differentiation. We inferred that these ncRNAs are important for the stages of cardiac differentiation. Moreover, transcriptional regulation analysis revealed that the expression of stage-specific lncRNAs is controlled by known key stage-specific transcription factors (TFs). In addition, circRNAs exhibited dynamic expression patterns independent from their host genes. Functional enrichment analysis revealed that lncRNAs and circRNAs play critical roles in pathways that are activated specifically during heart differentiation. We further identified candidate TF-ncRNA-gene network modules for each differentiation stage, suggesting the dynamic organization of lncRNAs and circRNAs collectively controlled cardiac differentiation, which may cause heart-related diseases when defective. Our study provides a foundation for understanding the dynamic regulation of ncRNA transcriptomes during heart differentiation and identifies the dynamic organization of novel key lncRNAs and circRNAs to collectively control cardiac differentiation. Copyright © 2017. Published by Elsevier B.V.

Emergence of the self-similar property in gene expression dynamics

NASA Astrophysics Data System (ADS)

Ochiai, T.; Nacher, J. C.; Akutsu, T.

2007-08-01

Many theoretical models have recently been proposed to understand the structure of cellular systems composed of various types of elements (e.g., proteins, metabolites and genes) and their interactions. However, the cell is a highly dynamic system with thousands of functional elements fluctuating across temporal states. Therefore, structural analysis alone is not sufficient to reproduce the cell's observed behavior. In this article, we analyze the gene expression dynamics (i.e., how the amount of mRNA molecules in cell fluctuate in time) by using a new constructive approach, which reveals a symmetry embedded in gene expression fluctuations and characterizes the dynamical equation of gene expression (i.e., a specific stochastic differential equation). First, by using experimental data of human and yeast gene expression time series, we found a symmetry in short-time transition probability from time t to time t+1. We call it self-similarity symmetry (i.e., the gene expression short-time fluctuations contain a repeating pattern of smaller and smaller parts that are like the whole, but different in size). Secondly, we reconstruct the global behavior of the observed distribution of gene expression (i.e., scaling-law) and the local behavior of the power-law tail of this distribution. This approach may represent a step forward toward an integrated image of the basic elements of the whole cell.

Switch-like reprogramming of gene expression after fusion of multinucleate plasmodial cells of two Physarum polycephalum sporulation mutants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walter, Pauline; Hoffmann, Xenia-Katharina; Ebeling, Britta

2013-05-24

Highlights: •We investigate reprogramming of gene expression in multinucleate single cells. •Cells of two differentiation control mutants are fused. •Fused cells proceed to alternative gene expression patterns. •The population of nuclei damps stochastic fluctuations in gene expression. •Dynamic processes of cellular reprogramming can be observed by repeated sampling of a cell. -- Abstract: Nonlinear dynamic processes involving the differential regulation of transcription factors are considered to impact the reprogramming of stem cells, germ cells, and somatic cells. Here, we fused two multinucleate plasmodial cells of Physarum polycephalum mutants defective in different sporulation control genes while being in different physiological states.more » The resulting heterokaryons established one of two significantly different expression patterns of marker genes while the plasmodial halves that were fused to each other synchronized spontaneously. Spontaneous synchronization suggests that switch-like control mechanisms spread over and finally control the entire plasmodium as a result of cytoplasmic mixing. Regulatory molecules due to the large volume of the vigorously streaming cytoplasm will define concentrations in acting on the population of nuclei and in the global setting of switches. Mixing of a large cytoplasmic volume is expected to damp stochasticity when individual nuclei deliver certain RNAs at low copy number into the cytoplasm. We conclude that spontaneous synchronization, the damping of molecular noise in gene expression by the large cytoplasmic volume, and the option to take multiple macroscopic samples from the same plasmodium provide unique options for studying the dynamics of cellular reprogramming at the single cell level.« less

Drp1 levels constitutively regulate mitochondrial dynamics and cell survival in cortical neurons.

PubMed

Uo, Takuma; Dworzak, Jenny; Kinoshita, Chizuru; Inman, Denise M; Kinoshita, Yoshito; Horner, Philip J; Morrison, Richard S

2009-08-01

Mitochondria exist as dynamic networks that are constantly remodeled through the opposing actions of fusion and fission proteins. Changes in the expression of these proteins alter mitochondrial shape and size, and may promote or inhibit the propagation of apoptotic signals. Using mitochondrially targeted EGFP or DsRed2 to identify mitochondria, we observed a short, distinctly tubular mitochondrial morphology in postnatal cortical neurons in culture and in retinal ganglion cells in vivo, whereas longer, highly interconnected mitochondrial networks were detected in cortical astrocytes in vitro and non-neuronal cells in the retina in vivo. Differential expression patterns of fusion and fission proteins, in part, appear to determine these morphological differences as neurons expressed markedly high levels of Drp1 and OPA1 proteins compared to non-neuronal cells. This finding was corroborated using optic tissue samples. Moreover, cortical neurons expressed several splice variants of Drp1 including a neuron-specific isoform which incorporates exon 3. Knockdown or dominant-negative interference of endogenous Drp1 significantly increased mitochondrial length in both neurons and non-neuronal cells, but caused cell death only in cortical neurons. Conversely, depletion of the fusion protein, Mfn2, but not Mfn1, caused extensive mitochondrial fission and cell death. Thus, Drp1 and Mfn2 in normal cortical neurons not only regulate mitochondrial morphology, but are also required for cell survival. The present findings point to unique patterns of Drp1 expression and selective vulnerability to reduced levels of Drp1 expression/activity in neurons, and demonstrate that the regulation of mitochondrial dynamics must be tightly regulated in neurons.

Drp1 levels constitutively regulate mitochondrial dynamics and cell survival in cortical neurons

PubMed Central

Uo, Takuma; Dworzak, Jenny; Kinoshita, Chizuru; Inman, Denise M.; Kinoshita, Yoshito; Horner, Philip J.; Morrison, Richard S.

2009-01-01

Mitochondria exist as dynamic networks that are constantly remodeled through the opposing actions of fusion and fission proteins. Changes in the expression of these proteins alter mitochondrial shape and size, and may promote or inhibit the propagation of apoptotic signals. Using mitochondrially targeted EGFP or DsRed2 to identify mitochondria, we observed a short, distinctly tubular mitochondrial morphology in postnatal cortical neurons in culture and in retinal ganglion cells in vivo, whereas longer, highly interconnected mitochondrial networks were detected in cortical astrocytes in vitro and non-neuronal cells in the retina in vivo. Differential expression patterns of fusion and fission proteins, in part, appear to determine these morphological differences as neurons expressed markedly high levels of Drp1 and OPA1 proteins compared to non-neuronal cells. This finding was corroborated using optic tissue samples. Moreover, cortical neurons expressed several splice variants of Drp1 including a neuron-specific isoform which incorporates exon 3. Knockdown or dominant negative interference of endogenous Drp1 significantly increased mitochondrial length in both neurons and non-neuronal cells, but caused cell death only in cortical neurons. Conversely, depletion of the fusion protein, Mfn2, but not Mfn1, caused extensive mitochondrial fission and cell death. Thus, Drp1 and Mfn2 in normal cortical neurons not only regulate mitochondrial morphology, but are also required for cell survival. The present findings point to unique patterns of Drp1 expression and selective vulnerability to reduced levels of Drp1 expression/activity in neurons, and demonstrate that the regulation of mitochondrial dynamics must be tightly regulated in neurons. PMID:19445933

Metatranscriptome sequence analysis reveals diel periodicity of microbial community gene expression in the ocean's interior

NASA Astrophysics Data System (ADS)

Vislova, A.; Aylward, F.; Sosa, O.; DeLong, E.

2016-02-01

Previous work has revealed diel periodicity of gene expression in key metabolic pathways in both autotrophic and heterotrophic microbes in the surface ocean. In this study, we investigated patterns of diel periodicity of gene expression in depth profiles (25, 75, 125 and 250 meters). We postulated that microbial diel transcriptional signals would be increasingly dampened with depth, and that the timing of peak expression of specific transcripts would be shifted in time between depths, in accordance with depth-dependent diel light variability. Bacterioplankton were sampled from four depths every four hours at station ALOHA (22° 45' N 158° W) over 2 days. RNA was extracted from cells preserved on filters, converted to cDNA, and sequenced on the Illumina platform. Surprisingly, harmonic regression analysis revealed an increasing proportion of genes with diel periodic expression patterns with increasing depth between 25- 125 meters. At 250 meters, the proportion of genes exhibiting diel expression patterns decreased an order of magnitude compared to the photic zone. Community composition, functional gene categories, and diel patterns of gene expression were significantly different between the photic zone and 250 meter samples. The signals driving diel periodic gene expression in microbes at 250 meters is under further investigation. These data are now beginning provide a better understanding of the tempo and mode of microbial dynamics among specific taxa, throughout the ocean's interior.

Application of dynamic topic models to toxicogenomics data.

PubMed

Lee, Mikyung; Liu, Zhichao; Huang, Ruili; Tong, Weida

2016-10-06

All biological processes are inherently dynamic. Biological systems evolve transiently or sustainably according to sequential time points after perturbation by environment insults, drugs and chemicals. Investigating the temporal behavior of molecular events has been an important subject to understand the underlying mechanisms governing the biological system in response to, such as, drug treatment. The intrinsic complexity of time series data requires appropriate computational algorithms for data interpretation. In this study, we propose, for the first time, the application of dynamic topic models (DTM) for analyzing time-series gene expression data. A large time-series toxicogenomics dataset was studied. It contains over 3144 microarrays of gene expression data corresponding to rat livers treated with 131 compounds (most are drugs) at two doses (control and high dose) in a repeated schedule containing four separate time points (4-, 8-, 15- and 29-day). We analyzed, with DTM, the topics (consisting of a set of genes) and their biological interpretations over these four time points. We identified hidden patterns embedded in this time-series gene expression profiles. From the topic distribution for compound-time condition, a number of drugs were successfully clustered by their shared mode-of-action such as PPARɑ agonists and COX inhibitors. The biological meaning underlying each topic was interpreted using diverse sources of information such as functional analysis of the pathways and therapeutic uses of the drugs. Additionally, we found that sample clusters produced by DTM are much more coherent in terms of functional categories when compared to traditional clustering algorithms. We demonstrated that DTM, a text mining technique, can be a powerful computational approach for clustering time-series gene expression profiles with the probabilistic representation of their dynamic features along sequential time frames. The method offers an alternative way for uncovering hidden patterns embedded in time series gene expression profiles to gain enhanced understanding of dynamic behavior of gene regulation in the biological system.

Deep sequencing of the Mexican avocado transcriptome, an ancient angiosperm with a high content of fatty acids.

PubMed

Ibarra-Laclette, Enrique; Méndez-Bravo, Alfonso; Pérez-Torres, Claudia Anahí; Albert, Victor A; Mockaitis, Keithanne; Kilaru, Aruna; López-Gómez, Rodolfo; Cervantes-Luevano, Jacob Israel; Herrera-Estrella, Luis

2015-08-13

Avocado (Persea americana) is an economically important tropical fruit considered to be a good source of fatty acids. Despite its importance, the molecular and cellular characterization of biochemical and developmental processes in avocado is limited due to the lack of transcriptome and genomic information. The transcriptomes of seeds, roots, stems, leaves, aerial buds and flowers were determined using different sequencing platforms. Additionally, the transcriptomes of three different stages of fruit ripening (pre-climacteric, climacteric and post-climacteric) were also analyzed. The analysis of the RNAseqatlas presented here reveals strong differences in gene expression patterns between different organs, especially between root and flower, but also reveals similarities among the gene expression patterns in other organs, such as stem, leaves and aerial buds (vegetative organs) or seed and fruit (storage organs). Important regulators, functional categories, and differentially expressed genes involved in avocado fruit ripening were identified. Additionally, to demonstrate the utility of the avocado gene expression atlas, we investigated the expression patterns of genes implicated in fatty acid metabolism and fruit ripening. A description of transcriptomic changes occurring during fruit ripening was obtained in Mexican avocado, contributing to a dynamic view of the expression patterns of genes involved in fatty acid biosynthesis and the fruit ripening process.

Expression of Glycosaminoglycan Epitopes During Zebrafish Skeletogenesis

PubMed Central

Hayes, Anthony J; Mitchell, Ruth E; Bashford, Andrew; Reynolds, Scott; Caterson, Bruce; Hammond, Chrissy L

2013-01-01

Background: The zebrafish is an important developmental model. Surprisingly, there are few studies that describe the glycosaminoglycan composition of its extracellular matrix during skeletogenesis. Glycosaminoglycans on proteoglycans contribute to the material properties of musculo skeletal connective tissues, and are important in regulating signalling events during morphogenesis. Sulfation motifs within the chain structure of glycosaminoglycans on cell-associated and extracellular matrix proteoglycans allow them to bind and regulate the sequestration/presentation of bioactive signalling molecules important in musculo-skeletal development. Results: We describe the spatio-temporal expression of different glycosaminoglycan moieties during zebrafish skeletogenesis with antibodies recognising (1) native sulfation motifs within chondroitin and keratan sulfate chains, and (2) enzyme-generated neoepitope sequences within the chain structure of chondroitin sulfate (i.e., 0-, 4-, and 6-sulfated isoforms) and heparan sulfate glycosaminoglycans. We show that all the glycosaminoglycan moieties investigated are expressed within the developing skeletal tissues of larval zebrafish. However, subtle changes in their patterns of spatio-temporal expression over the period examined suggest that their expression is tightly and dynamically controlled during development. Conclusions: The subtle differences observed in the domains of expression between different glycosaminoglycan moieties suggest differences in their functional roles during establishment of the primitive analogues of the skeleton. Developmental Dynamics 242:778–789, 2013. © 2013 Wiley Periodicals, Inc. Key Findings The developing zebrafish skeleton expresses many different glycosaminoglycan modifications. Multiple different glycosaminoglycan epitopes are dynamically expressed in the craniofacial skeleton. Expression of chondroitin sulfate moieties are dynamically expressed in the vertebral column and precede mineralisation. PMID:23576310

A microcosm of musical expression. III. Contributions of timing and dynamics to the aesthetic impression of pianists' performances of the initial measures of Chopin's Etude in E major.

PubMed

Repp, B H

1999-07-01

Four judges repeatedly assessed the overall aesthetic quality of more than 100 recorded performances of the opening of Chopin's Etude in E major on a 10-point scale. The judgments, which exhibited reasonable reliability and modest intercorrelations, were entered into regression analyses with 16 independent variables derived from earlier objective analyses of the expressive timing and dynamics of the performances [Repp, J. Acoust. Soc. Am. 104, 1085-1100 (1998); 105, 1972-1988 (1999)]. Only between 9% and 18% of the variance in the judges' ratings was accounted for. By contrast, timing variables accounted for 53% of the variance in one judge's ratings of synthesized performances that varied in timing only and mimicked the timing patterns of the original performances. These results indicate, first, that the aesthetic impression of the original recordings rested primarily on aspects other than those measured (such as texture, tone, or aspects of timing and dynamics that eluded the earlier analyses) and, second, that very different patterns of timing and dynamics are aesthetically acceptable for the same music, provided that other, aesthetically more crucial performance aspects are present.

Sequential pattern formation governed by signaling gradients

NASA Astrophysics Data System (ADS)

Jörg, David J.; Oates, Andrew C.; Jülicher, Frank

2016-10-01

Rhythmic and sequential segmentation of the embryonic body plan is a vital developmental patterning process in all vertebrate species. However, a theoretical framework capturing the emergence of dynamic patterns of gene expression from the interplay of cell oscillations with tissue elongation and shortening and with signaling gradients, is still missing. Here we show that a set of coupled genetic oscillators in an elongating tissue that is regulated by diffusing and advected signaling molecules can account for segmentation as a self-organized patterning process. This system can form a finite number of segments and the dynamics of segmentation and the total number of segments formed depend strongly on kinetic parameters describing tissue elongation and signaling molecules. The model accounts for existing experimental perturbations to signaling gradients, and makes testable predictions about novel perturbations. The variety of different patterns formed in our model can account for the variability of segmentation between different animal species.

From crater functions to partial differential equations: a new approach to ion bombardment induced nonequilibrium pattern formation.

PubMed

Norris, Scott A; Brenner, Michael P; Aziz, Michael J

2009-06-03

We develop a methodology for deriving continuum partial differential equations for the evolution of large-scale surface morphology directly from molecular dynamics simulations of the craters formed from individual ion impacts. Our formalism relies on the separation between the length scale of ion impact and the characteristic scale of pattern formation, and expresses the surface evolution in terms of the moments of the crater function. We demonstrate that the formalism reproduces the classical Bradley-Harper results, as well as ballistic atomic drift, under the appropriate simplifying assumptions. Given an actual set of converged molecular dynamics moments and their derivatives with respect to the incidence angle, our approach can be applied directly to predict the presence and absence of surface morphological instabilities. This analysis represents the first work systematically connecting molecular dynamics simulations of ion bombardment to partial differential equations that govern topographic pattern-forming instabilities.

Temporal Dynamics of Host Molecular Responses Differentiate Symptomatic and Asymptomatic Influenza A Infection

PubMed Central

Huang, Yongsheng; Zaas, Aimee K.; Rao, Arvind; Dobigeon, Nicolas; Woolf, Peter J.; Veldman, Timothy; Øien, N. Christine; McClain, Micah T.; Varkey, Jay B.; Nicholson, Bradley; Carin, Lawrence; Kingsmore, Stephen; Woods, Christopher W.; Ginsburg, Geoffrey S.; Hero, Alfred O.

2011-01-01

Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A infection, we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin) and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. Here we present distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infections. We show that symptomatic hosts invoke, simultaneously, multiple pattern recognition receptors-mediated antiviral and inflammatory responses that may relate to virus-induced oxidative stress. In contrast, asymptomatic subjects tightly regulate these responses and exhibit elevated expression of genes that function in antioxidant responses and cell-mediated responses. We reveal an ab initio molecular signature that strongly correlates to symptomatic clinical disease and biomarkers whose expression patterns best discriminate early from late phases of infection. Our results establish a temporal pattern of host molecular responses that differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique non-passive response signature, suggesting novel putative molecular targets for both prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza. PMID:21901105

The complexity of gene expression dynamics revealed by permutation entropy

PubMed Central

2010-01-01

Background High complexity is considered a hallmark of living systems. Here we investigate the complexity of temporal gene expression patterns using the concept of Permutation Entropy (PE) first introduced in dynamical systems theory. The analysis of gene expression data has so far focused primarily on the identification of differentially expressed genes, or on the elucidation of pathway and regulatory relationships. We aim to study gene expression time series data from the viewpoint of complexity. Results Applying the PE complexity metric to abiotic stress response time series data in Arabidopsis thaliana, genes involved in stress response and signaling were found to be associated with the highest complexity not only under stress, but surprisingly, also under reference, non-stress conditions. Genes with house-keeping functions exhibited lower PE complexity. Compared to reference conditions, the PE of temporal gene expression patterns generally increased upon stress exposure. High-complexity genes were found to have longer upstream intergenic regions and more cis-regulatory motifs in their promoter regions indicative of a more complex regulatory apparatus needed to orchestrate their expression, and to be associated with higher correlation network connectivity degree. Arabidopsis genes also present in other plant species were observed to exhibit decreased PE complexity compared to Arabidopsis specific genes. Conclusions We show that Permutation Entropy is a simple yet robust and powerful approach to identify temporal gene expression profiles of varying complexity that is equally applicable to other types of molecular profile data. PMID:21176199

Sig2GRN: a software tool linking signaling pathway with gene regulatory network for dynamic simulation.

PubMed

Zhang, Fan; Liu, Runsheng; Zheng, Jie

2016-12-23

Linking computational models of signaling pathways to predicted cellular responses such as gene expression regulation is a major challenge in computational systems biology. In this work, we present Sig2GRN, a Cytoscape plugin that is able to simulate time-course gene expression data given the user-defined external stimuli to the signaling pathways. A generalized logical model is used in modeling the upstream signaling pathways. Then a Boolean model and a thermodynamics-based model are employed to predict the downstream changes in gene expression based on the simulated dynamics of transcription factors in signaling pathways. Our empirical case studies show that the simulation of Sig2GRN can predict changes in gene expression patterns induced by DNA damage signals and drug treatments. As a software tool for modeling cellular dynamics, Sig2GRN can facilitate studies in systems biology by hypotheses generation and wet-lab experimental design. http://histone.scse.ntu.edu.sg/Sig2GRN/.

Harvest patterns and effort dynamics of indigenous and non-indigenous commercial sectors of the eastern Torres Strait reef line fishery

NASA Astrophysics Data System (ADS)

Williams, Ashley J.; Ballagh, Aaron C.; Begg, Gavin A.; Murchie, Cameron D.; Currey, Leanne M.

2008-09-01

The reef line fishery (RLF) in eastern Torres Strait (ETS) is unique in that it has both a commercial indigenous sector and a commercial non-indigenous sector. Recently, concerns have been expressed by all stakeholders about the long-term sustainability of the fishery. These concerns have been exacerbated by the lack of detailed catch and effort information from both sectors, which has precluded any formal assessment of the fishery. In this paper, we characterise the harvest patterns and effort dynamics of the indigenous and non-indigenous commercial sectors of the ETS RLF using a range of data sources including commercial logbooks, community freezer records, voluntary logbooks and observer surveys. We demonstrate that bycatch is a significant component of the catch for both sectors and identify substantial differences in harvest patterns and effort dynamics between the sectors. Differences between sectors were observed in species composition and spatial and temporal patterns in catch, effort and catch per unit effort. These results highlight the inherent variation in catch and effort dynamics between the two commercial sectors of the ETS RLF and provide valuable information for the development of future assessments and appropriate management strategies for the fishery. The more reliable estimates of harvest patterns and effort dynamics for both sectors obtained from observer surveys will also assist in resolving issues relating to allocation of reef fish resources in Torres Strait.

Mechanical Influences on Morphogenesis of the Knee Joint Revealed through Morphological, Molecular and Computational Analysis of Immobilised Embryos

PubMed Central

Roddy, Karen A.; Prendergast, Patrick J.; Murphy, Paula

2011-01-01

Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint. PMID:21386908

Immunohistochemical Analysis on Cortex-to-Cortex Healing After Mandibular Vertical Ramus Osteotomy: A Preliminary Study.

PubMed

Jung, Hwi-Dong; Kim, Sang Yoon; Jung, Han-Sung; Park, Hyung-Sik; Jung, Young-Soo

2018-02-01

The present study analyzed the expression of specific cytokines in the transforming growth factor (TGF)-β superfamily postoperatively after mandibular vertical ramus osteotomy (VRO). Four beagle dogs were enrolled and euthanized at 1, 2, 4, and 8 weeks postoperatively for immunohistochemical analysis using 6 specific antibodies (bone morphogenetic protein [BMP]-2/4, BMP-7, TGF-β2, TGF-β3, matrix metalloproteinase-3, and vascular endothelial growth factor [VEGF]). The results from the surgical site and control (adjacent area) were compared. Generalized upregulation of BMP-2/4 was observed in all healing periods, and the strongest expression of BMP-7 was observed at 1 week postoperatively. The strongest expression of TGF-β2 was observed at 8 weeks with increasing pattern. The strong expression of TGF-β3 was observed at 1 and 4 weeks, with the strongest expression of VEGF at 1 week, with a decreasing pattern. No notable uptake was detected with the 6 specific antibodies in the adjacent bone (control). The absence of internal fixation after VRO led to dynamic healing with a specific expression pattern of BMP-7 and TGF-β2. The anatomic factors, including sufficient preexisting vascularity, led to the earlier expression pattern of VEGF. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Dynamic patterning by the Drosophila pair-rule network reconciles long-germ and short-germ segmentation

PubMed Central

2017-01-01

Drosophila segmentation is a well-established paradigm for developmental pattern formation. However, the later stages of segment patterning, regulated by the “pair-rule” genes, are still not well understood at the system level. Building on established genetic interactions, I construct a logical model of the Drosophila pair-rule system that takes into account the demonstrated stage-specific architecture of the pair-rule gene network. Simulation of this model can accurately recapitulate the observed spatiotemporal expression of the pair-rule genes, but only when the system is provided with dynamic “gap” inputs. This result suggests that dynamic shifts of pair-rule stripes are essential for segment patterning in the trunk and provides a functional role for observed posterior-to-anterior gap domain shifts that occur during cellularisation. The model also suggests revised patterning mechanisms for the parasegment boundaries and explains the aetiology of the even-skipped null mutant phenotype. Strikingly, a slightly modified version of the model is able to pattern segments in either simultaneous or sequential modes, depending only on initial conditions. This suggests that fundamentally similar mechanisms may underlie segmentation in short-germ and long-germ arthropods. PMID:28953896

Role of genomic architecture in the expression dynamics of long noncoding RNAs during differentiation of human neuroblastoma cells.

PubMed

Batagov, Arsen O; Yarmishyn, Aliaksandr A; Jenjaroenpun, Piroon; Tan, Jovina Z; Nishida, Yuichiro; Kurochkin, Igor V

2013-10-16

Mammalian genomes are extensively transcribed producing thousands of long non-protein-coding RNAs (lncRNAs). The biological significance and function of the vast majority of lncRNAs remain unclear. Recent studies have implicated several lncRNAs as playing important roles in embryonic development and cancer progression. LncRNAs are characterized with different genomic architectures in relationship with their associated protein-coding genes. Our study aimed at bridging lncRNA architecture with dynamical patterns of their expression using differentiating human neuroblastoma cells model. LncRNA expression was studied in a 120-hours timecourse of differentiation of human neuroblastoma SH-SY5Y cells into neurons upon treatment with retinoic acid (RA), the compound used for the treatment of neuroblastoma. A custom microarray chip was utilized to interrogate expression levels of 9,267 lncRNAs in the course of differentiation. We categorized lncRNAs into 19 architecture classes according to their position relatively to protein-coding genes. For each architecture class, dynamics of expression of lncRNAs was studied in association with their protein-coding partners. It allowed us to demonstrate positive correlation of lncRNAs with their associated protein-coding genes at bidirectional promoters and for sense-antisense transcript pairs. In contrast, lncRNAs located in the introns and downstream of the protein-coding genes were characterized with negative correlation modes. We further classified the lncRNAs by the temporal patterns of their expression dynamics. We found that intronic and bidirectional promoter architectures are associated with rapid RA-dependent induction or repression of the corresponding lncRNAs, followed by their constant expression. At the same time, lncRNAs expressed downstream of protein-coding genes are characterized by rapid induction, followed by transcriptional repression. Quantitative RT-PCR analysis confirmed the discovered functional modes for several selected lncRNAs associated with proteins involved in cancer and embryonic development. This is the first report detailing dynamical changes of multiple lncRNAs during RA-induced neuroblastoma differentiation. Integration of genomic and transcriptomic levels of information allowed us to demonstrate specific behavior of lncRNAs organized in different genomic architectures. This study also provides a list of lncRNAs with possible roles in neuroblastoma.

Predicting and Detecting Emerging Cyberattack Patterns Using StreamWorks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chin, George; Choudhury, Sutanay; Feo, John T.

2014-06-30

The number and sophistication of cyberattacks on industries and governments have dramatically grown in recent years. To counter this movement, new advanced tools and techniques are needed to detect cyberattacks in their early stages such that defensive actions may be taken to avert or mitigate potential damage. From a cybersecurity analysis perspective, detecting cyberattacks may be cast as a problem of identifying patterns in computer network traffic. Logically and intuitively, these patterns may take on the form of a directed graph that conveys how an attack or intrusion propagates through the computers of a network. Such cyberattack graphs could providemore » cybersecurity analysts with powerful conceptual representations that are natural to express and analyze. We have been researching and developing graph-centric approaches and algorithms for dynamic cyberattack detection. The advanced dynamic graph algorithms we are developing will be packaged into a streaming network analysis framework known as StreamWorks. With StreamWorks, a scientist or analyst may detect and identify precursor events and patterns as they emerge in complex networks. This analysis framework is intended to be used in a dynamic environment where network data is streamed in and is appended to a large-scale dynamic graph. Specific graphical query patterns are decomposed and collected into a graph query library. The individual decomposed subpatterns in the library are continuously and efficiently matched against the dynamic graph as it evolves to identify and detect early, partial subgraph patterns. The scalable emerging subgraph pattern algorithms will match on both structural and semantic network properties.« less

Dynamic Patterns of Clonal Evolution in Tumor Vasculature Underlie Alterations in Lymphocyte-Endothelial Recognition to Foster Tumor Immune Escape.

PubMed

Corey, Daniel M; Rinkevich, Yuval; Weissman, Irving L

2016-03-15

Although tumor blood vessels have been a major therapeutic target for cancer chemotherapy, little is known regarding the stepwise development of the tumor microenvironment. Here, we use a multicolor Cre-dependent marker system to trace clonality within the tumor microenvironment to show that tumor blood vessels follow a pattern of dynamic clonal evolution. In an advanced melanoma tumor microenvironment, the vast majority of tumor vasculature clones are derived from a common precursor. Quantitative lineage analysis reveals founder clones diminish in frequency and are replaced by subclones as tumors evolve. These tumor-specific blood vessels are characterized by a developmental switch to a more invasive and immunologically silent phenotype. Gene expression profiling and pathway analysis reveals selection for traits promoting upregulation of alternative angiogenic programs such as unregulated HGF-MET signaling and enhanced autocrine signaling through VEGF and PDGF. Furthermore, we show a developmental switch in the expression of functionally significant primary lymphocyte adhesion molecules on tumor endothelium, such as the loss in expression of the mucosal addressin MAdCAM-1, whose counter receptor a4β7 on lymphocytes controls lymphocyte homing. Changes in adhesive properties on tumor endothelial subclones are accompanied by decreases in expression of lymphocyte chemokines CXCL16, CXCL13, CXCL12, CXCL9, CXCL10, and CCL19. These evolutionary patterns in the expressed genetic program within tumor endothelium will have both a quantitative and functional impact on lymphocyte distribution that may well influence tumor immune function and underlie escape mechanisms from current antiangiogenic pharmacotherapies. ©2015 American Association for Cancer Research.

Multiple abiotic stimuli are integrated in the regulation of rice gene expression under field conditions.

PubMed

Plessis, Anne; Hafemeister, Christoph; Wilkins, Olivia; Gonzaga, Zennia Jean; Meyer, Rachel Sarah; Pires, Inês; Müller, Christian; Septiningsih, Endang M; Bonneau, Richard; Purugganan, Michael

2015-11-26

Plants rely on transcriptional dynamics to respond to multiple climatic fluctuations and contexts in nature. We analyzed the genome-wide gene expression patterns of rice (Oryza sativa) growing in rainfed and irrigated fields during two distinct tropical seasons and determined simple linear models that relate transcriptomic variation to climatic fluctuations. These models combine multiple environmental parameters to account for patterns of expression in the field of co-expressed gene clusters. We examined the similarities of our environmental models between tropical and temperate field conditions, using previously published data. We found that field type and macroclimate had broad impacts on transcriptional responses to environmental fluctuations, especially for genes involved in photosynthesis and development. Nevertheless, variation in solar radiation and temperature at the timescale of hours had reproducible effects across environmental contexts. These results provide a basis for broad-based predictive modeling of plant gene expression in the field.

Dynamics of growth zone patterning in the milkweed bug Oncopeltus fasciatus

PubMed Central

Weiss, Aryeh; Williams, Terri A.; Nagy, Lisa M.

2017-01-01

We describe the dynamic process of abdominal segment generation in the milkweed bug Oncopeltus fasciatus. We present detailed morphological measurements of the growing germband throughout segmentation. Our data are complemented by cell division profiles and expression patterns of key genes, including invected and even-skipped as markers for different stages of segment formation. We describe morphological and mechanistic changes in the growth zone and in nascent segments during the generation of individual segments and throughout segmentation, and examine the relative contribution of newly formed versus existing tissue to segment formation. Although abdominal segment addition is primarily generated through the rearrangement of a pool of undifferentiated cells, there is nonetheless proliferation in the posterior. By correlating proliferation with gene expression in the growth zone, we propose a model for growth zone dynamics during segmentation in which the growth zone is functionally subdivided into two distinct regions: a posterior region devoted to a slow rate of growth among undifferentiated cells, and an anterior region in which segmental differentiation is initiated and proliferation inhibited. PMID:28432218

Uncovering a Dynamic Feature of the Transcriptional Regulatory Network for Anterior-Posterior Patterning in the Drosophila Embryo

PubMed Central

Liu, Junbo; Ma, Jun

2013-01-01

Anterior-posterior (AP) patterning in the Drosophila embryo is dependent on the Bicoid (Bcd) morphogen gradient. However, most target genes of Bcd also require additional inputs to establish their expression domains, reflective of the operation of a cross-regulatory network and contributions of other maternal signals. This is in contrast to hunchback (hb), which has an anterior expression domain driven by an enhancer that appears to respond primarily to the Bcd input. To gain a better understanding of the regulatory logic of the AP patterning network, we perform quantitative studies that specifically investigate the dynamics of hb transcription during development. We show that Bcd-dependent hb transcription, monitored by the intron-containing nascent transcripts near the P2 promoter, is turned off quickly–on the order of a few minutes–upon entering the interphase of nuclear cycle 14A. This shutdown contrasts with earlier cycles during which active hb transcription can persist until the moment when the nucleus enters mitosis. The shutdown takes place at a time when the nuclear Bcd gradient profile in the embryo remains largely intact, suggesting that this is a process likely subject to control of a currently unknown regulatory mechanism. We suggest that this dynamic feature offers a window of opportunity for hb to faithfully interpret, and directly benefit from, Bcd gradient properties, including its scaling properties, to help craft a robust AP patterning outcome. PMID:23646132

Changes in expression and secretion patterns of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway molecules during murine neural stem/progenitor cell differentiation in vitro☆

PubMed Central

Lu, Jiang; Lu, Kehuan; Li, Dongsheng

2012-01-01

In the present study, we investigated the dynamic expression of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway related factors in the process of in vitro hippocampal neural stem/progenitor cell differentiation from embryonic Sprague-Dawley rats or embryonic Kunming species mice, using fluorescent quantitative reverse transcription-PCR and western blot analyses. Results demonstrated that the dynamic expression of fibroblast growth factor 8 was similar to fibroblast growth factor receptor 1 expression but not to other fibroblast growth factor receptors. Enzyme-linked immunosorbent assay demonstrated that fibroblast growth factor 8 and Sonic Hedgehog signaling pathway protein factors were secreted by neural cells into the intercellular niche. Our experimental findings indicate that fibroblast growth factor 8 and Sonic Hedgehog expression may be related to the differentiation of neural stem/progenitor cells. PMID:25624789

Defining global neuroendocrine gene expression patterns associated with reproductive seasonality in fish.

PubMed

Zhang, Dapeng; Xiong, Huiling; Mennigen, Jan A; Popesku, Jason T; Marlatt, Vicki L; Martyniuk, Christopher J; Crump, Kate; Cossins, Andrew R; Xia, Xuhua; Trudeau, Vance L

2009-06-05

Many vertebrates, including the goldfish, exhibit seasonal reproductive rhythms, which are a result of interactions between external environmental stimuli and internal endocrine systems in the hypothalamo-pituitary-gonadal axis. While it is long believed that differential expression of neuroendocrine genes contributes to establishing seasonal reproductive rhythms, no systems-level investigation has yet been conducted. In the present study, by analyzing multiple female goldfish brain microarray datasets, we have characterized global gene expression patterns for a seasonal cycle. A core set of genes (873 genes) in the hypothalamus were identified to be differentially expressed between May, August and December, which correspond to physiologically distinct stages that are sexually mature (prespawning), sexual regression, and early gonadal redevelopment, respectively. Expression changes of these genes are also shared by another brain region, the telencephalon, as revealed by multivariate analysis. More importantly, by examining one dataset obtained from fish in October who were kept under long-daylength photoperiod (16 h) typical of the springtime breeding season (May), we observed that the expression of identified genes appears regulated by photoperiod, a major factor controlling vertebrate reproductive cyclicity. Gene ontology analysis revealed that hormone genes and genes functionally involved in G-protein coupled receptor signaling pathway and transmission of nerve impulses are significantly enriched in an expression pattern, whose transition is located between prespawning and sexually regressed stages. The existence of seasonal expression patterns was verified for several genes including isotocin, ependymin II, GABA(A) gamma2 receptor, calmodulin, and aromatase b by independent samplings of goldfish brains from six seasonal time points and real-time PCR assays. Using both theoretical and experimental strategies, we report for the first time global gene expression patterns throughout a breeding season which may account for dynamic neuroendocrine regulation of seasonal reproductive development.

Defining Global Neuroendocrine Gene Expression Patterns Associated with Reproductive Seasonality in Fish

PubMed Central

Mennigen, Jan A.; Popesku, Jason T.; Marlatt, Vicki L.; Martyniuk, Christopher J.; Crump, Kate; Cossins, Andrew R.; Xia, Xuhua; Trudeau, Vance L.

2009-01-01

Background Many vertebrates, including the goldfish, exhibit seasonal reproductive rhythms, which are a result of interactions between external environmental stimuli and internal endocrine systems in the hypothalamo-pituitary-gonadal axis. While it is long believed that differential expression of neuroendocrine genes contributes to establishing seasonal reproductive rhythms, no systems-level investigation has yet been conducted. Methodology/Principal Findings In the present study, by analyzing multiple female goldfish brain microarray datasets, we have characterized global gene expression patterns for a seasonal cycle. A core set of genes (873 genes) in the hypothalamus were identified to be differentially expressed between May, August and December, which correspond to physiologically distinct stages that are sexually mature (prespawning), sexual regression, and early gonadal redevelopment, respectively. Expression changes of these genes are also shared by another brain region, the telencephalon, as revealed by multivariate analysis. More importantly, by examining one dataset obtained from fish in October who were kept under long-daylength photoperiod (16 h) typical of the springtime breeding season (May), we observed that the expression of identified genes appears regulated by photoperiod, a major factor controlling vertebrate reproductive cyclicity. Gene ontology analysis revealed that hormone genes and genes functionally involved in G-protein coupled receptor signaling pathway and transmission of nerve impulses are significantly enriched in an expression pattern, whose transition is located between prespawning and sexually regressed stages. The existence of seasonal expression patterns was verified for several genes including isotocin, ependymin II, GABAA gamma2 receptor, calmodulin, and aromatase b by independent samplings of goldfish brains from six seasonal time points and real-time PCR assays. Conclusions/Significance Using both theoretical and experimental strategies, we report for the first time global gene expression patterns throughout a breeding season which may account for dynamic neuroendocrine regulation of seasonal reproductive development. PMID:19503831

Expression profiles of the Gα subunits during Xenopus tropicalis embryonic development.

PubMed

Fuentealba, Jaime; Toro-Tapia, Gabriela; Rodriguez, Marion; Arriagada, Cecilia; Maureira, Alejandro; Beyer, Andrea; Villaseca, Soraya; Leal, Juan I; Hinrichs, Maria V; Olate, Juan; Caprile, Teresa; Torrejón, Marcela

2016-09-01

Heterotrimeric G protein signaling plays major roles during different cellular events. However, there is a limited understanding of the molecular mechanisms underlying G protein control during embryogenesis. G proteins are highly conserved and can be grouped into four subfamilies according to sequence homology and function. To further studies on G protein function during embryogenesis, the present analysis identified four Gα subunits representative of the different subfamilies and determined their spatiotemporal expression patterns during Xenopus tropicalis embryogenesis. Each of the Gα subunit transcripts was maternally and zygotically expressed, and, as development progressed, dynamic expression patterns were observed. In the early developmental stages, the Gα subunits were expressed in the animal hemisphere and dorsal marginal zone. While expression was observed at the somite boundaries, in vascular structures, in the eye, and in the otic vesicle during the later stages, expression was mainly found in neural tissues, such as the neural tube and, especially, in the cephalic vesicles, neural crest region, and neural crest-derived structures. Together, these results support the pleiotropism and complexity of G protein subfamily functions in different cellular events. The present study constitutes the most comprehensive description to date of the spatiotemporal expression patterns of Gα subunits during vertebrate development. Copyright © 2016 Elsevier B.V. All rights reserved.

Coordination of Cellular Dynamics Contributes to Tooth Epithelium Deformations

PubMed Central

Morita, Ritsuko; Kihira, Miho; Nakatsu, Yousuke; Nomoto, Yohei; Ogawa, Miho; Ohashi, Kazumasa; Mizuno, Kensaku; Tachikawa, Tetsuhiko; Ishimoto, Yukitaka; Morishita, Yoshihiro; Tsuji, Takashi

2016-01-01

The morphologies of ectodermal organs are shaped by appropriate combinations of several deformation modes, such as invagination and anisotropic tissue elongation. However, how multicellular dynamics are coordinated during deformation processes remains to be elucidated. Here, we developed a four-dimensional (4D) analysis system for tracking cell movement and division at a single-cell resolution in developing tooth epithelium. The expression patterns of a Fucci probe clarified the region- and stage-specific cell cycle patterns within the tooth germ, which were in good agreement with the pattern of the volume growth rate estimated from tissue-level deformation analysis. Cellular motility was higher in the regions with higher growth rates, while the mitotic orientation was significantly biased along the direction of tissue elongation in the epithelium. Further, these spatio-temporal patterns of cellular dynamics and tissue-level deformation were highly correlated with that of the activity of cofilin, which is an actin depolymerization factor, suggesting that the coordination of cellular dynamics via actin remodeling plays an important role in tooth epithelial morphogenesis. Our system enhances the understanding of how cellular behaviors are coordinated during ectodermal organogenesis, which cannot be observed from histological analyses. PMID:27588418

Proteomics analysis reveals a dynamic diurnal pattern of photosynthesis-related pathways in maize leaves

PubMed Central

Lu, Tiegang; Zhang, Zhiguo

2017-01-01

Plant leaves exhibit differentiated patterns of photosynthesis rates under diurnal light regulation. Maize leaves show a single-peak pattern without photoinhibition at midday when the light intensity is maximized. This mechanism contributes to highly efficient photosynthesis in maize leaves. To understand the molecular basis of this process, an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics analysis was performed to reveal the dynamic pattern of proteins related to photosynthetic reactions. Steady, single-peak and double-peak protein expression patterns were discovered in maize leaves, and antenna proteins in these leaves displayed a steady pattern. In contrast, the photosystem, carbon fixation and citrate pathways were highly controlled by diurnal light intensity. Most enzymes in the limiting steps of these pathways were major sites of regulation. Thus, maize leaves optimize photosynthesis and carbon fixation outside of light harvesting to adapt to the changes in diurnal light intensity at the protein level. PMID:28732011

5D imaging via light sheet microscopy reveals cell dynamics during the eye-antenna disc primordium formation in Drosophila

NASA Astrophysics Data System (ADS)

Huang, Yu Shan; Ku, Hui Yu; Tsai, Yun Chi; Chang, Chin Hao; Pao, Sih Hua; Sun, Y. Henry; Chiou, Arthur

2017-03-01

5D images of engrailed (en) and eye gone (eyg) gene expressions during the course of the eye-antenna disc primordium (EADP) formation of Drosophila embryos from embryonic stages 13 through 16 were recorded via light sheet microscopy and analyzed to reveal the cell dynamics involved in the development of the EADP. Detailed analysis of the time-lapsed images revealed the process of EADP formation and its invagination trajectory, which involved an inversion of the EADP anterior-posterior axis relative to the body. Furthermore, analysis of the en-expression pattern in the EADP provided strong evidence that the EADP is derived from one of the en-expressing head segments.

Dynamics of gene expression with positive feedback to histone modifications at bivalent domains

NASA Astrophysics Data System (ADS)

Huang, Rongsheng; Lei, Jinzhi

2018-03-01

Experiments have shown that in embryonic stem cells, the promoters of many lineage-control genes contain “bivalent domains”, within which the nucleosomes possess both active (H3K4me3) and repressive (H3K27me3) marks. Such bivalent modifications play important roles in maintaining pluripotency in embryonic stem cells. Here, to investigate gene expression dynamics when there are regulations in bivalent histone modifications and random partition in cell divisions, we study how positive feedback to histone methylation/demethylation controls the transition dynamics of the histone modification patterns along with cell cycles. We constructed a computational model that includes dynamics of histone marks, three-stage chromatin state transitions, transcription and translation, feedbacks from protein product to enzymes to regulate the addition and removal of histone marks, and the inheritance of nucleosome state between cell cycles. The model reveals how dynamics of both nucleosome state transition and gene expression are dependent on the enzyme activities and feedback regulations. Results show that the combination of stochastic histone modification at each cell division and the deterministic feedback regulation work together to adjust the dynamics of chromatin state transition in stem cell regenerations.

Diverse Cis-Regulatory Mechanisms Contribute to Expression Evolution of Tandem Gene Duplicates

PubMed Central

Baudouin-Gonzalez, Luís; Santos, Marília A; Tempesta, Camille; Sucena, Élio; Roch, Fernando; Tanaka, Kohtaro

2017-01-01

Abstract Pairs of duplicated genes generally display a combination of conserved expression patterns inherited from their unduplicated ancestor and newly acquired domains. However, how the cis-regulatory architecture of duplicated loci evolves to produce these expression patterns is poorly understood. We have directly examined the gene-regulatory evolution of two tandem duplicates, the Drosophila Ly6 genes CG9336 and CG9338, which arose at the base of the drosophilids between 40 and 60 Ma. Comparing the expression patterns of the two paralogs in four Drosophila species with that of the unduplicated ortholog in the tephritid Ceratitis capitata, we show that they diverged from each other as well as from the unduplicated ortholog. Moreover, the expression divergence appears to have occurred close to the duplication event and also more recently in a lineage-specific manner. The comparison of the tissue-specific cis-regulatory modules (CRMs) controlling the paralog expression in the four Drosophila species indicates that diverse cis-regulatory mechanisms, including the novel tissue-specific enhancers, differential inactivation, and enhancer sharing, contributed to the expression evolution. Our analysis also reveals a surprisingly variable cis-regulatory architecture, in which the CRMs driving conserved expression domains change in number, location, and specificity. Altogether, this study provides a detailed historical account that uncovers a highly dynamic picture of how the paralog expression patterns and their underlying cis-regulatory landscape evolve. We argue that our findings will encourage studying cis-regulatory evolution at the whole-locus level to understand how interactions between enhancers and other regulatory levels shape the evolution of gene expression. PMID:28961967

Characterization of big bang, a novel gene encoding for PDZ domain-containing proteins that are dynamically expressed throughout Drosophila development.

PubMed

Kim, Sabrina Y; Renihan, Maia K; Boulianne, Gabrielle L

2006-06-01

PDZ (PSD-95, Discs-large, ZO-1) domain proteins often function as scaffolding proteins and have been shown to play important roles in diverse cellular processes such as the establishment and maintenance of cell polarity, and signal transduction. Here, we report the identification and cloning of a novel Drosophila melanogaster gene that is predicted to produce several different PDZ domain-containing proteins through alternative promoter usage and alternative splicing. This gene, that we have named big bang (bbg), was first identified as C96-GAL4, a GAL4 enhancer trap line that was generated in our lab. To further characterize bbg, its expression pattern was examined in ovaries, embryos, and late third instar larvae using UAS reporter gene constructs, in situ hybridization, or immunocytochemistry. In addition, the expression of alternatively spliced transcripts was examined in more detail using in situ hybridization. We find that during embryogenesis bbg is predominantly expressed in the developing gut, but it is also expressed in external sensory organs found in the epidermis. In the late third instar larva, bbg is expressed along the presumptive wing margin in the wing disc, broadly in the eye disc, and in other imaginal discs as well as in the brain. The expression patterns observed are dynamic and specific during development, suggesting that like other genes that encode for several different PDZ domain protein isoforms, bbg likely plays important roles in multiple developmental processes.

Temporal dynamics of the ABC transporter response to insecticide treatment: insights from the malaria vector Anopheles stephensi

NASA Astrophysics Data System (ADS)

Epis, Sara; Porretta, Daniele; Mastrantonio, Valentina; Urbanelli, Sandra; Sassera, Davide; De Marco, Leone; Mereghetti, Valeria; Montagna, Matteo; Ricci, Irene; Favia, Guido; Bandi, Claudio

2014-12-01

In insects, ABC transporters have been shown to contribute to defence/resistance to insecticides by reducing toxic concentrations in cells/tissues. Despite the extensive studies about this detoxifying mechanism, the temporal patterns of ABC transporter activation have been poorly investigated. Using the malaria vector Anopheles stephensi as a study system, we investigated the expression profile of ABC genes belonging to different subfamilies in permethrin-treated larvae at different time points (30 min to 48 h). Our results showed that the expression of ABCB and ABCG subfamily genes was upregulated at 1 h after treatment, with the highest expression observed at 6 h. Therefore, future investigations on the temporal dynamics of ABC gene expression will allow a better implementation of insecticide treatment regimens, including the use of specific inhibitors of ABC efflux pumps.

Spatial expression of Hox cluster genes in the ontogeny of a sea urchin

NASA Technical Reports Server (NTRS)

Arenas-Mena, C.; Cameron, A. R.; Davidson, E. H.

2000-01-01

The Hox cluster of the sea urchin Strongylocentrous purpuratus contains ten genes in a 500 kb span of the genome. Only two of these genes are expressed during embryogenesis, while all of eight genes tested are expressed during development of the adult body plan in the larval stage. We report the spatial expression during larval development of the five 'posterior' genes of the cluster: SpHox7, SpHox8, SpHox9/10, SpHox11/13a and SpHox11/13b. The five genes exhibit a dynamic, largely mesodermal program of expression. Only SpHox7 displays extensive expression within the pentameral rudiment itself. A spatially sequential and colinear arrangement of expression domains is found in the somatocoels, the paired posterior mesodermal structures that will become the adult perivisceral coeloms. No such sequential expression pattern is observed in endodermal, epidermal or neural tissues of either the larva or the presumptive juvenile sea urchin. The spatial expression patterns of the Hox genes illuminate the evolutionary process by which the pentameral echinoderm body plan emerged from a bilateral ancestor.

Analyzing gene expression time-courses based on multi-resolution shape mixture model.

PubMed

Li, Ying; He, Ye; Zhang, Yu

2016-11-01

Biological processes actually are a dynamic molecular process over time. Time course gene expression experiments provide opportunities to explore patterns of gene expression change over a time and understand the dynamic behavior of gene expression, which is crucial for study on development and progression of biology and disease. Analysis of the gene expression time-course profiles has not been fully exploited so far. It is still a challenge problem. We propose a novel shape-based mixture model clustering method for gene expression time-course profiles to explore the significant gene groups. Based on multi-resolution fractal features and mixture clustering model, we proposed a multi-resolution shape mixture model algorithm. Multi-resolution fractal features is computed by wavelet decomposition, which explore patterns of change over time of gene expression at different resolution. Our proposed multi-resolution shape mixture model algorithm is a probabilistic framework which offers a more natural and robust way of clustering time-course gene expression. We assessed the performance of our proposed algorithm using yeast time-course gene expression profiles compared with several popular clustering methods for gene expression profiles. The grouped genes identified by different methods are evaluated by enrichment analysis of biological pathways and known protein-protein interactions from experiment evidence. The grouped genes identified by our proposed algorithm have more strong biological significance. A novel multi-resolution shape mixture model algorithm based on multi-resolution fractal features is proposed. Our proposed model provides a novel horizons and an alternative tool for visualization and analysis of time-course gene expression profiles. The R and Matlab program is available upon the request. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative developmental transcriptomes of the Mediterranean sea urchin Paracentrotus lividus.

PubMed

Gildor, Tsvia; Malik, Assaf; Sher, Noa; Avraham, Linor; Ben-Tabou de-Leon, Smadar

2016-02-01

Embryonic development progresses through the timely activation of thousands of differentially activated genes. Quantitative developmental transcriptomes provide the means to relate global patterns of differentially expressed genes to the emerging body plans they generate. The sea urchin is one of the classic model systems for embryogenesis and the models of its developmental gene regulatory networks are of the most comprehensive of their kind. Thus, the sea urchin embryo is an excellent system for studies of its global developmental transcriptional profiles. Here we produced quantitative developmental transcriptomes of the sea urchin Paracentrotus lividus (P. lividus) at seven developmental stages from the fertilized egg to prism stage. We generated de-novo reference transcriptome and identified 29,817 genes that are expressed at this time period. We annotated and quantified gene expression at the different developmental stages and confirmed the reliability of the expression profiles by QPCR measurement of a subset of genes. The progression of embryo development is reflected in the observed global expression patterns and in our principle component analysis. Our study illuminates the rich patterns of gene expression that participate in sea urchin embryogenesis and provide an essential resource for further studies of the dynamic expression of P. lividus genes. Copyright © 2015 Elsevier B.V. All rights reserved.

A proteomic chronology of gene expression through the cell cycle in human myeloid leukemia cells.

PubMed

Ly, Tony; Ahmad, Yasmeen; Shlien, Adam; Soroka, Dominique; Mills, Allie; Emanuele, Michael J; Stratton, Michael R; Lamond, Angus I

2014-01-01

Technological advances have enabled the analysis of cellular protein and RNA levels with unprecedented depth and sensitivity, allowing for an unbiased re-evaluation of gene regulation during fundamental biological processes. Here, we have chronicled the dynamics of protein and mRNA expression levels across a minimally perturbed cell cycle in human myeloid leukemia cells using centrifugal elutriation combined with mass spectrometry-based proteomics and RNA-Seq, avoiding artificial synchronization procedures. We identify myeloid-specific gene expression and variations in protein abundance, isoform expression and phosphorylation at different cell cycle stages. We dissect the relationship between protein and mRNA levels for both bulk gene expression and for over ∼6000 genes individually across the cell cycle, revealing complex, gene-specific patterns. This data set, one of the deepest surveys to date of gene expression in human cells, is presented in an online, searchable database, the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd/). DOI: http://dx.doi.org/10.7554/eLife.01630.001.

A proteomic chronology of gene expression through the cell cycle in human myeloid leukemia cells

PubMed Central

Ly, Tony; Ahmad, Yasmeen; Shlien, Adam; Soroka, Dominique; Mills, Allie; Emanuele, Michael J; Stratton, Michael R; Lamond, Angus I

2014-01-01

Technological advances have enabled the analysis of cellular protein and RNA levels with unprecedented depth and sensitivity, allowing for an unbiased re-evaluation of gene regulation during fundamental biological processes. Here, we have chronicled the dynamics of protein and mRNA expression levels across a minimally perturbed cell cycle in human myeloid leukemia cells using centrifugal elutriation combined with mass spectrometry-based proteomics and RNA-Seq, avoiding artificial synchronization procedures. We identify myeloid-specific gene expression and variations in protein abundance, isoform expression and phosphorylation at different cell cycle stages. We dissect the relationship between protein and mRNA levels for both bulk gene expression and for over ∼6000 genes individually across the cell cycle, revealing complex, gene-specific patterns. This data set, one of the deepest surveys to date of gene expression in human cells, is presented in an online, searchable database, the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd/). DOI: http://dx.doi.org/10.7554/eLife.01630.001 PMID:24596151

Dynamic model based on voltage transfer curve for pattern formation in dielectric barrier glow discharge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Ben; He, Feng; Ouyang, Jiting, E-mail: jtouyang@bit.edu.cn

2015-12-15

Simulation work is very important for understanding the formation of self-organized discharge patterns. Previous works have witnessed different models derived from other systems for simulation of discharge pattern, but most of these models are complicated and time-consuming. In this paper, we introduce a convenient phenomenological dynamic model based on the basic dynamic process of glow discharge and the voltage transfer curve (VTC) to study the dielectric barrier glow discharge (DBGD) pattern. VTC is an important characteristic of DBGD, which plots the change of wall voltage after a discharge as a function of the initial total gap voltage. In the modeling,more » the combined effect of the discharge conditions is included in VTC, and the activation-inhibition effect is expressed by a spatial interaction term. Besides, the model reduces the dimensionality of the system by just considering the integration effect of current flow. All these greatly facilitate the construction of this model. Numerical simulations turn out to be in good accordance with our previous fluid modeling and experimental result.« less

Generative Models of Segregation: Investigating Model-Generated Patterns of Residential Segregation by Ethnicity and Socioeconomic Status

PubMed Central

Fossett, Mark

2011-01-01

This paper considers the potential for using agent models to explore theories of residential segregation in urban areas. Results of generative experiments conducted using an agent-based simulation of segregation dynamics document that varying a small number of model parameters representing constructs from urban-ecological theories of segregation can generate a wide range of qualitatively distinct and substantively interesting segregation patterns. The results suggest how complex, macro-level patterns of residential segregation can arise from a small set of simple micro-level social dynamics operating within particular urban-demographic contexts. The promise and current limitations of agent simulation studies are noted and optimism is expressed regarding the potential for such studies to engage and contribute to the broader research literature on residential segregation. PMID:21379372

Commensal-Associated Molecular Patterns Induce Selective Toll-Like Receptor-Trafficking from Apical Membrane to Cytoplasmic Compartments in Polarized Intestinal Epithelium

PubMed Central

Cario, Elke; Brown, Dennis; McKee, Mary; Lynch-Devaney, Kathryn; Gerken, Guido; Podolsky, Daniel K.

2002-01-01

Commensal-associated molecular patterns, the major products of nonpathogenic bacteria, are present at high concentrations at the apical surface of the intestinal epithelium. However, the nature of the interaction of commensal-associated molecular patterns with the lumenal surface of the epithelium has not been defined. We have recently demonstrated that intestinal epithelial cells constitutively express several Toll-like receptors (TLRs) in vitro and in vivo that seem to be the key receptors responsible for immune cell activation in response to various bacterial products. In this study we characterize the subcellular distribution of two major TLRs, TLR2 and TLR4, and their ligand-specific dynamic regulation in the model human intestinal epithelial cell line T84. Immunocytochemical studies indicate that TLR2 and TLR4 are constitutively expressed at the apical pole of differentiated T84 cells. After stimulation with lipopolysaccharide or peptidoglycan, TLRs selectively traffic to cytoplasmic compartments near the basolateral membrane. Thus, we demonstrate that TLRs are positioned at the apical pole where they are poised to monitor the sensitive balance of the lumenal microbial array. The results of this dynamic epithelial surveillance can then be conveyed to the underlying cell populations of the lamina propria via these innate immune pattern recognition receptors. PMID:11786410

Investigating circular patterns in linear polarization observations of Venus

NASA Astrophysics Data System (ADS)

Mahapatra, Gourav; Stam, Daphne; Rossi, Loic; Rodenhuis, Michiel; Snik, Frans

2017-04-01

ESA's Venus Express mission has revealed our neighbouring planet to be a highly dynamic world, with ever-changing cloud properties and structures, wind speeds that increase in time, and variable concentrations of atmospheric trace gases such as SO2. The SPICAV-IR instrument on Venus Express has provided us with close-up linear polarization data of sunlight reflected by Venus's clouds and hazes, that allows a characterisation of their composition and particle sizes. Here, we analyse linear polarization data of the planet at a distance, obtained with the Extreme Polarimeter (ExPo) on the William Herschel Telescope on La Palma. These spatially resolved, high-accuracy polarization observations of Venus show faint circular patterns centered on the sub-solar point that are absent in the flux observations. So far, careful analyses have ruled out instrumental effects which leaves us to wonder about atmospheric properties as the cause of the circular patterns. Using numerical simulations of the flux and polarization of sunlight that is reflected by Venus, we have investigated the relation between the observed patterns and several atmospheric properties, such as variations in particle sizes, composition, density and altitude. We discuss the plausibility of the possible causes in the view of the current knowledge of the composition and dynamical processes in Venus's atmosphere.

Stage-specific differential gene expression profiling and functional network analysis during morphogenesis of diphyodont dentition in miniature pigs, Sus Scrofa

PubMed Central

2014-01-01

Background Our current knowledge of tooth development derives mainly from studies in mice, which have only one set of non-replaced teeth, compared with the diphyodont dentition in humans. The miniature pig is also diphyodont, making it a valuable alternative model for understanding human tooth development and replacement. However, little is known about gene expression and function during swine odontogenesis. The goal of this study is to undertake the survey of differential gene expression profiling and functional network analysis during morphogenesis of diphyodont dentition in miniature pigs. The identification of genes related to diphyodont development should lead to a better understanding of morphogenetic patterns and the mechanisms of diphyodont replacement in large animal models and humans. Results The temporal gene expression profiles during early diphyodont development in miniature pigs were detected with the Affymetrix Porcine GeneChip. The gene expression data were further evaluated by ANOVA as well as pathway and STC analyses. A total of 2,053 genes were detected with differential expression. Several signal pathways and 151 genes were then identified through the construction of pathway and signal networks. Conclusions The gene expression profiles indicated that spatio-temporal down-regulation patterns of gene expression were predominant; while, both dynamic activation and inhibition of pathways occurred during the morphogenesis of diphyodont dentition. Our study offers a mechanistic framework for understanding dynamic gene regulation of early diphyodont development and provides a molecular basis for studying teeth development, replacement, and regeneration in miniature pigs. PMID:24498892

Specifying structural constraints of architectural patterns in the ARCHERY language

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanchez, Alejandro; HASLab INESC TEC and Universidade do Minho, Campus de Gualtar, 4710-057 Braga; Barbosa, Luis S.

ARCHERY is an architectural description language for modelling and reasoning about distributed, heterogeneous and dynamically reconfigurable systems in terms of architectural patterns. The language supports the specification of architectures and their reconfiguration. This paper introduces a language extension for precisely describing the structural design decisions that pattern instances must respect in their (re)configurations. The extension is a propositional modal logic with recursion and nominals referencing components, i.e., a hybrid µ-calculus. Its expressiveness allows specifying safety and liveness constraints, as well as paths and cycles over structures. Refinements of classic architectural patterns are specified.

A Conserved Developmental Patterning Network Produces Quantitatively Different Output in Multiple Species of Drosophila

PubMed Central

Meyer, Miriah; Wunderlich, Zeba; Simirenko, Lisa; Luengo Hendriks, Cris L.; Keränen, Soile V. E.; Henriquez, Clara; Knowles, David W.; Biggin, Mark D.; Eisen, Michael B.; DePace, Angela H.

2011-01-01

Differences in the level, timing, or location of gene expression can contribute to alternative phenotypes at the molecular and organismal level. Understanding the origins of expression differences is complicated by the fact that organismal morphology and gene regulatory networks could potentially vary even between closely related species. To assess the scope of such changes, we used high-resolution imaging methods to measure mRNA expression in blastoderm embryos of Drosophila yakuba and Drosophila pseudoobscura and assembled these data into cellular resolution atlases, where expression levels for 13 genes in the segmentation network are averaged into species-specific, cellular resolution morphological frameworks. We demonstrate that the blastoderm embryos of these species differ in their morphology in terms of size, shape, and number of nuclei. We present an approach to compare cellular gene expression patterns between species, while accounting for varying embryo morphology, and apply it to our data and an equivalent dataset for Drosophila melanogaster. Our analysis reveals that all individual genes differ quantitatively in their spatio-temporal expression patterns between these species, primarily in terms of their relative position and dynamics. Despite many small quantitative differences, cellular gene expression profiles for the whole set of genes examined are largely similar. This suggests that cell types at this stage of development are conserved, though they can differ in their relative position by up to 3–4 cell widths and in their relative proportion between species by as much as 5-fold. Quantitative differences in the dynamics and relative level of a subset of genes between corresponding cell types may reflect altered regulatory functions between species. Our results emphasize that transcriptional networks can diverge over short evolutionary timescales and that even small changes can lead to distinct output in terms of the placement and number of equivalent cells. PMID:22046143

Transcript Profiling Identifies Dynamic Gene Expression Patterns and an Important Role for Nrf2/Keap1 Pathway in the Developing Mouse Esophagus

PubMed Central

Li, Haiyan; Hu, Yuhui; Tevebaugh, Whitney; Yamamoto, Masayuki; Que, Jianwen; Chen, Xiaoxin

2012-01-01

Background and Aims Morphological changes during human and mouse esophageal development have been well characterized. However, changes at the molecular level in the course of esophageal morphogenesis remain unclear. This study aims to globally profile critical genes and signaling pathways during the development of mouse esophagus. By using microarray analysis this study also aims to determine how the Nrf2/Keap1 pathway regulates the morphogenesis of the esophageal epithelium. Methods Gene expression microarrays were used to survey gene expression in the esophagus at three critical phases: specification, metaplasia and maturation. The esophagi were isolated from wild-type, Nrf2−/−, Keap1−/−, or Nrf2−/−Keap1−/− embryos or young adult mice. Array data were statistically analyzed for differentially expressed genes and pathways. Histochemical and immunohistochemical staining were used to verify potential involvement of the Wnt pathway, Pparβ/δ and the PI3K/Akt pathway in the development of esophageal epithelium. Results Dynamic gene expression patterns accompanied the morphological changes of the developing esophagus at critical phases. Particularly, the Nrf2/Keap1 pathway had a baseline activity in the metaplasia phase and was further activated in the maturation phase. The Wnt pathway was active early and became inactive later in the metaplasia phase. In addition, Keap1−/− mice showed increased expression of Nrf2 downstream targets and genes involved in keratinization. Microarray and immunostaining data also suggested that esophageal hyperkeratosis in the Keap1−/− mice was due to activation of Pparβ/δ and the PI3K/Akt pathway. Conclusions Morphological changes of the esophageal epithelium are associated with dynamic changes in gene expression. Nrf2/Keap1 pathway activity is required for maturation of mouse esophageal epithelium. PMID:22567161

Divergent Expression Patterns and Function Implications of Four nanos Genes in a Hermaphroditic Fish, Epinephelus coioides.

PubMed

Sun, Zhi-Hui; Wang, Yang; Lu, Wei-Jia; Li, Zhi; Liu, Xiao-Chun; Li, Shui-Sheng; Zhou, Li; Gui, Jian-Fang

2017-03-23

Multiple nanos genes have been characterized in several fishes, but the functional implications of their various expression patterns remain unclear. In this study, we identified and characterized four nanos genes from a hermaphroditic fish orange-spotted grouper, Epinephelus coioides . Ecnanos1a and Ecnanos1b show divergent expression patterns, and the dynamic expression change of Ecnanos1a in pituitaries during sex change is associated with testis differentiation and spermatogenesis. Ecnanos2 and Ecnanos3 might be germline stem cells (GSCs) and primordial germ cells (PGCs)-specific markers, respectively. Significantly, Ecnanos3 3'-untranslated region (UTR) is necessary for PGC specific expression, where a non-canonical "GCACGTTT" sequence is required for miR-430-mediated repression of Ecnanos3 RNA. Furthermore, grouper Dead end (Dnd) can relieve miR-430 repression in PGCs by associating with a 23 bp U-rich region (URR) in Ecnanos3 3'-UTR. The current study revealed the functional association of multiple nanos genes with PGC formation and germ cell development in orange-spotted grouper, and opened up new possibilities for developing biotechnologies through utilizing the associations between Ecnanos3 and PGCs or between Ecnanos2 and GSCs in the hermaphroditic fish.

Dynamized Preparations in Cell Culture

PubMed Central

Sunila, Ellanzhiyil Surendran; Preethi, Korengath Chandran; Kuttan, Girija

2009-01-01

Although reports on the efficacy of homeopathic medicines in animal models are limited, there are even fewer reports on the in vitro action of these dynamized preparations. We have evaluated the cytotoxic activity of 30C and 200C potencies of ten dynamized medicines against Dalton's Lymphoma Ascites, Ehrlich's Ascites Carcinoma, lung fibroblast (L929) and Chinese Hamster Ovary (CHO) cell lines and compared activity with their mother tinctures during short-term and long-term cell culture. The effect of dynamized medicines to induce apoptosis was also evaluated and we studied how dynamized medicines affected genes expressed during apoptosis. Mother tinctures as well as some dynamized medicines showed significant cytotoxicity to cells during short and long-term incubation. Potentiated alcohol control did not produce any cytotoxicity at concentrations studied. The dynamized medicines were found to inhibit CHO cell colony formation and thymidine uptake in L929 cells and those of Thuja, Hydrastis and Carcinosinum were found to induce apoptosis in DLA cells. Moreover, dynamized Carcinosinum was found to induce the expression of p53 while dynamized Thuja produced characteristic laddering pattern in agarose gel electrophoresis of DNA. These results indicate that dynamized medicines possess cytotoxic as well as apoptosis-inducing properties. PMID:18955237

Transcriptomic and metabolite analyses of Cabernet Sauvignon grape berry development.

PubMed

Deluc, Laurent G; Grimplet, Jérôme; Wheatley, Matthew D; Tillett, Richard L; Quilici, David R; Osborne, Craig; Schooley, David A; Schlauch, Karen A; Cushman, John C; Cramer, Grant R

2007-11-22

Grape berry development is a dynamic process that involves a complex series of molecular genetic and biochemical changes divided into three major phases. During initial berry growth (Phase I), berry size increases along a sigmoidal growth curve due to cell division and subsequent cell expansion, and organic acids (mainly malate and tartrate), tannins, and hydroxycinnamates accumulate to peak levels. The second major phase (Phase II) is defined as a lag phase in which cell expansion ceases and sugars begin to accumulate. Véraison (the onset of ripening) marks the beginning of the third major phase (Phase III) in which berries undergo a second period of sigmoidal growth due to additional mesocarp cell expansion, accumulation of anthocyanin pigments for berry color, accumulation of volatile compounds for aroma, softening, peak accumulation of sugars (mainly glucose and fructose), and a decline in organic acid accumulation. In order to understand the transcriptional network responsible for controlling berry development, mRNA expression profiling was conducted on berries of V. vinifera Cabernet Sauvignon using the Affymetrix GeneChip Vitis oligonucleotide microarray ver. 1.0 spanning seven stages of berry development from small pea size berries (E-L stages 31 to 33 as defined by the modified E-L system), through véraison (E-L stages 34 and 35), to mature berries (E-L stages 36 and 38). Selected metabolites were profiled in parallel with mRNA expression profiling to understand the effect of transcriptional regulatory processes on specific metabolite production that ultimately influence the organoleptic properties of wine. Over the course of berry development whole fruit tissues were found to express an average of 74.5% of probes represented on the Vitis microarray, which has 14,470 Unigenes. Approximately 60% of the expressed transcripts were differentially expressed between at least two out of the seven stages of berry development (28% of transcripts, 4,151 Unigenes, had pronounced (> or =2 fold) differences in mRNA expression) illustrating the dynamic nature of the developmental process. The subset of 4,151 Unigenes was split into twenty well-correlated expression profiles. Expression profile patterns included those with declining or increasing mRNA expression over the course of berry development as well as transient peak or trough patterns across various developmental stages as defined by the modified E-L system. These detailed surveys revealed the expression patterns for genes that play key functional roles in phytohormone biosynthesis and response, calcium sequestration, transport and signaling, cell wall metabolism mediating expansion, ripening, and softening, flavonoid metabolism and transport, organic and amino acid metabolism, hexose sugar and triose phosphate metabolism and transport, starch metabolism, photosynthesis, circadian cycles and pathogen resistance. In particular, mRNA expression patterns of transcription factors, abscisic acid (ABA) biosynthesis, and calcium signaling genes identified candidate factors likely to participate in the progression of key developmental events such as véraison and potential candidate genes associated with such processes as auxin partitioning within berry cells, aroma compound production, and pathway regulation and sequestration of flavonoid compounds. Finally, analysis of sugar metabolism gene expression patterns indicated the existence of an alternative pathway for glucose and triose phosphate production that is invoked from véraison to mature berries. These results reveal the first high-resolution picture of the transcriptome dynamics that occur during seven stages of grape berry development. This work also establishes an extensive catalog of gene expression patterns for future investigations aimed at the dissection of the transcriptional regulatory hierarchies that govern berry development in a widely grown cultivar of wine grape. More importantly, this analysis identified a set of previously unknown genes potentially involved in critical steps associated with fruit development that can now be subjected to functional testing.

Transcriptomic and metabolite analyses of Cabernet Sauvignon grape berry development

PubMed Central

Deluc, Laurent G; Grimplet, Jérôme; Wheatley, Matthew D; Tillett, Richard L; Quilici, David R; Osborne, Craig; Schooley, David A; Schlauch, Karen A; Cushman, John C; Cramer, Grant R

2007-01-01

Background Grape berry development is a dynamic process that involves a complex series of molecular genetic and biochemical changes divided into three major phases. During initial berry growth (Phase I), berry size increases along a sigmoidal growth curve due to cell division and subsequent cell expansion, and organic acids (mainly malate and tartrate), tannins, and hydroxycinnamates accumulate to peak levels. The second major phase (Phase II) is defined as a lag phase in which cell expansion ceases and sugars begin to accumulate. Véraison (the onset of ripening) marks the beginning of the third major phase (Phase III) in which berries undergo a second period of sigmoidal growth due to additional mesocarp cell expansion, accumulation of anthocyanin pigments for berry color, accumulation of volatile compounds for aroma, softening, peak accumulation of sugars (mainly glucose and fructose), and a decline in organic acid accumulation. In order to understand the transcriptional network responsible for controlling berry development, mRNA expression profiling was conducted on berries of V. vinifera Cabernet Sauvignon using the Affymetrix GeneChip® Vitis oligonucleotide microarray ver. 1.0 spanning seven stages of berry development from small pea size berries (E-L stages 31 to 33 as defined by the modified E-L system), through véraison (E-L stages 34 and 35), to mature berries (E-L stages 36 and 38). Selected metabolites were profiled in parallel with mRNA expression profiling to understand the effect of transcriptional regulatory processes on specific metabolite production that ultimately influence the organoleptic properties of wine. Results Over the course of berry development whole fruit tissues were found to express an average of 74.5% of probes represented on the Vitis microarray, which has 14,470 Unigenes. Approximately 60% of the expressed transcripts were differentially expressed between at least two out of the seven stages of berry development (28% of transcripts, 4,151 Unigenes, had pronounced (≥2 fold) differences in mRNA expression) illustrating the dynamic nature of the developmental process. The subset of 4,151 Unigenes was split into twenty well-correlated expression profiles. Expression profile patterns included those with declining or increasing mRNA expression over the course of berry development as well as transient peak or trough patterns across various developmental stages as defined by the modified E-L system. These detailed surveys revealed the expression patterns for genes that play key functional roles in phytohormone biosynthesis and response, calcium sequestration, transport and signaling, cell wall metabolism mediating expansion, ripening, and softening, flavonoid metabolism and transport, organic and amino acid metabolism, hexose sugar and triose phosphate metabolism and transport, starch metabolism, photosynthesis, circadian cycles and pathogen resistance. In particular, mRNA expression patterns of transcription factors, abscisic acid (ABA) biosynthesis, and calcium signaling genes identified candidate factors likely to participate in the progression of key developmental events such as véraison and potential candidate genes associated with such processes as auxin partitioning within berry cells, aroma compound production, and pathway regulation and sequestration of flavonoid compounds. Finally, analysis of sugar metabolism gene expression patterns indicated the existence of an alternative pathway for glucose and triose phosphate production that is invoked from véraison to mature berries. Conclusion These results reveal the first high-resolution picture of the transcriptome dynamics that occur during seven stages of grape berry development. This work also establishes an extensive catalog of gene expression patterns for future investigations aimed at the dissection of the transcriptional regulatory hierarchies that govern berry development in a widely grown cultivar of wine grape. More importantly, this analysis identified a set of previously unknown genes potentially involved in critical steps associated with fruit development that can now be subjected to functional testing. PMID:18034876

Molecular anatomy of the developing limb in the coquí frog, Eleutherodactylus coqui.

PubMed

Gross, Joshua B; Kerney, Ryan; Hanken, James; Tabin, Clifford J

2011-01-01

The vertebrate limb demonstrates remarkable similarity in basic organization across phylogenetically disparate groups. To gain further insight into how this morphological similarity is maintained in different developmental contexts, we explored the molecular anatomy of size-reduced embryos of the Puerto Rican coquí frog, Eleutherodactylus coqui. This animal demonstrates direct development, a life-history strategy marked by rapid progression from egg to adult and absence of a free-living, aquatic larva. Nonetheless, coquí exhibits a basal anuran limb structure, with four toes on the forelimb and five toes on the hind limb. We investigated the extent to which coquí limb bud development conforms to the model of limb development derived from amniote studies. Toward this end, we characterized dynamic patterns of expression for 13 critical patterning genes across three principle stages of limb development. As expected, most genes demonstrate expression patterns that are essentially unchanged compared to amniote species. For example, we identified an EcFgf8-expression domain within the apical ectodermal ridge (AER). This expression pattern defines a putatively functional AER signaling domain, despite the absence of a morphological ridge in coquí embryos. However, two genes, EcMeis2 and EcAlx4, demonstrate altered domains of expression, which imply a potential shift in gene function between coquí frogs and amniote model systems. Unexpectedly, several genes thought to be critical for limb patterning in other systems, including EcFgf4, EcWnt3a, EcWnt7a, and EcGremlin, demonstrated no evident expression pattern in the limb at the three stages we analyzed. The absence of EcFgf4 and EcWnt3a expression during limb patterning is perhaps not surprising, given that neither gene is critical for proper limb development in the mouse, based on knockout and expression analyses. In contrast, absence of EcWnt7a and EcGremlin is surprising, given that expression of these molecules appears to be absolutely essential in all other model systems so far examined. Although this analysis substantiates the existence of a core set of ancient limb-patterning molecules, which likely mediate identical functions across highly diverse vertebrate forms, it also reveals remarkable evolutionary flexibility in the genetic control of a conserved morphological pattern across evolutionary time. © 2011 Wiley Periodicals, Inc.

The tailless Ortholog nhr-67 Regulates Patterning of Gene Expression and Morphogenesis in the C. elegans Vulva

PubMed Central

Fernandes, Jolene S; Sternberg, Paul W

2007-01-01

Regulation of spatio-temporal gene expression in diverse cell and tissue types is a critical aspect of development. Progression through Caenorhabditis elegans vulval development leads to the generation of seven distinct vulval cell types (vulA, vulB1, vulB2, vulC, vulD, vulE, and vulF), each with its own unique gene expression profile. The mechanisms that establish the precise spatial patterning of these mature cell types are largely unknown. Dissection of the gene regulatory networks involved in vulval patterning and differentiation would help us understand how cells generate a spatially defined pattern of cell fates during organogenesis. We disrupted the activity of 508 transcription factors via RNAi and assayed the expression of ceh-2, a marker for vulB fate during the L4 stage. From this screen, we identified the tailless ortholog nhr-67 as a novel regulator of gene expression in multiple vulval cell types. We find that one way in which nhr-67 maintains cell identity is by restricting inappropriate cell fusion events in specific vulval cells, namely vulE and vulF. nhr-67 exhibits a dynamic expression pattern in the vulval cells and interacts with three other transcriptional regulators cog-1 (Nkx6.1/6.2), lin-11 (LIM), and egl-38 (Pax2/5/8) to generate the composite expression patterns of their downstream targets. We provide evidence that egl-38 regulates gene expression in vulB1, vulC, vulD, vulE, as well as vulF cells. We demonstrate that the pairwise interactions between these regulatory genes are complex and vary among the seven cell types. We also discovered a striking regulatory circuit that affects a subset of the vulval lineages: cog-1 and nhr-67 inhibit both one another and themselves. We postulate that the differential levels and combinatorial patterns of lin-11, cog-1, and nhr-67 expression are a part of a regulatory code for the mature vulval cell types. PMID:17465684

Dynamic pattern of endothelial cell adhesion molecule expression in muscle and perineural vessels from patients with classic polyarteritis nodosa.

PubMed

Coll-Vinent, B; Cebrián, M; Cid, M C; Font, C; Esparza, J; Juan, M; Yagüe, J; Urbano-Márquez, A; Grau, J M

1998-03-01

To investigate endothelial cell adhesion molecule expression in vessels from patients with classic polyarteritis nodosa (PAN). Frozen sections of 21 muscle and 16 nerve samples from 30 patients with biopsy-proven PAN and 12 histologically normal muscle and 2 histologically normal nerve samples from 12 controls were studied immunohistochemically, using specific monoclonal antibodies (MAb) that recognize adhesion molecules. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lymphocyte function-associated antigen 1 (LFA-1), and very late activation antigen 4 (VLA-4). Neutrophils were identified with a MAb recognizing neutrophil elastase. Endothelial cells were identified with the lectin ulex europaeus. In early lesions, expression of PECAM-1, ICAM-1, ICAM-2, and P-selectin was similar to that in control samples, and VCAM-1 and E-selectin were induced in vascular endothelium. In advanced lesions, immunostaining for adhesion molecules diminished or disappeared in luminal endothelium, whereas these molecules were clearly expressed in microvessels within and surrounding inflamed vessels. Staining in endothelia from vessels in a healing stage tended to be negative. A high proportion of infiltrating leukocytes expressed LFA-1 and VLA-4, and only a minority expressed L-selectin. No relationship between the expression pattern of adhesion molecules and clinical features, disease duration, or previous corticosteroid treatment was observed. Endothelial adhesion molecule expression in PAN is a dynamic process that varies according to the histopathologic stage of the vascular lesions. The preferential expression of constitutive and inducible adhesion molecules in microvessels suggests that angiogenesis contributes to the persistence of inflammatory infiltration in PAN.

Dynamic processes at stress promoters regulate the bimodal expression of HOG response genes

PubMed Central

2011-01-01

Osmotic stress triggers the activation of the HOG (high osmolarity glycerol) pathway in Saccharomyces cerevisiae. This signaling cascade culminates in the activation of the MAPK (mitogen-activated protein kinase) Hog1. Quantitative single cell measurements revealed a discrepancy between kinase- and transcriptional activities of Hog1. While kinase activity increases proportionally to stress stimulus, gene expression is inhibited under low stress conditions. Interestingly, a slow stochastic gene activation process is responsible for setting a tunable threshold for gene expression under basal or low stress conditions, which generates a bimodal expression pattern at intermediate stress levels. PMID:22446531

Generation of Pax6-IRES-EGFP knock-in mouse via the cloning-free CRISPR/Cas9 system to reliably visualize neurodevelopmental dynamics.

PubMed

Inoue, Yukiko U; Morimoto, Yuki; Hoshino, Mikio; Inoue, Takayoshi

2018-07-01

Pax6 encodes a transcription factor that plays pivotal roles in eye development, early brain patterning, neocortical arealization, and so forth. Visualization of Pax6 expression dynamics in these events could offer numerous advantages to neurodevelopmental studies. While CRISPR/Cas9 system has dramatically accelerated one-step generation of knock-out mouse, establishment of gene-cassette knock-in mouse via zygote injection has been considered insufficient due to its low efficiency. Recently, an improved CRISPR/Cas9 system for effective gene-cassette knock-in has been reported, where the native form of guide RNAs (crRNA and tracrRNA) assembled with recombinant Cas9 protein are directly delivered into mouse fertilized eggs. Here we apply this strategy to insert IRES-EGFP-pA cassette into Pax6 locus and achieve efficient targeted insertions of the 1.8 kb reporter gene. In Pax6-IRES-EGFP mouse we have generated, EGFP-positive cells reside in the eyes and cerebellum as endogenous Pax6 expressing cells at postnatal day 2. At the early embryonic stages when the embryos are transparent, EGFP-positive regions can be easily identified without PCR-based genotyping, precisely recapitulating the endogenous Pax6 expression patterns. Remarkably, at E12.5, the graded expression patterns of Pax6 in the developing neocortex now become recognizable in our knock-in mice, serving a sufficiently sensitive and useful tool to precisely visualize neurodevelopmental processes. Copyright © 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

The roles of ERAS during cell lineage specification of mouse early embryonic development.

PubMed

Zhao, Zhen-Ao; Yu, Yang; Ma, Huai-Xiao; Wang, Xiao-Xiao; Lu, Xukun; Zhai, Yanhua; Zhang, Xiaoxin; Wang, Haibin; Li, Lei

2015-08-01

Eras encodes a Ras-like GTPase protein that was originally identified as an embryonic stem cell-specific Ras. ERAS has been known to be required for the growth of embryonic stem cells and stimulates somatic cell reprogramming, suggesting its roles on mouse early embryonic development. We now report a dynamic expression pattern of Eras during mouse peri-implantation development: its expression increases at the blastocyst stage, and specifically decreases in E7.5 mesoderm. In accordance with its expression pattern, the increased expression of Eras promotes cell proliferation through controlling AKT activation and the commitment from ground to primed state through ERK activation in mouse embryonic stem cells; and the reduced expression of Eras facilitates primitive streak and mesoderm formation through AKT inhibition during gastrulation. The expression of Eras is finely regulated to match its roles in mouse early embryonic development during which Eras expression is negatively regulated by the β-catenin pathway. Thus, beyond its well-known role on cell proliferation, ERAS may also play important roles in cell lineage specification during mouse early embryonic development. © 2015 The Authors.

Single-cell and coupled GRN models of cell patterning in the Arabidopsis thaliana root stem cell niche

PubMed Central

2010-01-01

Background Recent experimental work has uncovered some of the genetic components required to maintain the Arabidopsis thaliana root stem cell niche (SCN) and its structure. Two main pathways are involved. One pathway depends on the genes SHORTROOT and SCARECROW and the other depends on the PLETHORA genes, which have been proposed to constitute the auxin readouts. Recent evidence suggests that a regulatory circuit, composed of WOX5 and CLE40, also contributes to the SCN maintenance. Yet, we still do not understand how the niche is dynamically maintained and patterned or if the uncovered molecular components are sufficient to recover the observed gene expression configurations that characterize the cell types within the root SCN. Mathematical and computational tools have proven useful in understanding the dynamics of cell differentiation. Hence, to further explore root SCN patterning, we integrated available experimental data into dynamic Gene Regulatory Network (GRN) models and addressed if these are sufficient to attain observed gene expression configurations in the root SCN in a robust and autonomous manner. Results We found that an SCN GRN model based only on experimental data did not reproduce the configurations observed within the root SCN. We developed several alternative GRN models that recover these expected stable gene configurations. Such models incorporate a few additional components and interactions in addition to those that have been uncovered. The recovered configurations are stable to perturbations, and the models are able to recover the observed gene expression profiles of almost all the mutants described so far. However, the robustness of the postulated GRNs is not as high as that of other previously studied networks. Conclusions These models are the first published approximations for a dynamic mechanism of the A. thaliana root SCN cellular pattering. Our model is useful to formally show that the data now available are not sufficient to fully reproduce root SCN organization and genetic profiles. We then highlight some experimental holes that remain to be studied and postulate some novel gene interactions. Finally, we suggest the existence of a generic dynamical motif that can be involved in both plant and animal SCN maintenance. PMID:20920363

Disentangling dynamic networks: Separated and joint expressions of functional connectivity patterns in time.

PubMed

Leonardi, Nora; Shirer, William R; Greicius, Michael D; Van De Ville, Dimitri

2014-12-01

Resting-state functional connectivity (FC) is highly variable across the duration of a scan. Groups of coevolving connections, or reproducible patterns of dynamic FC (dFC), have been revealed in fluctuating FC by applying unsupervised learning techniques. Based on results from k-means clustering and sliding-window correlations, it has recently been hypothesized that dFC may cycle through several discrete FC states. Alternatively, it has been proposed to represent dFC as a linear combination of multiple FC patterns using principal component analysis. As it is unclear whether sparse or nonsparse combinations of FC patterns are most appropriate, and as this affects their interpretation and use as markers of cognitive processing, the goal of our study was to evaluate the impact of sparsity by performing an empirical evaluation of simulated, task-based, and resting-state dFC. To this aim, we applied matrix factorizations subject to variable constraints in the temporal domain and studied both the reproducibility of ensuing representations of dFC and the expression of FC patterns over time. During subject-driven tasks, dFC was well described by alternating FC states in accordance with the nature of the data. The estimated FC patterns showed a rich structure with combinations of known functional networks enabling accurate identification of three different tasks. During rest, dFC was better described by multiple FC patterns that overlap. The executive control networks, which are critical for working memory, appeared grouped alternately with externally or internally oriented networks. These results suggest that combinations of FC patterns can provide a meaningful way to disentangle resting-state dFC. © 2014 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.

Isolation and expression of scabrous, a gene regulating neurogenesis in Drosophila.

PubMed

Mlodzik, M; Baker, N E; Rubin, G M

1990-11-01

Mutations in the Drosophila scabrous (sca) gene affect eye and bristle development, leading to irregular spacing of ommatidia and bristle duplications in the adult fly. We have cloned the sca gene by P-element tagging. The sca transcription unit is 12 kb and consists of four exons that are joined in a 3.2-kb mRNA. In an enhancer trap screen we have isolated several P[lacZ] insertions close to the sca transcription start site. We have examined the expression pattern of sca by in situ hybridization to sca transcripts, by beta-galactosidase localization in the P[lacZ] lines, and by immunocytochemistry with an anti-sca antiserum. During embryogenesis, sca is expressed in a dynamic pattern associated with neural development. During imaginal development, sca is mainly expressed in the R8 photoreceptor precursor cells in the eye imaginal disc and in sensory organ precursor cells in other discs. In the wing disc, sca expression is coextensive with the anlagen for bristles and is controlled by genes of the achaete-scute complex. Based on its loss-of-function phenotype, expression pattern, and the predicted structure of its product, a secreted peptide with homology to the fibrinogen gene family, we propose that sca encodes a signal involved in lateral inhibition within individual domains of the developing nervous system.

Genomic Imprinting Was Evolutionarily Conserved during Wheat Polyploidization[OPEN

PubMed Central

Yang, Guanghui; Liu, Zhenshan; Gao, Lulu; Yu, Kuohai; Feng, Man; Peng, Huiru; Sun, Qixin; Ni, Zhongfu

2018-01-01

Genomic imprinting is an epigenetic phenomenon that causes genes to be differentially expressed depending on their parent of origin. To evaluate the evolutionary conservation of genomic imprinting and the effects of ploidy on this process, we investigated parent-of-origin-specific gene expression patterns in the endosperm of diploid (Aegilops spp), tetraploid, and hexaploid wheat (Triticum spp) at various stages of development via high-throughput transcriptome sequencing. We identified 91, 135, and 146 maternally or paternally expressed genes (MEGs or PEGs, respectively) in diploid, tetraploid, and hexaploid wheat, respectively, 52.7% of which exhibited dynamic expression patterns at different developmental stages. Gene Ontology enrichment analysis suggested that MEGs and PEGs were involved in metabolic processes and DNA-dependent transcription, respectively. Nearly half of the imprinted genes exhibited conserved expression patterns during wheat hexaploidization. In addition, 40% of the homoeolog pairs originating from whole-genome duplication were consistently maternally or paternally biased in the different subgenomes of hexaploid wheat. Furthermore, imprinted expression was found for 41.2% and 50.0% of homolog pairs that evolved by tandem duplication after genome duplication in tetraploid and hexaploid wheat, respectively. These results suggest that genomic imprinting was evolutionarily conserved between closely related Triticum and Aegilops species and in the face of polyploid hybridization between species in these genera. PMID:29298834

The sensitivity of Turing self-organization to biological feedback delays: 2D models of fish pigmentation.

PubMed

Gaffney, E A; Lee, S Seirin

2015-03-01

Turing morphogen models have been extensively explored in the context of large-scale self-organization in multicellular biological systems. However, reconciling the detailed biology of morphogen dynamics, while accounting for time delays associated with gene expression, reveals aberrant behaviours that are not consistent with early developmental self-organization, especially the requirement for exquisite temporal control. Attempts to reconcile the interpretation of Turing's ideas with an increasing understanding of the mechanisms driving zebrafish pigmentation suggests that one should reconsider Turing's model in terms of pigment cells rather than morphogens (Nakamasu et al., 2009, PNAS, 106: , 8429-8434; Yamaguchi et al., 2007, PNAS, 104: , 4790-4793). Here the dynamics of pigment cells is subject to response delays implicit in the cell cycle and apoptosis. Hence we explore simulations of fish skin patterning, focussing on the dynamical influence of gene expression delays in morphogen-based Turing models and response delays for cell-based Turing models. We find that reconciling the mechanisms driving the behaviour of Turing systems with observations of fish skin patterning remains a fundamental challenge. © The Authors 2013. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

Sterols in spermatogenesis and sperm maturation

PubMed Central

Keber, Rok; Rozman, Damjana; Horvat, Simon

2013-01-01

Mammalian spermatogenesis is a complex developmental program in which a diploid progenitor germ cell transforms into highly specialized spermatozoa. One intriguing aspect of sperm production is the dynamic change in membrane lipid composition that occurs throughout spermatogenesis. Cholesterol content, as well as its intermediates, differs vastly between the male reproductive system and nongonadal tissues. Accumulation of cholesterol precursors such as testis meiosis-activating sterol and desmosterol is observed in testes and spermatozoa from several mammalian species. Moreover, cholesterogenic genes, especially meiosis-activating sterol-producing enzyme cytochrome P450 lanosterol 14α-demethylase, display stage-specific expression patterns during spermatogenesis. Discrepancies in gene expression patterns suggest a complex temporal and cell-type specific regulation of sterol compounds during spermatogenesis, which also involves dynamic interactions between germ and Sertoli cells. The functional importance of sterol compounds in sperm production is further supported by the modulation of sterol composition in spermatozoal membranes during epididymal transit and in the female reproductive tract, which is a prerequisite for successful fertilization. However, the exact role of sterols in male reproduction is unknown. This review discusses sterol dynamics in sperm maturation and describes recent methodological advances that will help to illuminate the complexity of sperm formation and function. PMID:23093550

Multiple abiotic stimuli are integrated in the regulation of rice gene expression under field conditions

PubMed Central

Plessis, Anne; Hafemeister, Christoph; Wilkins, Olivia; Gonzaga, Zennia Jean; Meyer, Rachel Sarah; Pires, Inês; Müller, Christian; Septiningsih, Endang M; Bonneau, Richard; Purugganan, Michael

2015-01-01

Plants rely on transcriptional dynamics to respond to multiple climatic fluctuations and contexts in nature. We analyzed the genome-wide gene expression patterns of rice (Oryza sativa) growing in rainfed and irrigated fields during two distinct tropical seasons and determined simple linear models that relate transcriptomic variation to climatic fluctuations. These models combine multiple environmental parameters to account for patterns of expression in the field of co-expressed gene clusters. We examined the similarities of our environmental models between tropical and temperate field conditions, using previously published data. We found that field type and macroclimate had broad impacts on transcriptional responses to environmental fluctuations, especially for genes involved in photosynthesis and development. Nevertheless, variation in solar radiation and temperature at the timescale of hours had reproducible effects across environmental contexts. These results provide a basis for broad-based predictive modeling of plant gene expression in the field. DOI: http://dx.doi.org/10.7554/eLife.08411.001 PMID:26609814

Genome-wide DNA methylation drives human embryonic stem cell erythropoiesis by remodeling gene expression dynamics.

PubMed

Liu, Zhijing; Feng, Qiang; Sun, Pengpeng; Lu, Yan; Yang, Minlan; Zhang, Xiaowei; Jin, Xiangshu; Li, Yulin; Lu, Shi-Jiang; Quan, Chengshi

2017-12-01

To investigate the role of DNA methylation during erythrocyte production by human embryonic stem cells (hESCs). We employed an erythroid differentiation model from hESCs, and then tracked the genome-wide DNA methylation maps and gene expression patterns through an Infinium HumanMethylation450K BeadChip and an Ilumina Human HT-12 v4 Expression Beadchip, respectively. A negative correlation between DNA methylation and gene expression was substantially enriched during the later differentiation stage and was present in both the promoter and the gene body. Moreover, erythropoietic genes with differentially methylated CpG sites that were primarily enriched in nonisland regions were upregulated, and demethylation of their gene bodies was associated with the presence of enhancers and DNase I hypersensitive sites. Finally, the components of JAK-STAT-NF-κB signaling were DNA hypomethylated and upregulated, which targets the key genes for erythropoiesis. Erythroid lineage commitment by hESCs requires genome-wide DNA methylation modifications to remodel gene expression dynamics.

Caudal Regulates the Spatiotemporal Dynamics of Pair-Rule Waves in Tribolium

PubMed Central

El-Sherif, Ezzat; Zhu, Xin; Fu, Jinping; Brown, Susan J.

2014-01-01

In the short-germ beetle Tribolium castaneum, waves of pair-rule gene expression propagate from the posterior end of the embryo towards the anterior and eventually freeze into stable stripes, partitioning the anterior-posterior axis into segments. Similar waves in vertebrates are assumed to arise due to the modulation of a molecular clock by a posterior-to-anterior frequency gradient. However, neither a molecular candidate nor a functional role has been identified to date for such a frequency gradient, either in vertebrates or elsewhere. Here we provide evidence that the posterior gradient of Tc-caudal expression regulates the oscillation frequency of pair-rule gene expression in Tribolium. We show this by analyzing the spatiotemporal dynamics of Tc-even-skipped expression in strong and mild knockdown of Tc-caudal, and by correlating the extension, level and slope of the Tc-caudal expression gradient to the spatiotemporal dynamics of Tc-even-skipped expression in wild type as well as in different RNAi knockdowns of Tc-caudal regulators. Further, we show that besides its absolute importance for stripe generation in the static phase of the Tribolium blastoderm, a frequency gradient might serve as a buffer against noise during axis elongation phase in Tribolium as well as vertebrates. Our results highlight the role of frequency gradients in pattern formation. PMID:25329152

Transcriptional dynamics of a conserved gene expression network associated with craniofacial divergence in Arctic charr.

PubMed

Ahi, Ehsan Pashay; Kapralova, Kalina Hristova; Pálsson, Arnar; Maier, Valerie Helene; Gudbrandsson, Jóhannes; Snorrason, Sigurdur S; Jónsson, Zophonías O; Franzdóttir, Sigrídur Rut

2014-01-01

Understanding the molecular basis of craniofacial variation can provide insights into key developmental mechanisms of adaptive changes and their role in trophic divergence and speciation. Arctic charr (Salvelinus alpinus) is a polymorphic fish species, and, in Lake Thingvallavatn in Iceland, four sympatric morphs have evolved distinct craniofacial structures. We conducted a gene expression study on candidates from a conserved gene coexpression network, focusing on the development of craniofacial elements in embryos of two contrasting Arctic charr morphotypes (benthic and limnetic). Four Arctic charr morphs were studied: one limnetic and two benthic morphs from Lake Thingvallavatn and a limnetic reference aquaculture morph. The presence of morphological differences at developmental stages before the onset of feeding was verified by morphometric analysis. Following up on our previous findings that Mmp2 and Sparc were differentially expressed between morphotypes, we identified a network of genes with conserved coexpression across diverse vertebrate species. A comparative expression study of candidates from this network in developing heads of the four Arctic charr morphs verified the coexpression relationship of these genes and revealed distinct transcriptional dynamics strongly correlated with contrasting craniofacial morphologies (benthic versus limnetic). A literature review and Gene Ontology analysis indicated that a significant proportion of the network genes play a role in extracellular matrix organization and skeletogenesis, and motif enrichment analysis of conserved noncoding regions of network candidates predicted a handful of transcription factors, including Ap1 and Ets2, as potential regulators of the gene network. The expression of Ets2 itself was also found to associate with network gene expression. Genes linked to glucocorticoid signalling were also studied, as both Mmp2 and Sparc are responsive to this pathway. Among those, several transcriptional targets and upstream regulators showed differential expression between the contrasting morphotypes. Interestingly, although selected network genes showed overlapping expression patterns in situ and no morph differences, Timp2 expression patterns differed between morphs. Our comparative study of transcriptional dynamics in divergent craniofacial morphologies of Arctic charr revealed a conserved network of coexpressed genes sharing functional roles in structural morphogenesis. We also implicate transcriptional regulators of the network as targets for future functional studies.

Gaze Dynamics in the Recognition of Facial Expressions of Emotion.

PubMed

Barabanschikov, Vladimir A

2015-01-01

We studied preferably fixated parts and features of human face in the process of recognition of facial expressions of emotion. Photographs of facial expressions were used. Participants were to categorize these as basic emotions; during this process, eye movements were registered. It was found that variation in the intensity of an expression is mirrored in accuracy of emotion recognition; it was also reflected by several indices of oculomotor function: duration of inspection of certain areas of the face, its upper and bottom or right parts, right and left sides; location, number and duration of fixations, viewing trajectory. In particular, for low-intensity expressions, right side of the face was found to be attended predominantly (right-side dominance); the right-side dominance effect, was, however, absent for expressions of high intensity. For both low- and high-intensity expressions, upper face part was predominantly fixated, though with greater fixation of high-intensity expressions. The majority of trials (70%), in line with findings in previous studies, revealed a V-shaped pattern of inspection trajectory. No relationship, between accuracy of recognition of emotional expressions, was found, though, with either location and duration of fixations or pattern of gaze directedness in the face. © The Author(s) 2015.

Bringing an Ecological Perspective to the Study of Aging and Recognition of Emotional Facial Expressions: Past, Current, and Future Methods

PubMed Central

Isaacowitz, Derek M.; Stanley, Jennifer Tehan

2011-01-01

Older adults perform worse on traditional tests of emotion recognition accuracy than do young adults. In this paper, we review descriptive research to date on age differences in emotion recognition from facial expressions, as well as the primary theoretical frameworks that have been offered to explain these patterns. We propose that this is an area of inquiry that would benefit from an ecological approach in which contextual elements are more explicitly considered and reflected in experimental methods. Use of dynamic displays and examination of specific cues to accuracy, for example, may reveal more nuanced age-related patterns and may suggest heretofore unexplored underlying mechanisms. PMID:22125354

Dynamic Expression of the Translational Machinery during Bacillus subtilis Life Cycle at a Single Cell Level

PubMed Central

Rosenberg, Alex; Sinai, Lior; Smith, Yoav; Ben-Yehuda, Sigal

2012-01-01

The ability of bacteria to responsively regulate the expression of translation components is crucial for rapid adaptation to fluctuating environments. Utilizing Bacillus subtilis (B. subtilis) as a model organism, we followed the dynamics of the translational machinery at a single cell resolution during growth and differentiation. By comprehensive monitoring the activity of the major rrn promoters and ribosomal protein production, we revealed diverse dynamics between cells grown in rich and poor medium, with the most prominent dissimilarities exhibited during deep stationary phase. Further, the variability pattern of translational activity varied among the cells, being affected by nutrient availability. We have monitored for the first time translational dynamics during the developmental process of sporulation within the two distinct cellular compartments of forespore and mother-cell. Our study uncovers a transient forespore specific increase in expression of translational components. Finally, the contribution of each rrn promoter throughout the bacterium life cycle was found to be relatively constant, implying that differential expression is not the main purpose for the existence of multiple rrn genes. Instead, we propose that coordination of the rrn operons serves as a strategy to rapidly fine tune translational activities in a synchronized fashion to achieve an optimal translation level for a given condition. PMID:22848659

Long interspersed nuclear elements (LINEs) show tissue-specific, mosaic genome and methylation-unrestricted, widespread expression of noncoding RNAs in somatic tissues of the rat

PubMed Central

Singh, Deepak K.; Rath, Pramod C.

2012-01-01

We report strong somatic and germ line expression of LINE RNAs in eight different tissues of rat by using a novel ~2.8 kb genomic PstI-LINE DNA (P1-LINE) isolated from the rat brain. P1-LINE is present in a 93 kb LINE-SINE-cluster in sub-telomeric region of chromosome 12 (12p12) and as multiple truncated copies interspersed in all rat chromosomes. P1-LINEs occur as inverted repeats at multiple genomic loci in tissue-specific and mosaic patterns. P1-LINE RNAs are strongly expressed in brain, liver, lungs, heart, kidney, testes, spleen and thymus into large to small heterogeneous RNAs (~5.0 to 0.2 kb) in tissue-specific and dynamic patterns in individual rats. P1-LINE DNA is strongly methylated at CpG-dinucleotides in most genomic copies in all the tissues and weakly hypomethylated in few copies in some tissues. Small (700–75 nt) P1-LINE RNAs expressed in all tissues may be possible precursors for small regulatory RNAs (PIWI-interacting/piRNAs) bioinformatically derived from P1-LINE. The strong and dynamic expression of LINE RNAs from multiple chromosomal loci and the putative piRNAs in somatic tissues of rat under normal physiological conditions may define functional chromosomal domains marked by LINE RNAs as long noncoding RNAs (lncRNAs) unrestricted by DNA methylation. The tissue-specific, dynamic RNA expression and mosaic genomic distribution of LINEs representing a steady-state genomic flux of retrotransposon RNAs suggest for biological role of LINE RNAs as long ncRNAs and small piRNAs in mammalian tissues independent of their cellular fate for translation, reverse-transcription and retrotransposition. This may provide evolutionary advantages to LINEs and mammalian genomes. PMID:23064113

Modeling genome-wide dynamic regulatory network in mouse lungs with influenza infection using high-dimensional ordinary differential equations.

PubMed

Wu, Shuang; Liu, Zhi-Ping; Qiu, Xing; Wu, Hulin

2014-01-01

The immune response to viral infection is regulated by an intricate network of many genes and their products. The reverse engineering of gene regulatory networks (GRNs) using mathematical models from time course gene expression data collected after influenza infection is key to our understanding of the mechanisms involved in controlling influenza infection within a host. A five-step pipeline: detection of temporally differentially expressed genes, clustering genes into co-expressed modules, identification of network structure, parameter estimate refinement, and functional enrichment analysis, is developed for reconstructing high-dimensional dynamic GRNs from genome-wide time course gene expression data. Applying the pipeline to the time course gene expression data from influenza-infected mouse lungs, we have identified 20 distinct temporal expression patterns in the differentially expressed genes and constructed a module-based dynamic network using a linear ODE model. Both intra-module and inter-module annotations and regulatory relationships of our inferred network show some interesting findings and are highly consistent with existing knowledge about the immune response in mice after influenza infection. The proposed method is a computationally efficient, data-driven pipeline bridging experimental data, mathematical modeling, and statistical analysis. The application to the influenza infection data elucidates the potentials of our pipeline in providing valuable insights into systematic modeling of complicated biological processes.

Time Series Expression Analyses Using RNA-seq: A Statistical Approach

PubMed Central

Oh, Sunghee; Song, Seongho; Grabowski, Gregory; Zhao, Hongyu; Noonan, James P.

2013-01-01

RNA-seq is becoming the de facto standard approach for transcriptome analysis with ever-reducing cost. It has considerable advantages over conventional technologies (microarrays) because it allows for direct identification and quantification of transcripts. Many time series RNA-seq datasets have been collected to study the dynamic regulations of transcripts. However, statistically rigorous and computationally efficient methods are needed to explore the time-dependent changes of gene expression in biological systems. These methods should explicitly account for the dependencies of expression patterns across time points. Here, we discuss several methods that can be applied to model timecourse RNA-seq data, including statistical evolutionary trajectory index (SETI), autoregressive time-lagged regression (AR(1)), and hidden Markov model (HMM) approaches. We use three real datasets and simulation studies to demonstrate the utility of these dynamic methods in temporal analysis. PMID:23586021

Time series expression analyses using RNA-seq: a statistical approach.

PubMed

Oh, Sunghee; Song, Seongho; Grabowski, Gregory; Zhao, Hongyu; Noonan, James P

2013-01-01

RNA-seq is becoming the de facto standard approach for transcriptome analysis with ever-reducing cost. It has considerable advantages over conventional technologies (microarrays) because it allows for direct identification and quantification of transcripts. Many time series RNA-seq datasets have been collected to study the dynamic regulations of transcripts. However, statistically rigorous and computationally efficient methods are needed to explore the time-dependent changes of gene expression in biological systems. These methods should explicitly account for the dependencies of expression patterns across time points. Here, we discuss several methods that can be applied to model timecourse RNA-seq data, including statistical evolutionary trajectory index (SETI), autoregressive time-lagged regression (AR(1)), and hidden Markov model (HMM) approaches. We use three real datasets and simulation studies to demonstrate the utility of these dynamic methods in temporal analysis.

Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo.

PubMed

Woda, Juliana M; Calzonetti, Teresa; Hilditch-Maguire, Paige; Duyao, Mabel P; Conlon, Ronald A; MacDonald, Marcy E

2005-08-18

Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdh(ex4/5) huntingtin deficient embryos. In the absence of huntingtin, expression of nutritive genes appears normal but E7.0-7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE) are specified. Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in Huntington's disease.

Bayesian B-spline mapping for dynamic quantitative traits.

PubMed

Xing, Jun; Li, Jiahan; Yang, Runqing; Zhou, Xiaojing; Xu, Shizhong

2012-04-01

Owing to their ability and flexibility to describe individual gene expression at different time points, random regression (RR) analyses have become a popular procedure for the genetic analysis of dynamic traits whose phenotypes are collected over time. Specifically, when modelling the dynamic patterns of gene expressions in the RR framework, B-splines have been proved successful as an alternative to orthogonal polynomials. In the so-called Bayesian B-spline quantitative trait locus (QTL) mapping, B-splines are used to characterize the patterns of QTL effects and individual-specific time-dependent environmental errors over time, and the Bayesian shrinkage estimation method is employed to estimate model parameters. Extensive simulations demonstrate that (1) in terms of statistical power, Bayesian B-spline mapping outperforms the interval mapping based on the maximum likelihood; (2) for the simulated dataset with complicated growth curve simulated by B-splines, Legendre polynomial-based Bayesian mapping is not capable of identifying the designed QTLs accurately, even when higher-order Legendre polynomials are considered and (3) for the simulated dataset using Legendre polynomials, the Bayesian B-spline mapping can find the same QTLs as those identified by Legendre polynomial analysis. All simulation results support the necessity and flexibility of B-spline in Bayesian mapping of dynamic traits. The proposed method is also applied to a real dataset, where QTLs controlling the growth trajectory of stem diameters in Populus are located.

A Role for Caenorhabditis elegans Importin IMA-2 in Germ Line and Embryonic Mitosis

PubMed Central

Geles, Kenneth G.; Johnson, Jeffrey J.; Jong, Sena; Adam, Stephen A.

2002-01-01

The importin α family of nuclear-cytoplasmic transport factors mediates the nuclear localization of proteins containing classical nuclear localization signals. Metazoan animals express multiple importin α proteins, suggesting their possible roles in cell differentiation and development. Adult Caenorhabditis elegans hermaphrodites express three importin α proteins, IMA-1, IMA-2, and IMA-3, each with a distinct expression and localization pattern. IMA-2 was expressed exclusively in germ line cells from the early embryonic through adult stages. The protein has a dynamic pattern of localization dependent on the stage of the cell cycle. In interphase germ cells and embryonic cells, IMA-2 is cytoplasmic and nuclear envelope associated, whereas in developing oocytes, the protein is cytoplasmic and intranuclear. During mitosis in germ line cells and embryos, IMA-2 surrounded the condensed chromosomes but was not directly associated with the mitotic spindle. The timing of IMA-2 nuclear localization suggested that the protein surrounded the chromosomes after fenestration of the nuclear envelope in prometaphase. Depletion of IMA-2 by RNA-mediated gene interference (RNAi) resulted in embryonic lethality and a terminal aneuploid phenotype. ima-2(RNAi) embryos have severe defects in nuclear envelope formation, accumulating nucleoporins and lamin in the cytoplasm. We conclude that IMA-2 is required for proper chromosome dynamics in germ line and early embryonic mitosis and is involved in nuclear envelope assembly at the conclusion of mitosis. PMID:12221121

Separable roles of UFO during floral development revealed by conditional restoration of gene function.

PubMed

Laufs, Patrick; Coen, Enrico; Kronenberger, Jocelyne; Traas, Jan; Doonan, John

2003-02-01

The UNUSUAL FLORAL ORGANS (UFO) gene is required for several aspects of floral development in Arabidopsis including specification of organ identity in the second and third whorls and the proper pattern of primordium initiation in the inner three whorls. UFO is expressed in a dynamic pattern during the early phases of flower development. Here we dissect the role of UFO by ubiquitously expressing it in ufo loss-of-function flowers at different developmental stages and for various durations using an ethanol-inducible expression system. The previously known functions of UFO could be separated and related to its expression at specific stages of development. We show that a 24- to 48-hour period of UFO expression from floral stage 2, before any floral organs are visible, is sufficient to restore normal petal and stamen development. The earliest requirement for UFO is during stage 2, when the endogenous UFO gene is transiently expressed in the centre of the wild-type flower and is required to specify the initiation patterns of petal, stamen and carpel primordia. Petal and stamen identity is determined during stages 2 or 3, when UFO is normally expressed in the presumptive second and third whorl. Although endogenous UFO expression is absent from the stamen whorl from stage 4 onwards, stamen identity can be restored by UFO activation up to stage 6. We also observed floral phenotypes not observed in loss-of-function or constitutive gain-of-function backgrounds, revealing additional roles of UFO in outgrowth of petal primordia.

Divergent Expression Patterns and Function Implications of Four nanos Genes in a Hermaphroditic Fish, Epinephelus coioides

PubMed Central

Sun, Zhi-Hui; Wang, Yang; Lu, Wei-Jia; Li, Zhi; Liu, Xiao-Chun; Li, Shui-Sheng; Zhou, Li; Gui, Jian-Fang

2017-01-01

Multiple nanos genes have been characterized in several fishes, but the functional implications of their various expression patterns remain unclear. In this study, we identified and characterized four nanos genes from a hermaphroditic fish orange-spotted grouper, Epinephelus coioides. Ecnanos1a and Ecnanos1b show divergent expression patterns, and the dynamic expression change of Ecnanos1a in pituitaries during sex change is associated with testis differentiation and spermatogenesis. Ecnanos2 and Ecnanos3 might be germline stem cells (GSCs) and primordial germ cells (PGCs)-specific markers, respectively. Significantly, Ecnanos3 3′-untranslated region (UTR) is necessary for PGC specific expression, where a non-canonical “GCACGTTT” sequence is required for miR-430-mediated repression of Ecnanos3 RNA. Furthermore, grouper Dead end (Dnd) can relieve miR-430 repression in PGCs by associating with a 23 bp U-rich region (URR) in Ecnanos3 3′-UTR. The current study revealed the functional association of multiple nanos genes with PGC formation and germ cell development in orange-spotted grouper, and opened up new possibilities for developing biotechnologies through utilizing the associations between Ecnanos3 and PGCs or between Ecnanos2 and GSCs in the hermaphroditic fish. PMID:28333083

Oscillator Neural Network Retrieving Sparsely Coded Phase Patterns

NASA Astrophysics Data System (ADS)

Aoyagi, Toshio; Nomura, Masaki

1999-08-01

Little is known theoretically about the associative memory capabilities of neural networks in which information is encoded not only in the mean firing rate but also in the timing of firings. Particularly, in the case of sparsely coded patterns, it is biologically important to consider the timings of firings and to study how such consideration influences storage capacities and quality of recalled patterns. For this purpose, we propose a simple extended model of oscillator neural networks to allow for expression of a nonfiring state. Analyzing both equilibrium states and dynamical properties in recalling processes, we find that the system possesses good associative memory.

From cytoskeletal dynamics to organ asymmetry: a nonlinear, regulative pathway underlies left-right patterning.

PubMed

McDowell, Gary; Rajadurai, Suvithan; Levin, Michael

2016-12-19

Consistent left-right (LR) asymmetry is a fundamental aspect of the bodyplan across phyla, and errors of laterality form an important class of human birth defects. Its molecular underpinning was first discovered as a sequential pathway of left- and right-sided gene expression that controlled positioning of the heart and visceral organs. Recent data have revised this picture in two important ways. First, the physical origin of chirality has been identified; cytoskeletal dynamics underlie the asymmetry of single-cell behaviour and patterning of the LR axis. Second, the pathway is not linear: early disruptions that alter the normal sidedness of upstream asymmetric genes do not necessarily induce defects in the laterality of the downstream genes or in organ situs Thus, the LR pathway is a unique example of two fascinating aspects of biology: the interplay of physics and genetics in establishing large-scale anatomy, and regulative (shape-homeostatic) pathways that correct molecular and anatomical errors over time. Here, we review aspects of asymmetry from its intracellular, cytoplasmic origins to the recently uncovered ability of the LR control circuitry to achieve correct gene expression and morphology despite reversals of key 'determinant' genes. We provide novel functional data, in Xenopus laevis, on conserved elements of the cytoskeleton that drive asymmetry, and comparatively analyse it together with previously published results in the field. Our new observations and meta-analysis demonstrate that despite aberrant expression of upstream regulatory genes, embryos can progressively normalize transcriptional cascades and anatomical outcomes. LR patterning can thus serve as a paradigm of how subcellular physics and gene expression cooperate to achieve developmental robustness of a body axis.This article is part of the themed issue 'Provocative questions in left-right asymmetry'. © 2016 The Author(s).

From cytoskeletal dynamics to organ asymmetry: a nonlinear, regulative pathway underlies left–right patterning

PubMed Central

Rajadurai, Suvithan

2016-01-01

Consistent left–right (LR) asymmetry is a fundamental aspect of the bodyplan across phyla, and errors of laterality form an important class of human birth defects. Its molecular underpinning was first discovered as a sequential pathway of left- and right-sided gene expression that controlled positioning of the heart and visceral organs. Recent data have revised this picture in two important ways. First, the physical origin of chirality has been identified; cytoskeletal dynamics underlie the asymmetry of single-cell behaviour and patterning of the LR axis. Second, the pathway is not linear: early disruptions that alter the normal sidedness of upstream asymmetric genes do not necessarily induce defects in the laterality of the downstream genes or in organ situs. Thus, the LR pathway is a unique example of two fascinating aspects of biology: the interplay of physics and genetics in establishing large-scale anatomy, and regulative (shape-homeostatic) pathways that correct molecular and anatomical errors over time. Here, we review aspects of asymmetry from its intracellular, cytoplasmic origins to the recently uncovered ability of the LR control circuitry to achieve correct gene expression and morphology despite reversals of key ‘determinant’ genes. We provide novel functional data, in Xenopus laevis, on conserved elements of the cytoskeleton that drive asymmetry, and comparatively analyse it together with previously published results in the field. Our new observations and meta-analysis demonstrate that despite aberrant expression of upstream regulatory genes, embryos can progressively normalize transcriptional cascades and anatomical outcomes. LR patterning can thus serve as a paradigm of how subcellular physics and gene expression cooperate to achieve developmental robustness of a body axis. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821521

Young Children’s Affective Responses to Another’s Distress: Dynamic and Physiological Features

PubMed Central

Fink, Elian; Heathers, James A. J.; de Rosnay, Marc

2015-01-01

Two descriptive studies set out a new approach for exploring the dynamic features of children’s affective responses (sadness and interest-worry) to another’s distress. In two samples (N study1 = 75; N study2 = 114), Kindergarten children were shown a video-vignette depicting another child in distress and the temporal pattern of spontaneous expressions were examined across the unfolding vignette. Results showed, in both study 1 and 2, that sadness and interest-worry had distinct patterns of elicitation across the events of the vignette narrative and there was little co-occurrence of these affects within a given child. Temporal heart rate changes (study 2) were closely aligned to the events of the vignette and, furthermore, affective responses corresponded to distinctive physiological response profiles. The implications of distinct temporal patterns of elicitation for the meaning of sadness and interest-worry are discussed within the framework of emotion regulation and empathy. PMID:25874952

Genomic Imprinting Was Evolutionarily Conserved during Wheat Polyploidization.

PubMed

Yang, Guanghui; Liu, Zhenshan; Gao, Lulu; Yu, Kuohai; Feng, Man; Yao, Yingyin; Peng, Huiru; Hu, Zhaorong; Sun, Qixin; Ni, Zhongfu; Xin, Mingming

2018-01-01

Genomic imprinting is an epigenetic phenomenon that causes genes to be differentially expressed depending on their parent of origin. To evaluate the evolutionary conservation of genomic imprinting and the effects of ploidy on this process, we investigated parent-of-origin-specific gene expression patterns in the endosperm of diploid ( Aegilops spp), tetraploid, and hexaploid wheat ( Triticum spp) at various stages of development via high-throughput transcriptome sequencing. We identified 91, 135, and 146 maternally or paternally expressed genes (MEGs or PEGs, respectively) in diploid, tetraploid, and hexaploid wheat, respectively, 52.7% of which exhibited dynamic expression patterns at different developmental stages. Gene Ontology enrichment analysis suggested that MEGs and PEGs were involved in metabolic processes and DNA-dependent transcription, respectively. Nearly half of the imprinted genes exhibited conserved expression patterns during wheat hexaploidization. In addition, 40% of the homoeolog pairs originating from whole-genome duplication were consistently maternally or paternally biased in the different subgenomes of hexaploid wheat. Furthermore, imprinted expression was found for 41.2% and 50.0% of homolog pairs that evolved by tandem duplication after genome duplication in tetraploid and hexaploid wheat, respectively. These results suggest that genomic imprinting was evolutionarily conserved between closely related Triticum and Aegilops species and in the face of polyploid hybridization between species in these genera. © 2018 American Society of Plant Biologists. All rights reserved.

Dynamic transcriptional signatures and network responses for clinical symptoms in influenza-infected human subjects using systems biology approaches.

PubMed

Linel, Patrice; Wu, Shuang; Deng, Nan; Wu, Hulin

2014-10-01

Recent studies demonstrate that human blood transcriptional signatures may be used to support diagnosis and clinical decisions for acute respiratory viral infections such as influenza. In this article, we propose to use a newly developed systems biology approach for time course gene expression data to identify significant dynamically response genes and dynamic gene network responses to viral infection. We illustrate the methodological pipeline by reanalyzing the time course gene expression data from a study with healthy human subjects challenged by live influenza virus. We observed clear differences in the number of significant dynamic response genes (DRGs) between the symptomatic and asymptomatic subjects and also identified DRG signatures for symptomatic subjects with influenza infection. The 505 common DRGs shared by the symptomatic subjects have high consistency with the signature genes for predicting viral infection identified in previous works. The temporal response patterns and network response features were carefully analyzed and investigated.

Dynamic Encoding of Face Information in the Human Fusiform Gyrus

PubMed Central

Ghuman, Avniel Singh; Brunet, Nicolas M.; Li, Yuanning; Konecky, Roma O.; Pyles, John A.; Walls, Shawn A.; Destefino, Vincent; Wang, Wei; Richardson, R. Mark

2014-01-01

Humans’ ability to rapidly and accurately detect, identify, and classify faces under variable conditions derives from a network of brain regions highly tuned to face information. The fusiform face area (FFA) is thought to be a computational hub for face processing, however temporal dynamics of face information processing in FFA remains unclear. Here we use multivariate pattern classification to decode the temporal dynamics of expression-invariant face information processing using electrodes placed directly upon FFA in humans. Early FFA activity (50-75 ms) contained information regarding whether participants were viewing a face. Activity between 200-500 ms contained expression-invariant information about which of 70 faces participants were viewing along with the individual differences in facial features and their configurations. Long-lasting (500+ ms) broadband gamma frequency activity predicted task performance. These results elucidate the dynamic computational role FFA plays in multiple face processing stages and indicate what information is used in performing these visual analyses. PMID:25482825

Dynamic encoding of face information in the human fusiform gyrus.

PubMed

Ghuman, Avniel Singh; Brunet, Nicolas M; Li, Yuanning; Konecky, Roma O; Pyles, John A; Walls, Shawn A; Destefino, Vincent; Wang, Wei; Richardson, R Mark

2014-12-08

Humans' ability to rapidly and accurately detect, identify and classify faces under variable conditions derives from a network of brain regions highly tuned to face information. The fusiform face area (FFA) is thought to be a computational hub for face processing; however, temporal dynamics of face information processing in FFA remains unclear. Here we use multivariate pattern classification to decode the temporal dynamics of expression-invariant face information processing using electrodes placed directly on FFA in humans. Early FFA activity (50-75 ms) contained information regarding whether participants were viewing a face. Activity between 200 and 500 ms contained expression-invariant information about which of 70 faces participants were viewing along with the individual differences in facial features and their configurations. Long-lasting (500+ms) broadband gamma frequency activity predicted task performance. These results elucidate the dynamic computational role FFA plays in multiple face processing stages and indicate what information is used in performing these visual analyses.

Sonic Hedgehog functions through dynamic changes in temporal competence in the developing ventral telencephalon

PubMed Central

Sousa, Vitor H.; Fishell, Gord

2010-01-01

Morphogens act during development to provide graded spatial information that controls patterning and cell lineage specification in the nervous system. The role of morphogen signaling in instructing the expression of downstream effector transcription factors has been well established. However, a key requirement for morphogen signaling is the existence of functional intracellular machinery able to mediate the appropriate response in target cells. Here we suggest that dynamic changes in the temporal responses to Shh in the developing ventral telencephalon occur through alterations in progenitor competence. We suggest these developmental changes in competence are mediated by a transcriptional mechanism that intrinsically integrates information from the distinct signaling pathways that act to pattern the telencephalic neuroepithelium. PMID:20466536

Off-line monitoring of bacterial stress response during recombinant protein production using an optical biosensor.

PubMed

Vostiar, Igor; Tkac, Jan; Mandenius, Carl-Fredrik

2004-07-15

A surface plasmon resonance (SPR) biosensor was used to monitor the profiles of the heat-shock protein (DnaK) and the expression of a heterologous protein to map the dynamics of the cellular stress response in Escherichia coli. As expression system was used an E. coli strain overproducing human recombinant superoxide dismutase (rhSOD). Expression of DnaK showed complex patterns differing with strength of induction. The strong up-regulation of DnaK expression was observed in all cultivations which over-produced of rhSOD. Similar patterns were not observed in non-induced reference cultures. Differences in DnaK concentration profiles were correlated with induction strength. Presented data, carried out in shake flask and glucose limited fed-batch cultivation, show a good consistency with previously published transcriptional profiling results and provide complementary information to understand stress response related to overproduction of recombinant protein. The study also demonstrates the feasibility of using the SPR as a two channel protein array for monitoring of intracellular components.

Building quantitative, three-dimensional atlases of gene expression and morphology at cellular resolution.

PubMed

Knowles, David W; Biggin, Mark D

2013-01-01

Animals comprise dynamic three-dimensional arrays of cells that express gene products in intricate spatial and temporal patterns that determine cellular differentiation and morphogenesis. A rigorous understanding of these developmental processes requires automated methods that quantitatively record and analyze complex morphologies and their associated patterns of gene expression at cellular resolution. Here we summarize light microscopy-based approaches to establish permanent, quantitative datasets-atlases-that record this information. We focus on experiments that capture data for whole embryos or large areas of tissue in three dimensions, often at multiple time points. We compare and contrast the advantages and limitations of different methods and highlight some of the discoveries made. We emphasize the need for interdisciplinary collaborations and integrated experimental pipelines that link sample preparation, image acquisition, image analysis, database design, visualization, and quantitative analysis. Copyright © 2013 Wiley Periodicals, Inc.

Progestogen treatments for cycle management in a sheep model of assisted conception affect the growth patterns, the expression of luteinizing hormone receptors, and the progesterone secretion of induced corpora lutea.

PubMed

Letelier, Claudia; García-Fernández, Rosa Ana; Contreras-Solis, Ignacio; Sanchez, María Angeles; Garcia-Palencia, Pilar; Sanchez, Belen; Gonzalez-Bulnes, Antonio; Flores, Juana María

2010-03-01

To determine, in a sheep model, the effect of a short-term progestative treatment on growth dynamics and functionality of induced corpora lutea. Observational, model study. Public university. Sixty adult female sheep. Synchronization and induction of ovulation with progestogens and prostaglandin analogues; ovarian ultrasonography, blood sampling, and ovariectomy. Determination of pituitary function and morphologic characteristics, expression of luteinizing hormone (LH) receptors, and progesterone secretion of corpora lutea. The use of progestative pretreatments for assisted conception affect the growth patterns, the expression of LH receptors, and the progesterone secretion of induced corpora lutea. The current study indicates, in a sheep model, the existence of deleterious effects from progestogens on functionality of induced corpora lutea. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Automatic decoding of facial movements reveals deceptive pain expressions

PubMed Central

Bartlett, Marian Stewart; Littlewort, Gwen C.; Frank, Mark G.; Lee, Kang

2014-01-01

Summary In highly social species such as humans, faces have evolved to convey rich information for social interaction, including expressions of emotions and pain [1–3]. Two motor pathways control facial movement [4–7]. A subcortical extrapyramidal motor system drives spontaneous facial expressions of felt emotions. A cortical pyramidal motor system controls voluntary facial expressions. The pyramidal system enables humans to simulate facial expressions of emotions not actually experienced. Their simulation is so successful that they can deceive most observers [8–11]. Machine vision may, however, be able to distinguish deceptive from genuine facial signals by identifying the subtle differences between pyramidally and extrapyramidally driven movements. Here we show that human observers could not discriminate real from faked expressions of pain better than chance, and after training, improved accuracy to a modest 55%. However a computer vision system that automatically measures facial movements and performs pattern recognition on those movements attained 85% accuracy. The machine system’s superiority is attributable to its ability to differentiate the dynamics of genuine from faked expressions. Thus by revealing the dynamics of facial action through machine vision systems, our approach has the potential to elucidate behavioral fingerprints of neural control systems involved in emotional signaling. PMID:24656830

Epigenetic and Epitranscriptomic Factors Make a Mark on Hematopoietic Stem Cell Development.

PubMed

Kasper, Dionna M; Nicoli, Stefania

2018-03-01

Blood specification is a highly dynamic process, whereby committed hemogenic endothelial cells (ECs) progressively transdifferentiate into multipotent, self-renewing hematopoietic stem cells (HSCs). Massive changes in gene expression must occur to switch cell identity, however the factors that mediate such an effect were a mystery until recently. This review summarizes the higher-order mechanisms involved in endothelial to hematopoietic reprogramming identified thus far. Accumulating evidence from mouse and zebrafish studies reveal that numerous chromatin-modifying (epigenetic) and RNA-modifying (epitranscriptomic) factors are required for the formation of HSCs from hemogenic endothelium. These genes function throughout the endothelial-hematopoietic transition, suggesting a dynamic interplay between 'epi'-machineries. Epigenetic and epitranscriptomic regulation are key mechanisms for reshaping global EC gene expression patterns to those that support HSC production. Future studies that capture modification dynamics should bring us closer to a complete understanding of how HSCs transition from hemogenic endothelium at the molecular level.

Seasonal Changes in Bacterial and Archaeal Gene Expression Patterns across Salinity Gradients in the Columbia River Coastal Margin

PubMed Central

Smith, Maria W.; Herfort, Lydie; Tyrol, Kaitlin; Suciu, Dominic; Campbell, Victoria; Crump, Byron C.; Peterson, Tawnya D.; Zuber, Peter; Baptista, Antonio M.; Simon, Holly M.

2010-01-01

Through their metabolic activities, microbial populations mediate the impact of high gradient regions on ecological function and productivity of the highly dynamic Columbia River coastal margin (CRCM). A 2226-probe oligonucleotide DNA microarray was developed to investigate expression patterns for microbial genes involved in nitrogen and carbon metabolism in the CRCM. Initial experiments with the environmental microarrays were directed toward validation of the platform and yielded high reproducibility in multiple tests. Bioinformatic and experimental validation also indicated that >85% of the microarray probes were specific for their corresponding target genes and for a few homologs within the same microbial family. The validated probe set was used to query gene expression responses by microbial assemblages to environmental variability. Sixty-four samples from the river, estuary, plume, and adjacent ocean were collected in different seasons and analyzed to correlate the measured variability in chemical, physical and biological water parameters to differences in global gene expression profiles. The method produced robust seasonal profiles corresponding to pre-freshet spring (April) and late summer (August). Overall relative gene expression was high in both seasons and was consistent with high microbial abundance measured by total RNA, heterotrophic bacterial production, and chlorophyll a. Both seasonal patterns involved large numbers of genes that were highly expressed relative to background, yet each produced very different gene expression profiles. April patterns revealed high differential gene expression in the coastal margin samples (estuary, plume and adjacent ocean) relative to freshwater, while little differential gene expression was observed along the river-to-ocean transition in August. Microbial gene expression profiles appeared to relate, in part, to seasonal differences in nutrient availability and potential resource competition. Furthermore, our results suggest that highly-active particle-attached microbiota in the Columbia River water column may perform dissimilatory nitrate reduction (both dentrification and DNRA) within anoxic particle microniches. PMID:20967204

Transcriptional dynamics of the developing sweet cherry (Prunus avium L.) fruit: sequencing, annotation and expression profiling of exocarp-associated genes

PubMed Central

Alkio, Merianne; Jonas, Uwe; Declercq, Myriam; Van Nocker, Steven; Knoche, Moritz

2014-01-01

The exocarp, or skin, of fleshy fruit is a specialized tissue that protects the fruit, attracts seed dispersing fruit eaters, and has large economical relevance for fruit quality. Development of the exocarp involves regulated activities of many genes. This research analyzed global gene expression in the exocarp of developing sweet cherry (Prunus avium L., ‘Regina’), a fruit crop species with little public genomic resources. A catalog of transcript models (contigs) representing expressed genes was constructed from de novo assembled short complementary DNA (cDNA) sequences generated from developing fruit between flowering and maturity at 14 time points. Expression levels in each sample were estimated for 34 695 contigs from numbers of reads mapping to each contig. Contigs were annotated functionally based on BLAST, gene ontology and InterProScan analyses. Coregulated genes were detected using partitional clustering of expression patterns. The results are discussed with emphasis on genes putatively involved in cuticle deposition, cell wall metabolism and sugar transport. The high temporal resolution of the expression patterns presented here reveals finely tuned developmental specialization of individual members of gene families. Moreover, the de novo assembled sweet cherry fruit transcriptome with 7760 full-length protein coding sequences and over 20 000 other, annotated cDNA sequences together with their developmental expression patterns is expected to accelerate molecular research on this important tree fruit crop. PMID:26504533

GEM-TREND: a web tool for gene expression data mining toward relevant network discovery

PubMed Central

Feng, Chunlai; Araki, Michihiro; Kunimoto, Ryo; Tamon, Akiko; Makiguchi, Hiroki; Niijima, Satoshi; Tsujimoto, Gozoh; Okuno, Yasushi

2009-01-01

Background DNA microarray technology provides us with a first step toward the goal of uncovering gene functions on a genomic scale. In recent years, vast amounts of gene expression data have been collected, much of which are available in public databases, such as the Gene Expression Omnibus (GEO). To date, most researchers have been manually retrieving data from databases through web browsers using accession numbers (IDs) or keywords, but gene-expression patterns are not considered when retrieving such data. The Connectivity Map was recently introduced to compare gene expression data by introducing gene-expression signatures (represented by a set of genes with up- or down-regulated labels according to their biological states) and is available as a web tool for detecting similar gene-expression signatures from a limited data set (approximately 7,000 expression profiles representing 1,309 compounds). In order to support researchers to utilize the public gene expression data more effectively, we developed a web tool for finding similar gene expression data and generating its co-expression networks from a publicly available database. Results GEM-TREND, a web tool for searching gene expression data, allows users to search data from GEO using gene-expression signatures or gene expression ratio data as a query and retrieve gene expression data by comparing gene-expression pattern between the query and GEO gene expression data. The comparison methods are based on the nonparametric, rank-based pattern matching approach of Lamb et al. (Science 2006) with the additional calculation of statistical significance. The web tool was tested using gene expression ratio data randomly extracted from the GEO and with in-house microarray data, respectively. The results validated the ability of GEM-TREND to retrieve gene expression entries biologically related to a query from GEO. For further analysis, a network visualization interface is also provided, whereby genes and gene annotations are dynamically linked to external data repositories. Conclusion GEM-TREND was developed to retrieve gene expression data by comparing query gene-expression pattern with those of GEO gene expression data. It could be a very useful resource for finding similar gene expression profiles and constructing its gene co-expression networks from a publicly available database. GEM-TREND was designed to be user-friendly and is expected to support knowledge discovery. GEM-TREND is freely available at . PMID:19728865

GEM-TREND: a web tool for gene expression data mining toward relevant network discovery.

PubMed

Feng, Chunlai; Araki, Michihiro; Kunimoto, Ryo; Tamon, Akiko; Makiguchi, Hiroki; Niijima, Satoshi; Tsujimoto, Gozoh; Okuno, Yasushi

2009-09-03

DNA microarray technology provides us with a first step toward the goal of uncovering gene functions on a genomic scale. In recent years, vast amounts of gene expression data have been collected, much of which are available in public databases, such as the Gene Expression Omnibus (GEO). To date, most researchers have been manually retrieving data from databases through web browsers using accession numbers (IDs) or keywords, but gene-expression patterns are not considered when retrieving such data. The Connectivity Map was recently introduced to compare gene expression data by introducing gene-expression signatures (represented by a set of genes with up- or down-regulated labels according to their biological states) and is available as a web tool for detecting similar gene-expression signatures from a limited data set (approximately 7,000 expression profiles representing 1,309 compounds). In order to support researchers to utilize the public gene expression data more effectively, we developed a web tool for finding similar gene expression data and generating its co-expression networks from a publicly available database. GEM-TREND, a web tool for searching gene expression data, allows users to search data from GEO using gene-expression signatures or gene expression ratio data as a query and retrieve gene expression data by comparing gene-expression pattern between the query and GEO gene expression data. The comparison methods are based on the nonparametric, rank-based pattern matching approach of Lamb et al. (Science 2006) with the additional calculation of statistical significance. The web tool was tested using gene expression ratio data randomly extracted from the GEO and with in-house microarray data, respectively. The results validated the ability of GEM-TREND to retrieve gene expression entries biologically related to a query from GEO. For further analysis, a network visualization interface is also provided, whereby genes and gene annotations are dynamically linked to external data repositories. GEM-TREND was developed to retrieve gene expression data by comparing query gene-expression pattern with those of GEO gene expression data. It could be a very useful resource for finding similar gene expression profiles and constructing its gene co-expression networks from a publicly available database. GEM-TREND was designed to be user-friendly and is expected to support knowledge discovery. GEM-TREND is freely available at http://cgs.pharm.kyoto-u.ac.jp/services/network.

Dynamics of wound healing signaling as a potential therapeutic target for radiation-induced tissue damage.

PubMed

Chung, Yih-Lin; Pui, Newman N M

2015-01-01

We hypothesized the histone deacetylase inhibitor phenylbutyrate (PB) has beneficial effects on radiation-induced injury by modulating the expression of DNA repair and wound healing genes. Hamsters received a radiosurgical dose of radiation (40 Gy) to the cheek and were treated with varying PB dosing regimens. Gross alteration of the irradiated cheeks, eating function, histological changes, and gene expression during the course of wound healing were compared between treatment groups. Pathological analysis showed decreased radiation-induced mucositis, facilitated epithelial cell growth, and preventing ulcerative wound formation, after short-term PB treatment, but not after vehicle or sustained PB. The radiation-induced wound healing gene expression profile exhibited a sequential transition from the inflammatory and DNA repair phases to the tissue remodeling phase in the vehicle group. Sustained PB treatment resulted in a prolonged wound healing gene expression profile and delayed the wound healing process. Short-term PB shortened the duration of inflammatory cytokine expression, triggered repeated pulsed expression of cell cycle and DNA repair-regulating genes, and promoted earlier oscillatory expression of tissue remodeling genes. Distinct gene expression patterns between sustained and short-term treatment suggest dynamic profiling of wound healing gene expression can be an important part of a biological therapeutic strategy to mitigate radiation-related tissue injury. © 2015 by the Wound Healing Society.

Hox gene expression during postlarval development of the polychaete Alitta virens.

PubMed

Bakalenko, Nadezhda I; Novikova, Elena L; Nesterenko, Alexander Y; Kulakova, Milana A

2013-05-01

Hox genes are the family of transcription factors that play a key role in the patterning of the anterior-posterior axis of all bilaterian animals. These genes display clustered organization and colinear expression. Expression boundaries of individual Hox genes usually correspond with morphological boundaries of the body. Previously, we studied Hox gene expression during larval development of the polychaete Alitta virens (formerly Nereis virens) and discovered that Hox genes are expressed in nereid larva according to the spatial colinearity principle. Adult Alitta virens consist of multiple morphologically similar segments, which are formed sequentially in the growth zone. Since the worm grows for most of its life, postlarval segments constantly change their position along the anterior-posterior axis. We studied the expression dynamics of the Hox cluster during postlarval development of the nereid Alitta virens and found that 8 out of 11 Hox genes are transcribed as wide gene-specific gradients in the ventral nerve cord, ectoderm, and mesoderm. The expression domains constantly shift in accordance with the changing proportions of the growing worm, so expression domains of most Hox genes do not have stable anterior or/and posterior boundaries.In the course of our study, we revealed long antisense RNA (asRNA) for some Hox genes. Expression patterns of two of these genes were analyzed using whole-mount in-situ hybridization. This is the first discovery of antisense RNA for Hox genes in Lophotrochozoa. Hox gene expression in juvenile A. virens differs significantly from Hox gene expression patterns both in A. virens larva and in other Bilateria.We suppose that the postlarval function of the Hox genes in this polychaete is to establish and maintain positional coordinates in a constantly growing body, as opposed to creating morphological difference between segments.

Analysis of musical expression in audio signals

NASA Astrophysics Data System (ADS)

Dixon, Simon

2003-01-01

In western art music, composers communicate their work to performers via a standard notation which specificies the musical pitches and relative timings of notes. This notation may also include some higher level information such as variations in the dynamics, tempo and timing. Famous performers are characterised by their expressive interpretation, the ability to convey structural and emotive information within the given framework. The majority of work on audio content analysis focusses on retrieving score-level information; this paper reports on the extraction of parameters describing the performance, a task which requires a much higher degree of accuracy. Two systems are presented: BeatRoot, an off-line beat tracking system which finds the times of musical beats and tracks changes in tempo throughout a performance, and the Performance Worm, a system which provides a real-time visualisation of the two most important expressive dimensions, tempo and dynamics. Both of these systems are being used to process data for a large-scale study of musical expression in classical and romantic piano performance, which uses artificial intelligence (machine learning) techniques to discover fundamental patterns or principles governing expressive performance.

Integrated time-lapse and single-cell transcription studies highlight the variable and dynamic nature of human hematopoietic cell fate commitment

PubMed Central

Moussy, Alice; Cosette, Jérémie; Parmentier, Romuald; da Silva, Cindy; Corre, Guillaume; Richard, Angélique; Gandrillon, Olivier; Stockholm, Daniel

2017-01-01

Individual cells take lineage commitment decisions in a way that is not necessarily uniform. We address this issue by characterising transcriptional changes in cord blood-derived CD34+ cells at the single-cell level and integrating data with cell division history and morphological changes determined by time-lapse microscopy. We show that major transcriptional changes leading to a multilineage-primed gene expression state occur very rapidly during the first cell cycle. One of the 2 stable lineage-primed patterns emerges gradually in each cell with variable timing. Some cells reach a stable morphology and molecular phenotype by the end of the first cell cycle and transmit it clonally. Others fluctuate between the 2 phenotypes over several cell cycles. Our analysis highlights the dynamic nature and variable timing of cell fate commitment in hematopoietic cells, links the gene expression pattern to cell morphology, and identifies a new category of cells with fluctuating phenotypic characteristics, demonstrating the complexity of the fate decision process (which is different from a simple binary switch between 2 options, as it is usually envisioned). PMID:28749943

Improvisation and the self-organization of multiple musical bodies.

PubMed

Walton, Ashley E; Richardson, Michael J; Langland-Hassan, Peter; Chemero, Anthony

2015-01-01

Understanding everyday behavior relies heavily upon understanding our ability to improvise, how we are able to continuously anticipate and adapt in order to coordinate with our environment and others. Here we consider the ability of musicians to improvise, where they must spontaneously coordinate their actions with co-performers in order to produce novel musical expressions. Investigations of this behavior have traditionally focused on describing the organization of cognitive structures. The focus, here, however, is on the ability of the time-evolving patterns of inter-musician movement coordination as revealed by the mathematical tools of complex dynamical systems to provide a new understanding of what potentiates the novelty of spontaneous musical action. We demonstrate this approach through the application of cross wavelet spectral analysis, which isolates the strength and patterning of the behavioral coordination that occurs between improvising musicians across a range of nested time-scales. Revealing the sophistication of the previously unexplored dynamics of movement coordination between improvising musicians is an important step toward understanding how creative musical expressions emerge from the spontaneous coordination of multiple musical bodies.

Improvisation and the self-organization of multiple musical bodies

PubMed Central

Walton, Ashley E.; Richardson, Michael J.; Langland-Hassan, Peter; Chemero, Anthony

2015-01-01

Understanding everyday behavior relies heavily upon understanding our ability to improvise, how we are able to continuously anticipate and adapt in order to coordinate with our environment and others. Here we consider the ability of musicians to improvise, where they must spontaneously coordinate their actions with co-performers in order to produce novel musical expressions. Investigations of this behavior have traditionally focused on describing the organization of cognitive structures. The focus, here, however, is on the ability of the time-evolving patterns of inter-musician movement coordination as revealed by the mathematical tools of complex dynamical systems to provide a new understanding of what potentiates the novelty of spontaneous musical action. We demonstrate this approach through the application of cross wavelet spectral analysis, which isolates the strength and patterning of the behavioral coordination that occurs between improvising musicians across a range of nested time-scales. Revealing the sophistication of the previously unexplored dynamics of movement coordination between improvising musicians is an important step toward understanding how creative musical expressions emerge from the spontaneous coordination of multiple musical bodies. PMID:25941499

Molecular identification of PpHDAC1, the first histone deacetylase fron the slime mold Physarum polycephalum.

PubMed

Brandtner, Eva-Maria; Lechner, Thomas; Loidl, Peter; Lusser, Alexandra

2002-01-01

The dynamic state of post-translational acetylation of eukaryotic histones is maintained by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs and HDACs have been shown to be components of various regulatory protein complexes in the cell. Their enzymatic activities, intracellular localization and substrate specificities are regulated in a complex, cell cycle related manner. In the myxomycete Physarum polycephalum multiple HATs and HDACs can be distinguished in biochemical terms and they exhibit dynamic activity patterns depending on the cell cycle stage. Here we report on the cloning of the first P. polycephalum HDAC (PpHDAC1) related to the S. cerevisiae Rpd3 protein. The expression pattern of PpHDAC1 mRNA was analysed at different time points of the cell cycle and found to be largely constant. Treatment of macroplasmodia with the HDAC inhibitor trichostatin A at several cell cycle stages resulted in a significant delay in entry into mitosis of treated versus untreated plasmodia. No effect of TSA treatment could be observed on PpHDAC1 expression itself.

LateBiclustering: Efficient Heuristic Algorithm for Time-Lagged Bicluster Identification.

PubMed

Gonçalves, Joana P; Madeira, Sara C

2014-01-01

Identifying patterns in temporal data is key to uncover meaningful relationships in diverse domains, from stock trading to social interactions. Also of great interest are clinical and biological applications, namely monitoring patient response to treatment or characterizing activity at the molecular level. In biology, researchers seek to gain insight into gene functions and dynamics of biological processes, as well as potential perturbations of these leading to disease, through the study of patterns emerging from gene expression time series. Clustering can group genes exhibiting similar expression profiles, but focuses on global patterns denoting rather broad, unspecific responses. Biclustering reveals local patterns, which more naturally capture the intricate collaboration between biological players, particularly under a temporal setting. Despite the general biclustering formulation being NP-hard, considering specific properties of time series has led to efficient solutions for the discovery of temporally aligned patterns. Notably, the identification of biclusters with time-lagged patterns, suggestive of transcriptional cascades, remains a challenge due to the combinatorial explosion of delayed occurrences. Herein, we propose LateBiclustering, a sensible heuristic algorithm enabling a polynomial rather than exponential time solution for the problem. We show that it identifies meaningful time-lagged biclusters relevant to the response of Saccharomyces cerevisiae to heat stress.

Fundamental structures of dynamic social networks.

PubMed

Sekara, Vedran; Stopczynski, Arkadiusz; Lehmann, Sune

2016-09-06

Social systems are in a constant state of flux, with dynamics spanning from minute-by-minute changes to patterns present on the timescale of years. Accurate models of social dynamics are important for understanding the spreading of influence or diseases, formation of friendships, and the productivity of teams. Although there has been much progress on understanding complex networks over the past decade, little is known about the regularities governing the microdynamics of social networks. Here, we explore the dynamic social network of a densely-connected population of ∼1,000 individuals and their interactions in the network of real-world person-to-person proximity measured via Bluetooth, as well as their telecommunication networks, online social media contacts, geolocation, and demographic data. These high-resolution data allow us to observe social groups directly, rendering community detection unnecessary. Starting from 5-min time slices, we uncover dynamic social structures expressed on multiple timescales. On the hourly timescale, we find that gatherings are fluid, with members coming and going, but organized via a stable core of individuals. Each core represents a social context. Cores exhibit a pattern of recurring meetings across weeks and months, each with varying degrees of regularity. Taken together, these findings provide a powerful simplification of the social network, where cores represent fundamental structures expressed with strong temporal and spatial regularity. Using this framework, we explore the complex interplay between social and geospatial behavior, documenting how the formation of cores is preceded by coordination behavior in the communication networks and demonstrating that social behavior can be predicted with high precision.

Fundamental structures of dynamic social networks

PubMed Central

Sekara, Vedran; Stopczynski, Arkadiusz; Lehmann, Sune

2016-01-01

Social systems are in a constant state of flux, with dynamics spanning from minute-by-minute changes to patterns present on the timescale of years. Accurate models of social dynamics are important for understanding the spreading of influence or diseases, formation of friendships, and the productivity of teams. Although there has been much progress on understanding complex networks over the past decade, little is known about the regularities governing the microdynamics of social networks. Here, we explore the dynamic social network of a densely-connected population of ∼1,000 individuals and their interactions in the network of real-world person-to-person proximity measured via Bluetooth, as well as their telecommunication networks, online social media contacts, geolocation, and demographic data. These high-resolution data allow us to observe social groups directly, rendering community detection unnecessary. Starting from 5-min time slices, we uncover dynamic social structures expressed on multiple timescales. On the hourly timescale, we find that gatherings are fluid, with members coming and going, but organized via a stable core of individuals. Each core represents a social context. Cores exhibit a pattern of recurring meetings across weeks and months, each with varying degrees of regularity. Taken together, these findings provide a powerful simplification of the social network, where cores represent fundamental structures expressed with strong temporal and spatial regularity. Using this framework, we explore the complex interplay between social and geospatial behavior, documenting how the formation of cores is preceded by coordination behavior in the communication networks and demonstrating that social behavior can be predicted with high precision. PMID:27555584

Developmental and Individual Differences in the Neural Processing of Dynamic Expressions of Pain and Anger

PubMed Central

Missana, Manuela; Grigutsch, Maren; Grossmann, Tobias

2014-01-01

We examined the processing of facial expressions of pain and anger in 8-month-old infants and adults by measuring event-related brain potentials (ERPs) and frontal EEG alpha asymmetry. The ERP results revealed that while adults showed a late positive potential (LPP) to emotional expressions that was enhanced to pain expressions, reflecting increased evaluation and emotional arousal to pain expressions, infants showed a negative component (Nc) to emotional expressions that was enhanced to angry expressions, reflecting increased allocation of attention to angry faces. Moreover, infants and adults showed opposite patterns in their frontal asymmetry responses to pain and anger, suggesting developmental differences in the motivational processes engendered by these facial expressions. These findings are discussed in the light of associated individual differences in infant temperament and adult dispositional empathy. PMID:24705497

Heritable stress response dynamics revealed by single-cell genealogy

PubMed Central

2018-01-01

Cells often respond to environmental stimuli by activating specific transcription factors. Upon exposure to glucose limitation stress, it is known that yeast Saccharomyces cerevisiae cells dephosphorylate the general stress response factor Msn2, leading to its nuclear localization, which in turn activates the expression of many genes. However, the precise dynamics of Msn2 nucleocytoplasmic translocations and whether they are inherited over multiple generations in a stress-dependent manner are not well understood. Tracking Msn2 localization events in yeast lineages grown on a microfluidic chip, here we report how cells modulate the amplitude, duration, frequency, and dynamic pattern of the localization events in response to glucose limitation stress. Single yeast cells were found to modulate the amplitude and frequency of Msn2 nuclear localization, but not its duration. Moreover, the Msn2 localization frequency was epigenetically inherited in descendants of mother cells, leading to a decrease in cell-to-cell variation in localization frequency. An analysis of the time dynamic patterns of nuclear localizations between genealogically related cell pairs using an information theory approach found that the magnitude of pattern similarity increased with stress intensity and was strongly inherited by the descendant cells at the highest stress level. By dissecting how general stress response dynamics is contributed by different modulation schemes over long time scales, our work provides insight into which scheme evolution might have acted on to optimize fitness in stressful environments. PMID:29675464

Dynamic changes in gene expression during human trophoblast differentiation.

PubMed

Handwerger, Stuart; Aronow, Bruce

2003-01-01

The genetic program that directs human placental differentiation is poorly understood. In a recent study, we used DNA microarray analyses to determine genes that are dynamically regulated during human placental development in an in vitro model system in which highly purified cytotrophoblast cells aggregate spontaneously and fuse to form a multinucleated syncytium that expresses placental lactogen, human chorionic gonadotropin, and other proteins normally expressed by fully differentiated syncytiotrophoblast cells. Of the 6918 genes present on the Incyte Human GEM V microarray that we analyzed over a 9-day period, 141 were induced and 256 were downregulated by more than 2-fold. The dynamically regulated genes fell into nine distinct kinetic patterns of induction or repression, as detected by the K-means algorithm. Classifying the genes according to functional characteristics, the regulated genes could be divided into six overall categories: cell and tissue structural dynamics, cell cycle and apoptosis, intercellular communication, metabolism, regulation of gene expression, and expressed sequence tags and function unknown. Gene expression changes within key functional categories were tightly coupled to the morphological changes that occurred during trophoblast differentiation. Within several key gene categories (e.g., cell and tissue structure), many genes were strongly activated, while others with related function were strongly repressed. These findings suggest that trophoblast differentiation is augmented by "categorical reprogramming" in which the ability of induced genes to function is enhanced by diminished synthesis of other genes within the same category. We also observed categorical reprogramming in human decidual fibroblasts decidualized in vitro in response to progesterone, estradiol, and cyclic AMP. While there was little overlap between genes that are dynamically regulated during trophoblast differentiation versus decidualization, many of the categories in which genes were strongly activated also contained genes whose expression was strongly diminished. Taken together, these findings point to a fundamental role for simultaneous induction and repression of mRNAs that encode functionally related proteins during the differentiation process.

Dynamic gene and protein expression patterns of the autism-associated met receptor tyrosine kinase in the developing mouse forebrain.

PubMed

Judson, Matthew C; Bergman, Mica Y; Campbell, Daniel B; Eagleson, Kathie L; Levitt, Pat

2009-04-10

The establishment of appropriate neural circuitry depends on the coordination of multiple developmental events across space and time. These events include proliferation, migration, differentiation, and survival-all of which can be mediated by hepatocyte growth factor (HGF) signaling through the Met receptor tyrosine kinase. We previously found a functional promoter variant of the MET gene to be associated with autism spectrum disorder, suggesting that forebrain circuits governing social and emotional function may be especially vulnerable to developmental disruptions in HGF/Met signaling. However, little is known about the spatiotemporal distribution of Met expression in the forebrain during the development of such circuits. To advance our understanding of the neurodevelopmental influences of Met activation, we employed complementary Western blotting, in situ hybridization, and immunohistochemistry to comprehensively map Met transcript and protein expression throughout perinatal and postnatal development of the mouse forebrain. Our studies reveal complex and dynamic spatiotemporal patterns of expression during this period. Spatially, Met transcript is localized primarily to specific populations of projection neurons within the neocortex and in structures of the limbic system, including the amygdala, hippocampus, and septum. Met protein appears to be principally located in axon tracts. Temporally, peak expression of transcript and protein occurs during the second postnatal week. This period is characterized by extensive neurite outgrowth and synaptogenesis, supporting a role for the receptor in these processes. Collectively, these data suggest that Met signaling may be necessary for the appropriate wiring of forebrain circuits, with particular relevance to the social and emotional dimensions of behavior. (c) 2009 Wiley-Liss, Inc.

Expression and Localization of CLC Chloride Transport Proteins in the Avian Retina

PubMed Central

McMains, Emily; Krishnan, Vijai; Prasad, Sujitha; Gleason, Evanna

2011-01-01

Members of the ubiquitously expressed CLC protein family of chloride channels and transporters play important roles in regulating cellular chloride and pH. The CLCs that function as Cl−/H+ antiporters, ClCs 3–7, are essential in particular for the acidification of endosomal compartments and protein degradation. These proteins are broadly expressed in the nervous system, and mutations that disrupt their expression are responsible for several human genetic diseases. Furthermore, knock-out of ClC3 and ClC7 in the mouse result in the degeneration of the hippocampus and the retina. Despite this evidence of their importance in retinal function, the expression patterns of different CLC transporters in different retinal cell types are as yet undescribed. Previous work in our lab has shown that in chicken amacrine cells, internal Cl− can be dynamic. To determine whether CLCs have the potential to participate, we used PCR and immunohistochemical techniques to examine CLC transporter expression in the chicken retina. We observed a high level of variation in the retinal expression levels and patterns among the different CLC proteins examined. These findings, which represent the first systematic investigation of CLC transporter expression in the retina, support diverse functions for the different CLCs in this tissue. PMID:21408174

Transcriptome changes during fruit development and ripening of sweet orange (Citrus sinensis).

PubMed

Yu, Keqin; Xu, Qiang; Da, Xinlei; Guo, Fei; Ding, Yuduan; Deng, Xiuxin

2012-01-10

The transcriptome of the fruit pulp of the sweet orange variety Anliu (WT) and that of its red fleshed mutant Hong Anliu (MT) were compared to understand the dynamics and differential expression of genes expressed during fruit development and ripening. The transcriptomes of WT and MT were sampled at four developmental stages using an Illumina sequencing platform. A total of 19,440 and 18,829 genes were detected in MT and WT, respectively. Hierarchical clustering analysis revealed 24 expression patterns for the set of all genes detected, of which 20 were in common between MT and WT. Over 89% of the genes showed differential expression during fruit development and ripening in the WT. Functional categorization of the differentially expressed genes revealed that cell wall biosynthesis, carbohydrate and citric acid metabolism, carotenoid metabolism, and the response to stress were the most differentially regulated processes occurring during fruit development and ripening. A description of the transcriptomic changes occurring during fruit development and ripening was obtained in sweet orange, along with a dynamic view of the gene expression differences between the wild type and a red fleshed mutant. © 2012 Yu et al; licensee BioMed Central Ltd.

A dynamic Shh expression pattern, regulated by SHH and BMP signaling, coordinates fusion of primordia in the amniote face

PubMed Central

Hu, Diane; Young, Nathan M.; Li, Xin; Xu, Yanhua; Hallgrímsson, Benedikt; Marcucio, Ralph S.

2015-01-01

The mechanisms of morphogenesis are not well understood, yet shaping structures during development is essential for establishing correct organismal form and function. Here, we examine mechanisms that help to shape the developing face during the crucial period of facial primordia fusion. This period of development is a time when the faces of amniote embryos exhibit the greatest degree of similarity, and it probably results from the necessity for fusion to occur to establish the primary palate. Our results show that hierarchical induction mechanisms, consisting of iterative signaling by Sonic hedgehog (SHH) followed by Bone morphogenetic proteins (BMPs), regulate a dynamic expression pattern of Shh in the ectoderm covering the frontonasal (FNP) and maxillary (MxP) processes. Furthermore, this Shh expression domain contributes to the morphogenetic processes that drive the directional growth of the globular process of the FNP toward the lateral nasal process and MxP, in part by regulating cell proliferation in the facial mesenchyme. The nature of the induction mechanism that we discovered suggests that the process of fusion of the facial primordia is intrinsically buffered against producing maladaptive morphologies, such as clefts of the primary palate, because there appears to be little opportunity for variation to occur during expansion of the Shh expression domain in the ectoderm of the facial primordia. Ultimately, these results might explain why this period of development constitutes a phylotypic stage of facial development among amniotes. PMID:25605783

Ectopic KNOX Expression Affects Plant Development by Altering Tissue Cell Polarity and Identity[OPEN

PubMed Central

Rebocho, Alexandra B.

2016-01-01

Plant development involves two polarity types: tissue cell (asymmetries within cells are coordinated across tissues) and regional (identities vary spatially across tissues) polarity. Both appear altered in the barley (Hordeum vulgare) Hooded mutant, in which ectopic expression of the KNOTTED1-like Homeobox (KNOX) gene, BKn3, causes inverted polarity of differentiated hairs and ectopic flowers, in addition to wing-shaped outgrowths. These lemma-specific effects allow the spatiotemporal analysis of events following ectopic BKn3 expression, determining the relationship between KNOXs, polarity, and shape. We show that tissue cell polarity, based on localization of the auxin transporter SISTER OF PINFORMED1 (SoPIN1), dynamically reorients as ectopic BKn3 expression increases. Concurrently, ectopic expression of the auxin importer LIKE AUX1 and boundary gene NO APICAL MERISTEM is activated. The polarity of hairs reflects SoPIN1 patterns, suggesting that tissue cell polarity underpins oriented cell differentiation. Wing cell files reveal an anisotropic growth pattern, and computational modeling shows how polarity guiding growth can account for this pattern and wing emergence. The inverted ectopic flower orientation does not correlate with SoPIN1, suggesting that this form of regional polarity is not controlled by tissue cell polarity. Overall, the results suggest that KNOXs trigger different morphogenetic effects through interplay between tissue cell polarity, identity, and growth. PMID:27553356

Genome-Wide Identification and Expression Profiling Analysis of ZmPIN, ZmPILS, ZmLAX and ZmABCB Auxin Transporter Gene Families in Maize (Zea mays L.) under Various Abiotic Stresses

PubMed Central

Sun, Tao; Zhang, Lei; Yang, Yanjun; Qi, Jianshuang; Yan, Shufeng; Han, Xiaohua; Wang, Huizhong; Shen, Chenjia

2015-01-01

The auxin influx carriers auxin resistant 1/like aux 1 (AUX/LAX), efflux carriers pin-formed (PIN) (together with PIN-like proteins) and efflux/conditional P-glycoprotein (ABCB) are major protein families involved in auxin polar transport. However, how they function in responses to exogenous auxin and abiotic stresses in maize is largely unknown. In this work, the latest updated maize (Zea mays L.) reference genome sequence was used to characterize and analyze the ZmLAX, ZmPIN, ZmPILS and ZmABCB family genes from maize. The results showed that five ZmLAXs, fifteen ZmPINs, nine ZmPILSs and thirty-five ZmABCBs were mapped on all ten maize chromosomes. Highly diversified gene structures, nonconservative transmembrane helices and tissue-specific expression patterns suggested the possibility of function diversification for these genes. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression patterns of ZmLAX, ZmPIN, ZmPILS and ZmABCB genes under exogenous auxin and different environmental stresses. The expression levels of most ZmPIN, ZmPILS, ZmLAX and ZmABCB genes were induced in shoots and were reduced in roots by various abiotic stresses (drought, salt and cold stresses). The opposite expression response patterns indicated the dynamic auxin transport between shoots and roots under abiotic stresses. Analysis of the expression patterns of ZmPIN, ZmPILS, ZmLAX and ZmABCB genes under drought, salt and cold treatment may help us to understand the possible roles of maize auxin transporter genes in responses and tolerance to environmental stresses. PMID:25742625

Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature

NASA Astrophysics Data System (ADS)

Dai, Guohao; Kaazempur-Mofrad, Mohammad R.; Natarajan, Sripriya; Zhang, Yuzhi; Vaughn, Saran; Blackman, Brett R.; Kamm, Roger D.; García-Cardeña, Guillermo; Gimbrone, Michael A., Jr.

2004-10-01

Atherosclerotic lesion localization to regions of disturbed flow within certain arterial geometries, in humans and experimental animals, suggests an important role for local hemodynamic forces in atherogenesis. To explore how endothelial cells (EC) acquire functional/dysfunctional phenotypes in response to vascular region-specific flow patterns, we have used an in vitro dynamic flow system to accurately reproduce arterial shear stress waveforms on cultured human EC and have examined the effects on EC gene expression by using a high-throughput transcriptional profiling approach. The flow patterns in the carotid artery bifurcations of several normal human subjects were characterized by using 3D flow analysis based on actual vascular geometries and blood flow profiles. Two prototypic arterial waveforms, "athero-prone" and "athero-protective," were defined as representative of the wall shear stresses in two distinct regions of the carotid artery (carotid sinus and distal internal carotid artery) that are typically "susceptible" or "resistant," respectively, to atherosclerotic lesion development. These two waveforms were applied to cultured EC, and cDNA microarrays were used to analyze the differential patterns of EC gene expression. In addition, the differential effects of athero-prone vs. athero-protective waveforms were further characterized on several parameters of EC structure and function, including actin cytoskeletal organization, expression and localization of junctional proteins, activation of the NF-B transcriptional pathway, and expression of proinflammatory cytokines and adhesion molecules. These global gene expression patterns and functional data reveal a distinct phenotypic modulation in response to the wall shear stresses present in atherosclerosis-susceptible vs. atherosclerosis-resistant human arterial geometries.

Pex11α in brown trout (Salmo trutta f. fario): Expression dynamics during the reproductive cycle reveals sex-specific seasonal patterns.

PubMed

Castro, L Filipe C; Lobo-da-Cunha, Alexandre; Rocha, Maria J; Urbatzka, Ralph; Rocha, Eduardo

2013-01-01

A negative correlation between female gonadal maturation kinetics and size variations of hepatic peroxisomes was earlier documented in brown trout, as a probable impact of serum estrogen changes during the reproductive cycle. Herein, we investigated whether the organelle volume/surface dynamics seen in female brown trout liver peroxisomes - without numerical changes within each hepatocyte - is followed by variations in the expression of the membrane peroxisome protein Pex11α gene. For comparison, we also studied males. We find in females a seasonal variation with the highest Pex11α expression in February, which was statistically different from all other tested periods. Overall, the expression of PEX11α had over a fivefold decrease from February to September. This period coincides with the reproductive transition between the earlier post-spawning gonadal remodeling and preparatory staging and the pre-spawning period. Males did not show changes. Our approach allowed the first characterization of a peroxin gene in a teleost, the Pex11α, while offering a correlation scenario were, as we hypothesized, the peroxisomal size kinetics is paralleled by membrane-related gene alterations (measured herein as proxy of Pex11α gene expression). Our data support and expand previous results on the regulation, function and morphology of peroxisome dynamics in brown trout, with a broader interest. Copyright © 2012 Elsevier Inc. All rights reserved.

HIV promoter integration site primarily modulates transcriptional burst size rather than frequency.

PubMed

Skupsky, Ron; Burnett, John C; Foley, Jonathan E; Schaffer, David V; Arkin, Adam P

2010-09-30

Mammalian gene expression patterns, and their variability across populations of cells, are regulated by factors specific to each gene in concert with its surrounding cellular and genomic environment. Lentiviruses such as HIV integrate their genomes into semi-random genomic locations in the cells they infect, and the resulting viral gene expression provides a natural system to dissect the contributions of genomic environment to transcriptional regulation. Previously, we showed that expression heterogeneity and its modulation by specific host factors at HIV integration sites are key determinants of infected-cell fate and a possible source of latent infections. Here, we assess the integration context dependence of expression heterogeneity from diverse single integrations of a HIV-promoter/GFP-reporter cassette in Jurkat T-cells. Systematically fitting a stochastic model of gene expression to our data reveals an underlying transcriptional dynamic, by which multiple transcripts are produced during short, infrequent bursts, that quantitatively accounts for the wide, highly skewed protein expression distributions observed in each of our clonal cell populations. Interestingly, we find that the size of transcriptional bursts is the primary systematic covariate over integration sites, varying from a few to tens of transcripts across integration sites, and correlating well with mean expression. In contrast, burst frequencies are scattered about a typical value of several per cell-division time and demonstrate little correlation with the clonal means. This pattern of modulation generates consistently noisy distributions over the sampled integration positions, with large expression variability relative to the mean maintained even for the most productive integrations, and could contribute to specifying heterogeneous, integration-site-dependent viral production patterns in HIV-infected cells. Genomic environment thus emerges as a significant control parameter for gene expression variation that may contribute to structuring mammalian genomes, as well as be exploited for survival by integrating viruses.

Dynamic Variation in Pleasure in Children Predicts Nonlinear Change in Lateral Frontal Brain Electrical Activity

ERIC Educational Resources Information Center

Light, Sharee N.; Coan, James A.; Frye, Corrina; Goldsmith, H. Hill; Davidson, Richard J.

2009-01-01

Individual variation in the experience and expression of pleasure may relate to differential patterns of lateral frontal activity. Brain electrical measures have been used to study the asymmetric involvement of lateral frontal cortex in positive emotion, but the excellent time resolution of these measures has not been used to capture…

Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man.

PubMed

Kalafatakis, K; Russell, G M; Harmer, C J; Munafo, M R; Marchant, N; Wilson, A; Brooks, J C; Durant, C; Thakrar, J; Murphy, P; Thai, N J; Lightman, S L

2018-04-24

Glucocorticoids (GCs) are secreted in an ultradian, pulsatile pattern that emerges from delays in the feedforward-feedback interaction between the anterior pituitary and adrenal glands. Dynamic oscillations of GCs are critical for normal cognitive and metabolic function in the rat and have been shown to modulate the pattern of GC-sensitive gene expression, modify synaptic activity, and maintain stress responsiveness. In man, current cortisol replacement therapy does not reproduce physiological hormone pulses and is associated with psychopathological symptoms, especially apathy and attenuated motivation in engaging with daily activities. In this work, we tested the hypothesis that the pattern of GC dynamics in the brain is of crucial importance for regulating cognitive and behavioral processes. We provide evidence that exactly the same dose of cortisol administered in different patterns alters the neural processing underlying the response to emotional stimulation, the accuracy in recognition and attentional bias toward/away from emotional faces, the quality of sleep, and the working memory performance of healthy male volunteers. These data indicate that the pattern of the GC rhythm differentially impacts human cognition and behavior under physiological, nonstressful conditions and has major implications for the improvement of cortisol replacement therapy.

Identification of Reference Genes for RT-qPCR Data Normalization in Cannabis sativa Stem Tissues.

PubMed

Mangeot-Peter, Lauralie; Legay, Sylvain; Hausman, Jean-Francois; Esposito, Sergio; Guerriero, Gea

2016-09-15

Gene expression profiling via quantitative real-time PCR is a robust technique widely used in the life sciences to compare gene expression patterns in, e.g., different tissues, growth conditions, or after specific treatments. In the field of plant science, real-time PCR is the gold standard to study the dynamics of gene expression and is used to validate the results generated with high throughput techniques, e.g., RNA-Seq. An accurate relative quantification of gene expression relies on the identification of appropriate reference genes, that need to be determined for each experimental set-up used and plant tissue studied. Here, we identify suitable reference genes for expression profiling in stems of textile hemp (Cannabis sativa L.), whose tissues (isolated bast fibres and core) are characterized by remarkable differences in cell wall composition. We additionally validate the reference genes by analysing the expression of putative candidates involved in the non-oxidative phase of the pentose phosphate pathway and in the first step of the shikimate pathway. The goal is to describe the possible regulation pattern of some genes involved in the provision of the precursors needed for lignin biosynthesis in the different hemp stem tissues. The results here shown are useful to design future studies focused on gene expression analyses in hemp.

Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo

PubMed Central

Woda, Juliana M; Calzonetti, Teresa; Hilditch-Maguire, Paige; Duyao, Mabel P; Conlon, Ronald A; MacDonald, Marcy E

2005-01-01

Background Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdhex4/5 huntingtin deficient embryos. Results In the absence of huntingtin, expression of nutritive genes appears normal but E7.0–7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE) are specified. Conclusion Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in Huntington's disease. PMID:16109169

Transcriptome dynamics along axolotl regenerative development are consistent with an extensive reduction in gene expression heterogeneity in dedifferentiated cells

PubMed Central

2017-01-01

Although in recent years the study of gene expression variation in the absence of genetic or environmental cues or gene expression heterogeneity has intensified considerably, many basic and applied biological fields still remain unaware of how useful the study of gene expression heterogeneity patterns might be for the characterization of biological systems and/or processes. Largely based on the modulator effect chromatin compaction has for gene expression heterogeneity and the extensive changes in chromatin compaction known to occur for specialized cells that are naturally or artificially induced to revert to less specialized states or dedifferentiate, I recently hypothesized that processes that concur with cell dedifferentiation would show an extensive reduction in gene expression heterogeneity. The confirmation of the existence of such trend could be of wide interest because of the biomedical and biotechnological relevance of cell dedifferentiation-based processes, i.e., regenerative development, cancer, human induced pluripotent stem cells, or plant somatic embryogenesis. Here, I report the first empirical evidence consistent with the existence of an extensive reduction in gene expression heterogeneity for processes that concur with cell dedifferentiation by analyzing transcriptome dynamics along forearm regenerative development in Ambystoma mexicanum or axolotl. Also, I briefly discuss on the utility of the study of gene expression heterogeneity dynamics might have for the characterization of cell dedifferentiation-based processes, and the engineering of tools that afforded better monitoring and modulating such processes. Finally, I reflect on how a transitional reduction in gene expression heterogeneity for dedifferentiated cells can promote a long-term increase in phenotypic heterogeneity following cell dedifferentiation with potential adverse effects for biomedical and biotechnological applications. PMID:29134148

Inter-dependent tissue growth and Turing patterning in a model for long bone development

NASA Astrophysics Data System (ADS)

Tanaka, Simon; Iber, Dagmar

2013-10-01

The development of long bones requires a sophisticated spatial organization of cellular signalling, proliferation, and differentiation programs. How such spatial organization emerges on the growing long bone domain is still unresolved. Based on the reported biochemical interactions we developed a regulatory model for the core signalling factors IHH, PTCH1, and PTHrP and included two cell types, proliferating/resting chondrocytes and (pre-)hypertrophic chondrocytes. We show that the reported IHH-PTCH1 interaction gives rise to a Schnakenberg-type Turing kinetics, and that inclusion of PTHrP is important to achieve robust patterning when coupling patterning and tissue dynamics. The model reproduces relevant spatiotemporal gene expression patterns, as well as a number of relevant mutant phenotypes. In summary, we propose that a ligand-receptor based Turing mechanism may control the emergence of patterns during long bone development, with PTHrP as an important mediator to confer patterning robustness when the sensitive Turing system is coupled to the dynamics of a growing and differentiating tissue. We have previously shown that ligand-receptor based Turing mechanisms can also result from BMP-receptor, SHH-receptor, and GDNF-receptor interactions, and that these reproduce the wildtype and mutant patterns during digit formation in limbs and branching morphogenesis in lung and kidneys. Receptor-ligand interactions may thus constitute a general mechanism to generate Turing patterns in nature.

Distal-less regulates eyespot patterns and melanization in Bicyclus butterflies.

PubMed

Monteiro, Antónia; Chen, Bin; Ramos, Diane M; Oliver, Jeffrey C; Tong, Xiaoling; Guo, Min; Wang, Wen-Kai; Fazzino, Lisa; Kamal, Firdous

2013-07-01

Butterfly eyespots represent novel complex traits that display substantial diversity in number and size within and across species. Correlative gene expression studies have implicated a large suite of transcription factors, including Distal-less (Dll), Engrailed (En), and Spalt (Sal), in eyespot development in butterflies, but direct evidence testing the function of any of these proteins is still missing. Here we show that the characteristic two-eyespot pattern of wildtype Bicyclus anynana forewings is correlated with dynamic progression of Dll, En, and Sal expression in larval wings from four spots to two spots, whereas no such decline in gene expression ensues in a four-eyespot mutant. We then conduct transgenic experiments testing whether over-expression of any of these genes in a wild-type genetic background is sufficient to induce eyespot differentiation in these pre-patterned wing compartments. We also produce a Dll-RNAi transgenic line to test how Dll down-regulation affects eyespot development. Finally we test how ectopic expression of these genes during the pupal stages of development alters adults color patters. We show that over-expressing Dll in larvae is sufficient to induce the differentiation of additional eyespots and increase the size of eyespots, whereas down-regulating Dll leads to a decrease in eyespot size. Furthermore, ectopic expression of Dll in the early pupal wing led to the appearance of ectopic patches of black scales. We conclude that Dll is a positive regulator of focal differentiation and eyespot signaling and that this gene is also a possible selector gene for scale melanization in butterflies. Copyright © 2013 Wiley Periodicals, Inc.

Dynamic Analysis of Gene Expression in Rice Superior and Inferior Grains by RNA-Seq

PubMed Central

Sun, Hongzheng; Peng, Ting; Zhao, Yafan; Du, Yanxiu; Zhang, Jing; Li, Junzhou; Xin, Zeyu; Zhao, Quanzhi

2015-01-01

Poor grain filling of inferior grains located on lower secondary panicle branch causes great drop in rice yield and quality. Dynamic gene expression patterns between superior and inferior grains were examined from the view of the whole transcriptome by using RNA-Seq method. In total, 19,442 genes were detected during rice grain development. Genes involved in starch synthesis, grain storage and grain development were interrogated in particular in superior and inferior grains. Of the genes involved in sucrose to starch transformation process, most were expressed at lower level in inferior grains at early filling stage compared to that of superior grains. But at late filling stage, the expression of those genes was higher in inferior grains and lower in superior grains. The same trends were observed in the expression of grain storage protein genes. While, evidence that genes involved in cell cycle showed higher expression in inferior grains during whole period of grain filling indicated that cell proliferation was active till the late filling stage. In conclusion, delayed expression of most starch synthesis genes in inferior grains and low capacity of sink organ might be two important factors causing low filling rate of inferior grain at early filling stage, and shortage of carbohydrate supply was a limiting factor at late filling stage. PMID:26355995

Rapid evolution of regulatory element libraries for tunable transcriptional and translational control of gene expression.

PubMed

Jin, Erqing; Wong, Lynn; Jiao, Yun; Engel, Jake; Holdridge, Benjamin; Xu, Peng

2017-12-01

Engineering cell factories for producing biofuels and pharmaceuticals has spurred great interests to develop rapid and efficient synthetic biology tools customized for modular pathway engineering. Along the way, combinatorial gene expression control through modification of regulatory element offered tremendous opportunity for fine-tuning gene expression and generating digital-like genetic circuits. In this report, we present an efficient evolutionary approach to build a range of regulatory control elements. The reported method allows for rapid construction of promoter, 5'UTR, terminator and trans -activating RNA libraries. Synthetic overlapping oligos with high portion of degenerate nucleotides flanking the regulatory element could be efficiently assembled to a vector expressing fluorescence reporter. This approach combines high mutation rate of the synthetic DNA with the high assembly efficiency of Gibson Mix. Our constructed library demonstrates broad range of transcriptional or translational gene expression dynamics. Specifically, both the promoter library and 5'UTR library exhibits gene expression dynamics spanning across three order of magnitude. The terminator library and trans -activating RNA library displays relatively narrowed gene expression pattern. The reported study provides a versatile toolbox for rapidly constructing a large family of prokaryotic regulatory elements. These libraries also facilitate the implementation of combinatorial pathway engineering principles and the engineering of more efficient microbial cell factory for various biomanufacturing applications.

Videos of conspecifics elicit interactive looking patterns and facial expressions in monkeys

PubMed Central

Mosher, Clayton P.; Zimmerman, Prisca E.; Gothard, Katalin M.

2014-01-01

A broader understanding of the neural basis of social behavior in primates requires the use of species-specific stimuli that elicit spontaneous, but reproducible and tractable behaviors. In this context of natural behaviors, individual variation can further inform about the factors that influence social interactions. To approximate natural social interactions similar to those documented by field studies, we used unedited video footage to induce in viewer monkeys spontaneous facial expressions and looking patterns in the laboratory setting. Three adult male monkeys, previously behaviorally and genetically (5-HTTLPR) characterized (Gibboni et al., 2009), were monitored while they watched 10 s video segments depicting unfamiliar monkeys (movie monkeys) displaying affiliative, neutral, and aggressive behaviors. The gaze and head orientation of the movie monkeys alternated between ‘averted’ and ‘directed’ at the viewer. The viewers were not reinforced for watching the movies, thus their looking patterns indicated their interest and social engagement with the stimuli. The behavior of the movie monkey accounted for differences in the looking patterns and facial expressions displayed by the viewers. We also found multiple significant differences in the behavior of the viewers that correlated with their interest in these stimuli. These socially relevant dynamic stimuli elicited spontaneous social behaviors, such as eye-contact induced reciprocation of facial expression, gaze aversion, and gaze following, that were previously not observed in response to static images. This approach opens a unique opportunity to understanding the mechanisms that trigger spontaneous social behaviors in humans and non-human primates. PMID:21688888

Dynamics of entanglement and uncertainty relation in coupled harmonic oscillator system: exact results

NASA Astrophysics Data System (ADS)

Park, DaeKil

2018-06-01

The dynamics of entanglement and uncertainty relation is explored by solving the time-dependent Schrödinger equation for coupled harmonic oscillator system analytically when the angular frequencies and coupling constant are arbitrarily time dependent. We derive the spectral and Schmidt decompositions for vacuum solution. Using the decompositions, we derive the analytical expressions for von Neumann and Rényi entropies. Making use of Wigner distribution function defined in phase space, we derive the time dependence of position-momentum uncertainty relations. To show the dynamics of entanglement and uncertainty relation graphically, we introduce two toy models and one realistic quenched model. While the dynamics can be conjectured by simple consideration in the toy models, the dynamics in the realistic quenched model is somewhat different from that in the toy models. In particular, the dynamics of entanglement exhibits similar pattern to dynamics of uncertainty parameter in the realistic quenched model.

Emergent 1d Ising Behavior in AN Elementary Cellular Automaton Model

NASA Astrophysics Data System (ADS)

Kassebaum, Paul G.; Iannacchione, Germano S.

The fundamental nature of an evolving one-dimensional (1D) Ising model is investigated with an elementary cellular automaton (CA) simulation. The emergent CA simulation employs an ensemble of cells in one spatial dimension, each cell capable of two microstates interacting with simple nearest-neighbor rules and incorporating an external field. The behavior of the CA model provides insight into the dynamics of coupled two-state systems not expressible by exact analytical solutions. For instance, state progression graphs show the causal dynamics of a system through time in relation to the system's entropy. Unique graphical analysis techniques are introduced through difference patterns, diffusion patterns, and state progression graphs of the 1D ensemble visualizing the evolution. All analyses are consistent with the known behavior of the 1D Ising system. The CA simulation and new pattern recognition techniques are scalable (in both dimension, complexity, and size) and have many potential applications such as complex design of materials, control of agent systems, and evolutionary mechanism design.

Xyloglucan Deficiency Disrupts Microtubule Stability and Cellulose Biosynthesis in Arabidopsis, Altering Cell Growth and Morphogenesis1[OPEN

PubMed Central

Xiao, Chaowen; Zhang, Tian; Zheng, Yunzhen

2016-01-01

Xyloglucan constitutes most of the hemicellulose in eudicot primary cell walls and functions in cell wall structure and mechanics. Although Arabidopsis (Arabidopsis thaliana) xxt1 xxt2 mutants lacking detectable xyloglucan are viable, they display growth defects that are suggestive of alterations in wall integrity. To probe the mechanisms underlying these defects, we analyzed cellulose arrangement, microtubule patterning and dynamics, microtubule- and wall-integrity-related gene expression, and cellulose biosynthesis in xxt1 xxt2 plants. We found that cellulose is highly aligned in xxt1 xxt2 cell walls, that its three-dimensional distribution is altered, and that microtubule patterning and stability are aberrant in etiolated xxt1 xxt2 hypocotyls. We also found that the expression levels of microtubule-associated genes, such as MAP70-5 and CLASP, and receptor genes, such as HERK1 and WAK1, were changed in xxt1 xxt2 plants and that cellulose synthase motility is reduced in xxt1 xxt2 cells, corresponding with a reduction in cellulose content. Our results indicate that loss of xyloglucan affects both the stability of the microtubule cytoskeleton and the production and patterning of cellulose in primary cell walls. These findings establish, to our knowledge, new links between wall integrity, cytoskeletal dynamics, and wall synthesis in the regulation of plant morphogenesis. PMID:26527657

Xyloglucan Deficiency Disrupts Microtubule Stability and Cellulose Biosynthesis in Arabidopsis, Altering Cell Growth and Morphogenesis

DOE PAGES

Xiao, Chaowen; Zhang, Tian; Zheng, Yunzhen; ...

2015-11-02

Here, xyloglucan constitutes most of the hemicellulose in eudicot primary cell walls and functions in cell wall structure and mechanics. Although Arabidopsis ( Arabidopsis thaliana) xxt1 xxt2 mutants lacking detectable xyloglucan are viable, they display growth defects that are suggestive of alterations in wall integrity. To probe the mechanisms underlying these defects, we analyzed cellulose arrangement, microtubule patterning and dynamics, microtubule- and wall-integrity-related gene expression, and cellulose biosynthesis in xxt1 xxt2 plants. We found that cellulose is highly aligned in xxt1 xxt2 cell walls, that its three-dimensional distribution is altered, and that microtubule patterning and stability are aberrant in etiolatedmore » xxt1 xxt2 hypocotyls. We also found that the expression levels of microtubule-associated genes, such as MAP70-5 and CLASP, and receptor genes, such as HERK1 and WAK1, were changed in xxt1 xxt2 plants and that cellulose synthase motility is reduced in xxt1 xxt2 cells, corresponding with a reduction in cellulose content. Our results indicate that loss of xyloglucan affects both the stability of the microtubule cytoskeleton and the production and patterning of cellulose in primary cell walls. These findings establish, to our knowledge, new links between wall integrity, cytoskeletal dynamics, and wall synthesis in the regulation of plant morphogenesis.« less

Xyloglucan Deficiency Disrupts Microtubule Stability and Cellulose Biosynthesis in Arabidopsis, Altering Cell Growth and Morphogenesis.

PubMed

Xiao, Chaowen; Zhang, Tian; Zheng, Yunzhen; Cosgrove, Daniel J; Anderson, Charles T

2016-01-01

Xyloglucan constitutes most of the hemicellulose in eudicot primary cell walls and functions in cell wall structure and mechanics. Although Arabidopsis (Arabidopsis thaliana) xxt1 xxt2 mutants lacking detectable xyloglucan are viable, they display growth defects that are suggestive of alterations in wall integrity. To probe the mechanisms underlying these defects, we analyzed cellulose arrangement, microtubule patterning and dynamics, microtubule- and wall-integrity-related gene expression, and cellulose biosynthesis in xxt1 xxt2 plants. We found that cellulose is highly aligned in xxt1 xxt2 cell walls, that its three-dimensional distribution is altered, and that microtubule patterning and stability are aberrant in etiolated xxt1 xxt2 hypocotyls. We also found that the expression levels of microtubule-associated genes, such as MAP70-5 and CLASP, and receptor genes, such as HERK1 and WAK1, were changed in xxt1 xxt2 plants and that cellulose synthase motility is reduced in xxt1 xxt2 cells, corresponding with a reduction in cellulose content. Our results indicate that loss of xyloglucan affects both the stability of the microtubule cytoskeleton and the production and patterning of cellulose in primary cell walls. These findings establish, to our knowledge, new links between wall integrity, cytoskeletal dynamics, and wall synthesis in the regulation of plant morphogenesis. © 2016 American Society of Plant Biologists. All Rights Reserved.

Genetic Networks and Anticipation of Gene Expression Patterns

NASA Astrophysics Data System (ADS)

Gebert, J.; Lätsch, M.; Pickl, S. W.; Radde, N.; Weber, G.-W.; Wünschiers, R.

2004-08-01

An interesting problem for computational biology is the analysis of time-series expression data. Here, the application of modern methods from dynamical systems, optimization theory, numerical algorithms and the utilization of implicit discrete information lead to a deeper understanding. In [1], we suggested to represent the behavior of time-series gene expression patterns by a system of ordinary differential equations, which we analytically and algorithmically investigated under the parametrical aspect of stability or instability. Our algorithm strongly exploited combinatorial information. In this paper, we deepen, extend and exemplify this study from the viewpoint of underlying mathematical modelling. This modelling consists in evaluating DNA-microarray measurements as the basis of anticipatory prediction, in the choice of a smooth model given by differential equations, in an approach of the right-hand side with parametric matrices, and in a discrete approximation which is a least squares optimization problem. We give a mathematical and biological discussion, and pay attention to the special case of a linear system, where the matrices do not depend on the state of expressions. Here, we present first numerical examples.

Dynamic expression of the LAP family of genes during early development of Xenopus tropicalis.

PubMed

Yang, Qiutan; Lv, Xiaoyan; Kong, Qinghua; Li, Chaocui; Zhou, Qin; Mao, Bingyu

2011-10-01

The leucine-rich repeats and PDZ (LAP) family of genes are crucial for the maintenance of cell polarity as well as for epithelial homeostasis and tumor suppression in both vertebrates and invertebrates. Four members of this gene family are known: densin, erbin, scribble and lano. Here, we identified the four members of the LAP gene family in Xenopus tropicalis and studied their expression patterns during embryonic development. The Xenopus LAP proteins show a conserved domain structure that is similar to their homologs in other vertebrates. In Xenopus embryos, these genes were detected in animal cap cells at the early gastrula stage. At later stages of development, they were widely expressed in epithelial tissues that are highly polar in nature, including the neural epithelia, optic and otic vesicles, and in the pronephros. These data suggest that the roles of the Xenopus LAP genes in the control of cell polarity and morphogenesis are conserved during early development. Erbin and lano show similar expression patterns in the developing head, suggesting potential functional interactions between the two molecules in vivo.

Efficient Spatio-Temporal Local Binary Patterns for Spontaneous Facial Micro-Expression Recognition

PubMed Central

Wang, Yandan; See, John; Phan, Raphael C.-W.; Oh, Yee-Hui

2015-01-01

Micro-expression recognition is still in the preliminary stage, owing much to the numerous difficulties faced in the development of datasets. Since micro-expression is an important affective clue for clinical diagnosis and deceit analysis, much effort has gone into the creation of these datasets for research purposes. There are currently two publicly available spontaneous micro-expression datasets—SMIC and CASME II, both with baseline results released using the widely used dynamic texture descriptor LBP-TOP for feature extraction. Although LBP-TOP is popular and widely used, it is still not compact enough. In this paper, we draw further inspiration from the concept of LBP-TOP that considers three orthogonal planes by proposing two efficient approaches for feature extraction. The compact robust form described by the proposed LBP-Six Intersection Points (SIP) and a super-compact LBP-Three Mean Orthogonal Planes (MOP) not only preserves the essential patterns, but also reduces the redundancy that affects the discriminality of the encoded features. Through a comprehensive set of experiments, we demonstrate the strengths of our approaches in terms of recognition accuracy and efficiency. PMID:25993498

Propagating gene expression fronts in a one-dimensional coupled system of artificial cells

NASA Astrophysics Data System (ADS)

Tayar, Alexandra M.; Karzbrun, Eyal; Noireaux, Vincent; Bar-Ziv, Roy H.

2015-12-01

Living systems employ front propagation and spatiotemporal patterns encoded in biochemical reactions for communication, self-organization and computation. Emulating such dynamics in minimal systems is important for understanding physical principles in living cells and in vitro. Here, we report a one-dimensional array of DNA compartments in a silicon chip as a coupled system of artificial cells, offering the means to implement reaction-diffusion dynamics by integrated genetic circuits and chip geometry. Using a bistable circuit we programmed a front of protein synthesis propagating in the array as a cascade of signal amplification and short-range diffusion. The front velocity is maximal at a saddle-node bifurcation from a bistable regime with travelling fronts to a monostable regime that is spatially homogeneous. Near the bifurcation the system exhibits large variability between compartments, providing a possible mechanism for population diversity. This demonstrates that on-chip integrated gene circuits are dynamical systems driving spatiotemporal patterns, cellular variability and symmetry breaking.

Sorting Five Human Tumor Types Reveals Specific Biomarkers and Background Classification Genes.

PubMed

Roche, Kimberly E; Weinstein, Marvin; Dunwoodie, Leland J; Poehlman, William L; Feltus, Frank A

2018-05-25

We applied two state-of-the-art, knowledge independent data-mining methods - Dynamic Quantum Clustering (DQC) and t-Distributed Stochastic Neighbor Embedding (t-SNE) - to data from The Cancer Genome Atlas (TCGA). We showed that the RNA expression patterns for a mixture of 2,016 samples from five tumor types can sort the tumors into groups enriched for relevant annotations including tumor type, gender, tumor stage, and ethnicity. DQC feature selection analysis discovered 48 core biomarker transcripts that clustered tumors by tumor type. When these transcripts were removed, the geometry of tumor relationships changed, but it was still possible to classify the tumors using the RNA expression profiles of the remaining transcripts. We continued to remove the top biomarkers for several iterations and performed cluster analysis. Even though the most informative transcripts were removed from the cluster analysis, the sorting ability of remaining transcripts remained strong after each iteration. Further, in some iterations we detected a repeating pattern of biological function that wasn't detectable with the core biomarker transcripts present. This suggests the existence of a "background classification" potential in which the pattern of gene expression after continued removal of "biomarker" transcripts could still classify tumors in agreement with the tumor type.

Floral Morphogenesis: Stochastic Explorations of a Gene Network Epigenetic Landscape

PubMed Central

Aldana, Maximino; Benítez, Mariana; Cortes-Poza, Yuriria; Espinosa-Soto, Carlos; Hartasánchez, Diego A.; Lotto, R. Beau; Malkin, David; Escalera Santos, Gerardo J.; Padilla-Longoria, Pablo

2008-01-01

In contrast to the classical view of development as a preprogrammed and deterministic process, recent studies have demonstrated that stochastic perturbations of highly non-linear systems may underlie the emergence and stability of biological patterns. Herein, we address the question of whether noise contributes to the generation of the stereotypical temporal pattern in gene expression during flower development. We modeled the regulatory network of organ identity genes in the Arabidopsis thaliana flower as a stochastic system. This network has previously been shown to converge to ten fixed-point attractors, each with gene expression arrays that characterize inflorescence cells and primordial cells of sepals, petals, stamens, and carpels. The network used is binary, and the logical rules that govern its dynamics are grounded in experimental evidence. We introduced different levels of uncertainty in the updating rules of the network. Interestingly, for a level of noise of around 0.5–10%, the system exhibited a sequence of transitions among attractors that mimics the sequence of gene activation configurations observed in real flowers. We also implemented the gene regulatory network as a continuous system using the Glass model of differential equations, that can be considered as a first approximation of kinetic-reaction equations, but which are not necessarily equivalent to the Boolean model. Interestingly, the Glass dynamics recover a temporal sequence of attractors, that is qualitatively similar, although not identical, to that obtained using the Boolean model. Thus, time ordering in the emergence of cell-fate patterns is not an artifact of synchronous updating in the Boolean model. Therefore, our model provides a novel explanation for the emergence and robustness of the ubiquitous temporal pattern of floral organ specification. It also constitutes a new approach to understanding morphogenesis, providing predictions on the population dynamics of cells with different genetic configurations during development. PMID:18978941

Characterization and Expression Patterns of microRNAs Involved in Rice Grain Filling

PubMed Central

Du, Yanxiu; Zhang, Jing; Li, Junzhou; Liu, Yanxia; Zhao, Yafan; Zhao, Quanzhi

2013-01-01

MicroRNAs (miRNAs) are upstream gene regulators of plant development and hormone homeostasis through their directed cleavage or translational repression of the target mRNAs, which may play crucial roles in rice grain filling and determining the final grain weight and yield. In this study, high-throughput sequencing was performed to survey the dynamic expressions of miRNAs and their corresponding target genes at five distinct developmental stages of grain filling. In total, 445 known miRNAs and 45 novel miRNAs were detected with most of them expressed in a developmental stage dependent manner, and the majority of known miRNAs, which increased gradually with rice grain filling, showed negatively related to the grain filling rate. Detailed expressional comparisons revealed a clear negative correlation between most miRNAs and their target genes. It was found that specific miRNA cohorts are expressed in a developmental stage dependent manner during grain filling and the known functions of these miRNAs are involved in plant hormone homeostasis and starch accumulation, indicating that the expression dynamics of these miRNAs might play key roles in regulating rice grain filling. PMID:23365650

Gene Circuit Analysis of the Terminal Gap Gene huckebein

PubMed Central

Ashyraliyev, Maksat; Siggens, Ken; Janssens, Hilde; Blom, Joke; Akam, Michael; Jaeger, Johannes

2009-01-01

The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb) on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb) domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network. PMID:19876378

Gene circuit analysis of the terminal gap gene huckebein.

PubMed

Ashyraliyev, Maksat; Siggens, Ken; Janssens, Hilde; Blom, Joke; Akam, Michael; Jaeger, Johannes

2009-10-01

The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb) on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb) domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network.

Using NASA's GeneLab for VESGEN Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, P.; Weitzel, Alexander; Vyas, R. J.; Murray, M. C.; Vickerman, M. B.; Bhattacharya, S.; Wyatt, S. E.

2016-01-01

One fundamental requirement shared by humans with all higher terrestrial life forms, including other vertebrates, insects, and higher land plants, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. A unifying perspective is that vascular patterning offers a useful readout of molecular signaling that necessarily integrates these complex pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascularrelated changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the spatial and dynamic dimensions of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions. Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a Notch antagonist were analyzed by VESGEN. Other VESGEN research applications include the mouse retina, GI and coronary vessels, avian placental analogs and translational studies in the astronaut retina related to health challenges for long-duration missions.

NASAs VESGEN: Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways Using GeneLab.

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia A.; Weitzel, Alexander; Vyas, Ruchi J.; Murray, Matthew C.; Wyatt, Sarah E.

2016-01-01

One fundamental requirement shared by humans with all higher terrestrial life forms, including insect wings, higher land plants and other vertebrates, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. One unifying perspective is that vascular patterning offers a useful readout that necessarily integrates complex molecular signaling pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, stress response, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascular-related changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the Euclidean and dynamic dimensions (x,y,t) of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions (i,j,k,...). Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a Notch antagonist were analyzed by VESGEN. Other VESGEN research applications include the mouse retina, GI and coronary vessels, avian placental analogs and translational studies in the astronaut retina related to health challenges for long-duration missions.

Robust patterning of gene expression based on internal coordinate system of cells.

PubMed

Ogawa, Ken-ichiro; Miyake, Yoshihiro

2015-06-01

Cell-to-cell communication in multicellular organisms is established through the transmission of various kinds of chemical substances such as proteins. It is well known that gene expression triggered by a chemical substance in individuals has stable spatial patterns despite the individual differences in concentration patterns of the chemical substance. This fact reveals an important property of multicellular organisms called "robustness", which allows the organisms to generate their forms while maintaining proportion. Robustness has been conventionally accounted for by the stability of solutions of dynamical equations that represent a specific interaction network of chemical substances. However, any biological system is composed of autonomous elements. In general, an autonomous element does not merely accept information on the chemical substance from the environment; instead, it accepts the information based on its own criteria for reaction. Therefore, this phenomenon needs to be considered from the viewpoint of cells. Such a viewpoint is expected to allow the consideration of the autonomy of cells in multicellular organisms. This study aims to explain theoretically the robust patterning of gene expression from the viewpoint of cells. For this purpose, we introduced a new operator for transforming a state variable of a chemical substance from an external coordinate system to an internal coordinate system of each cell, which describes the observation of the chemical substance by cells. We then applied this operator to the simplest reaction-diffusion model of the chemical substance to investigate observation effects by cells. Our mathematical analysis of this extended model indicates that the robust patterning of gene expression against individual differences in concentration pattern of the chemical substance can be explained from the viewpoint of cells if there is a regulation field that compensates for the difference between cells seen in the observation results. This result provides a new insight into the investigation of the mechanism of robust patterning in biological systems composed of individual elements. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

GATE: software for the analysis and visualization of high-dimensional time series expression data.

PubMed

MacArthur, Ben D; Lachmann, Alexander; Lemischka, Ihor R; Ma'ayan, Avi

2010-01-01

We present Grid Analysis of Time series Expression (GATE), an integrated computational software platform for the analysis and visualization of high-dimensional biomolecular time series. GATE uses a correlation-based clustering algorithm to arrange molecular time series on a two-dimensional hexagonal array and dynamically colors individual hexagons according to the expression level of the molecular component to which they are assigned, to create animated movies of systems-level molecular regulatory dynamics. In order to infer potential regulatory control mechanisms from patterns of correlation, GATE also allows interactive interroga-tion of movies against a wide variety of prior knowledge datasets. GATE movies can be paused and are interactive, allowing users to reconstruct networks and perform functional enrichment analyses. Movies created with GATE can be saved in Flash format and can be inserted directly into PDF manuscript files as interactive figures. GATE is available for download and is free for academic use from http://amp.pharm.mssm.edu/maayan-lab/gate.htm

DTWscore: differential expression and cell clustering analysis for time-series single-cell RNA-seq data.

PubMed

Wang, Zhuo; Jin, Shuilin; Liu, Guiyou; Zhang, Xiurui; Wang, Nan; Wu, Deliang; Hu, Yang; Zhang, Chiping; Jiang, Qinghua; Xu, Li; Wang, Yadong

2017-05-23

The development of single-cell RNA sequencing has enabled profound discoveries in biology, ranging from the dissection of the composition of complex tissues to the identification of novel cell types and dynamics in some specialized cellular environments. However, the large-scale generation of single-cell RNA-seq (scRNA-seq) data collected at multiple time points remains a challenge to effective measurement gene expression patterns in transcriptome analysis. We present an algorithm based on the Dynamic Time Warping score (DTWscore) combined with time-series data, that enables the detection of gene expression changes across scRNA-seq samples and recovery of potential cell types from complex mixtures of multiple cell types. The DTWscore successfully classify cells of different types with the most highly variable genes from time-series scRNA-seq data. The study was confined to methods that are implemented and available within the R framework. Sample datasets and R packages are available at https://github.com/xiaoxiaoxier/DTWscore .

Cultural similarities and differences in the perception of emotional valence and intensity: a comparison of Americans and Hong Kong Chinese.

PubMed

Zhu, Zhuoying; Ho, Samuel M Y; Bonanno, George A

2013-01-01

Despite being challenged for their ecological validity, studies of emotion perception have often relied on static, posed expressions. One of the key reasons is that dynamic, spontaneous expressions are difficult to control because of the existence of display rules and frequent co-occurrence of non-emotion related facial movements. The present study investigated cross-cultural patterns in the perception of emotion using an expressive regulation paradigm for generating facial expressions. The paradigm largely balances out the competing concerns for ecological and internal validity. Americans and Hong Kong Chinese (expressors) were presented with positively and negatively valenced pictures and were asked to enhance, suppress, or naturally display their facial expressions according to their subjective emotions. Videos of naturalistic and dynamic expressions of emotions were rated by Americans and Hong Kong Chinese (judges) for valence and intensity. The 2 cultures agreed on the valence and relative intensity of emotion expressions, but cultural differences were observed in absolute intensity ratings. The differences varied between positive and negative expressions. With positive expressions, ratings were higher when there was a cultural match between the expressor and the judge and when the expression was enhanced by the expressor. With negative expressions, Chinese judges gave higher ratings than their American counterparts for Chinese expressions under all 3 expressive conditions, and the discrepancy increased with expression intensity; no cultural differences were observed when American expressions were judged. The results were discussed with respect to the "decoding rules" and "same-culture advantage" approaches of emotion perception and a negativity bias in the Chinese collective culture.

Theory of networked minority games based on strategy pattern dynamics.

PubMed

Lo, T S; Chan, H Y; Hui, P M; Johnson, N F

2004-11-01

We formulate a theory of agent-based models in which agents compete to be in a winning group. The agents may be part of a network or not, and the winning group may be a minority group or not. An important feature of the present formalism is its focus on the dynamical pattern of strategy rankings, and its careful treatment of the strategy ties which arise during the system's temporal evolution. We apply it to the minority game with connected populations. Expressions for the mean success rate among the agents and for the mean success rate for agents with k neighbors are derived. We also use the theory to estimate the value of connectivity p above which the binary-agent-resource system with high resource levels makes the transition into the high-connectivity state.

Gene expression patterns during the larval development of European sea bass (dicentrarchus labrax) by microarray analysis.

PubMed

Darias, M J; Zambonino-Infante, J L; Hugot, K; Cahu, C L; Mazurais, D

2008-01-01

During the larval period, marine teleosts undergo very fast growth and dramatic changes in morphology, metabolism, and behavior to accomplish their metamorphosis into juvenile fish. Regulation of gene expression is widely thought to be a key mechanism underlying the management of the biological processes required for harmonious development over this phase of life. To provide an overall analysis of gene expression in the whole body during sea bass larval development, we monitored the expression of 6,626 distinct genes at 10 different points in time between 7 and 43 days post-hatching (dph) by using heterologous hybridization of a rainbow trout cDNA microarray. The differentially expressed genes (n = 485) could be grouped into two categories: genes that were generally up-expressed early, between 7 and 23 dph, and genes up-expressed between 25 and 43 dph. Interestingly, among the genes regulated during the larval period, those related to organogenesis, energy pathways, biosynthesis, and digestion were over-represented compared with total set of analyzed genes. We discuss the quantitative regulation of whole-body contents of these specific transcripts with regard to the ontogenesis and maturation of essential functions that take place over larval development. Our study is the first utilization of a transcriptomic approach in sea bass and reveals dynamic changes in gene expression patterns in relation to marine finfish larval development.

Inconsistent emotion recognition deficits across stimulus modalities in Huntington׳s disease.

PubMed

Rees, Elin M; Farmer, Ruth; Cole, James H; Henley, Susie M D; Sprengelmeyer, Reiner; Frost, Chris; Scahill, Rachael I; Hobbs, Nicola Z; Tabrizi, Sarah J

2014-11-01

Recognition of negative emotions is impaired in Huntington׳s Disease (HD). It is unclear whether these emotion-specific problems are driven by dissociable cognitive deficits, emotion complexity, test cue difficulty, or visuoperceptual impairments. This study set out to further characterise emotion recognition in HD by comparing patterns of deficits across stimulus modalities; notably including for the first time in HD, the more ecologically and clinically relevant modality of film clips portraying dynamic facial expressions. Fifteen early HD and 17 control participants were tested on emotion recognition from static facial photographs, non-verbal vocal expressions and one second dynamic film clips, all depicting different emotions. Statistically significant evidence of impairment of anger, disgust and fear recognition was seen in HD participants compared with healthy controls across multiple stimulus modalities. The extent of the impairment, as measured by the difference in the number of errors made between HD participants and controls, differed according to the combination of emotion and modality (p=0.013, interaction test). The largest between-group difference was seen in the recognition of anger from film clips. Consistent with previous reports, anger, disgust and fear were the most poorly recognised emotions by the HD group. This impairment did not appear to be due to task demands or expression complexity as the pattern of between-group differences did not correspond to the pattern of errors made by either group; implicating emotion-specific cognitive processing pathology. There was however evidence that the extent of emotion recognition deficits significantly differed between stimulus modalities. The implications in terms of designing future tests of emotion recognition and care giving are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

YebC controls virulence by activating T3SS gene expression in the pathogen Edwardsiella piscicida.

PubMed

Wei, Lifan; Wu, Yanyan; Qiao, Haoxian; Xu, Wensheng; Zhang, Yuanxing; Liu, Xiaohong; Wang, Qiyao

2018-06-12

Edwardsiella piscicida is an infectious Gram-negative bacterium that causes great losses to the aquaculture industry worldwide. Based on pattern analysis of conditional essentiality (PACE), a new method for transposon insertion sequencing (Tn-seq) data analysis, we investigated the genome-wide genetic requirements during the dynamic process of infection and colonization in turbot in this study. As a result, disruption of ETAE_1437 was discovered to lead to substantially reduced colonization, which was similar to the in vivo dynamic patterns of the mutants of T3SS or T6SS. Bioinformatics analysis indicated that ETAE_1437 is a YebC/PmpR family regulator. Moreover, we found that ETAE_1437 not only regulated quorum sensing by directly binding to the edwR promoter region but also activated T3SS expression by directly binding to the promoter region of the T3SS gene ETAE_0873. In addition, ETAE_1437 mutants exhibited substantial colonization defects and significantly decreased virulence in turbot. Overall, this study identified ETAE_1437 as a novel virulence regulator in E. piscicida and enriched our understanding of the pathogenesis of E. piscicida in fish. We thus reannotated ETAE_1437 as YebC.

Profiling CCK-mediated pancreatic growth: the dynamic genetic program and the role of STATs as potential regulators.

PubMed

Gurda, Grzegorz T; Wang, Jackie Y; Guo, LiLi; Ernst, Stephen A; Williams, John A

2012-01-18

Feeding mice with protease inhibitor (PI) leads to increased endogenous cholecystokinin (CCK) release and results in pancreatic growth. This adaptive response requires calcineurin (CN)-NFAT and AKT-mTOR pathways, but the genes involved, the dynamics of their expression, and other regulatory pathways remain unknown. Here, we examined the early (1-8 h) transcriptional program that underlies pancreatic growth. We found 314 upregulated and 219 downregulated genes with diverse temporal and functional profiles. Several new identifications include the following: stress response genes Gdf15 and Txnip, metabolic mediators Pitpnc1 and Hmges2, as well as components of growth factor response Fgf21, Atf3, and Egr1. The genes fell into seven self-organizing clusters, each with a distinct pattern of expression; a representative gene within each of the upregulated clusters (Egr1, Gadd45b, Rgs2, and Serpinb1a) was validated by qRT-PCR. Genes up at any point throughout the time course and CN-dependent genes were subjected to further bioinformatics-based networking and promoter analysis, yielding STATs as potential transcriptional regulators. As shown by PCR, qPCR, and Western blots, the active phospho-form of STAT3 and the Jak-STAT feedback inhibitor Socs2 were both increased throughout early pancreatic growth. Moreover, immunohistochemistry showed a CCK-dependent and acinar cell-specific increase in nuclear localization of p-STAT3, with >75% nuclear occupancy in PI-fed mice vs. <0.1% in controls. Thus, the study identified novel genes likely to be important for CCK-driven pancreatic growth, characterized and biologically validated the dynamic pattern of their expression and investigated STAT-Socs signaling as a new player in this trophic response.

Global Genome and Transcriptome Analyses of Magnaporthe oryzae Epidemic Isolate 98-06 Uncover Novel Effectors and Pathogenicity-Related Genes, Revealing Gene Gain and Lose Dynamics in Genome Evolution

PubMed Central

Dong, Yanhan; Li, Ying; Zhao, Miaomiao; Jing, Maofeng; Liu, Xinyu; Liu, Muxing; Guo, Xianxian; Zhang, Xing; Chen, Yue; Liu, Yongfeng; Liu, Yanhong; Ye, Wenwu; Zhang, Haifeng; Wang, Yuanchao; Zheng, Xiaobo; Wang, Ping; Zhang, Zhengguang

2015-01-01

Genome dynamics of pathogenic organisms are driven by pathogen and host co-evolution, in which pathogen genomes are shaped to overcome stresses imposed by hosts with various genetic backgrounds through generation of a variety of isolates. This same principle applies to the rice blast pathogen Magnaporthe oryzae and the rice host; however, genetic variations among different isolates of M. oryzae remain largely unknown, particularly at genome and transcriptome levels. Here, we applied genomic and transcriptomic analytical tools to investigate M. oryzae isolate 98-06 that is the most aggressive in infection of susceptible rice cultivars. A unique 1.4 Mb of genomic sequences was found in isolate 98-06 in comparison to reference strain 70-15. Genome-wide expression profiling revealed the presence of two critical expression patterns of M. oryzae based on 64 known pathogenicity-related (PaR) genes. In addition, 134 candidate effectors with various segregation patterns were identified. Five tested proteins could suppress BAX-mediated programmed cell death in Nicotiana benthamiana leaves. Characterization of isolate-specific effector candidates Iug6 and Iug9 and PaR candidate Iug18 revealed that they have a role in fungal propagation and pathogenicity. Moreover, Iug6 and Iug9 are located exclusively in the biotrophic interfacial complex (BIC) and their overexpression leads to suppression of defense-related gene expression in rice, suggesting that they might participate in biotrophy by inhibiting the SA and ET pathways within the host. Thus, our studies identify novel effector and PaR proteins involved in pathogenicity of the highly aggressive M. oryzae field isolate 98-06, and reveal molecular and genomic dynamics in the evolution of M. oryzae and rice host interactions. PMID:25837042

Deep sequencing reveals cell-type-specific patterns of single-cell transcriptome variation.

PubMed

Dueck, Hannah; Khaladkar, Mugdha; Kim, Tae Kyung; Spaethling, Jennifer M; Francis, Chantal; Suresh, Sangita; Fisher, Stephen A; Seale, Patrick; Beck, Sheryl G; Bartfai, Tamas; Kuhn, Bernhard; Eberwine, James; Kim, Junhyong

2015-06-09

Differentiation of metazoan cells requires execution of different gene expression programs but recent single-cell transcriptome profiling has revealed considerable variation within cells of seeming identical phenotype. This brings into question the relationship between transcriptome states and cell phenotypes. Additionally, single-cell transcriptomics presents unique analysis challenges that need to be addressed to answer this question. We present high quality deep read-depth single-cell RNA sequencing for 91 cells from five mouse tissues and 18 cells from two rat tissues, along with 30 control samples of bulk RNA diluted to single-cell levels. We find that transcriptomes differ globally across tissues with regard to the number of genes expressed, the average expression patterns, and within-cell-type variation patterns. We develop methods to filter genes for reliable quantification and to calibrate biological variation. All cell types include genes with high variability in expression, in a tissue-specific manner. We also find evidence that single-cell variability of neuronal genes in mice is correlated with that in rats consistent with the hypothesis that levels of variation may be conserved. Single-cell RNA-sequencing data provide a unique view of transcriptome function; however, careful analysis is required in order to use single-cell RNA-sequencing measurements for this purpose. Technical variation must be considered in single-cell RNA-sequencing studies of expression variation. For a subset of genes, biological variability within each cell type appears to be regulated in order to perform dynamic functions, rather than solely molecular noise.

Conservation of Endo16 expression in sea urchins despite evolutionary divergence in both cis and trans-acting components of transcriptional regulation

NASA Technical Reports Server (NTRS)

Romano, Laura A.; Wray, Gregory A.

2003-01-01

Evolutionary changes in transcriptional regulation undoubtedly play an important role in creating morphological diversity. However, there is little information about the evolutionary dynamics of cis-regulatory sequences. This study examines the functional consequence of evolutionary changes in the Endo16 promoter of sea urchins. The Endo16 gene encodes a large extracellular protein that is expressed in the endoderm and may play a role in cell adhesion. Its promoter has been characterized in exceptional detail in the purple sea urchin, Strongylocentrotus purpuratus. We have characterized the structure and function of the Endo16 promoter from a second sea urchin species, Lytechinus variegatus. The Endo16 promoter sequences have evolved in a strongly mosaic manner since these species diverged approximately 35 million years ago: the most proximal region (module A) is conserved, but the remaining modules (B-G) are unalignable. Despite extensive divergence in promoter sequences, the pattern of Endo16 transcription is largely conserved during embryonic and larval development. Transient expression assays demonstrate that 2.2 kb of upstream sequence in either species is sufficient to drive GFP reporter expression that correctly mimics this pattern of Endo16 transcription. Reciprocal cross-species transient expression assays imply that changes have also evolved in the set of transcription factors that interact with the Endo16 promoter. Taken together, these results suggest that stabilizing selection on the transcriptional output may have operated to maintain a similar pattern of Endo16 expression in S. purpuratus and L. variegatus, despite dramatic divergence in promoter sequence and mechanisms of transcriptional regulation.

Interactions between Bmp-4 and Msx-1 act to restrict gene expression to odontogenic mesenchyme.

PubMed

Tucker, A S; Al Khamis, A; Sharpe, P T

1998-08-01

Tooth development is regulated by a reciprocal series of epithelial-mesenchymal interactions. Bmp4 has been identified as a candidate signalling molecule in these interactions, initially as an epithelial signal and then later at the bud stage as a mesenchymal signal (Vainio et al. [1993] Cell 75:45-58). A target gene for Bmp4 signalling is the homeobox gene Msx-1, identified by the ability of recombinant Bmp4 protein to induce expression in mesenchyme. There is, however, no evidence that Bmp4 is the endogenous inducer of Msx-1 expression. Msx-1 and Bmp-4 show dynamic, interactive patterns of expression in oral epithelium and ectomesenchyme during the early stages of tooth development. In this study, we compare the temporal and spatial expression of these two genes to determine whether the changing expression patterns of these genes are consistent with interactions between the two molecules. We show that changes in Bmp-4 expression precede changes in Msx-1 expression. At embryonic day (E)10.5-E11.0, expression patterns are consistent with BMP4 from the epithelium, inducing or maintaining Msx-1 in underlying mesenchyme. At E11.5, Bmp-4 expression shifts from epithelium to mesenchyme and is rapidly followed by localised up-regulation of Msx-1 expression at the sites of Bmp-4 expression. Using cultured explants of developing mandibles, we confirm that exogenous BMP4 is capable of replacing the endogenous source in epithelium and inducing Msx-1 gene expression in mesenchyme. By using noggin, a BMP inhibitor, we show that endogenous Msx-1 expression can be inhibited at E10.5 and E11.5, providing the first evidence that endogenous Bmp-4 from the epithelium is responsible for regulating the early spatial expression of Msx-1. We also show that the mesenchymal shift in Bmp-4 is responsible for up-regulating Msx-1 specifically at the sites of future tooth formation. Thus, we establish that a reciprocal series of interactions act to restrict expression of both genes to future sites of tooth formation, creating a positive feedback loop that maintains expression of both genes in tooth mesenchymal cells.

Foregut separation and tracheo-oesophageal malformations: The role of tracheal outgrowth, dorso-ventral patterning and programmed cell death

PubMed Central

Ioannides, Adonis S.; Massa, Valentina; Ferraro, Elisabetta; Cecconi, Francesco; Spitz, Lewis; Henderson, Deborah J.; Copp, Andrew J.

2010-01-01

Foregut division—the separation of dorsal (oesophageal) from ventral (tracheal) foregut components—is a crucial event in gastro-respiratory development, and frequently disturbed in clinical birth defects. Here, we examined three outstanding questions of foregut morphogenesis. The origin of the trachea is suggested to result either from respiratory outgrowth or progressive septation of the foregut tube. We found normal foregut lengthening despite failure of tracheo-oesophageal separation in Adriamycin-treated embryos, whereas active septation was observed only in normal foregut morphogenesis, indicating a primary role for septation. Dorso-ventral patterning of Nkx2.1 (ventral) and Sox2 (dorsal) expression is proposed to be critical for tracheo-oesophageal separation. However, normal dorso-ventral patterning of Nkx2.1 and Sox2 expression occurred in Adriamycin-treated embryos with defective foregut separation. In contrast, Shh expression shifts dynamically, ventral-to-dorsal, solely during normal morphogenesis, particularly implicating Shh in foregut morphogenesis. Dying cells localise to the fusing foregut epithelial ridges, with disturbance of this apoptotic pattern in Adriamycin, Shh and Nkx2.1 models. Strikingly, however, genetic suppression of apoptosis in the Apaf1 mutant did not prevent foregut separation, indicating that apoptosis is not required for tracheo-oesophageal morphogenesis. Epithelial remodelling during septation may cause loss of cell-cell or cell-matrix interactions, resulting in apoptosis (anoikis) as a secondary consequence. PMID:19913007

A transcriptional dynamic network during Arabidopsis thaliana pollen development.

PubMed

Wang, Jigang; Qiu, Xiaojie; Li, Yuhua; Deng, Youping; Shi, Tieliu

2011-01-01

To understand transcriptional regulatory networks (TRNs), especially the coordinated dynamic regulation between transcription factors (TFs) and their corresponding target genes during development, computational approaches would represent significant advances in the genome-wide expression analysis. The major challenges for the experiments include monitoring the time-specific TFs' activities and identifying the dynamic regulatory relationships between TFs and their target genes, both of which are currently not yet available at the large scale. However, various methods have been proposed to computationally estimate those activities and regulations. During the past decade, significant progresses have been made towards understanding pollen development at each development stage under the molecular level, yet the regulatory mechanisms that control the dynamic pollen development processes remain largely unknown. Here, we adopt Networks Component Analysis (NCA) to identify TF activities over time course, and infer their regulatory relationships based on the coexpression of TFs and their target genes during pollen development. We carried out meta-analysis by integrating several sets of gene expression data related to Arabidopsis thaliana pollen development (stages range from UNM, BCP, TCP, HP to 0.5 hr pollen tube and 4 hr pollen tube). We constructed a regulatory network, including 19 TFs, 101 target genes and 319 regulatory interactions. The computationally estimated TF activities were well correlated to their coordinated genes' expressions during the development process. We clustered the expression of their target genes in the context of regulatory influences, and inferred new regulatory relationships between those TFs and their target genes, such as transcription factor WRKY34, which was identified that specifically expressed in pollen, and regulated several new target genes. Our finding facilitates the interpretation of the expression patterns with more biological relevancy, since the clusters corresponding to the activity of specific TF or the combination of TFs suggest the coordinated regulation of TFs to their target genes. Through integrating different resources, we constructed a dynamic regulatory network of Arabidopsis thaliana during pollen development with gene coexpression and NCA. The network illustrated the relationships between the TFs' activities and their target genes' expression, as well as the interactions between TFs, which provide new insight into the molecular mechanisms that control the pollen development.

Human Endometrial DNA Methylome Is Cycle-Dependent and Is Associated With Gene Expression Regulation

PubMed Central

Houshdaran, Sahar; Zelenko, Zara; Irwin, Juan C.

2014-01-01

Human endometrium undergoes major gene expression changes, resulting in altered cellular functions in response to cyclic variations in circulating estradiol and progesterone, largely mediated by transcription factors and nuclear receptors. In addition to classic modulators, epigenetic mechanisms regulate gene expression during development in response to environmental factors and in some diseases and have roles in steroid hormone action. Herein, we tested the hypothesis that DNA methylation plays a role in gene expression regulation in human endometrium in different hormonal milieux. High throughput, genome-wide DNA methylation profiling of endometrial samples in proliferative, early secretory, and midsecretory phases revealed dynamic DNA methylation patterns with segregation of proliferative from secretory phase samples by unsupervised cluster analysis of differentially methylated genes. Changes involved different frequencies of gain and loss of methylation within or outside CpG islands. Comparison of changes in transcriptomes and corresponding DNA methylomes from the same samples revealed association of DNA methylation and gene expression in a number of loci, some important in endometrial biology. Human endometrial stromal fibroblasts treated in vitro with estradiol and progesterone exhibited DNA methylation changes in several genes observed in proliferative and secretory phase tissues, respectively. Taken together, the data support the observation that epigenetic mechanisms are involved in gene expression regulation in human endometrium in different hormonal milieux, adding endometrium to a small number of normal adult tissues exhibiting dynamic DNA methylation. The data also raise the possibility that the interplay between steroid hormone and methylome dynamics regulates normal endometrial functions and, if abnormal, may result in endometrial dysfunction and associated disorders. PMID:24877562

Decoding facial expressions based on face-selective and motion-sensitive areas.

PubMed

Liang, Yin; Liu, Baolin; Xu, Junhai; Zhang, Gaoyan; Li, Xianglin; Wang, Peiyuan; Wang, Bin

2017-06-01

Humans can easily recognize others' facial expressions. Among the brain substrates that enable this ability, considerable attention has been paid to face-selective areas; in contrast, whether motion-sensitive areas, which clearly exhibit sensitivity to facial movements, are involved in facial expression recognition remained unclear. The present functional magnetic resonance imaging (fMRI) study used multi-voxel pattern analysis (MVPA) to explore facial expression decoding in both face-selective and motion-sensitive areas. In a block design experiment, participants viewed facial expressions of six basic emotions (anger, disgust, fear, joy, sadness, and surprise) in images, videos, and eyes-obscured videos. Due to the use of multiple stimulus types, the impacts of facial motion and eye-related information on facial expression decoding were also examined. It was found that motion-sensitive areas showed significant responses to emotional expressions and that dynamic expressions could be successfully decoded in both face-selective and motion-sensitive areas. Compared with static stimuli, dynamic expressions elicited consistently higher neural responses and decoding performance in all regions. A significant decrease in both activation and decoding accuracy due to the absence of eye-related information was also observed. Overall, the findings showed that emotional expressions are represented in motion-sensitive areas in addition to conventional face-selective areas, suggesting that motion-sensitive regions may also effectively contribute to facial expression recognition. The results also suggested that facial motion and eye-related information played important roles by carrying considerable expression information that could facilitate facial expression recognition. Hum Brain Mapp 38:3113-3125, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A self-organized learning strategy for object recognition by an embedded line of attraction

NASA Astrophysics Data System (ADS)

Seow, Ming-Jung; Alex, Ann T.; Asari, Vijayan K.

2012-04-01

For humans, a picture is worth a thousand words, but to a machine, it is just a seemingly random array of numbers. Although machines are very fast and efficient, they are vastly inferior to humans for everyday information processing. Algorithms that mimic the way the human brain computes and learns may be the solution. In this paper we present a theoretical model based on the observation that images of similar visual perceptions reside in a complex manifold in an image space. The perceived features are often highly structured and hidden in a complex set of relationships or high-dimensional abstractions. To model the pattern manifold, we present a novel learning algorithm using a recurrent neural network. The brain memorizes information using a dynamical system made of interconnected neurons. Retrieval of information is accomplished in an associative sense. It starts from an arbitrary state that might be an encoded representation of a visual image and converges to another state that is stable. The stable state is what the brain remembers. In designing a recurrent neural network, it is usually of prime importance to guarantee the convergence in the dynamics of the network. We propose to modify this picture: if the brain remembers by converging to the state representing familiar patterns, it should also diverge from such states when presented with an unknown encoded representation of a visual image belonging to a different category. That is, the identification of an instability mode is an indication that a presented pattern is far away from any stored pattern and therefore cannot be associated with current memories. These properties can be used to circumvent the plasticity-stability dilemma by using the fluctuating mode as an indicator to create new states. We capture this behavior using a novel neural architecture and learning algorithm, in which the system performs self-organization utilizing a stability mode and an instability mode for the dynamical system. Based on this observation we developed a self- organizing line attractor, which is capable of generating new lines in the feature space to learn unrecognized patterns. Experiments performed on UMIST pose database and CMU face expression variant database for face recognition have shown that the proposed nonlinear line attractor is able to successfully identify the individuals and it provided better recognition rate when compared to the state of the art face recognition techniques. Experiments on FRGC version 2 database has also provided excellent recognition rate in images captured in complex lighting environments. Experiments performed on the Japanese female face expression database and Essex Grimace database using the self organizing line attractor have also shown successful expression invariant face recognition. These results show that the proposed model is able to create nonlinear manifolds in a multidimensional feature space to distinguish complex patterns.

The RNA-Seq-based high resolution gene expression atlas of chickpea (Cicer arietinum L.) reveals dynamic spatio-temporal changes associated with growth and development.

PubMed

Kudapa, Himabindu; Garg, Vanika; Chitikineni, Annapurna; Varshney, Rajeev K

2018-04-10

Chickpea is one of the world's largest cultivated food legumes and is an excellent source of high-quality protein to the human diet. Plant growth and development are controlled by programmed expression of a suite of genes at the given time, stage, and tissue. Understanding how the underlying genome sequence translates into specific plant phenotypes at key developmental stages, information on gene expression patterns is crucial. Here, we present a comprehensive Cicer arietinum Gene Expression Atlas (CaGEA) across different plant developmental stages and organs covering the entire life cycle of chickpea. One of the widely used drought tolerant cultivars, ICC 4958 has been used to generate RNA-Seq data from 27 samples at 5 major developmental stages of the plant. A total of 816 million raw reads were generated and of these, 794 million filtered reads after quality control (QC) were subjected to downstream analysis. A total of 15,947 unique number of differentially expressed genes across different pairwise tissue combinations were identified. Significant differences in gene expression patterns contributing in the process of flowering, nodulation, and seed and root development were inferred in this study. Furthermore, differentially expressed candidate genes from "QTL-hotspot" region associated with drought stress response in chickpea were validated. © 2018 The Authors. Plant, Cell & Environment Published by John Wiley & Sons Ltd.

Videos of conspecifics elicit interactive looking patterns and facial expressions in monkeys.

PubMed

Mosher, Clayton P; Zimmerman, Prisca E; Gothard, Katalin M

2011-08-01

A broader understanding of the neural basis of social behavior in primates requires the use of species-specific stimuli that elicit spontaneous, but reproducible and tractable behaviors. In this context of natural behaviors, individual variation can further inform about the factors that influence social interactions. To approximate natural social interactions similar to those documented by field studies, we used unedited video footage to induce in viewer monkeys spontaneous facial expressions and looking patterns in the laboratory setting. Three adult male monkeys (Macaca mulatta), previously behaviorally and genetically (5-HTTLPR) characterized, were monitored while they watched 10 s video segments depicting unfamiliar monkeys (movie monkeys) displaying affiliative, neutral, and aggressive behaviors. The gaze and head orientation of the movie monkeys alternated between "averted" and "directed" at the viewer. The viewers were not reinforced for watching the movies, thus their looking patterns indicated their interest and social engagement with the stimuli. The behavior of the movie monkey accounted for differences in the looking patterns and facial expressions displayed by the viewers. We also found multiple significant differences in the behavior of the viewers that correlated with their interest in these stimuli. These socially relevant dynamic stimuli elicited spontaneous social behaviors, such as eye-contact induced reciprocation of facial expression, gaze aversion, and gaze following, that were previously not observed in response to static images. This approach opens a unique opportunity to understanding the mechanisms that trigger spontaneous social behaviors in humans and nonhuman primates. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Spatially Restricted and Developmentally Dynamic Expression of Engrailed Genes in Multiple Cerebellar Cell Types

PubMed Central

Wilson, Sandra L.; Kalinovsky, Anna; Orvis, Grant D.

2011-01-01

The cerebellum is a highly organized structure partitioned into lobules along the anterior–posterior (A-P) axis and into striped molecular domains along the medial–lateral (M-L) axis. The Engrailed (En) homeobox genes are required for patterning the morphological and molecular domains along both axes, as well as for the establishment of the normal afferent topography required to generate a fully functional cerebellum. As a means to understand how the En genes regulate multiple levels of cerebellum construction, we characterized En1 and En2 expression around birth and at postnatal day (P)21 during the period when the cerebellum undergoes a remarkable transformation from a smooth ovoid structure to a highly foliated structure. We show that both En1 and En2 are expressed in many neuronal cell types in the cerebellum, and expression persists until at least P21. En1 and En2 expression, however, undergoes profound changes in their cellular and spatial distributions between embryonic stages and P21, and their expression domains become largely distinct. Comparison of the distribution of En-expressing Purkinje cells relative to early- and late-onset Purkinje cell M-L stripe proteins revealed that although En1- and En2-expressing Purkinje cell domains do not strictly align with those of ZEBRINII at P21, a clear pattern exists that is most evident at E17.5 by an inverse correlation between the level of En2 expression and PLCβ4 and EPHA4. PMID:21431469

The identification of age-associated cancer markers by an integrative analysis of dynamic DNA methylation changes.

PubMed

Wang, Yihan; Zhang, Jingyu; Xiao, Xingjun; Liu, Hongbo; Wang, Fang; Li, Song; Wen, Yanhua; Wei, Yanjun; Su, Jianzhong; Zhang, Yunming; Zhang, Yan

2016-03-07

As one of the most widely studied epigenetic modifications, DNA methylation has an important influence on human traits and cancers. Dynamic variations in DNA methylation have been reported in malignant neoplasm and aging; however, the mechanisms remain poorly understood. By constructing an age-associated and cancer-related weighted network (ACWN) based on the correlation of the methylation level and the protein-protein interaction, we found that DNA methylation changes associated with age were closely related to the occurrence of cancer. Additional analysis of 102 module genes mined from the ACWN revealed discrimination based on two main patterns. One pattern involved methylation levels that increased with aging and were higher in cancer patients compared with normal controls (HH pattern). The other pattern involved methylation levels that decreased with aging and were lower in cancer compared with normal (LL pattern). Upon incorporation with gene expression levels, 25 genes were filtered based on negative regulation by DNA methylation. These genes were regarded as potential cancer risk markers that were influenced by age in the process of carcinogenesis. Our results will facilitate further studies regarding the impact of the epigenetic effects of aging on diseases and will aid in the development of tailored cancer preventive strategies.

The identification of age-associated cancer markers by an integrative analysis of dynamic DNA methylation changes

PubMed Central

Wang, Yihan; Zhang, Jingyu; Xiao, Xingjun; Liu, Hongbo; Wang, Fang; Li, Song; Wen, Yanhua; Wei, Yanjun; Su, Jianzhong; Zhang, Yunming; Zhang, Yan

2016-01-01

As one of the most widely studied epigenetic modifications, DNA methylation has an important influence on human traits and cancers. Dynamic variations in DNA methylation have been reported in malignant neoplasm and aging; however, the mechanisms remain poorly understood. By constructing an age-associated and cancer-related weighted network (ACWN) based on the correlation of the methylation level and the protein-protein interaction, we found that DNA methylation changes associated with age were closely related to the occurrence of cancer. Additional analysis of 102 module genes mined from the ACWN revealed discrimination based on two main patterns. One pattern involved methylation levels that increased with aging and were higher in cancer patients compared with normal controls (HH pattern). The other pattern involved methylation levels that decreased with aging and were lower in cancer compared with normal (LL pattern). Upon incorporation with gene expression levels, 25 genes were filtered based on negative regulation by DNA methylation. These genes were regarded as potential cancer risk markers that were influenced by age in the process of carcinogenesis. Our results will facilitate further studies regarding the impact of the epigenetic effects of aging on diseases and will aid in the development of tailored cancer preventive strategies. PMID:26949191

Dynamics of immediate early gene and neuropeptide gene response to prolonged immobilization stress: evidence against a critical role of the termination of exposure to the stressor.

PubMed

Trnecková, Lenka; Rotllant, David; Klenerová, Vera; Hynie, Sixtus; Armario, Antonio

2007-02-01

Stress-induced expression of immediate early genes (IEGs) appears to be transient even if the exposure to the stressor persists. However, there are some exceptions which suggest that particular characteristics of stressors can affect the dynamics of IEG expression. We studied in selected telencephalic, diencephalic and brainstem regions the mRNA levels of two clearly distinct IEGs (c-fos and arc) during prolonged exposure to a severe stressor such as immobilization (IMO) and after releasing the rats from the situation. Although regional differences were observed with the two IEGs, overall, c-fos mRNA levels progressively declined over the course of 4 h of continuous exposure to IMO, whereas arc mRNA levels were maintained at high levels in the brain regions that express this gene under stress (telencephalon). Levels of CRF hnRNA in the hypothalamus paraventricular nucleus only slightly declined during prolonged exposure to IMO. Surprisingly, termination of exposure to IMO did not modify CRF gene expression in the paraventricular nucleus or the pattern of IEGs expression, with the exception of c-fos in the lateral septum. Thus, putative signals associated to the termination of exposure to IMO were unable to modify either IEG expression in most brain areas or CRF gene expression in the paraventricular nucleus.

Evolutionary genetics of maternal effects

PubMed Central

Wolf, Jason B.; Wade, Michael J.

2016-01-01

Maternal genetic effects (MGEs), where genes expressed by mothers affect the phenotype of their offspring, are important sources of phenotypic diversity in a myriad of organisms. We use a single‐locus model to examine how MGEs contribute patterns of heritable and nonheritable variation and influence evolutionary dynamics in randomly mating and inbreeding populations. We elucidate the influence of MGEs by examining the offspring genotype‐phenotype relationship, which determines how MGEs affect evolutionary dynamics in response to selection on offspring phenotypes. This approach reveals important results that are not apparent from classic quantitative genetic treatments of MGEs. We show that additive and dominance MGEs make different contributions to evolutionary dynamics and patterns of variation, which are differentially affected by inbreeding. Dominance MGEs make the offspring genotype‐phenotype relationship frequency dependent, resulting in the appearance of negative frequency‐dependent selection, while additive MGEs contribute a component of parent‐of‐origin dependent variation. Inbreeding amplifies the contribution of MGEs to the additive genetic variance and, therefore enhances their evolutionary response. Considering evolutionary dynamics of allele frequency change on an adaptive landscape, we show that this landscape differs from the mean fitness surface, and therefore, under some condition, fitness peaks can exist but not be “available” to the evolving population. PMID:26969266

When aging meets microgravity: whole genome promoters and enchancers transcription landscape in zebrafish onboard ISS

NASA Astrophysics Data System (ADS)

Arshanovskii, Kirill; Gusev, Oleg; Sychev, Vladimir; Poddubko, Svetlana; Deviatiiarov, Ruslan

2016-07-01

In order to gen new insights of gene regulation changes under conditions of real spaceflight, we have conducted whole-genome analysis of dynamic of promotes and enhancers transcriptional changes in zebrafish during prolonged exposure to real spaceflight. In the frame of Russia-Japan joint experiments "Aquatic Habitat"-"Aquarium" we have conducted Cap Analysis of Gene Expression (CAGE) assay of zebrafish in the rage from 7 to 40 days of real spaceflight onboard ISS. The analysis showed that both gene expression patterns and architecture of shapes and types of the promoters are affected by spaceflight environment.

Dynamics of Immune System Gene Expression upon Bacterial Challenge and Wounding in a Social Insect (Bombus terrestris)

PubMed Central

Erler, Silvio; Popp, Mario; Lattorff, H. Michael G.

2011-01-01

The innate immune system which helps individuals to combat pathogens comprises a set of genes representing four immune system pathways (Toll, Imd, JNK and JAK/STAT). There is a lack of immune genes in social insects (e.g. honeybees) when compared to Diptera. Potentially, this might be compensated by an advanced system of social immunity (synergistic action of several individuals). The bumble bee, Bombus terrestris, is a primitively eusocial species with an annual life cycle and colonies headed by a single queen. We used this key pollinator to study the temporal dynamics of immune system gene expression in response to wounding and bacterial challenge. Antimicrobial peptides (AMP) (abaecin, defensin 1, hymenoptaecin) were strongly up-regulated by wounding and bacterial challenge, the latter showing a higher impact on the gene expression level. Sterile wounding down-regulated TEP A, an effector gene of the JAK/STAT pathway, and bacterial infection influenced genes of the Imd (relish) and JNK pathway (basket). Relish was up-regulated within the first hour after bacterial challenge, but decreased strongly afterwards. AMP expression following wounding and bacterial challenge correlates with the expression pattern of relish whereas correlated expression with dorsal was absent. Although expression of AMPs was high, continuous bacterial growth was observed throughout the experiment. Here we demonstrate for the first time the temporal dynamics of immune system gene expression in a social insect. Wounding and bacterial challenge affected the innate immune system significantly. Induction of AMP expression due to wounding might comprise a pre-adaptation to accompanying bacterial infections. Compared with solitary species this social insect exhibits reduced immune system efficiency, as bacterial growth could not be inhibited. A negative feedback loop regulating the Imd-pathway is suggested. AMPs, the end product of the Imd-pathway, inhibited the up-regulation of the transcription factor relish, which is necessary for effector gene expression. PMID:21479237

The MADS transcription factor XAL2/AGL14 modulates auxin transport during Arabidopsis root development by regulating PIN expression

PubMed Central

Garay-Arroyo, Adriana; Ortiz-Moreno, Enrique; de la Paz Sánchez, María; Murphy, Angus S; García-Ponce, Berenice; Marsch-Martínez, Nayelli; de Folter, Stefan; Corvera-Poiré, Adriana; Jaimes-Miranda, Fabiola; Pacheco-Escobedo, Mario A; Dubrovsky, Joseph G; Pelaz, Soraya; Álvarez-Buylla, Elena R

2013-01-01

Elucidating molecular links between cell-fate regulatory networks and dynamic patterning modules is a key for understanding development. Auxin is important for plant patterning, particularly in roots, where it establishes positional information for cell-fate decisions. PIN genes encode plasma membrane proteins that serve as auxin efflux transporters; mutations in members of this gene family exhibit smaller roots with altered root meristems and stem-cell patterning. Direct regulators of PIN transcription have remained elusive. Here, we establish that a MADS-box gene (XAANTAL2, XAL2/AGL14) controls auxin transport via PIN transcriptional regulation during Arabidopsis root development; mutations in this gene exhibit altered stem-cell patterning, root meristem size, and root growth. XAL2 is necessary for normal shootward and rootward auxin transport, as well as for maintaining normal auxin distribution within the root. Furthermore, this MADS-domain transcription factor upregulates PIN1 and PIN4 by direct binding to regulatory regions and it is required for PIN4-dependent auxin response. In turn, XAL2 expression is regulated by auxin levels thus establishing a positive feedback loop between auxin levels and PIN regulation that is likely to be important for robust root patterning. PMID:24121311

Reaction-diffusion pattern in shoot apical meristem of plants.

PubMed

Fujita, Hironori; Toyokura, Koichi; Okada, Kiyotaka; Kawaguchi, Masayoshi

2011-03-29

A fundamental question in developmental biology is how spatial patterns are self-organized from homogeneous structures. In 1952, Turing proposed the reaction-diffusion model in order to explain this issue. Experimental evidence of reaction-diffusion patterns in living organisms was first provided by the pigmentation pattern on the skin of fishes in 1995. However, whether or not this mechanism plays an essential role in developmental events of living organisms remains elusive. Here we show that a reaction-diffusion model can successfully explain the shoot apical meristem (SAM) development of plants. SAM of plants resides in the top of each shoot and consists of a central zone (CZ) and a surrounding peripheral zone (PZ). SAM contains stem cells and continuously produces new organs throughout the lifespan. Molecular genetic studies using Arabidopsis thaliana revealed that the formation and maintenance of the SAM are essentially regulated by the feedback interaction between WUSHCEL (WUS) and CLAVATA (CLV). We developed a mathematical model of the SAM based on a reaction-diffusion dynamics of the WUS-CLV interaction, incorporating cell division and the spatial restriction of the dynamics. Our model explains the various SAM patterns observed in plants, for example, homeostatic control of SAM size in the wild type, enlarged or fasciated SAM in clv mutants, and initiation of ectopic secondary meristems from an initial flattened SAM in wus mutant. In addition, the model is supported by comparing its prediction with the expression pattern of WUS in the wus mutant. Furthermore, the model can account for many experimental results including reorganization processes caused by the CZ ablation and by incision through the meristem center. We thus conclude that the reaction-diffusion dynamics is probably indispensable for the SAM development of plants.

Reaction-Diffusion Pattern in Shoot Apical Meristem of Plants

PubMed Central

Fujita, Hironori; Toyokura, Koichi; Okada, Kiyotaka; Kawaguchi, Masayoshi

2011-01-01

A fundamental question in developmental biology is how spatial patterns are self-organized from homogeneous structures. In 1952, Turing proposed the reaction-diffusion model in order to explain this issue. Experimental evidence of reaction-diffusion patterns in living organisms was first provided by the pigmentation pattern on the skin of fishes in 1995. However, whether or not this mechanism plays an essential role in developmental events of living organisms remains elusive. Here we show that a reaction-diffusion model can successfully explain the shoot apical meristem (SAM) development of plants. SAM of plants resides in the top of each shoot and consists of a central zone (CZ) and a surrounding peripheral zone (PZ). SAM contains stem cells and continuously produces new organs throughout the lifespan. Molecular genetic studies using Arabidopsis thaliana revealed that the formation and maintenance of the SAM are essentially regulated by the feedback interaction between WUSHCEL (WUS) and CLAVATA (CLV). We developed a mathematical model of the SAM based on a reaction-diffusion dynamics of the WUS-CLV interaction, incorporating cell division and the spatial restriction of the dynamics. Our model explains the various SAM patterns observed in plants, for example, homeostatic control of SAM size in the wild type, enlarged or fasciated SAM in clv mutants, and initiation of ectopic secondary meristems from an initial flattened SAM in wus mutant. In addition, the model is supported by comparing its prediction with the expression pattern of WUS in the wus mutant. Furthermore, the model can account for many experimental results including reorganization processes caused by the CZ ablation and by incision through the meristem center. We thus conclude that the reaction-diffusion dynamics is probably indispensable for the SAM development of plants. PMID:21479227

Inferring the Limit Behavior of Some Elementary Cellular Automata

NASA Astrophysics Data System (ADS)

Ruivo, Eurico L. P.; de Oliveira, Pedro P. B.

Cellular automata locally define dynamical systems, discrete in space, time and in the state variables, capable of displaying arbitrarily complex global emergent behavior. One core question in the study of cellular automata refers to their limit behavior, that is, to the global dynamical features in an infinite time evolution. Previous works have shown that for finite time evolutions, the dynamics of one-dimensional cellular automata can be described by regular languages and, therefore, by finite automata. Such studies have shown the existence of growth patterns in the evolution of such finite automata for some elementary cellular automata rules and also inferred the limit behavior of such rules based upon the growth patterns; however, the results on the limit behavior were obtained manually, by direct inspection of the structures that arise during the time evolution. Here we present the formalization of an automatic method to compute such structures. Based on this, the rules of the elementary cellular automata space were classified according to the existence of a growth pattern in their finite automata. Also, we present a method to infer the limit graph of some elementary cellular automata rules, derived from the analysis of the regular expressions that describe their behavior in finite time. Finally, we analyze some attractors of two rules for which we could not compute the whole limit set.

Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing

PubMed Central

Gaublomme, Jellert; Shekhar, Karthik; Butty, Vincent; Yi, B. Alexander; Kralj, Joel M.; Bloxham, William; Boyer, Laurie A.; Regev, Aviv

2017-01-01

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising platform for cardiac studies in vitro, and possibly for tissue repair in humans. However, hiPSC-CM cells tend to retain morphology, metabolism, patterns of gene expression, and electrophysiology similar to that of embryonic cardiomyocytes. We grew hiPSC-CM in patterned islands of different sizes and shapes, and measured the effect of island geometry on action potential waveform and calcium dynamics using optical recordings of voltage and calcium from 970 islands of different sizes. hiPSC-CM in larger islands showed electrical and calcium dynamics indicative of greater functional maturity. We then compared transcriptional signatures of the small and large islands against a developmental time course of cardiac differentiation. Although island size had little effect on expression of most genes whose levels differed between hiPSC-CM and adult primary CM, we identified a subset of genes for which island size drove the majority (58%) of the changes associated with functional maturation. Finally, we patterned hiPSC-CM on islands with a variety of shapes to probe the relative contributions of soluble factors, electrical coupling, and direct cell-cell contacts to the functional maturation. Collectively, our data show that optical electrophysiology is a powerful tool for assaying hiPSC-CM maturation, and that island size powerfully drives activation of a subset of genes involved in cardiac maturation. PMID:28333933

Early demethylation of non-CpG, CpC-rich, elements in the myogenin 5′-flanking region

PubMed Central

Fuso, Andrea; Ferraguti, Giampiero; Grandoni, Francesco; Ruggeri, Raffaella; Scarpa, Sigfrido; Strom, Roberto

2010-01-01

The dynamic changes and structural patterns of DNA methylation of genes without CpG islands are poorly characterized. The relevance of CpG to the non-CpG methylation equilibrium in transcriptional repression is unknown. In this work, we analyzed the DNA methylation pattern of the 5′-flanking of the myogenin gene, a positive regulator of muscle differentiation with no CpG island and low CpG density, in both C2C12 muscle satellite cells and embryonic muscle. Embryonic brain was studied as a non-expressing tissue. High levels of both CpG and non-CpG methylation were observed in non-expressing experimental conditions. Both CpG and non-CpG methylation rapidly dropped during muscle differentiation and myogenin transcriptional activation with active demethylation dynamics. Non-CpG demethylation occurred more rapidly than CpG demethylation. Demethylation spread from initially highly methylated short CpC-rich elements to a virtually unmethylated status. These short elements have a high CpC content and density, share some motifs and largely coincide with putative recognition sequences of some differentiation-related transcription factors. Our findings point to a dynamically controlled equilibrium between CpG and non-CpG active demethylation in the transcriptional control of tissue-specific genes. The short CpC-rich elements are new structural features of the methylation machinery, whose functions may include priming the complete demethylation of a transcriptionally crucial DNA region. PMID:20935518

Molecular cloning, developmental expression, and cellular localization of the 70-kDa RPA-1 subunit of Drosophila melanogaster.

PubMed

Perdigão, J; Logarinho, E; Avides, M C; Sunkel, C E

1999-12-01

Replication protein A (RPA) is a highly conserved multifunctional heterotrimeric complex, involved in DNA replication, repair, recombination, and possibly transcription. Here, we report the cloning of the gene that codes for the largest subunit of the Drosophila melanogaster RPA homolog, dmRPA70. In situ hybridization showed that dmRPA70 RNA is present in developing embryos during the first 16 cycles. After this point, dm-RPA70 expression is downregulated in cells that enter a G1 phase and exit the mitotic cycle, becoming restricted to brief bursts of accumulation from late G1 to S phase. This pattern of regulated expression is also observed in the developing eye imaginal disc. In addition, we have shown that the presence of cyclin E is necessary and sufficient to drive the expression of dmRPA70 in embryonic cells arrested in G1 but is not required in tissues undergoing endoreduplication. Immunolocalization showed that in early developing embryos, the dmRPA70 protein associates with chromatin from the end of mitosis until the beginning of the next prophase in a dynamic speckled pattern that is strongly suggestive of its association with replication foci.

Absence of catalytic domain in a putative protein kinase C (PkcA) suppresses tip dominance in Dictyostelium discoideum

PubMed Central

Mohamed, Wasima; Ray, Sibnath; Brazill, Derrick; Baskar, Ramamurthy

2017-01-01

A number of organisms possess several isoforms of protein kinase C but little is known about the significance of any specific isoform during embryogenesis and development. To address this we characterized a PKC ortholog (PkcA; DDB_G0288147) in Dictyostelium discoideum. pkcA expression switches from prestalk in mound to prespore in slug, indicating a dynamic expression pattern. Mutants lacking the catalytic domain of PkcA (pkcA−) did not exhibit tip dominance. A striking phenotype of pkcA− was the formation of an aggregate with a central hollow, and aggregates later fragmented to form small mounds, each becoming a fruiting body. Optical density wave patterns of cAMP in the late aggregates showed several cAMP wave generation centers. We attribute these defects in pkcA− to impaired cAMP signaling, altered cell motility and decreased expression of the cell adhesion molecules – CadA and CsaA. pkcA− slugs showed ectopic expression of ecmA in the prespore region. Further, the use of a PKC-specific inhibitor, GF109203X that inhibits the activity of catalytic domain phenocopied pkcA−. PMID:26183108

Neutrality and Robustness in Evo-Devo: Emergence of Lateral Inhibition

PubMed Central

Munteanu, Andreea; Solé, Ricard V.

2008-01-01

Embryonic development is defined by the hierarchical dynamical process that translates genetic information (genotype) into a spatial gene expression pattern (phenotype) providing the positional information for the correct unfolding of the organism. The nature and evolutionary implications of genotype–phenotype mapping still remain key topics in evolutionary developmental biology (evo-devo). We have explored here issues of neutrality, robustness, and diversity in evo-devo by means of a simple model of gene regulatory networks. The small size of the system allowed an exhaustive analysis of the entire fitness landscape and the extent of its neutrality. This analysis shows that evolution leads to a class of robust genetic networks with an expression pattern characteristic of lateral inhibition. This class is a repertoire of distinct implementations of this key developmental process, the diversity of which provides valuable clues about its underlying causal principles. PMID:19023404

Temporal and spatial transcriptomic and microRNA dynamics of CAM photosynthesis in pineapple.

PubMed

Wai, Ching M; VanBuren, Robert; Zhang, Jisen; Huang, Lixian; Miao, Wenjing; Edger, Patrick P; Yim, Won C; Priest, Henry D; Meyers, Blake C; Mockler, Todd; Smith, J Andrew C; Cushman, John C; Ming, Ray

2017-10-01

The altered carbon assimilation pathway of crassulacean acid metabolism (CAM) photosynthesis results in an up to 80% higher water-use efficiency than C 3 photosynthesis in plants making it a potentially useful pathway for engineering crop plants with improved drought tolerance. Here we surveyed detailed temporal (diel time course) and spatial (across a leaf gradient) gene and microRNA (miRNA) expression patterns in the obligate CAM plant pineapple [Ananas comosus (L.) Merr.]. The high-resolution transcriptome atlas allowed us to distinguish between CAM-related and non-CAM gene copies. A differential gene co-expression network across green and white leaf diel datasets identified genes with circadian oscillation, CAM-related functions, and source-sink relations. Gene co-expression clusters containing CAM pathway genes are enriched with clock-associated cis-elements, suggesting circadian regulation of CAM. About 20% of pineapple microRNAs have diel expression patterns, with several that target key CAM-related genes. Expression and physiology data provide a model for CAM-specific carbohydrate flux and long-distance hexose transport. Together these resources provide a list of candidate genes for targeted engineering of CAM into C 3 photosynthesis crop species. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Emotions are emergent processes: they require a dynamic computational architecture

PubMed Central

Scherer, Klaus R.

2009-01-01

Emotion is a cultural and psychobiological adaptation mechanism which allows each individual to react flexibly and dynamically to environmental contingencies. From this claim flows a description of the elements theoretically needed to construct a virtual agent with the ability to display human-like emotions and to respond appropriately to human emotional expression. This article offers a brief survey of the desirable features of emotion theories that make them ideal blueprints for agent models. In particular, the component process model of emotion is described, a theory which postulates emotion-antecedent appraisal on different levels of processing that drive response system patterning predictions. In conclusion, investing seriously in emergent computational modelling of emotion using a nonlinear dynamic systems approach is suggested. PMID:19884141

Epidermal gene expression and ethnic pigmentation variations among individuals of Asian, European and African ancestry.

PubMed

Yin, Lanlan; Coelho, Sergio G; Ebsen, Dominik; Smuda, Christoph; Mahns, Andre; Miller, Sharon A; Beer, Janusz Z; Kolbe, Ludger; Hearing, Vincent J

2014-10-01

Differences in visible skin pigmentation give rise to the wide variation of skin colours seen in racial/ethnic populations. Skin pigmentation is important not only from cosmetic and psychological points of view, but more importantly because of its implications for the risk of all types of skin cancers, on photoaging, etc. Despite differences in those parameters in Caucasian and Asian skin types, they are remarkably similar in their production and distribution of melanins, and the mechanism(s) underlying their different characteristics have remained obscure. In this study, we used microarray analysis of skin suction blisters to investigate molecular differences underlying the determination of pigmentation in various skin types, and we used immunohistochemistry to validate the expression patterns of several interesting targets that were identified. Intriguingly, Caucasian and Asian skins had highly similar gene expression patterns that differed significantly from the pattern of African skin. The results of this study suggest the dynamic interactions of different types of cells in human skin that regulate its pigmentation, reveal that the known pigmentation genes have a limited contribution and uncover a new array of genes, including NINL and S100A4, that might be involved in that regulation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The neural dynamics underlying the interpersonal effects of emotional expression on decision making.

PubMed

Chen, Xuhai; Zheng, Tingting; Han, Lingzi; Chang, Yingchao; Luo, Yangmei

2017-04-20

Although numerous studies explore the effects of emotion on decision-making, the existing research has mainly focused on the influence of intrapersonal emotions, leaving the influence of one person's emotions on another's decisions underestimated. To specify how interpersonal emotions shape decision-making and delineate the underlying neural dynamics involved, the present study examined brain responses to utilitarian feedback combined with angry or happy faces in competitive and cooperative contexts. Behavioral results showed that participants responded slower following losses than wins when competitors express happiness but responded faster following losses than wins when cooperators express anger. Importantly, angry faces in competitive context reversed the differentiation pattern of feedback-related negativity (FRN) between losses and wins and diminished the difference between losses and wins on both P300 and theta power, but only diminished the difference on FRN between losses and wins in cooperative context. However, when partner displays happiness, losses versus wins elicited larger FRN and theta power in competitive context but smaller P300 in both contexts. These results suggest that interpersonal emotions shape decisions during both automatic motivational salience valuation (FRN) and conscious cognitive appraisal (P300) stages of processing, in which different emotional expressions exert interpersonal influence through different routes.

Advances in Quantitative Proteomics of Microbes and Microbial Communities

NASA Astrophysics Data System (ADS)

Waldbauer, J.; Zhang, L.; Rizzo, A. I.

2015-12-01

Quantitative measurements of gene expression are key to developing a mechanistic, predictive understanding of how microbial metabolism drives many biogeochemical fluxes and responds to environmental change. High-throughput RNA-sequencing can afford a wealth of information about transcript-level expression patterns, but it is becoming clear that expression dynamics are often very different at the protein level where biochemistry actually occurs. These divergent dynamics between levels of biological organization necessitate quantitative proteomic measurements to address many biogeochemical questions. The protein-level expression changes that underlie shifts in the magnitude, or even the direction, of metabolic and biogeochemical fluxes can be quite subtle and test the limits of current quantitative proteomics techniques. Here we describe methodologies for high-precision, whole-proteome quantification that are applicable to both model organisms of biogeochemical interest that may not be genetically tractable, and to complex community samples from natural environments. Employing chemical derivatization of peptides with multiple isotopically-coded tags, this strategy is rapid and inexpensive, can be implemented on a wide range of mass spectrometric instrumentation, and is relatively insensitive to chromatographic variability. We demonstrate the utility of this quantitative proteomics approach in application to both isolates and natural communities of sulfur-metabolizing and photosynthetic microbes.

Mouse Hair Cycle Expression Dynamics Modeled as Coupled Mesenchymal and Epithelial Oscillators

PubMed Central

Tasseff, Ryan; Bheda-Malge, Anjali; DiColandrea, Teresa; Bascom, Charles C.; Isfort, Robert J.; Gelinas, Richard

2014-01-01

The hair cycle is a dynamic process where follicles repeatedly move through phases of growth, retraction, and relative quiescence. This process is an example of temporal and spatial biological complexity. Understanding of the hair cycle and its regulation would shed light on many other complex systems relevant to biological and medical research. Currently, a systematic characterization of gene expression and summarization within the context of a mathematical model is not yet available. Given the cyclic nature of the hair cycle, we felt it was important to consider a subset of genes with periodic expression. To this end, we combined several mathematical approaches with high-throughput, whole mouse skin, mRNA expression data to characterize aspects of the dynamics and the possible cell populations corresponding to potentially periodic patterns. In particular two gene clusters, demonstrating properties of out-of-phase synchronized expression, were identified. A mean field, phase coupled oscillator model was shown to quantitatively recapitulate the synchronization observed in the data. Furthermore, we found only one configuration of positive-negative coupling to be dynamically stable, which provided insight on general features of the regulation. Subsequent bifurcation analysis was able to identify and describe alternate states based on perturbation of system parameters. A 2-population mixture model and cell type enrichment was used to associate the two gene clusters to features of background mesenchymal populations and rapidly expanding follicular epithelial cells. Distinct timing and localization of expression was also shown by RNA and protein imaging for representative genes. Taken together, the evidence suggests that synchronization between expanding epithelial and background mesenchymal cells may be maintained, in part, by inhibitory regulation, and potential mediators of this regulation were identified. Furthermore, the model suggests that impairing this negative regulation will drive a bifurcation which may represent transition into a pathological state such as hair miniaturization. PMID:25375120

Affective matching of odors and facial expressions in infants: shifting patterns between 3 and 7 months.

PubMed

Godard, Ornella; Baudouin, Jean-Yves; Schaal, Benoist; Durand, Karine

2016-01-01

Recognition of emotional facial expressions is a crucial skill for adaptive behavior. Past research suggests that at 5 to 7 months of age, infants look longer to an unfamiliar dynamic angry/happy face which emotionally matches a vocal expression. This suggests that they can match stimulations of distinct modalities on their emotional content. In the present study, olfaction-vision matching abilities were assessed across different age groups (3, 5 and 7 months) using dynamic expressive faces (happy vs. disgusted) and distinct hedonic odor contexts (pleasant, unpleasant and control) in a visual-preference paradigm. At all ages the infants were biased toward the disgust faces. This visual bias reversed into a bias for smiling faces in the context of the pleasant odor context in the 3-month-old infants. In infants aged 5 and 7 months, no effect of the odor context appeared in the present conditions. This study highlights the role of the olfactory context in the modulation of visual behavior toward expressive faces in infants. The influence of olfaction took the form of a contingency effect in 3-month-old infants, but later evolved to vanish or to take another form that could not be evidenced in the present study. © 2015 John Wiley & Sons Ltd.

Dynamic ride-sharing: Theory and practice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hall, R.W.; Qureshi, A.

1997-08-01

Dynamic Ride-sharing (DR) is envisioned as an automated process by which individuals find ride-matches on a trip by trip basis. This paper examines the DR concept on both a theoretical basis and on the basis of actual implementation in Los Angeles. Specifically, the paper investigates the likelihood that the user of a DR system would be successful in finding a ride-match. In a theoretical sense, this paper shows that dynamic ride-sharing is a viable concept. For a congested freeway corridor, the number of trips generated per unit time and space should be sufficient to yield a reasonably large population ofmore » potential ride-matches for a DR system. Unfortunately, as demonstrated in the experiment, theory and practice are not the same. Even when individuals share common trip patterns, consummating a ride-match is no easy task for logistical reasons. At best, one might expect a one in five change of someone offering a ride when trip patterns are similar. This probability would decline for casual trips, and when contacting individuals who have not expressed a prior willingness to carpool.« less

Micro-Expression Recognition Using Color Spaces.

PubMed

Wang, Su-Jing; Yan, Wen-Jing; Li, Xiaobai; Zhao, Guoying; Zhou, Chun-Guang; Fu, Xiaolan; Yang, Minghao; Tao, Jianhua

2015-12-01

Micro-expressions are brief involuntary facial expressions that reveal genuine emotions and, thus, help detect lies. Because of their many promising applications, they have attracted the attention of researchers from various fields. Recent research reveals that two perceptual color spaces (CIELab and CIELuv) provide useful information for expression recognition. This paper is an extended version of our International Conference on Pattern Recognition paper, in which we propose a novel color space model, tensor independent color space (TICS), to help recognize micro-expressions. In this paper, we further show that CIELab and CIELuv are also helpful in recognizing micro-expressions, and we indicate why these three color spaces achieve better performance. A micro-expression color video clip is treated as a fourth-order tensor, i.e., a four-dimension array. The first two dimensions are the spatial information, the third is the temporal information, and the fourth is the color information. We transform the fourth dimension from RGB into TICS, in which the color components are as independent as possible. The combination of dynamic texture and independent color components achieves a higher accuracy than does that of RGB. In addition, we define a set of regions of interests (ROIs) based on the facial action coding system and calculated the dynamic texture histograms for each ROI. Experiments are conducted on two micro-expression databases, CASME and CASME 2, and the results show that the performances for TICS, CIELab, and CIELuv are better than those for RGB or gray.

Direct multiplexed measurement of gene expression with color-coded probe pairs.

PubMed

Geiss, Gary K; Bumgarner, Roger E; Birditt, Brian; Dahl, Timothy; Dowidar, Naeem; Dunaway, Dwayne L; Fell, H Perry; Ferree, Sean; George, Renee D; Grogan, Tammy; James, Jeffrey J; Maysuria, Malini; Mitton, Jeffrey D; Oliveri, Paola; Osborn, Jennifer L; Peng, Tao; Ratcliffe, Amber L; Webster, Philippa J; Davidson, Eric H; Hood, Leroy; Dimitrov, Krassen

2008-03-01

We describe a technology, the NanoString nCounter gene expression system, which captures and counts individual mRNA transcripts. Advantages over existing platforms include direct measurement of mRNA expression levels without enzymatic reactions or bias, sensitivity coupled with high multiplex capability, and digital readout. Experiments performed on 509 human genes yielded a replicate correlation coefficient of 0.999, a detection limit between 0.1 fM and 0.5 fM, and a linear dynamic range of over 500-fold. Comparison of the NanoString nCounter gene expression system with microarrays and TaqMan PCR demonstrated that the nCounter system is more sensitive than microarrays and similar in sensitivity to real-time PCR. Finally, a comparison of transcript levels for 21 genes across seven samples measured by the nCounter system and SYBR Green real-time PCR demonstrated similar patterns of gene expression at all transcript levels.

The Drosophila Extradenticle and Homothorax selector proteins control branchless/FGF expression in mesodermal bridge-cells.

PubMed

Merabet, Samir; Ebner, Andreas; Affolter, Markus

2005-08-01

The stereotyped outgrowth of tubular branches of the Drosophila tracheal system is orchestrated by the local and highly dynamic expression profile of branchless (bnl), which encodes a secreted fibroblast growth factor (FGF)-like molecule. Despite the importance of the spatial and temporal bnl regulation, little is known about the upstream mechanisms that establish its complex expression pattern. Here, we show that the Extradenticle and Homothorax selector proteins control bnl transcription in a single cell per segment, the mesodermal bridge-cell. In addition, we observed that a key determinant of bridge-cell specification, the transcription factor Hunchback, is also required for bnl expression. Therefore, we propose that one of the functions of the bridge-cell is to synthesize and secrete the chemoattractant Bnl. These findings provide a hitherto unknown and interesting link between combinatorial inputs of transcription factors, cell-specific ligand expression and organ morphogenesis.

Scalable persistent identifier systems for dynamic datasets

NASA Astrophysics Data System (ADS)

Golodoniuc, P.; Cox, S. J. D.; Klump, J. F.

2016-12-01

Reliable and persistent identification of objects, whether tangible or not, is essential in information management. Many Internet-based systems have been developed to identify digital data objects, e.g., PURL, LSID, Handle, ARK. These were largely designed for identification of static digital objects. The amount of data made available online has grown exponentially over the last two decades and fine-grained identification of dynamically generated data objects within large datasets using conventional systems (e.g., PURL) has become impractical. We have compared capabilities of various technological solutions to enable resolvability of data objects in dynamic datasets, and developed a dataset-centric approach to resolution of identifiers. This is particularly important in Semantic Linked Data environments where dynamic frequently changing data is delivered live via web services, so registration of individual data objects to obtain identifiers is impractical. We use identifier patterns and pattern hierarchies for identification of data objects, which allows relationships between identifiers to be expressed, and also provides means for resolving a single identifier into multiple forms (i.e. views or representations of an object). The latter can be implemented through (a) HTTP content negotiation, or (b) use of URI querystring parameters. The pattern and hierarchy approach has been implemented in the Linked Data API supporting the United Nations Spatial Data Infrastructure (UNSDI) initiative and later in the implementation of geoscientific data delivery for the Capricorn Distal Footprints project using International Geo Sample Numbers (IGSN). This enables flexible resolution of multi-view persistent identifiers and provides a scalable solution for large heterogeneous datasets.

A Systematic Survey of Expression and Function of Zebrafish frizzled Genes

PubMed Central

Nikaido, Masataka; Law, Edward W. P.; Kelsh, Robert N.

2013-01-01

Wnt signaling is crucial for the regulation of numerous processes in development. Consistent with this, the gene families for both the ligands (Wnts) and receptors (Frizzleds) are very large. Surprisingly, while we have a reasonable understanding of the Wnt ligands likely to mediate specific Wnt-dependent processes, the corresponding receptors usually remain to be elucidated. Taking advantage of the zebrafish model's excellent genomic and genetic properties, we undertook a comprehensive analysis of the expression patterns of frizzled (fzd) genes in zebrafish. To explore their functions, we focused on testing their requirement in several developmental events known to be regulated by Wnt signaling, convergent extension movements of gastrulation, neural crest induction, and melanocyte specification. We found fourteen distinct fzd genes in the zebrafish genome. Systematic analysis of their expression patterns between 1-somite and 30 hours post-fertilization revealed complex, dynamic and overlapping expression patterns. This analysis demonstrated that only fzd3a, fzd9b, and fzd10 are expressed in the dorsal neural tube at stages corresponding to the timing of melanocyte specification. Surprisingly, however, morpholino knockdown of these, alone or in combination, gave no indication of reduction of melanocytes, suggesting the important involvement of untested fzds or another type of Wnt receptor in this process. Likewise, we found only fzd7b and fzd10 expressed at the border of the neural plate at stages appropriate for neural crest induction. However, neural crest markers were not reduced by knockdown of these receptors. Instead, these morpholino knockdown studies showed that fzd7a and fzd7b work co-operatively to regulate convergent extension movement during gastrulation. Furthermore, we show that the two fzd7 genes function together with fzd10 to regulate epiboly movements and mesoderm differentiation. PMID:23349976

Transcriptome Profiling of Wheat Inflorescence Development from Spikelet Initiation to Floral Patterning Identified Stage-Specific Regulatory Genes1[OPEN

PubMed Central

Feng, Nan; Song, Gaoyuan; Guan, Jiantao; Chen, Kai; Jia, Meiling; Huang, Dehua; Wu, Jiajie; Zhang, Lichao; Kong, Xiuying; Geng, Shuaifeng

2017-01-01

Early reproductive development in cereals is crucial for final grain number per spike and hence the yield potential of the crop. To date, however, no systematic analyses of gene expression profiles during this important process have been conducted for common wheat (Triticum aestivum). Here, we studied the transcriptome profiles at four stages of early wheat reproductive development, from spikelet initiation to floral organ differentiation. K-means clustering and stage-specific transcript identification detected dynamically expressed homeologs of important transcription regulators in spikelet and floral meristems that may be involved in spikelet initiation, floret meristem specification, and floral organ patterning, as inferred from their homologs in model plants. Small RNA transcriptome sequencing discovered key microRNAs that were differentially expressed during wheat inflorescence development alongside their target genes, suggesting that miRNA-mediated regulatory mechanisms for floral development may be conserved in cereals and Arabidopsis. Our analysis was further substantiated by the functional characterization of the ARGONAUTE1d (AGO1d) gene, which was initially expressed in stamen primordia and later in the tapetum during anther maturation. In agreement with its stage-specific expression pattern, the loss of function of the predominantly expressed B homeolog of AGO1d in a tetraploid durum wheat mutant resulted in smaller anthers with more infertile pollens than the wild type and a reduced grain number per spike. Together, our work provides a first glimpse of the gene regulatory networks in wheat inflorescence development that may be pivotal for floral and grain development, highlighting potential targets for genetic manipulation to improve future wheat yields. PMID:28515146

The Perception of Dynamic and Static Facial Expressions of Happiness and Disgust Investigated by ERPs and fMRI Constrained Source Analysis

PubMed Central

Trautmann-Lengsfeld, Sina Alexa; Domínguez-Borràs, Judith; Escera, Carles; Herrmann, Manfred; Fehr, Thorsten

2013-01-01

A recent functional magnetic resonance imaging (fMRI) study by our group demonstrated that dynamic emotional faces are more accurately recognized and evoked more widespread patterns of hemodynamic brain responses than static emotional faces. Based on this experimental design, the present study aimed at investigating the spatio-temporal processing of static and dynamic emotional facial expressions in 19 healthy women by means of multi-channel electroencephalography (EEG), event-related potentials (ERP) and fMRI-constrained regional source analyses. ERP analysis showed an increased amplitude of the LPP (late posterior positivity) over centro-parietal regions for static facial expressions of disgust compared to neutral faces. In addition, the LPP was more widespread and temporally prolonged for dynamic compared to static faces of disgust and happiness. fMRI constrained source analysis on static emotional face stimuli indicated the spatio-temporal modulation of predominantly posterior regional brain activation related to the visual processing stream for both emotional valences when compared to the neutral condition in the fusiform gyrus. The spatio-temporal processing of dynamic stimuli yielded enhanced source activity for emotional compared to neutral conditions in temporal (e.g., fusiform gyrus), and frontal regions (e.g., ventromedial prefrontal cortex, medial and inferior frontal cortex) in early and again in later time windows. The present data support the view that dynamic facial displays trigger more information reflected in complex neural networks, in particular because of their changing features potentially triggering sustained activation related to a continuing evaluation of those faces. A combined fMRI and EEG approach thus provides an advanced insight to the spatio-temporal characteristics of emotional face processing, by also revealing additional neural generators, not identifiable by the only use of an fMRI approach. PMID:23818974

Binocular pattern deprivation interferes with the expression of proteins involved in primary visual cortex maturation in the cat.

PubMed

Laskowska-Macios, Karolina; Nys, Julie; Hu, Tjing-Tjing; Zapasnik, Monika; Van der Perren, Anke; Kossut, Malgorzata; Burnat, Kalina; Arckens, Lutgarde

2015-08-14

Binocular pattern deprivation from eye opening (early BD) delays the maturation of the primary visual cortex. This delay is more pronounced for the peripheral than the central visual field representation within area 17, particularly between the age of 2 and 4 months [Laskowska-Macios, Cereb Cortex, 2014]. In this study, we probed for related dynamic changes in the cortical proteome. We introduced age, cortical region and BD as principal variables in a 2-D DIGE screen of area 17. In this way we explored the potential of BD-related protein expression changes between central and peripheral area 17 of 2- and 4-month-old BD (2BD, 4BD) kittens as a valid parameter towards the identification of brain maturation-related molecular processes. Consistent with the maturation delay, distinct developmental protein expression changes observed for normal kittens were postponed by BD, especially in the peripheral region. These BD-induced proteomic changes suggest a negative regulation of neurite outgrowth, synaptic transmission and clathrin-mediated endocytosis, thereby implicating these processes in normal experience-induced visual cortex maturation. Verification of the expression of proteins from each of the biological processes via Western analysis disclosed that some of the transient proteomic changes correlate to the distinct behavioral outcome in adult life, depending on timing and duration of the BD period [Neuroscience 2013;255:99-109]. Taken together, the plasticity potential to recover from BD, in relation to ensuing restoration of normal visual input, appears to rely on specific protein expression changes and cellular processes induced by the loss of pattern vision in early life.

Tissue-enriched expression profiles in Aedes aegypti identify hemocyte-specific transcriptome responses to infection

PubMed Central

Choi, Young-Jun; Fuchs, Jeremy F.; Mayhew, George F.; Yu, Helen E.; Christensen, Bruce M.

2012-01-01

Hemocytes are integral components of mosquito immune mechanisms such as phagocytosis, melanization, and production of antimicrobial peptides. However, our understanding of hemocyte-specific molecular processes and their contribution to shaping the host immune response remains limited. To better understand the immunophysiological features distinctive of hemocytes, we conducted genome-wide analysis of hemocyte-enriched transcripts, and examined how tissue-enriched expression patterns change with the immune status of the host. Our microarray data indicate that the hemocyte-enriched trascriptome is dynamic and context-dependent. Analysis of transcripts enriched after bacterial challenge in circulating hemocytes with respect to carcass added a dimension to evaluating infection-responsive genes and immune-related gene families. We resolved patterns of transcriptional change unique to hemocytes from those that are likely shared by other immune responsive tissues, and identified clusters of genes preferentially induced in hemocytes, likely reflecting their involvement in cell type specific functions. In addition, the study revealed conserved hemocyte-enriched molecular repertoires which might be implicated in core hemocyte function by cross-species meta-analysis of microarray expression data from Anopheles gambiae and Drosophila melanogaster. PMID:22796331

A Computational Algorithm for Functional Clustering of Proteome Dynamics During Development

PubMed Central

Wang, Yaqun; Wang, Ningtao; Hao, Han; Guo, Yunqian; Zhen, Yan; Shi, Jisen; Wu, Rongling

2014-01-01

Phenotypic traits, such as seed development, are a consequence of complex biochemical interactions among genes, proteins and metabolites, but the underlying mechanisms that operate in a coordinated and sequential manner remain elusive. Here, we address this issue by developing a computational algorithm to monitor proteome changes during the course of trait development. The algorithm is built within the mixture-model framework in which each mixture component is modeled by a specific group of proteins that display a similar temporal pattern of expression in trait development. A nonparametric approach based on Legendre orthogonal polynomials was used to fit dynamic changes of protein expression, increasing the power and flexibility of protein clustering. By analyzing a dataset of proteomic dynamics during early embryogenesis of the Chinese fir, the algorithm has successfully identified several distinct types of proteins that coordinate with each other to determine seed development in this forest tree commercially and environmentally important to China. The algorithm will find its immediate applications for the characterization of mechanistic underpinnings for any other biological processes in which protein abundance plays a key role. PMID:24955031

Dynamic Shifts in Corticostriatal Expression Patterns of the Immediate Early Genes "Homer 1a" and "Zif268" during Early and Late Phases of Instrumental Training

ERIC Educational Resources Information Center

Kelley, Ann E.; Hernandez, Pepe J.; Schiltz, Craig A.

2006-01-01

Adaptive motor actions require prior knowledge of instrumental contingencies. With practice, these actions can become highly automatic in nature. However, the molecular and anatomical substrates mediating these related forms of learning are not understood. In the present study, we used in situ hybridization to measure the mRNA levels of two…

A year in the life of a thrombolite: comparative metatranscriptomics reveals dynamic metabolic changes over diel and seasonal cycles.

PubMed

Louyakis, Artemis S; Gourlé, Hadrien; Casaburi, Giorgio; Bonjawo, Rachelle M E; Duscher, Alexandrea A; Foster, Jamie S

2018-02-01

Microbialites are one of the oldest known ecosystems on Earth and the coordinated metabolisms and activities of these mineral-depositing communities have had a profound impact on the habitability of the planet. Despite efforts to understand the diversity and metabolic potential of these systems, there has not been a systematic molecular analysis of the transcriptional changes that occur within a living microbialite over time. In this study, we generated metatranscriptomic libraries from actively growing thrombolites, a type of microbialite, throughout diel and seasonal cycles and observed dynamic shifts in the population and metabolic transcriptional activity. The most transcribed genes in all seasons were associated with photosynthesis, but only transcripts associated with photosystem II exhibited diel cycling. Photosystem I transcripts were constitutively expressed at all time points including midnight and sunrise. Transcripts associated with nitrogen fixation, methanogenesis and dissimilatory sulfate reduction exhibited diel cycling, and variability between seasons. Networking analysis of the metatranscriptomes showed correlated expression patterns helping to elucidate how metabolic interactions are coordinated within the thrombolite community. These findings have identified distinctive temporal patterns within the thrombolites and will serve an important foundation to understand the mechanisms by which these communities form and respond to changes in their environment. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Genome‐wide gene expression dynamics of the fungal pathogen Dothistroma septosporum throughout its infection cycle of the gymnosperm host Pinus radiata

PubMed Central

Guo, Yanan; Sim, Andre D.; Kabir, M. Shahjahan; Chettri, Pranav; Ozturk, Ibrahim K.; Hunziker, Lukas; Ganley, Rebecca J.; Cox, Murray P.

2015-01-01

Summary We present genome‐wide gene expression patterns as a time series through the infection cycle of the fungal pine needle blight pathogen, Dothistroma septosporum, as it invades its gymnosperm host, Pinus radiata. We determined the molecular changes at three stages of the disease cycle: epiphytic/biotrophic (early), initial necrosis (mid) and mature sporulating lesion (late). Over 1.7 billion combined plant and fungal reads were sequenced to obtain 3.2 million fungal‐specific reads, which comprised as little as 0.1% of the sample reads early in infection. This enriched dataset shows that the initial biotrophic stage is characterized by the up‐regulation of genes encoding fungal cell wall‐modifying enzymes and signalling proteins. Later necrotrophic stages show the up‐regulation of genes for secondary metabolism, putative effectors, oxidoreductases, transporters and starch degradation. This in‐depth through‐time transcriptomic study provides our first snapshot of the gene expression dynamics that characterize infection by this fungal pathogen in its gymnosperm host. PMID:25919703

The Expression Pattern of microRNAs in Granulosa Cells of Subordinate and Dominant Follicles during the Early Luteal Phase of the Bovine Estrous Cycle

PubMed Central

Gebremedhn, Samuel; Sahadevan, Sudeep; Hossain, MD Munir; Rings, Franca; Hoelker, Michael; Tholen, Ernst; Neuhoff, Christiane; Looft, Christian; Schellander, Karl; Tesfaye, Dawit

2014-01-01

This study aimed to investigate the miRNA expression patterns in granulosa cells of subordinate (SF) and dominant follicle (DF) during the early luteal phase of the bovine estrous cycle. For this, miRNA enriched total RNA isolated from granulosa cells of SF and DF obtained from heifers slaughtered at day 3 and day 7 of the estrous cycle was used for miRNAs deep sequencing. The results revealed that including 17 candidate novel miRNAs, several known miRNAs (n = 291–318) were detected in SF and DF at days 3 and 7 of the estrous cycle of which 244 miRNAs were common to all follicle groups. The let-7 families, bta-miR-10b, bta-miR-26a, bta-miR-99b and bta-miR-27b were among abundantly expressed miRNAs in both SF and DF at both days of the estrous cycle. Further analysis revealed that the expression patterns of 16 miRNAs including bta-miR-449a, bta-miR-449c and bta-miR-222 were differentially expressed between the granulosa cells of SF and DF at day 3 of the estrous cycle. However, at day 7 of the estrous cycle, 108 miRNAs including bta-miR-409a, bta-miR-383 and bta-miR-184 were differentially expressed between the two groups of granulosa cell revealing the presence of distinct miRNA expression profile changes between the two follicular stages at day 7 than day 3 of the estrous cycle. In addition, unlike the SF, marked temporal miRNA expression dynamics was observed in DF groups between day 3 and 7 of the estrous cycle. Target gene prediction and pathway analysis revealed that major signaling associated with follicular development including Wnt signaling, TGF-beta signaling, oocyte meiosis and GnRH signaling were affected by differentially expressed miRNAs. Thus, this study highlights the miRNA expression patterns of granulosa cells in subordinate and dominant follicles that could be associated with follicular recruitment, selection and dominance during the early luteal phase of the bovine estrous cycle. PMID:25192015

Positive Bioluminescence Imaging of MicroRNA Expression in Small Animal Models Using an Engineered Genetic-Switch Expression System, RILES.

PubMed

Baril, Patrick; Pichon, Chantal

2016-01-01

MicroRNAs (miRNAs) are a class of small, noncoding RNAs which regulate gene expression by directing their target mRNA for degradation or translational repression. Since their discovery in the early 1990s, miRNAs have emerged as key components in the posttranscriptional regulation of gene networks, shaping many biological processes from development, morphogenesis, differentiation, proliferation and apoptosis. Although understanding of the molecular basis of miRNA biology is improving, methods to monitor the dynamic and the spatiotemporal aspects of miRNA expression under physiopathological conditions are required. However, monitoring of miRNAs is difficult due to their small size, low abundance, high degree of sequence similarity, and their dynamic expression pattern which is subjected to tight transcriptional and post-transcriptional controls. Recently, we developed a miRNA monitoring system called RILES, standing for RNAi-inducible expression system, which relies on an engineered regulatable expression system, to switch on the expression of the luciferase gene when the targeted miRNA is expressed in cells. We demonstrated that RILES is a specific, sensitive, and robust method to determine the fine-tuning of miRNA expression during the development of an experimental pathological process in mice. Because RILES offers the possibility for longitudinal studies on individual subjects, sharper insights into miRNA regulation can be generated, with applications in physiology, pathophysiology and development of RNAi-based therapies. This chapter describes methods and protocols to monitor the expression of myomiR-206, -1, and -133 in the tibialis anterior muscle of mice. These protocols can be used and adapted to monitor the expression of other miRNAs in other biological processes.

Genome-scale gene expression characteristics define the follicular initiation and developmental rules during folliculogenesis.

PubMed

Shi, Kerong; He, Feng; Yuan, Xuefeng; Zhao, Yaofeng; Deng, Xuemei; Hu, Xiaoxiang; Li, Ning

2013-08-01

The ovarian follicle supplies a unique dynamic system for gametes that ensures the propagation of the species. During folliculogenesis, the vast majority of the germ cells are lost or inactivated because of ovarian follicle atresia, resulting in diminished reproductive potency and potential infertility. Understanding the underlying molecular mechanism of folliculogenesis rules is essential. Primordial (P), preantral (M), and large antral (L) porcine follicles were used to reveal their genome-wide gene expression profiles. Results indicate that primordial follicles (P) process a diverse gene expression pattern compared to growing follicles (M and L). The 5,548 differentially expressed genes display a similar expression mode in M and L, with a correlation coefficient of 0.892. The number of regulated (both up and down) genes in M is more than that in L. Also, their regulation folds in M (2-364-fold) are much more acute than in L (2-75-fold). Differentially expressed gene groups with different regulation patterns in certain follicular stages are identified and presumed to be closely related following follicular developmental rules. Interestingly, functional annotation analysis revealed that these gene groups feature distinct biological processes or molecular functions. Moreover, representative candidate genes from these gene groups have had their RNA or protein expressions within follicles confirmed. Our study emphasized genome-scale gene expression characteristics, which provide novel entry points for understanding the folliculogenesis rules on the molecular level, such as follicular initiation, atresia, and dominance. Transcriptional regulatory circuitries in certain follicular stages are expected to be found among the identified differentially expressed gene groups.

Gene Expression Profiling in the Hibernating Primate, Cheirogaleus Medius

PubMed Central

Faherty, Sheena L.; Villanueva-Cañas, José Luis; Klopfer, Peter H.; Albà, M. Mar; Yoder, Anne D.

2016-01-01

Hibernation is a complex physiological response that some mammalian species employ to evade energetic demands. Previous work in mammalian hibernators suggests that hibernation is activated not by a set of genes unique to hibernators, but by differential expression of genes that are present in all mammals. This question of universal genetic mechanisms requires further investigation and can only be tested through additional investigations of phylogenetically dispersed species. To explore this question, we use RNA-Seq to investigate gene expression dynamics as they relate to the varying physiological states experienced throughout the year in a group of primate hibernators—Madagascar’s dwarf lemurs (genus Cheirogaleus). In a novel experimental approach, we use longitudinal sampling of biological tissues as a method for capturing gene expression profiles from the same individuals throughout their annual hibernation cycle. We identify 90 candidate genes that have variable expression patterns when comparing two active states (Active 1 and Active 2) with a torpor state. These include genes that are involved in metabolic pathways, feeding behavior, and circadian rhythms, as might be expected to correlate with seasonal physiological state changes. The identified genes appear to be critical for maintaining the health of an animal that undergoes prolonged periods of metabolic depression concurrent with the hibernation phenotype. By focusing on these differentially expressed genes in dwarf lemurs, we compare gene expression patterns in previously studied mammalian hibernators. Additionally, by employing evolutionary rate analysis, we find that hibernation-related genes do not evolve under positive selection in hibernating species relative to nonhibernators. PMID:27412611

Candidate ionotropic taste receptors in the Drosophila larva.

PubMed

Stewart, Shannon; Koh, Tong-Wey; Ghosh, Arpan C; Carlson, John R

2015-04-07

We examine in Drosophila a group of ∼35 ionotropic receptors (IRs), the IR20a clade, about which remarkably little is known. Of 28 genes analyzed, GAL4 drivers representing 11 showed expression in the larva. Eight drivers labeled neurons of the pharynx, a taste organ, and three labeled neurons of the body wall that may be chemosensory. Expression was not observed in neurons of one taste organ, the terminal organ, although these neurons express many drivers of the Gr (Gustatory receptor) family. For most drivers of the IR20a clade, we observed expression in a single pair of cells in the animal, with limited coexpression, and only a fraction of pharyngeal neurons are labeled. The organization of IR20a clade expression thus appears different from the organization of the Gr family or the Odor receptor (Or) family in the larva. A remarkable feature of the larval pharynx is that some of its organs are incorporated into the adult pharynx, and several drivers of this clade are expressed in the pharynx of both larvae and adults. Different IR drivers show different developmental dynamics across the larval stages, either increasing or decreasing. Among neurons expressing drivers in the pharynx, two projection patterns can be distinguished in the CNS. Neurons exhibiting these two kinds of projection patterns may activate different circuits, possibly signaling the presence of cues with different valence. Taken together, the simplest interpretation of our results is that the IR20a clade encodes a class of larval taste receptors.

Towards understanding the breast cancer epigenome: a comparison of genome-wide DNA methylation and gene expression data

PubMed Central

Michiels, Stefan; Metzger-Filho, Otto; Saini, Kamal S.

2016-01-01

Until recently, an elevated disease risk has been ascribed to a genetic predisposition, however, exciting progress over the past years has discovered alternate elements of inheritance that involve epigenetic regulation. Epigenetic changes are heritably stable alterations that include DNA methylation, histone modifications and RNA-mediated silencing. Aberrant DNA methylation is a common molecular basis for a number of important human diseases, including breast cancer. Changes in DNA methylation profoundly affect global gene expression patterns. What is emerging is a more dynamic and complex association between DNA methylation and gene expression than previously believed. Although many tools have already been developed for analyzing genome-wide gene expression data, tools for analyzing genome-wide DNA methylation have not yet reached the same level of refinement. Here we provide an in-depth analysis of DNA methylation in parallel with gene expression data characteristics and describe the particularities of low-level and high-level analyses of DNA methylation data. Low-level analysis refers to pre-processing of methylation data (i.e. normalization, transformation and filtering), whereas high-level analysis is focused on illustrating the application of the widely used class comparison, class prediction and class discovery methods to DNA methylation data. Furthermore, we investigate the influence of DNA methylation on gene expression by measuring the correlation between the degree of CpG methylation and the level of expression and to explore the pattern of methylation as a function of the promoter region. PMID:26657508

Towards understanding the breast cancer epigenome: a comparison of genome-wide DNA methylation and gene expression data.

PubMed

Singhal, Sandeep K; Usmani, Nawaid; Michiels, Stefan; Metzger-Filho, Otto; Saini, Kamal S; Kovalchuk, Olga; Parliament, Matthew

2016-01-19

Until recently, an elevated disease risk has been ascribed to a genetic predisposition, however, exciting progress over the past years has discovered alternate elements of inheritance that involve epigenetic regulation. Epigenetic changes are heritably stable alterations that include DNA methylation, histone modifications and RNA-mediated silencing. Aberrant DNA methylation is a common molecular basis for a number of important human diseases, including breast cancer. Changes in DNA methylation profoundly affect global gene expression patterns. What is emerging is a more dynamic and complex association between DNA methylation and gene expression than previously believed. Although many tools have already been developed for analyzing genome-wide gene expression data, tools for analyzing genome-wide DNA methylation have not yet reached the same level of refinement. Here we provide an in-depth analysis of DNA methylation in parallel with gene expression data characteristics and describe the particularities of low-level and high-level analyses of DNA methylation data. Low-level analysis refers to pre-processing of methylation data (i.e. normalization, transformation and filtering), whereas high-level analysis is focused on illustrating the application of the widely used class comparison, class prediction and class discovery methods to DNA methylation data. Furthermore, we investigate the influence of DNA methylation on gene expression by measuring the correlation between the degree of CpG methylation and the level of expression and to explore the pattern of methylation as a function of the promoter region.

Self-Organizing Global Gene Expression Regulated through Criticality: Mechanism of the Cell-Fate Change

PubMed Central

Tsuchiya, Masa; Giuliani, Alessandro; Hashimoto, Midori; Erenpreisa, Jekaterina; Yoshikawa, Kenichi

2016-01-01

Background A fundamental issue in bioscience is to understand the mechanism that underlies the dynamic control of genome-wide expression through the complex temporal-spatial self-organization of the genome to regulate the change in cell fate. We address this issue by elucidating a physically motivated mechanism of self-organization. Principal Findings Building upon transcriptome experimental data for seven distinct cell fates, including early embryonic development, we demonstrate that self-organized criticality (SOC) plays an essential role in the dynamic control of global gene expression regulation at both the population and single-cell levels. The novel findings are as follows: i) Mechanism of cell-fate changes: A sandpile-type critical transition self-organizes overall expression into a few transcription response domains (critical states). A cell-fate change occurs by means of a dissipative pulse-like global perturbation in self-organization through the erasure of initial-state critical behaviors (criticality). Most notably, the reprogramming of early embryo cells destroys the zygote SOC control to initiate self-organization in the new embryonal genome, which passes through a stochastic overall expression pattern. ii) Mechanism of perturbation of SOC controls: Global perturbations in self-organization involve the temporal regulation of critical states. Quantitative evaluation of this perturbation in terminal cell fates reveals that dynamic interactions between critical states determine the critical-state coherent regulation. The occurrence of a temporal change in criticality perturbs this between-states interaction, which directly affects the entire genomic system. Surprisingly, a sub-critical state, corresponding to an ensemble of genes that shows only marginal changes in expression and consequently are considered to be devoid of any interest, plays an essential role in generating a global perturbation in self-organization directed toward the cell-fate change. Conclusion and Significance ‘Whole-genome’ regulation of gene expression through self-regulatory SOC control complements gene-by-gene fine tuning and represents a still largely unexplored non-equilibrium statistical mechanism that is responsible for the massive reprogramming of genome expression. PMID:27997556

Dynamics of the Venus upper atmosphere: Outstanding problems and new constraints expected from Venus Express

NASA Astrophysics Data System (ADS)

Bougher, S. W.; Rafkin, S.; Drossart, P.

2006-11-01

A consistent picture of the dynamics of the Venus upper atmosphere from ˜90 to 200 km has begun to emerge [e.g., Bougher, S.W., Alexander, M.J., Mayr, H.G., 1997. Upper Atmosphere Dynamics: Global Circulation and Gravity Waves. Venus II, CH. 2.4. University of Arizona Press, Tucson, pp. 259-292; Lellouch, E., Clancy, T., Crisp, D., Kliore, A., Titov, D., Bougher, S.W., 1997. Monitoring of Mesospheric Structure and Dynamics. Venus II, CH. 3.1. University of Arizona Press, Tucson, pp. 295-324]. The large-scale circulation of the Venus upper atmosphere (upper mesosphere and thermosphere) can be decomposed into two distinct flow patterns: (1) a relatively stable subsolar-to-antisolar (SS-AS) circulation cell driven by solar heating, and (2) a highly variable retrograde superrotating zonal (RSZ) flow. Wave-like perturbations have also been observed. However, the processes responsible for maintaining (and driving variations in) these SS-AS and RSZ winds are not well understood. Variations in winds are thought to result from gravity wave breaking and subsequent momentum and energy deposition in the upper atmosphere [Alexander, M.J., 1992. A mechanism for the Venus thermospheric superrotation. Geophys. Res. Lett. 19, 2207-2210; Zhang, S., Bougher, S.W., Alexander, M.J., 1996. The impact of gravity waves on the Venus thermosphere and O2 IR nightglow. J. Geophys. Res. 101, 23195-23205]. However, existing data sets are limited in their spatial and temporal coverage, thereby restricting our understanding of these changing circulation patterns. One of the major goals of the Venus Express (VEX) mission is focused upon increasing our understanding of the circulation and dynamical processes of the Venus atmosphere up to the exobase [Titov, D.V., Lellouch, E., Taylor, F.W., 2001. Venus Express: Response to ESA's call for ideas for the re-use of the Mars Express platform. Proposal to European Space Agency, 1-74]. Several VEX instruments are slated to obtain remote measurements (2006-2008) that will complement those obtained earlier by the Pioneer Venus Orbiter (PVO) between 1978 and 1992. These VEX measurements will provide a more comprehensive investigation of the Venus upper atmosphere (90-200 km) structure and dynamics over another period in the solar cycle and for variable lower atmosphere conditions. An expanded climatology of Venus upper atmosphere structure and wind components will be developed. In addition, gravity wave parameters above the cloud tops will be measured (or inferred), and used to constrain gravity wave breaking models. In this manner, the gravity wave breaking mechanism (thought to regulate highly variable RSZ winds) can be tested using Venus general circulation models (GCMs).

The biology and evolution of transposable elements in parasites.

PubMed

Thomas, M Carmen; Macias, Francisco; Alonso, Carlos; López, Manuel C

2010-07-01

Transposable elements (TEs) are dynamic elements that can reshape host genomes by generating rearrangements with the potential to create or disrupt genes, to shuffle existing genes, and to modulate their patterns of expression. In the genomes of parasites that infect mammals several TEs have been identified that probably have been maintained throughout evolution due to their contribution to gene function and regulation of gene expression. This review addresses how TEs are organized, how they colonize the genomes of mammalian parasites, the functional role these elements play in parasite biology, and the interactions between these elements and the parasite genome. Copyright 2010 Elsevier Ltd. All rights reserved.

Vigilance as a caring expression and Leininger's theory of cultural care diversity and universality.

PubMed

Carr, J M

1998-01-01

Vigilance, or the close, protective involvement of families caring for hospitalized relatives, was explored in this study using holistic ethnography. Leininger's theory of cultural care diversity and universality provided direction for the researcher to generate substantive data about the meanings, patterns, and day-to-day experience of vigilance. Five categories of meaning were derived from the data: commitment to care, emotional upheaval, dynamic nexus, transition, and resilience. The research findings expand understanding of vigilance as a caring expression, suggest direction for nursing practice, and contribute to Leininger's theory of cultural care diversity and universality and the development of nursing science.

An autocatalytic network model for stock markets

NASA Astrophysics Data System (ADS)

Caetano, Marco Antonio Leonel; Yoneyama, Takashi

2015-02-01

The stock prices of companies with businesses that are closely related within a specific sector of economy might exhibit movement patterns and correlations in their dynamics. The idea in this work is to use the concept of autocatalytic network to model such correlations and patterns in the trends exhibited by the expected returns. The trends are expressed in terms of positive or negative returns within each fixed time interval. The time series derived from these trends is then used to represent the movement patterns by a probabilistic boolean network with transitions modeled as an autocatalytic network. The proposed method might be of value in short term forecasting and identification of dependencies. The method is illustrated with a case study based on four stocks of companies in the field of natural resource and technology.

High-order rogue waves of the Benjamin-Ono equation and the nonlocal nonlinear Schrödinger equation

NASA Astrophysics Data System (ADS)

Liu, Wei

2017-10-01

High-order rogue wave solutions of the Benjamin-Ono equation and the nonlocal nonlinear Schrödinger equation are derived by employing the bilinear method, which are expressed by simple polynomials. Typical dynamics of these high-order rogue waves are studied by analytical and graphical ways. For the Benjamin-Ono equation, there are two types of rogue waves, namely, bright rogue waves and dark rogue waves. In particular, the fundamental rogue wave pattern is different from the usual fundamental rogue wave patterns in other soliton equations. For the nonlocal nonlinear Schrödinger equation, the exact explicit rogue wave solutions up to the second order are presented. Typical rogue wave patterns such as Peregrine-type, triple and fundamental rogue waves are put forward. These high-order rogue wave patterns have not been shown before in the nonlocal Schrödinger equation.

Involvement of Lypge in the formation of eye and pineal gland in zebrafish.

PubMed

Ji, Dongrui; Wang, Su; Li, Mingyue; Zhang, Shicui; Li, Hongyan

2018-02-05

The proteins of Ly-6 (lymphocyte antigen-6) family are involved in the regulation of immunoreaction, cell migration and adhesion, and neuronal excitability. However, little is known about the function of Ly-6 proteins in embryogenesis. Herein, we identified a GPI anchored Ly-6 member named ly6 expressed in pineal gland and eye (lypge). Dynamic expression pattern of lypge was revealed by whole mount in situ hybridization. It was strikingly expressed in the pineal gland and cone photoreceptor, and its expression was regulated by orthodenticle homolog 5 (otx5) which has been shown to control the expression of many pineal genes. In addition, we demonstrated that lypge was rhythmically expressed in larvae from 4dpf on. Moreover, knockdown of lypge resulted in small head and small eye formed in zebrafish embryos. These suggest that Lypge is involved in the formation of the eye and pineal gland in early development of zebrafish. Copyright © 2017 Elsevier B.V. All rights reserved.

Three-pattern decomposition of global atmospheric circulation: part II—dynamical equations of horizontal, meridional and zonal circulations

NASA Astrophysics Data System (ADS)

Hu, Shujuan; Cheng, Jianbo; Xu, Ming; Chou, Jifan

2018-04-01

The three-pattern decomposition of global atmospheric circulation (TPDGAC) partitions three-dimensional (3D) atmospheric circulation into horizontal, meridional and zonal components to study the 3D structures of global atmospheric circulation. This paper incorporates the three-pattern decomposition model (TPDM) into primitive equations of atmospheric dynamics and establishes a new set of dynamical equations of the horizontal, meridional and zonal circulations in which the operator properties are studied and energy conservation laws are preserved, as in the primitive equations. The physical significance of the newly established equations is demonstrated. Our findings reveal that the new equations are essentially the 3D vorticity equations of atmosphere and that the time evolution rules of the horizontal, meridional and zonal circulations can be described from the perspective of 3D vorticity evolution. The new set of dynamical equations includes decomposed expressions that can be used to explore the source terms of large-scale atmospheric circulation variations. A simplified model is presented to demonstrate the potential applications of the new equations for studying the dynamics of the Rossby, Hadley and Walker circulations. The model shows that the horizontal air temperature anomaly gradient (ATAG) induces changes in meridional and zonal circulations and promotes the baroclinic evolution of the horizontal circulation. The simplified model also indicates that the absolute vorticity of the horizontal circulation is not conserved, and its changes can be described by changes in the vertical vorticities of the meridional and zonal circulations. Moreover, the thermodynamic equation shows that the induced meridional and zonal circulations and advection transport by the horizontal circulation in turn cause a redistribution of the air temperature. The simplified model reveals the fundamental rules between the evolution of the air temperature and the horizontal, meridional and zonal components of global atmospheric circulation.

Evaluation of effect of oil film of rotor bearing

NASA Astrophysics Data System (ADS)

Alekseeva, L. B.; Maksarov, V. V.

2018-03-01

The high-rpm rotors were subjected to the dynamic analysis. Oscillations of a rotor spinning in gapped bearings were considered. It was stated that the rotor necks motion pattern depends on a lot of factors: a ratio of static and dynamic loads on the bearing, radial clearance size, presence of oil film between a neck and a bearing, elastic and inertial properties of a mounting group. The most unfavourable mode where static and dynamic loads are equal was detected without taking into account the oil film impact. The impact of oil film on the bearing assembly dynamics is significant in high-rpm rotors. The presence of oil film can possibly cause rotor buckling failure and self-starting. Rotor motion stability in small was studied. Herewith, various schemes were considered. Expressions, determining the stability zones of a rigid rotor on the fixed support and the supports with elastic and inertial elements, were given.

A Developmental Systems Perspective on Epistasis: Computational Exploration of Mutational Interactions in Model Developmental Regulatory Networks

PubMed Central

Gutiérrez, Jayson

2009-01-01

The way in which the information contained in genotypes is translated into complex phenotypic traits (i.e. embryonic expression patterns) depends on its decoding by a multilayered hierarchy of biomolecular systems (regulatory networks). Each layer of this hierarchy displays its own regulatory schemes (i.e. operational rules such as +/− feedback) and associated control parameters, resulting in characteristic variational constraints. This process can be conceptualized as a mapping issue, and in the context of highly-dimensional genotype-phenotype mappings (GPMs) epistatic events have been shown to be ubiquitous, manifested in non-linear correspondences between changes in the genotype and their phenotypic effects. In this study I concentrate on epistatic phenomena pervading levels of biological organization above the genetic material, more specifically the realm of molecular networks. At this level, systems approaches to studying GPMs are specially suitable to shed light on the mechanistic basis of epistatic phenomena. To this aim, I constructed and analyzed ensembles of highly-modular (fully interconnected) networks with distinctive topologies, each displaying dynamic behaviors that were categorized as either arbitrary or functional according to early patterning processes in the Drosophila embryo. Spatio-temporal expression trajectories in virtual syncytial embryos were simulated via reaction-diffusion models. My in silico mutational experiments show that: 1) the average fitness decay tendency to successively accumulated mutations in ensembles of functional networks indicates the prevalence of positive epistasis, whereas in ensembles of arbitrary networks negative epistasis is the dominant tendency; and 2) the evaluation of epistatic coefficients of diverse interaction orders indicates that, both positive and negative epistasis are more prevalent in functional networks than in arbitrary ones. Overall, I conclude that the phenotypic and fitness effects of multiple perturbations are strongly conditioned by both the regulatory architecture (i.e. pattern of coupled feedback structures) and the dynamic nature of the spatio-temporal expression trajectories displayed by the simulated networks. PMID:19738908

Recrudescence Mechanisms and Gene Expression Profile of the Reproductive Tracts from Chickens during the Molting Period

PubMed Central

Ahn, Suzie E.; Lim, Chul-Hong; Lee, Jin-Young; Bae, Seung-Min; Kim, Jinyoung; Bazer, Fuller W.; Song, Gwonhwa

2013-01-01

The reproductive system of chickens undergoes dynamic morphological and functional tissue remodeling during the molting period. The present study identified global gene expression profiles following oviductal tissue regression and regeneration in laying hens in which molting was induced by feeding high levels of zinc in the diet. During the molting and recrudescence processes, progressive morphological and physiological changes included regression and re-growth of reproductive organs and fluctuations in concentrations of testosterone, progesterone, estradiol and corticosterone in blood. The cDNA microarray analysis of oviductal tissues revealed the biological significance of gene expression-based modulation in oviductal tissue during its remodeling. Based on the gene expression profiles, expression patterns of selected genes such as, TF, ANGPTL3, p20K, PTN, AvBD11 and SERPINB3 exhibited similar patterns in expression with gradual decreases during regression of the oviduct and sequential increases during resurrection of the functional oviduct. Also, miR-1689* inhibited expression of Sp1, while miR-17-3p, miR-22* and miR-1764 inhibited expression of STAT1. Similarly, chicken miR-1562 and miR-138 reduced the expression of ANGPTL3 and p20K, respectively. These results suggest that these differentially regulated genes are closely correlated with the molecular mechanism(s) for development and tissue remodeling of the avian female reproductive tract, and that miRNA-mediated regulation of key genes likely contributes to remodeling of the avian reproductive tract by controlling expression of those genes post-transcriptionally. The discovered global gene profiles provide new molecular candidates responsible for regulating morphological and functional recrudescence of the avian reproductive tract, and provide novel insights into understanding the remodeling process at the genomic and epigenomic levels. PMID:24098561

Age Deficits in Facial Affect Recognition: The Influence of Dynamic Cues.

PubMed

Grainger, Sarah A; Henry, Julie D; Phillips, Louise H; Vanman, Eric J; Allen, Roy

2017-07-01

Older adults have difficulties in identifying most facial expressions of emotion. However, most aging studies have presented static photographs of intense expressions, whereas in everyday experience people see emotions that develop and change. The present study was designed to assess whether age-related difficulties with emotion recognition are reduced when more ecologically valid (i.e., dynamic) stimuli are used. We examined the effect of stimuli format (i.e., static vs. dynamic) on facial affect recognition in two separate studies that included independent samples and distinct stimuli sets. In addition to younger and older participants, a middle-aged group was included in Study 1 and eye gaze patterns were assessed in Study 2. Across both studies, older adults performed worse than younger adults on measures of facial affect recognition. In Study 1, older and-middle aged adults benefited from dynamic stimuli, but only when the emotional displays were subtle. Younger adults gazed more at the eye region of the face relative to older adults (Study 2), but dynamic presentation increased attention towards the eye region for younger adults only. Together, these studies provide important and novel insights into the specific circumstances in which older adults may be expected to experience difficulties in perceiving facial emotions. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The developmental transcriptome atlas of the spoon worm Urechis unicinctus (Echiurida: Annelida).

PubMed

Park, Chungoo; Han, Yong-Hee; Lee, Sung-Gwon; Ry, Kyoung-Bin; Oh, Jooseong; Kern, Elizabeth M A; Park, Joong-Ki; Cho, Sung-Jin

2018-03-01

Echiurida is one of the most intriguing major subgroups of annelida because, unlike most other annelids, echiurids lack metameric body segmentation as adults. For this reason, transcriptome analyses from various developmental stages of echiurid species can be of substantial value for understanding precise expression levels and the complex regulatory networks during early and larval development. A total of 914 million raw RNA-Seq reads were produced from 14 developmental stages of Urechis unicinctus and were de novo assembled into contigs spanning 63,928,225 bp with an N50 length of 2700 bp. The resulting comprehensive transcriptome database of the early developmental stages of U. unicinctus consists of 20,305 representative functional protein-coding transcripts. Approximately 66% of unigenes were assigned to superphylum-level taxa, including Lophotrochozoa (40%). The completeness of the transcriptome assembly was assessed using benchmarking universal single-copy orthologs; 75.7% of the single-copy orthologs were presented in our transcriptome database. We observed 3 distinct patterns of global transcriptome profiles from 14 developmental stages and identified 12,705 genes that showed dynamic regulation patterns during the differentiation and maturation of U. unicinctus cells. We present the first large-scale developmental transcriptome dataset of U. unicinctus and provide a general overview of the dynamics of global gene expression changes during its early developmental stages. The analysis of time-course gene expression data is a first step toward understanding the complex developmental gene regulatory networks in U. unicinctus and will furnish a valuable resource for analyzing the functions of gene repertoires in various developmental phases.

Cytological and Proteomic Analyses of Osmunda cinnamomea Germinating Spores Reveal Characteristics of Fern Spore Germination and Rhizoid Tip Growth.

PubMed

Suo, Jinwei; Zhao, Qi; Zhang, Zhengxiu; Chen, Sixue; Cao, Jian'guo; Liu, Guanjun; Wei, Xing; Wang, Tai; Yang, Chuanping; Dai, Shaojun

2015-09-01

Fern spore is a good single-cell model for studying the sophisticated molecular networks in asymmetric cell division, differentiation, and polar growth. Osmunda cinnamomea L. var. asiatica is one of the oldest fern species with typical separate-growing trophophyll and sporophyll. The chlorophyllous spores generated from sporophyll can germinate without dormancy. In this study, the spore ultrastructure, antioxidant enzyme activities, as well as protein and gene expression patterns were analyzed in the course of spore germination at five typical stages (i.e. mature spores, rehydrated spores, double-celled spores, germinated spores, and spores with protonemal cells). Proteomic analysis revealed 113 differentially expressed proteins, which were mainly involved in photosynthesis, reserve mobilization, energy supplying, protein synthesis and turnover, reactive oxygen species scavenging, signaling, and cell structure modulation. The presence of multiple proteoforms of 25 differentially expressed proteins implies that post-translational modification may play important roles in spore germination. The dynamic patterns of proteins and their encoding genes exhibited specific characteristics in the processes of cell division and rhizoid tip growth, which include heterotrophic and autotrophic metabolisms, de novo protein synthesis and active protein turnover, reactive oxygen species and hormone (brassinosteroid and ethylene) signaling, and vesicle trafficking and cytoskeleton dynamic. In addition, the function skew of proteins in fern spores highlights the unique and common mechanisms when compared with evolutionarily divergent spermatophyte pollen. These findings provide an improved understanding of the typical single-celled asymmetric division and polar growth during fern spore germination. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Formation and maintenance of nitrogen-fixing cell patterns in filamentous cyanobacteria.

PubMed

Muñoz-García, Javier; Ares, Saúl

2016-05-31

Cyanobacteria forming one-dimensional filaments are paradigmatic model organisms of the transition between unicellular and multicellular living forms. Under nitrogen-limiting conditions, in filaments of the genus Anabaena, some cells differentiate into heterocysts, which lose the possibility to divide but are able to fix environmental nitrogen for the colony. These heterocysts form a quasiregular pattern in the filament, representing a prototype of patterning and morphogenesis in prokaryotes. Recent years have seen advances in the identification of the molecular mechanism regulating this pattern. We use these data to build a theory on heterocyst pattern formation, for which both genetic regulation and the effects of cell division and filament growth are key components. The theory is based on the interplay of three generic mechanisms: local autoactivation, early long-range inhibition, and late long-range inhibition. These mechanisms can be identified with the dynamics of hetR, patS, and hetN expression. Our theory reproduces quantitatively the experimental dynamics of pattern formation and maintenance for wild type and mutants. We find that hetN alone is not enough to play the role as the late inhibitory mechanism: a second mechanism, hypothetically the products of nitrogen fixation supplied by heterocysts, must also play a role in late long-range inhibition. The preponderance of even intervals between heterocysts arises naturally as a result of the interplay between the timescales of genetic regulation and cell division. We also find that a purely stochastic initiation of the pattern, without a two-stage process, is enough to reproduce experimental observations.

Mapping MRI/MRS Parameters with Genetic Over-expression Profiles In Human Prostate Cancer: Demonstrating the Potential

PubMed Central

Lenkinski, Robert E.; Bloch, B. Nicholas; Liu, Fangbing; Frangioni, John V.; Perner, Sven; Rubin, Mark A.; Genega, Elizabeth; Rofsky, Neil M.; Gaston, Sandra M.

2009-01-01

Magnetic resonance imaging (MRI) and MR spectroscopy can probe a variety of physiological (e.g. blood vessel permeability) and metabolic characteristics of prostate cancer. However, little is known about the changes in gene expression that underlie the spectral and imaging features observed in prostate cancer. Tumor induced changes in vascular permeability and angiogenesis are thought to contribute to patterns of dynamic contrast enhanced (DCE) MRI images of prostate cancer even though the genetic basis of tumor vasculogenesis is complex and the specific mechanisms underlying these DCEMRI features have not yet been determined. In order to identify the changes in gene expression that correspond to MRS and DCEMRI patterns in human prostate cancers, we have utilized tissue print micropeel techniques to generate “whole mount” molecular maps of radical prostatectomy specimens that correspond to pre-surgical MRI/MRS studies. These molecular maps include RNA expression profiles from both Affymetrix GeneChip microarrays and quantitative reverse transcriptase PCR (qrt-PCR) analysis, as well as immunohistochemical studies. Using these methods on patients with prostate cancer, we found robust over-expression of choline kinase a in the majority of primary tumors. We also observed overexpression of neuropeptide Y (NPY), a newly identified angiogenic factor, in a subset of DCEMRI positive prostate cancers. These studies set the stage for establishing MRI/MRS parameters as validated biomarkers for human prostate cancer. PMID:18752015

Cell-type- and tissue-specific transcriptomes of the white spruce (Picea glauca) bark unmask fine-scale spatial patterns of constitutive and induced conifer defense.

PubMed

Celedon, Jose M; Yuen, Macaire M S; Chiang, Angela; Henderson, Hannah; Reid, Karen E; Bohlmann, Jörg

2017-11-01

Plant defenses often involve specialized cells and tissues. In conifers, specialized cells of the bark are important for defense against insects and pathogens. Using laser microdissection, we characterized the transcriptomes of cortical resin duct cells, phenolic cells and phloem of white spruce (Picea glauca) bark under constitutive and methyl jasmonate (MeJa)-induced conditions, and we compared these transcriptomes with the transcriptome of the bark tissue complex. Overall, ~3700 bark transcripts were differentially expressed in response to MeJa. Approximately 25% of transcripts were expressed in only one cell type, revealing cell specialization at the transcriptome level. MeJa caused cell-type-specific transcriptome responses and changed the overall patterns of cell-type-specific transcript accumulation. Comparison of transcriptomes of the conifer bark tissue complex and specialized cells resolved a masking effect inherent to transcriptome analysis of complex tissues, and showed the actual cell-type-specific transcriptome signatures. Characterization of cell-type-specific transcriptomes is critical to reveal the dynamic patterns of spatial and temporal display of constitutive and induced defense systems in a complex plant tissue or organ. This was demonstrated with the improved resolution of spatially restricted expression of sets of genes of secondary metabolism in the specialized cell types. © 2017 The Authors The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

Dynamic association with donor cell filopodia and lipid-modification are essential features of Wnt8a during patterning of the zebrafish neuroectoderm.

PubMed

Luz, Marta; Spannl-Müller, Stephanie; Özhan, Günes; Kagermeier-Schenk, Birgit; Rhinn, Muriel; Weidinger, Gilbert; Brand, Michael

2014-01-01

Wnt proteins are conserved signaling molecules that regulate pattern formation during animal development. Many Wnt proteins are post-translationally modified by addition of lipid adducts. Wnt8a provides a crucial signal for patterning the anteroposterior axis of the developing neural plate in vertebrates. However, it is not clear how this protein propagates from its source, the blastoderm margin, to the target cells in the prospective neural plate, and how lipid-modifications might influence Wnt8a propagation and activity. We have dynamically imaged biologically active, fluorescently tagged Wnt8a in living zebrafish embryos. We find that Wnt8a localizes to membrane-associated, punctate structures in live tissue. In Wnt8a expressing cells, these puncta are found on filopodial cellular processes, from where the protein can be released. In addition, Wnt8a is found colocalized with Frizzled receptor-containing clusters on signal receiving cells. Combining in vitro and in vivo assays, we compare the roles of conserved Wnt8a residues in cell and non-cell-autonomous signaling activity and secretion. Non-signaling Wnt8 variants show these residues can regulate Wnt8a distribution in producing cell membranes and filopodia as well as in the receiving tissue. Together, our results show that Wnt8a forms dynamic clusters found on filopodial donor cell and on signal receiving cell membranes. Moreover, they demonstrate a differential requirement of conserved residues in Wnt8a protein for distribution in producing cells and receiving tissue and signaling activity during neuroectoderm patterning.

Dynamic Association with Donor Cell Filopodia and Lipid-Modification Are Essential Features of Wnt8a during Patterning of the Zebrafish Neuroectoderm

PubMed Central

Luz, Marta; Spannl-Müller, Stephanie; Özhan, Günes; Kagermeier-Schenk, Birgit; Rhinn, Muriel; Weidinger, Gilbert; Brand, Michael

2014-01-01

Background Wnt proteins are conserved signaling molecules that regulate pattern formation during animal development. Many Wnt proteins are post-translationally modified by addition of lipid adducts. Wnt8a provides a crucial signal for patterning the anteroposterior axis of the developing neural plate in vertebrates. However, it is not clear how this protein propagates from its source, the blastoderm margin, to the target cells in the prospective neural plate, and how lipid-modifications might influence Wnt8a propagation and activity. Results We have dynamically imaged biologically active, fluorescently tagged Wnt8a in living zebrafish embryos. We find that Wnt8a localizes to membrane-associated, punctate structures in live tissue. In Wnt8a expressing cells, these puncta are found on filopodial cellular processes, from where the protein can be released. In addition, Wnt8a is found colocalized with Frizzled receptor-containing clusters on signal receiving cells. Combining in vitro and in vivo assays, we compare the roles of conserved Wnt8a residues in cell and non-cell-autonomous signaling activity and secretion. Non-signaling Wnt8 variants show these residues can regulate Wnt8a distribution in producing cell membranes and filopodia as well as in the receiving tissue. Conclusions Together, our results show that Wnt8a forms dynamic clusters found on filopodial donor cell and on signal receiving cell membranes. Moreover, they demonstrate a differential requirement of conserved residues in Wnt8a protein for distribution in producing cells and receiving tissue and signaling activity during neuroectoderm patterning. PMID:24427298

Simple Shared Motifs (SSM) in conserved region of promoters: a new approach to identify co-regulation patterns.

PubMed

Gruel, Jérémy; LeBorgne, Michel; LeMeur, Nolwenn; Théret, Nathalie

2011-09-12

Regulation of gene expression plays a pivotal role in cellular functions. However, understanding the dynamics of transcription remains a challenging task. A host of computational approaches have been developed to identify regulatory motifs, mainly based on the recognition of DNA sequences for transcription factor binding sites. Recent integration of additional data from genomic analyses or phylogenetic footprinting has significantly improved these methods. Here, we propose a different approach based on the compilation of Simple Shared Motifs (SSM), groups of sequences defined by their length and similarity and present in conserved sequences of gene promoters. We developed an original algorithm to search and count SSM in pairs of genes. An exceptional number of SSM is considered as a common regulatory pattern. The SSM approach is applied to a sample set of genes and validated using functional gene-set enrichment analyses. We demonstrate that the SSM approach selects genes that are over-represented in specific biological categories (Ontology and Pathways) and are enriched in co-expressed genes. Finally we show that genes co-expressed in the same tissue or involved in the same biological pathway have increased SSM values. Using unbiased clustering of genes, Simple Shared Motifs analysis constitutes an original contribution to provide a clearer definition of expression networks.

Simple Shared Motifs (SSM) in conserved region of promoters: a new approach to identify co-regulation patterns

PubMed Central

2011-01-01

Background Regulation of gene expression plays a pivotal role in cellular functions. However, understanding the dynamics of transcription remains a challenging task. A host of computational approaches have been developed to identify regulatory motifs, mainly based on the recognition of DNA sequences for transcription factor binding sites. Recent integration of additional data from genomic analyses or phylogenetic footprinting has significantly improved these methods. Results Here, we propose a different approach based on the compilation of Simple Shared Motifs (SSM), groups of sequences defined by their length and similarity and present in conserved sequences of gene promoters. We developed an original algorithm to search and count SSM in pairs of genes. An exceptional number of SSM is considered as a common regulatory pattern. The SSM approach is applied to a sample set of genes and validated using functional gene-set enrichment analyses. We demonstrate that the SSM approach selects genes that are over-represented in specific biological categories (Ontology and Pathways) and are enriched in co-expressed genes. Finally we show that genes co-expressed in the same tissue or involved in the same biological pathway have increased SSM values. Conclusions Using unbiased clustering of genes, Simple Shared Motifs analysis constitutes an original contribution to provide a clearer definition of expression networks. PMID:21910886

Unravelling proximate cues of mass flowering in the tropical forests of South-East Asia from gene expression analyses.

PubMed

Yeoh, Suat Hui; Satake, Akiko; Numata, Shinya; Ichie, Tomoaki; Lee, Soon Leong; Basherudin, Norlia; Muhammad, Norwati; Kondo, Toshiaki; Otani, Tatsuya; Hashim, Mazlan; Tani, Naoki

2017-10-01

Elucidating the physiological mechanisms of the irregular yet concerted flowering rhythm of mass flowering tree species in the tropics requires long-term monitoring of flowering phenology, exogenous and endogenous environmental factors, as well as identifying interactions and dependencies among these factors. To investigate the proximate factors for floral initiation of mast seeding trees in the tropics, we monitored the expression dynamics of two key flowering genes, meteorological conditions and endogenous resources over two flowering events of Shorea curtisii and Shorea leprosula in the Malay Peninsula. Comparisons of expression dynamics of genes studied indicated functional conservation of FLOWERING LOCUS T (FT) and LEAFY (LFY) in Shorea. The genes were highly expressed at least 1 month before anthesis for both species. A mathematical model considering the synergistic effect of cool temperature and drought on activation of the flowering gene was successful in predicting the observed gene expression patterns. Requirement of both cool temperature and drought for floral transition suggested by the model implies that flowering phenologies of these species are sensitive to climate change. Our molecular phenology approach in the tropics sheds light on the conserved role of flowering genes in plants inhabiting different climate zones and can be widely applied to dissect the flowering processes in other plant species. © 2017 John Wiley & Sons Ltd.

DREISS: Using State-Space Models to Infer the Dynamics of Gene Expression Driven by External and Internal Regulatory Networks

PubMed Central

Gerstein, Mark

2016-01-01

Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs), cellular growth factors and microRNAs. A subsystem’s gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally–e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution. We developed a computational method (DREISS, dreiss.gerteinlab.org) for analyzing the Dynamics of gene expression driven by Regulatory networks, both External and Internal based on State Space models. Given a subsystem, the “state” and “control” in the model refer to its own (internal) and another subsystem’s (external) gene expression levels. The state at a given time is determined by the state and control at a previous time. Because typical time-series data do not have enough samples to fully estimate the model’s parameters, DREISS uses dimensionality reduction, and identifies canonical temporal expression trajectories (e.g., degradation, growth and oscillation) representing the regulatory effects emanating from various subsystems. To demonstrate capabilities of DREISS, we study the regulatory effects of evolutionarily conserved vs. divergent TFs across distant species. In particular, we applied DREISS to the time-series gene expression datasets of C. elegans and D. melanogaster during their embryonic development. We analyzed the expression dynamics of the conserved, orthologous genes (orthologs), seeing the degree to which these can be accounted for by orthologous (internal) versus species-specific (external) TFs. We found that between two species, the orthologs have matched, internally driven expression patterns but very different externally driven ones. This is particularly true for genes with evolutionarily ancient functions (e.g. the ribosomal proteins), in contrast to those with more recently evolved functions (e.g., cell-cell communication). This suggests that despite striking morphological differences, some fundamental embryonic-developmental processes are still controlled by ancient regulatory systems. PMID:27760135

DREISS: Using State-Space Models to Infer the Dynamics of Gene Expression Driven by External and Internal Regulatory Networks.

PubMed

Wang, Daifeng; He, Fei; Maslov, Sergei; Gerstein, Mark

2016-10-01

Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs), cellular growth factors and microRNAs. A subsystem's gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally-e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution. We developed a computational method (DREISS, dreiss.gerteinlab.org) for analyzing the Dynamics of gene expression driven by Regulatory networks, both External and Internal based on State Space models. Given a subsystem, the "state" and "control" in the model refer to its own (internal) and another subsystem's (external) gene expression levels. The state at a given time is determined by the state and control at a previous time. Because typical time-series data do not have enough samples to fully estimate the model's parameters, DREISS uses dimensionality reduction, and identifies canonical temporal expression trajectories (e.g., degradation, growth and oscillation) representing the regulatory effects emanating from various subsystems. To demonstrate capabilities of DREISS, we study the regulatory effects of evolutionarily conserved vs. divergent TFs across distant species. In particular, we applied DREISS to the time-series gene expression datasets of C. elegans and D. melanogaster during their embryonic development. We analyzed the expression dynamics of the conserved, orthologous genes (orthologs), seeing the degree to which these can be accounted for by orthologous (internal) versus species-specific (external) TFs. We found that between two species, the orthologs have matched, internally driven expression patterns but very different externally driven ones. This is particularly true for genes with evolutionarily ancient functions (e.g. the ribosomal proteins), in contrast to those with more recently evolved functions (e.g., cell-cell communication). This suggests that despite striking morphological differences, some fundamental embryonic-developmental processes are still controlled by ancient regulatory systems.

Temporal Ordering of Dynamic Expression Data from Detailed Spatial Expression Maps.

PubMed

Bailey, Charlotte S L; Bone, Robert A; Murray, Philip J; Dale, J Kim

2017-02-09

During somitogenesis, pairs of epithelial somites form in a progressive manner, budding off from the anterior end of the pre-somitic mesoderm (PSM) with a strict species-specific periodicity. The periodicity of the process is regulated by a molecular oscillator, known as the "segmentation clock," acting in the PSM cells. This clock drives the oscillatory patterns of gene expression across the PSM in a posterior-anterior direction. These so-called clock genes are key components of three signaling pathways: Wnt, Notch, and fibroblast growth factor (FGF). In addition, Notch signaling is essential for synchronizing intracellular oscillations in neighboring cells. We recently gained insight into how this may be mechanistically regulated. Upon ligand activation, the Notch receptor is cleaved, releasing the intracellular domain (NICD), which moves to the nucleus and regulates gene expression. NICD is highly labile, and its phosphorylation-dependent turnover acts to restrict Notch signaling. The profile of NICD production (and degradation) in the PSM is known to be oscillatory and to resemble that of a clock gene. We recently reported that both the Notch receptor and the Delta ligand, which mediate intercellular coupling, themselves exhibit dynamic expression at both the mRNA and protein levels. In this article, we describe the sensitive detection methods and detailed image analysis tools that we used, in combination with the computational modeling that we designed, to extract and overlay expression data from distinct points in the expression cycle. This allowed us to construct a spatio-temporal picture of the dynamic expression profile for the receptor, the ligand, and the Notch target clock genes throughout an oscillation cycle. Here, we describe the protocols used to generate and culture the PSM explants, as well as the procedure to stain for the mRNA or protein. We also explain how the confocal images were subsequently analyzed and temporally ordered computationally to generate ordered sequences of clock expression snapshots, hereafter defined as "kymographs," for the visualization of the spatiotemporal expression of Delta-like1 (Dll1) and Notch1 throughout the PSM.

Distinguishing the rates of gene activation from phenotypic variations.

PubMed

Chen, Ye; Lv, Cheng; Li, Fangting; Li, Tiejun

2015-06-18

Stochastic genetic switching driven by intrinsic noise is an important process in gene expression. When the rates of gene activation/inactivation are relatively slow, fast, or medium compared with the synthesis/degradation rates of mRNAs and proteins, the variability of protein and mRNA levels may exhibit very different dynamical patterns. It is desirable to provide a systematic approach to identify their key dynamical features in different regimes, aiming at distinguishing which regime a considered gene regulatory network is in from their phenotypic variations. We studied a gene expression model with positive feedbacks when genetic switching rates vary over a wide range. With the goal of providing a method to distinguish the regime of the switching rates, we first focus on understanding the essential dynamics of gene expression system in different cases. In the regime of slow switching rates, we found that the effective dynamics can be reduced to independent evolutions on two separate layers corresponding to gene activation and inactivation states, and the transitions between two layers are rare events, after which the system goes mainly along deterministic ODE trajectories on a particular layer to reach new steady states. The energy landscape in this regime can be well approximated by using Gaussian mixture model. In the regime of intermediate switching rates, we analyzed the mean switching time to investigate the stability of the system in different parameter ranges. We also discussed the case of fast switching rates from the viewpoint of transition state theory. Based on the obtained results, we made a proposal to distinguish these three regimes in a simulation experiment. We identified the intermediate regime from the fact that the strength of cellular memory is lower than the other two cases, and the fast and slow regimes can be distinguished by their different perturbation-response behavior with respect to the switching rates perturbations. We proposed a simulation experiment to distinguish the slow, intermediate and fast regimes, which is the main point of our paper. In order to achieve this goal, we systematically studied the essential dynamics of gene expression system when the switching rates are in different regimes. Our theoretical understanding provides new insights on the gene expression experiments.

The modularity and dynamicity of miRNA-mRNA interactions in high-grade serous ovarian carcinomas and the prognostic implication.

PubMed

Zhang, Wensheng; Edwards, Andrea; Fan, Wei; Flemington, Erik K; Zhang, Kun

2016-08-01

Ovarian carcinoma is the fifth-leading cause of cancer death among women in the United States. Major reasons for this persistent mortality include the poor understanding of the underlying biology and a lack of reliable biomarkers. Previous studies have shown that aberrantly expressed MicroRNAs (miRNAs) are involved in carcinogenesis and tumor progression by post-transcriptionally regulating gene expression. However, the interference of miRNAs in tumorigenesis is quite complicated and far from being fully understood. In this work, by an integrative analysis of mRNA expression, miRNA expression and clinical data published by The Cancer Genome Atlas (TCGA), we studied the modularity and dynamicity of miRNA-mRNA interactions and the prognostic implications in high-grade serous ovarian carcinomas. With the top transcriptional correlations (Bonferroni-adjusted p-value<0.01) as inputs, we identified five miRNA-mRNA module pairs (MPs), each of which included one positive-connection (correlation) module and one negative-connection (correlation) module. The number of miRNAs or mRNAs in each module varied from 3 to 7 or from 2 to 873. Among the four major negative-connection modules, three fit well with the widely accepted miRNA-mediated post-transcriptional regulation theory. These modules were enriched with the genes relevant to cell cycle and immune response. Moreover, we proposed two novel algorithms to reveal the group or sample specific dynamic regulations between these two RNA classes. The obtained miRNA-mRNA dynamic network contains 3350 interactions captured across different cancer progression stages or tumor grades. We found that those dynamic interactions tended to concentrate on a few miRNAs (e.g. miRNA-936), and were more likely present on the miRNA-mRNA pairs outside the discovered modules. In addition, we also pinpointed a robust prognostic signature consisting of 56 modular protein-coding genes, whose co-expression patterns were predictive for the survival time of ovarian cancer patients in multiple independent cohorts. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neurocognitive mechanisms of gaze-expression interactions in face processing and social attention

PubMed Central

Graham, Reiko; LaBar, Kevin S.

2012-01-01

The face conveys a rich source of non-verbal information used during social communication. While research has revealed how specific facial channels such as emotional expression are processed, little is known about the prioritization and integration of multiple cues in the face during dyadic exchanges. Classic models of face perception have emphasized the segregation of dynamic versus static facial features along independent information processing pathways. Here we review recent behavioral and neuroscientific evidence suggesting that within the dynamic stream, concurrent changes in eye gaze and emotional expression can yield early independent effects on face judgments and covert shifts of visuospatial attention. These effects are partially segregated within initial visual afferent processing volleys, but are subsequently integrated in limbic regions such as the amygdala or via reentrant visual processing volleys. This spatiotemporal pattern may help to resolve otherwise perplexing discrepancies across behavioral studies of emotional influences on gaze-directed attentional cueing. Theoretical explanations of gaze-expression interactions are discussed, with special consideration of speed-of-processing (discriminability) and contextual (ambiguity) accounts. Future research in this area promises to reveal the mental chronometry of face processing and interpersonal attention, with implications for understanding how social referencing develops in infancy and is impaired in autism and other disorders of social cognition. PMID:22285906

The neural dynamics underlying the interpersonal effects of emotional expression on decision making

PubMed Central

Chen, Xuhai; Zheng, Tingting; Han, Lingzi; Chang, Yingchao; Luo, Yangmei

2017-01-01

Although numerous studies explore the effects of emotion on decision-making, the existing research has mainly focused on the influence of intrapersonal emotions, leaving the influence of one person’s emotions on another’s decisions underestimated. To specify how interpersonal emotions shape decision-making and delineate the underlying neural dynamics involved, the present study examined brain responses to utilitarian feedback combined with angry or happy faces in competitive and cooperative contexts. Behavioral results showed that participants responded slower following losses than wins when competitors express happiness but responded faster following losses than wins when cooperators express anger. Importantly, angry faces in competitive context reversed the differentiation pattern of feedback-related negativity (FRN) between losses and wins and diminished the difference between losses and wins on both P300 and theta power, but only diminished the difference on FRN between losses and wins in cooperative context. However, when partner displays happiness, losses versus wins elicited larger FRN and theta power in competitive context but smaller P300 in both contexts. These results suggest that interpersonal emotions shape decisions during both automatic motivational salience valuation (FRN) and conscious cognitive appraisal (P300) stages of processing, in which different emotional expressions exert interpersonal influence through different routes. PMID:28425491

Insights into the dynamics of hind leg development in honey bee (Apis mellifera L.) queen and worker larvae - A morphology/differential gene expression analysis

PubMed Central

Santos, Carolina Gonçalves; Hartfelder, Klaus

2015-01-01

Phenotypic plasticity is a hallmark of the caste systems of social insects, expressed in their life history and morphological traits. These are best studied in bees. In their co-evolution with angiosperm plants, the females of corbiculate bees have acquired a specialized structure on their hind legs for collecting pollen. In the highly eusocial bees (Apini and Meliponini), this structure is however only present in workers and absent in queens. By means of histological sections and cell proliferation analysis we followed the developmental dynamics of the hind legs of queens and workers in the fourth and fifth larval instars. In parallel, we generated subtractive cDNA libraries for hind leg discs of queen and worker larvae by means of a Representational Difference Analysis (RDA). From the total of 135 unique sequences we selected 19 for RT-qPCR analysis, where six of these were confirmed as differing significantly in their expression between the two castes in the larval spinning stage. The development of complex structures such as the bees’ hind legs, requires diverse patterning mechanisms and signaling modules, as indicated by the set of differentially expressed genes related with cell adhesion and signaling pathways. PMID:26500430

A Genome-Wide Screen Indicates Correlation between Differentiation and Expression of Metabolism Related Genes

PubMed Central

Shende, Akhilesh; Singh, Anupama; Meena, Anil; Ghosal, Ritika; Ranganathan, Madhav; Bandyopadhyay, Amitabha

2013-01-01

Differentiated tissues may be considered as materials with distinct properties. The differentiation program of a given tissue ensures that it acquires material properties commensurate with its function. It may be hypothesized that some of these properties are acquired through production of tissue-specific metabolites synthesized by metabolic enzymes. To establish correlation between metabolism and organogenesis we have carried out a genome-wide expression study of metabolism related genes by RNA in-situ hybridization. 23% of the metabolism related genes studied are expressed in a tissue-restricted but not tissue-exclusive manner. We have conducted the screen on whole mount chicken (Gallus gallus) embryos from four distinct developmental stages to correlate dynamic changes in expression patterns of metabolic enzymes with spatio-temporally unique developmental events. Our data strongly suggests that unique combinations of metabolism related genes, and not specific metabolic pathways, are upregulated during differentiation. Further, expression of metabolism related genes in well established signaling centers that regulate different aspects of morphogenesis indicates developmental roles of some of the metabolism related genes. The database of tissue-restricted expression patterns of metabolism related genes, generated in this study, should serve as a resource for systematic identification of these genes with tissue-specific functions during development. Finally, comprehensive understanding of differentiation is not possible unless the downstream genes of a differentiation cascade are identified. We propose, metabolic enzymes constitute a significant portion of these downstream target genes. Thus our study should help elucidate different aspects of tissue differentiation. PMID:23717462

A genome-wide screen indicates correlation between differentiation and expression of metabolism related genes.

PubMed

Roy, Priti; Kumar, Brijesh; Shende, Akhilesh; Singh, Anupama; Meena, Anil; Ghosal, Ritika; Ranganathan, Madhav; Bandyopadhyay, Amitabha

2013-01-01

Differentiated tissues may be considered as materials with distinct properties. The differentiation program of a given tissue ensures that it acquires material properties commensurate with its function. It may be hypothesized that some of these properties are acquired through production of tissue-specific metabolites synthesized by metabolic enzymes. To establish correlation between metabolism and organogenesis we have carried out a genome-wide expression study of metabolism related genes by RNA in-situ hybridization. 23% of the metabolism related genes studied are expressed in a tissue-restricted but not tissue-exclusive manner. We have conducted the screen on whole mount chicken (Gallus gallus) embryos from four distinct developmental stages to correlate dynamic changes in expression patterns of metabolic enzymes with spatio-temporally unique developmental events. Our data strongly suggests that unique combinations of metabolism related genes, and not specific metabolic pathways, are upregulated during differentiation. Further, expression of metabolism related genes in well established signaling centers that regulate different aspects of morphogenesis indicates developmental roles of some of the metabolism related genes. The database of tissue-restricted expression patterns of metabolism related genes, generated in this study, should serve as a resource for systematic identification of these genes with tissue-specific functions during development. Finally, comprehensive understanding of differentiation is not possible unless the downstream genes of a differentiation cascade are identified. We propose, metabolic enzymes constitute a significant portion of these downstream target genes. Thus our study should help elucidate different aspects of tissue differentiation.

Dynamic regulation of genetic pathways and targets during aging in Caenorhabditis elegans.

PubMed

He, Kan; Zhou, Tao; Shao, Jiaofang; Ren, Xiaoliang; Zhao, Zhongying; Liu, Dahai

2014-03-01

Numerous genetic targets and some individual pathways associated with aging have been identified using the worm model. However, less is known about the genetic mechanisms of aging in genome wide, particularly at the level of multiple pathways as well as the regulatory networks during aging. Here, we employed the gene expression datasets of three time points during aging in Caenorhabditis elegans (C. elegans) and performed the approach of gene set enrichment analysis (GSEA) on each dataset between adjacent stages. As a result, multiple genetic pathways and targets were identified as significantly down- or up-regulated. Among them, 5 truly aging-dependent signaling pathways including MAPK signaling pathway, mTOR signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway and ErbB signaling pathway as well as 12 significantly associated genes were identified with dynamic expression pattern during aging. On the other hand, the continued declines in the regulation of several metabolic pathways have been demonstrated to display age-related changes. Furthermore, the reconstructed regulatory networks based on three of aging related Chromatin immunoprecipitation experiments followed by sequencing (ChIP-seq) datasets and the expression matrices of 154 involved genes in above signaling pathways provide new insights into aging at the multiple pathways level. The combination of multiple genetic pathways and targets needs to be taken into consideration in future studies of aging, in which the dynamic regulation would be uncovered.

A physical model for earthquakes. I - Fluctuations and interactions. II - Application to southern California

NASA Technical Reports Server (NTRS)

Rundle, John B.

1988-01-01

The idea that earthquakes represent a fluctuation about the long-term motion of plates is expressed mathematically through the fluctuation hypothesis, under which all physical quantities which pertain to the occurance of earthquakes are required to depend on the difference between the present state of slip on the fault and its long-term average. It is shown that under certain circumstances the model fault dynamics undergo a sudden transition from a spatially ordered, temporally disordered state to a spatially disordered, temporally ordered state, and that the latter stages are stable for long intervals of time. For long enough faults, the dynamics are evidently chaotic. The methods developed are then used to construct a detailed model for earthquake dynamics in southern California. The result is a set of slip-time histories for all the major faults, which are similar to data obtained by geological trenching studies. Although there is an element of periodicity to the events, the patterns shift, change and evolve with time. Time scales for pattern evolution seem to be of the order of a thousand years for average recurring intervals of about a hundred years.

Regulation of DM-20 mRNA expression and intracellular translocation of glutathione-S-transferase pi isoform during oligodendrocyte differentiation in the adult rat spinal cord.

PubMed

Kitada, Masaaki; Takeda, Kazuya; Dezawa, Mari

2016-07-01

We previously demonstrated that NG2-positive oligodendrocyte precursor cells (OPCs) do not express DM-20 mRNA and identified a distinct DM-20 mRNA-positive cell population expressing glutathione-S-transferase pi isoform (GST-pi) in the nucleus (GST-pi(Nuc)) of the adult rat spinal cord. As GST-pi intranuclear localization correlates with progenitor cell properties, we examined the differentiation status of this cell population under the intensive 5-bromo-2'-deoxyuridine (BrdU) administration method, consisting of intraperitoneal BrdU injections every 2 h for 48 h. We observed that a certain population of proliferating/proliferated cells expressed DM-20 mRNA, and sometimes two proliferating/proliferated cells were observed still attached to each other. We performed triple staining for BrdU, DM-20 mRNA, and NG2 and found pairs of neighboring BrdU-positive cells, which were considered to originate from the same progenitor cells and where both cells expressed DM-20 mRNA. Triple staining for BrdU, DM-20 mRNA, and GST-pi detected proliferating/proliferated cells exhibiting the GST-pi(Nuc)/DM-20 mRNA-positive expression pattern. These findings suggested the presence of a GST-pi(Nuc)/DM-20 mRNA-positive oligodendrocyte-lineage progenitor cell population in the adult rat spinal cord. However, we did not find any pair of neighboring BrdU-positive cells with this expression pattern. These observations collectively support the idea that GST-pi(Nuc)/DM-20 mRNA-expressing cells are the progeny of NG2-positive OPCs rather than a novel type of oligodendrocyte-lineage progenitor cells and that DM-20 mRNA expression is dynamically regulated during differentiation of OPCs into oligodendrocytes.

A Common Neural Code for Perceived and Inferred Emotion

PubMed Central

Saxe, Rebecca

2014-01-01

Although the emotions of other people can often be perceived from overt reactions (e.g., facial or vocal expressions), they can also be inferred from situational information in the absence of observable expressions. How does the human brain make use of these diverse forms of evidence to generate a common representation of a target's emotional state? In the present research, we identify neural patterns that correspond to emotions inferred from contextual information and find that these patterns generalize across different cues from which an emotion can be attributed. Specifically, we use functional neuroimaging to measure neural responses to dynamic facial expressions with positive and negative valence and to short animations in which the valence of a character's emotion could be identified only from the situation. Using multivoxel pattern analysis, we test for regions that contain information about the target's emotional state, identifying representations specific to a single stimulus type and representations that generalize across stimulus types. In regions of medial prefrontal cortex (MPFC), a classifier trained to discriminate emotional valence for one stimulus (e.g., animated situations) could successfully discriminate valence for the remaining stimulus (e.g., facial expressions), indicating a representation of valence that abstracts away from perceptual features and generalizes across different forms of evidence. Moreover, in a subregion of MPFC, this neural representation generalized to trials involving subjectively experienced emotional events, suggesting partial overlap in neural responses to attributed and experienced emotions. These data provide a step toward understanding how the brain transforms stimulus-bound inputs into abstract representations of emotion. PMID:25429141

A common neural code for perceived and inferred emotion.

PubMed

Skerry, Amy E; Saxe, Rebecca

2014-11-26

Although the emotions of other people can often be perceived from overt reactions (e.g., facial or vocal expressions), they can also be inferred from situational information in the absence of observable expressions. How does the human brain make use of these diverse forms of evidence to generate a common representation of a target's emotional state? In the present research, we identify neural patterns that correspond to emotions inferred from contextual information and find that these patterns generalize across different cues from which an emotion can be attributed. Specifically, we use functional neuroimaging to measure neural responses to dynamic facial expressions with positive and negative valence and to short animations in which the valence of a character's emotion could be identified only from the situation. Using multivoxel pattern analysis, we test for regions that contain information about the target's emotional state, identifying representations specific to a single stimulus type and representations that generalize across stimulus types. In regions of medial prefrontal cortex (MPFC), a classifier trained to discriminate emotional valence for one stimulus (e.g., animated situations) could successfully discriminate valence for the remaining stimulus (e.g., facial expressions), indicating a representation of valence that abstracts away from perceptual features and generalizes across different forms of evidence. Moreover, in a subregion of MPFC, this neural representation generalized to trials involving subjectively experienced emotional events, suggesting partial overlap in neural responses to attributed and experienced emotions. These data provide a step toward understanding how the brain transforms stimulus-bound inputs into abstract representations of emotion. Copyright © 2014 the authors 0270-6474/14/3315997-12$15.00/0.

Salinity shifts in marine sediment: Importance of number of fluctuation rather than their intensities on bacterial denitrifying community.

PubMed

Zaghmouri, Imen; Michotey, Valerie D; Armougom, Fabrice; Guasco, Sophie; Bonin, Patricia C

2018-05-01

The sensitivity of denitrifying community to salinity fluctuations was studied in microcosms filled with marine coastal sediments subjected to different salinity disturbances over time (sediment under frequent salinity changes vs sediment with "stable" salinity pattern). Upon short-term salinity shift, denitrification rate and denitrifiers abundance showed high resistance whatever the sediment origin is. Denitrifying community adapted to frequent salinity changes showed high resistance when salinity increases, with a dynamic nosZ relative expression level. Marine sediment denitrifying community, characterized by more stable pattern, was less resistant when salinity decreases. However, after two successive variations of salinity, it shifted toward the characteristic community of fluctuating conditions, with larger proportion of Pseudomonas-nosZ, exhibiting an increase of nosZ relative expression level. The impact of long-term salinity variation upon bacterial community was confirmed at ribosomal level with a higher percentage of Pseudomonas and lower proportion of nosZII clade genera. Copyright © 2018 Elsevier Ltd. All rights reserved.

Caring more and knowing more reduces age-related differences in emotion perception.

PubMed

Stanley, Jennifer Tehan; Isaacowitz, Derek M

2015-06-01

Traditional emotion perception tasks show that older adults are less accurate than are young adults at recognizing facial expressions of emotion. Recently, we proposed that socioemotional factors might explain why older adults seem impaired in lab tasks but less so in everyday life (Isaacowitz & Stanley, 2011). Thus, in the present research we empirically tested whether socioemotional factors such as motivation and familiarity can alter this pattern of age effects. In 1 task, accountability instructions eliminated age differences in the traditional emotion perception task. Using a novel emotion perception paradigm featuring spontaneous dynamic facial expressions of a familiar romantic partner versus a same-age stranger, we found that age differences in emotion perception accuracy were attenuated in the familiar partner condition, relative to the stranger condition. Taken together, the results suggest that both overall accuracy as well as specific patterns of age effects differ appreciably between traditional emotion perception tasks and emotion perception within a socioemotional context. (c) 2015 APA, all rights reserved.

Caring More and Knowing More Reduces Age-Related Differences in Emotion Perception

PubMed Central

Stanley, Jennifer Tehan; Isaacowitz, Derek M.

2015-01-01

Traditional emotion perception tasks show that older adults are less accurate than young adults at recognizing facial expressions of emotion. Recently, we proposed that socioemotional factors might explain why older adults seem impaired in lab tasks but less so in everyday life (Isaacowitz & Stanley, 2011). Thus, in the present research we empirically tested whether socioemotional factors such as motivation and familiarity can alter this pattern of age effects. In one task, accountability instructions eliminated age differences in the traditional emotion perception task. Using a novel emotion perception paradigm featuring spontaneous dynamic facial expressions of a familiar romantic partner versus a same-age stranger, we found that age differences in emotion perception accuracy were attenuated in the familiar partner condition, relative to the stranger condition. Taken together, the results suggest that both overall accuracy as well as specific patterns of age effects differ appreciably between traditional emotion perception tasks and emotion perception within a socioemotional context. PMID:26030775

Parvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation

NASA Astrophysics Data System (ADS)

Ognjanovski, Nicolette; Schaeffer, Samantha; Wu, Jiaxing; Mofakham, Sima; Maruyama, Daniel; Zochowski, Michal; Aton, Sara J.

2017-04-01

Activity in hippocampal area CA1 is essential for consolidating episodic memories, but it is unclear how CA1 activity patterns drive memory formation. We find that in the hours following single-trial contextual fear conditioning (CFC), fast-spiking interneurons (which typically express parvalbumin (PV)) show greater firing coherence with CA1 network oscillations. Post-CFC inhibition of PV+ interneurons blocks fear memory consolidation. This effect is associated with loss of two network changes associated with normal consolidation: (1) augmented sleep-associated delta (0.5-4 Hz), theta (4-12 Hz) and ripple (150-250 Hz) oscillations; and (2) stabilization of CA1 neurons' functional connectivity patterns. Rhythmic activation of PV+ interneurons increases CA1 network coherence and leads to a sustained increase in the strength and stability of functional connections between neurons. Our results suggest that immediately following learning, PV+ interneurons drive CA1 oscillations and reactivation of CA1 ensembles, which directly promotes network plasticity and long-term memory formation.

Vegetation-induced spatial variability of soil redox properties in wetlands

NASA Astrophysics Data System (ADS)

Szalai, Zoltán; Jakab, Gergely; Kiss, Klaudia; Ringer, Marianna; Balázs, Réka; Zacháry, Dóra; Horváth Szabó, Kata; Perényi, Katalin

2016-04-01

Vegetation induced land patches may result spatial pattern of on soil Eh and pH. These spatial pattern are mainly emerged by differences of aeration and exudation of assimilates. Present paper focuses on vertical extent and temporal dynamics of these patterns in wetlands. Two study sites were selected: 1. a plain wetland on calcareous sandy parent material (Ceglédbercel, Danube-Tisza Interfluve, Hungary); 2. headwater wetland with calcareous loamy parent material (Bátaapáti, Hungary). Two vegetation patches were studied in site 1: sedgy (dominated by Carex riparia) and reedy (dominated by Phragmites australis). Three patches were studied in site2: sedgy1 (dominated by C vulpina), sedgy 2 (C. riparia); nettle-horsetail (Urtica dioica and Equisetum arvense). Boundaries between patches were studied separately. Soil redox, pH and temperature studied by automated remote controlled instruments. Three digital sensors (Ponsell) were installed in each locations: 20cm and 40cm sensors represent the solum and 100 cm sensor monitors the subsoil). Groundwater wells were installed near to triplets for soil water sampling. Soil Eh, pH and temperature values were recorded in each 10 minutes. Soil water sampling for iron and DOC were carried out during saturated periods. Spatial pattern of soil Eh is clearly caused by vegetation. We measured significant differences between Eh values of the studied patches in the solum. We did not find this kinds horizontal differences in the subsoil. Boundaries of the patches usually had more reductive soil environment than the core areas. We have found temporal dynamics of the spatial redox pattern. Differences were not so well expressed during wintertime. These spatial patterns had influence on the DOC and iron content of porewater, as well. Highest temporal dynamics of soil redox properties and porewater iron could be found in the boundaries. These observations refer to importance patchiness of vegetation on soil chemical properties in wetlands. Authors are grateful to Hungarian Scientific research Fund (K100180)

Dynamic biometric identification from multiple views using the GLBP-TOP method.

PubMed

Wang, Yu; Shen, Xuanjing; Chen, Haipeng; Zhai, Yujie

2014-01-01

To realize effective and rapid dynamic biometric identification with low computational complexity, a video-based facial texture program that extracts local binary patterns from three orthogonal planes in the frequency domain of the Gabor transform (GLBP-TOP) was proposed. Firstly, each normalized face was transformed by Gabor wavelet to get the enhanced Gabor magnitude map, and then the LBP-TOP operator was applied to the maps to extract video texture. Finally, weighted Chi square statistics based on the Fisher Criterion were used to realize the identification. The proposed algorithm was proved effective through the biometric experiments using the Honda/UCSD database, and was robust against changes of illumination and expressions.

Phenotypic models of evolution and development: geometry as destiny.

PubMed

François, Paul; Siggia, Eric D

2012-12-01

Quantitative models of development that consider all relevant genes typically are difficult to fit to embryonic data alone and have many redundant parameters. Computational evolution supplies models of phenotype with relatively few variables and parameters that allows the patterning dynamics to be reduced to a geometrical picture for how the state of a cell moves. The clock and wavefront model, that defines the phenotype of somitogenesis, can be represented as a sequence of two discrete dynamical transitions (bifurcations). The expression-time to space map for Hox genes and the posterior dominance rule are phenotypes that naturally follow from computational evolution without considering the genetics of Hox regulation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mouse Social Network Dynamics and Community Structure are Associated with Plasticity-Related Brain Gene Expression

PubMed Central

Williamson, Cait M.; Franks, Becca; Curley, James P.

2016-01-01

Laboratory studies of social behavior have typically focused on dyadic interactions occurring within a limited spatiotemporal context. However, this strategy prevents analyses of the dynamics of group social behavior and constrains identification of the biological pathways mediating individual differences in behavior. In the current study, we aimed to identify the spatiotemporal dynamics and hierarchical organization of a large social network of male mice. We also sought to determine if standard assays of social and exploratory behavior are predictive of social behavior in this social network and whether individual network position was associated with the mRNA expression of two plasticity-related genes, DNA methyltransferase 1 and 3a. Mice were observed to form a hierarchically organized social network and self-organized into two separate social network communities. Members of both communities exhibited distinct patterns of socio-spatial organization within the vivaria that was not limited to only agonistic interactions. We further established that exploratory and social behaviors in standard behavioral assays conducted prior to placing the mice into the large group was predictive of initial network position and behavior but were not associated with final social network position. Finally, we determined that social network position is associated with variation in mRNA levels of two neural plasticity genes, DNMT1 and DNMT3a, in the hippocampus but not the mPOA. This work demonstrates the importance of understanding the role of social context and complex social dynamics in determining the relationship between individual differences in social behavior and brain gene expression. PMID:27540359

Infection rates and comparative population dynamics of Peregrinus maidis (Hemiptera: Delphacidae) on corn plants with and without symptoms of maize mosaic virus (Rhabdoviridae: Nucleorhabdovirus) infection.

PubMed

Higashi, C H V; Bressan, A

2013-10-01

We examined the population dynamics of the corn planthopper Peregrinus maidis (Ashmead) (Hemiptera: Delphacidae) throughout a cycle of corn (Zea mays L.) production on plants with or without symptoms of maize mosaic virus (MMV) (Rhabdoviridae: Nucleorhabdovirus) infection. Our results indicate that the timing of MMV plant infection greatly influenced the planthopper's host plant colonization patterns. Corn plants that expressed symptoms of MMV infection early in the crop cycle (28 d after planting) harbored, on average, 40 and 48% fewer planthoppers than plants that expressed symptoms of MMV infection later in the crop cycle (49 d after planting) and asymptomatic plants, respectively. We also observed a change in the number of brachypterous (short-wing type) and macropterous (long-wing type) winged forms produced; plants expressing early symptoms of MMV infection harbored, on average, 41 and 47% more of the brachypterous form than plants with late infections of MMV and plants with no symptoms of MMV, respectively. Furthermore, we determined the rates of MMV-infected planthoppers relative to their wing morphology (macropterous or brachypterous) and gender. MMV infection was 5 and 12% higher in females than in males in field and greenhouse experiments, respectively; however, these differences were not significantly different. This research provides evidence that MMV similarly infects P. maidis planthoppers regardless of the gender and wing morphotype. These results also suggest that the timing of symptom development greatly affects the population dynamics of the planthopper vector, and likely has important consequences for the dynamics of the disease in the field.

Architectural patterns of p16 immunohistochemical expression associated with cancer immunity and prognosis of head and neck squamous cell carcinoma.

PubMed

Ryu, Hyang Joo; Kim, Eun Kyung; Heo, Su Jin; Cho, Byoung Chul; Kim, Hye Ryun; Yoon, Sun Och

2017-11-01

We evaluated the expression patterns of p16, which is used as a surrogate marker of HPV infection in head and neck squamous cell carcinoma (HNSCC), in regard to their biological and prognostic implications. p16 expression patterns and infiltrated immune cells were analyzed through immunohistochemistry of p16, CD3, CD8, PD-1, FOXP3, and CD163 on surgically resected HNSCCs (n = 393). Patterns of p16 immunoexpression were defined as STRONG (strong, diffuse expression in cytoplasm, and nucleus in >70% of tumor cells), MARGINAL (expression restricted to tumor margins), MOSAIC (ragged, discontinued expression), NUCLEAR (expression in nuclei only), and ABSENT (no expression). The STRONG pattern was more frequent in the oropharynx, and the MARGINAL pattern was noted only in the oral cavity. MOSAIC and NUCLEAR patterns were noted at variable sites. No two patterns of p16 expression showed the same immune cell composition of CD3+ T cells, CD8+ cytotoxic T cells, PD-1+ T cells, FOXP3+ regulatory T cells, and CD163+ macrophages. In overall and disease-free survival analyses, the STRONG pattern showed the most favorable prognosis, while the NUCLEAR pattern had the worst prognosis. HNSCC anatomical sites, tumor-related immune cell components, and patient outcomes were associated with p16 expression patterns. Each architectural pattern of p16 expression may be related to different biological and prognostic phenotypes. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Pervasive polymorphic imprinted methylation in the human placenta

PubMed Central

Hanna, Courtney W.; Peñaherrera, Maria S.; Saadeh, Heba; Andrews, Simon; McFadden, Deborah E.; Kelsey, Gavin; Robinson, Wendy P.

2016-01-01

The maternal and paternal copies of the genome are both required for mammalian development, and this is primarily due to imprinted genes, those that are monoallelically expressed based on parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are established in the germline and maintained after fertilization. There are a large number of germline DMRs that have not yet been associated with imprinting, and their function in development is unknown. In this study, we developed a genome-wide approach to identify novel imprinted DMRs in the human placenta and investigated the dynamics of these imprinted DMRs during development in somatic and extraembryonic tissues. DNA methylation was evaluated using the Illumina HumanMethylation450 array in 134 human tissue samples, publicly available reduced representation bisulfite sequencing in the human embryo and germ cells, and targeted bisulfite sequencing in term placentas. Forty-three known and 101 novel imprinted DMRs were identified in the human placenta by comparing methylation between diandric and digynic triploid conceptions in addition to female and male gametes. Seventy-two novel DMRs showed a pattern consistent with placental-specific imprinting, and this monoallelic methylation was entirely maternal in origin. Strikingly, these DMRs exhibited polymorphic imprinted methylation between placental samples. These data suggest that imprinting in human development is far more extensive and dynamic than previously reported and that the placenta preferentially maintains maternal germline-derived DNA methylation. PMID:26769960

Testing synaptic plasticity in dynamic mate choice decisions: N-methyl d-aspartate receptor blockade disrupts female preference

PubMed Central

Ramsey, Mary E.; Vu, Wendy; Cummings, Molly E.

2014-01-01

Social behaviours such as mate choice require context-specific responses, often with evolutionary consequences. Increasing evidence indicates that the behavioural plasticity associated with mate choice involves learning. For example, poeciliids show age-dependent changes in female preference functions and express synaptic-plasticity-associated molecular markers during mate choice. Here, we test whether social cognition is necessary for female preference behaviour by blocking the central player in synaptic plasticity, NMDAR (N-methyl d-aspartate receptor), in a poeciliid fish, Xiphophorus nigrensis. After subchronic exposure to NMDAR antagonist MK-801, female preference behaviours towards males were dramatically reduced. Overall activity levels were unaffected, but there was a directional shift from ‘social’ behaviours towards neutral activity. Multivariate gene expression patterns significantly discriminated between females with normal versus disrupted plasticity processes and correlated with preference behaviours—not general activity. Furthermore, molecular patterns support a distinction between ‘preference’ (e.g. neuroserpin, neuroligin-3, NMDAR) and ‘sociality’ (isotocin and vasotocin) gene clusters, highlighting a possible conservation between NMDAR disruption and nonapeptides in modulating behaviour. Our results suggest that mate preference may involve greater social memory processing than overall sociality, and that poeciliid preference functions integrate synaptic-plasticity-oriented ‘preference’ pathways with overall sociality to invoke dynamic, context-specific responses towards favoured males and away from unfavoured males. PMID:24807251

Decoding Task and Stimulus Representations in Face-responsive Cortex

PubMed Central

Kliemann, Dorit; Jacoby, Nir; Anzellotti, Stefano; Saxe, Rebecca R.

2017-01-01

Faces provide rich social information about others’ stable traits (e.g., age) and fleeting states of mind (e.g., emotional expression). While some of these facial aspects may be processed automatically, observers can also deliberately attend to some features while ignoring others. It remains unclear how internal goals (e.g., task context) influence the representational geometry of variable and stable facial aspects in face-responsive cortex. We investigated neural response patterns related to decoding i) the intention to attend to a facial aspect before its perception, ii) the attended aspect of a face and iii) stimulus properties. We measured neural responses while subjects watched videos of dynamic positive and negative expressions, and judged the age or the expression’s valence. Split-half multivoxel pattern analyses (MVPA) showed that (i) the intention to attend to a specific aspect of a face can be decoded from left fronto-lateral, but not face-responsive regions; (ii) during face perception, the attend aspect (age vs emotion) could be robustly decoded from almost all face-responsive regions; and (iii) a stimulus property (valence), was represented in right posterior superior temporal sulcus and medial prefrontal cortices. The effect of deliberately shifting the focus of attention on representations suggest a powerful influence of top-down signals on cortical representation of social information, varying across cortical regions, likely reflecting neural flexibility to optimally integrate internal goals and dynamic perceptual input. PMID:27978778

Validation of the Amsterdam Dynamic Facial Expression Set – Bath Intensity Variations (ADFES-BIV): A Set of Videos Expressing Low, Intermediate, and High Intensity Emotions

PubMed Central

Wingenbach, Tanja S. H.

2016-01-01

Most of the existing sets of facial expressions of emotion contain static photographs. While increasing demand for stimuli with enhanced ecological validity in facial emotion recognition research has led to the development of video stimuli, these typically involve full-blown (apex) expressions. However, variations of intensity in emotional facial expressions occur in real life social interactions, with low intensity expressions of emotions frequently occurring. The current study therefore developed and validated a set of video stimuli portraying three levels of intensity of emotional expressions, from low to high intensity. The videos were adapted from the Amsterdam Dynamic Facial Expression Set (ADFES) and termed the Bath Intensity Variations (ADFES-BIV). A healthy sample of 92 people recruited from the University of Bath community (41 male, 51 female) completed a facial emotion recognition task including expressions of 6 basic emotions (anger, happiness, disgust, fear, surprise, sadness) and 3 complex emotions (contempt, embarrassment, pride) that were expressed at three different intensities of expression and neutral. Accuracy scores (raw and unbiased (Hu) hit rates) were calculated, as well as response times. Accuracy rates above chance level of responding were found for all emotion categories, producing an overall raw hit rate of 69% for the ADFES-BIV. The three intensity levels were validated as distinct categories, with higher accuracies and faster responses to high intensity expressions than intermediate intensity expressions, which had higher accuracies and faster responses than low intensity expressions. To further validate the intensities, a second study with standardised display times was conducted replicating this pattern. The ADFES-BIV has greater ecological validity than many other emotion stimulus sets and allows for versatile applications in emotion research. It can be retrieved free of charge for research purposes from the corresponding author. PMID:26784347

Validation of the Amsterdam Dynamic Facial Expression Set--Bath Intensity Variations (ADFES-BIV): A Set of Videos Expressing Low, Intermediate, and High Intensity Emotions.

PubMed

Wingenbach, Tanja S H; Ashwin, Chris; Brosnan, Mark

2016-01-01

Most of the existing sets of facial expressions of emotion contain static photographs. While increasing demand for stimuli with enhanced ecological validity in facial emotion recognition research has led to the development of video stimuli, these typically involve full-blown (apex) expressions. However, variations of intensity in emotional facial expressions occur in real life social interactions, with low intensity expressions of emotions frequently occurring. The current study therefore developed and validated a set of video stimuli portraying three levels of intensity of emotional expressions, from low to high intensity. The videos were adapted from the Amsterdam Dynamic Facial Expression Set (ADFES) and termed the Bath Intensity Variations (ADFES-BIV). A healthy sample of 92 people recruited from the University of Bath community (41 male, 51 female) completed a facial emotion recognition task including expressions of 6 basic emotions (anger, happiness, disgust, fear, surprise, sadness) and 3 complex emotions (contempt, embarrassment, pride) that were expressed at three different intensities of expression and neutral. Accuracy scores (raw and unbiased (Hu) hit rates) were calculated, as well as response times. Accuracy rates above chance level of responding were found for all emotion categories, producing an overall raw hit rate of 69% for the ADFES-BIV. The three intensity levels were validated as distinct categories, with higher accuracies and faster responses to high intensity expressions than intermediate intensity expressions, which had higher accuracies and faster responses than low intensity expressions. To further validate the intensities, a second study with standardised display times was conducted replicating this pattern. The ADFES-BIV has greater ecological validity than many other emotion stimulus sets and allows for versatile applications in emotion research. It can be retrieved free of charge for research purposes from the corresponding author.

Expression Patterns of Odorant Receptors and Response Properties of Olfactory Sensory Neurons in Aged Mice

PubMed Central

Lee, Anderson C.; Tian, Huikai; Grosmaitre, Xavier

2009-01-01

The sense of smell deteriorates in normal aging, but the underling mechanisms are still elusive. Here we investigated age-related alterations in expression patterns of odorant receptor (OR) genes and functional properties of olfactory sensory neurons (OSNs)—2 critical factors that define the odor detection threshold in the olfactory epithelium. Using in situ hybridization for 9 representative OR genes, we compared the cell densities of each OR in coronal nose sections at different ages (3–27 months). The cell density for different ORs peaked at different time points and a decline was observed for 6 of 9 ORs at advanced ages. Using patch clamp recordings, we then examined the odorant responses of individual OSNs coexpressing a defined OR (MOR23) and green fluorescent protein. The MOR23 neurons recorded from aged animals maintained a similar sensitivity and dynamic range in response to the cognate odorant (lyral) as those from younger mice. The results indicate that although the cell densities of OSNs expressing certain types of ORs decline at advanced ages, individual OSNs can retain their sensitivity. The implications of these findings in age-related olfactory deterioration are discussed. PMID:19759360

Expression patterns of odorant receptors and response properties of olfactory sensory neurons in aged mice.

PubMed

Lee, Anderson C; Tian, Huikai; Grosmaitre, Xavier; Ma, Minghong

2009-10-01

The sense of smell deteriorates in normal aging, but the underling mechanisms are still elusive. Here we investigated age-related alterations in expression patterns of odorant receptor (OR) genes and functional properties of olfactory sensory neurons (OSNs)-2 critical factors that define the odor detection threshold in the olfactory epithelium. Using in situ hybridization for 9 representative OR genes, we compared the cell densities of each OR in coronal nose sections at different ages (3-27 months). The cell density for different ORs peaked at different time points and a decline was observed for 6 of 9 ORs at advanced ages. Using patch clamp recordings, we then examined the odorant responses of individual OSNs coexpressing a defined OR (MOR23) and green fluorescent protein. The MOR23 neurons recorded from aged animals maintained a similar sensitivity and dynamic range in response to the cognate odorant (lyral) as those from younger mice. The results indicate that although the cell densities of OSNs expressing certain types of ORs decline at advanced ages, individual OSNs can retain their sensitivity. The implications of these findings in age-related olfactory deterioration are discussed.

Theory of nonstationary Hawkes processes

NASA Astrophysics Data System (ADS)

Tannenbaum, Neta Ravid; Burak, Yoram

2017-12-01

We expand the theory of Hawkes processes to the nonstationary case, in which the mutually exciting point processes receive time-dependent inputs. We derive an analytical expression for the time-dependent correlations, which can be applied to networks with arbitrary connectivity, and inputs with arbitrary statistics. The expression shows how the network correlations are determined by the interplay between the network topology, the transfer functions relating units within the network, and the pattern and statistics of the external inputs. We illustrate the correlation structure using several examples in which neural network dynamics are modeled as a Hawkes process. In particular, we focus on the interplay between internally and externally generated oscillations and their signatures in the spike and rate correlation functions.

Expression Patterns and Subcellular Localization of Carbonic Anhydrases Are Developmentally Regulated during Tooth Formation

PubMed Central

Reibring, Claes-Göran; El Shahawy, Maha; Hallberg, Kristina; Kannius-Janson, Marie; Nilsson, Jeanette; Parkkila, Seppo; Sly, William S.; Waheed, Abdul; Linde, Anders; Gritli-Linde, Amel

2014-01-01

Carbonic anhydrases (CAs) play fundamental roles in several physiological events, and emerging evidence points at their involvement in an array of disorders, including cancer. The expression of CAs in the different cells of teeth is unknown, let alone their expression patterns during odontogenesis. As a first step towards understanding the role of CAs during odontogenesis, we used immunohistochemistry, histochemistry and in situ hybridization to reveal hitherto unknown dynamic distribution patterns of eight CAs in mice. The most salient findings include expression of CAII/Car2 not only in maturation-stage ameloblasts (MA) but also in the papillary layer, dental papilla mesenchyme, odontoblasts and the epithelial rests of Malassez. We uncovered that the latter form lace-like networks around incisors; hitherto these have been known to occur only in molars. All CAs studied were produced by MA, however CAIV, CAIX and CARPXI proteins were distinctly enriched in the ruffled membrane of the ruffled MA but exhibited a homogeneous distribution in smooth-ended MA. While CAIV, CAVI/Car6, CAIX, CARPXI and CAXIV were produced by all odontoblasts, CAIII distribution displayed a striking asymmetry, in that it was virtually confined to odontoblasts in the root of molars and root analog of incisors. Remarkably, from initiation until near completion of odontogenesis and in several other tissues, CAXIII localized mainly in intracellular punctae/vesicles that we show to overlap with LAMP-1- and LAMP-2-positive vesicles, suggesting that CAXIII localizes within lysosomes. We showed that expression of CAs in developing teeth is not confined to cells involved in biomineralization, pointing at their participation in other biological events. Finally, we uncovered novel sites of CA expression, including the developing brain and eye, the olfactory epithelium, melanoblasts, tongue, notochord, nucleus pulposus and sebaceous glands. Our study provides important information for future single or multiple gene targeting strategies aiming at deciphering the function of CAs during odontogenesis. PMID:24789143

H2A.Z Acidic Patch Couples Chromatin Dynamics to Regulation of Gene Expression Programs during ESC Differentiation

PubMed Central

Subramanian, Vidya; Mazumder, Aprotim; Surface, Lauren E.; Butty, Vincent L.; Fields, Paul A.; Alwan, Allison; Torrey, Lillian; Thai, Kevin K.; Levine, Stuart S.; Bathe, Mark; Boyer, Laurie A.

2013-01-01

The histone H2A variant H2A.Z is essential for embryonic development and for proper control of developmental gene expression programs in embryonic stem cells (ESCs). Divergent regions of amino acid sequence of H2A.Z likely determine its functional specialization compared to core histone H2A. For example, H2A.Z contains three divergent residues in the essential C-terminal acidic patch that reside on the surface of the histone octamer as an uninterrupted acidic patch domain; however, we know little about how these residues contribute to chromatin structure and function. Here, we show that the divergent amino acids Gly92, Asp97, and Ser98 in the H2A.Z C-terminal acidic patch (H2A.ZAP3) are critical for lineage commitment during ESC differentiation. H2A.Z is enriched at most H3K4me3 promoters in ESCs including poised, bivalent promoters that harbor both activating and repressive marks, H3K4me3 and H3K27me3 respectively. We found that while H2A.ZAP3 interacted with its deposition complex and displayed a highly similar distribution pattern compared to wild-type H2A.Z, its enrichment levels were reduced at target promoters. Further analysis revealed that H2A.ZAP3 was less tightly associated with chromatin, suggesting that the mutant is more dynamic. Notably, bivalent genes in H2A.ZAP3 ESCs displayed significant changes in expression compared to active genes. Moreover, bivalent genes in H2A.ZAP3 ESCs gained H3.3, a variant associated with higher nucleosome turnover, compared to wild-type H2A.Z. We next performed single cell imaging to measure H2A.Z dynamics. We found that H2A.ZAP3 displayed higher mobility in chromatin compared to wild-type H2A.Z by fluorescent recovery after photobleaching (FRAP). Moreover, ESCs treated with the transcriptional inhibitor flavopiridol resulted in a decrease in the H2A.ZAP3 mobile fraction and an increase in its occupancy at target genes indicating that the mutant can be properly incorporated into chromatin. Collectively, our work suggests that the divergent residues in the H2A.Z acidic patch comprise a unique domain that couples control of chromatin dynamics to the regulation of developmental gene expression patterns during lineage commitment. PMID:23990805

Profiling the dynamic expression of checkpoint molecules on cytokine-induced killer cells from non-small-cell lung cancer patients.

PubMed

Zhang, Lin; Wang, Jian; Wei, Feng; Wang, Kaiyuan; Sun, Qian; Yang, Fan; Jin, Hao; Zheng, Yu; Zhao, Hua; Wang, Limei; Yu, Wenwen; Zhang, Xiying; An, Yang; Yang, Lili; Zhang, Xinwei; Ren, Xiubao

2016-07-12

Immune checkpoints associate with dysfunctional T cells, which have a reduced ability to clear pathogens or cancer cells. T-cell checkpoint blockade may improve patient survival. However, checkpoint molecules on cytokine-induced killer (CIK) cell, a non-specific adoptive immunotherapy, remain unknown. In present study, we detected the dynamic expression of eight major checkpoint molecules (CTLA-4, PD-1, PD-L1, TIM- 3, CEACAM-1, LAG-3, TIGIT and BTLA) on CIK cells from NSCLC patients. The majority of these molecules, except BTLA, were sharply elevated during the early stage of CIK cell culture. Thereafter, PD-1 and TIGIT expressions decreased gradually towards the initial level (day 0). Moreover, CTLA-4 faded away during the later stage of CIK culture. LAG-3 expression decreased but was still significantly higher than the initial level. Of note, PD-L1 remained stably upregulated during CIK culture compared with PD-1, indicating that PD-L1 might act as an inhibitory molecule on CIK cells instead of PD-1. Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation. BTLA displayed a distinct pattern, and its expression gradually decreased throughout the CIK culture. These observations suggested that CIK cells might be partly exhausted before clinical transfusion, characterized by the high expression of PD-L1, LAG-3, TIM- 3, and CEACAM-1 and the low expression of TIGIT, BTLA, PD-1, and CTLA-4 compared with initial culture. Our results imply that implementing combined treatment on CIK cells before transfusion via antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients.

Dynamics of biomass partitioning, stem gene expression, cell wall biosynthesis, and sucrose accumulation during development of Sorghum bicolor.

PubMed

McKinley, Brian; Rooney, William; Wilkerson, Curtis; Mullet, John

2016-11-01

Biomass accumulated preferentially in leaves of the sweet sorghum Della until floral initiation, then stems until anthesis, followed by panicles until grain maturity, and apical tillers. Sorghum stem RNA-seq transcriptome profiles and composition data were collected for approximately 100 days of development beginning at floral initiation. The analysis identified >200 differentially expressed genes involved in stem growth, cell wall biology, and sucrose accumulation. Genes encoding expansins and xyloglucan endotransglucosylase/hydrolases were differentially expressed in growing stem internodes. Genes encoding enzymes involved in the synthesis of cellulose, lignin, and glucuronoarabinoxylan were expressed at elevated levels in stems until approximately 7 days before anthesis and then down-regulated. CESA genes involved in primary and secondary cell wall synthesis showed different temporal patterns of expression. Following floral initiation, the level of sucrose and other non-structural carbohydrates increased to approximately 50% of the stem's dry weight. Stem sucrose accumulation was inversely correlated with >100-fold down-regulation of SbVIN1, a gene encoding a vacuolar invertase. Accumulation of stem sucrose was also correlated with cessation of leaf and stem growth at anthesis, decreased expression of genes involved in stem cell wall synthesis, and approximately 10-fold lower expression of SbSUS4, a gene encoding sucrose synthase that generates UDP-glucose from sucrose for cell wall biosynthesis. Genes for mixed linkage glucan synthesis (CSLF) and turnover were expressed at high levels in stems throughout development. Overall, the stem transcription profile resource and the genes and regulatory dynamics identified in this study will be useful for engineering sorghum stem composition for improved conversion to biofuels and bio-products. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Patterns of Tree Species Diversity in Relation to Climatic Factors on the Sierra Madre Occidental, Mexico

PubMed Central

Silva-Flores, Ramón; Pérez-Verdín, Gustavo; Wehenkel, Christian

2014-01-01

Biological diversity can be defined as variability among living organisms from all sources, including terrestrial organisms, marine and other aquatic ecosystems, and the ecological complexes which they are part of. This includes diversity within species, between species, and of ecosystems. Numerous diversity indices combine richness and evenness in a single expression, and several climate-based explanations have been proposed to explain broad-scale diversity patterns. However, climate-based water-energy dynamics appears to be an essential factor that determines patterns of diversity. The Mexican Sierra Madre Occidental occupies an area of about 29 million hectares and is located between the Neotropical and Holarctic ecozones. It shelters a high diversity of flora, including 24 different species of Pinus (ca. 22% on the whole), 54 species of Quercus (ca. 9–14%), 7 species of Arbutus (ca. 50%) and many other trees species. The objectives of this study were to model how tree species diversity is related to climatic and geographic factors and stand density and to test the Metabolic Theory, Productivity-Diversity Hypothesis, Physiological Tolerance Hypothesis, Mid-Domain Effect, and the Water-Energy Dynamic Theory on the Sierra Madre Occidental, Durango. The results supported the Productivity-Diversity Hypothesis, Physiological Tolerance Hypothesis and Water-Energy Dynamic Theory, but not the Mid-Domain Effect or Metabolic Theory. The annual aridity index was the variable most closely related to the diversity indices analyzed. Contemporary climate was found to have moderate to strong effects on the minimum, median and maximum tree species diversity. Because water-energy dynamics provided a satisfactory explanation for the patterns of minimum, median and maximum diversity, an understanding of this factor is critical to future biodiversity research. Quantile regression of the data showed that the three diversity parameters of tree species are generally higher in cold, humid temperate climates than in dry, hot climates. PMID:25127455

Patterns of tree species diversity in relation to climatic factors on the Sierra Madre Occidental, Mexico.

PubMed

Silva-Flores, Ramón; Pérez-Verdín, Gustavo; Wehenkel, Christian

2014-01-01

Biological diversity can be defined as variability among living organisms from all sources, including terrestrial organisms, marine and other aquatic ecosystems, and the ecological complexes which they are part of. This includes diversity within species, between species, and of ecosystems. Numerous diversity indices combine richness and evenness in a single expression, and several climate-based explanations have been proposed to explain broad-scale diversity patterns. However, climate-based water-energy dynamics appears to be an essential factor that determines patterns of diversity. The Mexican Sierra Madre Occidental occupies an area of about 29 million hectares and is located between the Neotropical and Holarctic ecozones. It shelters a high diversity of flora, including 24 different species of Pinus (ca. 22% on the whole), 54 species of Quercus (ca. 9-14%), 7 species of Arbutus (ca. 50%) and many other trees species. The objectives of this study were to model how tree species diversity is related to climatic and geographic factors and stand density and to test the Metabolic Theory, Productivity-Diversity Hypothesis, Physiological Tolerance Hypothesis, Mid-Domain Effect, and the Water-Energy Dynamic Theory on the Sierra Madre Occidental, Durango. The results supported the Productivity-Diversity Hypothesis, Physiological Tolerance Hypothesis and Water-Energy Dynamic Theory, but not the Mid-Domain Effect or Metabolic Theory. The annual aridity index was the variable most closely related to the diversity indices analyzed. Contemporary climate was found to have moderate to strong effects on the minimum, median and maximum tree species diversity. Because water-energy dynamics provided a satisfactory explanation for the patterns of minimum, median and maximum diversity, an understanding of this factor is critical to future biodiversity research. Quantile regression of the data showed that the three diversity parameters of tree species are generally higher in cold, humid temperate climates than in dry, hot climates.

Scale-dependent erosional patterns in steady-state and transient-state landscapes.

PubMed

Tejedor, Alejandro; Singh, Arvind; Zaliapin, Ilya; Densmore, Alexander L; Foufoula-Georgiou, Efi

2017-09-01

Landscape topography is the expression of the dynamic equilibrium between external forcings (for example, climate and tectonics) and the underlying lithology. The magnitude and spatial arrangement of erosional and depositional fluxes dictate the evolution of landforms during both statistical steady state (SS) and transient state (TS) of major landscape reorganization. For SS landscapes, the common expectation is that any point of the landscape has an equal chance to erode below or above the landscape median erosion rate. We show that this is not the case. Afforded by a unique experimental landscape that provided a detailed space-time recording of erosional fluxes and by defining the so-called E50-area curve, we reveal for the first time that there exists a hierarchical pattern of erosion. Specifically, hillslopes and fluvial channels erode more rapidly than the landscape median erosion rate, whereas intervening parts of the landscape in terms of upstream contributing areas (colluvial regime) erode more slowly. We explain this apparent paradox by documenting the dynamic nature of SS landscapes-landscape locations may transition from being a hillslope to being a valley and then to being a fluvial channel due to ridge migration, channel piracy, and small-scale landscape dynamics through time. Under TS conditions caused by increased precipitation, we show that the E50-area curve drastically changes shape during landscape reorganization. Scale-dependent erosional patterns, as observed in this study, suggest benchmarks in evaluating numerical models and interpreting the variability of sampled erosional rates in field landscapes.

Scale-dependent erosional patterns in steady-state and transient-state landscapes

PubMed Central

Tejedor, Alejandro; Singh, Arvind; Zaliapin, Ilya; Densmore, Alexander L.; Foufoula-Georgiou, Efi

2017-01-01

Landscape topography is the expression of the dynamic equilibrium between external forcings (for example, climate and tectonics) and the underlying lithology. The magnitude and spatial arrangement of erosional and depositional fluxes dictate the evolution of landforms during both statistical steady state (SS) and transient state (TS) of major landscape reorganization. For SS landscapes, the common expectation is that any point of the landscape has an equal chance to erode below or above the landscape median erosion rate. We show that this is not the case. Afforded by a unique experimental landscape that provided a detailed space-time recording of erosional fluxes and by defining the so-called E50-area curve, we reveal for the first time that there exists a hierarchical pattern of erosion. Specifically, hillslopes and fluvial channels erode more rapidly than the landscape median erosion rate, whereas intervening parts of the landscape in terms of upstream contributing areas (colluvial regime) erode more slowly. We explain this apparent paradox by documenting the dynamic nature of SS landscapes—landscape locations may transition from being a hillslope to being a valley and then to being a fluvial channel due to ridge migration, channel piracy, and small-scale landscape dynamics through time. Under TS conditions caused by increased precipitation, we show that the E50-area curve drastically changes shape during landscape reorganization. Scale-dependent erosional patterns, as observed in this study, suggest benchmarks in evaluating numerical models and interpreting the variability of sampled erosional rates in field landscapes. PMID:28959728

Dynamic Response of Mycobacterium vanbaalenii PYR-1 to BP Deepwater Horizon Crude Oil

PubMed Central

Kim, Seong-Jae; Kweon, Ohgew; Sutherland, John B.; Kim, Hyun-Lee; Jones, Richard C.; Burback, Brian L.; Graves, Steven W.; Psurny, Edward

2015-01-01

We investigated the response of the hydrocarbon-degrading Mycobacterium vanbaalenii PYR-1 to crude oil from the BP Deepwater Horizon (DWH) spill, using substrate depletion, genomic, and proteome analyses. M. vanbaalenii PYR-1 cultures were incubated with BP DWH crude oil, and proteomes and degradation of alkanes and polycyclic aromatic hydrocarbons (PAHs) were analyzed at four time points over 30 days. Gas chromatography-mass spectrometry (GC-MS) analysis showed a chain length-dependent pattern of alkane degradation, with C12 and C13 being degraded at the highest rate, although alkanes up to C28 were degraded. Whereas phenanthrene and pyrene were completely degraded, a significantly smaller amount of fluoranthene was degraded. Proteome analysis identified 3,948 proteins, with 876 and 1,859 proteins up- and downregulated, respectively. We observed dynamic changes in protein expression during BP crude oil incubation, including transcriptional factors and transporters potentially involved in adaptation to crude oil. The proteome also provided a molecular basis for the metabolism of the aliphatic and aromatic hydrocarbon components in the BP DWH crude oil, which included upregulation of AlkB alkane hydroxylase and an expression pattern of PAH-metabolizing enzymes different from those in previous proteome expression studies of strain PYR-1 incubated with pure or mixed PAHs, particularly the ring-hydroxylating oxygenase (RHO) responsible for the initial oxidation of aromatic hydrocarbons. Based on these results, a comprehensive cellular response of M. vanbaalenii PYR-1 to BP crude oil was proposed. This study increases our fundamental understanding of the impact of crude oil on the cellular response of bacteria and provides data needed for development of practical bioremediation applications. PMID:25888169

Inferior olive mirrors joint dynamics to implement an inverse controller.

PubMed

Alvarez-Icaza, Rodrigo; Boahen, Kwabena

2012-10-01

To produce smooth and coordinated motion, our nervous systems need to generate precisely timed muscle activation patterns that, due to axonal conduction delay, must be generated in a predictive and feedforward manner. Kawato proposed that the cerebellum accomplishes this by acting as an inverse controller that modulates descending motor commands to predictively drive the spinal cord such that the musculoskeletal dynamics are canceled out. This and other cerebellar theories do not, however, account for the rich biophysical properties expressed by the olivocerebellar complex's various cell types, making these theories difficult to verify experimentally. Here we propose that a multizonal microcomplex's (MZMC) inferior olivary neurons use their subthreshold oscillations to mirror a musculoskeletal joint's underdamped dynamics, thereby achieving inverse control. We used control theory to map a joint's inverse model onto an MZMC's biophysics, and we used biophysical modeling to confirm that inferior olivary neurons can express the dynamics required to mirror biomechanical joints. We then combined both techniques to predict how experimentally injecting current into the inferior olive would affect overall motor output performance. We found that this experimental manipulation unmasked a joint's natural dynamics, as observed by motor output ringing at the joint's natural frequency, with amplitude proportional to the amount of current. These results support the proposal that the cerebellum-in particular an MZMC-is an inverse controller; the results also provide a biophysical implementation for this controller and allow one to make an experimentally testable prediction.

Retinal Expression of the Drosophila eyes absent Gene Is Controlled by Several Cooperatively Acting Cis-regulatory Elements

PubMed Central

Neuman, Sarah D.; Bashirullah, Arash; Kumar, Justin P.

2016-01-01

The eyes absent (eya) gene of the fruit fly, Drosophila melanogaster, is a member of an evolutionarily conserved gene regulatory network that controls eye formation in all seeing animals. The loss of eya leads to the complete elimination of the compound eye while forced expression of eya in non-retinal tissues is sufficient to induce ectopic eye formation. Within the developing retina eya is expressed in a dynamic pattern and is involved in tissue specification/determination, cell proliferation, apoptosis, and cell fate choice. In this report we explore the mechanisms by which eya expression is spatially and temporally governed in the developing eye. We demonstrate that multiple cis-regulatory elements function cooperatively to control eya transcription and that spacing between a pair of enhancer elements is important for maintaining correct gene expression. Lastly, we show that the loss of eya expression in sine oculis (so) mutants is the result of massive cell death and a progressive homeotic transformation of retinal progenitor cells into head epidermis. PMID:27930646

Dynamic Eye Tracking Based Metrics for Infant Gaze Patterns in the Face-Distractor Competition Paradigm

PubMed Central

Ahtola, Eero; Stjerna, Susanna; Yrttiaho, Santeri; Nelson, Charles A.; Leppänen, Jukka M.; Vanhatalo, Sampsa

2014-01-01

Objective To develop new standardized eye tracking based measures and metrics for infants’ gaze dynamics in the face-distractor competition paradigm. Method Eye tracking data were collected from two samples of healthy 7-month-old (total n = 45), as well as one sample of 5-month-old infants (n = 22) in a paradigm with a picture of a face or a non-face pattern as a central stimulus, and a geometric shape as a lateral stimulus. The data were analyzed by using conventional measures of infants’ initial disengagement from the central to the lateral stimulus (i.e., saccadic reaction time and probability) and, additionally, novel measures reflecting infants gaze dynamics after the initial disengagement (i.e., cumulative allocation of attention to the central vs. peripheral stimulus). Results The results showed that the initial saccade away from the centrally presented stimulus is followed by a rapid re-engagement of attention with the central stimulus, leading to cumulative preference for the central stimulus over the lateral stimulus over time. This pattern tended to be stronger for salient facial expressions as compared to non-face patterns, was replicable across two independent samples of 7-month-old infants, and differentiated between 7 and 5 month-old infants. Conclusion The results suggest that eye tracking based assessments of infants’ cumulative preference for faces over time can be readily parameterized and standardized, and may provide valuable techniques for future studies examining normative developmental changes in preference for social signals. Significance Standardized measures of early developing face preferences may have potential to become surrogate biomarkers of neurocognitive and social development. PMID:24845102

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain

PubMed Central

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain. PMID:23440889

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain.

PubMed

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

Identification and expression characterization of WntA during intestinal regeneration in the sea cucumber Apostichopus japonicus.

PubMed

Li, Xiaoni; Sun, Lina; Yang, Hongsheng; Zhang, Libin; Miao, Ting; Xing, Lili; Huo, Da

2017-08-01

Wnt genes encode secreted glycoproteins that act as signaling molecules; these molecules direct cell proliferation, migration, differentiation and survival during animal development, maintenance of homeostasis and regeneration. At present, although the regeneration mechanism in Apostichopus japonicus has been studied, there is a little research on the Wnt signaling pathway in A. japonicus. To understand the potential role of the Wnt signaling pathway in A. japonicus, we cloned and sequenced the WntA gene in A. japonicus. Protein localization analysis showed that WntA protein was ubiquitously expressed in epidermal cells, the muscle and submucosa of the intestinal tissue. After stimulation and evisceration, the dynamic changes in expression of the WntA gene and protein showed that WntA was constitutively expressed during different stages of intestine regeneration in A. japonicus, with higher levels during the early wound healing stage and late lumen formation in the residual and nascent intestinal tissues, indicating its response to intestinal regeneration. Simultaneously, cell proliferation and apoptosis analysis showed that the patterns of cell proliferation were similar to the patterns of WntA protein expression during different intestinal regeneration stages in this organism. Taken together, these results suggested that WntA might participate in intestinal regeneration and may be connected with cell proliferation, apoptosis in different intestinal layers. This research could establish a basis for further examination of WntA functions in A. japonicus and Wnt genes in other echinoderms. Copyright © 2017 Elsevier Inc. All rights reserved.

Estimating replicate time shifts using Gaussian process regression

PubMed Central

Liu, Qiang; Andersen, Bogi; Smyth, Padhraic; Ihler, Alexander

2010-01-01

Motivation: Time-course gene expression datasets provide important insights into dynamic aspects of biological processes, such as circadian rhythms, cell cycle and organ development. In a typical microarray time-course experiment, measurements are obtained at each time point from multiple replicate samples. Accurately recovering the gene expression patterns from experimental observations is made challenging by both measurement noise and variation among replicates' rates of development. Prior work on this topic has focused on inference of expression patterns assuming that the replicate times are synchronized. We develop a statistical approach that simultaneously infers both (i) the underlying (hidden) expression profile for each gene, as well as (ii) the biological time for each individual replicate. Our approach is based on Gaussian process regression (GPR) combined with a probabilistic model that accounts for uncertainty about the biological development time of each replicate. Results: We apply GPR with uncertain measurement times to a microarray dataset of mRNA expression for the hair-growth cycle in mouse back skin, predicting both profile shapes and biological times for each replicate. The predicted time shifts show high consistency with independently obtained morphological estimates of relative development. We also show that the method systematically reduces prediction error on out-of-sample data, significantly reducing the mean squared error in a cross-validation study. Availability: Matlab code for GPR with uncertain time shifts is available at http://sli.ics.uci.edu/Code/GPRTimeshift/ Contact: ihler@ics.uci.edu PMID:20147305

Identifying spatially similar gene expression patterns in early stage fruit fly embryo images: binary feature versus invariant moment digital representations

PubMed Central

Gurunathan, Rajalakshmi; Van Emden, Bernard; Panchanathan, Sethuraman; Kumar, Sudhir

2004-01-01

Background Modern developmental biology relies heavily on the analysis of embryonic gene expression patterns. Investigators manually inspect hundreds or thousands of expression patterns to identify those that are spatially similar and to ultimately infer potential gene interactions. However, the rapid accumulation of gene expression pattern data over the last two decades, facilitated by high-throughput techniques, has produced a need for the development of efficient approaches for direct comparison of images, rather than their textual descriptions, to identify spatially similar expression patterns. Results The effectiveness of the Binary Feature Vector (BFV) and Invariant Moment Vector (IMV) based digital representations of the gene expression patterns in finding biologically meaningful patterns was compared for a small (226 images) and a large (1819 images) dataset. For each dataset, an ordered list of images, with respect to a query image, was generated to identify overlapping and similar gene expression patterns, in a manner comparable to what a developmental biologist might do. The results showed that the BFV representation consistently outperforms the IMV representation in finding biologically meaningful matches when spatial overlap of the gene expression pattern and the genes involved are considered. Furthermore, we explored the value of conducting image-content based searches in a dataset where individual expression components (or domains) of multi-domain expression patterns were also included separately. We found that this technique improves performance of both IMV and BFV based searches. Conclusions We conclude that the BFV representation consistently produces a more extensive and better list of biologically useful patterns than the IMV representation. The high quality of results obtained scales well as the search database becomes larger, which encourages efforts to build automated image query and retrieval systems for spatial gene expression patterns. PMID:15603586

Comprehensive gene and microRNA expression profiling on cardiovascular system in zebrafish co-exposured of SiNPs and MeHg.

PubMed

Hu, Hejing; Shi, Yanfeng; Zhang, Yannan; Wu, Jing; Asweto, Collins Otieno; Feng, Lin; Yang, Xiaozhe; Duan, Junchao; Sun, Zhiwei

2017-12-31

Air pollution has been shown to increase cardiovascular diseases. However, little attention has been paid to the combined effects of PM and air pollutants on the cardiovascular system. To explore this, a high-throughput sequencing technology was used to determine combined effects of silica nanoparticles (SiNPs) and MeHg in zebrafish. Our study demonstrated that SiNPs and MeHg co-exposure could cause significant changes in mRNA and miRNA expression patterns in zebrafish. The differentially expressed (DE) genes in profiles 17 and 26 of STC analysis suggest that SiNPs and MeHg co-exposure had more proinflammatory and cardiovascular toxicity in zebrafish than single exposure. Major gene functions associated with cardiovascular system in the co-exposed zebrafish were discerned from the dynamic-gene-network, including stxbp1a, celf4, ahr1b and bai2. In addition, the prominently expressed pathway of cardiac muscle contraction was targeted by 3 DE miRNAs identified by the miRNA-pathway-network (dre-miR-7147, dre-miR-26a and dre-miR-375), which included 23 DE genes. This study presents a global view of the combined SiNPs and MeHg toxicity on the dynamic expression of both mRNAs and miRNAs in zebrafish, and could serve as fundamental research clues for future studies, especially on cardiovascular system toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

The yan gene is highly conserved in Drosophila and its expression suggests a complex role throughout development.

PubMed

Price, M D; Lai, Z

1999-04-01

Competence for cell fate determination and cellular differentiation is under tight control of regulatory genes. Yan, a nuclear target of receptor tyrosine kinase (RTK) signaling, is an E twenty six (ETS) DNA-binding protein that functions as a negative regulator of cell differentiation and proliferation in Drosophila. Most members of RTK signaling pathways are highly conserved through evolution, yet no yan orthologues have been identified to date in vertebrates. To investigate the degree of yan conservation during evolution, we have characterized a yan homologue from a sibling species of D. melanogaster, D. virilis. Our results show that the organization, primary structure and expression pattern of yan are highly conserved. Both genes span over 20 kb and contain four exons with introns at identical positions. The areas with highest amino acid similarity include the Pointed and ETS domain but there are other discrete regions with a high degree of similarity. Phylogenetic analysis reveals that yan's closest relative is the human tel gene, a negative regulator of differentiation in hematopoetic precursors. In both species, Yan is dynamically expressed beginning as early as stage 4/5 and persisting throughout embryogenesis. In third instar larvae, Yan is expressed in and behind the morphogenetic furrow of the eye imaginal disc as well as in the laminar precursor cells of the brain. Ovarian follicle cells also contain Yan protein. Conservation of the structure and expression patterns of yan genes strongly suggests that regulatory mechanisms for their expression are also conserved in these two species.

Transcriptional Activity, Chromosomal Distribution and Expression Effects of Transposable Elements in Coffea Genomes

PubMed Central

da Silva, Carlos R. M.; Andrade, Alan C.; Marraccini, Pierre; Teixeira, João B.; Carazzolle, Marcelo F.; Pereira, Gonçalo A. G.; Pereira, Luiz Filipe P.; Vanzela, André L. L.; Wang, Lu; Jordan, I. King; Carareto, Claudia M. A.

2013-01-01

Plant genomes are massively invaded by transposable elements (TEs), many of which are located near host genes and can thus impact gene expression. In flowering plants, TE expression can be activated (de-repressed) under certain stressful conditions, both biotic and abiotic, as well as by genome stress caused by hybridization. In this study, we examined the effects of these stress agents on TE expression in two diploid species of coffee, Coffea canephora and C. eugenioides, and their allotetraploid hybrid C. arabica. We also explored the relationship of TE repression mechanisms to host gene regulation via the effects of exonized TE sequences. Similar to what has been seen for other plants, overall TE expression levels are low in Coffea plant cultivars, consistent with the existence of effective TE repression mechanisms. TE expression patterns are highly dynamic across the species and conditions assayed here are unrelated to their classification at the level of TE class or family. In contrast to previous results, cell culture conditions per se do not lead to the de-repression of TE expression in C. arabica. Results obtained here indicate that differing plant drought stress levels relate strongly to TE repression mechanisms. TEs tend to be expressed at significantly higher levels in non-irrigated samples for the drought tolerant cultivars but in drought sensitive cultivars the opposite pattern was shown with irrigated samples showing significantly higher TE expression. Thus, TE genome repression mechanisms may be finely tuned to the ideal growth and/or regulatory conditions of the specific plant cultivars in which they are active. Analysis of TE expression levels in cell culture conditions underscored the importance of nonsense-mediated mRNA decay (NMD) pathways in the repression of Coffea TEs. These same NMD mechanisms can also regulate plant host gene expression via the repression of genes that bear exonized TE sequences. PMID:24244387

Cell Type-Specific Regulation of Immunological Synapse Dynamics by B7 Ligand Recognition

PubMed Central

Brzostek, Joanna; Gascoigne, Nicholas R. J.; Rybakin, Vasily

2016-01-01

B7 proteins CD80 (B7-1) and CD86 (B7-2) are expressed on most antigen-presenting cells and provide critical co-stimulatory or inhibitory input to T cells via their T-cell-expressed receptors: CD28 and CTLA-4. CD28 is expressed on effector T cells and regulatory T cells (Tregs), and CD28-dependent signals are required for optimum activation of effector T cell functions. CD28 ligation on effector T cells leads to formation of distinct molecular patterns and induction of cytoskeletal rearrangements at the immunological synapse (IS). CD28 plays a critical role in recruitment of protein kinase C (PKC)-θ to the effector T cell IS. CTLA-4 is constitutively expressed on the surface of Tregs, but it is expressed on effector T cells only after activation. As CTLA-4 binds to B7 proteins with significantly higher affinity than CD28, B7 ligand recognition by cells expressing both receptors leads to displacement of CD28 and PKC-θ from the IS. In Tregs, B7 ligand recognition leads to recruitment of CTLA-4 and PKC-η to the IS. CTLA-4 plays a role in regulation of T effector and Treg IS stability and cell motility. Due to their important roles in regulating T-cell-mediated responses, B7 receptors are emerging as important drug targets in oncology. In this review, we present an integrated summary of current knowledge about the role of B7 family receptor–ligand interactions in the regulation of spatial and temporal IS dynamics in effector and Tregs. PMID:26870040

Neuromorphic walking gait control.

PubMed

Still, Susanne; Hepp, Klaus; Douglas, Rodney J

2006-03-01

We present a neuromorphic pattern generator for controlling the walking gaits of four-legged robots which is inspired by central pattern generators found in the nervous system and which is implemented as a very large scale integrated (VLSI) chip. The chip contains oscillator circuits that mimic the output of motor neurons in a strongly simplified way. We show that four coupled oscillators can produce rhythmic patterns with phase relationships that are appropriate to generate all four-legged animal walking gaits. These phase relationships together with frequency and duty cycle of the oscillators determine the walking behavior of a robot driven by the chip, and they depend on a small set of stationary bias voltages. We give analytic expressions for these dependencies. This chip reduces the complex, dynamic inter-leg control problem associated with walking gait generation to the problem of setting a few stationary parameters. It provides a compact and low power solution for walking gait control in robots.

Segmentation of the zebrafish axial skeleton relies on notochord sheath cells and not on the segmentation clock

PubMed Central

Lleras Forero, Laura; Narayanan, Rachna; Huitema, Leonie FA; VanBergen, Maaike; Apschner, Alexander; Peterson-Maduro, Josi; Logister, Ive; Valentin, Guillaume

2018-01-01

Segmentation of the axial skeleton in amniotes depends on the segmentation clock, which patterns the paraxial mesoderm and the sclerotome. While the segmentation clock clearly operates in teleosts, the role of the sclerotome in establishing the axial skeleton is unclear. We severely disrupt zebrafish paraxial segmentation, yet observe a largely normal segmentation process of the chordacentra. We demonstrate that axial entpd5+ notochord sheath cells are responsible for chordacentrum mineralization, and serve as a marker for axial segmentation. While autonomous within the notochord sheath, entpd5 expression and centrum formation show some plasticity and can respond to myotome pattern. These observations reveal for the first time the dynamics of notochord segmentation in a teleost, and are consistent with an autonomous patterning mechanism that is influenced, but not determined by adjacent paraxial mesoderm. This behavior is not consistent with a clock-type mechanism in the notochord. PMID:29624170

Spatiotemporal pattern in somitogenesis: a non-Turing scenario with wave propagation.

PubMed

Nagahara, Hiroki; Ma, Yue; Takenaka, Yoshiko; Kageyama, Ryoichiro; Yoshikawa, Kenichi

2009-08-01

Living organisms maintain their lives under far-from-equilibrium conditions by creating a rich variety of spatiotemporal structures in a self-organized manner, such as temporal rhythms, switching phenomena, and development of the body. In this paper, we focus on the dynamical process of morphogens in somitogenesis in mice where propagation of the gene expression level plays an essential role in creating the spatially periodic patterns of the vertebral columns. We present a simple discrete reaction-diffusion model which includes neighboring interaction through an activator, but not diffusion of an inhibitor. We can produce stationary periodic patterns by introducing the effect of spatial discreteness to the field. Based on the present model, we discuss the underlying physical principles that are independent of the details of biomolecular reactions. We also discuss the framework of spatial discreteness based on the reaction-diffusion model in relation to a cellular array, by comparison with an actual experimental observation.

Segmentation and classification of cell cycle phases in fluorescence imaging.

PubMed

Ersoy, Ilker; Bunyak, Filiz; Chagin, Vadim; Cardoso, M Christina; Palaniappan, Kannappan

2009-01-01

Current chemical biology methods for studying spatiotemporal correlation between biochemical networks and cell cycle phase progression in live-cells typically use fluorescence-based imaging of fusion proteins. Stable cell lines expressing fluorescently tagged protein GFP-PCNA produce rich, dynamically varying sub-cellular foci patterns characterizing the cell cycle phases, including the progress during the S-phase. Variable fluorescence patterns, drastic changes in SNR, shape and position changes and abundance of touching cells require sophisticated algorithms for reliable automatic segmentation and cell cycle classification. We extend the recently proposed graph partitioning active contours (GPAC) for fluorescence-based nucleus segmentation using regional density functions and dramatically improve its efficiency, making it scalable for high content microscopy imaging. We utilize surface shape properties of GFP-PCNA intensity field to obtain descriptors of foci patterns and perform automated cell cycle phase classification, and give quantitative performance by comparing our results to manually labeled data.

Black-White Disparities in Breast Cancer Subtype: The Intersection of Socially Patterned Stress and Genetic Expression

PubMed Central

Linnenbringer, Erin; Gehlert, Sarah; Geronimus, Arline T.

2017-01-01

Hormone receptor negative (HR−) breast cancer subtypes are etiologically distinct from the more common, less aggressive, and more treatable form of estrogen receptor positive (ER+) breast cancer. Numerous population-based studies have found that, in the United States, Black women are 2 to 3 times more likely to develop HR− breast cancer than White women. Much of the existing research on racial disparities in breast cancer subtype has focused on identifying predisposing genetic factors associated with African ancestry. This approach fails to acknowledge that racial stratification shapes a wide range of environmental and social exposures over the life course. Human stress genomics considers the role of individual stress perceptions on gene expression. Yet, the role of structurally rooted biopsychosocial processes that may be activated by the social patterning of stressors in an historically unequal society, whether perceived by individual black women or not, could also impact cellular physiology and gene expression patterns relevant to HR− breast cancer etiology. Using the weathering hypothesis as our conceptual framework, we develop a structural perspective for examining racial disparities in breast cancer subtypes, integrating important findings from the stress biology, breast cancer epidemiology, and health disparities literatures. After integrating key findings from these largely independent literatures, we develop a theoretically and empirically guided framework for assessing potential multilevel factors relevant to the development of HR− breast cancer disproportionately among Black women in the US. We hypothesize that a dynamic interplay among socially patterned psychosocial stressors, physiological & behavioral responses, and genomic pathways contribute to the increased risk of HR− breast cancer among Black women. This work provides a basis for exploring potential alternative pathways linking the lived experience of race to the risk of HR- breast cancer, and suggests new avenues for research and public health action. PMID:29333472

Black-White Disparities in Breast Cancer Subtype: The Intersection of Socially Patterned Stress and Genetic Expression.

PubMed

Linnenbringer, Erin; Gehlert, Sarah; Geronimus, Arline T

2017-01-01

Hormone receptor negative (HR-) breast cancer subtypes are etiologically distinct from the more common, less aggressive, and more treatable form of estrogen receptor positive (ER+) breast cancer. Numerous population-based studies have found that, in the United States, Black women are 2 to 3 times more likely to develop HR- breast cancer than White women. Much of the existing research on racial disparities in breast cancer subtype has focused on identifying predisposing genetic factors associated with African ancestry. This approach fails to acknowledge that racial stratification shapes a wide range of environmental and social exposures over the life course. Human stress genomics considers the role of individual stress perceptions on gene expression. Yet, the role of structurally rooted biopsychosocial processes that may be activated by the social patterning of stressors in an historically unequal society, whether perceived by individual black women or not, could also impact cellular physiology and gene expression patterns relevant to HR- breast cancer etiology. Using the weathering hypothesis as our conceptual framework, we develop a structural perspective for examining racial disparities in breast cancer subtypes, integrating important findings from the stress biology, breast cancer epidemiology, and health disparities literatures. After integrating key findings from these largely independent literatures, we develop a theoretically and empirically guided framework for assessing potential multilevel factors relevant to the development of HR- breast cancer disproportionately among Black women in the US. We hypothesize that a dynamic interplay among socially patterned psychosocial stressors, physiological & behavioral responses, and genomic pathways contribute to the increased risk of HR- breast cancer among Black women. This work provides a basis for exploring potential alternative pathways linking the lived experience of race to the risk of HR- breast cancer, and suggests new avenues for research and public health action.

Interplay of Noisy Gene Expression and Dynamics Explains Patterns of Bacterial Operon Organization

NASA Astrophysics Data System (ADS)

Igoshin, Oleg

2011-03-01

Bacterial chromosomes are organized into operons -- sets of genes co-transcribed into polycistronic messenger RNA. Hypotheses explaining the emergence and maintenance of operons include proportional co-regulation, horizontal transfer of intact ``selfish'' operons, emergence via gene duplication, and co-production of physically interacting proteins to speed their association. We hypothesized an alternative: operons can reduce or increase intrinsic gene expression noise in a manner dependent on the post-translational interactions, thereby resulting in selection for or against operons in depending on the network architecture. We devised five classes of two-gene network modules and show that the effects of operons on intrinsic noise depend on class membership. Two classes exhibit decreased noise with co-transcription, two others reveal increased noise, and the remaining one does not show a significant difference. To test our modeling predictions we employed bioinformatic analysis to determine the relationship gene expression noise and operon organization. The results confirm the overrepresentation of noise-minimizing operon architectures and provide evidence against other hypotheses. Our results thereby suggest a central role for gene expression noise in selecting for or maintaining operons in bacterial chromosomes. This demonstrates how post-translational network dynamics may provide selective pressure for organizing bacterial chromosomes, and has practical consequences for designing synthetic gene networks. This work is supported by National Institutes of Health grant 1R01GM096189-01.

PINK1 is required for timely cell-type specific mitochondrial clearance during Drosophila midgut metamorphosis.

PubMed

Liu, Yan; Lin, Jingjing; Zhang, Minjie; Chen, Kai; Yang, Shengxi; Wang, Qun; Yang, Hongqin; Xie, Shusen; Zhou, Yongjian; Zhang, Xi; Chen, Fei; Yang, Yufeng

2016-11-15

Mitophagy is the selective degradation of mitochondria by autophagy, which is an important mitochondrial quality and quantity control process. During Drosophila metamorphosis, the degradation of midgut involves a large change in length and organization, which is mediated by autophagy. Here we noticed a cell-type specific mitochondrial clearance process that occurs in enterocytes (ECs), while most mitochondria remain in intestinal stem cells (ISCs) during metamorphosis. Although PINK1/PARKIN represent the canonical pathway for the elimination of impaired mitochondria in varied pathological conditions, their roles in developmental processes or normal physiological conditions have been less studied. To examine the potential contribution of PINK1 in developmental processes, we monitored the dynamic expression pattern of PINK1 in the midgut development by taking advantage of a newly CRISPR/Cas9 generated knock-in fly strain expressing PINK1-mCherry fusion protein that presumably recapitulates the endogenous expression pattern of PINK1. We disclosed a spatiotemporal correlation between the expression pattern of PINK1 and the mitochondrial clearance or persistence in ECs or ISCs respectively. By mosaic genetic analysis, we then demonstrated that PINK1 and PARKIN function epistatically to mediate the specific timely removal of mitochondria, and are involved in global autophagy in ECs during Drosophila midgut metamorphosis, with kinase-dead PINK1 exerting dominant negative effects. Taken together, our studies concluded that the PINK1/PARKIN is crucial for timely cell-type specific mitophagy under physiological conditions and demonstrated again that Drosophila midgut metamorphosis might serve as an elegant in vivo model to study autophagy. Copyright © 2016 Elsevier Inc. All rights reserved.

Modelling information dissemination under privacy concerns in social media

NASA Astrophysics Data System (ADS)

Zhu, Hui; Huang, Cheng; Lu, Rongxing; Li, Hui

2016-05-01

Social media has recently become an important platform for users to share news, express views, and post messages. However, due to user privacy preservation in social media, many privacy setting tools are employed, which inevitably change the patterns and dynamics of information dissemination. In this study, a general stochastic model using dynamic evolution equations was introduced to illustrate how privacy concerns impact the process of information dissemination. Extensive simulations and analyzes involving the privacy settings of general users, privileged users, and pure observers were conducted on real-world networks, and the results demonstrated that user privacy settings affect information differently. Finally, we also studied the process of information diffusion analytically and numerically with different privacy settings using two classic networks.

The dynamic landscape of gene regulation during Bombyx mori oogenesis.

PubMed

Zhang, Qiang; Sun, Wei; Sun, Bang-Yong; Xiao, Yang; Zhang, Ze

2017-09-11

Oogenesis in the domestic silkworm (Bombyx mori) is a complex process involving previtellogenesis, vitellogenesis and choriogenesis. During this process, follicles show drastic morphological and physiological changes. However, the genome-wide regulatory profiles of gene expression during oogenesis remain to be determined. In this study, we obtained time-series transcriptome data and used these data to reveal the dynamic landscape of gene regulation during oogenesis. A total of 1932 genes were identified to be differentially expressed among different stages, most of which occurred during the transition from late vitellogenesis to early choriogenesis. Using weighted gene co-expression network analysis, we identified six stage-specific gene modules that correspond to multiple regulatory pathways. Strikingly, the biosynthesis pathway of the molting hormone 20-hydroxyecdysone (20E) was enriched in one of the modules. Further analysis showed that the ecdysteroid 20-hydroxylase gene (CYP314A1) of steroidgenesis genes was mainly expressed in previtellogenesis and early vitellogenesis. However, the 20E-inactivated genes, particularly the ecdysteroid 26-hydroxylase encoding gene (Cyp18a1), were highly expressed in late vitellogenesis. These distinct expression patterns between 20E synthesis and catabolism-related genes might ensure the rapid decline of the hormone titer at the transition point from vitellogenesis to choriogenesis. In addition, we compared landscapes of gene regulation between silkworm (Lepidoptera) and fruit fly (Diptera) oogeneses. Our results show that there is some consensus in the modules of gene co-expression during oogenesis in these insects. The data presented in this study provide new insights into the regulatory mechanisms underlying oogenesis in insects with polytrophic meroistic ovaries. The results also provide clues for further investigating the roles of epigenetic reconfiguration and circadian rhythm in insect oogenesis.

Computational Micromodel for Epigenetic Mechanisms

PubMed Central

Raghavan, Karthika; Ruskin, Heather J.; Perrin, Dimitri; Goasmat, Francois; Burns, John

2010-01-01

Characterization of the epigenetic profile of humans since the initial breakthrough on the human genome project has strongly established the key role of histone modifications and DNA methylation. These dynamic elements interact to determine the normal level of expression or methylation status of the constituent genes in the genome. Recently, considerable evidence has been put forward to demonstrate that environmental stress implicitly alters epigenetic patterns causing imbalance that can lead to cancer initiation. This chain of consequences has motivated attempts to computationally model the influence of histone modification and DNA methylation in gene expression and investigate their intrinsic interdependency. In this paper, we explore the relation between DNA methylation and transcription and characterize in detail the histone modifications for specific DNA methylation levels using a stochastic approach. PMID:21152421

Micro-RNAs in cognition and cognitive disorders: Potential for novel biomarkers and therapeutics.

PubMed

Woldemichael, Bisrat T; Mansuy, Isabelle M

2016-03-15

Micro-RNAs (miRNAs) are small regulatory non-coding RNAs involved in the regulation of many biological functions. In the brain, they have distinct expression patterns depending on region, cell-type and developmental stage. Their expression profile is altered by neuronal activation in response to behavioral training or chemical/electrical stimulation. The dynamic changes in miRNA level regulate the expression of genes required for cognitive processes such as learning and memory. In addition, in cognitive dysfunctions such as dementias, expression levels of many miRNAs are perturbed, not only in brain areas affected by the pathology, but also in peripheral body fluids such as serum and cerebrospinal fluid. This presents an opportunity to utilize miRNAs as biomarkers for early detection and assessment of cognitive dysfunctions. Further, since miRNAs target many genes and pathways, they may represent key molecular signatures that can help understand the mechanisms of cognitive disorders and the development of potential therapeutic agents. Copyright © 2015 Elsevier Inc. All rights reserved.

Light-driven dynamic Archimedes spirals and periodic oscillatory patterns of topological solitons in anisotropic soft matter

DOE PAGES

Martinez, Angel; Smalyukh, Ivan I.

2015-02-12

Oscillatory and excitable systems very commonly exhibit formation of dynamic non-equilibrium patterns. For example, rotating spiral patterns are observed in biological, chemical, and physical systems ranging from organization of slime mold cells to Belousov-Zhabotinsky reactions, and to crystal growth from nuclei with screw dislocations. Here we describe spontaneous formation of spiral waves and a large variety of other dynamic patterns in anisotropic soft matter driven by low-intensity light. The unstructured ambient or microscope light illumination of thin liquid crystal films in contact with a self-assembled azobenzene monolayer causes spontaneous formation, rich spatial organization, and dynamics of twisted domains and topologicalmore » solitons accompanied by the dynamic patterning of azobenzene group orientations within the monolayer. Linearly polarized incident light interacts with the twisted liquid crystalline domains, mimicking their dynamics and yielding patterns in the polarization state of transmitted light, which can be transformed to similar dynamic patterns in its intensity and interference color. This shows that the delicate light-soft-matter interaction can yield complex self-patterning of both. Finally, we uncover underpinning physical mechanisms and discuss potential uses.« less

Comparative analysis of Six 3 and Six 6 distribution in the developing and adult mouse brain.

PubMed

Conte, Ivan; Morcillo, Julian; Bovolenta, Paola

2005-11-01

Six 3 and Six 6 genes are two closely related members of the Six/sine oculis family of homeobox containing transcription factors. Their expression and function at early stages of embryonic development has been widely addressed in a variety of species. However, their mRNA distribution during late embryonic, postnatal, and adult brain barely has been analyzed. Here, we show that despite their initial overlap in the anterior neural plate, the expression of Six 3 and Six 6 progressively segregates to different regions during mammalian brain development, maintaining only few areas of partial overlap in the thalamic and hypothalamic regions. Six 3, but not Six 6, is additionally expressed in the olfactory bulb, cerebral cortex, hippocampus, midbrain, and cerebellum. These distinct patterns support the idea that Six 3 and Six 6 are differentially required during forebrain development. Developmental Dynamics 234:718-725, 2005. (c) 2005 Wiley-Liss, Inc.

Emotional modulation of body-selective visual areas.

PubMed

Peelen, Marius V; Atkinson, Anthony P; Andersson, Frederic; Vuilleumier, Patrik

2007-12-01

Emotionally expressive faces have been shown to modulate activation in visual cortex, including face-selective regions in ventral temporal lobe. Here, we tested whether emotionally expressive bodies similarly modulate activation in body-selective regions. We show that dynamic displays of bodies with various emotional expressions vs neutral bodies, produce significant activation in two distinct body-selective visual areas, the extrastriate body area and the fusiform body area. Multi-voxel pattern analysis showed that the strength of this emotional modulation was related, on a voxel-by-voxel basis, to the degree of body selectivity, while there was no relation with the degree of selectivity for faces. Across subjects, amygdala responses to emotional bodies positively correlated with the modulation of body-selective areas. Together, these results suggest that emotional cues from body movements produce topographically selective influences on category-specific populations of neurons in visual cortex, and these increases may implicate discrete modulatory projections from the amygdala.

Identification of embryonic pancreatic genes using Xenopus DNA microarrays.

PubMed

Hayata, Tadayoshi; Blitz, Ira L; Iwata, Nahoko; Cho, Ken W Y

2009-06-01

The pancreas is both an exocrine and endocrine endodermal organ involved in digestion and glucose homeostasis. During embryogenesis, the anlagen of the pancreas arise from dorsal and ventral evaginations of the foregut that later fuse to form a single organ. To better understand the molecular genetics of early pancreas development, we sought to isolate markers that are uniquely expressed in this tissue. Microarray analysis was performed comparing dissected pancreatic buds, liver buds, and the stomach region of tadpole stage Xenopus embryos. A total of 912 genes were found to be differentially expressed between these organs during early stages of organogenesis. K-means clustering analysis predicted 120 of these genes to be specifically enriched in the pancreas. Of these, we report on the novel expression patterns of 24 genes. Our analyses implicate the involvement of previously unsuspected signaling pathways during early pancreas development. Developmental Dynamics 238:1455-1466, 2009. (c) 2009 Wiley-Liss, Inc.

The dynamic-stimulus advantage of visual symmetry perception.

PubMed

Niimi, Ryosuke; Watanabe, Katsumi; Yokosawa, Kazuhiko

2008-09-01

It has been speculated that visual symmetry perception from dynamic stimuli involves mechanisms different from those for static stimuli. However, previous studies found no evidence that dynamic stimuli lead to active temporal processing and improve symmetry detection. In this study, four psychophysical experiments investigated temporal processing in symmetry perception using both dynamic and static stimulus presentations of dot patterns. In Experiment 1, rapid successive presentations of symmetric patterns (e.g., 16 patterns per 853 ms) produced more accurate discrimination of orientations of symmetry axes than static stimuli (single pattern presented through 853 ms). In Experiments 2-4, we confirmed that the dynamic-stimulus advantage depended upon presentation of a large number of unique patterns within a brief period (853 ms) in the dynamic conditions. Evidently, human vision takes advantage of temporal processing for symmetry perception from dynamic stimuli.

A nonlinear dynamics approach for incorporating wind-speed patterns into wind-power project evaluation.

PubMed

Huffaker, Ray; Bittelli, Marco

2015-01-01

Wind-energy production may be expanded beyond regions with high-average wind speeds (such as the Midwest U.S.A.) to sites with lower-average speeds (such as the Southeast U.S.A.) by locating favorable regional matches between natural wind-speed and energy-demand patterns. A critical component of wind-power evaluation is to incorporate wind-speed dynamics reflecting documented diurnal and seasonal behavioral patterns. Conventional probabilistic approaches remove patterns from wind-speed data. These patterns must be restored synthetically before they can be matched with energy-demand patterns. How to accurately restore wind-speed patterns is a vexing problem spurring an expanding line of papers. We propose a paradigm shift in wind power evaluation that employs signal-detection and nonlinear-dynamics techniques to empirically diagnose whether synthetic pattern restoration can be avoided altogether. If the complex behavior of observed wind-speed records is due to nonlinear, low-dimensional, and deterministic system dynamics, then nonlinear dynamics techniques can reconstruct wind-speed dynamics from observed wind-speed data without recourse to conventional probabilistic approaches. In the first study of its kind, we test a nonlinear dynamics approach in an application to Sugarland Wind-the first utility-scale wind project proposed in Florida, USA. We find empirical evidence of a low-dimensional and nonlinear wind-speed attractor characterized by strong temporal patterns that match up well with regular daily and seasonal electricity demand patterns.

Contrasting Fish Behavior in Artificial Seascapes with Implications for Resources Conservation

PubMed Central

Koeck, Barbara; Alós, Josep; Caro, Anthony; Neveu, Reda; Crec'hriou, Romain; Saragoni, Gilles; Lenfant, Philippe

2013-01-01

Artificial reefs are used by many fisheries managers as a tool to mitigate the impact of fisheries on coastal fish communities by providing new habitat for many exploited fish species. However, the comparison between the behavior of wild fish inhabiting either natural or artificial habitats has received less attention. Thus the spatio-temporal patterns of fish that establish their home range in one habitat or the other and their consequences of intra-population differentiation on life-history remain largely unexplored. We hypothesize that individuals with a preferred habitat (i.e. natural vs. artificial) can behave differently in terms of habitat use, with important consequences on population dynamics (e.g. life-history, mortality, and reproductive success). Therefore, using biotelemetry, 98 white seabream (Diplodus sargus) inhabiting either artificial or natural habitats were tagged and their behavior was monitored for up to eight months. Most white seabreams were highly resident either on natural or artificial reefs, with a preference for the shallow artificial reef subsets. Connectivity between artificial and natural reefs was limited for resident individuals due to great inter-habitat distances. The temporal behavioral patterns of white seabreams differed between artificial and natural reefs. Artificial-reef resident fish had a predominantly nocturnal diel pattern, whereas natural-reef resident fish showed a diurnal diel pattern. Differences in diel behavioral patterns of white seabream inhabiting artificial and natural reefs could be the expression of realized individual specialization resulting from differences in habitat configuration and resource availability between these two habitats. Artificial reefs have the potential to modify not only seascape connectivity but also the individual behavioral patterns of fishes. Future management plans of coastal areas and fisheries resources, including artificial reef implementation, should therefore consider the potential effect of habitat modification on fish behavior, which could have key implications on fish dynamics. PMID:23935978

Contrasting fish behavior in artificial seascapes with implications for resources conservation.

PubMed

Koeck, Barbara; Alós, Josep; Caro, Anthony; Neveu, Reda; Crec'hriou, Romain; Saragoni, Gilles; Lenfant, Philippe

2013-01-01

Artificial reefs are used by many fisheries managers as a tool to mitigate the impact of fisheries on coastal fish communities by providing new habitat for many exploited fish species. However, the comparison between the behavior of wild fish inhabiting either natural or artificial habitats has received less attention. Thus the spatio-temporal patterns of fish that establish their home range in one habitat or the other and their consequences of intra-population differentiation on life-history remain largely unexplored. We hypothesize that individuals with a preferred habitat (i.e. natural vs. artificial) can behave differently in terms of habitat use, with important consequences on population dynamics (e.g. life-history, mortality, and reproductive success). Therefore, using biotelemetry, 98 white seabream (Diplodus sargus) inhabiting either artificial or natural habitats were tagged and their behavior was monitored for up to eight months. Most white seabreams were highly resident either on natural or artificial reefs, with a preference for the shallow artificial reef subsets. Connectivity between artificial and natural reefs was limited for resident individuals due to great inter-habitat distances. The temporal behavioral patterns of white seabreams differed between artificial and natural reefs. Artificial-reef resident fish had a predominantly nocturnal diel pattern, whereas natural-reef resident fish showed a diurnal diel pattern. Differences in diel behavioral patterns of white seabream inhabiting artificial and natural reefs could be the expression of realized individual specialization resulting from differences in habitat configuration and resource availability between these two habitats. Artificial reefs have the potential to modify not only seascape connectivity but also the individual behavioral patterns of fishes. Future management plans of coastal areas and fisheries resources, including artificial reef implementation, should therefore consider the potential effect of habitat modification on fish behavior, which could have key implications on fish dynamics.

Dynamic distribution of spindlin in nucleoli, nucleoplasm and spindle from primary oocytes to mature eggs and its critical function for oocyte-to-embryo transition in gibel carp.

PubMed

Sun, Min; Li, Zhi; Gui, Jian-Fang

2010-10-01

Spindlin (Spin) was thought as a maternal-effect factor associated with meiotic spindle. Its role for the oocyte-to-embryo transition was suggested in mouse, but its direct evidence for the function had been not obtained in other vertebrates. In this study, we used the CagSpin-specific antibody to investigate CagSpin expression pattern and distribution during oogenesis of gibel carp (Carassius auratus gibelio). First, the oocyte-specific expression pattern and dynamic distribution was revealed in nucleoli, nucleoplasm, and spindle from primary oocytes to mature eggs by immunofluorescence localization. In primary oocytes and growth stage oocytes, CagSpin accumulates in nucleoli in increasing numbers along with the oocyte growth, and its disassembly occurs in vitellogenic oocytes, which implicates that CagSpin may be a major component of a large number of nucleoli in fish growth oocytes. Then, co-localization of CagSpin and β-tubulin was revealed in meiotic spindle of mature egg, indicating that CagSpin is one spindle-associated factor. Moreover, microinjection of CagSpin-specific antibody into the fertilized eggs blocked the first cleavage, and found that the CagSpin depletion resulted in spindle assembly disturbance. Thereby, our study provided the first direct evidence for the critical oocyte-to-embryo transition function of Spin in vertebrates, and confirmed that Spin is one important maternal-effect factor that participates in oocyte growth, oocyte maturation, and oocyte-to-embryo transition.

Predicting Depression From Language-Based Emotion Dynamics: Longitudinal Analysis of Facebook and Twitter Status Updates

PubMed Central

Kern, Margaret L; Fulcher, Ben D; Rickard, Nikki S

2018-01-01

Background Frequent expression of negative emotion words on social media has been linked to depression. However, metrics have relied on average values, not dynamic measures of emotional volatility. Objective The aim of this study was to report on the associations between depression severity and the variability (time-unstructured) and instability (time-structured) in emotion word expression on Facebook and Twitter across status updates. Methods Status updates and depression severity ratings of 29 Facebook users and 49 Twitter users were collected through the app MoodPrism. The average proportion of positive and negative emotion words used, within-person variability, and instability were computed. Results Negative emotion word instability was a significant predictor of greater depression severity on Facebook (rs(29)=.44, P=.02, 95% CI 0.09-0.69), even after controlling for the average proportion of negative emotion words used (partial rs(26)=.51, P=.006) and within-person variability (partial rs(26)=.49, P=.009). A different pattern emerged on Twitter where greater negative emotion word variability indicated lower depression severity (rs(49)=−.34, P=.01, 95% CI −0.58 to 0.09). Differences between Facebook and Twitter users in their emotion word patterns and psychological characteristics were also explored. Conclusions The findings suggest that negative emotion word instability may be a simple yet sensitive measure of time-structured variability, useful when screening for depression through social media, though its usefulness may depend on the social media platform. PMID:29739736

Brain response to empathy-eliciting scenarios involving pain in incarcerated psychopaths

PubMed Central

Decety, Jean; Skelly, Laurie R.; Kiehl, Kent A.

2013-01-01

Context A marked lack of empathy is a hallmark characteristic of individuals with psychopathy. However, neural response associated to empathic processing has not yet been directly examined in psychopathy especially in response to the perception of other people in pain and distress. Objective To identify potential differences in patterns of neural activity in incarcerated psychopaths and incarcerated controls during the perception of empathy-eliciting stimuli depicting other people in pain. Design In a case-control study, brain activation patterns elicited by dynamic stimuli depicting individuals being harmed and facial expression of pain were compared between incarcerated psychopaths and incarcerated controls. Setting Participants were scanned in on the grounds of a correctional facility using the Mind Research Network's mobile 1.5 T MRI system. Participants Eighty incarcerated males were classified according to scores on the Hare Psychopathy Checklist-Revised (PCL-R) as high (n = 27; PCL-R =30), intermediate (n = 28; PCL-R between 21–29), or low (n = 25; PCL-R ≤20) on psychopathy. Main Outcome Measure Neuro-hemodynamic response to empathy-eliciting dynamic scenarios revealed by functional magnetic resonance imaging. Results Psychopaths exhibited significantly less activation in the ventromedial prefrontal cortex, lateral orbitofrontal cortex, and periaqueductal gray relative to controls, but showed greater activation in the insula. Conclusion In response to pain cues expressed by others, psychopaths exhibit deficits in vmPFC and OFC regardless of stimulus type, but display selective impairment in processing facial cues of distress in regions associated with cognitive mentalizing. PMID:23615636

Building the Vertebrate Spine

NASA Astrophysics Data System (ADS)

Pourquié, Olivier

2008-03-01

The vertebrate body can be subdivided along the antero-posterior (AP) axis into repeated structures called segments. This periodic pattern is established during embryogenesis by the somitogenesis process. Somites are generated in a rhythmic fashion from the paraxial mesoderm and subsequently differentiate to give rise to the vertebrae and skeletal muscles of the body. Somite formation involves an oscillator-the segmentation clock-whose periodic signal is converted into the periodic array of somite boundaries. This clock drives the dynamic expression of cyclic genes in the presomitic mesoderm and requires Notch and Wnt signaling. Microarray studies of the mouse presomitic mesoderm transcriptome reveal that the segmentation clock drives the periodic expression of a large network of cyclic genes involved in cell signaling. Mutually exclusive activation of the Notch/FGF and Wnt pathways during each cycle suggests that coordinated regulation of these three pathways underlies the clock oscillator. In humans, mutations in the genes associated to the function of this oscillator such as Dll3 or Lunatic Fringe result in abnormal segmentation of the vertebral column such as those seen in congenital scoliosis. Whereas the segmentation clock is thought to set the pace of vertebrate segmentation, the translation of this pulsation into the reiterated arrangement of segment boundaries along the AP axis involves dynamic gradients of FGF and Wnt signaling. The FGF signaling gradient is established based on an unusual mechanism involving mRNA decay which provides an efficient means to couple the spatio-temporal activation of segmentation to the posterior elongation of the embryo. Another striking aspect of somite production is the strict bilateral symmetry of the process. Retinoic acid was shown to control aspects of this coordination by buffering destabilizing effects from the embryonic left-right machinery. Defects in this embryonic program controlling vertebral symmetry might lead to scoliosis in humans. Finally, the subsequent regional differentiation of the precursors of the vertebrae is controlled by Hox genes, whose collinear expression controls both gastrulation of somite precursors and their subsequent patterning into region-specific types of structures. Therefore somite development provides an outstanding paradigm to study patterning and differentiation in vertebrate embryos.

NF-κB oscillations translate into functionally related patterns of gene expression

PubMed Central

Zambrano, Samuel; De Toma, Ilario; Piffer, Arianna; Bianchi, Marco E; Agresti, Alessandra

2016-01-01

Several transcription factors (TFs) oscillate, periodically relocating between the cytoplasm and the nucleus. NF-κB, which plays key roles in inflammation and cancer, displays oscillations whose biological advantage remains unclear. Recent work indicated that NF-κB displays sustained oscillations that can be entrained, that is, reach a persistent synchronized state through small periodic perturbations. We show here that for our GFP-p65 knock-in cells NF-κB behaves as a damped oscillator able to synchronize to a variety of periodic external perturbations with no memory. We imposed synchronous dynamics to prove that transcription of NF-κB-controlled genes also oscillates, but mature transcript levels follow three distinct patterns. Two sets of transcripts accumulate fast or slowly, respectively. Another set, comprising chemokine and chemokine receptor mRNAs, oscillates and resets at each new stimulus, with no memory of the past. We propose that TF oscillatory dynamics is a means of segmenting time to provide renewing opportunity windows for decision. DOI: http://dx.doi.org/10.7554/eLife.09100.001 PMID:26765569

The dynamics of color signals in male threespine sticklebacks Gasterosteus aculeatus

PubMed Central

Hiermes, Meike

2016-01-01

Abstract Body coloration and color patterns are ubiquitous throughout the animal kingdom and vary between and within species. Recent studies have dealt with individual dynamics of various aspects of coloration, as it is in many cases a flexible trait and changes in color expression may be context-dependent. During the reproductive phase, temporal changes of coloration in the visible spectral range (400–700 nm) have been shown for many animals but corresponding changes in the ultraviolet (UV) waveband (300–400 nm) have rarely been studied. Threespine stickleback Gasterosteus aculeatus males develop conspicuous orange–red breeding coloration combined with UV reflectance in the cheek region. We investigated dynamics of color patterns including UV throughout a male breeding cycle, as well as short-term changes in coloration in response to a computer-animated rival using reflectance spectrophotometry and visual modeling, to estimate how colors would be perceived by conspecifics. We found the orange–red component of coloration to vary during the breeding cycle with respect to hue (theta/R50) and intensity (achieved chroma/red chroma). Furthermore, color intensity in the orange–red spectral part (achieved chroma) tended to be increased after the presentation of an artificial rival. Dynamic changes in specific measures of hue and intensity in the UV waveband were not found. In general, the orange–red component of the signal seems to be dynamic with respect to color intensity and hue. This accounts in particular for color changes during the breeding cycle, presumably to signal reproductive status, and with limitations as well in the intrasexual context, most likely to signal dominance or inferiority. PMID:29491887

The dynamics of color signals in male threespine sticklebacks Gasterosteus aculeatus.

PubMed

Hiermes, Meike; Rick, Ingolf P; Mehlis, Marion; Bakker, Theo C M

2016-02-01

Body coloration and color patterns are ubiquitous throughout the animal kingdom and vary between and within species. Recent studies have dealt with individual dynamics of various aspects of coloration, as it is in many cases a flexible trait and changes in color expression may be context-dependent. During the reproductive phase, temporal changes of coloration in the visible spectral range (400-700 nm) have been shown for many animals but corresponding changes in the ultraviolet (UV) waveband (300-400 nm) have rarely been studied. Threespine stickleback Gasterosteus aculeatus males develop conspicuous orange-red breeding coloration combined with UV reflectance in the cheek region. We investigated dynamics of color patterns including UV throughout a male breeding cycle, as well as short-term changes in coloration in response to a computer-animated rival using reflectance spectrophotometry and visual modeling, to estimate how colors would be perceived by conspecifics. We found the orange-red component of coloration to vary during the breeding cycle with respect to hue ( theta /R50) and intensity (achieved chroma/red chroma). Furthermore, color intensity in the orange-red spectral part (achieved chroma) tended to be increased after the presentation of an artificial rival. Dynamic changes in specific measures of hue and intensity in the UV waveband were not found. In general, the orange-red component of the signal seems to be dynamic with respect to color intensity and hue. This accounts in particular for color changes during the breeding cycle, presumably to signal reproductive status, and with limitations as well in the intrasexual context, most likely to signal dominance or inferiority.

Brain coordination dynamics: True and false faces of phase synchrony and metastability

PubMed Central

Tognoli, Emmanuelle; Kelso, J.A. Scott

2009-01-01

Understanding the coordination of multiple parts in a complex system such as the brain is a fundamental challenge. We present a theoretical model of cortical coordination dynamics that shows how brain areas may cooperate (integration) and at the same time retain their functional specificity (segregation). This model expresses a range of desirable properties that the brain is known to exhibit, including self-organization, multi-functionality, metastability and switching. Empirically, the model motivates a thorough investigation of collective phase relationships among brain oscillations in neurophysiological data. The most serious obstacle to interpreting coupled oscillations as genuine evidence of inter-areal coordination in the brain stems from volume conduction of electrical fields. Spurious coupling due to volume conduction gives rise to zero-lag (inphase) and antiphase synchronization whose magnitude and persistence obscure the subtle expression of real synchrony. Through forward modeling and the help of a novel colorimetric method, we show how true synchronization can be deciphered from continuous EEG patterns. Developing empirical efforts along the lines of continuous EEG analysis constitutes a major response to the challenge of understanding how different brain areas work together. Key predictions of cortical coordination dynamics can now be tested thereby revealing the essential modus operandi of the intact living brain. PMID:18938209

Expression of parasite genetic variation changes over the course of infection: implications of within-host dynamics for the evolution of virulence

PubMed Central

Clerc, Melanie; Ebert, Dieter; Hall, Matthew D.

2015-01-01

How infectious disease agents interact with their host changes during the course of infection and can alter the expression of disease-related traits. Yet by measuring parasite life-history traits at one or few moments during infection, studies have overlooked the impact of variable parasite growth trajectories on disease evolution. Here we show that infection-age-specific estimates of host and parasite fitness components can reveal new insight into the evolution of parasites. We do so by characterizing the within-host dynamics over an entire infection period for five genotypes of the castrating bacterial parasite Pasteuria ramosa infecting the crustacean Daphnia magna. Our results reveal that genetic variation for parasite-induced gigantism, host castration and parasite spore loads increases with the age of infection. Driving these patterns appears to be variation in how well the parasite maintains control of host reproduction late in the infection process. We discuss the evolutionary consequences of this finding with regard to natural selection acting on different ages of infection and the mechanism underlying the maintenance of castration efficiency. Our results highlight how elucidating within-host dynamics can shed light on the selective forces that shape infection strategies and the evolution of virulence. PMID:25761710

Sexually Dimorphic Expression of Secreted Frizzled-Related (SFRP) Genes in the Developing Mouse Müllerian Duct

PubMed Central

COX, SAM; SMITH, LEE; BOGANI, DEBORA; CHEESEMAN, MICHAEL; SIGGERS, PAM; GREENFIELD, ANDY

2007-01-01

In developing male embryos, the female reproductive tract primordia (Müllerian ducts) regress due to the production of testicular anti-Müllerian hormone (AMH). Because of the association between secreted frizzled-related proteins (SFRPs) and apoptosis, their reported developmental expression patterns and the role of WNT signaling in female reproductive tract development, we examined expression of Sfrp2 and Sfrp5 during development of the Müllerian duct in male (XY) and female (XX) mouse embryos. We show that expression of both Sfrp2 and Sfrp5 is dynamic and sexually dimorphic. In addition, the male-specific expression observed for both genes prior to the onset of regression is absent in mutant male embryos that fail to undergo Müllerian duct regression. We identified ENU-induced point mutations in Sfrp5 and Sfrp2 that are predicted to severely disrupt the function of these genes. Male embryos and adults homozygous for these mutations, both individually and in combination, are viable and apparently fertile with no overt abnormalities of reproductive tract development. PMID:16700072

Testability of evolutionary game dynamics based on experimental economics data

NASA Astrophysics Data System (ADS)

Wang, Yijia; Chen, Xiaojie; Wang, Zhijian

In order to better understand the dynamic processes of a real game system, we need an appropriate dynamics model, so to evaluate the validity of a model is not a trivial task. Here, we demonstrate an approach, considering the dynamical macroscope patterns of angular momentum and speed as the measurement variables, to evaluate the validity of various dynamics models. Using the data in real time Rock-Paper-Scissors (RPS) games experiments, we obtain the experimental dynamic patterns, and then derive the related theoretical dynamic patterns from a series of typical dynamics models respectively. By testing the goodness-of-fit between the experimental and theoretical patterns, the validity of the models can be evaluated. One of the results in our study case is that, among all the nonparametric models tested, the best-known Replicator dynamics model performs almost worst, while the Projection dynamics model performs best. Besides providing new empirical macroscope patterns of social dynamics, we demonstrate that the approach can be an effective and rigorous tool to test game dynamics models. Fundamental Research Funds for the Central Universities (SSEYI2014Z) and the National Natural Science Foundation of China (Grants No. 61503062).

LHP1 Regulates H3K27me3 Spreading and Shapes the Three-Dimensional Conformation of the Arabidopsis Genome

PubMed Central

Ariel, Federico; Latrasse, David; Mariappan, Kiruthiga Gayathri; Kim, Soon-Kap; Crespi, Martin; Hirt, Heribert; Bergounioux, Catherine; Raynaud, Cécile; Benhamed, Moussa

2016-01-01

Precise expression patterns of genes in time and space are essential for proper development of multicellular organisms. Dynamic chromatin conformation and spatial organization of the genome constitute a major step in this regulation to modulate developmental outputs. Polycomb repressive complexes (PRCs) mediate stable or flexible gene repression in response to internal and environmental cues. In Arabidopsis thaliana, LHP1 co-localizes with H3K27me3 epigenetic marks throughout the genome and interacts with PRC1 and PRC2 members as well as with a long noncoding RNA. Here, we show that LHP1 is responsible for the spreading of H3K27me3 towards the 3’ end of the gene body. We also identified a subset of LHP1-activated genes and demonstrated that LHP1 shapes local chromatin topology in order to control transcriptional co-regulation. Our work reveals a general role of LHP1 from local to higher conformation levels of chromatin configuration to determine its accessibility to define gene expression patterns. PMID:27410265

Abnormal patterns of displacement activities: a review and reinterpretation.

PubMed

Anselme, Patrick

2008-09-01

A series of important theoretical contributions flourished in the years 1950-1970 about displacement activities -- those 'out-of-context' actions expressed by organisms in stressful situations. Nothing really new has appeared thereafter. Although the models address different issues, such as causal factors of displacement, it appears obvious that they do not provide a unified (coherent) approach; they often explain the same phenomena using very different means and turn out to be contradictory on several points. In addition, some problems currently remain unsolved, especially concerning the fact that displacement activities exhibit 'abnormalities' of expression in comparison with the same activities performed in usual context. Each model is here described and criticized in order to evaluate its explanatory power and allow the identification of specific limits. A new, integrative model -- the Anticipatory Dynamics Model (or ADM) -- then attempts to overcome the failures of previous models. The ADM suggests that abnormal patterns of displacement activities result from attentional interference caused by a thwarting experience or conflicting motivations. At least one theoretical prediction of the ADM can be differentiated from that of any other model.

In Silico Computational Transcriptomics Reveals Novel Endocrine Disruptors in Largemouth Bass ( Micropterus salmoides).

PubMed

Basili, Danilo; Zhang, Ji-Liang; Herbert, John; Kroll, Kevin; Denslow, Nancy D; Martyniuk, Christopher J; Falciani, Francesco; Antczak, Philipp

2018-06-15

In recent years, decreases in fish populations have been attributed, in part, to the effect of environmental chemicals on ovarian development. To understand the underlying molecular events we developed a dynamic model of ovary development linking gene transcription to key physiological end points, such as gonadosomatic index (GSI), plasma levels of estradiol (E2) and vitellogenin (VTG), in largemouth bass ( Micropterus salmoides). We were able to identify specific clusters of genes, which are affected at different stages of ovarian development. A subnetwork was identified that closely linked gene expression and physiological end points and by interrogating the Comparative Toxicogenomic Database (CTD), quercetin and tretinoin (ATRA) were identified as two potential candidates that may perturb this system. Predictions were validated by investigation of reproductive associated transcripts using qPCR in ovary and in the liver of both male and female largemouth bass treated after a single injection of quercetin and tretinoin (10 and 100 μg/kg). Both compounds were found to significantly alter the expression of some of these genes. Our findings support the use of omics and online repositories for identification of novel, yet untested, compounds. This is the first study of a dynamic model that links gene expression patterns across stages of ovarian development.

Testability of evolutionary game dynamics based on experimental economics data

NASA Astrophysics Data System (ADS)

Wang, Yijia; Chen, Xiaojie; Wang, Zhijian

2017-11-01

Understanding the dynamic processes of a real game system requires an appropriate dynamics model, and rigorously testing a dynamics model is nontrivial. In our methodological research, we develop an approach to testing the validity of game dynamics models that considers the dynamic patterns of angular momentum and speed as measurement variables. Using Rock-Paper-Scissors (RPS) games as an example, we illustrate the geometric patterns in the experiment data. We then derive the related theoretical patterns from a series of typical dynamics models. By testing the goodness-of-fit between the experimental and theoretical patterns, we show that the validity of these models can be evaluated quantitatively. Our approach establishes a link between dynamics models and experimental systems, which is, to the best of our knowledge, the most effective and rigorous strategy for ascertaining the testability of evolutionary game dynamics models.

An optimized ERP brain-computer interface based on facial expression changes.

PubMed

Jin, Jing; Daly, Ian; Zhang, Yu; Wang, Xingyu; Cichocki, Andrzej

2014-06-01

Interferences from spatially adjacent non-target stimuli are known to evoke event-related potentials (ERPs) during non-target flashes and, therefore, lead to false positives. This phenomenon was commonly seen in visual attention-based brain-computer interfaces (BCIs) using conspicuous stimuli and is known to adversely affect the performance of BCI systems. Although users try to focus on the target stimulus, they cannot help but be affected by conspicuous changes of the stimuli (such as flashes or presenting images) which were adjacent to the target stimulus. Furthermore, subjects have reported that conspicuous stimuli made them tired and annoyed. In view of this, the aim of this study was to reduce adjacent interference, annoyance and fatigue using a new stimulus presentation pattern based upon facial expression changes. Our goal was not to design a new pattern which could evoke larger ERPs than the face pattern, but to design a new pattern which could reduce adjacent interference, annoyance and fatigue, and evoke ERPs as good as those observed during the face pattern. Positive facial expressions could be changed to negative facial expressions by minor changes to the original facial image. Although the changes are minor, the contrast is big enough to evoke strong ERPs. In this paper, a facial expression change pattern between positive and negative facial expressions was used to attempt to minimize interference effects. This was compared against two different conditions, a shuffled pattern containing the same shapes and colours as the facial expression change pattern, but without the semantic content associated with a change in expression, and a face versus no face pattern. Comparisons were made in terms of classification accuracy and information transfer rate as well as user supplied subjective measures. The results showed that interferences from adjacent stimuli, annoyance and the fatigue experienced by the subjects could be reduced significantly (p < 0.05) by using the facial expression change patterns in comparison with the face pattern. The offline results show that the classification accuracy of the facial expression change pattern was significantly better than that of the shuffled pattern (p < 0.05) and the face pattern (p < 0.05). The facial expression change pattern presented in this paper reduced interference from adjacent stimuli and decreased the fatigue and annoyance experienced by BCI users significantly (p < 0.05) compared to the face pattern.

An optimized ERP brain-computer interface based on facial expression changes

NASA Astrophysics Data System (ADS)

Jin, Jing; Daly, Ian; Zhang, Yu; Wang, Xingyu; Cichocki, Andrzej

2014-06-01

Objective. Interferences from spatially adjacent non-target stimuli are known to evoke event-related potentials (ERPs) during non-target flashes and, therefore, lead to false positives. This phenomenon was commonly seen in visual attention-based brain-computer interfaces (BCIs) using conspicuous stimuli and is known to adversely affect the performance of BCI systems. Although users try to focus on the target stimulus, they cannot help but be affected by conspicuous changes of the stimuli (such as flashes or presenting images) which were adjacent to the target stimulus. Furthermore, subjects have reported that conspicuous stimuli made them tired and annoyed. In view of this, the aim of this study was to reduce adjacent interference, annoyance and fatigue using a new stimulus presentation pattern based upon facial expression changes. Our goal was not to design a new pattern which could evoke larger ERPs than the face pattern, but to design a new pattern which could reduce adjacent interference, annoyance and fatigue, and evoke ERPs as good as those observed during the face pattern. Approach. Positive facial expressions could be changed to negative facial expressions by minor changes to the original facial image. Although the changes are minor, the contrast is big enough to evoke strong ERPs. In this paper, a facial expression change pattern between positive and negative facial expressions was used to attempt to minimize interference effects. This was compared against two different conditions, a shuffled pattern containing the same shapes and colours as the facial expression change pattern, but without the semantic content associated with a change in expression, and a face versus no face pattern. Comparisons were made in terms of classification accuracy and information transfer rate as well as user supplied subjective measures. Main results. The results showed that interferences from adjacent stimuli, annoyance and the fatigue experienced by the subjects could be reduced significantly (p < 0.05) by using the facial expression change patterns in comparison with the face pattern. The offline results show that the classification accuracy of the facial expression change pattern was significantly better than that of the shuffled pattern (p < 0.05) and the face pattern (p < 0.05). Significance. The facial expression change pattern presented in this paper reduced interference from adjacent stimuli and decreased the fatigue and annoyance experienced by BCI users significantly (p < 0.05) compared to the face pattern.

Microbial phylogeny determines transcriptional response of resistome to dynamic composting processes.

PubMed

Wang, Cheng; Dong, Da; Strong, P J; Zhu, Weijing; Ma, Zhuang; Qin, Yong; Wu, Weixiang

2017-08-16

Animal manure is a reservoir of antibiotic resistance genes (ARGs) that pose a potential health risk globally, especially for resistance to the antibiotics commonly used in livestock production (such as tetracycline, sulfonamide, and fluoroquinolone). Currently, the effects of biological treatment (composting) on the transcriptional response of manure ARGs and their microbial hosts are not well characterized. Composting is a dynamic process that consists of four distinct phases that are distinguished by the temperature resulting from microbial activity, namely the mesophilic, thermophilic, cooling, and maturing phases. In this study, changes of resistome expression were determined and related to active microbiome profiles during the dynamic composting process. This was achieved by integrating metagenomic and time series metatranscriptomic data for the evolving microbial community during composting. Composting noticeably reduced the aggregated expression level of the manure resistome, which primarily consisted of genes encoding for tetracycline, vancomycin, fluoroquinolone, beta-lactam, and aminoglycoside resistance, as well as efflux pumps. Furthermore, a varied transcriptional response of resistome to composting at the ARG levels was highlighted. The expression of tetracycline resistance genes (tetM-tetW-tetO-tetS) decreased during composting, where distinctive shifts in the four phases of composting were related to variations in antibiotic concentration. Composting had no effect on the expression of sulfonamide and fluoroquinolone resistance genes, which increased slightly during the thermophilic phase and then decreased to initial levels. As indigenous populations switched greatly throughout the dynamic composting, the core resistome persisted and their reservoir hosts' composition was significantly correlated with dynamic active microbial phylogenetic structure. Hosts for sulfonamide and fuoroquinolone resistance genes changed notably in phylognetic structure and underwent an initial increase and then a decrease in abundance. By contrast, hosts for tetracycline resistance genes (tetM-tetW-tetO-tetS) exhibited a constant decline through time. The transcriptional patterns of a core resistome over the course of composting were identified, and microbial phylogeny was the key determinant in defining the varied transcriptional response of resistome to this dynamic biological process. This research demonstrated the benefits of composting for manure treatment. It reduced the risk of emerging environmental contaminants such as tetracyclines, tetracycline resistance genes, and clinically relevant pathogens carrying ARGs, as well as RNA viruses and bacteriophages.

Dynamic nuclear envelope phenotype in rats overexpressing mutated human torsinA protein.

PubMed

Yu-Taeger, Libo; Gaiser, Viktoria; Lotzer, Larissa; Roenisch, Tina; Fabry, Benedikt Timo; Stricker-Shaver, Janice; Casadei, Nicolas; Walter, Michael; Schaller, Martin; Riess, Olaf; Nguyen, Huu Phuc; Ott, Thomas; Grundmann-Hauser, Kathrin

2018-05-08

A three-base-pair deletion in the human TOR1A gene is causative for the most common form of primary dystonia, the early-onset dystonia type 1 (DYT1 dystonia). The pathophysiological consequences of this mutation are still unknown.To study the pathology of the mutant torsinA (TOR1A) protein, we have generated a transgenic rat line that overexpresses the human mutant protein under the control of the human TOR1A promoter. This new animal model was phenotyped with several approaches, including behavioral tests and neuropathological analyses. A motor phenotype and cellular and ultrastructural key features of torsinA pathology were found in this new transgenic rat line supporting that it can be used as a model system for investigating the disease development. Analyses of mutant TOR1A protein expression in various brain regions also showed a dynamic expression pattern and a reversible nuclear envelope pathology. These findings suggest the differential vulnerabilities of distinct neuronal subpopulations. Furthermore the reversibility of the nuclear envelope pathology might be a therapeutic target to treat the disease. © 2018. Published by The Company of Biologists Ltd.

Antagonistic autoregulation speeds up a homogeneous response in Escherichia coli.

PubMed

Rodrigo, Guillermo; Bajic, Djordje; Elola, Ignacio; Poyatos, Juan F

2016-10-31

By integrating positive and negative feedback loops, biological systems establish intricate gene expression patterns linked to multistability, pulsing, and oscillations. This depends on the specific characteristics of each interlinked feedback, and thus one would expect additional expression programs to be found. Here, we investigate one such program associated with an antagonistic positive and negative transcriptional autoregulatory motif derived from the multiple antibiotic resistance (mar) system of Escherichia coli. We studied the dynamics of the system by combining a predictive mathematical model with high-resolution experimental measures of the response both at the population and single-cell level. We show that in this motif the weak positive autoregulation does not slow down but rather enhances response speedup in combination with a strong negative feedback loop. This balance of feedback strengths anticipates a homogeneous population phenotype, which we corroborate experimentally. Theoretical analysis also emphasized the specific molecular properties that determine the dynamics of the mar phenotype. More broadly, response acceleration could provide a rationale for the presence of weak positive feedbacks in other biological scenarios exhibiting these interlinked regulatory architectures.

Metastable dynamical patterns and their stabilization in arrays of bidirectionally coupled sigmoidal neurons

NASA Astrophysics Data System (ADS)

Horikawa, Yo

2013-12-01

Transient patterns in a bistable ring of bidirectionally coupled sigmoidal neurons were studied. When the system had a pair of spatially uniform steady solutions, the instability of unstable spatially nonuniform steady solutions decreased exponentially with the number of neurons because of the symmetry of the system. As a result, transient spatially nonuniform patterns showed dynamical metastability: Their duration increased exponentially with the number of neurons and the duration of randomly generated patterns obeyed a power-law distribution. However, these metastable dynamical patterns were easily stabilized in the presence of small variations in coupling strength. Metastable rotating waves and their pinning in the presence of asymmetry in the direction of coupling and the disappearance of metastable dynamical patterns due to asymmetry in the output function of a neuron were also examined. Further, in a two-dimensional array of neurons with nearest-neighbor coupling, intrinsically one-dimensional patterns were dominant in transients, and self-excitation in these neurons affected the metastable dynamical patterns.

Percolator: Scalable Pattern Discovery in Dynamic Graphs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choudhury, Sutanay; Purohit, Sumit; Lin, Peng

We demonstrate Percolator, a distributed system for graph pattern discovery in dynamic graphs. In contrast to conventional mining systems, Percolator advocates efficient pattern mining schemes that (1) support pattern detection with keywords; (2) integrate incremental and parallel pattern mining; and (3) support analytical queries such as trend analysis. The core idea of Percolator is to dynamically decide and verify a small fraction of patterns and their in- stances that must be inspected in response to buffered updates in dynamic graphs, with a total mining cost independent of graph size. We demonstrate a) the feasibility of incremental pattern mining by walkingmore » through each component of Percolator, b) the efficiency and scalability of Percolator over the sheer size of real-world dynamic graphs, and c) how the user-friendly GUI of Percolator inter- acts with users to support keyword-based queries that detect, browse and inspect trending patterns. We also demonstrate two user cases of Percolator, in social media trend analysis and academic collaboration analysis, respectively.« less

Dynamic Transcription Factor Networks in Epithelial-Mesenchymal Transition in Breast Cancer Models

PubMed Central

Siletz, Anaar; Schnabel, Michael; Kniazeva, Ekaterina; Schumacher, Andrew J.; Shin, Seungjin; Jeruss, Jacqueline S.; Shea, Lonnie D.

2013-01-01

The epithelial-mesenchymal transition (EMT) is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs) are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy. PMID:23593114

Dynamic transcription factor networks in epithelial-mesenchymal transition in breast cancer models.

PubMed

Siletz, Anaar; Schnabel, Michael; Kniazeva, Ekaterina; Schumacher, Andrew J; Shin, Seungjin; Jeruss, Jacqueline S; Shea, Lonnie D

2013-01-01

The epithelial-mesenchymal transition (EMT) is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs) are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy.

A Nonlinear Dynamics Approach for Incorporating Wind-Speed Patterns into Wind-Power Project Evaluation

PubMed Central

Huffaker, Ray; Bittelli, Marco

2015-01-01

Wind-energy production may be expanded beyond regions with high-average wind speeds (such as the Midwest U.S.A.) to sites with lower-average speeds (such as the Southeast U.S.A.) by locating favorable regional matches between natural wind-speed and energy-demand patterns. A critical component of wind-power evaluation is to incorporate wind-speed dynamics reflecting documented diurnal and seasonal behavioral patterns. Conventional probabilistic approaches remove patterns from wind-speed data. These patterns must be restored synthetically before they can be matched with energy-demand patterns. How to accurately restore wind-speed patterns is a vexing problem spurring an expanding line of papers. We propose a paradigm shift in wind power evaluation that employs signal-detection and nonlinear-dynamics techniques to empirically diagnose whether synthetic pattern restoration can be avoided altogether. If the complex behavior of observed wind-speed records is due to nonlinear, low-dimensional, and deterministic system dynamics, then nonlinear dynamics techniques can reconstruct wind-speed dynamics from observed wind-speed data without recourse to conventional probabilistic approaches. In the first study of its kind, we test a nonlinear dynamics approach in an application to Sugarland Wind—the first utility-scale wind project proposed in Florida, USA. We find empirical evidence of a low-dimensional and nonlinear wind-speed attractor characterized by strong temporal patterns that match up well with regular daily and seasonal electricity demand patterns. PMID:25617767

Aberrant cytokine pattern of the nasal mucosa in granulomatosis with polyangiitis

PubMed Central

2012-01-01

Introduction In granulomatosis with polyangiitis (GPA), a complex autoimmune small-vessel vasculitis frequently associated with chronic necrotizing inflammation of the nasal mucosa, elevated nasal Staphylococcus (S.) aureus carrier rates are a risk factor for relapse. As cytokines are primarily involved in the regulation of defense against potentially pathogenic microorganisms, the aim of this study was to compare healthy individuals and GPA patients with respect to their baseline cytokine expression of nasal epithelial cells (NEC), which form the first barrier against such triggers. The ability of S. aureus to influence the nasal microenvironment's cytokine secretion was assessed by exemplary stimulation experiments. Methods Baseline expression of 19 cytokines of primary NEC of GPA patients and normal controls (NC) was quantified by a multiplex cytokine assay. Stimulation experiments were performed with supernatants of S. aureus and expression of interleukin-8 was determined by ELISA. Results In GPA, an altered pattern of baseline cytokine expression with significantly up-regulated G-CSF and reduced interleukin (IL)-8 concentrations was observed. Both NEC of GPA patients and NC responded to stimulation with S. aureus, but GPA patients displayed a significantly lower IL-8 secretion and a diminished dynamic range of response towards the stimulus. Conclusions The data presented underline the hypothesis of a disturbed epithelial nasal barrier function in GPA. The dysregulated baseline expression of G-CSF and IL-8 and the reduced response to microbial stimulation may facilitate changes in the composition of the nasal flora and favour an imbalanced inflammatory response, which might be relevant for the disease course. PMID:23031229

Dynamic gene expression in the song system of zebra finches during the song learning period.

PubMed

Olson, Christopher R; Hodges, Lisa K; Mello, Claudio V

2015-12-01

The brain circuitry that controls song learning and production undergoes marked changes in morphology and connectivity during the song learning period in juvenile zebra finches, in parallel to the acquisition, practice and refinement of song. Yet, the genetic programs and timing of regulatory change that establish the neuronal connectivity and plasticity during this critical learning period remain largely undetermined. To address this question, we used in situ hybridization to compare the expression patterns of a set of 30 known robust molecular markers of HVC and/or area X, major telencephalic song nuclei, between adult and juvenile male zebra finches at different ages during development (20, 35, 50 days post-hatch, dph). We found that several of the genes examined undergo substantial changes in expression within HVC or its surrounds, and/or in other song nuclei. They fit into broad patterns of regulation, including those whose expression within HVC during this period increases (COL12A1, COL 21A1, MPZL1, PVALB, and CXCR7) or decreases (e.g., KCNT2, SAP30L), as well as some that show decreased expression in the surrounding tissue with little change within song nuclei (e.g. SV2B, TAC1). These results reveal a broad range of molecular changes that occur in the song system in concert with the song learning period. Some of the genes and pathways identified are potential modulators of the developmental changes associated with the emergence of the adult properties of the song control system, and/or the acquisition of learned vocalizations in songbirds. © 2015 Wiley Periodicals, Inc.

Expression dynamics of HSP70 during chronic heat stress in Tharparkar cattle.

PubMed

Bharati, Jaya; Dangi, S S; Chouhan, V S; Mishra, S R; Bharti, M K; Verma, V; Shankar, O; Yadav, V P; Das, K; Paul, A; Bag, S; Maurya, V P; Singh, G; Kumar, P; Sarkar, M

2017-06-01

Six male Tharparkar cattle aged 2-3 years were selected for the study. The animals were acclimatized in the psychrometric chamber at thermoneutral zone (TNZ) for 15 days and then exposed to 42 °C temperature up to 23 days followed by 12 days of recovery period. Physiological responses were estimated, and peripheral blood mononuclear cells (PBMCs) were isolated at TNZ on day 1, day 5, and day 12; after 6 h of heat stress exposure on day 16 to day 20, day 25, day 30, day 32, day 34, day 36, and day 38; and a recovery period on day 45 and day 50. The PBMCs were cultured to study the effect of thermal challenge on HSP70 messenger RNA (mRNA) expression pattern at different temperature-time combinations. The mRNA and protein expression of HSP70 in PBMCs along with serum extracellular HSP70 (eHSP70) was increased (P < 0.05) and showed two peaks on day 17 and day 32 (2nd and 17th days of thermal challenge, respectively). The HSP70 mRNA expression was increased (P < 0.05) in a temperature- and time-dependent manner in heat stress challenge treatment as compared to control in cultured PBMCs. HSP70 expression was found to be higher (P < 0.05) after 10 days of heat exposure (corresponds to chronic heat stress) as compared to the first 5 days of heat stress (corresponds to short-term heat stress) and control period at TNZ. The present findings indicate that HSP70 is possibly involved in heat stress adaptive response in Tharparkar cattle and the biphasic expression pattern may be providing a second window of protection during chronic heat stress.

Dynamic Skin Patterns in Cephalopods

PubMed Central

How, Martin J.; Norman, Mark D.; Finn, Julian; Chung, Wen-Sung; Marshall, N. Justin

2017-01-01

Cephalopods are unrivaled in the natural world in their ability to alter their visual appearance. These mollusks have evolved a complex system of dermal units under neural, hormonal, and muscular control to produce an astonishing variety of body patterns. With parallels to the pixels on a television screen, cephalopod chromatophores can be coordinated to produce dramatic, dynamic, and rhythmic displays, defined collectively here as “dynamic patterns.” This study examines the nature, context, and potential functions of dynamic patterns across diverse cephalopod taxa. Examples are presented for 21 species, including 11 previously unreported in the scientific literature. These range from simple flashing or flickering patterns, to highly complex passing wave patterns involving multiple skin fields. PMID:28674500

Brief report: Representational momentum for dynamic facial expressions in pervasive developmental disorder.

PubMed

Uono, Shota; Sato, Wataru; Toichi, Motomi

2010-03-01

Individuals with pervasive developmental disorder (PDD) have difficulty with social communication via emotional facial expressions, but behavioral studies involving static images have reported inconsistent findings about emotion recognition. We investigated whether dynamic presentation of facial expression would enhance subjective perception of expressed emotion in 13 individuals with PDD and 13 typically developing controls. We presented dynamic and static emotional (fearful and happy) expressions. Participants were asked to match a changeable emotional face display with the last presented image. The results showed that both groups perceived the last image of dynamic facial expression to be more emotionally exaggerated than the static facial expression. This finding suggests that individuals with PDD have an intact perceptual mechanism for processing dynamic information in another individual's face.

Automating Network Node Behavior Characterization by Mining Communication Patterns

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carroll, Thomas E.; Chikkagoudar, Satish; Arthur-Durett, Kristine M.

Enterprise networks of scale are complex, dynamic computing environments that respond to evolv- ing business objectives and requirements. Characteriz- ing system behaviors in these environments is essential for network management and cyber security operations. Characterization of system’s communication is typical and is supported using network flow information (NetFlow). Related work has characterized behavior using theoretical graph metrics; results are often difficult to interpret by enterprise staff. We propose a different approach, where flow information is mapped to sets of tags that contextualize the data in terms of network principals and enterprise concepts. Frequent patterns are then extracted and are expressedmore » as behaviors. Behaviors can be com- pared, identifying systems expressing similar behaviors. We evaluate the approach using flow information collected by a third party.« less

Contribution of Circulatory Disturbances in Subchondral Bone to the Pathophysiology of Osteoarthritis.

PubMed

Aaron, Roy K; Racine, Jennifer; Dyke, Jonathan P

2017-08-01

This review describes the contributions of abnormal bone circulation to the pathophysiology of osteoarthritis. Combining dynamic imaging with MRI and PET with previous observations reveals that venous stasis and a venous outlet syndrome is most likely the key circulatory pathology associated with the initiation or progression of osteoarthritis. MRI and PET have revealed that venous outflow obstruction results in physicochemical changes in subchondral bone to which osteoblasts are responsive. The osteoblasts express an altered pattern of cytokines, many of which can serve as structural or signaling molecules contributing to both bone remodeling and cartilage degeneration. The patterns of circulatory changes are associated with alterations in the physicochemical environment of subchondral bone, including hypoxia. Osteoblast cytokines can transit the subchondral bone plate and calcified cartilage and communicate with chondrocytes.

Dynamic Modulation of Expression of Lentiviral Restriction Factors in Primary CD4+ T Cells following Simian Immunodeficiency Virus Infection.

PubMed

Rahmberg, Andrew R; Rajakumar, Premeela A; Billingsley, James M; Johnson, R Paul

2017-04-01

Although multiple restriction factors have been shown to inhibit HIV/SIV replication, little is known about their expression in vivo Expression of 45 confirmed and putative HIV/SIV restriction factors was analyzed in CD4 + T cells from peripheral blood and the jejunum in rhesus macaques, revealing distinct expression patterns in naive and memory subsets. In both peripheral blood and the jejunum, memory CD4 + T cells expressed higher levels of multiple restriction factors compared to naive cells. However, relative to their expression in peripheral blood CD4 + T cells, jejunal CCR5 + CD4 + T cells exhibited significantly lower expression of multiple restriction factors, including APOBEC3G , MX2 , and TRIM25 , which may contribute to the exquisite susceptibility of these cells to SIV infection. In vitro stimulation with anti-CD3/CD28 antibodies or type I interferon resulted in upregulation of distinct subsets of multiple restriction factors. After infection of rhesus macaques with SIVmac239, the expression of most confirmed and putative restriction factors substantially increased in all CD4 + T cell memory subsets at the peak of acute infection. Jejunal CCR5 + CD4 + T cells exhibited the highest levels of SIV RNA, corresponding to the lower restriction factor expression in this subset relative to peripheral blood prior to infection. These results illustrate the dynamic modulation of confirmed and putative restriction factor expression by memory differentiation, stimulation, tissue microenvironment and SIV infection and suggest that differential expression of restriction factors may play a key role in modulating the susceptibility of different populations of CD4 + T cells to lentiviral infection. IMPORTANCE Restriction factors are genes that have evolved to provide intrinsic defense against viruses. HIV and simian immunodeficiency virus (SIV) target CD4 + T cells. The baseline level of expression in vivo and degree to which expression of restriction factors is modulated by conditions such as CD4 + T cell differentiation, stimulation, tissue location, or SIV infection are currently poorly understood. We measured the expression of 45 confirmed and putative restriction factors in primary CD4 + T cells from rhesus macaques under various conditions, finding dynamic changes in each state. Most dramatically, in acute SIV infection, the expression of almost all target genes analyzed increased. These are the first measurements of many of these confirmed and putative restriction factors in primary cells or during the early events after SIV infection and suggest that the level of expression of restriction factors may contribute to the differential susceptibility of CD4 + T cells to SIV infection. Copyright © 2017 American Society for Microbiology.

A proteomic analysis of contextual fear conditioned rats reveals dynamic modifications in neuron and oligodendrocyte protein expression in the dentate gyrus.

PubMed

Houyoux, Nicolas; Wattiez, Ruddy; Ris, Laurence

2017-09-01

Contextual memory is an intricate process involving synaptic plasticity and network rearrangement. Both are governed by many molecular processes including phosphorylation and modulation of protein expression. However, little is known about the molecules involved in it. Here, we exploited the advantages of a quantitative proteomic approach to identify a great number of molecules in the rat dentate gyrus after a contextual fear conditioning session. Our results allowed us to highlight protein expression patterns, not only related to neuroplasticity, but also to myelin structure, such as myelin basic protein and myelin proteolipid protein showing a decrease in expression. Validation of the modification in protein expression reveals a dynamic profile during the 48 h following the fear conditioning session. The expression of proteins involved in neurite outgrowth, such as BASP-1 and calcineurin B1, and in synaptic structure and function, VAMP2 and RAB3C, was increased in the dentate gyrus of rats submitted to fear conditioning compared to controls. We showed that the increase in BASP-1 protein was specific to fear conditioning learning as it was not present in immediate-shock rats, neither in rats exposed to a novel environment without being shocked. As myelin is known to stabilise synaptic network, the decrease in myelin proteins suggests a neuroglia interactive process taking place in the dentate gyrus in the 24 h following contextual fear learning, which has never been demonstrated before. These results therefore open the way to the study of new plasticity mechanisms underlying learning and memory. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Decoding the Long Noncoding RNA During Cardiac Maturation: A Roadmap for Functional Discovery.

PubMed

Touma, Marlin; Kang, Xuedong; Zhao, Yan; Cass, Ashley A; Gao, Fuying; Biniwale, Reshma; Coppola, Giovanni; Xiao, Xinshu; Reemtsen, Brian; Wang, Yibin

2016-10-01

Cardiac maturation during perinatal transition of heart is critical for functional adaptation to hemodynamic load and nutrient environment. Perturbation in this process has major implications in congenital heart defects. Transcriptome programming during perinatal stages is an important information but incomplete in current literature, particularly, the expression profiles of the long noncoding RNAs (lncRNAs) are not fully elucidated. From comprehensive analysis of transcriptomes derived from neonatal mouse heart left and right ventricles, a total of 45 167 unique transcripts were identified, including 21 916 known and 2033 novel lncRNAs. Among these lncRNAs, 196 exhibited significant dynamic regulation along maturation process. By implementing parallel weighted gene co-expression network analysis of mRNA and lncRNA data sets, several lncRNA modules coordinately expressed in a developmental manner similar to protein coding genes, while few lncRNAs revealed chamber-specific patterns. Out of 2262 lncRNAs located within 50 kb of protein coding genes, 5% significantly correlate with the expression of their neighboring genes. The impact of Ppp1r1b-lncRNA on the corresponding partner gene Tcap was validated in cultured myoblasts. This concordant regulation was also conserved in human infantile hearts. Furthermore, the Ppp1r1b-lncRNA/Tcap expression ratio was identified as a molecular signature that differentiated congenital heart defect phenotypes. The study provides the first high-resolution landscape on neonatal cardiac lncRNAs and reveals their potential interaction with mRNA transcriptome during cardiac maturation. Ppp1r1b-lncRNA was identified as a regulator of Tcap expression, with dynamic interaction in postnatal cardiac development and congenital heart defects. © 2016 American Heart Association, Inc.

Genetic Architecture and Molecular Networks Underlying Leaf Thickness in Desert-Adapted Tomato Solanum pennellii1[OPEN

PubMed Central

Frank, Margaret H.; Balaguer, Maria A. de Luis; Li, Mao

2017-01-01

Thicker leaves allow plants to grow in water-limited conditions. However, our understanding of the genetic underpinnings of this highly functional leaf shape trait is poor. We used a custom-built confocal profilometer to directly measure leaf thickness in a set of introgression lines (ILs) derived from the desert tomato Solanum pennellii and identified quantitative trait loci. We report evidence of a complex genetic architecture of this trait and roles for both genetic and environmental factors. Several ILs with thick leaves have dramatically elongated palisade mesophyll cells and, in some cases, increased leaf ploidy. We characterized the thick IL2-5 and IL4-3 in detail and found increased mesophyll cell size and leaf ploidy levels, suggesting that endoreduplication underpins leaf thickness in tomato. Next, we queried the transcriptomes and inferred dynamic Bayesian networks of gene expression across early leaf ontogeny in these lines to compare the molecular networks that pattern leaf thickness. We show that thick ILs share S. pennellii-like expression profiles for putative regulators of cell shape and meristem determinacy as well as a general signature of cell cycle-related gene expression. However, our network data suggest that leaf thickness in these two lines is patterned at least partially by distinct mechanisms. Consistent with this hypothesis, double homozygote lines combining introgression segments from these two ILs show additive phenotypes, including thick leaves, higher ploidy levels, and larger palisade mesophyll cells. Collectively, these data establish a framework of genetic, anatomical, and molecular mechanisms that pattern leaf thickness in desert-adapted tomato. PMID:28794258

Effects of dynamic information in recognising facial expressions on dimensional and categorical judgments.

PubMed

Fujimura, Tomomi; Suzuki, Naoto

2010-01-01

We investigated the effects of dynamic information on decoding facial expressions. A dynamic face entailed a change from a neutral to a full-blown expression, whereas a static face included only the full-blown expression. Sixty-eight participants were divided into two groups, the dynamic condition and the static condition. The facial stimuli expressed eight kinds of emotions (excited, happy, calm, sleepy, sad, angry, fearful, and surprised) according to a dimensional perspective. Participants evaluated each facial stimulus using two methods, the Affect Grid (Russell et al, 1989 Personality and Social Psychology 29 497-510) and the forced-choice task, allowing for dimensional and categorical judgment interpretations. For activation ratings in dimensional judgments, the results indicated that dynamic calm faces, low-activation expressions were rated as less activated than static faces. For categorical judgments, dynamic excited, happy, and fearful faces, which are high- and middle-activation expressions, had higher ratings than did those under the static condition. These results suggest that the beneficial effect of dynamic information depends on the emotional properties of facial expressions.

A cognitive-affective system theory of personality: reconceptualizing situations, dispositions, dynamics, and invariance in personality structure.

PubMed

Mischel, W; Shoda, Y

1995-04-01

A theory was proposed to reconcile paradoxical findings on the invariance of personality and the variability of behavior across situations. For this purpose, individuals were assumed to differ in (a) the accessibility of cognitive-affective mediating units (such as encodings, expectancies and beliefs, affects, and goals) and (b) the organization of relationships through which these units interact with each other and with psychological features of situations. The theory accounts for individual differences in predictable patterns of variability across situations (e.g., if A then she X, but if B then she Y), as well as for overall average levels of behavior, as essential expressions or behavioral signatures of the same underlying personality system. Situations, personality dispositions, dynamics, and structure were reconceptualized from this perspective.

Genome-wide coexpression dynamics: Theory and application

PubMed Central

Li, Ker-Chau

2002-01-01

High-throughput expression profiling enables the global study of gene activities. Genes with positively correlated expression profiles are likely to encode functionally related proteins. However, all biological processes are interlocked, and each protein may play multiple cellular roles. Thus the coexpression of any two functionally related genes may depend on the constantly varying, yet often-unknown cellular state. To initiate a systematic study on this issue, a theory of coexpression dynamics is presented. This theory is used to rationalize a strategy of conducting a genome-wide search for the most critical cellular players that may affect the coexpression pattern of any two genes. In one example, using a yeast data set, our method reveals how the enzymes associated with the urea cycle are expressed to ensure proper mass flow of the involved metabolites. The correlation between ARG2 and CAR2 is found to change from positive to negative as the expression level of CPA2 increases. This delicate interplay in correlation signifies a remarkable control on the influx and efflux of ornithine and reflects well the intrinsic cellular demand for arginine. In addition to the urea cycle, our examples include SCH9 and CYR1 (both implicated in a recent longevity study), cytochrome c1 (mitochondrial electron transport), calmodulin (main calcium-binding protein), PFK1 and PFK2 (glycolysis), and two genes, ECM1 and YNL101W, the functions of which are newly revealed. The complexity in computation is eased by a new result from mathematical statistics. PMID:12486219

Turgor-responsive starch phosphorylation in Oryza sativa stems: A primary event of starch degradation associated with grain-filling ability.

PubMed

Wada, Hiroshi; Masumoto-Kubo, Chisato; Tsutsumi, Koichi; Nonami, Hiroshi; Tanaka, Fukuyo; Okada, Haruka; Erra-Balsells, Rosa; Hiraoka, Kenzo; Nakashima, Taiken; Hakata, Makoto; Morita, Satoshi

2017-01-01

Grain filling ability is mainly affected by the translocation of carbohydrates generated from temporarily stored stem starch in most field crops including rice (Oryza sativa L.). The partitioning of non-structural stem carbohydrates has been recognized as an important trait for raising the yield ceiling, yet we still do not fully understand how carbohydrate partitioning occurs in the stems. In this study, two rice subspecies that exhibit different patterns of non-structural stem carbohydrates partitioning, a japonica-dominant cultivar, Momiroman, and an indica-dominant cultivar, Hokuriku 193, were used as the model system to study the relationship between turgor pressure and metabolic regulation of non-structural stem carbohydrates, by combining the water status measurement with gene expression analysis and a dynamic prefixed 13C tracer analysis using a mass spectrometer. Here, we report a clear varietal difference in turgor-associated starch phosphorylation occurred at the initiation of non-structural carbohydrate partitioning. The data indicated that starch degradation in Hokuriku 193 stems occurred at full-heading, 5 days earlier than in Momiroman, contributing to greater sink filling. Gene expression analysis revealed that expression pattern of the gene encoding α-glucan, water dikinase (GWD1) was similar between two varieties, and the maximum expression level in Hokuriku 193, reached at full heading (4 DAH), was greater than in Momiroman, leading to an earlier increase in a series of amylase-related gene expression in Hokuriku 193. In both varieties, peaks in turgor pressure preceded the increases in GWD1 expression, and changes in GWD1 expression was correlated with turgor pressure. Additionally, a threshold is likely to exist for GWD1 expression to facilitate starch degradation. Taken together, these results raise the possibility that turgor-associated starch phosphorylation in cells is responsible for the metabolism that leads to starch degradation. Because the two cultivars exhibited remarkable varietal differences in the pattern of non-structural carbohydrate partitioning, our findings propose that the observed difference in grain-filling ability originated from turgor-associated regulation of starch phosphorylation in stem parenchyma cells. Further understanding of the molecular mechanism of turgor-regulation may provide a new selection criterion for breaking the yield barriers in crop production.

Turgor-responsive starch phosphorylation in Oryza sativa stems: A primary event of starch degradation associated with grain-filling ability

PubMed Central

Tsutsumi, Koichi; Nonami, Hiroshi; Tanaka, Fukuyo; Okada, Haruka; Erra-Balsells, Rosa; Hiraoka, Kenzo; Nakashima, Taiken; Hakata, Makoto; Morita, Satoshi

2017-01-01

Grain filling ability is mainly affected by the translocation of carbohydrates generated from temporarily stored stem starch in most field crops including rice (Oryza sativa L.). The partitioning of non-structural stem carbohydrates has been recognized as an important trait for raising the yield ceiling, yet we still do not fully understand how carbohydrate partitioning occurs in the stems. In this study, two rice subspecies that exhibit different patterns of non-structural stem carbohydrates partitioning, a japonica-dominant cultivar, Momiroman, and an indica-dominant cultivar, Hokuriku 193, were used as the model system to study the relationship between turgor pressure and metabolic regulation of non-structural stem carbohydrates, by combining the water status measurement with gene expression analysis and a dynamic prefixed 13C tracer analysis using a mass spectrometer. Here, we report a clear varietal difference in turgor-associated starch phosphorylation occurred at the initiation of non-structural carbohydrate partitioning. The data indicated that starch degradation in Hokuriku 193 stems occurred at full-heading, 5 days earlier than in Momiroman, contributing to greater sink filling. Gene expression analysis revealed that expression pattern of the gene encoding α-glucan, water dikinase (GWD1) was similar between two varieties, and the maximum expression level in Hokuriku 193, reached at full heading (4 DAH), was greater than in Momiroman, leading to an earlier increase in a series of amylase-related gene expression in Hokuriku 193. In both varieties, peaks in turgor pressure preceded the increases in GWD1 expression, and changes in GWD1 expression was correlated with turgor pressure. Additionally, a threshold is likely to exist for GWD1 expression to facilitate starch degradation. Taken together, these results raise the possibility that turgor-associated starch phosphorylation in cells is responsible for the metabolism that leads to starch degradation. Because the two cultivars exhibited remarkable varietal differences in the pattern of non-structural carbohydrate partitioning, our findings propose that the observed difference in grain-filling ability originated from turgor-associated regulation of starch phosphorylation in stem parenchyma cells. Further understanding of the molecular mechanism of turgor-regulation may provide a new selection criterion for breaking the yield barriers in crop production. PMID:28727805

Lindemann histograms as a new method to analyse nano-patterns and phases

NASA Astrophysics Data System (ADS)

Makey, Ghaith; Ilday, Serim; Tokel, Onur; Ibrahim, Muhamet; Yavuz, Ozgun; Pavlov, Ihor; Gulseren, Oguz; Ilday, Omer

The detection, observation, and analysis of material phases and atomistic patterns are of great importance for understanding systems exhibiting both equilibrium and far-from-equilibrium dynamics. As such, there is intense research on phase transitions and pattern dynamics in soft matter, statistical and nonlinear physics, and polymer physics. In order to identify phases and nano-patterns, the pair correlation function is commonly used. However, this approach is limited in terms of recognizing competing patterns in dynamic systems, and lacks visualisation capabilities. In order to solve these limitations, we introduce Lindemann histogram quantification as an alternative method to analyse solid, liquid, and gas phases, along with hexagonal, square, and amorphous nano-pattern symmetries. We show that the proposed approach based on Lindemann parameter calculated per particle maps local number densities to material phase or particles pattern. We apply the Lindemann histogram method on dynamical colloidal self-assembly experimental data and identify competing patterns.

With the future behind them: convergent evidence from aymara language and gesture in the crosslinguistic comparison of spatial construals of time.

PubMed

Núñez, Rafael E; Sweetser, Eve

2006-05-06

Cognitive research on metaphoric concepts of time has focused on differences between moving Ego and moving time models, but even more basic is the contrast between Ego- and temporal-reference-point models. Dynamic models appear to be quasi-universal cross-culturally, as does the generalization that in Ego-reference-point models, FUTURE IS IN FRONT OF EGO and PAST IS IN BACK OF EGO. The Aymara language instead has a major static model of time wherein FUTURE IS BEHIND EGO and PAST IS IN FRONT OF EGO; linguistic and gestural data give strong confirmation of this unusual culture-specific cognitive pattern. Gestural data provide crucial information unavailable to purely linguistic analysis, suggesting that when investigating conceptual systems both forms of expression should be analyzed complementarily. Important issues in embodied cognition are raised: how fully shared are bodily grounded motivations for universal cognitive patterns, what makes a rare pattern emerge, and what are the cultural entailments of such patterns? 2006 Lawrence Erlbaum Associates, Inc.

Pattern Formation and Strong Nonlinear Interactions in Exciton-Polariton Condensates

NASA Astrophysics Data System (ADS)

Ge, Li; Nersisyan, Ani; Oztop, Baris; Tureci, Hakan

2014-03-01

Exciton-polaritons generated by light-induced potentials can spontaneously condense into macroscopic quantum states that display nontrivial spatial and temporal density modulation. While these patterns and their dynamics can be reproduced through the solution of the generalized Gross-Pitaevskii equation, a predictive theory of their thresholds, oscillation frequencies, and multi-pattern interactions has so far been lacking. Here we represent such an approach based on current-carrying quasi-modes of the non-Hermitian potential induced by the pump. The presented theory allows us to capture the patterns formed in the steady-state directly and account for nonlinearities exactly. We find a simple but powerful expression for thresholds of condensation and the associated frequencies of oscillations, quantifying the contribution of particle formation, leakage, and interactions. We also show that the evolution of the condensate with increasing pump strength is strongly geometry dependent and can display contrasting features such as enhancement or reduction of the spatial localization of the condensate. We acknowledge support by DARPA under Grant No. N66001-11-1-4162 and NSF under CAREER Grant No. DMR-1151810.

Temporal gene expression profiling of the rat knee joint capsule during immobilization-induced joint contractures.

PubMed

Wong, Kayleigh; Sun, Fangui; Trudel, Guy; Sebastiani, Paola; Laneuville, Odette

2015-05-26

Contractures of the knee joint cause disability and handicap. Recovering range of motion is recognized by arthritic patients as their preference for improved health outcome secondary only to pain management. Clinical and experimental studies provide evidence that the posterior knee capsule prevents the knee from achieving full extension. This study was undertaken to investigate the dynamic changes of the joint capsule transcriptome during the progression of knee joint contractures induced by immobilization. We performed a microarray analysis of genes expressed in the posterior knee joint capsule following induction of a flexion contracture by rigidly immobilizing the rat knee joint over a time-course of 16 weeks. Fold changes of expression values were measured and co-expressed genes were identified by clustering based on time-series analysis. Genes associated with immobilization were further analyzed to reveal pathways and biological significance and validated by immunohistochemistry on sagittal sections of knee joints. Changes in expression with a minimum of 1.5 fold changes were dominated by a decrease in expression for 7732 probe sets occurring at week 8 while the expression of 2251 probe sets increased. Clusters of genes with similar profiles of expression included a total of 162 genes displaying at least a 2 fold change compared to week 1. Functional analysis revealed ontology categories corresponding to triglyceride metabolism, extracellular matrix and muscle contraction. The altered expression of selected genes involved in the triglyceride biosynthesis pathway; AGPAT-9, and of the genes P4HB and HSP47, both involved in collagen synthesis, was confirmed by immunohistochemistry. Gene expression in the knee joint capsule was sensitive to joint immobility and provided insights into molecular mechanisms relevant to the pathophysiology of knee flexion contractures. Capsule responses to immobilization was dynamic and characterized by modulation of at least three reaction pathways; down regulation of triglyceride biosynthesis, alteration of extracellular matrix degradation and muscle contraction gene expression. The posterior knee capsule may deploy tissue-specific patterns of mRNA regulatory responses to immobilization. The identification of altered expression of genes and biochemical pathways in the joint capsule provides potential targets for the therapy of knee flexion contractures.

The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer

PubMed Central

Munkley, Jennifer; Oltean, Sebastian; Vodák, Daniel; Wilson, Brian T.; Livermore, Karen E.; Zhou, Yan; Star, Eleanor; Floros, Vasileios I.; Johannessen, Bjarne; Knight, Bridget; McCullagh, Paul; McGrath, John; Crundwell, Malcolm; Skotheim, Rolf I.; Robson, Craig N.; Leung, Hing Y.; Harries, Lorna W.; Rajan, Prabhakar; Mills, Ian G.; Elliott, David J.

2015-01-01

Patterns of glycosylation are important in cancer, but the molecular mechanisms that drive changes are often poorly understood. The androgen receptor drives prostate cancer (PCa) development and progression to lethal metastatic castration-resistant disease. Here we used RNA-Seq coupled with bioinformatic analyses of androgen-receptor (AR) binding sites and clinical PCa expression array data to identify ST6GalNAc1 as a direct and rapidly activated target gene of the AR in PCa cells. ST6GalNAc1 encodes a sialytransferase that catalyses formation of the cancer-associated sialyl-Tn antigen (sTn), which we find is also induced by androgen exposure. Androgens induce expression of a novel splice variant of the ST6GalNAc1 protein in PCa cells. This splice variant encodes a shorter protein isoform that is still fully functional as a sialyltransferase and able to induce expression of the sTn-antigen. Surprisingly, given its high expression in tumours, stable expression of ST6GalNAc1 in PCa cells reduced formation of stable tumours in mice, reduced cell adhesion and induced a switch towards a more mesenchymal-like cell phenotype in vitro. ST6GalNAc1 has a dynamic expression pattern in clinical datasets, being significantly up-regulated in primary prostate carcinoma but relatively down-regulated in established metastatic tissue. ST6GalNAc1 is frequently upregulated concurrently with another important glycosylation enzyme GCNT1 previously associated with prostate cancer progression and implicated in Sialyl Lewis X antigen synthesis. Together our data establishes an androgen-dependent mechanism for sTn antigen expression in PCa, and are consistent with a general role for the androgen receptor in driving important coordinate changes to the glycoproteome during PCa progression. PMID:26452038

Function and Evolution of DNA Methylation in Nasonia vitripennis

PubMed Central

Wang, Xu; Wheeler, David; Avery, Amanda; Rago, Alfredo; Choi, Jeong-Hyeon; Colbourne, John K.; Clark, Andrew G.; Werren, John H.

2013-01-01

The parasitoid wasp Nasonia vitripennis is an emerging genetic model for functional analysis of DNA methylation. Here, we characterize genome-wide methylation at a base-pair resolution, and compare these results to gene expression across five developmental stages and to methylation patterns reported in other insects. An accurate assessment of DNA methylation across the genome is accomplished using bisulfite sequencing of adult females from a highly inbred line. One-third of genes show extensive methylation over the gene body, yet methylated DNA is not found in non-coding regions and rarely in transposons. Methylated genes occur in small clusters across the genome. Methylation demarcates exon-intron boundaries, with elevated levels over exons, primarily in the 5′ regions of genes. It is also elevated near the sites of translational initiation and termination, with reduced levels in 5′ and 3′ UTRs. Methylated genes have higher median expression levels and lower expression variation across development stages than non-methylated genes. There is no difference in frequency of differential splicing between methylated and non-methylated genes, and as yet no established role for methylation in regulating alternative splicing in Nasonia. Phylogenetic comparisons indicate that many genes maintain methylation status across long evolutionary time scales. Nasonia methylated genes are more likely to be conserved in insects, but even those that are not conserved show broader expression across development than comparable non-methylated genes. Finally, examination of duplicated genes shows that those paralogs that have lost methylation in the Nasonia lineage following gene duplication evolve more rapidly, show decreased median expression levels, and increased specialization in expression across development. Methylation of Nasonia genes signals constitutive transcription across developmental stages, whereas non-methylated genes show more dynamic developmental expression patterns. We speculate that loss of methylation may result in increased developmental specialization in evolution and acquisition of methylation may lead to broader constitutive expression. PMID:24130511

EphrinA5 protein distribution in the developing mouse brain

PubMed Central

2010-01-01

Background EphrinA5 is one of the best-studied members of the Eph-ephrin family of guidance molecules, known to be involved in brain developmental processes. Using in situ hybridization, ephrinA5 mRNA expression has been detected in the retinotectal, the thalamocortical, and the olfactory systems; however, no study focused on the distribution of the protein. Considering that this membrane-anchored molecule may act far from the neuron soma expressing the transcript, it is of a crucial interest to localize ephrinA5 protein to better understand its function. Results Using immunohistochemistry, we found that ephrinA5 protein is highly expressed in the developing mouse brain from E12.5 to E16.5. The olfactory bulb, the cortex, the striatum, the thalamus, and the colliculi showed high intensity of labelling, suggesting its implication in topographic mapping of olfactory, retinocollicular, thalamocortical, corticothalamic and mesostriatal systems. In the olfactory nerve, we found an early ephrinA5 protein expression at E12.5 suggesting its implication in the guidance of primary olfactory neurons into the olfactory bulb. In the thalamus, we detected a dynamic graduated protein expression, suggesting its role in the corticothalamic patterning, whereas ephrinA5 protein expression in the target region of mesencephalic dopaminergic neurones indicated its involvement in the mesostriatal topographic mapping. Following E16.5, the signal faded gradually and was barely detectable at P0, suggesting a main role for ephrinA5 in primary molecular events in topographic map formation. Conclusion Our work shows that ephrinA5 protein is expressed in restrictive regions of the developing mouse brain. This expression pattern points out the potential sites of action of this molecule in the olfactory, retinotectal, thalamocortical, corticothalamic and mesostriatal systems, during development. This study is essential to better understand the role of ephrinA5 during developmental topographic mapping of connections and to further characterise the mechanisms involved in pathway restoration following cell transplantation in the damaged brain. PMID:20738842

Conserved and divergent expression patterns of markers of axial development in the laboratory opossum, Monodelphis domestica.

PubMed

Yoshida, Michio; Kajikawa, Eriko; Yamamoto, Daisuke; Kurokawa, Daisuke; Yonemura, Shigenobu; Kobayashi, Kensaku; Kiyonari, Hiroshi; Aizawa, Shinichi

2016-12-01

Previous comparative studies suggest that the requirement for Nodal in epiblast and hypoblast development is unique to mammalians. Expression of anterior visceral endoderm (AVE) genes in the visceral endoderm and of their orthologs in the hypoblast may be unique to mammalians and avians, and is absent in the reptilian hypoblast. Axis formation in reptiles is signaled by the formation of the posterior marginal epiblast (PME), which expresses a series of primitive streak genes. To assess the phylogenetic origin of Nodal and AVE gene expression and axis formation in amniotes, we examined marker gene expression in gray short-tailed opossum, a metatherian. Nodal was expressed in neither epiblast nor hypoblast of opossum embryos. No AVE genes were expressed in the opossum hypoblast. Attainment of polarity in the embryonic disk was signaled by Nodal, Wnt3a, Fgf8, and Bra expression in the PME at 8.5 days post-coitus. Nodal expression in epiblast or hypoblast may be unique to eutherians. AVE gene expression in visceral endoderm and hypoblast may have been independently acquired in eutherian and avian lineages. PME formation appears to be the event that signals axis formation in reptilian and metatherian embryos, and thus may be an ancestral characteristic of basal amniotes. Developmental Dynamics 245:1176-1188, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Spontaneous Facial Mimicry in Response to Dynamic Facial Expressions

ERIC Educational Resources Information Center

Sato, Wataru; Yoshikawa, Sakiko

2007-01-01

Based on previous neuroscientific evidence indicating activation of the mirror neuron system in response to dynamic facial actions, we hypothesized that facial mimicry would occur while subjects viewed dynamic facial expressions. To test this hypothesis, dynamic/static facial expressions of anger/happiness were presented using computer-morphing…

Isoform-level gene expression patterns in single-cell RNA-sequencing data.

PubMed

Vu, Trung Nghia; Wills, Quin F; Kalari, Krishna R; Niu, Nifang; Wang, Liewei; Pawitan, Yudi; Rantalainen, Mattias

2018-02-27

RNA sequencing of single cells enables characterization of transcriptional heterogeneity in seemingly homogeneous cell populations. Single-cell sequencing has been applied in a wide range of researches fields. However, few studies have focus on characterization of isoform-level expression patterns at the single-cell level. In this study we propose and apply a novel method, ISOform-Patterns (ISOP), based on mixture modeling, to characterize the expression patterns of isoform pairs from the same gene in single-cell isoform-level expression data. We define six principal patterns of isoform expression relationships and describe a method for differential-pattern analysis. We demonstrate ISOP through analysis of single-cell RNA-sequencing data from a breast cancer cell line, with replication in three independent datasets. We assigned the pattern types to each of 16,562 isoform-pairs from 4,929 genes. Among those, 26% of the discovered patterns were significant (p<0.05), while remaining patterns are possibly effects of transcriptional bursting, drop-out and stochastic biological heterogeneity. Furthermore, 32% of genes discovered through differential-pattern analysis were not detected by differential-expression analysis. The effect of drop-out events, mean expression level, and properties of the expression distribution on the performances of ISOP were also investigated through simulated datasets. To conclude, ISOP provides a novel approach for characterization of isoformlevel preference, commitment and heterogeneity in single-cell RNA-sequencing data. The ISOP method has been implemented as a R package and is available at https://github.com/nghiavtr/ISOP under a GPL-3 license. mattias.rantalainen@ki.se. Supplementary data are available at Bioinformatics online.

FoxP2 expression in the cerebellum and inferior olive: development of the transverse stripe-shaped expression pattern in the mouse cerebellar cortex.

PubMed

Fujita, Hirofumi; Sugihara, Izumi

2012-02-15

Many molecules are expressed heterogeneously in subpopulations of cerebellar Purkinje cells (PCs) and inferior olive (IO) neurons during development or in adulthood. These expression patterns are often organized in longitudinal stripes in the cerebellar cortex, which may be related to functional compartmentalization. FoxP2, a transcription factor, is expressed in PCs and IO neurons, but the details of its expression pattern remain unclear. Here we examined FoxP2 expression patterns systematically by immunostaining serial sections of the hindbrain from embryonic day 14.5 to adulthood in mice. FoxP2 was highly expressed in virtually all PCs at and before postnatal day 6 (P6), except for those in the flocculus and small parts of the nodulus (vermal lobule X), where FoxP2 expression was moderate or absent. After P6, FoxP2 expression gradually diminished in PCs in some areas. In adults, FoxP2 was expressed, less intensely than in earlier stages, in subsets of PCs that were mostly arranged transversely along the folial apices. In contrast, FoxP2 was expressed intensely in most IO neurons during development and in adulthood. FoxP2 was also expressed in a small population of neurons in the cerebellar nuclei. FoxP2 expression in adult rats and chicks was generally comparable to that in adult mice, suggesting evolutionary conservation of the expression pattern. Thus, the FoxP2 expression pattern reflects new transverse compartmentalization in the adult cerebellar cortex, although its functional significance remains unclear. Copyright © 2011 Wiley-Liss, Inc.

Gene expression underlying adaptive variation in Heliconius wing patterns: non-modular regulation of overlapping cinnabar and vermilion prepatterns.

PubMed

Reed, Robert D; McMillan, W Owen; Nagy, Lisa M

2008-01-07

Geographical variation in the mimetic wing patterns of the butterfly Heliconius erato is a textbook example of adaptive polymorphism; however, little is known about how this variation is controlled developmentally. Using microarrays and qPCR, we identified and compared expression of candidate genes potentially involved with a red/yellow forewing band polymorphism in H. erato. We found that transcripts encoding the pigment synthesis enzymes cinnabar and vermilion showed pattern- and polymorphism-related expression patterns, respectively. cinnabar expression was associated with the forewing band regardless of pigment colour, providing the first gene expression pattern known to be correlated with a major Heliconius colour pattern. In contrast, vermilion expression changed spatially over time in red-banded butterflies, but was not expressed at detectable levels in yellow-banded butterflies, suggesting that regulation of this gene may be involved with the red/yellow polymorphism. Furthermore, we found that the yellow pigment, 3-hydroxykynurenine, is incorporated into wing scales from the haemolymph rather than being synthesized in situ. We propose that some aspects of Heliconius colour patterns are determined by spatio-temporal overlap of pigment gene transcription prepatterns and speculate that evolutionary changes in vermilion regulation may in part underlie an adaptive colour pattern polymorphism.

Spatiotemporal ecohydrological patterns and processes in temperate uplands: linking field observations and model results

NASA Astrophysics Data System (ADS)

Dodd, N. H.; Baird, A. J.; Wainwright, J.; Dunn, S. M.

2011-12-01

There are obvious surface expressions - in terms of vegetation patterning - of ecohydrological feedbacks on dryland and peatland hillslopes. Much less is known about subsurface ecohydrological patterns, and whether or not they 'map onto' surface patterns. Likewise, few attempts have been made to investigate how such ecohydrological patterns affect whole-hillslope hydrological behaviour or how widespread they are in non-dryland and non-peatland hillslopes. In this study we investigate surface and near- surface patterning in temperate hillslopes, which to date have been the focus of much hydrological work but little ecohydrological work. In particular, we consider the extent to which the direct and the indirect effects of past and present plant assemblages on local and whole-hillslope soil moisture conditions may contribute to patterning. We have conducted a field study of two temperate upland hillslopes in Northern Scotland, UK, on one of which human intervention plays a major part in shaping the landscape. Repeat measurements have been made of near- surface soil-moisture content, taken at lag distances of 0.25 m to 20 m, under different antecedent hydrological conditions together with characterisation of plant assemblages at the same points through both ground-based vegetation surveys of 1 m × 1 m plots and kite aerial photography (KAP) of > 20 m2 plots. Results from this have indicated that changes in ecohydrological patterns can occur over small spatial scales (< 1 m2) and short time scales (< 1 day). Comparison of values of near-surface soil moisture content with topographic wetness indices, calculated using 1 -m resolution topographic data collected in the field, has highlighted that topography does not explain all of the spatial variation in soil moisture content at this scale. KAP images allowed detection of vegetation patterns not obvious from the ground. Comparison of KAP images and historic aerial photographs has highlighted the persistence of vegetation patterns over time at both sites, and that the current structure of the landscape is clearly related to current and past vegetation management practices. Evidence of sustained patterning under relatively steady environmental conditions has prompted us to consider how internal system dynamics such as competition and facilitation between different plant assemblages, and persistence of ecological memory at a range of timescales may lead to a range of ecohydrological behaviours at the scale of whole hillslopes. To help conceptualize ways in which patterning may arise, we have built a two-dimensional cellular automata-type model in which local interactions between biotic and abiotic components have the potential to lead to emergence of larger-scale patterns within the model landscape. Results from the field study have been used to gauge how well temperate hillslope ecohydrological dynamics are represented in our model, and to check that local neighbourhood patterns in the model outputs resemble real-world patterning. Key words: temperate upland ecohydrology, plant assemblage dynamics, ecological memory, kite aerial photography, cellular automata.

GEsture: an online hand-drawing tool for gene expression pattern search.

PubMed

Wang, Chunyan; Xu, Yiqing; Wang, Xuelin; Zhang, Li; Wei, Suyun; Ye, Qiaolin; Zhu, Youxiang; Yin, Hengfu; Nainwal, Manoj; Tanon-Reyes, Luis; Cheng, Feng; Yin, Tongming; Ye, Ning

2018-01-01

Gene expression profiling data provide useful information for the investigation of biological function and process. However, identifying a specific expression pattern from extensive time series gene expression data is not an easy task. Clustering, a popular method, is often used to classify similar expression genes, however, genes with a 'desirable' or 'user-defined' pattern cannot be efficiently detected by clustering methods. To address these limitations, we developed an online tool called GEsture. Users can draw, or graph a curve using a mouse instead of inputting abstract parameters of clustering methods. GEsture explores genes showing similar, opposite and time-delay expression patterns with a gene expression curve as input from time series datasets. We presented three examples that illustrate the capacity of GEsture in gene hunting while following users' requirements. GEsture also provides visualization tools (such as expression pattern figure, heat map and correlation network) to display the searching results. The result outputs may provide useful information for researchers to understand the targets, function and biological processes of the involved genes.

Expression of the Norrie disease gene (Ndp) in developing and adult mouse eye, ear, and brain.

PubMed

Ye, Xin; Smallwood, Philip; Nathans, Jeremy

2011-01-01

The Norrie disease gene (Ndp) codes for a secreted protein, Norrin, that activates canonical Wnt signaling by binding to its receptor, Frizzled-4. This signaling system is required for normal vascular development in the retina and for vascular survival in the cochlea. In mammals, the pattern of Ndp expression beyond the retina is poorly defined due to the low abundance of Norrin mRNA and protein. Here, we characterize Ndp expression during mouse development by studying a knock-in mouse that carries the coding sequence of human placental alkaline phosphatase (AP) inserted at the Ndp locus (Ndp(AP)). In the CNS, Ndp(AP) expression is apparent by E10.5 and is dynamic and complex. The anatomically delimited regions of Ndp(AP) expression observed prenatally in the CNS are replaced postnatally by widespread expression in astrocytes in the forebrain and midbrain, Bergman glia in the cerebellum, and Müller glia in the retina. In the developing and adult cochlea, Ndp(AP) expression is closely associated with two densely vascularized regions, the stria vascularis and a capillary plexus between the organ of Corti and the spiral ganglion. These observations suggest the possibility that Norrin may have developmental and/or homeostatic functions beyond the retina and cochlea. Copyright © 2010 Elsevier B.V. All rights reserved.

Expression of the Norrie disease gene (Ndp) in developing and adult mouse eye, ear, and brain

PubMed Central

Ye, Xin; Smallwood, Philip; Nathans, Jeremy

2011-01-01

The Norrie disease gene (Ndp) codes for a secreted protein, Norrin, that activates canonical Wnt signaling by binding to its receptor, Frizzled-4. This signaling system is required for normal vascular development in the retina and for vascular survival in the cochlea. In mammals, the pattern of Ndp expression beyond the retina is poorly defined due to the low abundance of Norrin mRNA and protein. Here we characterize Ndp expression during mouse development by studying a knock-in mouse that carries the coding sequence of human placental alkaline phosphatase (AP) inserted at the Ndp locus (NdpAP). In the CNS, NdpAP expression is apparent by E10.5 and is dynamic and complex. The anatomically delimited regions of NdpAP expression observed prenatally in the CNS are replaced postnatally by widespread expression in astrocytes in the forebrain and midbrain, Bergman glia in the cerebellum, and Müller glia in the retina. In the developing and adult cochlea, NdpAP expression is closely associated with two densely vascularized regions, the stria vascularis and a capillary plexus between the organ of Corti and the spiral ganglion. These observations suggest the possibility that Norrin may have developmental and/or homeostatic functions beyond the retina and cochlea. PMID:21055480

Patterns of Stochastic Behavior in Dynamically Unstable High-Dimensional Biochemical Networks

PubMed Central

Rosenfeld, Simon

2009-01-01

The question of dynamical stability and stochastic behavior of large biochemical networks is discussed. It is argued that stringent conditions of asymptotic stability have very little chance to materialize in a multidimensional system described by the differential equations of chemical kinetics. The reason is that the criteria of asymptotic stability (Routh-Hurwitz, Lyapunov criteria, Feinberg’s Deficiency Zero theorem) would impose the limitations of very high algebraic order on the kinetic rates and stoichiometric coefficients, and there are no natural laws that would guarantee their unconditional validity. Highly nonlinear, dynamically unstable systems, however, are not necessarily doomed to collapse, as a simple Jacobian analysis would suggest. It is possible that their dynamics may assume the form of pseudo-random fluctuations quite similar to a shot noise, and, therefore, their behavior may be described in terms of Langevin and Fokker-Plank equations. We have shown by simulation that the resulting pseudo-stochastic processes obey the heavy-tailed Generalized Pareto Distribution with temporal sequence of pulses forming the set of constituent-specific Poisson processes. Being applied to intracellular dynamics, these properties are naturally associated with burstiness, a well documented phenomenon in the biology of gene expression. PMID:19838330

Segmentation of the zebrafish axial skeleton relies on notochord sheath cells and not on the segmentation clock.

PubMed

Lleras Forero, Laura; Narayanan, Rachna; Huitema, Leonie Fa; VanBergen, Maaike; Apschner, Alexander; Peterson-Maduro, Josi; Logister, Ive; Valentin, Guillaume; Morelli, Luis G; Oates, Andrew C; Schulte-Merker, Stefan

2018-04-06

Segmentation of the axial skeleton in amniotes depends on the segmentation clock, which patterns the paraxial mesoderm and the sclerotome. While the segmentation clock clearly operates in teleosts, the role of the sclerotome in establishing the axial skeleton is unclear. We severely disrupt zebrafish paraxial segmentation, yet observe a largely normal segmentation process of the chordacentra. We demonstrate that axial entpd5+ notochord sheath cells are responsible for chordacentrum mineralization, and serve as a marker for axial segmentation. While autonomous within the notochord sheath, entpd5 expression and centrum formation show some plasticity and can respond to myotome pattern. These observations reveal for the first time the dynamics of notochord segmentation in a teleost, and are consistent with an autonomous patterning mechanism that is influenced, but not determined by adjacent paraxial mesoderm. This behavior is not consistent with a clock-type mechanism in the notochord. © 2018, Lleras Forero et al.

Emotional facial activation induced by unconsciously perceived dynamic facial expressions.

PubMed

Kaiser, Jakob; Davey, Graham C L; Parkhouse, Thomas; Meeres, Jennifer; Scott, Ryan B

2016-12-01

Do facial expressions of emotion influence us when not consciously perceived? Methods to investigate this question have typically relied on brief presentation of static images. In contrast, real facial expressions are dynamic and unfold over several seconds. Recent studies demonstrate that gaze contingent crowding (GCC) can block awareness of dynamic expressions while still inducing behavioural priming effects. The current experiment tested for the first time whether dynamic facial expressions presented using this method can induce unconscious facial activation. Videos of dynamic happy and angry expressions were presented outside participants' conscious awareness while EMG measurements captured activation of the zygomaticus major (active when smiling) and the corrugator supercilii (active when frowning). Forced-choice classification of expressions confirmed they were not consciously perceived, while EMG revealed significant differential activation of facial muscles consistent with the expressions presented. This successful demonstration opens new avenues for research examining the unconscious emotional influences of facial expressions. Copyright © 2016 Elsevier B.V. All rights reserved.

Dynamic facial expression recognition based on geometric and texture features

NASA Astrophysics Data System (ADS)

Li, Ming; Wang, Zengfu

2018-04-01

Recently, dynamic facial expression recognition in videos has attracted growing attention. In this paper, we propose a novel dynamic facial expression recognition method by using geometric and texture features. In our system, the facial landmark movements and texture variations upon pairwise images are used to perform the dynamic facial expression recognition tasks. For one facial expression sequence, pairwise images are created between the first frame and each of its subsequent frames. Integration of both geometric and texture features further enhances the representation of the facial expressions. Finally, Support Vector Machine is used for facial expression recognition. Experiments conducted on the extended Cohn-Kanade database show that our proposed method can achieve a competitive performance with other methods.

Cocaine dynamically regulates heterochromatin and repetitive element unsilencing in nucleus accumbens.

PubMed

Maze, Ian; Feng, Jian; Wilkinson, Matthew B; Sun, HaoSheng; Shen, Li; Nestler, Eric J

2011-02-15

Repeated cocaine exposure induces persistent alterations in genome-wide transcriptional regulatory networks, chromatin remodeling activity and, ultimately, gene expression profiles in the brain's reward circuitry. Virtually all previous investigations have centered on drug-mediated effects occurring throughout active euchromatic regions of the genome, with very little known concerning the impact of cocaine exposure on the regulation and maintenance of heterochromatin in adult brain. Here, we report that cocaine dramatically and dynamically alters heterochromatic histone H3 lysine 9 trimethylation (H3K9me3) in the nucleus accumbens (NAc), a key brain reward region. Furthermore, we demonstrate that repeated cocaine exposure causes persistent decreases in heterochromatization in this brain region, suggesting a potential role for heterochromatic regulation in the long-term actions of cocaine. To identify precise genomic loci affected by these alterations, chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-Seq) was performed on NAc. ChIP-Seq analyses confirmed the existence of the H3K9me3 mark mainly within intergenic regions of the genome and identified specific patterns of cocaine-induced H3K9me3 regulation at repetitive genomic sequences. Cocaine-mediated decreases in H3K9me3 enrichment at specific genomic repeats [e.g., long interspersed nuclear element (LINE)-1 repeats] were further confirmed by the increased expression of LINE-1 retrotransposon-associated repetitive elements in NAc. Such increases likely reflect global patterns of genomic destabilization in this brain region after repeated cocaine administration and open the door for future investigations into the epigenetic and genetic basis of drug addiction.

The dynamic pattern of PLIN3 in pig oocytes and cumulus cells during in vitro maturation.

PubMed

Xu, Mingzhu; Zeng, Yaqiong; Chi, Daming; Si, Linan; Qu, Xiao; Li, Juan

2018-02-01

Lipid droplets (LDs) are the main energy resource for porcine preimplantation embryonic development. PLIN3 has been implicated in LD formation and regulation. Therefore, this study aimed to detect the dynamic pattern of PLIN3 in pig oocytes and cumulus cells (CC) during in vitro maturation (IVM), and to determine the relationship between PLIN3 and LD content. IVM with cumulus-enclosed oocytes (CEO), cumulus-denuded oocytes (DO) and the CCs denuded from the corresponding oocytes (DCC) was performed in porcine follicular fluid (PFF) or PFF-free optimized medium. DO and the DCC were cultured together under the same conditions as described above, while the DO was named DTO and the DCC was named DTCC in this group. Firstly, our results revealed LDs distributed widely in oocytes and CC, while the PLIN3 protein coated these LDs and spread out ubiquitously in the cytoplasm. Secondly, not only the mRNA level but also at protein level of PLIN3 in immature naked oocytes (IO) was higher than that in matured CEO, DO and DTO. Although PLIN3 was expressed at lower levels in CC from immature oocytes (ICC), the protein level of PLIN3 was comparably higher in the ECC and DCC groups. The triglyceride (TG) content in CEO and DO was significantly less abundant compared with that in IO. Therefore, our results indicated that co-culturing of oocytes and CC might affect PLIN3 expression levels in CC but not in oocytes. Lipid accumulation in pig oocytes during maturation might be affected by PLIN3 cross-talk between oocytes and CC.

Localization of Brachyury (T) in embryonic and extraembryonic tissues during mouse gastrulation.

PubMed

Inman, Kimberly E; Downs, Karen M

2006-10-01

T-box gene family members have important roles during murine embryogenesis, gastrulation, and organogenesis. Although relatively little is known about how T-box genes are regulated, published gene expression studies have revealed dynamic and specific patterns in both embryonic and extraembryonic tissues of the mouse conceptus. Mutant alleles of the T-box gene Brachyury (T) have identified roles in formation of mesoderm and its derivatives, such as somites and the allantois. However, given the cell autonomous nature of T gene activity and conflicting results of gene expression studies, it has been difficult to attribute a primary function to T in normal allantoic development. We report localization of T protein by sectional immunohistochemistry in both embryonic and extraembryonic tissues during mouse gastrulation, emphasizing T localization within the allantois. T was detected in all previously reported sites within the conceptus, including the primitive streak and its derivatives, nascent embryonic mesoderm, the node and notochord, as well as notochord-associated endoderm and posterior neurectoderm. In addition, we have clarified T within the allantois, where it was first detected in the proximal midline of the late allantoic bud (approximately 7.5 days postcoitum, dpc) and persisted within an expanded midline domain until 6-somite pairs (s; approximately 8.5 dpc). Lastly, we have discovered several novel T sites, including the developing heart, visceral endoderm, extraembryonic ectoderm, and its derivative, chorionic ectoderm. Together, these data provide a unified picture of T in the mammalian conceptus, and demonstrate T's presence in unrelated cell types and tissues in highly dynamic spatiotemporal patterns in both embryonic and extraembryonic tissues.

Tracking Spatial and Temporal Changes in Microbial Metabolic Potential and Gene Expression Patterns Across Geochemical Gradients at Axial Seamount

NASA Astrophysics Data System (ADS)

Fortunato, C. S.; Butterfield, D. A.; Larson, B.; Algar, C. K.; Huber, J. A.

2016-12-01

Microbial communities living both near and within the subseafloor are important players in the biogeochemical cycling of the deep ocean. To better understand the metabolic and gene expression patterns of these understudied communities, we collected low-temperature diffuse fluids for metagenomic, metatranscriptomic, and geochemical analyses from Axial Seamount, an active submarine volcano off the coast of Oregon, USA in 2013-2015. In April of 2015 Axial Seamount erupted along its north rift, five months before the 2015 samples were collected. This study thus provides both spatial and temporal analysis of subseafloor microbial communities pre and post eruption. The time series for this study focused on three vents at the south end of the caldera: Anemone, Marker 33, and Marker 113. Chemistry data shows that at each vent there are different geochemical conditions and thus a potentially different microbial metabolic profile. Anemone has the most oxidizing conditions and the highest abundance and expression of sulfur oxidation genes, attributed to both SUP05 and Epsilonproteobacteria. The most reducing conditions were observed at Marker 113, the site with the lowest oxygen concentration and where methanogenesis was the dominant metabolism, with 18.5% of all annotated transcripts attributed to methanogenesis. Although individual vents were metabolically distinct, there was very little variation in the overall taxonomic and metabolic profiles of each vent across years, even after the 2015 eruption. A diffuse fluid sample taken from the North Rift Zone post eruption showed similar community taxonomy to both Anemone and Marker 33; analyses of the metabolic potential and gene expression at this site is ongoing and will act as a comparison between the communities of the time series vents and those that were closer to the eruption site. Together, these chemical and `omic datasets reveal a dynamic microbial community at each vent, taxonomically diverse and involved in a wide array of biogeochemical transformations. Results are being used to model the functional dynamics and fluxes of vent communities to more closely link microbiological productivity at hydrothermal systems to deep-sea biogeochemical processes and will be also used to inform future projects using instrumentation on the cabled array at Axial Seamount.

What determines blood vessel structure? Genetic prespecification vs. hemodynamics.

PubMed

Jones, Elizabeth A V; le Noble, Ferdinand; Eichmann, Anne

2006-12-01

Vascular network remodeling, angiogenesis, and arteriogenesis play an important role in the pathophysiology of ischemic cardiovascular diseases and cancer. Based on recent studies of vascular network development in the embryo, several novel aspects to angiogenesis have been identified as crucial to generate a functional vascular network. These aspects include specification of arterial and venous identity in vessels and network patterning. In early embryogenesis, vessel identity and positioning are genetically hardwired and involve neural guidance genes expressed in the vascular system. We demonstrated that, during later stages of embryogenesis, blood flow plays a crucial role in regulating vessel identity and network remodeling. The flow-evoked remodeling process is dynamic and involves a high degree of vessel plasticity. The open question in the field is how genetically predetermined processes in vessel identity and patterning balance with the contribution of blood flow in shaping a functional vascular architecture. Although blood flow is essential, it remains unclear to what extent flow is able to act on the developing cardiovascular system. There is significant evidence that mechanical forces created by flowing blood are biologically active within the embryo and that the level of mechanical forces and the type of flow patterns present in the embryo are able to affect gene expression. Here, we highlight the pivotal role for blood flow and physical forces in shaping the cardiovascular system.

RILES, a novel method for temporal analysis of the in vivo regulation of miRNA expression

PubMed Central

Ezzine, Safia; Vassaux, Georges; Pitard, Bruno; Barteau, Benoit; Malinge, Jean-Marc; Midoux, Patrick; Pichon, Chantal; Baril, Patrick

2013-01-01

Novel methods are required to investigate the complexity of microRNA (miRNA) biology and particularly their dynamic regulation under physiopathological conditions. Herein, a novel plasmid-based RNAi-Inducible Luciferase Expression System (RILES) was engineered to monitor the activity of endogenous RNAi machinery. When RILES is transfected in a target cell, the miRNA of interest suppresses the expression of a transcriptional repressor and consequently switch-ON the expression of the luciferase reporter gene. Hence, miRNA expression in cells is signed by the emission of bioluminescence signals that can be monitored using standard bioluminescence equipment. We validated this approach by monitoring in mice the expression of myomiRs-133, −206 and −1 in skeletal muscles and miRNA-122 in liver. Bioluminescence experiments demonstrated robust qualitative and quantitative data that correlate with the miRNA expression pattern detected by quantitative RT-PCR (qPCR). We further demonstrated that the regulation of miRNA-206 expression during the development of muscular atrophy is individual-dependent, time-regulated and more complex than the information generated by qPCR. As RILES is simple and versatile, we believe that this methodology will contribute to a better understanding of miRNA biology and could serve as a rationale for the development of a novel generation of regulatable gene expression systems with potential therapeutic applications. PMID:24013565

RILES, a novel method for temporal analysis of the in vivo regulation of miRNA expression.

PubMed

Ezzine, Safia; Vassaux, Georges; Pitard, Bruno; Barteau, Benoit; Malinge, Jean-Marc; Midoux, Patrick; Pichon, Chantal; Baril, Patrick

2013-11-01

Novel methods are required to investigate the complexity of microRNA (miRNA) biology and particularly their dynamic regulation under physiopathological conditions. Herein, a novel plasmid-based RNAi-Inducible Luciferase Expression System (RILES) was engineered to monitor the activity of endogenous RNAi machinery. When RILES is transfected in a target cell, the miRNA of interest suppresses the expression of a transcriptional repressor and consequently switch-ON the expression of the luciferase reporter gene. Hence, miRNA expression in cells is signed by the emission of bioluminescence signals that can be monitored using standard bioluminescence equipment. We validated this approach by monitoring in mice the expression of myomiRs-133, -206 and -1 in skeletal muscles and miRNA-122 in liver. Bioluminescence experiments demonstrated robust qualitative and quantitative data that correlate with the miRNA expression pattern detected by quantitative RT-PCR (qPCR). We further demonstrated that the regulation of miRNA-206 expression during the development of muscular atrophy is individual-dependent, time-regulated and more complex than the information generated by qPCR. As RILES is simple and versatile, we believe that this methodology will contribute to a better understanding of miRNA biology and could serve as a rationale for the development of a novel generation of regulatable gene expression systems with potential therapeutic applications.

Dynamic Imaging of Mouse Embryos and Cardiodynamics in Static Culture.

PubMed

Lopez, Andrew L; Larina, Irina V

2018-01-01

The heart is a dynamic organ that quickly undergoes morphological and mechanical changes through early embryonic development. Characterizing these early moments is important for our understanding of proper embryonic development and the treatment of heart disease. Traditionally, tomographic imaging modalities and fluorescence-based microscopy are excellent approaches to visualize structural features and gene expression patterns, respectively, and connect aberrant gene programs to pathological phenotypes. However, these approaches usually require static samples or fluorescent markers, which can limit how much information we can derive from the dynamic and mechanical changes that regulate heart development. Optical coherence tomography (OCT) is unique in this circumstance because it allows for the acquisition of three-dimensional structural and four-dimensional (3D + time) functional images of living mouse embryos without fixation or contrast reagents. In this chapter, we focus on how OCT can visualize heart morphology at different stages of development and provide cardiodynamic information to reveal mechanical properties of the developing heart.

The sleeping brain as a complex system.

PubMed

Olbrich, Eckehard; Achermann, Peter; Wennekers, Thomas

2011-10-13

'Complexity science' is a rapidly developing research direction with applications in a multitude of fields that study complex systems consisting of a number of nonlinear elements with interesting dynamics and mutual interactions. This Theme Issue 'The complexity of sleep' aims at fostering the application of complexity science to sleep research, because the brain in its different sleep stages adopts different global states that express distinct activity patterns in large and complex networks of neural circuits. This introduction discusses the contributions collected in the present Theme Issue. We highlight the potential and challenges of a complex systems approach to develop an understanding of the brain in general and the sleeping brain in particular. Basically, we focus on two topics: the complex networks approach to understand the changes in the functional connectivity of the brain during sleep, and the complex dynamics of sleep, including sleep regulation. We hope that this Theme Issue will stimulate and intensify the interdisciplinary communication to advance our understanding of the complex dynamics of the brain that underlies sleep and consciousness.

Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids

PubMed Central

Shvets, Elena; Bitsikas, Vassilis; Howard, Gillian; Hansen, Carsten Gram; Nichols, Benjamin J.

2015-01-01

Caveolae have long been implicated in endocytosis. Recent data question this link, and in the absence of specific cargoes the potential cellular function of caveolar endocytosis remains unclear. Here we develop new tools, including doubly genome-edited cell lines, to assay the subcellular dynamics of caveolae using tagged proteins expressed at endogenous levels. We find that around 5% of the cellular pool of caveolae is present on dynamic endosomes, and is delivered to endosomes in a clathrin-independent manner. Furthermore, we show that caveolae are indeed likely to bud directly from the plasma membrane. Using a genetically encoded tag for electron microscopy and ratiometric light microscopy, we go on to show that bulk membrane proteins are depleted within caveolae. Although caveolae are likely to account for only a small proportion of total endocytosis, cells lacking caveolae show fundamentally altered patterns of membrane traffic when loaded with excess glycosphingolipid. Altogether, these observations support the hypothesis that caveolar endocytosis is specialized for transport of membrane lipid. PMID:25897946

Natural Human Mobility Patterns and Spatial Spread of Infectious Diseases

NASA Astrophysics Data System (ADS)

Belik, Vitaly; Geisel, Theo; Brockmann, Dirk

2011-08-01

We investigate a model for spatial epidemics explicitly taking into account bidirectional movements between base and destination locations on individual mobility networks. We provide a systematic analysis of generic dynamical features of the model on regular and complex metapopulation network topologies and show that significant dynamical differences exist to ordinary reaction-diffusion and effective force of infection models. On a lattice we calculate an expression for the velocity of the propagating epidemic front and find that, in contrast to the diffusive systems, our model predicts a saturation of the velocity with an increasing traveling rate. Furthermore, we show that a fully stochastic system exhibits a novel threshold for the attack ratio of an outbreak that is absent in diffusion and force of infection models. These insights not only capture natural features of human mobility relevant for the geographical epidemic spread, they may serve as a starting point for modeling important dynamical processes in human and animal epidemiology, population ecology, biology, and evolution.

Stability and nuclear dynamics of the Bicoid morphogen gradient

PubMed Central

Gregor, Thomas; Wieschaus, Eric F.; McGregor, Alistair P.; Bialek, William; Tank, David W.

2008-01-01

Patterning in multicellular organisms results from spatial gradients in morphogen concentration, but the dynamics of these gradients remains largely unexplored. We characterize, through in vivo optical imaging, the development and stability of the Bicoid morphogen gradient in Drosophila embryos that express a Bicoid-eGFP fusion protein. The gradient is established rapidly (~1 hour after fertilization) with nuclear Bicoid concentration rising and falling during mitosis. Interphase levels result from a rapid equilibrium between Bicoid uptake and removal. Initial interphase concentration in nuclei in successive cycles is constant (±10%), demonstrating a form of gradient stability, but subsequently decays by approximately 30%. Both direct photobleaching measurements and indirect estimates of Bicoid-eGFP diffusion constants (D ≤ 1 μm2/s), provide a consistent picture of Bicoid transport on short (~min) time scales, but challenge traditional models of long range gradient formation. A new model is presented emphasizing the possible role of nuclear dynamics in shaping and scaling the gradient. PMID:17632061

Reorientation Timescales and Pattern Dynamics for Titan's Dunes: Does the Tail Wag the Dog or the Dragon?

NASA Astrophysics Data System (ADS)

Hayes, A. G.; Ewing, R. C.; Cassini Radar Science Team, T.

2011-12-01

Fields of bedform patterns persist across many orders of magnitude, from cm-scale sub-aqueous current ripples to km-scale aeolian dunes, and form with surprisingly little difference in expression despite a range of formative environments. Because of the remarkable similarity between and among patterns, extracting information about climate and environment from these patterns is a challenge. For example, crest orientation is not diagnostic of a particular flow regime; similar patterns form under many different flow configurations. On Titan, these challenges have played out with many attempts to reconcile dune-field patterns with modeled and expected wind regimes. We propose that thinking about the change in dune orientation, rather than the orientation itself, can provide new insights on the long-term stability of the dune-field patterns and the formative wind regime. In this work, we apply the re-orientation model presented by Werner and Kocurek [Geology, 1997] to the equatorial dune fields of Titan. We measure variations in pattern parameters (crest spacing, crest length and defect density, which is the number of defect pairs per total crest length) both within and between Titan's dune fields to describe pattern maturity and identify areas where changes in dune orientation are likely to occur (or may already be occurring). Measured defect densities are similar to Earth's largest linear dune fields, such as the Namib Sand Sea and the Simpson Desert. We use measured defect densities in the Werner and Kocurek model to estimate crestline reorientation rates. We find reorientation timescales varying from ten to a hundred thousand times the average migration timescale (time to migrate a bedform one meter, ~1 Titan year according to Tokano (Aeolian Research, 2010)). Well organized patterns have the longest reorientation time scales (~10^5 migration timescales), while the topographically or spatially isolated patches of dunes show the shortest reorientation times (~10^3 migration timescales). In addition, comparisons between spacing and defect density of Titan's dunes and some of the largest fields observed on Earth and Mars reveal that dune patterns on all three planets are geometrically similar, suggesting that growth and organization share common pattern dynamics. Our results suggest that Titan's dunes may react to gross bedform transport averaged over orbital timescales, relaxing the requirement that a single modern wind regime is required to produce the observed pattern.

The Cluster Variation Method: A Primer for Neuroscientists.

PubMed

Maren, Alianna J

2016-09-30

Effective Brain-Computer Interfaces (BCIs) require that the time-varying activation patterns of 2-D neural ensembles be modelled. The cluster variation method (CVM) offers a means for the characterization of 2-D local pattern distributions. This paper provides neuroscientists and BCI researchers with a CVM tutorial that will help them to understand how the CVM statistical thermodynamics formulation can model 2-D pattern distributions expressing structural and functional dynamics in the brain. The premise is that local-in-time free energy minimization works alongside neural connectivity adaptation, supporting the development and stabilization of consistent stimulus-specific responsive activation patterns. The equilibrium distribution of local patterns, or configuration variables , is defined in terms of a single interaction enthalpy parameter ( h ) for the case of an equiprobable distribution of bistate (neural/neural ensemble) units. Thus, either one enthalpy parameter (or two, for the case of non-equiprobable distribution) yields equilibrium configuration variable values. Modeling 2-D neural activation distribution patterns with the representational layer of a computational engine, we can thus correlate variational free energy minimization with specific configuration variable distributions. The CVM triplet configuration variables also map well to the notion of a M = 3 functional motif. This paper addresses the special case of an equiprobable unit distribution, for which an analytic solution can be found.

Solution NMR studies provide structural basis for endotoxin pattern recognition by the innate immune receptor CD14

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albright, Seth; Chen Bin; Holbrook, Kristen

CD14 functions as a key pattern recognition receptor for a diverse array of Gram-negative and Gram-positive cell-wall components in the host innate immune response by binding to pathogen-associated molecular patterns (PAMPs) at partially overlapping binding site(s). To determine the potential contribution of CD14 residues in this pattern recognition, we have examined using solution NMR spectroscopy, the binding of three different endotoxin ligands, lipopolysaccharide, lipoteichoic acid, and a PGN-derived compound, muramyl dipeptide to a {sup 15}N isotopically labeled 152-residue N-terminal fragment of sCD14 expressed in Pichia pastoris. Mapping of NMR spectral changes upon addition of ligands revealed that the pattern ofmore » residues affected by binding of each ligand is partially similar and partially different. This first direct structural observation of the ability of specific residue combinations of CD14 to differentially affect endotoxin binding may help explain the broad specificity of CD14 in ligand recognition and provide a structural basis for pattern recognition. Another interesting finding from the observed spectral changes is that the mode of binding may be dynamically modulated and could provide a mechanism for binding endotoxins with structural diversity through a common binding site.« less

The Cluster Variation Method: A Primer for Neuroscientists

PubMed Central

Maren, Alianna J.

2016-01-01

Effective Brain–Computer Interfaces (BCIs) require that the time-varying activation patterns of 2-D neural ensembles be modelled. The cluster variation method (CVM) offers a means for the characterization of 2-D local pattern distributions. This paper provides neuroscientists and BCI researchers with a CVM tutorial that will help them to understand how the CVM statistical thermodynamics formulation can model 2-D pattern distributions expressing structural and functional dynamics in the brain. The premise is that local-in-time free energy minimization works alongside neural connectivity adaptation, supporting the development and stabilization of consistent stimulus-specific responsive activation patterns. The equilibrium distribution of local patterns, or configuration variables, is defined in terms of a single interaction enthalpy parameter (h) for the case of an equiprobable distribution of bistate (neural/neural ensemble) units. Thus, either one enthalpy parameter (or two, for the case of non-equiprobable distribution) yields equilibrium configuration variable values. Modeling 2-D neural activation distribution patterns with the representational layer of a computational engine, we can thus correlate variational free energy minimization with specific configuration variable distributions. The CVM triplet configuration variables also map well to the notion of a M = 3 functional motif. This paper addresses the special case of an equiprobable unit distribution, for which an analytic solution can be found. PMID:27706022

Divergent and nonuniform gene expression patterns in mouse brain

PubMed Central

Morris, John A.; Royall, Joshua J.; Bertagnolli, Darren; Boe, Andrew F.; Burnell, Josh J.; Byrnes, Emi J.; Copeland, Cathy; Desta, Tsega; Fischer, Shanna R.; Goldy, Jeff; Glattfelder, Katie J.; Kidney, Jolene M.; Lemon, Tracy; Orta, Geralyn J.; Parry, Sheana E.; Pathak, Sayan D.; Pearson, Owen C.; Reding, Melissa; Shapouri, Sheila; Smith, Kimberly A.; Soden, Chad; Solan, Beth M.; Weller, John; Takahashi, Joseph S.; Overly, Caroline C.; Lein, Ed S.; Hawrylycz, Michael J.; Hohmann, John G.; Jones, Allan R.

2010-01-01

Considerable progress has been made in understanding variations in gene sequence and expression level associated with phenotype, yet how genetic diversity translates into complex phenotypic differences remains poorly understood. Here, we examine the relationship between genetic background and spatial patterns of gene expression across seven strains of mice, providing the most extensive cellular-resolution comparative analysis of gene expression in the mammalian brain to date. Using comprehensive brainwide anatomic coverage (more than 200 brain regions), we applied in situ hybridization to analyze the spatial expression patterns of 49 genes encoding well-known pharmaceutical drug targets. Remarkably, over 50% of the genes examined showed interstrain expression variation. In addition, the variability was nonuniformly distributed across strain and neuroanatomic region, suggesting certain organizing principles. First, the degree of expression variance among strains mirrors genealogic relationships. Second, expression pattern differences were concentrated in higher-order brain regions such as the cortex and hippocampus. Divergence in gene expression patterns across the brain could contribute significantly to variations in behavior and responses to neuroactive drugs in laboratory mouse strains and may help to explain individual differences in human responsiveness to neuroactive drugs. PMID:20956311

Mutations in the Katnb1 gene cause left-right asymmetry and heart defects.

PubMed

Furtado, Milena B; Merriner, D Jo; Berger, Silke; Rhodes, Danielle; Jamsai, Duangporn; O'Bryan, Moira K

2017-12-01

The microtubule-severing protein complex katanin is composed two subunits, the ATPase subunit, KATNA1, and the noncatalytic regulatory subunit, KATNB1. Recently, the Katnb1 gene has been linked to infertility, regulation of centriole and cilia formation in fish and mammals, as well as neocortical brain development. KATNB1 protein is expressed in germ cells in humans and mouse, mitotic/meiotic spindles and cilia, although the full expression pattern of the Katnb1 gene has not been described. Using a knockin-knockout mouse model of Katnb1 dysfunction we demonstrate that Katnb1 is ubiquitously expressed during embryonic development, although a stronger expression is seen in the crown cells of the gastrulation organizer, the murine node. Furthermore, null and hypomorphic Katnb1 gene mutations show a novel correlation between Katnb1 dysregulation and the development of impaired left-right signaling, including cardiac malformations. Katanin function is a critical regulator of heart development in mice. These findings are potentially relevant to human cardiac development. Developmental Dynamics 246:1027-1035, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Transient gene expression in epidermal cells of plant leaves by biolistic DNA delivery.

PubMed

Ueki, Shoko; Magori, Shimpei; Lacroix, Benoît; Citovsky, Vitaly

2013-01-01

Transient gene expression is a useful approach for studying the functions of gene products. In the case of plants, Agrobacterium infiltration is a method of choice for transient introduction of genes for many species. However, this technique does not work efficiently in some species, such as Arabidopsis thaliana. Moreover, the infection of Agrobacterium is known to induce dynamic changes in gene expression patterns in the host plants, possibly affecting the function and localization of the proteins to be tested. These problems can be circumvented by biolistic delivery of the genes of interest. Here, we present an optimized protocol for biolistic delivery of plasmid DNA into epidermal cells of plant leaves, which can be easily performed using the Bio-Rad Helios gene gun system. This protocol allows efficient and reproducible transient expression of diverse genes in Arabidopsis, Nicotiana benthamiana and N. tabacum, and is suitable for studies of the biological function and subcellular localization of the gene products directly in planta. The protocol also can be easily adapted to other species by optimizing the delivery gas pressure.

Binary Gene Expression Patterning of the Molt Cycle: The Case of Chitin Metabolism

PubMed Central

Abehsera, Shai; Glazer, Lilah; Tynyakov, Jenny; Plaschkes, Inbar; Chalifa-Caspi, Vered; Khalaila, Isam; Aflalo, Eliahu D.; Sagi, Amir

2015-01-01

In crustaceans, like all arthropods, growth is accompanied by a molting cycle. This cycle comprises major physiological events in which mineralized chitinous structures are built and degraded. These events are in turn governed by genes whose patterns of expression are presumably linked to the molting cycle. To study these genes we performed next generation sequencing and constructed a molt-related transcriptomic library from two exoskeletal-forming tissues of the crayfish Cherax quadricarinatus, namely the gastrolith and the mandible cuticle-forming epithelium. To simplify the study of such a complex process as molting, a novel approach, binary patterning of gene expression, was employed. This approach revealed that key genes involved in the synthesis and breakdown of chitin exhibit a molt-related pattern in the gastrolith-forming epithelium. On the other hand, the same genes in the mandible cuticle-forming epithelium showed a molt-independent pattern of expression. Genes related to the metabolism of glucosamine-6-phosphate, a chitin precursor synthesized from simple sugars, showed a molt-related pattern of expression in both tissues. The binary patterning approach unfolds typical patterns of gene expression during the molt cycle of a crustacean. The use of such a simplifying integrative tool for assessing gene patterning seems appropriate for the study of complex biological processes. PMID:25919476

Ontogeny of hepatic energy metabolism genes in mice as revealed by RNA-sequencing.

PubMed

Renaud, Helen J; Cui, Yue Julia; Lu, Hong; Zhong, Xiao-bo; Klaassen, Curtis D

2014-01-01

The liver plays a central role in metabolic homeostasis by coordinating synthesis, storage, breakdown, and redistribution of nutrients. Hepatic energy metabolism is dynamically regulated throughout different life stages due to different demands for energy during growth and development. However, changes in gene expression patterns throughout ontogeny for factors important in hepatic energy metabolism are not well understood. We performed detailed transcript analysis of energy metabolism genes during various stages of liver development in mice. Livers from male C57BL/6J mice were collected at twelve ages, including perinatal and postnatal time points (n = 3/age). The mRNA was quantified by RNA-Sequencing, with transcript abundance estimated by Cufflinks. One thousand sixty energy metabolism genes were examined; 794 were above detection, of which 627 were significantly changed during at least one developmental age compared to adult liver. Two-way hierarchical clustering revealed three major clusters dependent on age: GD17.5-Day 5 (perinatal-enriched), Day 10-Day 20 (pre-weaning-enriched), and Day 25-Day 60 (adolescence/adulthood-enriched). Clustering analysis of cumulative mRNA expression values for individual pathways of energy metabolism revealed three patterns of enrichment: glycolysis, ketogenesis, and glycogenesis were all perinatally-enriched; glycogenolysis was the only pathway enriched during pre-weaning ages; whereas lipid droplet metabolism, cholesterol and bile acid metabolism, gluconeogenesis, and lipid metabolism were all enriched in adolescence/adulthood. This study reveals novel findings such as the divergent expression of the fatty acid β-oxidation enzymes Acyl-CoA oxidase 1 and Carnitine palmitoyltransferase 1a, indicating a switch from mitochondrial to peroxisomal β-oxidation after weaning; as well as the dynamic ontogeny of genes implicated in obesity such as Stearoyl-CoA desaturase 1 and Elongation of very long chain fatty acids-like 3. These data shed new light on the ontogeny of homeostatic regulation of hepatic energy metabolism, which could ultimately provide new therapeutic targets for metabolic diseases.

Computational strategies to address chromatin structure problems

NASA Astrophysics Data System (ADS)

Perišić, Ognjen; Schlick, Tamar

2016-06-01

While the genetic information is contained in double helical DNA, gene expression is a complex multilevel process that involves various functional units, from nucleosomes to fully formed chromatin fibers accompanied by a host of various chromatin binding enzymes. The chromatin fiber is a polymer composed of histone protein complexes upon which DNA wraps, like yarn upon many spools. The nature of chromatin structure has been an open question since the beginning of modern molecular biology. Many experiments have shown that the chromatin fiber is a highly dynamic entity with pronounced structural diversity that includes properties of idealized zig-zag and solenoid models, as well as other motifs. This diversity can produce a high packing ratio and thus inhibit access to a majority of the wound DNA. Despite much research, chromatin’s dynamic structure has not yet been fully described. Long stretches of chromatin fibers exhibit puzzling dynamic behavior that requires interpretation in the light of gene expression patterns in various tissue and organisms. The properties of chromatin fiber can be investigated with experimental techniques, like in vitro biochemistry, in vivo imagining, and high-throughput chromosome capture technology. Those techniques provide useful insights into the fiber’s structure and dynamics, but they are limited in resolution and scope, especially regarding compact fibers and chromosomes in the cellular milieu. Complementary but specialized modeling techniques are needed to handle large floppy polymers such as the chromatin fiber. In this review, we discuss current approaches in the chromatin structure field with an emphasis on modeling, such as molecular dynamics and coarse-grained computational approaches. Combinations of these computational techniques complement experiments and address many relevant biological problems, as we will illustrate with special focus on epigenetic modulation of chromatin structure.

Evolution of the β-adrenoreceptors in vertebrates.

PubMed

Zavala, Kattina; Vandewege, Michael W; Hoffmann, Federico G; Opazo, Juan C

2017-01-01

The study of the evolutionary history of genes related to human disease lies at the interface of evolution and medicine. These studies provide the evolutionary context on which medical researchers should work, and are also useful in providing information to suggest further genetic experiments, especially in model species where genetic manipulations can be made. Here we studied the evolution of the β-adrenoreceptor gene family in vertebrates with the aim of adding an evolutionary framework to the already abundant physiological information. Our results show that in addition to the three already described vertebrate β-adrenoreceptor genes there is an additional group containing cyclostome sequences. We suggest that β-adrenoreceptors diversified as a product of the two whole genome duplications that occurred in the ancestor of vertebrates. Gene expression patterns are in general consistent across species, suggesting that expression dynamics were established early in the evolutionary history of vertebrates, and have been maintained since then. Finally, amino acid polymorphisms that are associated to pathological conditions in humans appear to be common in non-human mammals, suggesting that the phenotypic effects of these mutations depend on epistatic interaction with other positions. The evolutionary analysis of the β-adrenoreceptors delivers new insights about the diversity of these receptors in vertebrates, the evolution of the expression patterns and a comparative perspective regarding the polymorphisms that in humans are linked to pathological conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Expression of parasite genetic variation changes over the course of infection: implications of within-host dynamics for the evolution of virulence.

PubMed

Clerc, Melanie; Ebert, Dieter; Hall, Matthew D

2015-04-07

How infectious disease agents interact with their host changes during the course of infection and can alter the expression of disease-related traits. Yet by measuring parasite life-history traits at one or few moments during infection, studies have overlooked the impact of variable parasite growth trajectories on disease evolution. Here we show that infection-age-specific estimates of host and parasite fitness components can reveal new insight into the evolution of parasites. We do so by characterizing the within-host dynamics over an entire infection period for five genotypes of the castrating bacterial parasite Pasteuria ramosa infecting the crustacean Daphnia magna. Our results reveal that genetic variation for parasite-induced gigantism, host castration and parasite spore loads increases with the age of infection. Driving these patterns appears to be variation in how well the parasite maintains control of host reproduction late in the infection process. We discuss the evolutionary consequences of this finding with regard to natural selection acting on different ages of infection and the mechanism underlying the maintenance of castration efficiency. Our results highlight how elucidating within-host dynamics can shed light on the selective forces that shape infection strategies and the evolution of virulence. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Fetal eye movements on magnetic resonance imaging.

PubMed

Woitek, Ramona; Kasprian, Gregor; Lindner, Christian; Stuhr, Fritz; Weber, Michael; Schöpf, Veronika; Brugger, Peter C; Asenbaum, Ulrika; Furtner, Julia; Bettelheim, Dieter; Seidl, Rainer; Prayer, Daniela

2013-01-01

Eye movements are the physical expression of upper fetal brainstem function. Our aim was to identify and differentiate specific types of fetal eye movement patterns using dynamic MRI sequences. Their occurrence as well as the presence of conjugated eyeball motion and consistently parallel eyeball position was systematically analyzed. Dynamic SSFP sequences were acquired in 72 singleton fetuses (17-40 GW, three age groups [17-23 GW, 24-32 GW, 33-40 GW]). Fetal eye movements were evaluated according to a modified classification originally published by Birnholz (1981): Type 0: no eye movements; Type I: single transient deviations; Type Ia: fast deviation, slower reposition; Type Ib: fast deviation, fast reposition; Type II: single prolonged eye movements; Type III: complex sequences; and Type IV: nystagmoid. In 95.8% of fetuses, the evaluation of eye movements was possible using MRI, with a mean acquisition time of 70 seconds. Due to head motion, 4.2% of the fetuses and 20.1% of all dynamic SSFP sequences were excluded. Eye movements were observed in 45 fetuses (65.2%). Significant differences between the age groups were found for Type I (p = 0.03), Type Ia (p = 0.031), and Type IV eye movements (p = 0.033). Consistently parallel bulbs were found in 27.3-45%. In human fetuses, different eye movement patterns can be identified and described by MRI in utero. In addition to the originally classified eye movement patterns, a novel subtype has been observed, which apparently characterizes an important step in fetal brainstem development. We evaluated, for the first time, eyeball position in fetuses. Ultimately, the assessment of fetal eye movements by MRI yields the potential to identify early signs of brainstem dysfunction, as encountered in brain malformations such as Chiari II or molar tooth malformations.

Structural changes in lymphocytes membrane of Chernobyl clean-up workers from Latvia.

PubMed

Kalnina, Inta; Zvagule, Tija; Gabruseva, Natalija; Kirilova, Jelena; Kurjane, Natalja; Bruvere, Ruta; Kesters, Andris; Kizane, Gunta; Kirilovs, Georgijs; Meirovics, Imants

2007-11-01

ABM (3-aminobenzanthrrone derivative) developed at the Riga Technical University, Riga, Latvia) has been previously shown as a potential probe for determination of the immune state of patients with different pathologies . The fist study (using probe ABM) of peripheral blood mononuclear cells (PBMC) membranes of 97 Chernobyl clean-up workers from Latvia was conducted in 1997. Now we repeatedly examine the same (n = 54) individuals in dynamics. ABM spectral parameters in PBMC suspension, fluorescence anisotropy and blood plasma albumin characteristics were recorded. In 1997 screening showed 5 different patterns of fluorescence spectra, from which in 2007 we obtained only two. These patterns of spectra had never been previously seen in healthy individuals or patients with tuberculosis, multiple sclerosis, rheumatoid arthritis, etc., examined by us. Patterns of ABM fluorescence spectra are associated with membrane anisotropy and conformational changes of blood plasma albumin. We observed that in dynamics 1997-2007 the lipid compartment of the membrane became more fluid while the lipid-protein interface became more rigid. The use of probe ANS and albumin auto-fluorescence allowed show conformational alterations in Chernobyl clean-up workers blood plasma. It is necessary to note that all investigated parameters significantly differ in observed groups of patients. These findings reinforce our understanding that that the cell membrane is a significant biological target of radiation. The role of the membrane in the expression and course of cell damage after radiation exposure must be considered. So ten years dynamic of PBMC membrane characteristics by ABM (spectral shift and anisotropy indexes) in Chernobyl clean-up workers reveal progressive trend toward certain resemblance with those of chronic B-cell lymphoid leukemia.

Cerebellar damage diminishes long-latency responses to multijoint perturbations

PubMed Central

Trautman, Paxson; Rasquinha, Russell J.; Bhanpuri, Nasir H.; Scott, Stephen H.; Bastian, Amy J.

2013-01-01

Damage to the cerebellum can cause significant problems in the coordination of voluntary arm movements. One prominent idea is that incoordination stems from an inability to predictively account for the complex mechanical interactions between the arm's several joints. Motivated by growing evidence that corrective feedback control shares important capabilities and neural substrates with feedforward control, we asked whether cerebellar damage impacts feedback stabilization of the multijoint arm appropriate for the arm's intersegmental dynamics. Specifically, we tested whether cerebellar dysfunction impacts the ability of posterior deltoid to incorporate elbow motion in its long-latency response (R2 = 45–75 ms and R3 = 75–100 ms after perturbation) to an unexpected torque perturbation. Healthy and cerebellar-damaged subjects were exposed to a selected pattern of shoulder-elbow displacements to probe the response pattern from this shoulder extensor muscle. The healthy elderly subjects expressed a long-latency response linked to both shoulder and elbow motion, including an increase/decrease in shoulder extensor activity with elbow flexion/extension. Critically, cerebellar-damaged subjects displayed the normal pattern of activity in the R3 period indicating an intact ability to rapidly integrate multijoint motion appropriate to the arm's intersegmental dynamics. However, cerebellar-damaged subjects had a lower magnitude of activity that was specific to the long-latency period (both R2 and R3) and a slightly delayed onset of multijoint sensitivity. Taken together, our results suggest that the basic motor pattern of the long-latency response is housed outside the cerebellum and is scaled by processes within the cerebellum. PMID:23390311

Dynamical origin of complex motor patterns

NASA Astrophysics Data System (ADS)

Alonso, L. M.; Alliende, J. A.; Mindlin, G. B.

2010-11-01

Behavior emerges as the nervous system generates motor patterns in charge of driving a peripheral biomechanical device. For several cases in the animal kingdom, it has been identified that the motor patterns used in order to accomplish a diversity of tasks are the different solutions of a simple, low dimensional nonlinear dynamical system. Yet, motor patterns emerge from the interaction of an enormous number of individual dynamical units. In this work, we study the dynamics of the average activity of a large set of coupled excitable units which are periodically forced. We show that low dimensional, yet non trivial dynamics emerges. As a case study, we analyze the air sac pressure patterns used by domestic canaries during song, which consists of a succession of repetitions of different syllable types. We show that the pressure patterns used to generate different syllables can be approximated by the solutions of the investigated model. In this way, we are capable of integrating different description scales of our problem.

Dynamics and regulation of glycolysis-tricarboxylic acid metabolism in the midgut of Spodoptera litura during metamorphosis.

PubMed

Hu, D; Luo, W; Fan, L F; Liu, F L; Gu, J; Deng, H M; Zhang, C; Huang, L H; Feng, Q L

2016-04-01

Significant changes usually take place in the internal metabolism of insects during metamorphosis. The glycolysis-tricarboxylic acid (glycolysis-TCA) pathway is important for energy metabolism. To elucidate its dynamics, the mRNA levels of genes involved in this pathway were examined in the midgut of Spodoptera litura during metamorphosis, and the pyruvate content was quantified. The expression patterns of these genes in response to starvation were examined, and the interaction between protein phosphatase 1 (PP1) and phosphofructokinase (PFK) was studied. The results revealed that the expression or activities of most glycolytic enzymes was down-regulated in prepupae and then recovered in some degree in pupae, and all TCA-related genes were remarkably suppressed in both the prepupae and pupae. Pyruvate was enriched in the pupal midgut. Taken together, these results suggest that insects decrease both glycolysis and TCA in prepupae to save energy and then up-regulate glycolysis but down-regulate TCA in pupae to increase the supply of intermediates for construction of new organs. The expression of all these genes were down-regulated by starvation, indicating that non-feeding during metamorphosis may be a regulator of glycolysis-TCA pathway in the midgut. Importantly, interaction between PP1 and PFK was identified and is suggested to be involved in the regulation of glycolysis. © 2015 The Royal Entomological Society.

Construction and comparison of gene co-expression networks shows complex plant immune responses

PubMed Central

López, Camilo; López-Kleine, Liliana

2014-01-01

Gene co-expression networks (GCNs) are graphic representations that depict the coordinated transcription of genes in response to certain stimuli. GCNs provide functional annotations of genes whose function is unknown and are further used in studies of translational functional genomics among species. In this work, a methodology for the reconstruction and comparison of GCNs is presented. This approach was applied using gene expression data that were obtained from immunity experiments in Arabidopsis thaliana, rice, soybean, tomato and cassava. After the evaluation of diverse similarity metrics for the GCN reconstruction, we recommended the mutual information coefficient measurement and a clustering coefficient-based method for similarity threshold selection. To compare GCNs, we proposed a multivariate approach based on the Principal Component Analysis (PCA). Branches of plant immunity that were exemplified by each experiment were analyzed in conjunction with the PCA results, suggesting both the robustness and the dynamic nature of the cellular responses. The dynamic of molecular plant responses produced networks with different characteristics that are differentiable using our methodology. The comparison of GCNs from plant pathosystems, showed that in response to similar pathogens plants could activate conserved signaling pathways. The results confirmed that the closeness of GCNs projected on the principal component space is an indicative of similarity among GCNs. This also can be used to understand global patterns of events triggered during plant immune responses. PMID:25320678

Multimodal human communication--targeting facial expressions, speech content and prosody.

PubMed

Regenbogen, Christina; Schneider, Daniel A; Gur, Raquel E; Schneider, Frank; Habel, Ute; Kellermann, Thilo

2012-05-01

Human communication is based on a dynamic information exchange of the communication channels facial expressions, prosody, and speech content. This fMRI study elucidated the impact of multimodal emotion processing and the specific contribution of each channel on behavioral empathy and its prerequisites. Ninety-six video clips displaying actors who told self-related stories were presented to 27 healthy participants. In two conditions, all channels uniformly transported only emotional or neutral information. Three conditions selectively presented two emotional channels and one neutral channel. Subjects indicated the actors' emotional valence and their own while fMRI was recorded. Activation patterns of tri-channel emotional communication reflected multimodal processing and facilitative effects for empathy. Accordingly, subjects' behavioral empathy rates significantly deteriorated once one source was neutral. However, emotionality expressed via two of three channels yielded activation in a network associated with theory-of-mind-processes. This suggested participants' effort to infer mental states of their counterparts and was accompanied by a decline of behavioral empathy, driven by the participants' emotional responses. Channel-specific emotional contributions were present in modality-specific areas. The identification of different network-nodes associated with human interactions constitutes a prerequisite for understanding dynamics that underlie multimodal integration and explain the observed decline in empathy rates. This task might also shed light on behavioral deficits and neural changes that accompany psychiatric diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

Isolation of chicken homolog of the FOXL2 gene and comparison of its expression patterns with those of aromatase during ovarian development.

PubMed

Govoroun, Marina S; Pannetier, Maëlle; Pailhoux, Eric; Cocquet, Julie; Brillard, Jean-Pierre; Couty, Isabelle; Batellier, Florence; Cotinot, Corinne

2004-12-01

Mutations in the forkhead transcription factor gene FOXL2 are involved in ovarian failure, which occurs in human BPES syndrome. This syndrome presents a sexually dimorphic expression, specific to the ovary in several vertebrates. We cloned the open reading frame of chicken FOXL2 (cFoxL2) and studied cFoxL2 expression in developing gonads and during adulthood to examine the role of FOXL2 in ovarian differentiation and function in birds. The spatial and temporal dynamics of cFoxL2 and aromatase expression were analyzed in parallel by using real-time quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry in attempt to investigate the possible role of cFoxL2 in the regulation of aromatase. The expression patterns of cFoxL2 and aromatase transcripts were highly correlated during the sex-differentiation period (4.7-12.7 days of incubation). Aromatase and cFoxL2 proteins were colocalized in the medullar part of female gonads on embryonic day 14. Fourteen days after hatching, cFoxL2 protein was mainly detected in granulosa cells of developing follicles. In adult ovary follicular envelopes, apart from granulosa cells, cFoxL2 transcript and protein were detected at lower levels in theca cells where aromatase was present. A high level of cFoxL2 transcription was also observed in maturing and ovulated oocytes. Our results confirm that FoxL2 is an early regulator of ovarian development in birds and may be involved in aromatase transcription regulation. Copyright (c) 2004 Wiley-Liss, Inc.

Dynamic transcriptomic analysis in hircine longissimus dorsi muscle from fetal to neonatal development stages.

PubMed

Zhan, Siyuan; Zhao, Wei; Song, Tianzeng; Dong, Yao; Guo, Jiazhong; Cao, Jiaxue; Zhong, Tao; Wang, Linjie; Li, Li; Zhang, Hongping

2018-01-01

Muscle growth and development from fetal to neonatal stages consist of a series of delicately regulated and orchestrated changes in expression of genes. In this study, we performed whole transcriptome profiling based on RNA-Seq of caprine longissimus dorsi muscle tissue obtained from prenatal stages (days 45, 60, and 105 of gestation) and neonatal stage (the 3-day-old newborn) to identify genes that are differentially expressed and investigate their temporal expression profiles. A total of 3276 differentially expressed genes (DEGs) were identified (Q value < 0.01). Time-series expression profile clustering analysis indicated that DEGs were significantly clustered into eight clusters which can be divided into two classes (Q value < 0.05), class I profiles with downregulated patterns and class II profiles with upregulated patterns. Based on cluster analysis, GO enrichment analysis found that 75, 25, and 8 terms to be significantly enriched in biological process (BP), cellular component (CC), and molecular function (MF) categories in class I profiles, while 35, 21, and 8 terms to be significantly enriched in BP, CC, and MF in class II profiles. KEGG pathway analysis revealed that DEGs from class I profiles were significantly enriched in 22 pathways and the most enriched pathway was Rap1 signaling pathway. DEGs from class II profiles were significantly enriched in 17 pathways and the mainly enriched pathway was AMPK signaling pathway. Finally, six selected DEGs from our sequencing results were confirmed by qPCR. Our study provides a comprehensive understanding of the molecular mechanisms during goat skeletal muscle development from fetal to neonatal stages and valuable information for future studies of muscle development in goats.

Contrasting Levels of Molecular Evolution on the Mouse X Chromosome

PubMed Central

Larson, Erica L.; Vanderpool, Dan; Keeble, Sara; Zhou, Meng; Sarver, Brice A. J.; Smith, Andrew D.; Dean, Matthew D.; Good, Jeffrey M.

2016-01-01

The mammalian X chromosome has unusual evolutionary dynamics compared to autosomes. Faster-X evolution of spermatogenic protein-coding genes is known to be most pronounced for genes expressed late in spermatogenesis, but it is unclear if these patterns extend to other forms of molecular divergence. We tested for faster-X evolution in mice spanning three different forms of molecular evolution—divergence in protein sequence, gene expression, and DNA methylation—across different developmental stages of spermatogenesis. We used FACS to isolate individual cell populations and then generated cell-specific transcriptome profiles across different stages of spermatogenesis in two subspecies of house mice (Mus musculus), thereby overcoming a fundamental limitation of previous studies on whole tissues. We found faster-X protein evolution at all stages of spermatogenesis and faster-late protein evolution for both X-linked and autosomal genes. In contrast, there was less expression divergence late in spermatogenesis (slower late) on the X chromosome and for autosomal genes expressed primarily in testis (testis-biased). We argue that slower-late expression divergence reflects strong regulatory constraints imposed during this critical stage of sperm development and that these constraints are particularly acute on the tightly regulated sex chromosomes. We also found slower-X DNA methylation divergence based on genome-wide bisulfite sequencing of sperm from two species of mice (M. musculus and M. spretus), although it is unclear whether slower-X DNA methylation reflects development constraints in sperm or other X-linked phenomena. Our study clarifies key differences in patterns of regulatory and protein evolution across spermatogenesis that are likely to have important consequences for mammalian sex chromosome evolution, male fertility, and speciation. PMID:27317678

Spontaneous and electrically modulated spatiotemporal dynamics of the neocortical slow oscillation and associated local fast activity.

PubMed

Greenberg, Anastasia; Dickson, Clayton T

2013-12-01

The neocortical slow oscillation (SO; ~1Hz) of non-REM sleep and anesthesia reflects synchronized network activity composed of alternating active and silent (ON/OFF) phases at the local network and cellular level. The SO itself shows self-organized spatiotemporal dynamics as it appears to originate at unique foci on each cycle and then propagates across the cortical surface. During sleep, this rhythm is relevant for neuroplastic processes mediating memory consolidation especially since its enhancement by slow, rhythmic electrical fields improves subsequent recall. However, the neurobiological mechanism by which spontaneous or enhanced SO activity might operate on memory traces is unknown. Here we show a series of original results, using cycle to cycle tracking across multiple neocortical sites in urethane anesthetized rats: The spontaneous spatiotemporal dynamics of the SO are complex, showing interfering propagation patterns in the anterior-to-posterior plane. These patterns compete for expression and tend to alternate following phase resets that take place during the silent OFF phase of the SO. Applying sinusoidal electrical field stimulation to the anterior pole of the cerebral cortex progressively entrained local field, gamma, and multi-unit activity at all sites, while disrupting the coordination of endogenous SO activity. Field stimulation also biased propagation in the anterior-to-posterior direction and more notably, enhanced the long-range gamma synchrony between cortical regions. These results are the first to show that changes to slow wave dynamics cause enhancements in high frequency cortico-cortical communication and provide mechanistic clues into how the SO is relevant for sleep-dependent memory consolidation. © 2013.

Distinct spatiotemporal activity in principal neurons of the mouse olfactory bulb in anesthetized and awake states

PubMed Central

Blauvelt, David G.; Sato, Tomokazu F.; Wienisch, Martin; Murthy, Venkatesh N.

2013-01-01

The acquisition of olfactory information and its early processing in mammals are modulated by brain states through sniffing behavior and neural feedback. We imaged the spatiotemporal pattern of odor-evoked activity in a population of output neurons (mitral/tufted cells, MTCs) in the olfactory bulb (OB) of head-restrained mice expressing a genetically-encoded calcium indicator. The temporal dynamics of MTC population activity were relatively simple in anesthetized animals, but were highly variable in awake animals. However, the apparently irregular activity in awake animals could be predicted well using sniff timing measured externally, or inferred through fluctuations in the global responses of MTC population even without explicit knowledge of sniff times. The overall spatial pattern of activity was conserved across states, but odor responses had a diffuse spatial component in anesthetized mice that was less prominent during wakefulness. Multi-photon microscopy indicated that MTC lateral dendrites were the likely source of spatially disperse responses in the anesthetized animal. Our data demonstrate that the temporal and spatial dynamics of MTCs can be significantly modulated by behavioral state, and that the ensemble activity of MTCs can provide information about sniff timing to downstream circuits to help decode odor responses. PMID:23543674

We can't all be supermodels: the value of comparative transcriptomics to the study of non-model insects

PubMed Central

Oppenheim, Sara J; Baker, Richard H; Simon, Sabrina; DeSalle, Rob

2015-01-01

Insects are the most diverse group of organisms on the planet. Variation in gene expression lies at the heart of this biodiversity and recent advances in sequencing technology have spawned a revolution in researchers' ability to survey tissue-specific transcriptional complexity across a wide range of insect taxa. Increasingly, studies are using a comparative approach (across species, sexes and life stages) that examines the transcriptional basis of phenotypic diversity within an evolutionary context. In the present review, we summarize much of this research, focusing in particular on three critical aspects of insect biology: morphological development and plasticity; physiological response to the environment; and sexual dimorphism. A common feature that is emerging from these investigations concerns the dynamic nature of transcriptome evolution as indicated by rapid changes in the overall pattern of gene expression, the differential expression of numerous genes with unknown function, and the incorporation of novel, lineage-specific genes into the transcriptional profile. PMID:25524309

Temporal and Spatial Expression of CCN Genes in Zebrafish

PubMed Central

Fernando, Carol A; Conrad, Patricia A; Bartels, Cynthia F; Marques, Tomas; To, Michael; Balow, Stephanie A; Nakamura, Yukio; Warman, Matthew L

2010-01-01

The six mammalian CCN genes (Cyr61, CTGF, Nov, WISP1, WISP2, WISP3) encode a family of secreted, cysteine-rich, multimodular proteins having roles in cell proliferation, adhesion, migration, and differentiation during embryogenesis, wound healing, and angiogenesis. We used bioinformatics to identify 9 CCN genes in zebrafish (zCCNs), 6 of which have not been previously described. When compared with mammalian CCN family members, 3 were paralogs of Cyr61, 2 of CTGF, 2 of WISP1, 1 of WISP2, and 1 of WISP3. No paralog of Nov was found. In situ hybridization was performed to characterize the sites of expression of the zCCNs during early zebrafish development. zCCNs demonstrated both unique and overlapping patterns of expression, suggesting potential division of labor between orthologous genes and providing an alternate approach to gene function studies that will complement studies in mammalian models. Developmental Dynamics 239:1755–1767, 2010. © 2010 Wiley-Liss, Inc. PMID:20503371

Timescales and bottlenecks in miRNA-dependent gene regulation.

PubMed

Hausser, Jean; Syed, Afzal Pasha; Selevsek, Nathalie; van Nimwegen, Erik; Jaskiewicz, Lukasz; Aebersold, Ruedi; Zavolan, Mihaela

2013-12-03

MiRNAs are post-transcriptional regulators that contribute to the establishment and maintenance of gene expression patterns. Although their biogenesis and decay appear to be under complex control, the implications of miRNA expression dynamics for the processes that they regulate are not well understood. We derived a mathematical model of miRNA-mediated gene regulation, inferred its parameters from experimental data sets, and found that the model describes well time-dependent changes in mRNA, protein and ribosome density levels measured upon miRNA transfection and induction. The inferred parameters indicate that the timescale of miRNA-dependent regulation is slower than initially thought. Delays in miRNA loading into Argonaute proteins and the slow decay of proteins relative to mRNAs can explain the typically small changes in protein levels observed upon miRNA transfection. For miRNAs to regulate protein expression on the timescale of a day, as miRNAs involved in cell-cycle regulation do, accelerated miRNA turnover is necessary.

Generation and precise control of dynamic biochemical gradients for cellular assays

NASA Astrophysics Data System (ADS)

Saka, Yasushi; MacPherson, Murray; Giuraniuc, Claudiu V.

2017-03-01

Spatial gradients of diffusible signalling molecules play crucial roles in controlling diverse cellular behaviour such as cell differentiation, tissue patterning and chemotaxis. In this paper, we report the design and testing of a microfluidic device for diffusion-based gradient generation for cellular assays. A unique channel design of the device eliminates cross-flow between the source and sink channels, thereby stabilizing gradients by passive diffusion. The platform also enables quick and flexible control of chemical concentration that makes highly dynamic gradients in diffusion chambers. A model with the first approximation of diffusion and surface adsorption of molecules recapitulates the experimentally observed gradients. Budding yeast cells cultured in a gradient of a chemical inducer expressed a reporter fluorescence protein in a concentration-dependent manner. This microfluidic platform serves as a versatile prototype applicable to a broad range of biomedical investigations.

Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

PubMed

Gonçalves, Joana P; Aires, Ricardo S; Francisco, Alexandre P; Madeira, Sara C

2012-01-01

Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched processes related to these biological events were identified. Ranking scores further suggested ability to discern the primary role of a gene (target or regulator). Prototype is available at: http://kdbio.inesc-id.pt/software/regulatorysnapshots.

Regulatory Snapshots: Integrative Mining of Regulatory Modules from Expression Time Series and Regulatory Networks

PubMed Central

Gonçalves, Joana P.; Aires, Ricardo S.; Francisco, Alexandre P.; Madeira, Sara C.

2012-01-01

Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched processes related to these biological events were identified. Ranking scores further suggested ability to discern the primary role of a gene (target or regulator). Prototype is available at: http://kdbio.inesc-id.pt/software/regulatorysnapshots. PMID:22563474

Dynamic change of SGK expression and its role in neuron apoptosis after traumatic brain injury.

PubMed

Wu, Xinmin; Mao, Hui; Liu, Jiao; Xu, Jian; Cao, Jianhua; Gu, Xingxing; Cui, Gang

2013-01-01

Activation of specific signaling pathways in response to mechanical trauma causes delayed neuronal apoptosis; GSK-3β/β-catenin signaling plays a critical role in the apoptosis of neurons in CNS diseases, SGK was discovered as a regulator of GSK-3β/β-catenin pathway, The goal of this study was to determine if the mechanism of cell death or survival mediated by the SGK/GSK-3β/β-catenin pathway is involved in a rat model of TBI. Here, an acute traumatic brain injury model was applied to investigate the expression change and possible roles of SGK, Expression of SGK, and total-GSK-3β, phospho-GSK3β on ser-9, beta-catenin, and caspase-3 were examined by immunohistochemistry and Western blot analysis. Double immunofluorescent staining was used to observe the SGK localizations. Si-RNA was performed to identify whether SGK regulates neuron apoptosis via GSK-3β/β-catenin pathway, ultimately inhibit caspase-3 activation. Temporally, SGK expression showed an increase pattern after TBI and reached a peak at day 3. Spatially, SGK was widely expressed in the neuron, rarely in astrocytes and oligodendrocytes; in addition, the expression patterns of active caspase-3 and phospho-GSK3β were parallel with that of SGK, at the same time, the expression of β-catenin shows similarity with SGK. In vitro, to further investigate the function of SGK, a neuronal cell line PC12 was employed to establish an apoptosis model. We analyzed the association of SGK with apoptosis on PC12 cells by western blot, immunofluorescent labeling and siRNA. the results implied that SGK plays an important role in neuron apoptosis via the regulation of GSK3β/β-catenin signaling pathway; ultimately inhibit caspase-3 activation. Taken together, we inferred traumatic brain injury induced an upregulation of SGK in the central nervous system, which show a protective role in neuron apoptosis.

Pattern identification in time-course gene expression data with the CoGAPS matrix factorization.

PubMed

Fertig, Elana J; Stein-O'Brien, Genevieve; Jaffe, Andrew; Colantuoni, Carlo

2014-01-01

Patterns in time-course gene expression data can represent the biological processes that are active over the measured time period. However, the orthogonality constraint in standard pattern-finding algorithms, including notably principal components analysis (PCA), confounds expression changes resulting from simultaneous, non-orthogonal biological processes. Previously, we have shown that Markov chain Monte Carlo nonnegative matrix factorization algorithms are particularly adept at distinguishing such concurrent patterns. One such matrix factorization is implemented in the software package CoGAPS. We describe the application of this software and several technical considerations for identification of age-related patterns in a public, prefrontal cortex gene expression dataset.

Dynamic Proteomic Characteristics and Network Integration Revealing Key Proteins for Two Kernel Tissue Developments in Popcorn.

PubMed

Dong, Yongbin; Wang, Qilei; Zhang, Long; Du, Chunguang; Xiong, Wenwei; Chen, Xinjian; Deng, Fei; Ma, Zhiyan; Qiao, Dahe; Hu, Chunhui; Ren, Yangliu; Li, Yuling

2015-01-01

The formation and development of maize kernel is a complex dynamic physiological and biochemical process that involves the temporal and spatial expression of many proteins and the regulation of metabolic pathways. In this study, the protein profiles of the endosperm and pericarp at three important developmental stages were analyzed by isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with LC-MS/MS in popcorn inbred N04. Comparative quantitative proteomic analyses among developmental stages and between tissues were performed, and the protein networks were integrated. A total of 6,876 proteins were identified, of which 1,396 were nonredundant. Specific proteins and different expression patterns were observed across developmental stages and tissues. The functional annotation of the identified proteins revealed the importance of metabolic and cellular processes, and binding and catalytic activities for the development of the tissues. The whole, endosperm-specific and pericarp-specific protein networks integrated 125, 9 and 77 proteins, respectively, which were involved in 54 KEGG pathways and reflected their complex metabolic interactions. Confirmation for the iTRAQ endosperm proteins by two-dimensional gel electrophoresis showed that 44.44% proteins were commonly found. However, the concordance between mRNA level and the protein abundance varied across different proteins, stages, tissues and inbred lines, according to the gene cloning and expression analyses of four relevant proteins with important functions and different expression levels. But the result by western blot showed their same expression tendency for the four proteins as by iTRAQ. These results could provide new insights into the developmental mechanisms of endosperm and pericarp, and grain formation in maize.

Dynamic Proteomic Characteristics and Network Integration Revealing Key Proteins for Two Kernel Tissue Developments in Popcorn

PubMed Central

Du, Chunguang; Xiong, Wenwei; Chen, Xinjian; Deng, Fei; Ma, Zhiyan; Qiao, Dahe; Hu, Chunhui; Ren, Yangliu; Li, Yuling

2015-01-01

The formation and development of maize kernel is a complex dynamic physiological and biochemical process that involves the temporal and spatial expression of many proteins and the regulation of metabolic pathways. In this study, the protein profiles of the endosperm and pericarp at three important developmental stages were analyzed by isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with LC-MS/MS in popcorn inbred N04. Comparative quantitative proteomic analyses among developmental stages and between tissues were performed, and the protein networks were integrated. A total of 6,876 proteins were identified, of which 1,396 were nonredundant. Specific proteins and different expression patterns were observed across developmental stages and tissues. The functional annotation of the identified proteins revealed the importance of metabolic and cellular processes, and binding and catalytic activities for the development of the tissues. The whole, endosperm-specific and pericarp-specific protein networks integrated 125, 9 and 77 proteins, respectively, which were involved in 54 KEGG pathways and reflected their complex metabolic interactions. Confirmation for the iTRAQ endosperm proteins by two-dimensional gel electrophoresis showed that 44.44% proteins were commonly found. However, the concordance between mRNA level and the protein abundance varied across different proteins, stages, tissues and inbred lines, according to the gene cloning and expression analyses of four relevant proteins with important functions and different expression levels. But the result by western blot showed their same expression tendency for the four proteins as by iTRAQ. These results could provide new insights into the developmental mechanisms of endosperm and pericarp, and grain formation in maize. PMID:26587848

Heterogeneous Cadherin Expression and Multicellular Aggregate Dynamics in Ovarian Cancer Dissemination.

PubMed

Klymenko, Yuliya; Johnson, Jeffrey; Bos, Brandi; Lombard, Rachel; Campbell, Leigh; Loughran, Elizabeth; Stack, M Sharon

2017-07-01

Epithelial ovarian carcinoma spreads via shedding of cells and multicellular aggregates (MCAs) from the primary tumor into peritoneal cavity, with subsequent intraperitoneal tumor cell:mesothelial cell adhesion as a key early event in metastatic seeding. Evaluation of human tumor extracts and tissues confirms that well-differentiated ovarian tumors express abundant E-cadherin (Ecad), whereas advanced lesions exhibit upregulated N-cadherin (Ncad). Two expression patterns are observed: "mixed cadherin," in which distinct cells within the same tumor express either E- or Ncad, and "hybrid cadherin," wherein single tumor cell(s) simultaneously expresses both cadherins. We demonstrate striking cadherin-dependent differences in cell-cell interactions, MCA formation, and aggregate ultrastructure. Mesenchymal-type Ncad+ cells formed stable, highly cohesive solid spheroids, whereas Ecad+ epithelial-type cells generated loosely adhesive cell clusters covered by uniform microvilli. Generation of "mixed cadherin" MCAs using fluorescently tagged cell populations revealed preferential sorting into cadherin-dependent clusters, whereas mixing of cell lines with common cadherin profiles generated homogeneous aggregates. Recapitulation of the "hybrid cadherin" Ecad+/Ncad+ phenotype, via insertion of the CDH2 gene into Ecad+ cells, resulted in the ability to form heterogeneous clusters with Ncad+ cells, significantly enhanced adhesion to organotypic mesomimetic cultures and peritoneal explants, and increased both migration and matrix invasion. Alternatively, insertion of CDH1 gene into Ncad+ cells greatly reduced cell-to-collagen, cell-to-mesothelium, and cell-to-peritoneum adhesion. Acquisition of the hybrid cadherin phenotype resulted in altered MCA surface morphology with increased surface projections and increased cell proliferation. Overall, these findings support the hypothesis that MCA cadherin composition impacts intraperitoneal cell and MCA dynamics and thereby affects ultimate metastatic success. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Dynamic in vivo binding of transcription factors to cis-regulatory modules of cer and gsc in the stepwise formation of the Spemann–Mangold organizer

PubMed Central

Sudou, Norihiro; Yamamoto, Shinji; Ogino, Hajime; Taira, Masanori

2012-01-01

How multiple developmental cues are integrated on cis-regulatory modules (CRMs) for cell fate decisions remains uncertain. The Spemann–Mangold organizer in Xenopus embryos expresses the transcription factors Lim1/Lhx1, Otx2, Mix1, Siamois (Sia) and VegT. Reporter analyses using sperm nuclear transplantation and DNA injection showed that cerberus (cer) and goosecoid (gsc) are activated by the aforementioned transcription factors through CRMs conserved between X. laevis and X. tropicalis. ChIP-qPCR analysis for the five transcription factors revealed that cer and gsc CRMs are initially bound by both Sia and VegT at the late blastula stage, and subsequently bound by all five factors at the gastrula stage. At the neurula stage, only binding of Lim1 and Otx2 to the gsc CRM, among others, persists, which corresponds to their co-expression in the prechordal plate. Based on these data, together with detailed expression pattern analysis, we propose a new model of stepwise formation of the organizer, in which (1) maternal VegT and Wnt-induced Sia first bind to CRMs at the blastula stage; then (2) Nodal-inducible Lim1, Otx2, Mix1 and zygotic VegT are bound to CRMs in the dorsal endodermal and mesodermal regions where all these genes are co-expressed; and (3) these two regions are combined at the gastrula stage to form the organizer. Thus, the in vivo dynamics of multiple transcription factors highlight their roles in the initiation and maintenance of gene expression, and also reveal the stepwise integration of maternal, Nodal and Wnt signaling on CRMs of organizer genes to generate the organizer. PMID:22492356

Dynamic in vivo binding of transcription factors to cis-regulatory modules of cer and gsc in the stepwise formation of the Spemann-Mangold organizer.

PubMed

Sudou, Norihiro; Yamamoto, Shinji; Ogino, Hajime; Taira, Masanori

2012-05-01

How multiple developmental cues are integrated on cis-regulatory modules (CRMs) for cell fate decisions remains uncertain. The Spemann-Mangold organizer in Xenopus embryos expresses the transcription factors Lim1/Lhx1, Otx2, Mix1, Siamois (Sia) and VegT. Reporter analyses using sperm nuclear transplantation and DNA injection showed that cerberus (cer) and goosecoid (gsc) are activated by the aforementioned transcription factors through CRMs conserved between X. laevis and X. tropicalis. ChIP-qPCR analysis for the five transcription factors revealed that cer and gsc CRMs are initially bound by both Sia and VegT at the late blastula stage, and subsequently bound by all five factors at the gastrula stage. At the neurula stage, only binding of Lim1 and Otx2 to the gsc CRM, among others, persists, which corresponds to their co-expression in the prechordal plate. Based on these data, together with detailed expression pattern analysis, we propose a new model of stepwise formation of the organizer, in which (1) maternal VegT and Wnt-induced Sia first bind to CRMs at the blastula stage; then (2) Nodal-inducible Lim1, Otx2, Mix1 and zygotic VegT are bound to CRMs in the dorsal endodermal and mesodermal regions where all these genes are co-expressed; and (3) these two regions are combined at the gastrula stage to form the organizer. Thus, the in vivo dynamics of multiple transcription factors highlight their roles in the initiation and maintenance of gene expression, and also reveal the stepwise integration of maternal, Nodal and Wnt signaling on CRMs of organizer genes to generate the organizer.

Parallels between Global Transcriptional Programs of Polarizing Caco-2 Intestinal Epithelial Cells In Vitro and Gene Expression Programs in Normal Colon and Colon Cancer

PubMed Central

Sääf, Annika M.; Halbleib, Jennifer M.; Chen, Xin; Yuen, Siu Tsan; Leung, Suet Yi

2007-01-01

Posttranslational mechanisms are implicated in the development of epithelial cell polarity, but little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized temporal patterns of gene expression during cell–cell adhesion-initiated polarization of cultured human Caco-2 cells, which develop structural and functional polarity resembling enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell–cell contacts. Comparison to gene expression patterns in normal human colon and colon tumors revealed that the pattern in proliferating, nonpolarized Caco-2 cells paralleled patterns seen in human colon cancer in vivo, including expression of genes involved in cell proliferation. The pattern switched in polarized Caco-2 cells to one more closely resembling that in normal colon tissue, indicating that regulation of transcription underlying Caco-2 cell polarization is similar to that during enterocyte differentiation in vivo. Surprisingly, the temporal program of gene expression in polarizing Caco-2 cells involved changes in signaling pathways (e.g., Wnt, Hh, BMP, FGF) in patterns similar to those during migration and differentiation of intestinal epithelial cells in vivo, despite the absence of morphogen gradients and interactions with stromal cells characteristic of enterocyte differentiation in situ. The full data set is available at http://microarray-pubs.stanford.edu/CACO2. PMID:17699589

Patterns of activity expressed by juvenile horseshoe crabs.

PubMed

Dubofsky, E A; Simpson, S D; Chabot, Christopher C; Watson, Winsor H

2013-09-01

Adult American horseshoe crabs, Limulus polyphemus, possess endogenous circadian and circatidal clocks controlling visual sensitivity and locomotion, respectively. The goal of this study was to determine the types of activity rhythms expressed by juvenile horseshoe crabs (n = 24) when exposed to a 14:10 light/dark cycle (LD) for 10 days, followed by 10 days of constant darkness (DD). Horseshoe crab activity was recorded with a digital time-lapse video system that used an infrared-sensitive camera so animals could be monitored at night. In LD, 15 animals expressed daily patterns of activity, 6 displayed a circatidal pattern, and the remaining 3 were arrhythmic. Of the 15 animals with daily patterns of locomotion, 7 had a significant preference (P < 0.05) for diurnal activity and 3 for nocturnal activity; the remainder did not express a significant preference for day or night activity. In DD, 13 horseshoe crabs expressed circatidal rhythms and 8 maintained a pattern of about 24 h. Although these results suggest the presence of a circadian clock influencing circatidal patterns of locomotion, these apparent circadian rhythms may actually represent the expression of just one of the two bouts of activity driven by the putative circalunidian clocks that control their tidal rhythms. Overall, these results indicate that, like adults, juvenile horseshoe crabs express both daily and tidal patterns of activity and that at least one, and maybe both, of these patterns is driven by endogenous clocks.

Dynamic Tumor Growth Patterns in a Novel Murine Model of Colorectal Cancer

PubMed Central

Olson, Terrah J. Paul; Hadac, Jamie N.; Sievers, Chelsie K.; Leystra, Alyssa A.; Deming, Dustin A.; Zahm, Christopher D.; Albrecht, Dawn M.; Nomura, Alice; Nettekoven, Laura A.; Plesh, Lauren K.; Clipson, Linda; Sullivan, Ruth; Newton, Michael A.; Schelman, William R.; Halberg, Richard B.

2014-01-01

Colorectal cancer (CRC) often arises from adenomatous colonic polyps. Polyps can grow and progress to cancer, but may also remain static in size, regress, or resolve. Predicting which progress and which remain benign is difficult. We developed a novel long-lived murine model of CRC with tumors that can be followed by colonoscopy. Our aim was to assess whether these tumors have similar growth patterns and histologic fates to human colorectal polyps to identify features to aid in risk-stratification of colonic tumors. Long-lived ApcMin/+ mice were treated with dextran sodium sulfate to promote colonic tumorigenesis. Tumor growth patterns were characterized by serial colonoscopy with biopsies obtained for immunohistochemistry and gene expression profiling. Tumors grew, remained static, regressed, or resolved over time with different relative frequencies. Newly developed tumors demonstrated higher rates of growth and resolution than more established tumors that tended to remain static in size. Colonic tumors were hyperplastic lesions (3%), adenomas (73%), intramucosal carcinomas (20%), or adenocarcinomas (3%). Interestingly, the level of β-catenin was higher in adenomas that became intratumoral carcinomas as compared to those that failed to progress. In addition, differentially expressed genes between adenomas and intramucosal carcinomas were identified. This novel murine model of intestinal tumorigenesis develops colonic tumors that can be monitored by serial colonoscopy, mirror growth patterns seen in human colorectal polyps, and progress to CRC. Further characterization of cellular and molecular features are needed to determine which features can be used to risk-stratify polyps for progression to CRC and potentially guide prevention strategies. PMID:24196829

Quantifying Postural Control during Exergaming Using Multivariate Whole-Body Movement Data: A Self-Organizing Maps Approach

PubMed Central

van Diest, Mike; Stegenga, Jan; Wörtche, Heinrich J.; Roerdink, Jos B. T. M; Verkerke, Gijsbertus J.; Lamoth, Claudine J. C.

2015-01-01

Background Exergames are becoming an increasingly popular tool for training balance ability, thereby preventing falls in older adults. Automatic, real time, assessment of the user’s balance control offers opportunities in terms of providing targeted feedback and dynamically adjusting the gameplay to the individual user, yet algorithms for quantification of balance control remain to be developed. The aim of the present study was to identify movement patterns, and variability therein, of young and older adults playing a custom-made weight-shifting (ice-skating) exergame. Methods Twenty older adults and twenty young adults played a weight-shifting exergame under five conditions of varying complexity, while multi-segmental whole-body movement data were captured using Kinect. Movement coordination patterns expressed during gameplay were identified using Self Organizing Maps (SOM), an artificial neural network, and variability in these patterns was quantified by computing Total Trajectory Variability (TTvar). Additionally a k Nearest Neighbor (kNN) classifier was trained to discriminate between young and older adults based on the SOM features. Results Results showed that TTvar was significantly higher in older adults than in young adults, when playing the exergame under complex task conditions. The kNN classifier showed a classification accuracy of 65.8%. Conclusions Older adults display more variable sway behavior than young adults, when playing the exergame under complex task conditions. The SOM features characterizing movement patterns expressed during exergaming allow for discriminating between young and older adults with limited accuracy. Our findings contribute to the development of algorithms for quantification of balance ability during home-based exergaming for balance training. PMID:26230655

Quantifying Postural Control during Exergaming Using Multivariate Whole-Body Movement Data: A Self-Organizing Maps Approach.

PubMed

van Diest, Mike; Stegenga, Jan; Wörtche, Heinrich J; Roerdink, Jos B T M; Verkerke, Gijsbertus J; Lamoth, Claudine J C

2015-01-01

Exergames are becoming an increasingly popular tool for training balance ability, thereby preventing falls in older adults. Automatic, real time, assessment of the user's balance control offers opportunities in terms of providing targeted feedback and dynamically adjusting the gameplay to the individual user, yet algorithms for quantification of balance control remain to be developed. The aim of the present study was to identify movement patterns, and variability therein, of young and older adults playing a custom-made weight-shifting (ice-skating) exergame. Twenty older adults and twenty young adults played a weight-shifting exergame under five conditions of varying complexity, while multi-segmental whole-body movement data were captured using Kinect. Movement coordination patterns expressed during gameplay were identified using Self Organizing Maps (SOM), an artificial neural network, and variability in these patterns was quantified by computing Total Trajectory Variability (TTvar). Additionally a k Nearest Neighbor (kNN) classifier was trained to discriminate between young and older adults based on the SOM features. Results showed that TTvar was significantly higher in older adults than in young adults, when playing the exergame under complex task conditions. The kNN classifier showed a classification accuracy of 65.8%. Older adults display more variable sway behavior than young adults, when playing the exergame under complex task conditions. The SOM features characterizing movement patterns expressed during exergaming allow for discriminating between young and older adults with limited accuracy. Our findings contribute to the development of algorithms for quantification of balance ability during home-based exergaming for balance training.

Dynamic Connectivity Patterns in Conscious and Unconscious Brain

PubMed Central

Ma, Yuncong; Hamilton, Christina

2017-01-01

Abstract Brain functional connectivity undergoes dynamic changes from the awake to unconscious states. However, how the dynamics of functional connectivity patterns are linked to consciousness at the behavioral level remains elusive. In this study, we acquired resting-state functional magnetic resonance imaging data during wakefulness and graded levels of consciousness in rats. Data were analyzed using a dynamic approach combining the sliding window method and k-means clustering. Our results demonstrate that whole-brain networks contained several quasi-stable patterns that dynamically recurred from the awake state into anesthetized states. Remarkably, two brain connectivity states with distinct spatial similarity to the structure of anatomical connectivity were strongly biased toward high and low consciousness levels, respectively. These results provide compelling neuroimaging evidence linking the dynamics of whole-brain functional connectivity patterns and states of consciousness at the behavioral level. PMID:27846731

Exposure of honey bees (Apis mellifera) to different classes of insecticides exhibit distinct molecular effect patterns at concentrations that mimic environmental contamination.

PubMed

Christen, Verena; Fent, Karl

2017-07-01

Pesticides are implicated in the decline of honey bee populations. Many insecticides are neurotoxic and act by different modes of actions. Although a link between insecticide exposure and changed behaviour has been made, molecular effects underlying these effects are poorly understood. Here we elucidated molecular effects at environmental realistic concentrations of two organophosphates, chlorpyrifos and malathion, the pyrethroid cypermethrin, and the ryanodine receptor activator, chlorantraniliprole. We assessed transcriptional alterations of selected genes at three exposure times (24 h, 48 h, 72 h) in caged honey bees exposed to different concentrations of these compounds. Our targeted gene expression concept focused on several transcripts, including nicotinic acetylcholine receptor α 1 and α 2 (nAChRα1, nAChRα2) subunits, the multifunctional gene vitellogenin, immune system related genes of three immune system pathways, genes belonging to the detoxification system and ER stress genes. Our data indicate a dynamic pattern of expressional changes at different exposure times. All four insecticides induced strong alterations in the expression of immune system related genes suggesting negative implications for honey bee health, as well as cytochrome P450 enzyme transcripts suggesting an interference with metabolism. Exposure to neurotoxic chlorpyrifos, malathion and cypermethrin resulted in up-regulation of nAChRα1 and nAChRα2. Moreover, alterations in the expression of vitellogenin occurred, which suggests implications on foraging activity. Chlorantraniliprole induced ER stress which may be related to toxicity. The comparison of all transcriptional changes indicated that the expression pattern is rather compound-specific and related to its mode of action, but clusters of common transcriptional changes between different compounds occurred. As transcriptional alterations occurred at environmental concentrations our data provide a molecular basis for observed adverse effects of these insecticides to bees. Copyright © 2017 Elsevier Ltd. All rights reserved.

Suppression of the endoplasmic reticulum calcium pump during zebrafish gastrulation affects left-right asymmetry of the heart and brain.

PubMed

Kreiling, Jill A; Balantac, Zaneta L; Crawford, Andrew R; Ren, Yuexin; Toure, Jamal; Zchut, Sigalit; Kochilas, Lazaros; Creton, Robbert

2008-01-01

Vertebrate embryos generate striking Ca(2+) patterns, which are unique regulators of dynamic developmental events. In the present study, we used zebrafish embryos as a model system to examine the developmental roles of Ca(2+) during gastrulation. We found that gastrula stage embryos maintain a distinct pattern of cytosolic Ca(2+) along the dorsal-ventral axis, with higher Ca(2+) concentrations in the ventral margin and lower Ca(2+) concentrations in the dorsal margin and dorsal forerunner cells. Suppression of the endoplasmic reticulum Ca(2+) pump with 0.5 microM thapsigargin elevates cytosolic Ca(2+) in all embryonic regions and induces a randomization of laterality in the heart and brain. Affected hearts, visualized in living embryos by a subtractive imaging technique, displayed either a reversal or loss of left-right asymmetry. Brain defects include a left-right reversal of pitx2 expression in the dorsal diencephalon and a left-right reversal of the prominent habenular nucleus in the brain. Embryos are sensitive to inhibition of the endoplasmic reticulum Ca(2+) pump during early and mid gastrulation and lose their sensitivity during late gastrulation and early segmentation. Suppression of the endoplasmic reticulum Ca(2+) pump during gastrulation inhibits expression of no tail (ntl) and left-right dynein related (lrdr) in the dorsal forerunner cells and affects development of Kupffer's vesicle, a ciliated organ that generates a counter-clockwise flow of fluid. Previous studies have shown that Ca(2+) plays a role in Kupffer's vesicle function, influencing ciliary motility and translating the vesicle's counter-clockwise flow into asymmetric patterns of gene expression. The present results suggest that Ca(2+) plays an additional role in the formation of Kupffer's vesicle.

Insight into Buffalo (Bubalus bubalis) RIG1 and MDA5 Receptors: A Comparative Study on dsRNA Recognition and In-Vitro Antiviral Response

PubMed Central

Singh, Manvender; Brahma, Biswajit; Maharana, Jitendra; Patra, Mahesh Chandra; Kumar, Sushil; Mishra, Purusottam; Saini, Megha; De, Bidhan Chandra; Mahanty, Sourav; Datta, Tirtha Kumar; De, Sachinandan

2014-01-01

RIG1 and MDA5 have emerged as important intracellular innate pattern recognition receptors that recognize viral RNA and mediate cellular signals controlling Type I interferon (IFN-I) response. Buffalo RIG1 and MDA5 genes were investigated to understand the mechanism of receptor induced antiviral response. Sequence analysis revealed that RIG1 and MDA5 maintain a domain arrangement that is common in mammals. Critical binding site residues of the receptors are evolutionary conserved among mammals. Molecular dynamics simulations suggested that RIG1 and MDA5 follow a similar, if not identical, dsRNA binding pattern that has been previously reported in human. Moreover, binding free energy calculation revealed that MDA5 had a greater affinity towards dsRNA compared to RIG1. Constitutive expressions of RLR genes were ubiquitous in different tissues without being specific to immune organs. Poly I:C stimulation induced elevated expressions of IFN-β and IFN-stimulated genes (ISGs) through interferon regulatory factors (IRFs) mediated pathway in buffalo foetal fibroblast cells. The present study provides crucial insights into the structure and function of RIG1 and MDA5 receptors in buffalo. PMID:24587036

Phenotypic stability and plasticity in GMP-derived cells as determined by their underlying regulatory network.

PubMed

Ramírez, Carlos; Mendoza, Luis

2018-04-01

Blood cell formation has been recognized as a suitable system to study celular differentiation mainly because of its experimental accessibility, and because it shows characteristics such as hierarchical and gradual bifurcated patterns of commitment, which are present in several developmental processes. Although hematopoiesis has been extensively studied and there is a wealth of molecular and cellular data about it, it is not clear how the underlying molecular regulatory networks define or restrict cellular differentiation processes. Here, we infer the molecular regulatory network that controls the differentiation of a blood cell subpopulation derived from the granulocyte-monocyte precursor (GMP), comprising monocytes, neutrophils, eosinophils, basophils and mast cells. We integrate published qualitative experimental data into a model to describe temporal expression patterns observed in GMP-derived cells. The model is implemented as a Boolean network, and its dynamical behavior is studied. Steady states of the network can be clearly identified with the expression profiles of monocytes, mast cells, neutrophils, basophils, and eosinophils, under wild-type and mutant backgrounds. All scripts are publicly available at https://github.com/caramirezal/RegulatoryNetworkGMPModel. lmendoza@biomedicas.unam.mx. Supplementary data are available at Bioinformatics online.

Visual Cortex Plasticity: A Complex Interplay of Genetic and Environmental Influences

PubMed Central

Maya-Vetencourt, José Fernando; Origlia, Nicola

2012-01-01

The central nervous system architecture is highly dynamic and continuously modified by sensory experience through processes of neuronal plasticity. Plasticity is achieved by a complex interplay of environmental influences and physiological mechanisms that ultimately activate intracellular signal transduction pathways regulating gene expression. In addition to the remarkable variety of transcription factors and their combinatorial interaction at specific gene promoters, epigenetic mechanisms that regulate transcription have emerged as conserved processes by which the nervous system accomplishes the induction of plasticity. Experience-dependent changes of DNA methylation patterns and histone posttranslational modifications are, in fact, recruited as targets of plasticity-associated signal transduction mechanisms. Here, we shall concentrate on structural and functional consequences of early sensory deprivation in the visual system and discuss how intracellular signal transduction pathways associated with experience regulate changes of chromatin structure and gene expression patterns that underlie these plastic phenomena. Recent experimental evidence for mechanisms of cross-modal plasticity following congenital or acquired sensory deprivation both in human and animal models will be considered as well. We shall also review different experimental strategies that can be used to achieve the recovery of sensory functions after long-term deprivation in humans. PMID:22852098

Genomic Pangea: coordinate gene regulation and cell-specific chromosomal topologies.

PubMed

Laster, Kyle; Kosak, Steven T

2010-06-01

The eukaryotic nucleus is functionally organized. Gene loci, for example, often reveal altered localization patterns according to their developmental regulation. Whole chromosomes also demonstrate non-random nuclear positions, correlated with inherent characteristics such as gene density or size. Given that hundreds to thousands of genes are coordinately regulated in any given cell type, interest has grown in whether chromosomes may be specifically localized according to gene regulation. A synthesis of the evidence for preferential chromosomal organization suggests that, beyond basic characteristics, chromosomes can assume positions functionally related to gene expression. Moreover, analysis of total chromosome organization during cellular differentiation indicates that unique chromosome topologies, albeit probabilistic, in effect define a cell lineage. Future work with new techniques, including the advanced forms of the chromosome conformation capture (3C), and the development of next-generation whole-genome imaging approaches, will help to refine our view of chromosomal organization. We suggest that genomic organization during cellular differentiation should be viewed as a dynamic process, with gene expression patterns leading to chromosome associations that feed back on themselves, leading to the self-organization of the genome according to coordinate gene regulation. Copyright 2010 Elsevier Ltd. All rights reserved.

Network Analysis Reveals a Common Host-Pathogen Interaction Pattern in Arabidopsis Immune Responses.

PubMed

Li, Hong; Zhou, Yuan; Zhang, Ziding

2017-01-01

Many plant pathogens secrete virulence effectors into host cells to target important proteins in host cellular network. However, the dynamic interactions between effectors and host cellular network have not been fully understood. Here, an integrative network analysis was conducted by combining Arabidopsis thaliana protein-protein interaction network, known targets of Pseudomonas syringae and Hyaloperonospora arabidopsidis effectors, and gene expression profiles in the immune response. In particular, we focused on the characteristic network topology of the effector targets and differentially expressed genes (DEGs). We found that effectors tended to manipulate key network positions with higher betweenness centrality. The effector targets, especially those that are common targets of an individual effector, tended to be clustered together in the network. Moreover, the distances between the effector targets and DEGs increased over time during infection. In line with this observation, pathogen-susceptible mutants tended to have more DEGs surrounding the effector targets compared with resistant mutants. Our results suggest a common plant-pathogen interaction pattern at the cellular network level, where pathogens employ potent local impact mode to interfere with key positions in the host network, and plant organizes an in-depth defense by sequentially activating genes distal to the effector targets.

A transcription factor hierarchy defines an environmental stress response network.

PubMed

Song, Liang; Huang, Shao-Shan Carol; Wise, Aaron; Castanon, Rosa; Nery, Joseph R; Chen, Huaming; Watanabe, Marina; Thomas, Jerushah; Bar-Joseph, Ziv; Ecker, Joseph R

2016-11-04

Environmental stresses are universally encountered by microbes, plants, and animals. Yet systematic studies of stress-responsive transcription factor (TF) networks in multicellular organisms have been limited. The phytohormone abscisic acid (ABA) influences the expression of thousands of genes, allowing us to characterize complex stress-responsive regulatory networks. Using chromatin immunoprecipitation sequencing, we identified genome-wide targets of 21 ABA-related TFs to construct a comprehensive regulatory network in Arabidopsis thaliana Determinants of dynamic TF binding and a hierarchy among TFs were defined, illuminating the relationship between differential gene expression patterns and ABA pathway feedback regulation. By extrapolating regulatory characteristics of observed canonical ABA pathway components, we identified a new family of transcriptional regulators modulating ABA and salt responsiveness and demonstrated their utility to modulate plant resilience to osmotic stress. Copyright © 2016, American Association for the Advancement of Science.