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Results for “Promoter dynamics”

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At least 109 records · Page 6Linked to original sources
PubMed1997

Ca2+-mediated GTP-dependent dynamic assembly of bacterial cell division protein FtsZ into asters and polymer networks in vitro.

FtsZ, a tubulin-like GTPase that forms a dynamic ring marking the division plane of prokaryotic cells, is essential for cytokinesis. It is not known what triggers FtsZ ring assembly. In this work, we use a FtsZ-green fluorescent protein (Gfp) chimera to assay FtsZ assembly over time by using fluorescence microscopy. We show that FtsZ polymers can assemble dynamically in solution in a GTP-dependent manner. Initially, FtsZ nucleation centers grow into aster-like structures that dramatically resemble microtubule organizing centers. As assembly proceeds further, protofilament bundles emanating from different asters interconnect, mimicking the closure of the FtsZ ring in vivo. Surprisingly, millimolar levels of Ca2+ promote FtsZ dynamic assembly. FtsZ can undergo repeated GTP-dependent assembly and disassembly in solution by sequential addition and removal of Ca2+. In addition, GTP binding and hydrolysis by FtsZ are regulated by Ca2+ concentration. Although the concentration of Ca2+ required for FtsZ assembly in vitro is high, its clear and specific effect on FtsZ dynamics suggests the possibility that Ca2+ may have a role in regulating FtsZ ring assembly in the cell.

Bacterial Proteins↗
PubMed2006

Combined functional task practice and dynamic high intensity resistance training promotes recovery of upper-extremity motor function in post-stroke hemiparesis: a case study.

BACKGROUND AND PURPOSE: Weakness is a significant impairment in persons with post-stroke hemiparesis, yet traditional clinical perspectives caution against strengthening in neurological populations. Significant correlations between weakness and functional movement have been demonstrated, however, a clear relationship between increased strength and functional improvement has been elusive. This case study describes a combined program of dynamic, high-intensity resistance training and functional task practice for the upper-extremity in adult hemiparesis. CASE DESCRIPTION: The patient was a 65-year-old, right hand dominant woman who presented to the Neural Control of Movement Laboratory at the Palo Alto VA Rehabilitation Research and Development Center 16 weeks following clipping of an unruptured aneurysm with consequent dense right hemiparesis. She received 7 weeks of acute rehabilitation according to CARF guidelines (ie, at least 3 hours of two or more disciplines, 6 days per week). Her baseline research evaluation revealed significant upperextremity deficits at the ICF body structure/function level including: weakness, shoulder pain, mild resistance to passive movement, and need for moderate to maximal assistance in many activities of daily living including bathing and dressing. The Stroke Impact Scale score reporting her perspective indicated she had recovered from her stroke only 50%. The hybrid resistance training-functional task practice intervention, detailed in this report, was delivered 3 times per week for 6 weeks with each session lasting 75:00. OUTCOMES: The subject revealed marked improvements in isometric and dynamic force production in 5 key upper-extremity actions: elbow flexion, elbow extension, shoulder flexion, shoulder abduction, and shoulder external rotation. Strength gains were accompanied by increased EMG activation immediately postintervention and by a combination of increased activation and apparent hypertrophic effects at 6 month follow up. Marked improvements were noted in all clinical and functional measures and in an elbow trajectorytracking task which served as a surrogate measure of motor control. DISCUSSION: Improvements in strength and positive outcome effects at the physiological, clinical, and functional levels were observed in this subject following the experimental hybrid upper-extremity rehabilitation intervention described. Importantly, no deleterious effects were observed including exacerbation of spasticity or musculoskeletal compromise. Observations of improved EMG activation in this case study suggest that improvements in motor activation underlie these strength gains and can likely be attributed to working at a high intensity level.

Activities of Daily Living↗
PubMed2005

Conservation and evolvability in regulatory networks: the evolution of ribosomal regulation in yeast.

Transcriptional modules of coregulated genes play a key role in regulatory networks. Comparative studies show that modules of coexpressed genes are conserved across taxa. However, little is known about the mechanisms underlying the evolution of module regulation. Here, we explore the evolution of cis-regulatory programs associated with conserved modules by integrating expression profiles for two yeast species and sequence data for a total of 17 fungal genomes. We show that although the cis-elements accompanying certain conserved modules are strictly conserved, those of other conserved modules are remarkably diverged. In particular, we infer the evolutionary history of the regulatory program governing ribosomal modules. We show how a cis-element emerged concurrently in dozens of promoters of ribosomal protein genes, followed by the loss of a more ancient cis-element. We suggest that this formation of an intermediate redundant regulatory program allows conserved transcriptional modules to gradually switch from one regulatory mechanism to another while maintaining their functionality. Our work provides a general framework for the study of the dynamics of promoter evolution at the level of transcriptional modules and may help in understanding the evolvability and increased redundancy of transcriptional regulation in higher organisms.

Computational Biology↗
PubMed1998

On the relationship between genomic regulatory element organization and gene regulatory dynamics.

In this project we study the relationship between genomic regulatory element organization and gene regulatory dynamics. This paper illustrates an approach to investigating this relationship based on the application of classical nonlinear system analysis techniques to a transcription level, statistical thermodynamical model like that used in Shea & Ackers (1985). Preliminary ideas presented at the ICMCM conference (Wolf & Eeckman, 1998) are developed in this manuscript. We show that, for prokaryotic gene circuits dominated by local promoter control, dynamical system behavior descriptors like the number and stability of equilibrium point steady states and their bifurcation potential can be largely determined from genomic organization (e.g. the number, type, and placement of regulatory protein binding sites). Concepts are illustrated on hypothetical gene regulation systems with one or two genes and varying numbers of regulatory protein binding sites (operators). Gene regulatory systems with a single gene and an arbitrary number of operator sites are shown to be globally stable, with the potential for having multiple equilibrium points and capable of bifurcating. A monomer-controlled gene regulation system with n operator sites is proven to have a maximum of 1+n/2 stable equilibria for even n, and (n+1)/2 for odd n, while a multimer-controlled, n operator site system is shown to have a maximum of 2+n/2 stable equilibria for even n, and (n+3)/2 for odd n. These results are applied to the design of a two-state switch using a gene regulation system with two operator sites. The question "what is the simplest possible gene regulation system capable of acting like a switch?" is answered. The paper ends with an analysis of a two-gene regulation system, the results of which point to the existence of a "soft-switching" mechanism that may account for the "on-off" hypothesized behavior of some gene networks.

Animals↗
PubMed2006

Oxidized LDL specifically promotes the initiation of monocyte invasion during transendothelial migration with upregulated PECAM-1 and downregulated VE-cadherin on endothelial junctions.

It is poorly understood how oxidized LDL (oxLDL) promotes monocyte dynamics in transendothelial migration (TEM) in atherogenesis. We developed an in vitro 3D-live-single cell TEM assay system with subendothelial oxLDL embedded in ultra-thin collagen gels, mimicking subendothelial oxLDL accumulation in vivo. With dividing monocyte dynamics into three stages (1: adhesion on endothelium, 2: invasion and 3: complete transmigration below endothelium), we analyzed the stage transition dynamics of individual living human monocytes. OxLDL did not enhance initial monocyte adhesion to endothelium (stage 1), but it specifically primed adherent monocytes to start invasion (stage 1-->2). Once invasion started, it had no effect thereafter on monocyte stage transition (stage 2-->3). OxLDL upregulated PECAM-1 and downregulated VE-cadherin on endothelial junctions without monocyte addition, both of which could promote monocyte entry by enhanced homophilic binding to monocyte PECAM-1, and by disrupted junctional barrier, respectively. Meanwhile, monocyte speed at neither locomotion on endothelium (stage 1) nor subendothelial migration (stage 3) was altered by oxLDL. These data indicate that before monocyte adhesion, endothelial junctions changed their conformation to more monocyte-acceptable state in response to oxLDL, resulting the stage-specific promotion of monocyte TEM (stage 1-->2; initiation of invasion) with no enhancement of its initial adhesion or migration speed.

Antigens, CD↗
PubMed2006

Gamma-tubulin is required for proper recruitment and assembly of Kar9-Bim1 complexes in budding yeast.

Microtubule plus-end-interacting proteins (+TIPs) promote the dynamic interactions between the plus ends (+ends) of astral microtubules and cortical actin that are required for preanaphase spindle positioning. Paradoxically, +TIPs such as the EB1 orthologue Bim1 and Kar9 also associate with spindle pole bodies (SPBs), the centrosome equivalent in budding yeast. Here, we show that deletion of four C-terminal residues of the budding yeast gamma-tubulin Tub4 (tub4-delta dsyl) perturbs Bim1 and Kar9 localization to SPBs and Kar9-dependent spindle positioning. Surprisingly, we find Kar9 localizes to microtubule +ends in tub4-delta dsyl cells, but these microtubules fail to position the spindle when targeted to the bud. Using cofluorescence and coaffinity purification, we show Kar9 complexes in tub4-delta dsyl cells contain reduced levels of Bim1. Astral microtubule dynamics is suppressed in tub4-delta dsyl cells, but it are restored by deletion of Kar9. Moreover, Myo2- and F-actin-dependent dwelling of Kar9 in the bud is observed in tub4-delta dsyl cells, suggesting defective Kar9 complexes tether microtubule +ends to the cortex. Overproduction of Bim1, but not Kar9, restores Kar9-dependent spindle positioning in the tub4-delta dsyl mutant, reduces cortical dwelling, and promotes Bim1-Kar9 interactions. We propose that SPBs, via the tail of Tub4, promote the assembly of functional +TIP complexes before their deployment to microtubule +ends.

Actins↗
PubMed2003

A dynamic dendritic refractory period regulates burst discharge in the electrosensory lobe of weakly electric fish.

Na+-dependent spikes initiate in the soma or axon hillock region and actively backpropagate into the dendritic arbor of many central neurons. Inward currents underlying spike discharge are offset by outward K+ currents that repolarize a spike and establish a refractory period to temporarily prevent spike discharge. We show in a sensory neuron that somatic and dendritic K+ channels differentially control burst discharge by regulating the extent to which backpropagating dendritic spikes can re-excite the soma. During repetitive discharge a progressive broadening of dendritic spikes promotes a dynamic increase in dendritic spike refractory period. A leaky integrate-and-fire model shows that spike bursts are terminated when a decreasing somatic interspike interval and an increasing dendritic spike refractory period synergistically act to block backpropagation. The time required for the somatic interspike interval to intersect with dendritic refractory period determines burst frequency, a time that is regulated by somatic and dendritic spike repolarization. Thus, K+ channels involved in spike repolarization can efficiently control the pattern of spike output by establishing a soma-dendritic interaction that invokes dynamic shifts in dendritic spike properties.

Action Potentials↗
PubMed1996

International migration and national development.

"In this review, we examine theories, data, and research on the macroeconomic relationship between international migration and national development in all world regions. Earlier reviews have generally been pessimistic about the prospects for economic development as a result of international migration. Until recently, however, theories and data have not recognized the complex, multifaceted, and often indirect ways that international migration can influence the economic status of households, communities, and nations, and they have generally failed to appreciate how these relationships can change over time. When these complexities are incorporated into theoretical models, research designs, and data collection, a more nuanced and far more positive picture emerges. Given a supportive mix of macroeconomic policies and infrastructure, international migration may function as a dynamic force promoting economic growth and national development, so long as it does not bring about the selective emigration of scarce human capital needed for development at home."

Demography↗
PubMed1997

The motility-associated proteins GAP-43, MARCKS, and CAP-23 share unique targeting and surface activity-inducing properties.

Local regulation of the cortical cytoskeleton controls cell surface dynamics. GAP-43 and MARCKS are two abundant cytosolic protein kinase C substrates that are anchored to the cell membrane via acyl groups and interact with the cortical cytoskeleton. Each of them has been implicated in several forms of motility involving the cell surface. Although their primary sequences do not reveal significant homologies, GAP-43, MARCKS, and the cortical cytoskeleton-associated protein CAP-23 (in the following, the three proteins will be abbreviated as GMC) share a number of characteristic biochemical and biophysical properties and an unusual amino acid composition. In this study we determined whether GMC may be related functionally. In double-labeling immunocytochemistry experiments GMC accumulated at unique surface-associated structures, where they codistributed. In transfected cells GMC induced the same range of characteristic changes in cell morphology and cell surface activities, including prominent blebs and filopodia. These activities correlated with local accumulation of transgene and had characteristic features of locally elevated actin dynamics, including loss of stress fiber structures, accumulation of beta-(cytosolic) actin at cell surface protrusions, and dynamic blebbing activity. Analysis of appropriate deletion and fusion constructs revealed that the surface accumulation pattern and cell surface activities were correlated and that minimal structural requirements included acylation-mediated targeting to the cell membrane and the presence of a predominantly GMC-type sequence composition. Based on these experiments and on the results of previous studies on GAP-43, MARCKS, and CAP-23, we propose that GMC may define a class of functionally related proteins whose local accumulation promotes actin dynamics and the formation of dynamic structures at the cell periphery. Superimposed on these general properties, differences in the regulation of membrane association and binding properties of effector domains would confer individual properties to each of these proteins.

3T3 Cells↗
PubMedDate not supplied

Breast feeding practices in a resettlement colony and its implications for promotional activities.

The mothers of 547 children less than three years of age were interviewed for breastfeeding practices using WHO suggested methodology in a resettlement colony of South Delhi. Only 1.8% of children were never breastfed. Prelacteal feeds were given in 90.9% of infants. More than half received their first breastfeed on 3rd day or later. Among children under three months of age, one third were already receiving top milk. 68.4% of mothers felt that the child should be breastfed for as long as possible. Demand feeding was practised by 95% of the mothers. Most of the mothers did not seek privacy to breastfeed their children. The need to identify desirable and undesirable infant feeding practices prevalent in an area has been stressed so that appropriate promotional activities can be carried out more effectively.

Attitude to Health↗
PubMed2006

Nonlinear modelling approach to human promoter sequences.

By means of the nonlinear modelling technique, we find the nonlinear deterministic structures in the totally 4737 human promoter sequences. These deterministic structures prefer to occur much more outside of a special region around the transcriptional start site. The number and positions of the deterministic structures are basically different for different promoter sequences. Generally, they do not coincide with the CpG islands, the simple repetitive sequences and the low-complexity sequences, which tell us that they should be special structures with biological functions rather than these special segments.

CpG Islands↗
PubMed2006

The proteasome restricts permissive transcription at tissue-specific gene loci in embryonic stem cells.

The ability of stem cells to activate different gene expression programs requires the choreographed assembly of trans-acting factors at enhancers and promoters during cell differentiation. In this study, we show that the proteasome acts on specific regulatory regions in embryonic stem (ES) cells to prevent incorrect transcriptional initiation. Chemical or siRNA-mediated inhibition of proteasome activity results in increased transcription factor and RNA polymerase II binding and leads to activation of cryptic promoters. Analysis of the binding profiles of different proteasome subunits in normal ES cells and following RNAi knockdown of individual subunits provides evidence for a targeted assembly of the 26S proteasome at specific regulatory elements. Our results suggest that the proteasome promotes a dynamic turnover of transcription factor and Pol II binding at tissue-specific gene domains in ES cells, thereby restricting permissive transcriptional activity and keeping the genes in a potentiated state, ready for activation at later stages.

Animals↗
PubMed2001

Cell-type-specific regulation of the two foamy virus promoters.

The foamy virus (FV) genome contains two promoters, the canonical long terminal repeat (LTR) promoter, containing three consensus AP-1 binding sites, and an internal promoter (IP) within the env gene. We investigated the regulation of the two promoters in lytic and persistent infections and found that in the presence of a constitutive source of the viral transactivator protein Tas, transactivation of the LTR promoter and that of the IP differ. In lytic infections, both the LTR promoter and the IP are efficiently transactivated by Tas, while in persistent infections, the IP is efficiently transactivated by Tas, but the LTR promoter is not. Analysis of proteins expressed from the LTR promoter and the IP during infection indicated that IP transcription is more robust than that of the LTR promoter in persistently infected cells, while the opposite is true for lytically infected cells. Coculture experiments also showed that LTR promoter transcription is greatest in cells which support lytic replication. Replacement of much of the LTR promoter with the IP leads to increased viral replication in persistent but not lytic infections. We also found that the induction of persistently infected cells with phorbol 12-myristate 13-acetate (PMA) greatly enhanced viral replication and transcription from the SFVcpz(hu) (new name for human FV) LTR promoter. However, mutation of three consensus AP-1 binding sites in the FV LTR promoter did not affect viral replication in lytically or persistently infected cells, nor did the same mutations affect LTR promoter transactivation by Tas in PMA-treated cells. Our data indicate that differential regulation of transcription is important in the outcome of FV infection but is unlikely to depend on AP-1.

Animals↗
PubMed2003

Real-time imaging of gene promoter activity using an adenoviral reporter construct demonstrates transcriptional dynamics in normal anterior pituitary cells.

Although analysis of luciferase activity using luminescence imaging has provided new insights into the dynamic regulation of gene expression in living tIssues, studies in vitro have relied on stably transfected clonal cell lines, limiting the choice of cell type and species, or DNA microinjection, which is arduous and highly selective. We report here the first use of a recombinant adenovirus in which the firefly luciferase reporter gene was regulated by the prolactin gene promoter, to study temporal dynamics of promoter activity. This vector was used to infect the pituitary GH3 cell line, and also primary cultures of Syrian hamster pituitary cells. We show that adenovirally transduced cells retained normal regulation of the promoter-reporter transgene by appropriate signals. Furthermore, microscopic imaging studies indicated that both clonal and primary pituitary cells were transduced efficiently, giving readily detectable luminescence signals in real-time over long periods. Finally, analysis of single-cell expression patterns indicated that prolactin promoter activity was highly dynamic with pulses in gene expression, revealing that the transcriptional instability seen in clonal cells is a feature of normal pituitary cells. Adenoviral vectors offer a valuable tool for studies of gene regulation where conventional transgenesis and clonal cell lines are not available.

Adenoviridae↗
PubMed2005

Plant growth promotion abilities and microscale bacterial dynamics in the rhizosphere of Lupin analysed by phytate utilization ability.

In the rhizosphere, phosphorus (P) levels are low because of P uptake into the roots. Rhizobacteria live on carbon (C) exuded from roots, and may contribute to plant nutrition by liberating P from organic compounds such as phytates. We isolated over 300 phytate (Na-inositol hexa-phosphate; Na-IHP)-utilizing bacterial strains from the rhizosheath and the rhizoplane of Lupinus albus (L.). Almost all of the isolates were classified as Burkholderia based on 16S rDNA sequence analysis. Rhizosheath isolates cultured with Na-IHP as the only source of C and P showed lower P uptake at the same extracellular phytase activity than rhizoplane strains, suggesting that bacteria from the rhizosheath utilized phytate as a C source. Many isolates also utilized insoluble phytate (Al-IHP and/or Fe-IHP). In co-culture with Lotus japonicus seedlings, some isolates promoted plant growth significantly.

Burkholderia↗
PubMed2006

The microtubule-severing protein Spastin is essential for axon outgrowth in the zebrafish embryo.

Hereditary spastic paraplegia (HSP) is a collection of neurological disorders characterized by developmental failure or degeneration of motor axons in the corticospinal tract and progressive lower limb spasticity. SPG4 mutations are the most common cause of autosomal dominant HSP and Spastin (the SPG4 gene product) is a microtubule severing protein that shares homology with katanin, the microtubule severing activity of which promotes axon growth in cultured neurons. Given the sequence and functional similarity between spastin and katanin, we hypothesized that spastin promotes the dynamic disassembly and remodelling of microtubules required for robust, properly directed motor axon outgrowth. To investigate this hypothesis, we cloned the zebrafish spg4 orthologue and used morpholino antisense oligonucleotides directed against the translation start site and the intron 7-8 splice donor site to knock down spastin function in the developing zebrafish embryo. Reduced spg4 function caused dramatic defects in motor axon outgrowth without affecting the events driving the initial specification of motor neurones. Other neuronal subtypes also exhibited a requirement for spg4 function, since spg4 knock down caused both widespread defects in neuronal connectivity and extensive CNS-specific apoptosis. Our results reveal a critical requirement for spastin to promote axonal outgrowth during embryonic development, and they validate the zebrafish embryo as a novel model system to dissect the pathogenetic mechanisms underlying HSP. Taken together with other recent studies, our findings suggest that axon outgrowth defects may be a common feature of childhood SPG3A and SPG4 cases.

Adenosine Triphosphatases↗
PubMed2004

Filopodia formation and Disabled degradation downstream of Reelin.

During Drosophila embryogenesis, Abl (Abelson tyrosine kinase) is localized in the axons of the CNS (central nervous system). Mutations in Abl have a subtle effect on the morphology of the embryonic CNS, and the mutant animals survive to the pupal and adult stages. However, genetic screens have identified several genes that, when mutated along with the Abl gene, modified the phenotypes. Two prominent genes that arose from these screens were enabled (Ena) and disabled (Dab). It has been known for some time that Enabled and its mammalian homologues are involved in the regulation of actin dynamics, and promote actin polymerization at the leading edge of motile cells. It was a defect in actin polymerization in migrating neurons in particular that resulted in the identification of Enabled as an important regulator of neuronal migration. Defects in Disabled, in both Drosophila and mammals, also gave rise to neuronal defects which, in mice, were indistinguishable from phenotypes observed in the reeler mouse. These observations suggested that mDab1 (mammalian Disabled homologue 1) acted in a pathway downstream of Reelin, the product of the reelin gene found to be defective in reeler mice. Now, in this issue of the Biochemical Journal, Takenawa and colleagues have demonstrated that Disabled also acts in a pathway to regulate actin dynamics through the direct activation of N-WASP (neuronal Wiskott-Aldrich syndrome protein). Furthermore, they were also able to link several lines of investigation from other groups to show that the ability of mDab1 to regulate actin dynamics during cell motility was under the negative control of tyrosine phosphorylation, leading to ubiquitin-mediated degradation of mDab1.

3' Flanking Region↗