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Results for “Promoter dynamics”

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At least 55 records · Page 3Linked to original sources
PubMed2000

Role of inspiratory capacity on exercise tolerance in COPD patients with and without tidal expiratory flow limitation at rest.

Expiratory flow limitation promotes dynamic hyperinflation during exercise in chronic obstructive pulmonary disease (COPD) patients with a consequent reduction in inspiratory capacity (IC), limiting their exercise tolerance. Therefore, the exercise capacity of patients with tidal expiratory flow limitation (FL) at rest should depend on the magnitude of IC. The presented study was designed to evaluate the role of FL on the relationship between resting IC, other respiratory function variables and exercise performance in COPD patients. Fifty-two patients were included in the study. Negative expiratory pressure (NEP) uptake (VO2,max) were measured during an incremental symptom-limited cycle exercise. Twenty-nine patients were FL at rest. The IC was normal in all non-FL patients, while in most FL subjects it was decreased. Both WRmax and VO2,max were lower in FL patients (p<0.001, each). A close relationship of WRmax and O2,max to IC was found (r=0.73 and 0.75, respectively; p<0.0001, each). In the whole group, stepwise regression analysis selected IC and forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) (% predicted) as the only significant contributors to exercise tolerance. Subgroup analysis showed that IC was the sole predictor in FL patients, and FEV1/FVC in non-FL patients. Detection of flow limitation provides useful information on the factors that influence exercise capacity in chronic obstructive pulmonary disease patients. Accordingly, in patients with flow limitation, inspiratory capacity appears as the best predictor of exercise tolerance, reflecting the presence of dynamic hyperinflation.

Aged↗
PubMed2006

Insights into the mechanism of microtubule stabilization by Taxol.

The antitumor drug Taxol stabilizes microtubules and reduces their dynamicity, promoting mitotic arrest and cell death. Upon assembly of the alpha/beta-tubulin heterodimer, GTP bound to beta-tubulin is hydrolyzed to GDP reaching a steady-state equilibrium between free tubulin dimers and microtubules. The binding of Taxol to beta-tubulin in the polymer results in cold-stable microtubules at the expense of tubulin dimers, even in the absence of exogenous GTP. However, there is little biochemical insight into the mechanism(s) by which Taxol stabilizes microtubules. Here, we analyze the structural changes occurring in both beta- and alpha-tubulin upon microtubule stabilization by Taxol. Hydrogen/deuterium exchange (HDX) coupled to liquid chromatography-electrospray ionization MS demonstrated a marked reduction in deuterium incorporation in both beta-and alpha-tubulin when Taxol was present. Decreased local HDX in peptic peptides was mapped on the tubulin structure and revealed both expected and new dimer-dimer interactions. The increased rigidity in Taxol microtubules was distinct from and complementary to that due to GTP-induced polymerization. The Taxol-induced changes in tubulin conformation act against microtubule depolymerization in a precise directional way. These results demonstrate that HDX coupled to liquid chromatography-electrospray ionization MS can be effectively used to study conformational effects induced by small ligands on microtubules. The present study also opens avenues for locating drug and protein binding sites and for deciphering the mechanisms by which their interactions alter the conformation of microtubules and tubulin dimers.

Animals↗
PubMedDate not supplied

The role of proprioception in the management and rehabilitation of athletic injuries.

Rehabilitation continues to evolve with the increased emphasis on patient management and proprioceptive training. Proprioception can be defined as a specialized variation of the sensory modality of touch that encompasses the sensation of joint movement (kinesthesia) and joint position (joint position sense). Numerous investigators have observed that afferent feedback to the brain and spinal pathways is mediated by skin, articular, and muscle mechanoreceptors. Examining the effects of ligamentous injury, surgical intervention, and proprioceptively mediated activities in the rehabilitation program provides an understanding of the complexity of this system responsible for motor control. It appears that this neuromuscular feedback mechanism becomes interrupted with injury and abnormalities, and approaches restoration after surgical intervention and rehabilitation. Rehabilitation programs should be designed to include a proprioceptive component that addresses the following three levels of motor control: spinal reflexes, cognitive programming, and brainstem activity. Such a program is highly recommended to promote dynamic joint and functional stability. Thus far, current knowledge regarding the basic science and clinical application of proprioception has led the profession of sports medicine one step closer to its ultimate goal of restoring function.

Adaptation, Physiological↗
PubMed2001

Breathing pattern and gas exchange at peak exercise in COPD patients with and without tidal flow limitation at rest.

Expiratory flow limitation (FL) at rest is frequently present in chronic obstructive pulmonary disease (COPD) patients. It promotes dynamic hyperinflation with a consequent decrease in inspiratory capacity (IC). Since in COPD resting IC is strongly correlated with exercise tolerance, this study hypothesized that this is due to limitation of the maximal tidal volume (VT,max) during exercise by the reduced IC. The present study investigated the role of tidal FL at rest on: 1) the relationship of resting IC to VT,max; and 2) on gas exchange during peak exercise in COPD patients. Fifty-two stable COPD patients were studied at rest, using the negative expiratory pressure technique to assess the presence of FL, and during incremental symptom-limited cycling exercise to evaluate exercise performance. At rest, FL was present in 29 patients. In the 52 patients, a close relationship of VT,max to IC was found using non-normalized values (r=0.77; p < 0.0001), and stepwise regression analysis selected IC as the only significant predictor of VT,max. Subgroup analysis showed that this was also the case for patients both with and without FL (r=0.70 and 0.76, respectively). In addition, in FL patients there was an increase (p < 0.002) in arterial carbon dioxide partial pressure at peak exercise, mainly due to a relatively low VT,max and consequent increase in the physiological dead space (VD)/VT ratio. The arterial oxygen partial pressure also decreased at peak exercise in the FL patients (p < 0.05). In conclusion, in chronic obstructive pulmonary disease patients the maximal tidal volume, and hence maximal oxygen consumption, are closely related to the reduced inspiratory capacity. The flow limited patients also exhibit a significant increase in arterial carbon dioxide partial pressure and a decrease in arterial oxygen partial pressure during peak exercise.

Aged↗
PubMed2006

Does expiratory flow limitation predict chronic dyspnoea in adults with cystic fibrosis?

Tidal expiratory flow limitation (EFL) may promote dynamic hyperinflation and contribute to chronic dyspnoea. The purpose of this study was to assess the contribution of EFL to chronic dyspnoea in adults with cystic fibrosis (CF). The presence of EFL was determined in 102 adults with stable CF (forced expiratory volume in one second (FEV1) 17.3-91.5% predicted) and 20 age-matched control subjects using the negative expiratory pressure technique. Measurements of inspiratory capacity (IC) and spirometry were performed, and chronic dyspnoea was evaluated using the modified Medical Research Council scale. EFL was present in 34 subjects (33%), with 18 subjects flow limited in the sitting position and 16 subjects flow limited only in the supine position. Flow limitation in the sitting position was associated with older age and lower FEV1 compared with flow-limited supine position and non-flow-limited subjects. A significant reduction in IC accompanied EFL in both the sitting and supine positions. Flow limitation in the sitting position was associated with significantly higher levels of chronic dyspnoea. Ordinal regression analysis indicated that EFL was the best predictor of chronic dyspnoea in a model that included FEV1 % pred. Expiratory flow limitation in cystic fibrosis is associated with reduced forced expiratory volume in one second, older age and dynamic hyperinflation. Expiratory flow limitation significantly contributes to chronic dyspnoea in cystic fibrosis.

Adult↗
PubMedDate not supplied

Codependency in nursing: using a simulation/gaming teaching method.

Practicing nurses can benefit by learning to differentiate their caretaking (potentially destructive) from their caregiving (constructive) behaviors, and by learning strategies to facilitate caregiving. A new simulation/game was developed to assist nurses to recognize codependent behaviors in themselves and others and to practice some alternative patterns of behavior. This team-based simulation/game, "The Climb," uses the metaphor of a mountain-climbing expedition. The experiences of the journey promote dynamic insights into the consequences of codependency in the professional and personal lives of the nurse.

Caregivers↗
PubMed1999

Flow limitation: an overview.

Expiratory flow limitation (EFL) refers to a functional condition in which expiratory flow cannot increase and, hence, is maximal under the prevailing conditions. Many factors, alone or combined, may cause EFL. Among them, airway obstruction, expiratory flow rate and body posture are the most important. EFL normally occurs during the forced expiratory manoeuvre after peak expiratory flow. However, its presence during tidal breathing either throughout exercise or at rest, initially in the supine and then in the seated position, is an abnormal finding which reflects progressively greater mechanical impairment. EFL promotes dynamic pulmonary hyperinflation (DH) by prolonging the time required for the respiratory system to reach its relaxation volume during expiration. Moreover, in the presence of EFL, any increase in expiratory flow can be accomplished only by raising the end-expiratory lung volume allowing tidal breathing to occur at a higher absolute lung volume. This mechanism, however, besides being physically limited, leads to an increment in DH and intrinsic end-expiratory alveolar pressure, adding an increasing threshold load on the inspiratory muscles, which become functionally weaker, and eliciting dyspnoea. In advanced chronic obstructive pulmonary disease, bronchodilators and lung volume reduction surgery do not usually reverse expiratory flow limitation, but they appear to be useful because they often allow expiratory flow limitation to occur at a lower absolute lung volume, thus reducing dynamic pulmonary hyperinflation and limiting exertional dyspnoea.

Dyspnea↗
PubMed1999

Yeast Bim1p promotes the G1-specific dynamics of microtubules.

Microtubule dynamics vary during the cell cycle, and microtubules appear to be more dynamic in vivo than in vitro. Proteins that promote dynamic instability are therefore central to microtubule behavior in living cells. Here, we report that a yeast protein of the highly conserved EB1 family, Bim1p, promotes cytoplasmic microtubule dynamics specifically during G1. During G1, microtubules in cells lacking BIM1 showed reduced dynamicity due to a slower shrinkage rate, fewer rescues and catastrophes, and more time spent in an attenuated/paused state. Human EB1 was identified as an interacting partner for the adenomatous polyposis coli (APC) tumor suppressor protein. Like human EB1, Bim1p localizes to dots at the distal ends of cytoplasmic microtubules. This localization, together with data from electron microscopy and a synthetic interaction with the gene encoding the kinesin Kar3p, suggests that Bim1p acts at the microtubule plus end. Our in vivo data provide evidence of a cell cycle-specific microtubule-binding protein that promotes microtubule dynamicity.

Cell Cycle Proteins↗
PubMed2004

Filling the GAPs in cell dynamics control: BPGAP1 promotes cortactin translocation to the cell periphery for enhanced cell migration.

Cells undergo dynamic changes in morphology or motility during cellular division and proliferation, differentiation, neuronal pathfinding, wound healing, apoptosis, host defense and organ development. These processes are controlled by signalling events relayed through cascades of protein interactions leading to the establishment and maintenance of cytoskeletal networks of microtubules and actin. Various regulators, including the Rho small GTPases (guanine nucleotide triphosphatases), serve as master switches to fine-tune the amplitude, duration as well as the integration of such circuitry responses. Rho GTPases are activated by guanine nucleotide-exchange factors and inactivated by GAPs (GTPase-activating proteins). Although normally down-regulating signalling pathways by catalysing their GTPase activity, many GAPs exist with various protein modules, the functions of which still largely remain unknown. BPGAP1 is a novel RhoGAP that co-ordinately regulates pseudopodia and cell migration through the interplay of its BNIP-2 and Cdc42GAP homology domains serving as a homophilic/heterophilic interaction device, an enzymic RhoGAP domain that inactivates RhoA and a proline-rich region that binds the Src homology-3 domain of cortactin. Both proteins co-localize to cell periphery and enhance cell migration. As a molecular scaffold in cortical actin assembly and organization, cortactin and its interaction with small GTPases, GAPs and tyrosine kinases seems set to provide further insights to the multiplicity and complexity of cell dynamics control. Elucidating how these processes might be individually or co-ordinately regulated through cortactin remains an exciting future challenge.

Amino Acid Sequence↗
PubMed2005

Regional expression of brain derived neurotrophic factor (BDNF) is correlated with dynamic patterns of promoter methylation in the developing mouse forebrain.

Brain Derived Neurotrophic Factor (BDNF) plays an important role in brain development and plasticity. BDNF gene expression is known to be dynamically regulated during development, but the regulatory controls of normal differential expression are not well understood. Methylation of CpG dinucleotides within gene promoters is emerging as an important epigenetic control mechanism of transcription, and the BDNF complex promoter contains several CpG dinucleotides. We determined BDNF expression in the developing mouse forebrain and examined whether there were correlated patterns of methylation at CpG dinucleotides within the BDNF promoter. The data show that BDNF is dynamically expressed in the mouse forebrain and that expression is correlated with differential methylation specifically at CpG dinucleotides in eIV of the mouse BDNF promoter. These studies demonstrate that DNA methylation of this regulatory region may be an important mechanism controlling differential expression of BDNF during forebrain development.

Animals↗
PubMed2004

Encounters between dynamic cortical microtubules promote ordering of the cortical array through angle-dependent modifications of microtubule behavior.

Ordered cortical microtubule arrays are essential for normal plant morphogenesis, but how these arrays form is unclear. The dynamics of individual cortical microtubules are stochastic and cannot fully account for the observed order; however, using tobacco (Nicotiana tabacum) cells expressing either the MBD-DsRed (microtubule binding domain of the mammalian MAP4 fused to the Discosoma sp red fluorescent protein) or YFP-TUA6 (yellow fluorescent protein fused to the Arabidopsis alpha-tubulin 6 isoform) microtubule markers, we identified intermicrotubule interactions that modify their stochastic behaviors. The intermicrotubule interactions occur when the growing plus-ends of cortical microtubules encounter previously existing cortical microtubules. Importantly, the outcome of such encounters depends on the angle at which they occur: steep-angle collisions are characterized by approximately sevenfold shorter microtubule contact times compared with shallow-angle encounters, and steep-angle collisions are twice as likely to result in microtubule depolymerization. Hence, steep-angle collisions promote microtubule destabilization, whereas shallow-angle encounters promote both microtubule stabilization and coalignment. Monte Carlo modeling of the behavior of simulated microtubules, according to the observed behavior of transverse and longitudinally oriented cortical microtubules in cells, reveals that these simple rules for intermicrotubule interactions are necessary and sufficient to facilitate the self-organization of dynamic microtubules into a parallel configuration.

Bacterial Proteins↗
PubMed1992

Active conformation of a tumor promoter, teleocidin. A molecular dynamics study.

Telecidins are potent tumor promoters, having a nine-membered lactam structure. Teleocidins and their small-molecular-sized active congeners (indolactams) are known to exist in an equilibrium between at least two conformational states, the twist and the sofa form. Molecular dynamics (MD) calculations were performed on four indolactams, in order to examine the relationships between preferred ring conformations and the biological activities. It was shown that the tumor-promoting activities are closely related with the existence ratio of the sofa form among 10 possible conformations. This implies that the sofa form is the active ring conformation, which is compatible with the previous result obtained independently from the superposition of teleocidin and phorbol ester. The predicted ratios of conformers for each indolactam were in good agreement with those observed by NMR spectral analysis. The high-temperature MD method proved to be very useful for predicting the preferred structures of these cyclic compounds, in which the overall stabilities are strongly influenced by the conformations of substituent groups on the ring.

Carcinogens↗
PubMed2006

Effects of cross-linking type II collagen-GAG scaffolds on chondrogenesis in vitro: dynamic pore reduction promotes cartilage formation.

Articular cartilage tissue-engineering investigations often implement bioassays for chondrogenesis in vitro using articular chondrocytes or mesenchymal stem cells in cell pellets that contract with time in culture, suggesting an association between the processes of contraction of the cell pellet and cartilage formation. The objective of the present study was to investigate this relationship further using adult canine articular chondrocyte-seeded type II collagen-GAG scaffolds. The collagen-GAG scaffolds were chemically cross-linked to achieve a range of cross-link densities. Chondrocyte-seeded scaffolds of varying cross-link densities were then cultured for 2 weeks to evaluate the effect of crosslink density on scaffold contraction and chondrogenesis. Scaffolds with low cross-link densities experienced cell-mediated contraction, increased cell number densities, a greater degree of chondrogenesis (viz., chondrocytic morphology of cells, synthesis of type II collagen), and an apparent increase in the rate of degradation of the scaffold compared to more highly cross-linked scaffolds that resisted cellular contraction. The results of this study suggest the promise of "dynamic pore reduction" for scaffolds for articular cartilage tissue engineering. In this approach, scaffolds would have an initial pore diameter large enough to facilitate cell seeding and a mechanical stiffness low enough to allow for cell-mediated contraction to yield a reduced pore volume to favor chondrogenesis. This approach may provide a useful alternative to traditional means of increasing cell number density and retention of synthesized molecules that promote cartilage formation in tissue-engineered constructs.

Animals↗
PubMed2001

Molecular structure, dynamic expression, and promoter analysis of zebrafish (Danio rerio) myf-5 gene.

We isolated a 1,438 bp cDNA fragment that encoded Myf-5 myogenic factor of zebrafish. The deduced amino acid contained 237 residues, including the basic helix-loop-helix domain that is conserved in all known Myf-5. The zebrafish myf-5 transcripts were first detectable at 7.5 hpf, increased substantially until 16 hpf, and then declined gradually to an undetectable level by 26 hpf. During somitogenesis, zebrafish myf-5 transcripts were distributed mainly in the somites and segmental plates. Prominent signals occurred transiently in adaxial cells in two parallel rows but did not extend beyond the positive-signal somites. Various lengths of upstream region of zebrafish myf-5 fused with EGFP gene were used to carry out transgenic analysis. Results showed that a small, 82 bp (nucleotide positions from -82 to -1), regulatory cassette is sufficient to control the somite- and stage-specific expression of zebrafish myf-5 during early development.

Amino Acid Sequence↗
PubMed2006

Stability via asynchrony in Drosophila metapopulations with low migration rates.

Very few experimental studies have examined how migration rate affects metapopulation dynamics and stability. We studied the dynamics of replicate laboratory metapopulations of Drosophila under different migration rates. Low migration stabilized metapopulation dynamics, while promoting unstable subpopulation dynamics, by inducing asynchrony among neighboring subpopulations. High migration synchronized subpopulation dynamics, thereby destabilizing the metapopulations. Contrary to some theoretical predictions, increased migration did not affect average population size. Simulations based on a simple non-species-specific population growth model captured most features of the data, which suggests that our results are generalizable.

Animal Migration↗
PubMed2006

A hyper-dynamic equilibrium between promoter-bound and nucleoplasmic dimers controls NF-kappaB-dependent gene activity.

Because of its very high affinity for DNA, NF-kappaB is believed to make long-lasting contacts with cognate sites and to be essential for the nucleation of very stable enhanceosomes. However, the kinetic properties of NF-kappaB interaction with cognate sites in vivo are unknown. Here, we show that in living cells NF-kappaB is immobilized onto high-affinity binding sites only transiently, and that complete NF-kappaB turnover on active chromatin occurs in less than 30 s. Therefore, promoter-bound NF-kappaB is in dynamic equilibrium with nucleoplasmic dimers; promoter occupancy and transcriptional activity oscillate synchronously with nucleoplasmic NF-kappaB and independently of promoter occupancy by other sequence-specific transcription factors. These data indicate that changes in the nuclear concentration of NF-kappaB directly impact on promoter function and that promoters sample nucleoplasmic levels of NF-kappaB over a timescale of seconds, thus rapidly re-tuning their activity. We propose a revision of the enhanceosome concept in this dynamic framework.

Biological Clocks↗
PubMed2002

Dynamics of enhancer-promoter communication during differentiation-induced gene activation.

We analyzed the order of recruitment of factors to the HNF-4alpha regulatory regions upon the initial activation of the gene during enterocyte differentiation. An initially independent assembly of regulatory complexes at the proximal promoter and the upstream enhancer regions was followed by the tracking of the entire DNA-protein complex formed on the enhancer along the intervening DNA until it encountered the proximal promoter. This movement correlated with a unidirectional spreading of histone hyperacetylation. Transcription initiation coincided with the formation of a stable enhancer-promoter complex and remodeling of the nucleosome situated at the transcription start site. The results provide experimental evidence for the involvement of a dynamic process culminating in enhancer-promoter communication during long-distance gene activation.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗