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Results for “Promoter dynamics”

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At least 397 records · Page 22Linked to original sources

PubMed2000

Occlusion of experimentally created fusiform aneurysms with porous metallic stents.

BACKGROUND AND PURPOSE: Carotid fusiform aneurysms are most commonly treated with occlusion of the parent vessel. The purpose of our study was to assess the effectiveness of self-expanding, cobalt-alloy stents in the ablation of experimental fusiform aneurysms with preservation of the parent vessel in a carotid artery model. METHODS: Porous metallic stents were placed endovascularly along the lengths of experimentally created fusiform aneurysms in the carotid arteries of dogs; aneurysms were also created in the animals' opposite carotid arteries to serve as controls. RESULTS: Before stent placement, angiography of the carotid arteries showed large fusiform aneurysms along the lengths of the common carotid arteries and complex patterns of flow. Immediately after stent placement there was disruption of the usual flow patterns within the lumens of the fusiform aneurysms. The lumen between the wall of the aneurysm and stented carotid showed stasis of contrast material and blood. Near-complete ablation of all aneurysms was observed 8 weeks after stent placement. The stented carotid arteries remained widely patent; control aneurysms and carotid arteries were patent and unchanged. Histopathologic analysis revealed fibrotic reactive scar tissue filling the space between the stent wires and outer wall of the fusiform aneurysm. CONCLUSION: Changing blood flow dynamics within an aneurysm can promote thrombus formation. The stent promotes stasis and thrombus within the residual lumen between the stent wall and the outer wall of the aneurysm because its woven wire mesh interferes with usual blood flow patterns, which then promotes formation of thrombus and fibrosis within the residual aneurysmal lumen.

Aneurysm↗

PubMed2006

A mental health clinician's guide to death notification.

The purpose of this article is to present an overview of past and present research to promote further understanding of the dynamics and process of death notification for mental health practitioners. This article includes information for interventionists to gain a better understanding of how their primary professional role and their own emotional vulnerabilities can impact the process. Additionally, the stress imposed on the interventionist, expected survivor reactions, and traumatic loss are discussed. Lastly, to help prepare mental health professionals who may be asked to assist in the process, a protocol for the systematic delivery of death notification information is suggested.

Attitude to Death↗

PubMed2006

[The morpho-functional changes of the follicular apparatus and yellow body of the ovary in women of the reproductive age with myoma].

It have been studied the morpho-functional changes of the ovaries in women of reproductive age with proliferative myoma of uteri. Based on the analysis of the result of the investigation on the myomatic knots of the women in the condition of high activity of proliferation of myocytes a very complexes, multifactorial pathogenetic mechanisms of the myoma has been outlined. Switch in the common changes in the dynamic oxidative stress and hyperestrogenemia promotes development of the myoma.

Adult↗

PubMed2003

Mechanical coupling via the membrane fusion SNARE protein syntaxin 1A: a molecular dynamics study.

SNARE trans complexes between membranes likely promote membrane fusion. For the t-SNARE syntaxin 1A involved in synaptic transmission, the secondary structure and bending stiffness of the five-residue juxtamembrane linker is assumed to determine the required mechanical energy transfer from the cytosolic core complex to the membrane. These properties have here been studied by molecular dynamics and annealing simulations for the wild-type and a C-terminal-prolongated mutant within a neutral and an acidic bilayer, suggesting linker stiffnesses above 1.7 but below 50 x 10(-3) kcal mol(-1) deg(-2). The transmembrane helix was found to be tilted by 15 degrees and tightly anchored within the membrane with a stiffness of 4-5 kcal mol(-1) A(-2). The linker turned out to be marginally helical and strongly influenced by its lipid environment. Charged lipids increased the helicity and H3 helix tilt stiffness. For the wild type, the linker was seen embedded deeply within the polar region of the bilayer, whereas the prolongation shifted the linker outward. This reduced its helicity and increased its average tilt, thereby presumably reducing fusion efficiency. Our results suggest that partially unstructured linkers provide considerable mechanical coupling; the energy transduced cooperatively by the linkers in a native fusion event is thus estimated to be 3-8 kcal/mol, implying a two-to-five orders of magnitude fusion rate increase.

Antigens, Surface↗

PubMed2026

Integrative analysis of transcriptome and DNA methylome dynamics during caudal fin regeneration in silver pomfret (Pampus argenteus).

Caudal fin regeneration in teleost fish is a complex, multi-stage process involving coordinated molecular and cellular changes. While the role of epigenetic regulation particularly DNA methylation has been studied in model freshwater species such as zebrafish, its contribution to regeneration in marine teleosts remains largely unexplored. In this study, we integrated transcriptomic and DNA methylomic data to characterize the temporal dynamics of gene expression and methylation during caudal fin regeneration in the silver pomfret (Pampus argenteus). Using RNA-sequencing and reduced representation bisulfite sequencing (RRBS) at three biologically critical time points 1, 3, and 7 days post-amputation (dpa), we characterized the spatiotemporal molecular landscape of caudal fin regeneration. These time points capture the key transitional phases of wound healing and inflammation (1 dpa), blastema formation and progenitor proliferation (3 dpa), and regenerative outgrowth with tissue remodeling (7 dpa), enabling robust detection of the major molecular programs underlying epimorphic regeneration. Concurrently, CG-methylome analysis identified thousands of dynamically changing differentially methylated regions (DMRs). A strong global inverse correlation was observed between promoter methylation and gene expression. Integrative analysis pinpointed key regeneration genes (fgf20a, msxb, sox9b) whose expression was associated with dynamic methylation changes in their promoters or gene bodies. We conclude that DNA methylation is a dynamic and key regulatory layer that acts in concert with transcriptional reprogramming to coordinate tissue regeneration, providing new insights into the epigenetic mechanisms underlying complex regenerative processes in teleosts.

Animals↗

PubMed2004

CLIP-170/tubulin-curved oligomers coassemble at microtubule ends and promote rescues.

BACKGROUND: CLIP-170 is a microtubule binding protein specifically located at microtubule plus ends, where it modulates their dynamic properties and their interactions with intracellular organelles. The mechanism by which CLIP-170 is targeted to microtubule ends remains unclear today, as well as its precise effect on microtubule dynamics. RESULTS: We used the N-terminal part of CLIP-170 (named H2), which contains the microtubule binding domains, to investigate how it modulates in vitro microtubule dynamics and structure. We found that H2 primarily promoted rescues (transitions from shrinkage to growth) of microtubules nucleated from pure tubulin and isolated centrosomes, and stimulated microtubule nucleation. Electron cryomicroscopy revealed that H2 induced the formation of tubulin rings in solution and curved oligomers at the extremities of microtubules in assembly conditions. CONCLUSIONS: These results suggest that CLIP-170 targets specifically at microtubule plus ends by copolymerizing with tubulin and modulates microtubule nucleation, polymerization, and rescues by the same basic mechanism with tubulin oligomers as intermediates.

Cryoelectron Microscopy↗

PubMed2005

[Application of green fluorescent protein gene in study of adipocyte differentiation].

OBJECTIVE: To establish a model for dynamic detection of adipocyte differentiation in vivo by green fluorescent protein (GFP). METHODS: The promoter of peroxisome proliferators-activated receptor gamma 2 (PPARgamma2) gene was amplified by PCR from the genomic DNA of human preadipocytes, inserted into the eukaryotic expression vector pEGFP-1 and transferred into NIH3T3 fibroblasts and preadipocytes which were induced to differentiate into adipocyte. RESULTS: Upon induction with insulin, dexamethasone and 3-isobutyl-1-methyl xanthine, the transformed human preadipocytes differentiated into mature adipocytes and expressed GFP, but NIH3T3 fibroblasts could not differentiate into adipocytes or express GFP. CONCLUSION: Transformation of human preadipocytes with the recombinant of PPARgamma2 promoter with GFP gene can be employed to dynamically detect the differentiation of adipocytes in vivo.

Adipocytes↗

PubMed2007

Carboxymethyl beta-glucan binds to corneal epithelial cells and increases cell adhesion to laminin and resistance to oxidative stress.

PURPOSE: Polysaccharides are frequently used as viscoelastic agents to improve pharmacokinetics of ophthalmic preparations. Recently, polysaccharides from yeast cell walls such as beta-glucans have emerged as bioactive molecules endowed with immunomodulatory and cytoprotective properties. In this study, we investigated the effects of carboxymethyl beta-glucan (CMG), a water-soluble derivative of yeast beta-glucan, on cultured rabbit corneal epithelial cells. METHODS: We developed a fluorescein-labeled CMG to visualize its binding to corneal cells by means of digital microscopy and image deconvolution. The effects of CMG on adhesion and survival of corneal epithelial cells exposed to noxious stimuli were also studied. RESULTS: CMG binds defined regions scattered throughout the body of corneal cells, suggesting binding specificity. Tridimensional reconstruction of fluorescence shows that binding is localized mainly at the plasma and nuclear membranes. Interestingly, CMG binding is highly represented at the level of focal adhesion of cells spreading onto laminin. Accordingly, CMG promotes adhesion of corneal epithelial cells to laminin without affecting their proliferation rate. CMG also protects cells from oxidative stress-dependent cell death, being ineffective in preventing ultraviolet B cytotoxicity. CONCLUSIONS: Data show that CMG dynamically binds to corneal epithelial cells, promoting cell adhesion and resistance to oxidative stress.

Animals↗

PubMed2001

The brain decade in debate: VI. Sensory and motor maps: dynamics and plasticity.

This article is an edited transcription of a virtual symposium promoted by the Brazilian Society of Neuroscience and Behavior (SBNeC). Although the dynamics of sensory and motor representations have been one of the most studied features of the central nervous system, the actual mechanisms of brain plasticity that underlie the dynamic nature of sensory and motor maps are not entirely unraveled. Our discussion began with the notion that the processing of sensory information depends on many different cortical areas. Some of them are arranged topographically and others have non-topographic (analytical) properties. Besides a sensory component, every cortical area has an efferent output that can be mapped and can influence motor behavior. Although new behaviors might be related to modifications of the sensory or motor representations in a given cortical area, they can also be the result of the acquired ability to make new associations between specific sensory cues and certain movements, a type of learning known as conditioning motor learning. Many types of learning are directly related to the emotional or cognitive context in which a new behavior is acquired. This has been demonstrated by paradigms in which the receptive field properties of cortical neurons are modified when an animal is engaged in a given discrimination task or when a triggering feature is paired with an aversive stimulus. The role of the cholinergic input from the nucleus basalis to the neocortex was also highlighted as one important component of the circuits responsible for the context-dependent changes that can be induced in cortical maps.

Animals↗

PubMed2004

The dynamic character of the G-quadruplex element in the c-MYC promoter and modification by TMPyP4.

The nuclease hypersensitivity element III1 (NHE III1) upstream of the P1 and P2 promoters of c-MYC controls 80-90% of the transcriptional activity of this gene. The purine-rich strand in this region can form a G-quadruplex structure that is a critical part of the silencer element for this promoter. We have demonstrated that this G-quadruplex structure can form a mixture of four biologically relevant parallel-loop isomers, which upon interaction with the cationic porphyrin TMPyP4 are converted to mixed parallel/antiparallel G-quadruplex structures.

DNA↗

PubMed2003

Dynamic recruitment of NF-Y and histone acetyltransferases on cell-cycle promoters.

Regulation of transcription during the cell-cycle is under the control of E2 factors (E2Fs), often in cooperation with nuclear factor Y (NF-Y), a histone-like CCAAT-binding trimer. NF-Y is paradigmatic of a constitutive, ubiquitous factor that pre-sets the promoter architecture for other regulatory proteins to access it. We analyzed the recruitment of NF-Y, E2F1/4/6, histone acetyltransferases, and histone deacetylase (HDAC) 1/3/4 to several cell-cycle promoters by chromatin immunoprecipitation assays in serum-starved and restimulated NIH3T3 cells. NF-Y binding is not constitutive but timely regulated in all promoters tested, being displaced when promoters are repressed. p300 association correlates with activation, and it is never found in the absence of NF-Y, whereas PCAF/hGCN5 is often found before NF-Y association. E2F4 and E2F6, together with HDACs, are bound to repressed promoters, including the G2/M Cyclin B2. As expected, an inverse relationship between HDACs association and histones H3/H4 acetylation is observed. Blocking cells in G1 with the cyclin-dependent kinase 2 inhibitor R-roscovitine confirms that NF-Y is bound to G1/S but not to G2/M promoters in G1. These data indicate that following the release of E2Fs/HDACs, a hierarchy of PCAF-NF-Y-p300 interactions and H3-H4 acetylations are required for activation of cell-cycle promoters.

3T3 Cells↗

PubMedDate not supplied

Future burden and costs of smoking-related disease in the Netherlands: a dynamic modeling approach.

OBJECTIVES: In this article, we explore the future health gain of different policy measures to reduce smoking prevalence: health education campaigns specifically aimed at keeping (young) people from starting to smoke, campaigns aimed at persuading smokers to quit, and tax measures. METHODS: We drew up different policy scenarios based on evaluations of several health promotion campaigns. Implementing these into the dynamic multistate models, we simulated smoking prevalence, loss of life-years, and costs for several decades into the next century. RESULTS: In the short run, campaigns aimed at potential "quitters" appear to be most effective in terms of health gain. However, their effect fades away after several decades, while campaigns aimed at young "starters" or tax measures in the end yield a larger and more lasting decrease in smoking attributable disease burden. CONCLUSION: Dynamic modeling is very useful tool in calculating costs and effects of preventive public health measures.

Adult↗

PubMed2005

The role of the extracellular matrix in angiogenesis in malignant glioma tumors.

Angiogenesis is a promising target for the development of effective strategies for the treatment of malignant brain tumors in that it has the potential to starve large tumors and prevent the regrowth of residual margins. Two critical steps in angiogenesis, the proliferation of activated endothelial cells and their migration into the perivascular space (sprouting), require adherence of the endothelial cells to the extracellular matrix (ECM). Thus, the availability of the appropriate ligands within the ECM contributes to the regulation of angiogenesis. In addition, several components of the ECM can act through other mechanisms to further promote angiogenesis or inhibit it. Current evidence suggests that the regulation of angiogenesis is a dynamic process in which the endothelial cells can promote angiogenesis by secreting proteases that remodel the ECM, tumor cells can further promote angiogenesis by secreting ECM components and actively remodeling their environment, and stromal cells may respond to angiogenesis associated with tumors and inflammatory reactions by secreting inhibitory molecules. Here, we provide a critical review of the protein and proteoglycan components of the ECM that have been implicated in angiogenesis with an emphasis on their role in promoting or inhibiting angiogenesis in brain tumors.

Animals↗

PubMedDate not supplied

Key elements for church-based health promotion programs: outcome-based literature review.

Although not a new concept, church-based health promotion programs have yet to be widely researched. Few of the initial studies used randomized and controlled designs. Dissemination of study results has been sporadic, with findings often reported in church periodicals. A renewed interest in church-based health promotion programs (CBHPP) is emerging. The purpose of this article is to propose seven key elements found in a literature review to be beneficial in establishing church-based community health promotion programs that demonstrated desired health promotion outcomes. Based on the outcomes of successful CBHPP, the following key elements have been identified: partnerships, positive health values, availability of services, access to church facilities, community-focused interventions, health behavior change, and supportive social relationships. An example of one program that embodies these elements is presented. The Heart and Soul Program, designed to increase physical activity in midlife women to reduce their risk of cardiovascular disease with advancing age, is discussed within the context of the elements for successful church-based programs. CBHPP have effectively promoted health behaviors within certain communities. To promote health and wellness in light of our diverse society and health needs, health promotion professionals and churches can be dynamic partners.

Black or African American↗

PubMed2004

GFP as a tool to analyze the organization, dynamics and function of nuclei and microtubules in Neurospora crassa.

We report the construction of a versatile GFP expression plasmid and demonstrate its utility in Neurospora crassa. To visualize nuclei and microtubules, we generated carboxy-terminal fusions of sgfp to Neurospora histone H1 (hH1) and beta-tubulin (Bml). Strong expression of GFP fusion proteins was achieved with the inducible Neurospora ccg-1 promoter. Nuclear and microtubule organization and dynamics were observed in live vegetative hyphae, developing asci, and ascospores by conventional and confocal laser scanning fluorescence microscopy. Observations of GFP fusion proteins in live cells largely confirmed previous results obtained by examination of fixed cells with various microscopic techniques. H1-GFP revealed dynamic nuclear shapes. Microtubules were mostly aligned parallel to the growth axis in apical compartments but more randomly arranged in sub-apical compartments. Time-lapse imaging of beta-tubulin-GFP in germinating macroconidia revealed polymerization and depolymerization of microtubules. In heterozygous crosses, H1-GFP and beta-tubulin-GFP expression was silenced, presumably by meiotic silencing. H1-GFP was translated in the vicinity of hH1+-sgfp+ nuclei in the common cytoplasm of giant Banana ascospores, but it diffused into all nuclei, another illustration of the utility of GFP fusion proteins.

Artificial Gene Fusion↗

PubMed2025

RNA Pol I activity is required for meiotic chromatin organization and the H3K4me3 gradient essential for oogenesis, independent of ribosome synthesis.

Oogenesis requires extensive and dynamic chromatin remodeling that primes gene promoters for later transcriptional activation during embryonic development. Here, we uncover a pivotal, non-canonical role for RNA Polymerase I (Pol I) in driving these chromatin state transitions during Caenorhabditis elegans oogenesis. Using the auxin-inducible degron system to selectively deplete either Pol I catalytic subunits or ribosome assembly factors, we disentangle the consequences of impaired nucleolar integrity from reductions in ribosome biogenesis. Strikingly, although disrupting ribosome assembly caused minimal effects on oocyte production, loss of Pol I activity led to widespread changes in chromatin accessibility, a dampening of the distal-proximal H3K4me3 gradient required for oogenesis, reduced synapsis, and elevated ATM/ATR phosphorylation, resulting in fewer but significantly larger oocytes. Despite their promoters becoming more accessible, oogenesis genes did not show large changes in steady-state mRNA, consistent with transcriptional repression prior to fertilization. Instead, Pol I depletion prematurely remodeled oogenic chromatin, through a misdirection of H3K4me3 deposition towards promoters normally primed for zygotic genome activation. These findings reveal an epigenetic gating function for nucleolar integrity in oocyte maturation: Pol I preserves three-dimensional chromatin organization and maintains proper spatiotemporal regulation of histone modifications, independent of ribosome production. Given the evolutionary conservation of nucleolar dynamics and histone modifications during gametogenesis, our work suggests that nucleolar stress, whether from environmental factors, aging, or genetic disorders, could broadly compromise fertility by disrupting oogenic chromatin priming.

Journal Article↗

PubMed2001

Protein kinase C activation promotes microtubule advance in neuronal growth cones by increasing average microtubule growth lifetimes.

We describe a novel mechanism for protein kinase C regulation of axonal microtubule invasion of growth cones. Activation of PKC by phorbol esters resulted in a rapid, robust advance of distal microtubules (MTs) into the F-actin rich peripheral domain of growth cones, where they are normally excluded. In contrast, inhibition of PKC activity by bisindolylmaleimide and related compounds had no perceptible effect on growth cone motility, but completely blocked phorbol ester effects. Significantly, MT advance occurred despite continued retrograde F-actin flow-a process that normally inhibits MT advance. Polymer assembly was necessary for PKC-mediated MT advance since it was highly sensitive to a range of antagonists at concentrations that specifically interfere with microtubule dynamics. Biochemical evidence is presented that PKC activation promotes formation of a highly dynamic MT pool. Direct assessment of microtubule dynamics and translocation using the fluorescent speckle microscopy microtubule marking technique indicates PKC activation results in a nearly twofold increase in the typical lifetime of a MT growth episode, accompanied by a 1.7-fold increase and twofold decrease in rescue and catastrophe frequencies, respectively. No significant effects on instantaneous microtubule growth, shortening, or sliding rates (in either anterograde or retrograde directions) were observed. MTs also spent a greater percentage of time undergoing retrograde transport after PKC activation, despite overall MT advance. These results suggest that regulation of MT assembly by PKC may be an important factor in determining neurite outgrowth and regrowth rates and may play a role in other cellular processes dependent on directed MT advance.

Actins↗

PubMed2003

Triple analysis of the cancer epigenome: an integrated microarray system for assessing gene expression, DNA methylation, and histone acetylation.

We developed a novel microarray system to assess gene expression, DNA methylation, and histone acetylation in parallel, and to dissect the complex hierarchy of epigenetic changes in cancer. An integrated microarray panel consisting of 1507 short CpG island tags located at the 5'-end regions (including the first exons) was used to assess effects of epigenetic treatments on a human epithelial ovarian cancer cell line. Treatment with methylation (5-aza-2'-deoxycytidine) or deacetylation (trichostatin A) inhibitors alone resulted in up-regulation of 1.9 or 1.1% of the genes analyzed; however, the combined treatment resulted in synergistic reactivation of more genes (10.4%; P < 0.001 versus either treatment alone). On the basis of either primary or secondary responses to the treatments, genes were identified as methylation-dependent or -independent. Synergistic reactivation of the methylation-dependent genes by 5-aza-2'-deoxycytidine plus trichostatin A revealed a functional interaction between methylated promoters and deacetylated histones. Increased expression of some methylation-independent genes was associated with enhanced histone acetylation, but up-regulation of most of the genes identified using this technology was because of events downstream of the epigenetic cascade. We demonstrate proof of principle for using the triple microarray system in analyzing the dynamic relationship between transcription factors and promoter targets in cancer genomes.

Acetylation↗