SEARCH · PubMed Health

Results for “Promoter dynamics”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50Linked to original sources

PubMed2004

ERM proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation.

During activation, T cells associate with antigen-presenting cells, a dynamic process that involves the formation of a broad area of intimate membrane contact known as the immunological synapse. The molecular intermediates that link initial antigen recognition to the cytoskeletal changes involved in this phenomenon have not yet been defined. Here we demonstrate that ezrin-radixin-moesin proteins are rapidly inactivated after antigen recognition through a Vav1-Rac1 pathway. The resulting disanchoring of the cortical actin cytoskeleton from the plasma membrane decreased cellular rigidity, leading to more efficient T cell-antigen-presenting cell conjugate formation. These findings identify an antigen-dependent molecular pathway that favors immunological synapse formation and the subsequent development of an effective immune response.

Actin Cytoskeleton↗

PubMed1999

A developmental performance framework for primary care.

Primary care in the NHS changed substantially during the 1990s. In recent years, structural changes, most notably the introduction of primary care groups as an administrative centre for planning, have added impetus to the need for adopting meaningful measures of quality of the primary care service. This qualitative study reports the views of a sample of general practitioners, primary care nurses, and practice managers on the development and refinement of current performance indicators. Seven themes were identified as key areas for development of indicators of performance: patient experience, clinical activity, service development and innovation, access, health promotion, cost effectiveness, and quality of life outcomes. These themes are incorporated into a dynamic framework for development where improved outcomes (including quality of life measures) are seen as central to the evaluation of quality, and inter-professional collaboration in the delivery and evaluation of quality of the new primary care is called for.

Attitude of Health Personnel↗

PubMed2005

Age-dependent variations of cell response to oxidative stress: proteomic approach to protein expression and phosphorylation.

We investigated the protein profiles of variously aged rat astrocytes in response to oxidative stress. After H2O2-exposure of cells at 100 microM for 30 min, the relative intensity of ten protein spots changed on two-dimensional (2-D) gels compared with control gels after silver staining. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) analysis after in-gel digestion revealed that six of these spots corresponded to three kinds of proteins, each of which was composed of a protein and its modified form with a different isoelectric point (pI). These three proteins were identified as peroxiredoxins (PRDXs) II and III, and calpactin I light chain (p11). H2O2-exposure increased the intensity of the spot with lower pI and simultaneously decreased that of the spot with higher pI for both PRDXs II and III. In addition, the expression of annexin VII, S-adenosyl-L-homocysteine hydrolase, elongation factor II fragment (EF-II), and adenosine deaminase was increased by H2O2-exposure in astrocytes from variously aged rats. Using the Pro-Q Diamond staining, heat shock protein 60 kDa (Hsp 60) and alpha-tubulin were observed to be phosphorylated upon H2O2-exposure. While phosphorylation of alpha-tubulin was correlated positively with age, the changes in abundance of ten protein spots as described above were independent of age. These results suggest that aging does not suppress the responses aimed at limiting injury and promoting repair brought about by severe oxidative stress, and might affect cell dynamics including the formation of microtubules.

Animals↗

PubMed1992

Charge balance in the alpha-hydroxyacid dehydrogenase vacuole: an acid test.

The proposal that the active site vacuole of NAD(+)-S-lactate dehydrogenase is unable to accommodate any imbalance in electrostatic charge was tested by genetically manipulating the cDNA coding for human muscle lactate dehydrogenase to make a protein with an aspartic acid introduced at position 140 instead of the wild-type asparagine. The Asn 140-Asp mutant enzyme has the same kcat as the wild type (Asn 140) at low pH (4.5), and at higher pH the Km for pyruvate increases 10-fold for each unit increase in pH up to pH 9. We conclude that the anion of Asp 140 is completely inactive and that it binds pyruvate with a Km that is over 1,000 times that of the Km of the neutral, protonated aspartic-140. Experimental results and molecular modeling studies indicate the pKa of the active site histidine-195 in the enzyme-NADH complex is raised to greater than 10 by the presence of the anion at position 140. Energy minimization and molecular dynamics studies over 36 ps suggest that the anion at position 140 promotes the opening of and the entry of mobile solvent beneath the polypeptide loop (98-110), which normally seals off the internal active site vacuole from external bulk solvent.

Amino Acid Sequence↗

PubMed2002

Seed bank in annuals: competition between banker and non-banker morphs.

Seed bank is a plant life history strategy against the unpredictability of the biotic and the abiotic environment. We simulated competition between a seed banking and a non-banking morph of an annual plant. A constant fraction of the banker morph seeds was allocated to the seed bank, where they had a constant mortality and germination rate. All surviving seeds of the non-banker morph germinated in the next generation. The seedlings of both morphs experienced similar density-dependent mortality. Whether one of the morphs wins or the morphs coexist was evaluated from parameter space plots and statistically with logistic regression analysis. All parameters of the model had a significant, nonlinear effect on the persistence of the morphs, supporting our approach of numerically covering a wide range of parameter values. The seed production of a focal morph increased its survival and decreased the survival of the other morph. Otherwise, the morphs showed opposite response to changes in the model parameters. The banker morph was usually the winning strategy when it had a higher seed production than the non-banker morph. The banker morph benefitted from high germination probability, while the non-banker benefitted from high allocation to seed bank and high seed mortality. The coexistence of the morphs was inhibited by high banker morph seed production and seed mortality and promoted by high values of all other parameters. The system showed complex dynamics when banking was the winning strategy or the morphs coexisted. In addition, a part of the parameter space where the non-banker morph wins showed complex dynamics. Our results suggest that seed banking is a beneficial strategy if seed number is increased consequently, e.g. due to a decreased seed size. If banking decreases seed number, the non-banker morph wins or the two morphs coexist.

Ecosystem↗

PubMed1998

Coastal Environmental Impacts Brought About by Alterations to Freshwater Flow in the Gulf of Mexico

/ Freshwater inflow is one of the most influential landscape processes affecting community structure and function in lagoons, estuaries, and deltas of the world; nevertheless there are few reviews of coastal impacts associated with altered freshwater inputs. A conceptual model of the possible influences of freshwater inflows on biogeochemical and trophic interactions was used to structure this review, evaluate dominant effects, and discuss tools for coastal management. Studies in the Gulf of Mexico were used to exemplify problems commonly encountered by coastal zone managers and scientists around the world. Landscape alteration, impacting the timing and volume of freshwater inflow, was found to be the most common stress on estuarine systems. Poorly planned upstream landscape alterations can impact wetland and open-water salinity patterns, nutrients, sediment fertility, bottom topography, dissolved oxygen, and concentrations of xenobiotics. These, in turn, influence productivity, structure, and behavior of coastal plant and animal populations. Common biogeochemical impacts include excessive stratification, eutrophication, sediment deprivation, hypoxia, and contamination. Common biological impacts include reduction in livable habitats, promotion of "exotic" species, and decreased diversity. New multiobjective statistical models and dynamic landscape simulations, used to conduct policy-relevant experiments and integrate a wide variety of coastal data for freshwater inflow management, assume that optimum estuarine productivity and diversity is found somewhere between the stress associated with altered freshwater flow and the subsidy associated with natural flow. These models attempt to maximize the area of spatial overlap where favorable dynamic substrates, such as salinity, coincide with favorable fixed substrates, such as bottom topography. Based upon this principle of spatial overlap, a statistical performance model demonstrates how population vitality measurements (growth, survival, and reproduction) can be used to define sediment, freshwater, and nutrient loading limits. Similarly, a spatially articulate landscape simulation model demonstrates how cumulative impacts and ecosystem processes can be predicted as a function of changes in freshwater, sediment, and nutrient inflows.KEY WORDS: Resource management; Landscape impacts; Freshwater discharge; Coastal, ecosystem models; Coastal wetlands

Journal Article↗

PubMed2006

Study of the interaction between Apis mellifera venom and micro-heterogeneous systems.

The bee venom, used in treatment of inflammatory and articular diseases, is a complex mixture of peptides and enzymes and the presence of tryptophan allows the investigation by fluorescence techniques. Steady state and time-resolved fluorescence spectroscopy were used to study the interaction between bee venom extracted from Apis mellifera and three micro heterogeneous systems: sodium dodecylsulphate (SDS) micelles, sodium dodecylsulphate-poly(ethylene oxide) (SDS-PEO) aggregates, and the polymeric micelles LUTROL F127, formed by poly(ethylene oxide)-poly(propylene oxide)- poly(ethylene oxide). Fluorescence parameters in buffer solution were typical of peptides containing tryptophan exposed to the aqueous medium, and they gradually changed upon the addition of surfactant and polymeric micelles, demonstrating the interaction of the peptides with the micro heterogeneous systems. Quenching experiments were carried out using the N-alkylpyridinium ions (ethyl, hexyl, and dodecyl) as quenchers. In buffer solution the quenching has low efficiency and is independent of the alkyl chain length of the quencher. In the presence of the micro heterogeneous systems the extent of static and dynamic quenching enhanced, showing that both fluorophore and quenchers reside in the microvolume of the aggregates. The more hydrophobic quencher (dodecyl pyridinium ion) provides higher values for K (SV) and dynamic quenching constants, and SDS-PEO aggregates are most efficient to promote interaction between peptides and alkyl pyridinium ions. The results proved that bee venom interacts with drug delivery micelles of the copolymer LUTROL F127.

Animals↗

PubMed2026

Chromatin context shapes SPT5 regulation of promoter-proximal Pol II, fine-tuning gene expression changes during Drosophila embryogenesis.

Transcription involves initiation, pausing, elongation, and termination. Suppressor of Ty5 (SPT5) regulates promoter-proximal pausing and elongation, but how it orchestrates both steps during dynamic developmental changes in gene expression remains unclear. Here, using rapid optogenetic depletion in Drosophila embryos, we uncover different consequences of SPT5 removal at different developmental stages. In early embryos, SPT5 depletion causes a shift of RNA polymerase II (Pol II) from the canonical pausing site to the +1 nucleosome, which is strongly positioned. In late embryos, SPT5 depletion similarly reduces pausing at the canonical site, but the transcriptional machinery can overcome the +1 nucleosome-which appears more labile at this time point-moving into the gene body. This results in lethality and both up- and downregulation of expression, depending on the balance between Pol II entering the gene body and defective elongation. This is intensified for genes naturally increasing or decreasing their expression, indicating that SPT5 contributes to fine-tuning dynamic expression changes.

+1 nucleosome↗

PubMed2004

SVZa neural stem cells differentiate into distinct lineages in response to BMP4.

Neural stem cells (NSCs) reside in the anterior portion of the forebrain subventricular zone (SVZa) and generate the progenitors which will differentiate into neurons, and via a tangential migratory pathway, known as the rostral migratory stream (RMS), migrate to the olfactory bulbs (OB). Bone morphogenetic proteins (BMPs) play significant roles in neural development at different stages and locations, but their roles have not been determined in the SVZa. To explore possible roles of BMPs in SVZa NSCs, BMP4 at various concentrations were tested for their capacity to induce SVZa NSCs. The expression of BMP4 was also examined in living cells using a reportor vector, in which the BMP4 promotor was conjugated with red fluorescent protein (RFP). In the meantime, the differentiation of SVZa NSCs was dynamically monitored by using reportor vectors of the Nestin enhancer and the promoters of TH and GFAP. In the OB, high expression of BMP4 was found using both promoter activity analysis and in situ hybridization. However, low BMP4 expression was found in the RMS and only moderate expression of BMP4 was displayed in the SVZa. The results also demonstrated that low concentrations (1-5 ng/ml) of BMP4 promoted the proliferation of SVZa NSCs but high concentrations (10-100 ng/ml) of BMP4 inhibited this proliferation. BMP4 enhanced neuron commitment before 4 days but inhibited it after 4 days. As the antagonist of BMP4, Noggin almost completely blocked all these BMP4 responses. Thus, our findings indicate that BMP4 promotes the exit from the cell cycle and triggers the differentiation of neuron progenitors in the OB. BMP4 also promotes the proliferation of the committed neuron progenitors in the RMS, but in the SVZa, BMP4 may facilitate the commitment of NSCs into astrocytes.

Animals↗

PubMed2005

osni.info-Using free/libre/open source software to build a virtual international community for open source nursing informatics.

Many health informatics organizations seem to be slow to take up the advantages of dynamic, web-based technologies for providing services to, and interaction with, their members; these are often the very technologies they promote for use within healthcare environments. This paper aims to introduce some of the many free/libre/open source (FLOSS) applications that are now available to develop interactive websites and dynamic online communities as part of the structure of health informatics organizations, and to show how the Open Source Nursing Informatics Working Group (OSNI) of the special interest group in nursing informatics of the International Medical Informatics Association (IMIA-NI) is using some of these tools to develop an online community of nurse informaticians through their website, at . Some background introduction to FLOSS applications is used for the benefit of those less familiar with such tools, and examples of some of the FLOSS content management systems (CMS) being used by OSNI are described. The experiences of the OSNI will facilitate a knowledgeable nursing contribution to the wider discussions on the applications of FLOSS within health and healthcare, and provides a model that many other groups could adopt.

Database Management Systems↗

PubMed2006

Nucleosome core particles containing a poly(dA.dT) sequence element exhibit a locally distorted DNA structure.

Poly(dA.dT) DNA sequence elements are thought to promote transcription by either excluding nucleosomes or by altering their structural or dynamic properties. Here, the stability and structure of a defined nucleosome core particle containing a 16 base-pair poly(dA.dT) element (A16 NCP) was investigated. The A16 NCP requires a significantly higher temperature for histone octamer sliding in vitro compared to comparable nucleosomes that do not contain a poly(dA.dT) element. Fluorescence resonance energy transfer showed that the interactions between the nucleosomal DNA ends and the histone octamer were destabilized in A16 NCP. The crystal structure of A16 NCP was determined to a resolution of 3.2 A. The overall structure was maintained except for local deviations in DNA conformation. These results are consistent with previous in vivo and in vitro observations that poly(dA.dT) elements cause only modest changes in DNA accessibility and modest increases in steady-state transcription levels.

Crystallography, X-Ray↗

PubMed2003

The pH dependence of HIV-1 capsid assembly and its interaction with cyclophilin A.

Immature HIV-1 virions have spherical cores which become conical due to cleavage of the capsid domain of Gag. Here, we have used an immature form of capsid and show by electron microscopy, atomic force microscopy and single angle light scattering that it aggregates to spherical cores resembling immature virions at high ionic strengths and at pH values above 6. Dynamic angle light scattering of the dissociated protein shows structural changes that promote oligomerization above pH 6. We then examined the role of the required host protein cyclophilin A on assembly. Cyclophilin A is incorporated into virions at a 1:10 cyclophilin A/capsid ratio. We find that although cyclophilin A does not affect the oligomerization rate or stability of immature capsid cores, it does bind strongly to immature capsid at physiological stoichiometry above pH 6. This association serves as an entry route of cyclophilin A into HIV-1 virions.

Capsid↗

PubMed2002

Effects of maintaining and redirecting infant attention on the production of referential communication in infants with and without Down syndrome.

The effects of maternal interactive styles on the production of referential communication were assessed in four groups of infants whose chronological ages ranged between 0;6 and 1;8. Two groups of infants with Down syndrome (DS), one (n = 11) with a mean mental age (MA) of 0;8.6, and the other (n = 11) of 1;4.5, were matched on MA with two groups (n = 10 each) of typically developing infants. Infants were seen bi-monthly, for 8 months, with mothers, same-aged peers, and mothers of the peers. Results showed that High MA non-Down syndrome (ND) infants produced more words, and High MA DS infants produced more gestures when playing with mothers than peers. Mothers exhibited more attentional maintaining behaviours than peers, in particular to High MA infants, but they redirected the attentional focus of Low MA infants more. Sequential loglinear analyses revealed interesting contingencies between the interactive strategies of mothers and the referential communicative behaviours of their infants. Whereas maintaining attention increased, redirecting attention decreased the likelihood of the production of gestures and words in children. However, redirecting attention was followed by maintaining attention. Thus, mothers redirect the attentional focus in order to promote joint attention and referential communication. Furthermore, words and gestures of the children also promote joint attention in mothers. This highlights the reciprocal nature of these dynamic communicative interactions.

Attention↗

PubMed2002

Elevated c-Src is linked to altered cell-matrix adhesion rather than proliferation in KM12C human colorectal cancer cells.

Elevated expression and/or activity of c-Src, the prototype of the Src family of protein tyrosine kinases, is associated with the development of human colon cancer. However, despite the known pleiotropic effects of these kinases in promoting (a) cell growth downstream of growth factor receptors, and (b) the dynamic regulation of integrin adhesions in fibroblast model systems, their precise role in epithelial cancer cells is unknown. Here we addressed whether elevated expression and activity of cellular Src alters cell proliferation and/or cell-matrix adhesion in cancer cells from the Fidler model of colorectal metastasis. Although elevated Src correlates with ability to metastasise to the liver after intrasplenic injection, we found that this was not linked to enhanced growth, either in vitro or in vivo as sub-cutaneous tumours. However, elevated Src was associated with enhanced attachment to extracellular matrix. In addition, adhesion to fibronectin, was suppressed by agents that inhibited Src activity, while enforced elevation of Src in non-metastatic cells was sufficient to stimulate adhesion to fibronectin and enhanced assembly of adhesion complexes, without influencing cell growth. Thus, we conclude that one role of elevated Src in human colon cancer cells is to modulate integrin-dependent cell-matrix attachment and formation of adhesion structures, which may, in turn, influence cell motility and integrin-dependent cellular responses.

Cell Adhesion↗

PubMed2004

Dynamic interactions between 14-3-3 proteins and phosphoproteins regulate diverse cellular processes.

14-3-3 proteins exert an extraordinarily widespread influence on cellular processes in all eukaryotes. They operate by binding to specific phosphorylated sites on diverse target proteins, thereby forcing conformational changes or influencing interactions between their targets and other molecules. In these ways, 14-3-3s 'finish the job' when phosphorylation alone lacks the power to drive changes in the activities of intracellular proteins. By interacting dynamically with phosphorylated proteins, 14-3-3s often trigger events that promote cell survival--in situations from preventing metabolic imbalances caused by sudden darkness in leaves to mammalian cell-survival responses to growth factors. Recent work linking specific 14-3-3 isoforms to genetic disorders and cancers, and the cellular effects of 14-3-3 agonists and antagonists, indicate that the cellular complement of 14-3-3 proteins may integrate the specificity and strength of signalling through to different cellular responses.

14-3-3 Proteins↗

PubMed2004

Strand invasion promoted by recombination protein beta of coliphage lambda.

Studies of phage lambda in vivo have indicated that its own recombination enzymes, beta protein and lambda exonuclease, are capable of catalyzing two dissimilar pathways of homologous recombination that are widely distributed in nature: single-strand annealing and strand invasion. The former is an enzymatic splicing of overlapping ends of broken homologous DNA molecules, whereas the latter is characterized by the formation of a three-stranded synaptic intermediate and subsequent strand exchange. Previous studies in vitro have shown that beta protein has annealing activity, and that lambda exonuclease, acting on branched substrates, can produce a perfect splice that requires only ligation for completion. The present study shows that beta protein can initiate strand invasion in vitro, as evidenced both by the formation of displacement loops (D-loops) in superhelical DNA and by strand exchange between colinear single-stranded and double-stranded molecules. Thus, beta protein can catalyze steps that are central to both strand annealing and strand invasion pathways of recombination. These observations add beta protein to a set of diverse proteins that appear to promote recognition of homology by a unitary mechanism governed by the intrinsic dynamic properties of base pairs in DNA.

Bacteriophage lambda↗

PubMed2024

Extreme elevational migration spurred cryptic speciation in giant hummingbirds.

The ecoevolutionary drivers of species niche expansion or contraction are critical for biodiversity but challenging to infer. Niche expansion may be promoted by local adaptation or constrained by physiological performance trade-offs. For birds, evolutionary shifts in migratory behavior permit the broadening of the climatic niche by expansion into varied, seasonal environments. Broader niches can be short-lived if diversifying selection and geography promote speciation and niche subdivision across climatic gradients. To illuminate niche breadth dynamics, we can ask how "outlier" species defy constraints. Of the 363 hummingbird species, the giant hummingbird (Patagona gigas) has the broadest climatic niche by a large margin. To test the roles of migratory behavior, performance trade-offs, and genetic structure in maintaining its exceptional niche breadth, we studied its movements, respiratory traits, and population genomics. Satellite and light-level geolocator tracks revealed an >8,300-km loop migration over the Central Andean Plateau. This migration included a 3-wk, ~4,100-m ascent punctuated by upward bursts and pauses, resembling the acclimatization routines of human mountain climbers, and accompanied by surging blood-hemoglobin concentrations. Extreme migration was accompanied by deep genomic divergence from high-elevation resident populations, with decisive postzygotic barriers to gene flow. The two forms occur side-by-side but differ almost imperceptibly in size, plumage, and respiratory traits. The high-elevation resident taxon is the world's largest hummingbird, a previously undiscovered species that we describe and name here. The giant hummingbirds demonstrate evolutionary limits on niche breadth: when the ancestral niche expanded due to evolution (or loss) of an extreme migratory behavior, speciation followed.

Animals↗

PubMed2002

Phospholipid-induced monomerization and signal-peptide-induced oligomerization of SecA.

The SecA ATPase drives the processive translocation of the N terminus of secreted proteins through the cytoplasmic membrane in eubacteria via cycles of binding and release from the SecYEG translocon coupled to ATP turnover. SecA forms a physiological dimer with a dissociation constant that has previously been shown to vary with temperature and ionic strength. We now present data showing that the oligomeric state of SecA in solution is altered by ligands that it interacts with during protein translocation. Analytical ultracentrifugation, chemical cross-linking, and fluorescence anisotropy measurements show that the physiological dimer of SecA is monomerized by long-chain phospholipid analogues. Addition of wild-type but not mutant signal sequence peptide to these SecA monomers redimerizes the protein. Physiological dimers of SecA do not change their oligomeric state when they bind signal sequence peptide in the compact, low temperature conformational state but polymerize when they bind the peptide in the domain-dissociated, high-temperature conformational state that interacts with SecYEG. This last result shows that, at least under some conditions, signal peptide interactions drive formation of new intermolecular contacts distinct from those stabilizing the physiological dimer. The observations that signal peptides promote conformationally specific oligomerization of SecA while phospholipids promote subunit dissociation suggest that the oligomeric state of SecA could change dynamically during the protein translocation reaction. Cycles of SecA subunit recruitment and dissociation could potentially be employed to achieve processivity in polypeptide transport.

Adenosine Triphosphatases↗