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Results for “Promoter dynamics”

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PubMed2003

TAC-1 and ZYG-9 form a complex that promotes microtubule assembly in C. elegans embryos.

BACKGROUND: Modulation of microtubule dynamics is crucial for proper cell division. While a large body of work has made important contributions to our understanding of the mechanisms governing microtubule dynamics in vitro, much remains to be learned about how these mechanisms operate in vivo. RESULTS: We identified TAC-1 as the sole TACC (Transforming Acidic Coiled Coil) protein in C. elegans. TAC-1 consists essentially of a TACC domain, in contrast to the much larger members of this protein family in other species. We find that tac-1 is essential for pronuclear migration and spindle elongation in one-cell-stage C. elegans embryos. Using an in vivo FRAP-based assay, we establish that inactivation of tac-1 results in defective microtubule assembly. TAC-1 is present in the cytoplasm and is enriched at centrosomes in a cell cycle-dependent manner. Centrosomal localization is independent of microtubules but requires the activity of gamma-tubulin and the Aurora-A kinase AIR-1. By conducting FRAP analysis in embryos expressing GFP-TAC-1, we find that centrosomal TAC-1 exchanges rapidly with the cytoplasmic pool. Importantly, we establish that TAC-1 physically interacts with ZYG-9, a microtubule-associated protein (MAP) of the XMAP215 family, both in vitro and in vivo. Furthermore, we also uncover that TAC-1 and ZYG-9 stabilize each other in C. elegans embryos. CONCLUSIONS: Our findings identify TAC-1 as a core structural and functional member of the evolutionarily conserved TACC family of proteins and suggest that mutual stabilization between TACC and XMAP215 proteins is a key feature ensuring microtubule assembly in vivo.

Animals↗

PubMed2002

Using patterned substrates to promote mixing in microchannels.

Using a lattice Boltzmann model for fluid dynamics, we investigate the flow and phase behavior of a binary fluid moving over a patterned substrate within a microchannel. The binary fluid consists of two immiscible components, A and B, and this liquid is subjected to a Poiseuille flow. The substrate is decorated with a checkerboard pattern of A- and B-like patches. Through a coupling of hydrodynamics and thermodynamics, each component is driven to flow from the nonwettable domains to wettable regions. As a consequence, the A and B fluids undergo extensive mixing within the microchannels. We investigate how the degree of mixing depends on the size of the patches, the velocity of the imposed flow field, and the characteristics of the fluid. The results provide guidelines for creating localized "mixing stations" within microfluidic devices. The findings also reveal how a combination of imposed flow fields and surface patterning can be exploited to control the phase behavior of complex fluids.

Journal Article↗

PubMed2006

Identifying optimal lipid raft characteristics required to promote nanoscale protein-protein interactions on the plasma membrane.

The dynamic lateral segregation of signaling proteins into microdomains is proposed to facilitate signal transduction, but the constraints on microdomain size, mobility, and diffusion that might realize this function are undefined. Here we interrogate a stochastic spatial model of the plasma membrane to determine how microdomains affect protein dynamics. Taking lipid rafts as representative microdomains, we show that reduced protein mobility in rafts segregates dynamically partitioning proteins, but the equilibrium concentration is largely independent of raft size and mobility. Rafts weakly impede small-scale protein diffusion but more strongly impede long-range protein mobility. The long-range mobility of raft-partitioning and raft-excluded proteins, however, is reduced to a similar extent. Dynamic partitioning into rafts increases specific interprotein collision rates, but to maximize this critical, biologically relevant function, rafts must be small (diameter, 6 to 14 nm) and mobile. Intermolecular collisions can also be favored by the selective capture and exclusion of proteins by rafts, although this mechanism is generally less efficient than simple dynamic partitioning. Generalizing these results, we conclude that microdomains can readily operate as protein concentrators or isolators but there appear to be significant constraints on size and mobility if microdomains are also required to function as reaction chambers that facilitate nanoscale protein-protein interactions. These results may have significant implications for the many signaling cascades that are scaffolded or assembled in plasma membrane microdomains.

Animals↗

PubMed1999

Nutrition advocacy and national development: the PROFILES programme and its application.

Investment in nutritional programmes can contribute to economic growth and is cost-effective in improving child survival and development. In order to communicate this to decision-makers, the PROFILES nutrition advocacy and policy development programme was applied in certain developing countries. Effective advocacy is necessary to generate financial and political support for scaling up from small pilot projects and maintaining successful national programmes. The programme uses scientific knowledge to estimate development indicators such as mortality, morbidity, fertility, school performance and labour productivity from the size and nutritional condition of populations. Changes in nutritional condition are estimated from the costs, coverage and effectiveness of proposed programmes. In Bangladesh this approach helped to gain approval and funding for a major nutrition programme. PROFILES helped to promote the nutrition component of an early childhood development programme in the Philippines, and to make nutrition a top priority in Ghana's new national child survival strategy. The application of PROFILES in these and other countries has been supported by the United States Agency for International Development, the United Nations Children's Fund, the World Bank, the Asian Development Bank, the Micronutrient Initiative and other bodies.

Africa, Western↗

PubMed1991

Talin binds to actin and promotes filament nucleation.

Platelet talin binds to actin in vitro and hence is an actin binding protein. By four different non-interfering assay conditions (fluorescence, fluorescence recovery after photobleaching, (FRAP), dynamic light scattering and DNase-I inhibition) we show that talin promotes filament nucleation, raises the filament number concentration and increases the net rate of actin polymerization but has no inhibitory effect on filament elongation. Binding of talin to actin occurs at a maximal molar ratio of 1:3 as determined by fluorescencetitration under G-buffer conditions. The overall binding constant was approximately 0.25 microM.

Actins↗

PubMed2006

Are there distinct neural representations of object and limb dynamics?

In recent studies of human motor learning, subjects learned to move the arm while grasping a robotic device that applied novel patterns of forces to the hand. Here, we examined the generality of force field learning. We tested the idea that contextual cues associated with grasping a novel object promote the acquisition and use of a distinct internal model, associated with that object. Subjects learned to produce point-to-point arm movements to targets in a horizontal plane while grasping a robotic linkage that applied either a velocity-dependent counter-clockwise or clockwise force field to the hand. Following adaptation, subjects let go of the robot and were asked to generate the same movements in free space. Small but reliable after-effects were observed during the first eight movements in free space, however, these after-effects were significantly smaller than those observed for control subjects who moved the robot in a null field. No reduction in retention was observed when subjects subsequently returned to the force field after moving in free space. In contrast, controls who reached with the robot in a NF showed much poorer retention when returning to a force field. These findings are consistent with the idea that contextual cues associated with grasping a novel object may promote the acquisition of a distinct internal model of the dynamics of the object, separate from internal models used to control limb dynamics alone.

Adolescent↗

PubMed1989

Designing interventions to prevent HIV-1 infection by promoting use of condoms and spermicides among intravenous drug abusers and their sexual partners.

This paper summarizes the results of a 2-day workshop to identify the most effective educational strategies to promote use of condoms and spermicides for preventing heterosexual transmission of HIV-1 virus from intravenous drug abusers (IVDA) to their steady, nonintravenous drug abusing (NIVDA) sexual partners. Representatives from health departments, drug abuse treatment centers, academic institutions, service organizations, and the community discussed issues relating to population characteristics, educational strategies and recruitment techniques. A consensus document that identifies the most effective recruitment and intervention strategies was developed. Recruitment issues include locations, recruitment targets, anticipated difficulties, and ethical considerations. The majority of workshop participants agreed that an intervention should target the couple (both IVDA and NIVDA). Intervention concerns encompass obtaining trust, maintaining participation, and identifying guidelines to maximize program impact.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Functional and structural roles of the glutathione-binding residues in maize (Zea mays) glutathione S-transferase I.

The isoenzyme glutathione S-transferase (GST) I from maize (Zea mays) was cloned and expressed in Escherichia coli, and its catalytic mechanism was investigated by site-directed mutagenesis and dynamic studies. The results showed that the enzyme promotes proton dissociation from the GSH thiol and creates a thiolate anion with high nucleophilic reactivity by lowering the pK(a) of the thiol from 8.7 to 6.2. Steady-state kinetics fit well to a rapid equilibrium, random sequential Bi Bi mechanism, with intrasubunit modulation between the GSH binding site (G-site) and the electrophile binding site (H-site). The rate-limiting step of the reaction is viscosity-dependent, and thermodynamic data suggest that product release is rate-limiting. Five residues of GST I (Ser(11), His(40), Lys(41), Gln(53) and Ser(67)), which are located in the G-site, were individually replaced with alanine and their structural and functional roles in the 1-chloro-2,4-dinitrobenzene (CDNB) conjugation reaction were investigated. On the basis of steady-state kinetics, difference spectroscopy and limited proteolysis studies it is concluded that these residues: (1) contribute to the affinity of the G-site for GSH, as they are involved in side-chain interaction with GSH; (2) influence GSH thiol ionization, and thus its reactivity; (3) participate in k(cat) regulation by affecting the rate-limiting step of the reaction; and (4) in the cases of His(40), Lys(41) and Gln(53) play an important role in the structural integrity of, and probably in the flexibility of, the highly mobile short 3(10)-helical segment of alpha-helix 2 (residues 35-46), as shown by limited proteolysis experiments. These structural perturbations are probably transmitted to the H-site through changes in Phe(35) conformation. This accounts for the modulation of K(CDNB)(m) by His(40), Lys(41) and Gln(53), and also for the intrasubunit communication between the G- and H-sites. Computer simulations using CONCOORD were applied to maize GST I monomer and dimer structures, each with bound lactoylglutathione, and the results were analysed by the essential dynamics technique. Differences in dynamics were found between the monomer and the dimer simulations showing the importance of using the whole structure in dynamic analysis. The results obtained confirm that the short 3(10)-helical segment of alpha-helix 2 (residues 35-46) undergoes the most significant structural rearrangements. These rearrangements are discussed in terms of enzyme catalytic mechanism.

Binding Sites↗

PubMed2005

Adrenocorticotropic hormone-mediated signaling cascades coordinate a cyclic pattern of steroidogenic factor 1-dependent transcriptional activation.

Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that has emerged as a critical mediator of endocrine function at multiple levels of the hypothalamic-pituitary-steroidogenic axis. Within the adrenal cortex, ACTH-dependent transcriptional responses, including transcriptional activation of several key steroidogenic enzymes within the steroid biosynthetic pathway, are largely dependent upon SF-1 action. The absence of a bona fide endogenous eukaryotic ligand for SF-1 suggests that signaling pathway activation downstream of the melanocortin 2 receptor (Mc2r) modulates this transcriptional response. We have used the chromatin immunoprecipitation assay to examine the temporal formation of ACTH-dependent transcription complexes on the Mc2r gene promoter. In parallel, ACTH-dependent signaling events were examined in an attempt to correlate transcriptional events with the upstream activation of signaling pathways. Our results demonstrate that ACTH-dependent signaling cascades modulate the temporal dynamics of SF-1-dependent complex assembly on the Mc2r promoter. Strikingly, the pattern of SF-1 recruitment and the subsequent attainment of active rounds of transcription support a kinetic model of SF-1 transcriptional activation, a model originally established in the context of ligand-dependent transcription by several classical nuclear hormone receptors. An assessment of the major ACTH-dependent signaling pathways highlights pivotal roles for the MAPK as well as the cAMP-dependent protein kinase A pathway in the entrainment of SF-1-mediated transcriptional events. In addition, the current study demonstrates that specific enzymatic activities are capable of regulating distinct facets of a highly ordered transcriptional response.

Acetylation↗

PubMed2002

Transcriptional regulation of fis operon involves a module of multiple coupled promoters.

The transcription of the Escherichia coli fis gene is strongly activated during the outgrowth of cells from stationary phase. The high activity of the promoter of the fis operon requires the transcription factor IHF. Previously, we identified a divergent promoter, div, located upstream of the fis promoter. In this study we demonstrate that at least two additional promoters, designated fis P2 and fis P3, are located in the control region of the fis operon. The fis P2 and div promoters overlap completely, whereas fis P3 and div P are arranged as face-to-face divergent promoters. We show that the div and the tandem fis promoters counterbalance each other, such that their activity is kept on a lower than potentially attainable level. Furthermore, we demonstrate an unusual activation mechanism by IHF, involving a coordinated shift in the balance of promoter activities. We infer that these coupled promoters represent a regulatory module and propose a novel "dynamic balance" mechanism involved in the transcriptional control of the fis operon.

Base Sequence↗

PubMed2003

Roles for BTAF1 and Mot1p in dynamics of TATA-binding protein and regulation of RNA polymerase II transcription.

Regulation of RNA polymerase II (pol II) transcription is a highly dynamic process requiring the coordinated interaction of an array of regulatory proteins. Central to this process is the TATA-binding protein (TBP), the key component of the multiprotein complex TFIID. Interaction of TBP with core promoters nucleates the assembly of the preinitiation complex and subsequent recruitment of pol II. Despite recent advances in our understanding of the dynamic nature of the pol II transcription apparatus, the dynamics of TBP function on pol II promoters has remained largely unexplored. Human BTAF1 (TAF(II)170/TAF-172) and its yeast ortholog, Mot1p, are evolutionarily conserved members of the SNF2-like family of ATPase proteins. Genetic identification of Mot1p as a repressor of pol II transcription was supported by findings that Mot1p and BTAF1 could dissociate TBP from TATA DNA complexes using the energy of ATP hydrolysis. Recent data have revealed new aspects of BTAF1 and Mot1p as positive regulators of TBP function in the pol II system and have described new observations relating to their molecular mechanism of action. We review these data in the context of previous findings with particular attention paid to how human BTAF1 and Mot1p may dynamically regulate TBP function on pol II promoters in cells.

Adenosine Triphosphatases↗

PubMed2001

Assessment of trachoma prevalence in a mobile population in Central Australia.

Trachoma is reported to be hyperendemic in Australia. This study was conducted in a desert area of Central Australia to implement and evaluate the WHO SAFE strategy to control trachoma. The aim of the study was to obtain baseline trachoma prevalence data and to determine whether a single annual visit is adequate for a treatment program targeting households with active cases in a highly mobile population. All registered residents of two Aboriginal communities were eligible for examination. Four visits over the course of 13 months were made to the communities for ocular examinations of residents present at the time of the visit. Examination, diagnosis, and grading of trachoma followed WHO guidelines. The overall examination rate was 75%, refusal rate was <1%, but approximately 50% of community residents were absent during the examination period. Prevalence varied on each visit, but the overall prevalence of active trachoma was 49% over the 13-month period. Children less than 10 years of age had the highest prevalence of active trachoma (79%), over the course of the 13 months, yet the prevalence at any one visit was approximately 60%. Trachomatous scarring was present in 23% of the population. These results suggest that many cases of active trachoma may be missed if a prevalence survey is conducted at only one point in time. Multiple examinations should be conducted to adequately establish prevalence in the population. Antibiotic treatment and health promotion campaigns need to be developed in consideration of local community dynamics.

Adolescent↗

PubMed1993

Experimental molecular dynamics of an alanine-based helical peptide determined by spin label electron spin resonance.

The alanine-based 3K(I) peptide is reported to be very helical in aqueous solution. We have prepared a series of six nitroxide spin labeled analogs of the 3K(I) sequence and measured the variable-temperature ESR spectra for each in order to reveal the position-dependent peptide dynamics. From analysis of these local dynamics under helix-forming conditions at 1 degree C, we find that the helix termini show greater local dynamics than the peptide cancer. Further, the C-terminus is more mobile than the N-terminus. Even in the helix-promoting solvent trifluoroethanol, the results indicate that there is still substantially greater dynamics at the helix termini than at the peptide center. The unfolded state is also investigated, and we find that the peptide unfolded by guanidine hydrochloride is somewhat different than that found for high-temperature aqueous solution. Recently it was suggested that short 16-mer peptides may adopt a 3(10)-helix structure instead of the expected alpha-helix. The data presented here at 1 degree C show that there is sufficient disorder within the peptide to accommodate the 3(10) structure. Also calculated are the backbone torsional fluctuations, and the results compare well to those from computer molecular dynamics studies. A proposal is outlined that explains how the enhanced dynamics found at the C-terminus results from the exposure of the helix hydrogen bonds to aqueous solvent in this region of the peptide.

Alanine↗

PubMed2001

Mechanism of transcription initiation and promoter escape by RNA polymerase II.

Recently, key advances in biochemical and structural studies of RNA polymerase II (pol II) and the basal transcriptional machinery have shed considerable light on the basic mechanisms underlying the initiation stage of eukaryotic mRNA synthesis. The development of methods for obtaining crystal structures of pol II and its complexes has revolutionized transcriptional studies and holds promise that aspects of initiation will soon be understood at atomic resolution; crosslinking studies have revealed intriguing features of the topology of the pol II initiation complex and provided working models for dynamic steps of initiation; and mechanistic studies have identified promoter escape as a critical step during initiation and brought to light novel roles for the general initiation factors TFIIE, TFIIF, and TFIIH in this process.

Adenosine Triphosphatases↗

PubMed2002

TBP dynamics in living human cells: constitutive association of TBP with mitotic chromosomes.

The recruitment of TATA binding protein (TBP) to gene promoters is a critical rate-limiting step in transcriptional regulation for all three eukaryotic RNA polymerases. However, little is known regarding the dynamics of TBP in live mammalian cells. In this report, we examined the distribution and dynamic behavior of green fluorescence protein (GFP)-tagged TBP in live HeLa cells using fluorescence recovery after photobleaching (FRAP) analyses. We observed that GFP-TBP associates with condensed chromosomes throughout mitosis without any FRAP. These results suggest that TBP stably associates with the condensed chromosomes during mitosis. In addition, endogenous TBP and TBP-associated factors (TAFs), specific for RNA polymerase II and III transcription, cofractionated with mitotic chromatin, suggesting that TBP is retained as a TBP-TAF complex on transcriptionally silent chromatin throughout mitosis. In interphase cells, GFP-TBP distributes throughout the nucleoplasm and shows a FRAP that is 100-fold slower than the general transcription factor GFP-TFIIB. This difference supports the idea that TBP and, most likely, TBP-TAF complexes, remain promoter- bound for multiple rounds of transcription. Altogether, our observations demonstrate that there are cell cycle specific characteristics in the dynamic behavior of TBP. We propose a novel model in which the association of TBP-TAF complexes with chromatin during mitosis marks genes for rapid transcriptional activation as cells emerge from mitosis.

Chromatin↗

PubMed1996

The tau proteins in neuronal growth and development.

The neuronal microtubule-associated protein tau has been implicated as having a role in the outgrowth of neural processes and the development of neuronal polarity. In vitro, tau promotes microtubule assembly, stabilizes cellular microtubules, and affects their dynamic behavior. Antisense experiments using cultured neurons provided evidence for an essential role of tau in the development of axons. However, tau knockout mice turned out to be surprisingly healthy and developed neurons which were functionally and structurally almost normal. This raises the question of how essential tau is for neuronal development. In the first part of this paper, data on the function of tau as a microtubule assembly-promoting and stabilizing factor are reviewed. Then, studies investigating the role of tau in the development of neuronal polarity are discussed. In the last part, recent results which provide evidence for a role of tau not directly related to its activity on microtubule assembly are summarized.

Aging↗

PubMed1984

Context and coping: toward a unifying conceptual framework.

After offering a conceptual framework to unify the domains of context and coping, some conclusions are drawn about the underlying patterns of social climate and the characteristics of growth-promoting environments. New directions of research on the dynamics of the environmental system are described. The conceptual framework is used to exemplify ways to explore the stress and coping process in regard to such issues as stress and resource predictors of adaptation, stress prevention and resistance, and cross-situational influences. The foregoing material then highlights implications of a social ecological perspective for conducting conceptually informed evaluation research and changing and improving community settings. Finally, such conceptual problems as person-environment matching and the need to formulate unified perspectives of stressors and resources are discussed to identify promising ways to spark the maturation of community psychology.

Adaptation, Psychological↗

PubMed2006

Morphological and molecular analyses of ectomycorrhizal diversity in a man-made T. melanosporum plantation: description of novel truffle-like morphotypes.

Below-ground ectomycorrhizal communities are often species-rich, and monitoring their dynamics is important to understand the conditions that promote truffle fructification. Characterization of the different ectomycorrhizas (ECM) at the species level can now be achieved by combining detailed morphological and anatomical descriptions with molecular approaches. Following this strategy, we have characterized ectomycorrhizal biodiversity in an artificial Tuber melanosporum plantation. Although the plantation was unproductive, T. melanosporum mycorrhizas were the most present and two Tuber-like mycorrhizal morphotypes, named ECMm1 and ECMm3, showing distinctive features were found. Internal transcribed spacer (ITS) phylogenetic analysis demonstrated that ECMm3 is related to the Tuber rufum/Tuber ferrugineum species complex, whereas ECMm1 shows the highest ITS similarity with Tuber scruposum and fungi-colonizing Epipactis roots. The results presented here provide more insights into genetic variability, mycorrhizal morphology, and below-ground distribution of fungi associated with artificial truffle plantations.

Agriculture↗