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Results for “Promoter dynamics”

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At least 451 records · Page 25Linked to original sources

PubMed1988

Effect of two types of hospital feeding gift packs on duration of breast-feeding among adolescent mothers.

Two hundred forty-four adolescent mothers under 18 years of age were surveyed during a 15-month period, and 53% elected to breast-feed. A subset of 60 primiparous breast-feeding adolescents were enrolled in an investigator-blind, randomized, prospective study to compare the effects on breast-feeding duration of a standard hospital discharge feeding gift pack containing formula and a specially designed study pack that was free of infant formula. Thirty-five percent of the 60 women breast-fed less than 1 month; 22% nursed longer than 1 month but less than 2 months; and 43% breast-fed more than 2 months. There was no significant difference in breast-feeding duration among mothers by gift pack group, although those who received the study gift pack rated it higher in usefulness (p less than (0.025). The provision of infant formula samples did not appear to have a deleterious effect on the duration of breast-feeding among a population of adolescent mothers.

Adolescent↗

PubMed2004

Using a quantitative blueprint to reprogram the dynamics of the flagella gene network.

Detailed understanding and control of biological networks will require a level of description similar to that of electronic engineering blueprints. Currently, however, even the best-studied systems are usually described using qualitative arrow diagrams. A quantitative blueprint requires in vivo measurements of (1) the relative strength of the interactions (numbers on the arrows) and (2) the functions that integrate multiple inputs. Here, we address this using a well-studied system, the flagella biosynthesis transcription network in Escherichia coli. We use theory and high-resolution experiments to obtain a quantitative blueprint with (1) numbers on the arrows, finding different hierarchies of activation coefficients for the two regulators, FlhDC and FliA; and (2) cis-regulatory input functions, which summate the input from the two regulators (SUM gates). We then demonstrate experimentally how this blueprint can be used to reprogram temporal expression patterns in this system, using controlled expression of the regulators or point mutations in their binding sites. The present approach can be used to define blueprints of other gene networks and to quantitatively reprogram their dynamics.

Algorithms↗

PubMed2005

Construction of a 3D model of nattokinase, a novel fibrinolytic enzyme from Bacillus natto. A novel nucleophilic catalytic mechanism for nattokinase.

A three-dimensional structural model of nattokinase (NK) from Bacillus natto was constructed by homology modeling. High-resolution X-ray structures of Subtilisin BPN' (SB), Subtilisin Carlsberg (SC), Subtilisin E (SE) and Subtilisin Savinase (SS), four proteins with sequential, structural and functional homology were used as templates. Initial models of NK were built by MODELLER and analyzed by the PROCHECK programs. The best quality model was chosen for further refinement by constrained molecular dynamics simulations. The overall quality of the refined model was evaluated. The refined model NKC1 was analyzed by different protein analysis programs including PROCHECK for the evaluation of Ramachandran plot quality, PROSA for testing interaction energies and WHATIF for the calculation of packing quality. This structure was found to be satisfactory and also stable at room temperature as demonstrated by a 300ps long unconstrained molecular dynamics (MD) simulation. Further docking analysis promoted the coming of a new nucleophilic catalytic mechanism for NK, which is induced by attacking of hydroxyl rich in catalytic environment and locating of S221.

Amino Acid Sequence↗

PubMed2005

Microenvironmental control of premalignant disease: the role of intercellular adhesion in the progression of squamous cell carcinoma.

Interactions between potentially neoplastic cells and their normal neighbors act as an important microenvironmental control during the premalignant, intraepithelial (IE) stage of squamous cell cancer development. Using human three-dimensional (3D) tissue models, it has been shown that such interactions induce a state of IE dormancy in which cancer progression is suppressed. This dormant state can be overcome by altering tissue dynamics in response to the tumor promoter TPA, UV irradiation, decreasing adhesive interactions between tumor cells and adjacent epithelia or enabling tumor cells to interact with basement membrane proteins. This chapter will provide an overview of investigations that have characterized how the tissue microenvironment can regulate the incipient development of squamous cell carcinoma.

Animals↗

PubMed1996

Intra-abdominal fat: is it a major factor in developing diabetes and coronary artery disease?

Abdominal obesity has emerged as a strong and independent predictor for non-insulin dependent diabetes mellitus (NIDDM). Adiposity located centrally in the abdominal region, and particularly visceral as opposed to subcutaneous fat, is also distinctly associated with hyperlipidemia, compared with generalized distributions of body fat. These lipoprotein abnormalities are characterized by elevated very low density lipoprotein (VLDL) and low density lipoprotein (LDL) levels, small dense LDL with elevated apolipoprotein B levels, and decreased high density lipoprotein2b (HDL2b) levels. This is the same pattern seen in both familial combined hyperlipidemia and NIDDM. The pronounced hyperinsulinemia of upper-body obesity supports the overproduction of VLDL and the increased LDL turnover. We have proposed that an increase in the size of the visceral fat depot is a precursor to the increased lipolysis and elevated free fatty acid (FFA) flux and metabolism and to subsequent overexposure of hepatic and extrahepatic tissues to FFA, which then, in part, promotes aberrations in insulin actions and dynamics. The resultant changes in glucose/insulin homeostasis, lipoprotein metabolism, and vascular events then lead to metabolic morbidities such as glucose intolerance, NIDDM, dyslipidemia, and increased risk for coronary heart disease.

Abdomen↗

PubMed1979

Modulation of behavioral inhibition in appetitive extinction following manipulation of adrenal steroids in rats: implications for involvement of the hippocampus.

Corticosterone, the principal glucocorticoid in the rat, binds selectively to the CA1 pyramidal neurons of the hippocampus where the hormone has been demonstrated to exert a moderate chronic suppression of spontaneous activity. In the first experiment of the current study, the functional behavioral significance of this hormone--brain interaction was investigated in the extinction of an appetitive runway response in normal rats and those with lesions of the hippocampus. During extinction, half of the animals in each group were given daily subcutaneous injections of corticosterone. Whie the classical retardation effect of hippocampal lesions on appetitive extinction was replicated, hormone treatment was without effect in normal or hippocampally damaged subjects. The absence of a hormone effect in normals was primarily attributed to a saturated limited-binding system operating in the normal animal. Experiment 2 tested this notion, repeating the first experiment, with adrenal-ectomized (ADX), ADX + corticosterone replacement, and normal groups of animals. Adrenalectomy produced a striking facilitation of extinction which was speculated to be the result of a hyperactive inhibitory neural organ free from an inhibitory endocrine feedback. Corticosterone treatment normalized the progress of extinction in ADX animals, providing support for the afore-mentioned speculation. In the normal animal, it appears that a stress-induced surge in hormone level interacts with a limited-capacity neural binding to produce a transient dynamic range of behavioral disinhibition, perhaps promoting persistence during initial stages of frustrative nonreward in moderate stress tasks.

Animals↗

PubMed1995

Defective recycling of synaptic vesicles in synaptotagmin mutants of Caenorhabditis elegans.

Synaptotagmin, an integral membrane protein of the synaptic vesicle, binds calcium and interacts with proteins of the plasma membrane. These observations suggest several possible functions for synaptotagmin in synaptic vesicle dynamics: it could facilitate exocytosis by promoting calcium-dependent fusion, inhibit exocytosis by preventing fusion, or facilitate endocytosis of synaptic vesicles from the plasma membrane by acting as a receptor for the endocytotic proteins of the clathrin AP2 complex. Here we show that synaptic vesicles are depleted at synaptic terminals in synaptotagmin mutants of the nematode Caenorhabditis elegans. This depletion is not caused by a defect in transport or by increased synaptic vesicle release, but rather by a defect in retrieval or synaptic vesicles from the plasma membrane. Thus we propose that, as well as being involved in exocytosis, synaptotagmin functions in vesicular recycling.

Aldicarb↗

PubMed2001

Modifications of intracellular Ca2+ signalling during nerve growth factor-induced neuronal differentiation of rat adrenal chromaffin cells.

Postnatal sympathetic neurons (SNs) and chromaffin cells (CCs) derive from neural crest precursors. CCs can differentiate in vitro into SN-like cells after nerve growth factor (NGF) exposure. This study examines changes of intracellular Ca2+ homeostasis and dynamics of CCs under conditions that promote a neuronal phenotype. Spontaneous Ca2+ fluctuations, a frequent observation in early cultures of CCs, diminished after > 10 days in vitro in control cells and ceased in NGF-treated ones. At the same time, Ca2+ rises resulting from entry upon membrane depolarization, gradually increased both their size and peak d[Ca2+]i/dt, resembling those recorded in SNs. Concomitantly, caffeine-induced Ca2+ rises, resulting from Ca2+ release from intracellular stores, increased their size and their peak d[Ca2+]i/dt by > 1000%, and developed transient and sustained release components, similar to those of SNs. The transient component, linked to regenerative Ca2+ release, appeared after > 10 days of NGF treatment, suggesting a delayed steep enhancement of Ca2+-induced Ca2+ release (CICR). Immunostaining showed that proteins coded by the three known isoforms of ryanodine receptors (RyRs) are present in CCs, but that only RyR2 increased significantly after NGF treatment. Since the transient release component increased more steeply than RyR2 immunostaining, we suggest that the development of robust CICR requires both an increased expression of RyRs and more efficient functional coupling among them. NGF-induced transdifferentiation of chromaffin cells involves the enhancement of both voltage-gated Ca2+ influx and Ca2+ release from intracellular stores. These modifications are likely to complement the extensive morphological and functional reorganization required for the replacement of the endocrine phenotype with the neuronal one.

Adrenal Glands↗

PubMed2003

Identification of nucleocytoplasmic cycling as a remote sensor in cellular signaling by databased modeling.

Considerable progress has been made in identifying the molecular composition of complex signaling networks controlling cell proliferation, differentiation, and survival. However, to discover general building principles and predict the dynamic behavior of signaling networks, it is necessary to develop quantitative models based on experimental observations. Here we report a mathematical model of the core module of the Janus family of kinases (JAK)-signal transducer and activator of transcription (STAT) signaling pathway based on time-resolved measurements of receptor and STAT5 phosphorylation. Applying the fitted model, we can determine the quantitative behavior of STAT5 populations not accessible to experimental measurement. By in silico investigations, we identify the parameters of nuclear shuttling as the most sensitive to perturbations and verify experimentally the model prediction that inhibition of nuclear export results in a reduced transcriptional yield. The model reveals that STAT5 undergoes rapid nucleocytoplasmic cycles, continuously coupling receptor activation and target gene transcription, thereby forming a remote sensor between nucleus and receptor. Thus, dynamic modeling of signaling pathways can promote functional understanding at the systems level.

Animals↗

PubMed1999

Endogenous activation of metabotropic glutamate receptors in neocortical development causes neuronal calcium oscillations.

Oscillations in intracellular free calcium concentration ([Ca(2+)](i)) occur spontaneously in immature neurons of the developing cerebral cortex. Here, we show that developing murine cortical neurons exhibit calcium oscillations in response to direct activation of the mGluR5 subtype of the group I metabotropic glutamate receptor (mGluR). In contrast, other manipulations that elicit [Ca(2+)](i) increases produce simple, nonoscillatory changes. Furthermore, we find that spontaneous oscillatory [Ca(2+)](i) activity is blocked by antagonists of group I mGluRs, suggesting a specific role for mGluR activation in the promotion of oscillatory [Ca(2+)](i) dynamics in immature cortical neurons. The oscillatory pattern of [Ca(2+)](i) increases produced by mGluR activation might play a role in the regulation of gene expression and the control of developmental events.

Animals↗

PubMed2006

The Nup107-160 nucleoporin complex is required for correct bipolar spindle assembly.

The Nup107-160 complex is a critical subunit of the nuclear pore. This complex localizes to kinetochores in mitotic mammalian cells, where its function is unknown. To examine Nup107-160 complex recruitment to kinetochores, we stained human cells with antisera to four complex components. Each antibody stained not only kinetochores but also prometaphase spindle poles and proximal spindle fibers, mirroring the dual prometaphase localization of the spindle checkpoint proteins Mad1, Mad2, Bub3, and Cdc20. Indeed, expanded crescents of the Nup107-160 complex encircled unattached kinetochores, similar to the hyperaccumulation observed of dynamic outer kinetochore checkpoint proteins and motors at unattached kinetochores. In mitotic Xenopus egg extracts, the Nup107-160 complex localized throughout reconstituted spindles. When the Nup107-160 complex was depleted from extracts, the spindle checkpoint remained intact, but spindle assembly was rendered strikingly defective. Microtubule nucleation around sperm centrosomes seemed normal, but the microtubules quickly disassembled, leaving largely unattached sperm chromatin. Notably, Ran-GTP caused normal assembly of microtubule asters in depleted extracts, indicating that this defect was upstream of Ran or independent of it. We conclude that the Nup107-160 complex is dynamic in mitosis and that it promotes spindle assembly in a manner that is distinct from its functions at interphase nuclear pores.

Animals↗

PubMedDate not supplied

Researcher for a day: a simulation game.

Nursing students often consider research dull, with little relevance to their clinical practice. Dynamic teaching strategies are needed to promote positive attitudes toward research. A simulation game, "Researcher for a Day," was developed. The game was designed to be a challenging and enjoyable research learning experience and to provide an applied experience for the theoretical content of the research process. It also exposes students to potential obstacles to data collection. Evaluation indicates that students are enthusiastic while they learn the major objectives of the game.

Education, Nursing, Baccalaureate↗

PubMed1986

Multiple triangulation: a methodology for nursing science.

The discipline of nursing needs methodological strategies that promote the study of complex and dynamic phenomena like human health behavior. Triangulation is an approach conductive to studying such complex behavior. The purpose of this article is to discuss the four basic types of triangulation and to examine several issues and problems related to the use of a more complex form, multiple triangulation. Solutions are proposed for dealing with each of the problems involved in the research application of triangulation.

Humans↗

PubMedDate not supplied

Limb lengthening by callus distraction (callotasis).

Callotasis is a new technique of limb lengthening involving slow distraction of the callus formed in response to a proximal submetaphyseal corticotomy. Using a dynamic axial fixator with telescoping capabilities, distraction begins after 2 weeks. When the required length is attained, the fixator is held in the rigid mode until radiographic evidence of callus is observed. The locking screw is then released, and dynamic axial loading is instituted to promote corticalization. One hundred bony segments have been lengthened; 50 patients had limb length inequality, and 23 had achondroplasia. The mean lengthening achieved was 22% (maximum, 58%). There were 14 complications (14%).

Achondroplasia↗

PubMed1999

Generosity: a psychological and interpersonal motivational factor of therapeutic relevance.

This paper examines the role of generosity in analysis. Generosity represents a complex constellation of cognitions and affects that is antithetical to those states of super-ego harshness that characterize many forms of human psychopathology. In development, generosity is evoked by idealization, and a dynamic axis of idealization-generosity promotes relational proximity between the child and its caretakers, and eventually fosters separation and individuation. Generosity is highly sensitive to adverse conditions, and requires environmental conditions that are conducive to psychosomatic well-being. The imaginal basis of generosity is rooted in the myth of the 'hero and the return', which is the mythic foundation of the analyst's role as psychopomp. It is argued that the generosity of the analyst is a cardinal therapeutic factor in treatment.

Adult↗

PubMed2001

Electrophysiological heterogeneity and stability of reentry in simulated cardiac tissue.

Generation of wave break is a characteristic feature of cardiac fibrillation. In this study, we investigated how dynamic factors and fixed electrophysiological heterogeneity interact to promote wave break in simulated two-dimensional cardiac tissue, by using the Luo-Rudy (LR1) ventricular action potential model. The degree of dynamic instability of the action potential model was controlled by varying the maximal amplitude of the slow inward Ca(2+) current to produce spiral waves in homogeneous tissue that were either nearly stable, meandering, hypermeandering, or in breakup regimes. Fixed electrophysiological heterogeneity was modeled by randomly varying action potential duration over different spatial scales to create dispersion of refractoriness. We found that the degree of dispersion of refractoriness required to induce wave break decreased markedly as dynamic instability of the cardiac model increased. These findings suggest that reducing the dynamic instability of cardiac cells by interventions, such as decreasing the steepness of action potential duration restitution, may still have merit as an antifibrillatory strategy.

Action Potentials↗

PubMed2003

Nil per os encodes a conserved RNA recognition motif protein required for morphogenesis and cytodifferentiation of digestive organs in zebrafish.

Digestive organ development occurs through a sequence of morphologically distinct stages, from overtly featureless endoderm, through organ primordia to, ultimately, adult form. The developmental controls that govern progression from one stage to the next are not well understood. To identify genes required for the formation of vertebrate digestive organs we performed a genetic screen in zebrafish. We isolated the nil per os (npo) mutation, which arrests morphogenesis and cytodifferentiation of the gut and exocrine pancreas in a primordial state. We identified the npo gene by positional cloning. It encodes a conserved protein, with multiple RNA recognition motifs, that is related to the yeast protein Mrd1p. During development npo is expressed in a dynamic fashion, functioning cell autonomously to promote organ cytodifferentiation. Antisense-mediated knockdown of npo results in organ hypoplasia, and overexpression of npo causes an overgrowth of gastrointestinal organs. Thus, npo is a gene essential for a key step in the gut morphogenetic sequence.

Amino Acid Motifs↗

PubMedDate not supplied

[Scientific production in public health and the international bibliographic data bases].

This study begins by briefly situating the development of indexing procedures in the scientific literature, dating to the latter half of the 19th century. Next, taking public health in Latin America as its reference, it analyzes the current use of indexing for the evaluation of scientific production, and thus that of scientific periodicals. The argument is that for various reasons, international indexing should not be used as the only parameter for evaluating the impact of Latin American scientific production in public health. Criteria other than impact indices should be developed to promote a broader understanding of the dynamics of scientific production in the Latin America public health field.

Abstracting and Indexing↗