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Results for “Promoter dynamics”

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At least 235 records · Page 13Linked to original sources
PubMed2002

[Mechanisms of ureteral contraction-relaxation in nephritic colic].

OBJECTIVE: From the clinical perspective, pharmacological research on ureteral dynamics--the contraction-relaxation mechanisms of the ureter--, has been prompted by renal colic. Studies of the events triggered by the calculus have been conducted to identify the pharmacological aspects that permit pain relief, passage of the calculus and protection of the kidney from injury caused by acute obstruction. METHODS: Many and varied studies on ureteral pharmacology, both in vivo and in vitro, have been carried out since the beginning of the 20th century. Numerous studies on the anatomical, neurophysiological and hormonal aspects, and different neuroactive substances have attempted to identify the behavior of the ureter under normal and pathological conditions. Since 1967, the Urology Department of the 'Jiménez Díaz' Foundation has investigated the mechanisms of ureteropelvic dynamics utilizing techniques developed at this institution, such as pyelomanometry, pressure/flow to constant pressure studies and antegrade pyelography. RESULTS: The different behavior of the ureter and the stimuli it receives according to the zone analyzed, are known. The classical neurohumoral mechanisms (adrenergic and cholinergic), ureteral pacemaker, effects of urinary pH and infection, action of glucagons, prostaglandins, as well as the new mechanisms of action mediated by substances and non-adrenergic non-cholinergic (NANC) receptors (tachykinins, nitric oxide (NO), vasoactive intestinal peptide (VIP), neuropeptide Y, etc.) have led to new concepts of ureteral contraction-relaxation. CONCLUSIONS: The current therapeutic strategy in renal colic utilizes non-steroidal antiinflammatory drugs (NSAID) and extracorporeal shock wave lithotripsy (ESWL) in situ for analgesia and resolution. Recent insight into ureteral dynamics attempt to promote the development of new drugs for enhanced and more effective management of renal colic.

Acute Disease↗
PubMed2002

Let's put consumers in charge of health care.

Businesses spend billions on health insurance. And what do they get for their money? A lot of unhappy employees. Workers fret about the quality of the care they receive, the burden of their out-of-pocket expenses, and the gaps in their coverage. For businesses, health care has become a lose-lose proposition: They pay way too much, and they get way too little. The problem is that the health care industry has been shielded from consumer pressure--by employers, insurers, and the government. As a result, costs have exploded even as choices have narrowed. But if companies embrace a new model of health coverage--one that places control over both costs and care directly into the hands of employees--the competitive forces that spur productivity and innovation in consumer markets can be loosed upon the inefficient, tradition-bound health care system. Moving to consumer-driven health care requires that companies revamp their health benefits in six ways: Give employees incentives to shop intelligently; offer a real choice of insurance plans; charge employees prices that accurately reflect the company's costs; let providers set their own prices; adjust payments for each enrollee based on need; and provide relevant information. Putting consumers in charge of health care may seem like a radical approach. But individuals are highly motivated to educate themselves about their health, their insurance, and their care, and they want to seek the most value for their money. Promoting that economic dynamic--the same that fuels consumer markets everywhere--is the best way to enhance the health care industry's productivity and quality.

Consumer Behavior↗
PubMed2004

[The cause of re-stenosis in the stent].

One of the probable causes of restenosis occurrence in the stent was analyzed. Experience of surgical treatment of 59 patients with an acute vascular trauma, of the complex cutaneous flaps transplantation and of interventions on lymphovenous system was summarized. There were also conducted experimental investigations in 64 rats and in 54 rabbits, histological preparations of the vessels wall were studied. There was proved that restenosis in the stent may occur due to atrophy of muscular layer of artery, migration and subsequent proliferation of the smooth muscle cells in neointyma after sclerosis of adventitia. It is necessary to use for the stents manufacturing an expansible-dynamical constructions, which promote an active functioning of muscular layer of arterial wall without causing its atrophy.

Adolescent↗
PubMed2005

[Effectiveness of using the biologically active additive to food from Laminaria in adolescents during complex treatment of the pulmonary tuberculosis].

Main component of biologically active additive to food on the basis of sea alga Laminaria of which are copper derivatives of a chlorophyll. Application of this biologically active to food in complex with tuberculosis chemotherapy of 48 adolescents (14-17 years old) at a sanatorium stage of treatment was investigated. The comparison group were 30 patients, receiving chemotherapy without utilize of biologically active to food. It is established, that mentioned biologically active additive to food promotes favorable radiological dynamic of process, improvement of functional activity T-lymphocites and the contents of substances of low and average molecular weight and malonic dialdehyde in plasma.

Adolescent↗
PubMedDate not supplied

[Physical factors in the comprehensive therapy of purulent wounds in diabetes mellitus].

Various physical therapeutic methods were used in 256 patients with purulent wounds against a background of diabetes mellitus. Comparative evaluation of various therapeutic methods has shown that the use of physical factors lowers intoxication, stabilizes the blood level of glucose, improves indices of immunological reactivity, promotes a more dynamic course of a wound process, and reduces the time of treatment. Ultrasound cavitation and application of adsorbents to wounds proved to be the most effective physical methods for therapy of purulent wounds in patients with diabetes mellitus.

Adolescent↗
PubMed1995

[Pathogenetic mechanisms and neurophysiological diagnosis of trigeminal neuralgia].

58 patients with trigeminal nerve neuralgia (TNN) were examined in terms of somatosensory evoked potentials (SSEP). The increase of latence as well as the decrease of contra- and ipsilateral SSEP components amplitude were observed in the interval N13-P45. Either bylateral hypersynchronization or desynchronization of SSEP were observed at affect side of face during TNN paroxismal period. It was believed that both variations of entrance of two currents of impulses which had been caused either by face electrostimulation or by pathological trigeminal irritation in brain cortex. The structural defect of trigeminal radix was considered to be the primary pathogenetic factor which became the cause of constant additional impulsation. The irritation processes became as a result the dominant ones in trigenal system forming in turn the generator of pathological increased irritation in nucleus complex mainly. The conclusion was made that dynamic SSEP investigations promoted to make more precise the damage localization as well as to estimate more objectively trigeminal hypperactivity in patients with TNN.

Adult↗
PubMed1997

Proliferative stimulation of lymphocytes by calmodulin binding proteins isolated from amniotic fluid.

In view of the role of calmodulin and calmodulin binding proteins in modulating the second messenger functions of Ca2+, we studied the presence of such proteins in amniotic fluid, which may be considered as a dynamic medium for promoting foetal growth. Affinity chromatography of amniotic fluid proteins revealed the presence of calmodulin binding proteins in samples obtained either at 28 or 36 wk of pregnancy. The relative content of these proteins increased in amniotic fluid from 1.5 mg/g total protein at 28 wk to 3.6 mg/g at full term of pregnancy. Culturing murine splenocytes in presence of the isolated calmodulin binding proteins (10 micrograms protein/10(6) cells) resulted in nearly 4-fold enhancement of 3H-thymidine incorporation into them as compared to controls. In comparison, similar incorporation of the radiolabel into lymphocytes obtained from cord blood was enhanced only by 2 fold in presence of calmodulin binding proteins, though at a much lower protein concentration (50 ng/10(6) cells). SDS-PAGE on 12.5 per cent gels of eluates obtained from calmodulin-agarose columns, followed by overlay of corresponding western blots with biotinylated calmodulin revealed the presence of a 68 kDa calmodulin binding protein in samples collected either at 28 wk or at full-term of pregnancy. In addition, the amniotic fluid also contained 83 kDa calmodulin binding protein at 28 wk. This first-time demonstration of mitogenic, calmodulin binding proteins in amniotic fluid suggests that such mitogens may participate in promoting foetal growth.

Amniotic Fluid↗
PubMed2004

Focal adhesion and actin dynamics: a place where kinases and proteases meet to promote invasion.

Integrin-linked focal adhesion complexes provide the main sites of cell adhesion to extracellular matrix and associate with the actin cytoskeleton to control cell movement. Dynamic regulation of focal adhesions and reorganization of the associated actin cytoskeleton are crucial determinants of cell migration. There are important roles for tyrosine kinases, extracellular signal-regulated protein kinase/mitogen-activated protein kinase signalling, and intracellular and extracellular proteases during actin and adhesion modulation. Dysregulation of these is associated with tumour cell invasion. In this article, we discuss established roles for these signalling pathways, as well as the functional interplay between them in controlling the migratory phenotype.

Actins↗
PubMed2006

Gangliosides promote platelet adhesion and facilitate neuroblastoma cell adhesion under dynamic conditions simulating blood flow.

BACKGROUND: Aberrant gangliosides are produced and shed by some tumors into the extracellular milieu. Their concentration is related to disease progression in children with neuroblastoma and in experimental models. The mechanism for this tumor promoting effect is not known. PURPOSE: Here, we investigated the effect of gangliosides on platelet and tumor cell adhesion under shear forces simulating venous and arterial flow. RESULTS: High shear force increased platelet adhesion 2.5-fold compared to low force. Pre-incubation of platelets with gangliosides increased adhesion at low shear to a level comparable to high shear alone. The addition of gangliosides to platelets perfused at high shear did not further increase adhesion. LAN1 neuroblastoma cells are adherent to collagen in static assays. No effect of either shear or gangliosides was observed on cell adhesion under dynamic conditions. However, when perfused in the presence of platelets, an increase in binding of tumor cells was observed at both shear forces compared to cells alone. CONCLUSIONS: These results demonstrate that shear and gangliosides increase dynamic platelet adhesion to collagen. In addition, platelets facilitate tumor cell binding. Therefore, by acting as a mediator of platelet activation, gangliosides may promote blood borne metastasis by increasing platelet binding to the vessel wall and in turn facilitate tumor cell arrest in circulation.

Blood Flow Velocity↗
PubMed2006

Dynamic and transient remodeling of the macrophage IL-10 promoter during transcription.

To gain insight into the molecular mechanism(s) whereby macrophages produce large amounts of IL-10, we analyzed IL-10 gene expression and temporally correlated it with modifications to chromatin associated with the IL-10 promoter. In resting cells, which make essentially no cytokines, the IL-10 promoter is associated with histones containing little or no detectable modifications. Macrophages stimulated in the presence of immune complexes begin to produce high levels of IL-10 pre-mRNA transcripts within minutes of stimulation. Coincident with this transcription was a rapid and dynamic phosphorylation of histone H3 at specific sites in the IL-10 promoter. Histone phosphorylation was closely followed by the binding of transcription factors to the IL-10 promoter. Blocking the activation of ERK prevented histone phosphorylation and transcription factor binding to the IL-10 promoter. In contrast to histone phosphorylation, the peak of histone acetylation at this promoter did not occur until after transcription had peaked. Inhibition of histone deactylase did not alter IL-10 gene expression, suggesting that phosphorylation but not acetylation was the proximal event responsible for IL-10 transcription. Our findings reveal a rapid and well-orchestrated series of events in which ERK activation causes a rapid and transient phosphorylation of histone H3 at specific regions of the IL-10 promoter, resulting in a transient exposure of the IL-10 promoter to the transcription factors that bind there. This exposure is essential for the efficient induction of IL-10 gene expression in macrophages. To our knowledge, this represents a unique way in which the expression of a cytokine gene is regulated in macrophages.

Acetylation↗
PubMed2003

Cyclin E expression during development in Caenorhabditis elegans.

Our interest in the coordination of cell cycle control and differentiation has led us to investigate the Caenorhabditis elegans cye-1 gene encoding the G(1) cell cycle regulator cyclin E. We have studied the expression and function of cye-1 by using monoclonal antibodies directed against CYE-1 protein, cye-1::GFP reporter genes, and a cye-1 chromosomal deletion mutation. We show that a ubiquitous embryonic pattern of expression becomes restricted and dynamic during postembryonic development. Promoter analysis reveals a relatively small region of cis-acting sequences that are necessary for the complex pattern of expression of this gene. Our studies demonstrate that two other G(1) cell cycle genes, encoding cyclin D and CDK4/6, have similarly compact promoter requirements. This suggests that a relatively simple mechanism of regulation may underlie the dynamic developmental patterns of expression exhibited by these three G(1) cell cycle genes. Our analysis of a new cye-1 deletion allele confirms and extends previous studies of two point mutations in the gene.

Amino Acid Sequence↗
PubMedDate not supplied

Participation by sedentary elderly persons in an exercise promotion session.

BACKGROUND: Little is known regarding the dynamics of elderly persons' participation in health promotion programs. We studied factors influencing the participation of 337 sedentary elderly persons in an exercise promotion session. All study participants were members of a health maintenance organization. METHODS: Baseline data were obtained on 337 persons age 65 and older who exercised irregularly or not at all. These individuals were then offered a class emphasizing individualized exercise activities for elderly persons. Participation in the exercise program was used as the dependent variable, and the baseline data were analyzed to identify factors associated with participation. RESULTS: There was no difference between participants and nonparticipants for age and sex. Baseline physical activity, as measured by the Paffenbarger index and self-report of physical activity, also did not differentiate participants from nonparticipants, nor did frequency of self-reported medical conditions. Participants were more likely to be nonsmokers, but the two groups did not differ with respect to other preventive health practices. Participants were characterized by more social interactions, as reflected by attendance at at least two meetings per month. Participants also were more likely to report three or more close friends. Perceived quality of life and self-reported health status were not significantly different between the two groups. Participants rated their current health slightly worse than nonparticipants. In a logistic regression model controlling for age and sex, lower current health perceptions, greater number of friends, prior expressed intent to participate in an exercise program, being a nonsmoker, and having received an influenza vaccination in the past year were significantly associated with participation. CONCLUSIONS: Participation in this exercise program may have appealed to persons with higher levels of social interaction. In this population, age, sex, and the number and type of self-reported medical conditions at baseline were not predictive of participation.

Aged↗
PubMed2004

Promoting vibrations in human purine nucleoside phosphorylase. A molecular dynamics and hybrid quantum mechanical/molecular mechanical study.

Crystallographic studies of human purine nucleoside phosphorylase (hPNP) with several transition-state (TS) analogues in the immucillin family showed an unusual geometric arrangement of the atoms O-5', O-4', and O(P), the nucleophilic phosphate oxygen, lying in a close three-oxygen stack. These observations were corroborated by extensive experimental kinetic isotope effect analysis. We propose that protein-facilitated dynamic modes in hPNP cause this stack, centered on the ribosyl O-4' oxygen, to squeeze together and push electrons toward the purine ring, stabilizing the oxacarbenium character of the TS. As the N-ribosidic bond is cleaved during the reaction, the pK(a) values of N-7 and O-6 increase by the electron density expelled by the oxygen-stack compression toward the purine ring. Increased electron density in the purine ring improves electrostatic interactions with nearby residues and facilitates the abstraction of a proton from a solvent proton or an unidentified general acid, making the purine a better leaving group, and accelerating catalysis. Classical and mixed quantum/classical molecular dynamics (MD) simulations of the Michaelis complex of hPNP with the substrates guanosine and phosphate were performed to assess the existence of protein-promoting vibrations (PPVs). Analogous simulations were performed for the substrates in aqueous solution. In the catalytic site, the O-5', O-4', and O(P) oxygens vibrate at frequencies of ca. 125 and 465 cm(-1), as opposed to 285 cm(-1) in the absence of hPNP. The hybrid quantum mechanical/molecular mechanical method was used to assess whether this enzymatic vibration pushing the oxygens together is coupled to the reaction coordinate, and thus has a direct positive impact on catalysis. The potential energy surface for the phosphorolysis reaction for several snapshots taken from the classical MD simulation showed substantial differences in oxygen compression. Our calculations showed the existence of PPVs coupled to the reaction coordinate, which effect electronic alterations in the active site by pushing the three oxygen centers together in proximity, and accelerate substrate turnover in the phosphorolysis reaction catalyzed by hPNP.

Animals↗
PubMed2003

Finding signals for plant promoters.

The strongest signal of plant promoter is searched with the model of single motif with two types. It turns out that the dominant type is the TATA-box. The other type may be called TATA-less signal, and may be used in gene finders for promoter recognition. While the TATA signals are very close for the monocot and the dicot, their TATA-less signals are significantly different. A general and flexible multi-motif model is also proposed for promoter analysis based on dynamic programming. By extending the Gibbs sampler to the dynamic programming and introducing temperature, an efficient algorithm is developed for searching signals in plant promoters.

Algorithms↗
PubMed2026

Improving a Tn7-based luciferase reporter system for promoter activity studies.

Single-copy chromosomal integration systems are essential tools for stable gene expression in bacteria, minimizing variability associated with plasmid-based systems. The Tn7 transposon-based system is widely used for this purpose, and one important application is the generation of reporter systems, such as the bioluminescent luxCDABE operon (lux). However, current Tn7-lux vectors exhibit undesirable background expression due to cryptic promoter activity near the antibiotic resistance cassette. Here, we report the construction of an improved vector, pTn7-lux-B0015, incorporating a strong synthetic terminator upstream of the lux operon. This modification effectively eliminated basal luminescence in the absence of a promoter and enhanced the dynamic range and responsiveness of the reporter. Using a Xanthomonas citri type III secretion system promoter as a model, we demonstrate that pTn7-lux-B0015 enables more accurate detection of gene expression under relevant growth conditions. This vector provides a valuable tool for the development of precise and tunable bioluminescent reporters in bacterial systems.

Promoter Regions, Genetic↗
PubMed2005

The basic helix-loop-helix transcription factor Nex-1/Math-2 promotes neuronal survival of PC12 cells by modulating the dynamic expression of anti-apoptotic and cell cycle regulators.

The basic helix-loop-helix transcription factor Nex1/Math-2 belongs to the NeuroD subfamily, which plays a critical role during neuronal differentiation and maintenance of the differentiated state. Previously, we demonstrated that Nex1 is a key regulatory component of the nerve growth factor (NGF) pathway. Further supporting this hypothesis, this study shows that Nex1 has survival-inducing properties similar to NGF, as Nex1-overexpressing PC12 cells survive in the absence of trophic factors. We dissected the molecular mechanism by which Nex1 confers neuroprotection upon serum removal and found that constitutive expression of Nex1 maintained the expression of specific G1 phase cyclin-dependent kinase inhibitors and concomitantly induced a dynamic expression profile of key anti-apoptotic regulators. This study provides the first evidence of the underlying mechanism by which a member of the NeuroD-subfamily promotes an active anti-apoptotic program essential to the survival of neurons. Our results suggest that the survival program may be viewed as an integral component of the intrinsic programming of the differentiated state.

Animals↗
PubMed2005

Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss.

Histone variants help specialize chromatin regions; however, their impact on transcriptional regulation is largely unknown. Here, we determined the genome-wide localization and dynamics of Htz1, the yeast histone H2A variant. Htz1 localizes to hundreds of repressed/basal Pol II promoters and prefers TATA-less promoters. Specific Htz1 deposition requires the SWR1 complex, which largely colocalizes with Htz1. Htz1 occupancy correlates with particular histone modifications, and Htz1 deposition is partially reliant on Gcn5 (a histone acetyltransferase) and Bdf1, an SWR1 complex member that binds acetylated histones. Changes in growth conditions cause a striking redistribution of Htz1 from activated to repressed/basal promoters. Furthermore, Htz1 promotes full gene activation but does not generally impact repression. Importantly, Htz1 releases from purified chromatin in vitro under conditions where H2A and H3 remain associated. We suggest that Htz1-bearing nucleosomes are deposited at repressed/basal promoters but facilitate activation through their susceptibility to loss, thereby helping to expose promoter DNA.

Acetylation↗