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Results for “Promoter dynamics”

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At least 379 records · Page 21Linked to original sources

PubMed2003

Subthreshold sodium currents and pacemaking of subthalamic neurons: modulation by slow inactivation.

Neurons of the subthalamic nucleus (STN) are spontaneously active. By voltage clamping dissociated rat STN neurons with their own firing patterns, we found that pacemaking is driven by two kinds of subthreshold sodium current: a steady-state "persistent" sodium current and a dynamic "resurgent" sodium current, which promotes rapid firing by flowing immediately after a spike. These currents are strongly regulated by a process of slow inactivation that is active at physiological firing frequencies. Slow inactivation of the pacemaking sodium currents promotes a constant frequency of tonic firing in the face of small, steady changes in input and constitutes a form of adaptation at the single-cell level. Driving cells at a high rate (75 Hz) produced pronounced slow inactivation (60%-70%) of resurgent, persistent, and transient components of sodium current. This inactivation is likely to contribute to effects of clinical deep-brain stimulation on STN excitability.

Action Potentials↗

PubMed1997

Characterization of dynamics of the psbD light-induced transcription in mature wheat chloroplasts.

Dynamical aspects of three chloroplast promoters responding to change in light condition were examined in mature chloroplasts of wheat (Triticum aestivum) by in vitro transcription. The wheat psbD/C operon has four distinct promoters, two of which named as D/C-3 and D/C-4 promoters dominantly function in mature chloroplasts to produce the mRNAs encoding D2/CP43 and CP43 alone, respectively. Activity of the D/C-3 promoter in mature chloroplasts was reduced to less than 30% by 24 h dark adaptation and recovered by re-illumination to the original level within 30 to 60 min. The activation of the D/C-3 promoter which requires de novo cytoplasmic protein synthesis was induced by low fluence of light (e.g. 16 microE m(-2) s(-1)), but the extent of activation increased with increasing light fluence. The accumulation of mRNAs from the D/C-3 promoter saturated at 2- to 3-fold higher level within 2 h when the dark-adapted seedlings were transferred to the light at 72 microE m(-2) s(-1), concomitant with the increase in rate of D2 synthesis, suggesting that synthesis of D2 in mature chloroplasts is controlled via the D/C-3 promoter activity in a light-dependent way. Activity of the D/C-4 promoter slightly increased in the dark and decreased in the light. Effect of light on the psbA promoter activity was not observed at all in mature chloroplasts. In vitro transcriptional analysis of the D/C-3 promoter with 5' deletion mutations revealed that at least two cis elements which are located within the sequences of -78 to -47 and -46 to -29 of the transcription initiation site, respectively, act as enhancing elements in the D/C-3 promoter. The light-switching element of the transcription, however, was suggested to be located in the core promoter sequence downstream of the -35 element.

Chloroplasts↗

PubMed1979

Voicing duration and vocal SPL changes associated with stuttering reduction during singing.

This study was conducted to determine if stuttering reduction during singing is associated with increased voicing duration and increased vocal SPL. Eight moderate to severe stutterers comprised the experimental group. Eight normal speakers, matched pairwise with the stutterers for sex and age, served as controls. Pre-experimental testing indicated that all subjects knew from memory the melody of the well-known song "Home on the Range." Subsequently, subjects were asked to read aloud and sing altered lyrics of this song to the conventional melody. Results showed that from reading to singing, disfluency frequency decreased significantly among the stutterers. Both groups of subjects significantly increased voicing durations across the two conditions, but only the normal speakers increased vocal SPL during song. These results indicated that the reduction in stutterers' disfluency (stutterings included) during singing was attended by an altered pattern of vocalization that included an increase in voicing duration, but no significant change in vocal SPL. These findings are discussed with reference to vocal tract dynamics, especially those that might promote higher levels of fluency among stutterers.

Adolescent↗

PubMed2002

Anaesthesia for thoracoscopic surgery.

The surgical requirement for thoracoscopy is a good view of the contents of the thorax. This is achieved by capitalizing on natural consequences and the skills of anaesthesiologists to produce a pneumothorax and collapse the ipsilateral lung--a process that is commonly enhanced by insufflating carbon dioxide. Insufflating CO2 to actively promote lung collapse creates the dynamics of a tension pneumothorax. Complications are clinically insignificant if CO2 is used judiciously. There is a body of experience using ordinary endotracheal tubes and two-lung ventilation. Techniques of one-lung ventilation are more widely reported. All the factors known to contribute to the significant increase in shunt fraction associated with one-lung ventilation apply. The manoeuvre of collapsing a lung is no longer regarded as benign. Chemical attempts to produce a reversible post-pneumonectomy pulmonary circulation have not been shown to be an improvement. Post-operative pain can be severe. The mechanism is not defined but it differs from that associated with thoracotomy. Epidural analgesia and opioids may be required. Chronic pain syndromes have been described as complications.

Anesthesia↗

PubMed1985

Correlation of ouabain-sensitive ion movements with cell-cycle activation.

The role of tumor-promoter-induced Na+, K+-ATPase activity in cell proliferation and the extent of coupling of Na+ and K+ movements to cell-cycle control under differing physiological states was examined. Earlier studies indicated that staging of cells in G1 by serum deprivation in the presence of phorbol esters such as phorbol 12-myristate 13-acetate (PMA) induced a state(s) in which postconfluent C3H 10T1/2 fibroblasts were refractory to ouabain inhibition of DNA synthesis, and the present study further examines this property. Previous findings suggested that the promoter can act in either of two ways: (i) it can act by inducing an alternative pathway to S-phase independent of Na+,K+-ATPase activity, or (ii) the promoter can advance the cells in G1 to a point beyond which Na+, K+-ATPase activity is no longer required for the induction of DNA synthesis. When ouabain (0.3 mM) was added simultaneously with tumor promoters, such as dihydroteleocidin B, to cells arrested in the G1 phase, [3H]thymidine incorporation was inhibited greater than 90%. These data suggest that an alternative pathway is not likely the explanation but that tumor promoters advance cells through a dynamic state in G1, during which progression toward S-phase entry is independent of a Na+,K+-ATPase dependent regulatory step. Ouabain sensitivity kinetics measured by two independent methods indicated that the development of ouabain insensitivity is found in G1 approximately equal to 2 hr prior to S phase. This study indicates that the measured ion movements are markedly dependent on cell-cycle state and describes the criteria required to obtain reproducible responses.

Animals↗

PubMed2000

Dimer formation by ternary complex factor ELK-1.

Ternary complex factors (TCFs), a subgroup of the ets protein family, bind with a dimer of serum response factor to the c-fos serum response element. Both DNA binding and transcriptional activation by TCFs are regulated by mitogen-activated protein kinases. When activated, mitogen-activated protein kinases form homodimers that translocate to the nucleus, where they interact with TCFs via specific docking sites. Here we show by three different criteria that Elk-1 is capable of forming dimers in eukaryotic cells through two distinct interaction domains. These observations are consistent with a dynamic model of TCF-promoter interactions.

Animals↗

PubMed2003

Constitutively elevated nuclear export activity opposes Ca2+-dependent NFATc3 nuclear accumulation in vascular smooth muscle: role of JNK2 and Crm-1.

The transcription factor NFAT (nuclear factor of activated T-cells) is a cytosolic phosphoprotein that accumulates in the nucleus following dephosphorylation by the calcium (Ca2+)/calmodulin-dependent phosphatase, calcineurin. A defining feature of stimuli that induce NFAT nuclear accumulation/activation is a sustained increase in global intracellular Ca2+. Contrary to expectations, we have found that a sustained elevation of intracellular Ca2+, induced by membrane potential depolarization and mediated by voltage-dependent Ca2+ channels, does not result in nuclear localization of the NFATc3 isoform in smooth muscle. However, vasoconstrictors (e.g. uridine triphosphate (UTP)) and growth factors, which elevate intracellular Ca2+ and engage multiple intracellular signaling pathways, induce a robust increase in smooth muscle nuclear NFATc3. Here we show that depolarizing stimuli that normally fail to induce NFATc3 nuclear accumulation in arterial smooth muscle effectively induce nuclear accumulation under conditions in which Crm-1-dependent or JNK2-mediated nuclear export processes are disrupted. Consistent with an important regulatory role for JNK, UTP exerts a suppressive effect on JNK activity in smooth muscle. Export of nuclear NFATc3 following UTP-induced nuclear accumulation is dramatically slowed in cerebral arteries from JNK2-/- animals. These data indicate that in smooth muscle, stimulation of Ca2+-dependent, calcineurin-mediated nuclear import and suppression of Crm-1/JNK-dependent nuclear export are both required for induction of NFATc3 nuclear accumulation. These results highlight the dynamic interplay between influences that promote and oppose NFAT nuclear accumulation and suggest that in arterial smooth muscle suppression of constitutive nuclear export activity is an important property of NFAT-activating stimuli.

Active Transport, Cell Nucleus↗

PubMed1997

Management of 1000 vestibular schwannomas (acoustic neuromas): clinical presentation.

OBJECTIVE: Despite good knowledge of the key symptoms of vestibular schwannomas and their significance for surgical results, the evolution of symptoms and signs and their relation to tumor extension still need thorough investigation. METHODS: From 1978 to 1993, operations were performed by the same surgeon (M.S.) on 1000 vestibular schwannomas at the Neurosurgical Department of Nordstadt Hospital. The vestibular schwannomas were diagnosed in 962 patients, including 522 female patients (54%) and 440 male patients (46%); the mean age was significantly higher in female patients (47.6 yr) than in men (45.2 yr). We focused our analysis on the incidence of subjective disturbances versus objective morbidity, on the sequence of symptom onset, and on symptom duration and symptomatology versus tumor size and extension. RESULTS: The most frequent clinical symptoms were disturbances of the acoustic (95%), vestibular (61%), trigeminal (9%), and facial (6%) nerves. Symptom duration was 3.7 years for hearing loss, 1.9 years for facial paresis, and 1.3 years for trigeminal disturbances. Symptom incidence and duration did not strictly correlate with tumor size. Key symptoms of various tumor extension classes precipitated the diagnosis, such as trigeminal disturbances in large tumors with brain stem compression or tinnitus in small neuromas. In cases of trigeminal or facial nerve symptoms, the overall duration of symptomatology was much shorter. According to the subjective perception of the patients, between only one- and two-thirds of nerve disturbances were noticed. Patients with preoperative deafness had become deaf either chronically (23%) or suddenly (3%); even in cases of moderate hearing deficit that lasts a long time, deafness can occur suddenly. The rate of tinnitus was higher in hearing than in deaf patients; however, deafness does not mean relief from tinnitus, because this symptom persists in 46% of preoperatively deaf patients. Vestibular disturbances most often occur as some unsteadiness while walking or as vertigo, and the symptoms frequently are fluctuating, not constant. CONCLUSION: Differences in tumor biology can be underestimated and are not visible on radiological scans. For example, intrameatal tumors, despite their small size, present with a duration of symptoms that is representative of the larger tumors and are most frequently associated with vestibular symptoms and with tinnitus. Large tumors with brain stem compression present with relatively shorter symptom durations and at a younger age; both factors are suggestive of especially fast tumor growth. The clinical findings presented in this study promote new consideration of the dynamics of tumor growth and of the affected neural tissues.

Adult↗

PubMed2001

A case-control study of beliefs and behaviors associated with sexually transmitted disease occurrence in Estonia.

BACKGROUND: Epidemiologic data document rapidly increasing sexually transmitted disease (STD) rates throughout Eastern Europe. GOAL: This case-control study was designed to delineate factors contributing to the STD epidemic in Estonia. STUDY DESIGN: For this study, 189 study participants and 112 control subjects completed a behavioral questionnaire and underwent testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum. RESULTS: The prevalence of STDs among the control subjects was 32%. Although the participants believed that condoms prevent STDs, only 17% reported consistent use. Methods believed to prevent transmission included washing the genitals (65%), urinating (26%), douching (35%), and using oral contraceptives (19%). An interaction between sex and travel outside Estonia (odds ratio, 0.1; 95% CI, 0-0.7) reflects the fact that males with STDs were more likely to report travel (46% of participants and 45.5% of control subjects with STD) than were those without STD (16.1% of controls without STD). CONCLUSIONS: STD rates are related to high-risk sexual behavior among males traveling outside of Estonia. Intervention is needed to promote understanding of disease transmission dynamics in this area, and to decrease sexual risk behavior, particularly in the context of travel.

Adolescent↗

PubMed2005

Chaos supported stochastic resonance in a metal-ferroelectric-semiconductor heterostructure.

An experimental study is presented on a complex nonlinear system showing a particular type of dynamics that can be interpreted as stochastic resonance. The system consists of a metal-ferroelectric-semiconductor structure, which plays the role of a nonlinear element in an electric circuit with linear resistance, inductance, and capacitance connected in series (RLC series circuit) driven externally by a high-amplitude harmonic voltage source. The system presents various kinds of nonlinear behavior, of which the simplest, consisting of a period-doubling evolution to chaos, is of interest to this study. The broadband intrinsic chaos emerging after a period-doubling sequence exists for a large range of frequencies of the driving voltage. The appearance of the chaotic dynamics is associated with the promotion of a low-frequency harmonic spectral component. This is interpreted as stochastic resonance with intrinsic chaos replacing noise, the usual variable in regular SR.

Journal Article↗

PubMed1997

Experimental study of steady and pulsatile flows in cerebral aneurysm model of various sizes at branching site.

Pulsatile and steady flow fields in cerebrovascular aneurysm models of various sizes are presented in terms of laser-Doppler velocimetry measurements and flow visualization. The bifurcation angle was 140 deg and volume flow rate ratio between the branches was 3:1. The mean, peak, and minimal Reynolds numbers based on the bulk average velocity and diameter of the parent vessel were 600, 800, and 280, respectively. It is found that among the tested sizes there exists a middle range of aneurysm sizes, above and below which the forced-vortex inside the aneurysmal model is weaker and lacking, respectively, whereas in the middle range of the tested sizes the forced vortex is stronger and the fluctuation level is higher near the dome. The present results also identify the major fluid dynamic factors of the aneurysmal promotion or rupture for the medium and larger aneurysms, respectively. Furthermore, the maximum fluctuation intensity is found to increase with aneurysm size. The locations of the maximum fluctuation intensity are found to occur in the bifurcation area or at the neck instead of intra-aneurysm.

Aneurysm, Ruptured↗

PubMed2002

Tightly regulated gene expression system in Salmonella enterica serovar Typhimurium.

A new Salmonella enterica serovar Typhimurium strain has been constructed to facilitate tightly regulated gene expression. Arabinose-inducible and glucose-repressible expression of a T7 RNA polymerase gene that has been integrated with an adjacent araC-P(BAD) control element into the bacterial chromosome allows dynamic control of T7 promoter-driven RNA transcription.

AraC Transcription Factor↗

PubMed1999

Strong selective pressure for evolution of an Epstein-Barr virus LMP2B homologue in the rhesus lymphocryptovirus.

Latent membrane protein 2B (LMP2B) is expressed during latent Epstein-Barr virus (EBV) infection, but little is known about its role. The goal of this study was to determine whether an LMP2B homologue is conserved in the rhesus monkey lymphocryptovirus (LCV). Both rhesus LCV LMP2A and LMP2B genes were cloned and sequenced. The rhesus LCV LMP2B gene is positionally conserved, and the EBNA-2 responsiveness and the bidirectional nature of the LMP1-LMP2B promoter have also been functionally conserved. However, this region of the genome encoding the LMP1, LMP1-LMP2B promoter, and LMP2B first exon demonstrates the most dramatic nucleotide sequence divergence between human and nonhuman LCV observed to date. Evolution of the rhesus LCV LMP2B promoter and transcript despite the dynamic nature of this genomic region reflects strong selective pressure for a yet-to-be-identified LMP2B function.

Amino Acid Sequence↗

PubMed2026

NAT10 is critical to block RNA sensing-induced IFN-β transactivation in viral infection.

UNLABELLED: Cells detect invading viruses and produce type I interferons (IFNs) to stimulate an innate antiviral effector response. However, IFN levels must be fine-tuned to achieve antiviral efficacy while limiting hyperinflammatory and tissue-damaging effects. Here, we report that NAT10, a histone and cytidine acetyltransferase, regulates the production of type I IFNs and RNA virus infections. Depletion of NAT10 increased the expression of IFN-β and IFN-stimulated genes, and correspondingly impaired viral replication. Mechanistically, NAT10 dynamically associated with the IFN-β promoter and also negatively regulated IRF3's chromatin associations through modulation of long noncoding RNAs that inhibit IRF3. Treatment of cells with Remodelin, a NAT10 inhibitor, similarly increased IFN-β expression and inhibited viral infections. Overall, our findings reveal NAT10 is a potential host-directed target for antiviral treatment via regulation of type I IFN. IMPORTANCE: Type I interferons (IFNs) signaling pathway is critical to cellular defense and innate immunity against evading pathogens, including viruses. However, induction of type I IFNs is fine-tuned to achieve the antiviral consequence while maintaining host cellular homeostasis. This paper presents a novel mechanism for the NAT10 protein to silence IFN-β induction through modulation of IRF3 activity at the promoter of IFN-β, and further demonstrates the therapeutic potential of the NAT10 inhibitor Remodelin to restrict viral infection while inducing IFN-β.

Interferon-beta↗

PubMed2002

Plk phosphorylation regulates the microtubule-stabilizing protein TCTP.

The mitotic polo-like kinases have been implicated in the formation and function of bipolar spindles on the basis of their respective localizations and mutant phenotypes. To date, this putative regulation has been limited to a kinesin-like motor protein, a centrosomal structural protein, and two microtubule-associated proteins (MAPs). In this study, another spindle-regulating protein, the mammalian non-MAP microtubule-binding and -stabilizing protein, the translationally controlled tumor protein (TCTP), was identified as a putative Plk-interacting clone by a two-hybrid screen. Plk phosphorylates TCTP on two serine residues in vitro and cofractionates with the majority of kinase activity toward TCTP in mitotic cell lysates. In addition, these sites were demonstrated to be phosphorylated in vivo. Overexpression of a Plk phosphorylation site-deficient mutant of TCTP induced a dramatic increase in the number of multinucleate cells, rounded cells with condensed ball-like nuclei, and cells undergoing cell death, similar to both the reported anti-Plk antibody microinjection and the low-concentration taxol treatment phenotypes. These results suggest that phosphorylation decreases the microtubule-stabilizing activity of TCTP and promotes the increase in microtubule dynamics that occurs after metaphase.

Amino Acid Motifs↗

PubMed2024

Disassembly of the TRIM56-ATR complex promotes cytoDNA/cGAS/STING axis-dependent intervertebral disc inflammatory degeneration.

As the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socioeconomic challenge to the aging population and is largely attributed to intervertebral disc degeneration (IVDD). Elastic nucleus pulposus (NP) tissue is essential for the maintenance of IVD structural and functional integrity. The accumulation of senescent NP cells with an inflammatory hypersecretory phenotype due to aging and other damaging factors is a distinctive hallmark of IVDD initiation and progression. In this study, we reveal a mechanism of IVDD progression in which aberrant genomic DNA damage promoted NP cell inflammatory senescence via activation of the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) axis but not of absent in melanoma 2 (AIM2) inflammasome assembly. Ataxia-telangiectasia-mutated and Rad3-related protein (ATR) deficiency destroyed genomic integrity and led to cytosolic mislocalization of genomic DNA, which acted as a powerful driver of cGAS/STING axis-dependent inflammatory phenotype acquisition during NP cell senescence. Mechanistically, disassembly of the ATR-tripartite motif-containing 56 (ATR-TRIM56) complex with the enzymatic liberation of ubiquitin-specific peptidase 5 (USP5) and TRIM25 drove changes in ATR ubiquitination, with ATR switching from K63- to K48-linked modification, c thereby promoting ubiquitin-proteasome-dependent dynamic instability of ATR protein during NP cell senescence progression. Importantly, an engineered extracellular vesicle-based strategy for delivering ATR-overexpressing plasmid cargo efficiently diminished DNA damage-associated NP cell senescence and substantially mitigated IVDD progression, indicating promising targets and effective approaches to ameliorate the chronic pain and disabling effects of IVDD.

Humans↗

PubMed2006

Palladin binds to Eps8 and enhances the formation of dorsal ruffles and podosomes in vascular smooth muscle cells.

Palladin is a widely expressed phosphoprotein that plays an important role in organizing the actin cytoskeleton. Palladin is concentrated in multiple actin-based structures involved in cell motility and adhesion, including stress fibers, focal adhesions, cell-cell junctions, growth cones and Z-discs. Here, we show that palladin also localizes to the dorsal, circular ruffles that form transiently in response to growth factor stimulation. More importantly, palladin knockdown results in decreased ruffle formation and decreased Rac activation following PDGF treatment. In addition, we describe a novel interaction between palladin and Eps8, a receptor tyrosine kinase (RTK) substrate that participates in the activation of the Rac-specific guanine nucleotide-exchange function of Sos-1. Eps8 was identified as a molecular partner for palladin in a yeast two-hybrid screen, and the interaction was confirmed biochemically in co-immunoprecipitation assays. The two proteins were found to colocalize extensively in dorsal ruffles. Palladin also localizes to podosomes after phorbol ester stimulation, and palladin knockdown results in decreased podosome formation in response to PDBu. Together, these data provide strong evidence for a direct and specific interaction between palladin and Eps8, and suggest that they act together in the rapid and transient remodeling of the actin cytoskeleton, which promotes the formation of highly dynamic membrane protrusions in response to PDGF and phorbol ester treatment.

Actins↗

PubMed1988

Hyperplastic response of adipose tissue to caloric overconsumption in sexually mature chickens.

Two experiments were conducted to determine the hyperplastic response of adipose tissue from sexually mature chickens in response to caloric overconsumption. In the first experiment, birds were either force-fed or allowed to consume feed ad libitum, whereas in the second experiment, a feed-restriction regimen was also implemented. In both experiments feeding treatments were applied for 19 consecutive days, and a diet high in energy and low in protein was fed to all birds to promote lipogenesis. To monitor adipocyte dynamics, birds in Experiment 1 received an intramuscular injection of [methyl-3H]thymidine on Day 15, whereas in Experiment 2 birds were injected on Days 1 and 10. In both Experiments 1 and 2, body weight gain and percentage weight gain were greater in the force-fed birds. Furthermore the retroperitoneal (abdominal), and right sartorial fat depots increased in weight as a result of force-feeding, and there were concomitant increases in total adipocyte DNA content and total radiotracer uptake by these tissues. The results indicate that expansion of adipose tissue in sexually mature chickens is not restricted solely to cellular hypertrophy, but periodic hyperplastic activity also occurs in response to caloric overconsumption.

Adipose Tissue↗