UK PubMed Central (United Kingdom)

Growth hormone (GH) has an important role in the regulation of hepatic LDL receptor expression and plasma lipoprotein levels. This investigation was undertaken to evaluate if these effects of GH on...Full Text Available

UK PubMed Central (United Kingdom)

The expression status of the estrogen receptor alpha (ERα) and that of the epidermal growth factor receptor Her-2/neu frequently correlate inversely in breast cancers. While ERα-dependent...Full Text Available

UK PubMed Central (United Kingdom)

The capacity of bones to adjust their mass and architecture to withstand the loads of everyday activity derives from the ability of their resident cells to respond appropriately to the strains engendered....Full Text Available

UK PubMed Central (United Kingdom)

Mechanisms regulating sexual differentiation of the zebra finch song system appear to include both genetic and hormonal factors. Sorting Nexin 2 (SNX2), which is involved in trafficking proteins...Full Text Available

UK PubMed Central (United Kingdom)

Hormone potency depends on receptor availability, regulated via gene expression and receptor trafficking. To ascertain how central leptin receptors are regulated, the effects of leptin challenge, high-fat...Full Text Available

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Somatogenic hormones play an important role in regulation of receptors for prolactin (PRL) and estrogen. Plerocercoids of the tapeworm, S. mansonoides produce a factor which mimics some, but not all of the actions reported for GH. Intact female rats were subjected to a constant infusion of plerocercoid growth factor (PGF) via a subcutaneous infection for two weeks to determine if PGF influences receptors for PRL, GH or estradiol. The rate of weight gain in the PGF-treated rats was accelerated in spite of a marked reduction in serum GH. Partially-purified PGF specifically displaced [125I]hGH from rat liver receptors but microsomes prepared from rats treated with PGF specifically bound significantly less [125I]hGH than microsomes from control rats. The reduction in [125I]hGH binding was not due to occupancy or to a change in affinity but to a suppression in ...

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Glucagon plays critical roles in regulating glucose homeostasis, mainly by counteracting the effects of insulin. Consequently, the dysregulated glucagon secretion that is evident in type 2 diabetes has significant implications in the pathophysiology of the disease. Glucagon secretion from pancreatic -cells has been suggested to be modulated by blood glucose, signals from the nervous system and endocrine components. In addition to these regulators, intraislet factors acting in a paracrine manner from neighbouring -cells are emerging as central modulator(s) of -cell biology. One of the most important of these paracrine factors, insulin, modulates glucagon secretion. Indeed, the -cell-specific insulin receptor knockout (IRKO) mouse manifests hypersecretion of glucagon in the postprandial stag...

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To study the effect of agonist on the TRH (thyrotrophin-releasing hormone) receptor protein, an epitope-tagged receptor was stably expressed in HEK-293 cells (human embryonic kidney 293 cells) and receptor...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundThe pregnane X receptor (PXR; NR1I2), a member of the nuclear receptor superfamily, regulates the expression of metabolic enzymes and transporters involved...Full Text Available

UK PubMed Central (United Kingdom)

The retinoic acid receptor-related orphan receptors α and γ (RORα (NR1F1) and RORγ (NR1F3)) are orphan nuclear receptors and perform critical roles in regulation of development,...Full Text Available

UK PubMed Central (United Kingdom)

The extracellular domain of human fibroblast growth factor receptor (XC-FGF-R) was expressed in Escherichia coli. The protein was purified to homogeneity and the interaction with basic fibroblast growth...Full Text Available

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Background:Increasing evidence shows the importance of young age, estrogen receptor (ER), progesterone receptor (PR) status, and HER-2 expression in patients with breast cancers.Patients...Full Text Available

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SUMMARYThe cytolytic activity of natural killer (NK) cells is regulated by inhibitory receptors that detect the absence of self molecules on target cells. Structural studies of...Full Text Available

UK PubMed Central (United Kingdom)

Since a large body of data has suggested a significant role for alpha-fetoprotein (AFP) in the regulation of the immune response at a number of levels, we examined the possibility of a specific receptor...Full Text Available

International Nuclear Information System (INIS)

Neuron-restrictive silencer factor (NRSF) binds its consensus element to repress the transcription of various genes. The dominant-negative form (dnNRSF) has a hypertrophic effect on cardiogenesis through an unidentified mechanism. We examined the involvement of transient receptor potential (TRP) channel proteins, using transgenic mice overexpressing dnNRSF (dnNRSF mice). Electrophoretic mobility-shift assays revealed an interaction between NRSF and a neuron-restrictive silencer element-like sequence in intron 4 of TRPC1 genomic DNA. According to RT-PCR and Western analyses, TRPC1 was up-regulated in dnNRSF mouse heart. Transient overexpression of TRPC1 in HEK 293T cells increased the activity of the nuclear factor in activated T cells (NFAT) promoter and stimulated store-operated Ca"2"+ channel (SOCC)-mediated Ca"2"+ entry. Transfection of TRPC1 into primary cardiomyocytes increased NFAT activity, ...

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Binding of epidermal growth factor (EGF) to the EGF receptor (EGFR) initiates signal transduction, ultimately leading to altered gene expression. Ligand-activated EGFR is also rapidly internalized...Full Text Available

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BackgroundPolymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung...Full Text Available

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SummaryMammalian iron homeostasis is regulated by the interaction of the liver-produced peptide hepcidin and its receptor, the iron transporter ferroportin. Hepcidin binds to...Full Text Available

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BackgroundNFκB signaling is of paramount importance in the regulation of apoptosis, proliferation, and inflammatory responses during human development and homeostasis, as...Full Text Available

UK PubMed Central (United Kingdom)

The ventromedial hypothalamus (VMH) plays a central role in the regulation of the female reproductive behavior lordosis, a behavior dependent upon the sequential activation of receptors for the ovarian...Full Text Available

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P2X1 receptors for ATP contribute to signalling in a variety of cell types and following stimulation undergo rapid desensitisation (within 1 s), and require ∼5 min to recover. In HEK293 cells...Full Text Available

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Vascular endothelial growth factor (VEGF) is a mitogen that is critically involved in vasculogenesis, angiogenesis, and hematopoiesis. However, what and how transcription factors participate in the regulation of vegf gene expression are not fully understood. Here we report the cloning and sequencing of the zebrafish vegf promoter which revealed that the promoter contains a number of bone morphogenetic protein (BMP)-activated Smad binding elements (SBE), implicating Smad1 and Smad5 in the regulation of BMP-induced expression of vegf. Electrophoretic mobility shift assays of adding recombinant Smad proteins to the SBE-containing DNA oligonucleotides that represent portions of zebrafish vegf promoter resulted in mobility shift of the oligonucleotides. These changes demonstrate potential interactions between Smad1/5 and the vegf promoter. Reporter activity assays using the wild-type or SBE-deleted vegf ...

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Exogenous adenosine 5{prime}-triphosphate (ATP) mobilized intracellular calcium in human carcinoma A43l cells and in Swiss 3T3 and 3T6 mouse fibroblasts by increasing inositol trisphosphate similar to well down growth factors (platelet-derived growth factor (PDGF), epidermal growth factor (EGF), bradykinin (BK), serum). Calcium mobilization was examined by video imaging of fura-2 fluorescence is single cells, following the radioactive isotope {sup 45}Ca, and monitoring the decrease in fluorescence of cells loaded with chlortetracycline. Uridine 5{prime}-triphosphate, but not other nucleotides, mimicked ATP. Single-cell analysis revealed synchronous responses in 10 sec to ATP, BK or serum, while PDGF (3T3) and EGF (A431) produced slower signals with significant cell-to-cell variation. PDGF desensitized 3T3 cells to ATP and BK added 100 sec later but ATP or BK did not desensitized to PDGF. Homologous desensitization was seen ...

UK PubMed Central (United Kingdom)

Aim: Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone...Full Text Available

UK PubMed Central (United Kingdom)

Epidermal growth factor receptor (EGFR)-specific monoclonal antibodies predominantly inhibit colorectal cancer (CRC) growth by interfering with receptor signaling. Recent analyses have shown that patients...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundApolipoprotein E (ApoE), a cholesterol carrier associated with atherosclerosis, is a major risk factor for Alzheimer's disease (AD). The low-density lipoprotein receptor...Full Text Available

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The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, the role of the AHR...Full Text Available

UK PubMed Central (United Kingdom)

As many as 59% of the transcription factors in Escherichia coli regulate the transcription rate of their own genes. This suggests that auto-regulation has one or more important...Full Text Available

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C-type natriuretic peptide (CNP) is a member of the small family of natriuretic peptides that also includes atrial natriuretic peptide (ANP) and brain, or B-type natriuretic peptide (BNP). Unlike them, it performs its major functions in an autocrine or paracrine manner. Those functions, mediated through binding to the membrane guanylyl cyclase natriuretic peptide receptor B (NPR-B), or by signaling through the non-enzyme natriuretic peptide receptor C (NPR-C), include the regulation of endochondral ossification, reproduction, nervous system development, and the maintenance of cardiovascular health. To date, the regulation of CNP gene expression has not received the attention that has been paid to regulation of the ANP and BNP genes. CNP expression in vitro is regulated by TGF-b and recepto...

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The regulation of blood vessel formation is of fundamental importance to many physiological processes, and angiogenesis is a major area for novel therapeutic approaches to diseases from ischemia to...Full Text Available

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To study the regulation of adipose tissue lipoprotein lipase (LPL) in human adipocytes, omental adipose tissue was obtained from healthy subjects and digested in collagenase. The isolated adipocytes thus obtained were suspended in Medium 199 and cultured at 37 degrees C. Cell viability was demonstrated in adipocytes cultured for up to 72 h by constancy of cell number, cell size, trypan-blue exclusion, and specific /sup 125/I-insulin binding. In addition, chloroquine induced an increase in cell-associated /sup 125/I-insulin at 24, 48, and 72 h after preparation. Thus, isolated adipocytes retained their ability to bind, internalize, and degrade insulin. LPL was measured as activity secreted into the culture medium (CM), released from cells by heparin (HR), and extracted from cell digests. A broad range of heparin concentrations produced a prompt release of LPL from a rapidly replenishable pool of cellular activity. When cells were cultured in medium containing 10% ...

UK PubMed Central (United Kingdom)

The effect of A₁-adenosine receptor antagonism via 8-cyclopentyl-1,3-dipropyl-xanthine (CPDPX) on the stimulation of skeletal muscle glucose uptake by...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundGlucocorticoids down-regulate cytokine synthesis and suppress inflammatory responses. The glucocorticoid receptor (GR) antagonist RU486 may exacerbate the inflammatory...Full Text Available

UK PubMed Central (United Kingdom)

Hematopoiesis is the cumulative result of intricately regulated signaling pathways that are mediated by cytokines and their receptors. Studies conducted over the past 10 to 15 years have revealed that...Full Text Available

UK PubMed Central (United Kingdom)

Recently, we demonstrated that the central ghrelin signalling system, involving the ghrelin receptor (GHS-R1A), is important for alcohol reinforcement. Ghrelin targets a key mesolimbic circuit involved...Full Text Available

UK PubMed Central (United Kingdom)

Although peroxisome proliferator-activated receptor alpha (PPARα) is closely associated with myocardial fatty acid metabolism, the pathophysiological role of PPARα in myocardial infarction...Full Text Available

UK PubMed Central (United Kingdom)

T-cell activation requires the influx of extracellular calcium, although mechanistic details regarding such activation are not fully defined. Here, we show that P2X₇ receptors play a key...Full Text Available

UK PubMed Central (United Kingdom)

The ζ chain-associated 70-kDa protein (ZAP-70) of tyrosine kinase plays a critical role in T cell receptor-mediated signal transduction and the immune response. A high level of ZAP-70 expression...Full Text Available

UK PubMed Central (United Kingdom)

The agglutination of human platelets by ristocetin and von Willebrand factor was inhibited by aggregated immunoglobulin (Ig)G and by Fc fragments of IgG, but not by Fab, F(ab′)₂ or...Full Text Available

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BackgroundThe mammalian FoxO transcription factors function to regulate diverse physiological processes. Emerging evidence that both BDNF and lithium suppress FoxO...Full Text Available

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Hepatocyte nuclear factor (HNF) 4α is a key transcription factor regulating endo/xenobiotic-metabolizing enzymes and transporters. We investigated whether microRNAs are involved in the regulation...Full Text Available

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Receptor interacting protein 140 (RIP140) is a coregulator for numerous nuclear receptors and transcription factors and primarily exerts gene-repressive activities on various target genes. We previously identified a spectrum of posttranslational modifications on RIP140 that augment its property and biological activity. In T(3)-triggered biphasic regulation of cellular retinoic acid binding protein 1 (Crabp1) gene along the course of fibroblast-adipocyte differentiation, we found TRAP220(MED1) critical for T(3)-activated chromatin remodeling whereas RIP140 essential for T(3)-repressive chromatin remodeling of this gene promoter. In this current study, we aim to examine whether and how RIP140 replaces TRAP220(MED1) on the CrabpI promoter in differentiating adipocyte cultures. We find increasing recruitment of RIP140 to this promoter, with corresponding reduction in TRAP220(MED1) recruitment during the ...

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Keratinocyte growth factor receptor (KGFR) and fibroblast growth factor receptor (FGFR) 2c share identical amino acid sequences, except for a 46-amino acid domain in the extracellular region. Monoclonal antibodies (MAbs) specific to KGFR have not been reported nor are commercially available. In this study, we generated murine MAbs specific to KGFR in non-obese diabetic (NOD) mice using a modified Repeated Immunizations at Multiple Sites (RIMMS) technology. Stable cell lines expressing the full-length human KGFR or FGFR2c were produced to facilitate the identification of KGFR-specific MAbs. Following the initial screening of hybridoma clones with a fluorescence-based, confocal cell detection method and ELISA, KGFR-specific MAbs were selected and confirmed by flow cytometry and Western blot ...

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Eukaryotic genomes encode a zinc finger protein (ZPR1) with tandem ZPR1 domains. In response to growth stimuli, ZPR1 assembles into complexes with eukaryotic translation elongation factor 1A (eEF1A) and the survival motor neurons protein. To gain insight into the structural mechanisms underlying the essential function of ZPR1 in diverse organisms, we determined the crystal structure of a ZPR1 domain tandem and characterized the interaction with eEF1A. The ZPR1 domain consists of an elongation initiation factor 2-like zinc finger and a double-stranded {beta} helix with a helical hairpin insertion. ZPR1 binds preferentially to GDP-bound eEF1A but does not directly influence the kinetics of nucleotide exchange or GTP hydrolysis. However, ZPR1 efficiently displaces the exchange factor eEF1B from preformed nucleotide-free complexes, suggesting that it may function as a negative regulator of eEF1A activation. ...

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Using an anti-receptor mAb that blocks the attachment of echovirus 7 and related viruses (echoviruses 13, 21, 29 and 33), we have isolated a complementary DNA clone that encodes the human decay-accelerating...Full Text Available

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The effects of muscarinic agonists and diisopropylfluorophosphate (DFP) on muscarinic receptor density and muscarinic receptor-mediated responses was assessed in mouse brain and mouse neuroblastoma cells (clone N1E-115). Utilizing the antagonist ({sup 3}H)quinuclidinyl benzilate (({sup 3}H)QNB), there was no difference in the maximal binding capacity (B{sub max}) or equilibrium dissociation constant (K{sub d}) between untreated and 24 hour DFP-treated mice. However, one administration of DFP produced a 24% and 33% decrease in B{sub max} measured by ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) after 18 and 24 hours which was rapidly reversible within 36 hours after DFP treatment. The loss of ({sup 3}H)NMS binding sites following acute DFP treatment was not accompanied by a change in a particular muscarinic receptor binding conformation. Furthermore, the magnitude of muscarinic receptor-mediated ...

UK PubMed Central (United Kingdom)

BackgroundThe lactogenic hormones prolactin (PRL) and placental lactogens (PL) play central roles in reproduction and mammary development. Their actions are mediated via binding...Full Text Available

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Hyperproliferation of the colonic epithelium, leading to expansion of colonic crypt progenitors, is a recognized risk factor for colorectal cancer. Overexpression of progastrin, a nonamidated and incompletely...Full Text Available

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Fibroblast growth factor (FGF) signaling is involved in skeletal development of the vertebrate. Gain-of-function mutations of FGF receptors (FGFR) cause craniosynostosis, premature fusion of the skull,...Full Text Available

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Bacterial pathogens use virulence strategies to invade epithelial barriers, but active processes of epithelial cells may also contribute to the endocytosis of microbial particles. To focus on the latter,...Full Text Available

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Although acetylated α-tubulin is known to be a marker of stable microtubules in neurons, precise factors that regulate α-tubulin acetylation are, to date, largely unknown. Therefore,...Full Text Available

International Nuclear Information System (INIS)

Full text: The maturation of chicken forebrain is protracted and occurs well after synapse formation providing a good model for studying mechanisms of brain maturation. Using microslices from immature (10 day) and adult chicken forebrain prepared after decapitation, we have examined functional properties of NMDA and AMPA receptors by measuring agonist-induced uptake of "4"5Ca"2"+ . The rate and extent of NMDA induced "4"5Ca"2"+ accumulation decreased during maturation with no change in EC_5_0. The rate and extent of the AMPA induced response also decreased with a 60-fold increase in EC_5_0. However, the total NMDA receptor content did not change as indicated by 3 H-MK801 binding and NR1 immunoreactivity in P2 fractions. Similarly, there was no change in the B_m_a_x of "3H-AMPA, though there was a two-fold increase in K_D, and little or no change in the immunoreactivity in GluR1, 2, 2/3 or 4. These results suggest that it is the ...

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BACKGROUND Hypermethylation of CpG islands is a common epigenetic alteration associated with cancer. Tumor suppressor genes retinoic acid receptor beta (RARb) and PDLIM4 are hypermethylated and silenced in prostate cancer (PCa) tissues and PCa cell lines compared to normal prostate cells. METHODS In this study, a benign prostate epithelial cell line RWPE1 was used as a model to study the epigenetic regulation of Myc on the RARb and PDLIM4 promoters. Forced Myc overexpression inhibited the RARb and PDLIM4 expression. RESULTS Pyrosequencing study showed that Myc overexpression increased methylation in several CpG sites of both promoters. A DNA methylation inhibitor 5-aza-2prime-deoxycytidine reversed the epigenetic alteration effect of Myc on both RARb and PDLIM4. CONCLUSION The epigenetic r...

International Nuclear Information System (INIS)

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and ...

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It is now known that various growth factors may also act in the central nervous system. Among them, it has recently been shown that epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) may possess trophic effects in the mammalian brain. We report here on the respective autoradiographic distribution of ["1"2"5I]EGF and ["1"2"5I]IGF-I receptor binding sites in the rat brain, both during ontogeny and in adulthood. It appears that ["1"2"5I]EGF sites are mostly found in the rat forebrain during brain development. On the other hand, ["1"2"5I]IGF-I sites are more widely distributed both during ontogeny and in adulthood. These results reveal the plasticity of the expression of EGF and IGF-I receptor sites in the mammalian brain. This could be relevant for the respective role of these two growth factors in the development and maintenance of neuronal ...

UK PubMed Central (United Kingdom)

c-Jun N-terminal kinase 2 (JNK2) isoforms are transcribed from the jnk2 gene and are highly homologous with jnk1 and jnk3 transcriptional products....Full Text Available

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α7 neuronal nicotinic acetylcholine receptors (α7-nAChR) form Ca²⁺-permeable homopentameric channels modulating cortical network activity and cognitive processing....Full Text Available

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LRP1 is a type-1 transmembrane receptor that mediates the endocytosis of diverse ligands. LRP1 β-chain proteolysis results in release of sLRP1 that is present in human plasma. In this study,...Full Text Available

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We have previously described a monoclonal antibody (FA6-152), obtained by immunizing mice with fetal human erythrocytes [Edelman, Vinci, Villeval, Vainchenker, Henri, Miglierina, Rouger, Reviron, Breton-Gorius,...Full Text Available

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Gonadotropin–releasing hormone (GnRH) neurons are the central regulators of reproduction. GABAergic transmission plays a critical role in pubertal activation of pulsatile GnRH secretion....Full Text Available

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Hypoxia inducible factor-1 (HIF-1) promotes tumor cell adaptation to microenvironmental stress. HIF-1 is up-regulated in irradiated tumors and serves as a promising target for radiosensitization....Full Text Available

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Cellular hypertrophy is regulated by coordinated pro- and antigrowth machineries. Foxo transcription factors initiate an atrophy-related gene program to counter hypertrophic growth. This study was designed...Full Text Available

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The endothelin-B (ETB) receptor is a G-protein-coupled receptor that binds endothelin ligands and is essential for the development of epidermal melanocytes and enteric neurons. Recent reports indicate that ETB is localized to nuclei in cardiac ventricular myocytes, although it has been thought that ETB is localized mainly on the plasma membrane. It remains unknown, however, whether this unique distribution of ETB occurs in other tissues. To elucidate the subcellular distribution of ETB in the intestine, we performed immunofluorescence of ETB in mouse intestine using a specific antibody. ETB-like immunoreactivity was detected in both the mucosal and muscle layers. In the mucosal layer, villous epithelial cells, stromal cells of the lamina propria, and cryptic cells were immunostained. Subcellularly, ETB is localized mainly to the nuclei of villous epithelial cells. In the muscle layer, immunoreactivity of ETB was localized to the myenteric ...

International Nuclear Information System (INIS)

Increased levels of epidermal growth factor receptor have been reported in a variety of tumors, including pulmonary squamous cell carcinomas in man. The purpose of this study was to determine if increased levels of epidermal growth factor (EGFR) were present in lung tumors from Beagle dogs that had been exposed to "2"3"9PuO_2- Using immunohistochemical techniques, sections from 17 lung tumors were examined for the presence of EGFR. Seven of the tumors were strongly positive for EGFR; the remainder of the tumors and the normal lung sections were negative. The positive immunostaining could not be correlated with the histologic phenotype of the tumors. Work is in progress to determine the level of EGFR in preneoplastic, proliferative epithelial foci in the Iung. (author)

Scientific Electronic Library Online (English)

Abstract in english Cytokines are molecules that were initially discovered in the immune system as mediators of communication between various types of immune cells. However, it soon became evident that cytokines exert profound effects on key functions of the central nervous system, such as food intake, fever, neuroendocrine regulation, long-term potentiation, and behavior. In the 80's and 90's our group and others discovered that the genes encoding various cytokines and their receptors are e (more) xpressed in vascular, glial, and neuronal structures of the adult brain. Most cytokines act through cell surface receptors that have one transmembrane domain and which transduce a signal through the JAK/STAT pathway. Of particular physiological and pathophysiological relevance is the fact that cytokines are potent regulators of hypothalamic neuropeptidergic systems that maintain neuroendocrine homeostasis and ...

British Library Electronic Table of Contents (United Kingdom)

A promising drug target currently under investigation to improve cognitive deficits in neuropsychiatric and neurological disorders is the neuronal nicotinic alpha7 acetylcholine receptor (a7nAChR). Improving cognitive impairments in diseases such as Alzheimer's (AD) and schizophrenia remains a large unmet medical need, and the a7nAChR has many properties that make it an attractive therapeutic target. The a7nAChR is a ligand gated ion channel that has particularly high permeability to Ca^2^+ and is expressed in key brain regions involved in cognitive processes (e.g., hippocampus). The a7nAChRs are localized both pre-synaptically, where they can regulate neurotransmitter release, and post-synaptically where they can activate intracellular signaling cascades and influence downstream processes...

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Abstract. Objective: Lapatinib (Tykerb, GW572016), a potent inhibitor of the catalytic activities of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (ErbB2), inhibits population growth of selected EGFR and HER2 overexpressing cell lines. Previous studies with a small number of cell lines suggest a correlation between overexpression of EGFR and/or HER2 and sensitivity to growth inhibition by lapatinib; however, the precise determinants of lapatinib selectivity for tumour and/or other cells remain unclear. Materials and methods: To clarify the determinants of its selectivity in cultured cells, lapatinib-induced cell population growth inhibition and relative EGFR and HER2 protein expression were quantified in 61 different human tumour cell lines fro...

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Targeted studies completed include the evaluation of tritiated N-0437, evaluation of "3"5S-cysteamine, evaluation of "1"8F-FDG and initiation of synthetic efforts towards the synthesis of iodinated N-0437 and pergolide analogs. The direction of the project has been changed due to several factors which include the decided lack of favorable experimental results, the excellence of results using muscarinic receptor ligands in pituitary, brain and heart and the contention of the DOE review panel that the original grant proposal was based on flawed assumptions together with their perceived lack of importance to pituitary imaging. In the final year of this grant, three studies will be completed. The first study is the continuation of synthetic efforts to prepare iodinated N-0437 and pergolide analogs for possible use as brain imaging agents. The second study is directed towards completion of biochemical evaluation of various muscarinic ...

British Library Electronic Table of Contents (United Kingdom)

Nerve growth factor (NGF), a survival factor for neurons enforces pain by sensitizing nociceptors. Also in the pancreas, NGF was associated with pain and it can stimulate the proliferation of pancreatic cancer cells. Hepatic stellate cells (HSC) respond to NGF with apoptosis. Transforming growth factor (TGF)-b, one of the strongest pro-fibrogenic activators of pancreatic stellate cells (PSC) induced NGF and its two receptors in an immortalized human cell line (ihPSC) and primary rat PSC (prPSC) as determined by RT-PCR, western blot, and immunofluorescence. In contrast to HSC, PSC expressed both NGF receptors, although p75NTR expression was weak in prPSC. In contrast to ihPSC TGF-b activated both Smad signaling cascades in prPSC. NGF secretion was diminished by the activin-like kinase (ALK)...

International Nuclear Information System (INIS)

Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. We demonstrated that the up-regulation of Redd1 transcription by hypoxia and high cell density (HCD) depends on cooperation between Sp1 and HIF-1#alpha# downstream of the PI3K/Akt pathway.

Science.gov (United States)

... time, sucrase activity, a marker of intestinal epithelium (Matsushita, 1983) was observed in epithelial cells with CdxA ... PubMed, CSAIshii, Y., K. Fukuda, H. Saiga, S. Matsushita, and S. Yasugi. 1997. E...

UK PubMed Central (United Kingdom)

CBP and its paralog p300 are histone acetyl transferases that regulate gene expression by interacting with multiple transcription factors via specialized domains. The structure...Full Text Available

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The processes regulating telomere function have major impacts on fundamental issues in human cancer biology. First, active telomere maintenance is almost always required for full oncogenic transformation...Full Text Available

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A mild reduction in mitochondrial respiration extends the life span of many species, including C. elegans. We recently showed that hypoxia-inducible factor 1 (HIF-1) is required for...Full Text Available

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Dissecting the genes involved in complex traits can be confounded by multiple factors, including extensive epistatic interactions among genes, the involvement of epigenetic regulators, and the variable...Full Text Available

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Skeletal formation is an essential and intricately regulated part of vertebrate development. Humans and mice deficient in Growth and Differentiation Factor 6 (Gdf6) have numerous...Full Text Available

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The sirtuin Sirt6 is a NAD-dependent histone deacetylase that is implicated in gene regulation and lifespan control. Sirt6 can interact with the stress-responsive transcription factor NF-κB...Full Text Available

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Circadian clock is implicated in the regulation of aging. The transcription factor CLOCK, a core component of the circadian system, operates in complex with another circadian clock protein BMAL1. Recently...Full Text Available

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Psychopathic individuals are generally unresponsive to motivational and emotional cues that facilitate behavioral regulation. A putative mechanism for this deficiency is Gray’s (1971)...Full Text Available

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SummaryActivating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines...Full Text Available

UK PubMed Central (United Kingdom)

KLF1 regulates a diverse suite of genes to direct erythroid cell differentiation from bipotent progenitors. To determine the local cis-regulatory contexts and transcription factor networks...Full Text Available

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The resulting emissions of the firing of ceramic products of all type are described, the factors are enumerated to diminish the emissions in the kilns and the technologies applied in the kilns to reduce these emissions while carrying out energy saving are described briefly. (author)

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Purpose : To detect differentially expressed genes in the patients with uterine cervical cancer during the radiation therapy. Materials and Methods : In patients with biopsy proven uterine cervical cancer, we took a tumor tissue just before radiation therapy and at 40 minutes after external irradiation of 1.8 Gy. Total RNAs isolated from non-irradiated and irradiated tumor tissue samples were analyzed using the differential-display reverse transcription-polymerase chain reaction (DDRT-PCR). Complementary DNA (cDNA) fragments corresponding to differentially expressed messenger RNAs(mRNAs) were eluted, and cloned. The differential expression of the corresponding mRNAs was confirmed by reverse northern blot. Differentially expressed cDNA bands were sequenced. Nucleotide sequence data were analyzed in the Gene Bank and EMBL databases via the BLAST network server to identify homologies to known genes or cDNA fragments. Expression pattern of down-regulated clone was ...

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RIN proteins serve as guanine nucleotide exchange factors for Rab5a. They are characterized by the presence of a RIN homology domain and a C-terminal Vps9 domain. Currently three family members have...Full Text Available

International Nuclear Information System (INIS)

The human causal factors for all human error licensing operational events on Daya Bay nuclear power station since 1993 to 2003 are categorized, the trend of these causal factors is analyzed. The emphasis is placed on analyzing the deficiencies on complying with and executing regulations and procedures. The results provide directional reference for nuclear power station to improve human performance. (author)

UK PubMed Central (United Kingdom)

Arf GTPases control vesicle formation from different intracellular membranes and are regulated by Arf guanine nucleotide exchange factors (GEFs). Outside of their conserved catalytic domains, known...Full Text Available

International Nuclear Information System (INIS)

We examined the effect of the trophic protein, nerve growth factor (NGF), on cultures of fetal rat neostriatum and basal forebrain-medial septal area (BF-MS) to define its role in brain development. Treatment of cultures with NGF resulted in an increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT) in both brain areas. CAT was immunocytochemically localized to neurons. In the BF-MS, NGF treatment elicited a marked increase in staining intensity and an apparent increase in the number of CAT-positive neurons. Moreover, treatment of BF-MS cultures with NGF increased the activity of acetylcholinesterase, suggesting that the cholinergic neuron as a whole was affected. To begin defining mechanisms of action of NGF in the BF-MS, we detected NGF receptors by two independent methods. Receptors were localized to two different cellular populations: neuron-like cells, and non-neuron-like cells. ...

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Mesenchymal stem cells (MSCs) are a potential source of smooth muscle cells (SMCs) for constructing tissue-engineered vascular grafts. However, the details of how specific combinations of vascular microenvironmental factors regulate MSCs are not well understood. Previous studies have suggested that both mechanical stimulation with uniaxial cyclic strain and chemical stimulation with transforming growth factor {beta}1 (TGF-{beta}1) can induce smooth muscle markers in MSCs. In this study, we investigated the combined effects of uniaxial cyclic strain and TGF-{beta}1 stimulation on MSCs. By using a proteomic analysis, we found differential regulation of several proteins and genes, such as the up-regulation of TGF-{beta}1-induced protein ig-h3 (BGH3) protein levels by TGF-{beta}1 and up-regulation of calponin 3 protein level by cyclic strain. At the gene expression ...

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[alpha]-Melanocyte stimulating hormone ([alpha]-MSH), a hormone originally named for its ability to regulate pigmentation of melanocytes, is a 13-amino-acid post-translational product of the pro-opiomelanocortin (POMC) gene. [alpha]-MSH and the other products of POMC processing, which share the core heptapeptide amino acid sequence Met-Glu (Gly)-His-Phe-Arg-Trp-Gly (Asp), the adrenocorticotropic hormone (ACTH), [beta]-MSH, and [gamma]-MSH, are collectively referred to as melanocortins. While best known for their effects on the melanocyte (pigmentation) and adrenal cortical cells (steroidogenesis), melanocortins have been postulated to function in diverse activities, including enhancement of learning and memory, control of the cardiovascular system, analgesia, thermoregulation, immunomodulation, parturition, and neurotrophism. To identify the chromosomal band encoding the human melanocortin-1 receptor gene, 1 [mu]g of an EMBL clone coding region ...

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Genome-wide association studies have linked lung cancer risk with a region of chromosome 15q25.1 containing CHRNA3, CHRNA5 and CHRNB4 encoding a3, a5 and b4 subunits of nicotinic acetylcholine receptors (nAChR), respectively. One of the strongest associations was observed for a non-silent single-nucleotide polymorphism at codon 398 in CHRNA5. Here, we have used pharmacological (antagonists) or genetic (RNA interference) interventions to modulate the activity of CHRNA5 in non-transformed bronchial cells and in lung cancer cell lines. In both cell types, silencing CHRNA5 or inhibiting receptors containing nAChR a5 with a-conotoxin MII exerted a nicotine-like effect, with increased motility and invasiveness in vitro and increasing calcium influx. The effects on motility were enhanced by addit...

UK PubMed Central (United Kingdom)

Structural analysis of an acetylcholine receptor from Torpedo californica leads to a three-dimensional model in which a "monomeric" receptor is shown to contain subunits arranged around a central ionophoretic...Full Text Available

UK PubMed Central (United Kingdom)

Many microbial pathogens recognize oligosaccharides displayed on the surface of host cells as receptors for toxins and adhesins. These ligand-receptor interactions are critical for disease pathogenesis,...Full Text Available

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Anxiety disorders are a highly prevalent and disabling class of psychiatric disorders. This review focuses on new directions in neurobiological research and implications for the development of novel psychopharmacological treatments. Neuroanatomical and neuroimaging research in anxiety disorders has centered on the role of the amygdala, reciprocal connections between the amygdala and the prefrontal cortex, and, most recently, alterations in interoceptive processing by the anterior insula. Anxiety disorders are characterized by alterations in a diverse range of neurochemical systems, suggesting ample novel targets for drug therapies. Corticotropin-releasing factor (CRF) concentrations are elevated in a subset of anxiety disorders, which suggests the potential utility of CRF receptor antagoni...

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Many advances have been carried out on the estrogens, GnRH and endocannabinoid system that have impact in the reproductive field. Indeed, estrogens, the generally accepted female hormones, have performed an unsuspected role in male sexual functions thanks to studies on non-mammalian vertebrates. Similarly, these animal models have provided important contributions to the identification of several GnRH ligand and receptor variants and their possible involvement in sexual behavior and gonadal function regulation. Moreover, the use of non-mammalian animal models has contributed to a better comprehension about the endocannabinoid system action in several mammalian reproductive events. We wish to highlight here how non-mammalian vertebrate animal model research contributes to advancements with i...

British Library Electronic Table of Contents (United Kingdom)

Apelin is a peptide known as the ligand of the G-protein-coupled receptor APJ. Several active apelin forms exist such as apelin-36, apelin-17, apelin-13, and the pyroglutamated form of apelin-13. Apelin and APJ are expressed in the central nervous system, particularly in the hypothalamus and in many peripheral tissues. Apelin has been shown to be involved in the regulation of cardiovascular and fluid homeostasis, food intake, cell proliferation, and angiogenesis. In addition to be an ubiquitous peptide, apelin is also produced and secreted by adipocytes and thus considered as an adipokine. This has opened a new field of investigation establishing a link between apelin and metabolic disorders (obesity, type 2 diabetes, etc.) which is the focus of the present review. Several studies, but not...

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This document includes the following topics: Background; Data Collection; Scope/Applicability of the Proposed Regulation; Description of the Industry; Industry Subcategorization; Pollutants of Concern for the Centralized Waste Treatment Industry; Pollutants Selected for Regulation; Wastewater Treatment Technologies; Regulatory Options Considered and Selected for Basis of Regulation; Long-Term Averages, Variability Factors, and Limitations and Standards; Cost of Treatment Technologies; Pollutant Loading and Removal Estimates; Non-Water Quality Impacts; Implementation; Analytical Methods and Baseline Values; List of Definitions; List of Acronyms; Appendix A--Pollutant Groups; Appendix B--Listing of Characerization Data From Non-Hazardous Oils Facilities; Appendix C--Listing of Daily Influent and Effluent Measuements; Appendix D--Facility-Specific Compliance Costs; Appendix E--Attachements to Chapter 10; ...

UK PubMed Central (United Kingdom)

Gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor superfamily, has been utilized for receptor-mediated targeting of imaging and therapeutic agents; here we extend...Full Text Available

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Acute Asthma

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The p75 neurotrophin receptor (p75"N"T"R) is a death receptor which belongs to the tumor necrosis factor receptor super-family of membrane proteins. This study shows that p75"N"T"R retarded cell cycle progression by induced accumulation of cells in G0/G1 and a reduction in the S phase of the cell cycle. The rescue of tumor cells from cell cycle progression by a death domain deleted (#DELTA#DD) dominant-negative antagonist of p75"N"T"R showed that the death domain transduced anti-proliferative activity in a ligand-independent manner. Conversely, addition of NGF ligand rescued retardation of cell cycle progression with commensurate changes in components of the cyclin/cdk holoenzyme complex. In the absence of ligand, p75"N"T"R-dependent cell cycle arrest facilitated an increase in apoptotic nuclear fragmentation of the prostate cancer cells. Apoptosis of p75"N"T"R expressing cells occurred via the ...

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Although the intracellular ultrastructural processing of epidermal growth factor (EGF) and its receptor have been described in cell culture systems, very few studies have examined this phenomenon in intact tissues. We have examined the ultrastructural and biochemical handling of ["1"2"5I]EGF in the epidermis and hair follicle bulb of intact, viable, 3- to 5-day-old rat skin the EGF receptor distribution of which has already been documented and in which EGF has been shown to be biologically active. After incubation of explants with 10 nM ["1"2"5I]EGF for 2.5 h at 25 degrees or 37 degrees C, radiolabel was detected over the basal cells of the epidermis and hair follicle outer root sheath, confirming previous light microscope observations. More specifically, silver grains were observed near coated and uncoated plasma membrane and coated membrane invaginations, Golgi apparatus, lysosomal structures, and nuclei. Sodium azide ...

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Endoreduplication represents a cell cycle variant during which multiple rounds of DNA replication occur without subsequent chromosome separation and cytokinesis, resulting into a cellular increase of the DNA content. Although the DNA ploidy level of cells is controlled by external stimuli such as light, currently limited knowledge is available on how environmental signals regulate the endoreduplication cycle at the molecular level. Previously, we have demonstrated that the conversion from the mitotic cell cycle into an endoreduplication cycle is mediated by the atypical E2F transcription factor DEL1 that operates as a repressor of endocycle onset. Here, we identified DEL1 as a transcriptional target of the classical E2Fb and E2Fc transcription factors that antagonistically control DEL1 transcript levels through competition for a single E2F cis-acting binding site. Correspondingly with the reported opposite effect of light ...

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Epidermal growth factor receptor (EGFR) gene alterations have been found in human lung cancers. However, there is no information on the factors inducing EGFR mutations. In rodents, K-ras mutations are frequently found in many lung carcinogenesis models, but hitherto, Egfr mutations have not been reported. Their presence was therefore investigated in representative lung carcinogenesis models with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosobis(2-hydroxypropyl)amine (BHP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) and ethyl carbamate (urethane), as well as X-ray irradiation. With the chemical carcinogenesis models, no mutations were detected in Egfr, which is in clear contrast to the high rates observed in either codon 12 or 61 of K-ras (21/23 of the lung tumors induced with NNK, 4/5 with MelQx, 1/4 with urethane and 7/18 with BHP). However, in the X-ray-induced lung tumors, Egfr mutations with ...

UK PubMed Central (United Kingdom)

The cell cycle-regulatory transcription factor E2F-1 is regulated by interactions with proteins such as the retinoblastoma gene product and by cell cycle-dependent alterations in E2F-1 mRNA abundance....Full Text Available

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BackgroundCoiled-coil domain containing 115 (Ccdc115) or coiled coil protein-1 (ccp1) was previously identified as a downstream gene of Fibroblast Growth Factor 2 (FGF2) highly expressed...Full Text Available

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In clause it is shown a method optimization of brake of forces in view of a bias road it is established, that in mountain conditions of loss of coupling weight of automobiles than 2-3 times concerning flat conditions therma are more. The degree of use of coupling weight in result use of a regulator of brake forces very much increases also efficiency of brake systems such a kind of automobiles is provided with definition of optimum factor of coupling at which value of loss of coupling weight is provided minimal

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Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is an aggressive non-Hodgkin lymphoma of T/null immunophenotype that is most prevalent in children and young adults. The...Full Text Available

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The UK Pipelines Safety Regulations require the pipeline operator to ensure that a pipeline, once decommissioned, does not become a source of danger. Elsewhere, Regulatory Authorities require consideration of the possible issues which pipeline decommissioning may raise. This paper considers current practice with respect to pipeline decommissioning and abandonment, and sets out the range of factors which the operator must take into account. (author)

UK PubMed Central (United Kingdom)

Cyclin-Dependent Kinase 1 (CDK1) is the major M-phase kinase known also as the M-phase Promoting Factor or MPF. Studies performed during the last decade have shown many details of how CDK1 is regulated...Full Text Available

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Objective: Atherosclerosis is an inflammatory disease, modulated by plaque stabilizing and de-stabilizing cell populations such as infiltrating monocytes and vascular smooth muscle cells (vSMCs). Transcription factors regulating proliferation and differentiation of atherosclerosis relevant cell types are of interest in this context. The forkhead box transcription factor FoxP1 modulates monocyte differentiation. We studied FoxP1 expression in atherosclerotic tissue, correlated FoxP1 expression with plaque characteristics and identified associations between FoxP1 and plaque proteins. Methods: 116 Atherosclerotic plaques from carotid endarterectomy samples were histologically classified (fibrous, fibroatheromatous, atheromatous) and subjected to semi-quantitative protein analysis. Macrophage,...

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The gastrin releasing peptide (GRP) receptor is becoming an increasingly attractive target for development of new radiolabeled peptides with diagnostic and therapeutic potential. The attractiveness of the GRP receptor as a target is based upon the functional expression of GRP receptors in several tumors of neuroendocrine origin including prostate, breast, and small cell lung cancer. This concise review outlines some of the efforts currently underway to develop new GRP receptor specific radiopharmaceuticals by employing a variety of radiometal chelation systems.

Science.gov (United States)

HEMATOLOGICAL MALIGNANCIES IN HUMANS TYPICALLY INVOLVE TWO TYPES OF GENETIC CHANGES: those that promote hematopoietic cell proliferation and survival (often the result of activation of tyrosine kinases) and those that impair hematopoietic cell differentiation (often the result of changes in transcription factors). The multi-stage erythroleukemia induced in mice by Friend spleen focus-forming virus (SFFV) is an excellent animal model for studying the molecular basis for both of these changes. Significant progress has been made in understanding the molecular basis for the multi-stage erythroleukemia induced by Friend SFFV. In the first stage of leukemia, the envelope protein encoded by SFFV interacts with and activates the erythropoietin (Epo) receptor and the receptor tyrosine kinase sf-Stk in erythroid cells, causing their Epo-independent proliferation, differentiation and survival. In the second stage, SFFV integration ...

International Nuclear Information System (INIS)

Bisaminoethanethiol (BAT) ligands with various gem-dimethyl and amide groups were prepared, and the corresponding neutral Tc-99m complexes were prepared and evaluated for their relative stabilities by ligand-exchange reactions. It was demonstrated that technetium complexes containing gem-dimethyl substituents have higher lipophilicities, whereas those with an amide group possess greater stability, which enhances ligand-exchange reaction. The most interesting observation was that the brain uptake in rats is not determined only by lipophilicity. Apparently, Tc-99m complexes with an amide functional group display lower brain uptakes in rats compared to those without an amide group. The brain uptake was strongly influenced by substituents on the BAT ligand. These factors are critically important and should be taken into consideration when designing Tc-99m-labeled agents for CNS receptor imaging.

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This analysis is one of 10 reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN) biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. Inhalation Exposure Input Parameters for the Biosphere Model is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the ...

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When the transmission line is very long or the generator is operated at a power factor nearly equal to 1.0, the machine regulated by an automatic voltage regulator (AVR) cannot be operated stably due to poor dynamic stability. To overcome this difficulty, the so called power system stabilizer (PSS) is very useful, in that output power or rotor speed of the generator is used as a feedback signal. The primary obective of the PSS is to damp the swing of the generator as quickly as possible. A method is proposed for designing PSS which yields a given eigenvalue. In the second method, the use of a Heffron-Phillips model is discussed. Next, a detailed procedure for the proposed design method is presented. A generalized method of a PSS design based on Park's equation and matrix operation is proposed.

UK PubMed Central (United Kingdom)

Selective estrogen receptor modulators (SERMs) represent a class with a growing number of compounds that act as either estrogen receptor agonists or antagonists in a tissue-specific manner. This article...Full Text Available

UK PubMed Central (United Kingdom)

Chemokine receptors control leukocyte chemotaxis and cell-cell communication but have also been associated with pathogen entry. GPR33, an orphan member of the chemokine-like receptor family,...Full Text Available

UK PubMed Central (United Kingdom)

The nicotinic acetylcholine receptor (AChR) controls signal transmission between cells in the nervous system. Abused drugs such as cocaine inhibit this receptor. Transient kinetic investigations indicate...Full Text Available

UK PubMed Central (United Kingdom)

BACKGROUND: H2-histamine receptors mediate a wide range of physiological functions extending from stimulation of gastric acid secretion to induction of human promyelocyte differentiation. We have previously...Full Text Available

UK PubMed Central (United Kingdom)

The vanilloid receptor-1 (VR1, or transient receptor potential vanilloid-1 receptor, TRPV1) is activated by capsaicin, the key ingredient of hot peppers. TRPV1 was originally described on sensory neurons...Full Text Available

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... Award Number: DAMD17-02-1-0151 TITLE: Paracrine Regulation of Prostatic Carcinogenesis ... Paracrine Regulation of Prostatic Carcinogenesis ...

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Unlike in normal rabbits, pulmonary rapidly adapting receptors (RARs) in rabbits with chronic mitral regurgitation (MR) do not respond to small changes in extravascular...Full Text Available

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The paper evaluates standardization of regulations on safety of electrical equipment for underground coal mines in the USSR. Factors increasing hazards of electrical failures of equipment in underground coal mines are analyzed: reduced lighting, increased humidity and dusts, damage caused by falling rocks or damage during haulage in underground workings, installation of electrical equipment in places easily accessible to untrained personnel. Standards on safety of electrical equipment for underground coal mining valid in the USSR are reviewed: the PIRNEh regulations on production of electrical equipment for coal mines developed by the VNIIVEh Institute, and the GOST national standards. International cooperation within the COMECON on safety of mining electrical equipment (the Interelectro Committee of the COMECON) is described. Certification of electrical equipment for coal mines is discussed on the example of electrical ...

Science.gov (United States)

Poncirin, flavanone glycoside, isolated from the fruit of Poncirus trifoliata, has anti-bacterial and anti-inflammatory activities. In this study, the effects of poncirin on the differentiation of mesenchymal stem cells were investigated. The C3H10T1/2 mesenchymal stem cells and primary bone marrow mesenchymal stem cells were studied. In the C3H10T1/2 cells, poncirin prevented adipocyte differentiation, as demonstrated by inhibition of cytoplasm lipid droplet accumulation and peroxisome proliferator-activating receptor-? (PPAR-?) and CCAAT-enhancer-binding protein-? (C/EBP-?) mRNA expression. By contrast, poncirin enhanced the expression of the key osteogenic transcription factors, runt-related transcription factor 2 (Runx2) and transcriptional coactivator with PDZ-binding motif (TAZ). Poncirin also enhanced expression of the osteogenic marker genes including alkaline phosphatase (ALP) and osteocalcin (OC). Poncirin ...

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Radiation protection programs for workers are based, in the United States, on a hierarchy of limitations stemming from Federal guidance approved by the President. This guidance, which consists of principles, policies, and numerical primary guides, is used by Federal agencies as the basis for developing and implementing their own regulatory standards. The primary guides are usually expressed in terms of limiting doses to workers. The protection of workers against taking radioactive materials into the body, however, is accomplished largely through the use of regulations based on derived guides expressed in terms of quantities or concentrations of radionuclides. The values of these derived guides are chosen so as to assure that workers in work environments that conform to them are unlikely to receive radiation doses that exceed the primary guides. The purpose of the present report is to set forth derived guides that are consistent with current Federal radiation ...

International Nuclear Information System (INIS)

This paper reports regulation of hypoxia inducible factor-1 ? (HIF-1 ?)in hepatoma cells by irradiation. Cobalt chloride (CoCl2), a chemical mimic agent for hypoxia research, was utilized to induce the stable expression of HIF-1 ? in HepG2 cells. The HepG2 cells were irradiated to different doses to observe the changes of HIF-1 ?. The level of intracellular reactive oxygen species (ROS) was assayed by fluorescent microscope and flow cytometry (FCM). The results showed that there were obvious changes in expression of HIF-1 ? after HepG2 cells exposed to radiation, and the changes were positively related with the irradiation dose from 1 Gy to 5 Gy. Moreover, contents of incellular ROS were negatively correlated with above levels of HIF-1 ? from 1 Gy to 3 Gy. The results indicate that irradiation may enhance hypoxic cells HIF-1 ?, and the reduction of intracellular ROS can contribute to the regulation of ionizing radiation on ...

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A reliable source of specific criteria for recognizing a wetland, as defined for regulatory purposes would be valuable. In 1987 the Army Corps of Engineers developed a technical manual for identifying wetlands (1987 Wetlands Manual). An interagency manual (1989 Wetlands Manual) was later developed. This manual has been used to identify wetlands according to three evidentiary factors: vegetation, hydrology, and soil. This paper addresses the development of criteria to delineate wetlands, and describes some of the logic used by federal courts to uphold the limited constitutional use of the 1989 Wetlands Manual.

British Library Electronic Table of Contents (United Kingdom)

Purpose To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Methods Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular KATP (PNU-37883A) or BKCa [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-?B) was assessed by electrophoretic mobility shift as...

British Library Electronic Table of Contents (United Kingdom)

The cAMP response element-binding protein (CREB) is a highly conserved transcription factor that integrates signaling through the cAMP-dependent protein kinase A (PKA) in many eukaryotes. PKA plays a critical role in Dictyostelium development but no CREB homologue has been identified in this system. Here we show that Dictyostelium utilizes a CREB-like protein, BzpF, to integrate PKA signaling during late development. bzpF^- mutants produce compromised spores, which are extremely unstable and germination defective. Previously, we have found that BzpF binds the canonical CRE motif in vitro. In this paper, we determined the DNA binding specificity of BzpF using protein binding microarray (PBM) and showed that the motif with the highest specificity is a CRE-like sequence. BzpF is necessary to ...

Science.gov (United States)

Background: Protein disulfide isomerase (PDI) controls platelet integrin function, tissue-factor (TF) activation, and concentrates at fibrin and thrombus formation sites of vascular injury. Objective: We investigated involvement of surface thiol isomerases and especially PDI, in thrombin-mediated thrombin amplification on human platelets. Methods/Results: Using a new developed thrombin-dependent platelet thrombin generation assay we observed that the feedback activation of thrombin generation on the platelet surface does not depend on TF, as anti-TF antibodies inhibiting TF-induced thrombin formation in platelet-depleted plasma had no effect compared to vehicle-treated controls. Feedback activation of thrombin generation in the presence of platelets was significantly diminished by membrane impermeant thiol blockers or by the thiol isomerase-inhibitors bacitracin and anti-PDI antibody RL90, respectively. Platelet thrombin formation depends on binding of coagulation ...

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Pain; Pain Threshold; Labour Pain

KoreaScience (Korea)

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UK PubMed Central (United Kingdom)

BackgroundThe effects of single or combined histamine H₁-receptor and leukotriene CysLT₁-receptor antagonism on nasal adenosine monophosphate (AMP) challenge...Full Text Available

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Although the radioreceptor method is widely used for estrogen receptor assay in human tissue, it has several limitations and a number of alternative methods are being explored. An immunohistochemical method of estrogen receptor assay using a specific antibody to estradiol has been proposed as a suitable alternative. The present study was designed to evaluate the validity of this method in detecting true estrogen receptors in human tumor tissue. Using radioiodinated antibody to estrogen, we have demonstrated that the estrogen antibody can detect the estrogen when it is bound to 4S type receptor but is unable to bind to estrogen when the hormone is bound to 8S type receptor. Our observations suggest that the immunohistochemical method of detection of intracellular cytosolic receptor for estrogen is not a suitable alternative to the currently used radioreceptor ...

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Insulin receptors on the surface of isolated rat adipocytes were photoaffinity labeled at 12 degrees C with the iodinated photoreactive insulin analogue, 125I-B2 (2-nitro-4-azidophenylacetyl)-des-PheB1-insulin, and the pathways in the intracellular processing of the labeled receptors were studied at 37 degrees C. During 37 degrees C incubations, the labeled 440-kDa insulin receptors were continuously internalized (as assessed by trypsin inaccessibility) and degraded such that up to 50% of the initially labeled receptors were lost by 120 min. Metabolic poisons (0.125-0.75 mM 2,4-dinitrophenol (DNP) and 1-10 mM NaF), which led to dose-dependent depletion of adipocyte ATP pools, inhibited receptor loss, and caused up to 3-fold increase in intracellular receptor accumulation. This effect was due to inhibition of intracellular receptor ...

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Before large-scale anthropogenetic emissions the environmental factors have been rather stable for thousands of years, varying yearly, seasonally and daily in rather regular manners around some mean values. In this century the emissions of CO{sub 2}, sulphur and nitrogen from society to atmosphere are changing both atmospheric and soil environment at rates not experienced before. The fluxes to soil affect the contents of plant available nutrients and solubility of toxic compounds in the forest soil. Additionally, the chemical state of soil environment is coupled to tree growth, litter production and nutrient uptake as well as to the activity of biological organisms in soil, which decompose litter and release nutrients from it. Trees have developed effective regulation systems to cope with the environment during the evolution. The resulting acclimations improve the functioning of the trees if the environmental factors remain ...

International Nuclear Information System (INIS)

The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate [U-"1"4C]glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity. To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10"5 cells/ml) were incubated with either ["1"2"5I]insulin or ["1"2"5I]hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and "1"4C-incorporation into lipids. Insulin, hGH and PGF ...

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This analysis report is one of a series of technical reports that document the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the total system performance assessment (TSPA) for the geologic repository at Yucca Mountain. This report is one of the five biosphere reports that develop input parameter values for the biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes the conceptual model, as well as the mathematical model and its input parameters. Figure 1-1 is a graphical representation of the documentation hierarchy for the ERMYN. This figure shows relationships among the products (i.e., scientific analyses and model reports) developed for biosphere modeling and biosphere abstraction products for TSPA, as identified in the ''Technical Work Plan: for Biosphere Modeling and Expert Support'' (BSC 2004 [DIRS 169573]). The purpose of this ...

British Library Electronic Table of Contents (United Kingdom)

Summary Metabotropic GABAB receptors play a fundamental role in modulating the excitability of neurons and circuits throughout the brain. These receptors influence synaptic transmission by inhibiting presynaptic release or activating postsynaptic potassium channels. However, their ability to directly influence different types of postsynaptic glutamate receptors remains unresolved. Here we examine GABAB receptor modulation in layer 2/3 pyramidal neurons from the mouse prefrontal cortex. We use two-photon laser-scanning microscopy to study synaptic modulation at individual dendritic spines. Using two-photon optical quantal analysis, we first demonstrate robust presynaptic modulation of multivesicular release at single synapses. Using two-photon glutamate uncaging, we then reveal that GABAB r...

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... (tb*it 06(M WfIio[td) Page 2. Asynchronous Digital Regulators Vernon Scott Ritchey, Ph.D. ... Page 3. ASYNCHRONOUS DIGITAL REGULATORS ...

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Bisaminoethanethiol (BAT) ligands with various gem-dimethyl and amide groups were prepared, and the corresponding neutral Tc-99m complexes were prepared and evaluated for their relative stabilities by ligand-exchange reactions. It was demonstrated that technetium complexes containing gem-dimethyl substituents have higher lipophilicities, whereas those with an amide group possess greater stability, which enhances ligand-exchange reaction. The most interesting observation was that the brain uptake in rats is not determined only by lipophilicity. Apparently, Tc-99m complexes with an amide functional group display lower brain uptakes in rats compared to those without an amide group. The brain uptake was strongly influenced by substituents on the BAT ligand. These factors are critically important and should be taken into consideration when designing Tc-99m-labeled agents for CNS receptor imaging.

British Library Electronic Table of Contents (United Kingdom)

Objective: To study the effects of minocycline hydrochloride (MINO) on the formation of tartrate-resistant acid phosphatase (TRAP) staining-positive multinucleated osteoclast-like cells in mouse bone marrow cells (BMCs) treated with 1@a,25(OH)"2D"3 or soluble receptor activator of nuclear factor-@kB ligand (s-RANKL). Materials and methods: Mouse BMCs were cultured in alpha-modified minimum essential medium containing foetal calf serum (10%) and tetracyclines (2.5, 5 and 10@mM), such as MINO, tetracycline hydrochloride (TC), oxytetracycline hydrochloride (OXT) or doxycycline (DOXY) in the presence of 1@a,25(OH)"2D"3 (10nM) or s-RANKL (20ng/ml) for 7 days, and the number of TRAP staining-positive osteoclast-like cells was counted. In RNA isolated from BMCs treated with 1@a,25(OH)"2D"3 or s-R...

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This report surveys the possibilities and restrictions of different construction materials for the purpose of the blades of a small stall regulated turbine. For example scaling up, material saving at decreasing of static or dynamic loads, comparisons of global costs based on prices per unit of weight, etc. For the mutual comparison of construction materials for turbine blades the starting point is a stall regulated horizontal axis turbine with a rotor diameter of 16 m and a tipvane speed of about 64 m/s. Short descriptions are given of the materials and of the applied production methods with the resulting blade geometry. The blade skins are dimensionized for storm loads after the optimalization of the blade geometry, needed for the design wind speed, is recorded. The resulting blade skins are mutually compared as for weight, mass inertia and bending stiffness. Also a comparison took place of the resulting reserve factors ...

International Nuclear Information System (INIS)

The predicted results of INDAC code were compared with measured "3H concentrations in air and pine-needle around the Wolsung site. The optimal sets of input data to INDAC were in addition selected by comparing the measured values with the predicted values of INDAC based on various conditions such as the release modes of effluents into the environment, the classification of wind classes, and the consideration of terrain. The predicted "3H concentrations in air and pine-needle were shown to have good agreement with measured values, although there are some limitations such as uncertainties in measured values, complex topology around the site, and the land-sea breeze effects. The assumption on the "3H behavior in vegetables or plants that the ratio of "3H concentration in plant water to "3H concentration in atmospheric water is 1/2 was shown to be conservative in terms of the audit calculation performed by the regulator. It was also found that data sets based on mixed ...

Science.gov (United States)

A factor produced by plerocercoids of the tapeworm Spirometra mansonoides is similar to human growth hormone (hGH) in that it stimulates body growth, binds to hGH receptors, cross-reacts with anti-hGH antibodies, and has lactogenic and insulin-like activities. The purpose of this study was to determine whether plerocercoid growth factor (PGF) is similar to hGH in expressing diabetogenic activity in the genetically obese (ob/ob) mouse. To determine an effective dose for use in the obese mice, the ability of daily injections of PGF to stimulate growth of phenotypically normal mice of the same strain was assessed in a 10-day weight gain assay. Injections of PGF stimulated a dose-dependent weight gain (r = 0.83) and 25 ng eq/day of PGF stimulated a response not significantly different from that produced by 100 micrograms of bovine growth hormone/day. Diabetogenicity was assessed using fasting blood glucose and glucose tolerance ...

Science.gov (United States)

A factor produced by the plerocercoid stage of S. mansonoides mimics some, but not all, of the actions reported for hGH. The biological actions of plerocercoid growth factor (PGF) suggest structural similarity to human GH (hGH). Plerocercoid membranes were solubilized, and PGF was purified more than 1000-fold by hGH receptor affinity chromatography. The ability of purified PGF to displace [125I]hGH from monoclonal antibodies specific for four distinct nonoverlapping antigenic determinants of hGH and from an anti-hGH polyclonal antibody was tested in liquid phase RIA. All of the hGH antibodies cross-reacted with PGF, with potencies ranging from more than 60% to less than 1% that of the hGH standard. Of the four major epitopes of hGH defined by the monoclonal antibodies used in this study, only one is not represented to a significant extent in PGF. The epitope of hGH that is only marginally present in PGF is highly ...

UK PubMed Central (United Kingdom)

The purpose of this study was to determine whether resistance exercise training-induced reductions in inflammation are mediated via melanocortin 3 receptor expression in obese (BMI 32.7 ± 3.7)...Full Text Available

UK PubMed Central (United Kingdom)

Current concepts of the pathogenesis of sarcoidosis suggest that the expanded numbers of activated T-helper/inducer cells at sites of disease activity result, at least in part, from their proliferation...Full Text Available

UK PubMed Central (United Kingdom)

G-protein-coupled receptor signalling has been suggested to be voltage dependent in a number of cell types; however, the limits of sensitivity of this potentially important phenomenon are unknown. Using...Full Text Available

UK PubMed Central (United Kingdom)

1. The structural requirements of an allosteric barbiturate binding site on acetylcholine receptor-rich membranes isolated from Torpedo electroplaques have been characterized by the ability of fourteen...Full Text Available

UK PubMed Central (United Kingdom)

There is increasing evidence that receptor-mediated events impact one or more stages responsible for tumor development in experimental animals and humans. Although many chemicals and endogenous hormones...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundBaculovirus, which has a width of 40 nm and a length of 250-300 nm, can display functional peptides, receptors and antigens on its surface by their fusion with a baculovirus...Full Text Available

UK PubMed Central (United Kingdom)

Ionotropic P2X and metabotropic P2Y purinergic receptors are expressed in the central nervous system and participate in the synaptic process particularly associated with acetylcholine, GABA, and glutamate...Full Text Available

UK PubMed Central (United Kingdom)

The 37/67-kd laminin receptor, LAMR, is a multifunctional protein that associates with the 40S ribosomal subunit and also localizes to the cell membrane to interact with the extracellular matrix. LAMR...Full Text Available

UK PubMed Central (United Kingdom)

TCDD and other polyhalogenated aromatic hydrocarbon ligands of the aryl hydrocarbon receptor (AHR) have been classically considered as non-genotoxic compounds because they fail to be directly mutagenic...Full Text Available

UK PubMed Central (United Kingdom)

To study the expression of Fc receptors in human alveolar macrophages (AM), the cells were collected from 12 healthy controls and 22 patients with sarcoidosis and the activity involved in binding to...Full Text Available

UK PubMed Central (United Kingdom)

OBJECTIVEPrevious studies showed that genetic deletion or pharmacological blockade of the receptor for advanced glycation end products (RAGE) prevents the early structural changes...Full Text Available

UK PubMed Central (United Kingdom)

Astrocytes have long been perceived only as structural and supporting cells within the central nervous system (CNS). However, the discovery that these glial cells may potentially express receptors capable...Full Text Available

UK PubMed Central (United Kingdom)

Several investigations suggested abnormalities in circadian rhythms are related to the pathophysiology of psychiatric disorders, including drug addiction. Recently, orphan nuclear receptor rev-erb alpha...Full Text Available

UK PubMed Central (United Kingdom)

The Wistar Kyoto (WKY) rat strain is a putative genetic model of comorbid depression and anxiety. Previous research showing increased κ-opioid receptor (KOR)...Full Text Available

UK PubMed Central (United Kingdom)

Single-channel currents from acetylcholine receptor channels of garter snake neuromuscular junctions were recorded using the patch-clamp technique. Low concentrations of acetylcholine or carbamylcholine...Full Text Available

UK PubMed Central (United Kingdom)

BACKGROUNDOff-pump coronary artery bypass (OPCAB) surgery is associated with a hypercoagulable state in which the platelet thrombin receptor, protease-activated receptor-1...Full Text Available

KoreaScience (Korea)

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Energy Technology Data Exchange (ETDEWEB)

The University of Maryland at Baltimore was awarded a grant from the Department of Energy to test a specially modified incinerator to burn biomedical radioactive waste. In preparation for the incinerator, the Radiation Safety Office devised a comprehensive plan for its safe and effective use. The incinerator plan includes a discussion of regulations regarding on-site incineration of radioactive waste, plans for optimum use in burning four principal waste forms, controlled air incineration technology, and standard health physics safety practices; a use plan, including waste categorization and segregation, processing, and ash disposition; safety procedures, including personnel and area monitoring; and methods to evaluate the incinerator's effectiveness by estimating its volume reduction factors, mass and activity balances, and by determining the cost effectiveness of incineration versus commercial shallow land burial.

British Library Electronic Table of Contents (United Kingdom)

Fibroblast growth factor (FGF) signaling has been shown to regulate lung epithelial development but its influence on mesenchymal differentiation has been poorly investigated. To study the role of mesenchymal FGF signaling in the differentiation of the mesenchyme and its impact on epithelial morphogenesis, we took advantage of Fgfr2c+/? mice, which due to a splicing switch express Fgfr2b in mesenchymal tissues and manifest Apert syndrome-like phenotypes. Using a set of in vivo and in vitro studies, we show that an autocrine FGF10?FGFR2b signaling loop is established in the mutant lung mesenchyme, which has several consequences. It prevents the entry of the smooth muscle progenitors into the smooth muscle cell (SMC) lineage and results in reduced fibronectin and elastin deposition. Levels of...

British Library Electronic Table of Contents (United Kingdom)

Cytoreductive conditioning regimes designed to allow for successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) paradoxically are also detrimental to recovery of the immune system in general but lymphopoiesis in particular. Post-transplant immune depletion is particularly striking within the T cell compartment which is exquisitely sensitive to negative regulation, evidenced by the profound decline in thymic function with age. As a consequence, regeneration of the immune system remains a significant unmet clinical need. Over the past decade studies have revealed several promising therapeutic strategies to address ineffective lymphopoiesis and post-transplant immune deficiency. These include the use of cytokines such as IL-7, IL-12 and IL-15; growth factors and hormones li...

International Nuclear Information System (INIS)

Purpose: To provide a feedwater control device capable of minimizing the adverse response of steam drum level at low power. Consitution: In order to perform feedwater control at low power by the substantial control of three factors, that is, main steam flow rate, feedwater flow rate and steam drum level, the main steam flow rate is determined from the reactor output and feedwater rate is determined from the changes in the feedwater temperature due to the mixing of waters in the reactor clean up system and feedwater. If a difference is resulted between these flow rates, a starting feedwater regulator is controlled instantly to eliminate the difference. The water level in the steam drum is used for amending the difference from the final set value of the drum water level, by which the adverse response of the steam drum level can be minimized. (Seki, T.).

Science.gov (United States)

;Table of Contents: Legal authority; Summary of proposed regulations; Industry definition and waste streams; Industry description; Data and information gathering; Selection of pollutant parameters; Drilling wastes-characterization, control, and treatment technologies; Produced water-characterization, control, and treatment technologies; Miscellaneous waste-characterization, control, and treatment technologies; Cost and pollutant loading determination of drilling fluids and drill cuttings; Compliance cost and pollutant load determination of produced water; Compliance cost and pollutant load determination of well treatment, workover, and completion fluids; Cost and pollutant loading determination of deck drainage; Options selection-rationale and total costs; Pretreatment standards; Non-water quality environmental impacts and other factors; Best Management Practices; and Appendices.

International Nuclear Information System (INIS)

Linear and nonlinear state feedback controllers are proposed to control the bifurcation of a phenomenon in power system, this phenomenon of electro-mechanical interaction between the series resonant circuits and torsional mechanical frequencies of the turbine-generator sections, which known as subsynchronous resonance (SSR). The first system of the IEEE second benchmark model is considered. The dynamics of the two axes damper windings, automatic voltage regulator and power system stabilizer are included. The linear controller gives better initial disturbance response than that of the nonlinear, but in a small narrow region of compensation factors. The nonlinear controller not only can be easily implemented, but also it stabilizes the operating point for all values of the bifurcation parameter.

International Nuclear Information System (INIS)

... carbon 14 cholera gels labelling membranes molecules proteins receptors

UK PubMed Central (United Kingdom)

BackgroundTo evaluate whether P2X receptors are involved in responses to noxious pulp stimulation, the P2X₃ and P2X_2/3 receptor agonist α,β-methyleneATP...Full Text Available

UK PubMed Central (United Kingdom)

Dopamine (DA) D3 and D2 receptor mechanisms are implicated in cocaine's abuse-related behavioral effects, but the relative contribution of the two receptor subtypes is only partially characterized....Full Text Available

Science.gov (United States)

In APCs, presentation by MHC II molecules of the chemically dominant peptide from the protein hen egg white lysozyme (HEL) generates different conformational isomers of the peptide-MHC II complexes (pMHC). Type B pMHCs are formed in early endosomes from exogenous peptides in the absence of H2-DM, whereas in contrast, type A pMHC complexes are formed from HEL protein in late vesicles after editing by H2-DM. Thus, H2-DM edits off the more unstable pMHC complexes, which are not presented from HEL. In this study, we show that type B pMHC complexes were presented from HEL protein only after stimulation of dendritic cells (DC) with TLR ligands or type I IFN. Type I IFN contributed to most TLR ligand-induced type B pMHC generation, as presentation decreased in DC lacking the receptor for type I IFNs (IFNAR1(-/-)). In contrast, presentation of type A pMHC from HEL and from peptide was minimally affected by TLR ligands. The relative effectiveness of CD8?(+) DC or CD8?(-) DC ...

International Nuclear Information System (INIS)

The present study was designed to assess the radioprotective effects of amifostine on ovarian follicles. Three week-old female mice with or without pretreatment of amifostine were irradiated with 6.42 Gy of #gamma# -ray. Ovaries were collected 0 and 6h after irradiation. DNA fragmentation pattern and expression of genes and activity of proteins related with apoptosis were investigated by means of RT-PCR and Western blot. Proliferation of granulosa cells was reduced and incidence rate of follicular atresia was increased in ovarian follicles in #gamma# -ray irradiated mice compared to those in control or amifostine-treated group. DNA fragmentation was increased in time-dependent manner in granulosa cells of all irradiated groups. However, no difference between amifostine pre-treated group and irradiated groups was found and the expression of p53 as tumor suppressor gene and Bax as one of pro-apoptotic Bcl-2 family was increased in irradiated mice ovaries. PARP as DNA damage sensor was ...

British Library Electronic Table of Contents (United Kingdom)

Abstract Background/Aims: Transforming growth factor-b (TGF-b) initiates and maintains epithelial-mesenchymal transition (EMT), which causes disassembly of tight junctions and loss of epithelial cell polarity. In mature hepatocytes during EMT induced by TGF-b, changes in the expression of tight junction proteins and the fence function indicated that epithelial cell polarity remains unclear. Methods: In the present study, using primary cultures of adult rat hepatocytes at day 10 after plating, in which epithelial cell polarity is well maintained by tight junctions, we examined the effects of 0.01-20 ng/ml TGF-b on the expression of the integral tight junction proteins, claudin-1, -2 and occludin, as well as the fence function. Results: In adult rat hepatocytes, TGF-b induced EMT, which was ...

Energy Technology Data Exchange (ETDEWEB)

This paper examines the dynamic international political economic environment in which petroleum exploration and production companies must operate when considering investments in the economically transitional nations of the former Soviet Union or developing nations In this period of critical global changes low oil prices is only one factor with which petroleum companies Must be. concerned in their investment decisions Other factors include the transition from a bipolar world to a multipolar world of free trade zones. the general malaise of the international economy public and political recognition that nations and industries can no longer practice environmental {open_quotes}beggar-thy-neighbor{close_quotes} policies, and the rejection of aggregate national economic growth policies for sustainable economic development policies in both the Developed and developing world This paper focuses on actions which investing petroleum exploration and ...

Science.gov (United States)

The Drosophila melanogaster tissue-specific transcription factor NTF-1 was originally identified in vitro as a protein that could bind to and activate transcription from the Dopa decarboxylase (Ddc) gene. A structure-function analysis of NTF-1 led to the identification of a discrete amino-terminal activation domain. Here, we report that an NTF-1 mutant lacking the activation domain acts as a trans-dominant inhibitor of NTF-1 activation in tissue culture cells by forming inactive heterodimers with the full-length protein. Ectopically expressing this dominant-negative protein or the full-length protein in developing Drosophila embryos leads to dire developmental consequences. Overexpressing the trans-dominant NTF-1 leads to lethality, while overexpressing full-length NTF-1 results in both lethality and morphogenetic defects. Our results suggest that both the activity and the regulation of NTF-1 are critical for viability and proper development of ...

Energy Technology Data Exchange (ETDEWEB)

Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. ...

Energy Technology Data Exchange (ETDEWEB)

The study of chemoattractant receptors on human monocytes had been limited by the lack of a radioligand suitable for use with the small numbers of cells routinely available from human donors. A new synthetic oligopeptide radioligand f(/sup 35/S)Met-leu-phe, with a higher specific radioactivity than was available with the tritiated compound, was used to characterize a chemoattractant receptor on freshly isolated human blood monocytes. These cells bind f(/sup 35/)met-leu-phe with a dissociation constant (KD) of 30.2 +/- 5.6 nM and contain 84,000 +/- 11,300 receptors per cell. f(/sup 35/)met-leu-phe does not bind specifically to blood lymphocytes. The specificity of the oligopeptide receptor on monocytes is indistinguishable from the oligopeptide chemoattractant receptor on human polymorphonuclear leukocytes. Using f(/sup 35/)met-leu-phe, it will now be feasible to study the ...

Energy Technology Data Exchange (ETDEWEB)

This analysis report is one of a series of technical reports that document the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the total system performance assessment (TSPA) for the geologic repository at Yucca Mountain. This report is one of the five biosphere reports that develop input parameter values for the biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes the conceptual model, as well as the mathematical model and its input parameters. Figure 1-1 is a graphical representation of the documentation hierarchy for the ERMYN. This figure shows relationships among the products (i.e., scientific analyses and model reports) developed for biosphere modeling and biosphere abstraction products for TSPA, as identified in the ''Technical Work Plan for Biosphere Modeling and Expert Support'' (BSC 2005 [DIRS 172782]). The purpose of this ...

Energy Technology Data Exchange (ETDEWEB)

The authors have investigated insulin receptor phosphorylation in differentiated cultured BC3H-1 myocytes. As for other insulin-responsive cell systems in partially purified wheat germ agglutinin receptor preparations, insulin stimulates the phosphorylation of its own receptor (95K ..beta..-subunits) in a dose dependent manner (0-400 nM), as identified by immunoprecipitation with antiinsulin receptor antibodies and SDS-PAGE. In the same preparations they show that 12-0-tetradecanyl phorbol acetate (TPA), which in many respect ..beta..-subunits in the same dose dependent manner (0-5 ..mu..M). In addition, antiinsulin receptor antibodies (B-10) also induced phosphorylation of mimics insulin action, also induced phosphorylation of the insulin receptor and HPLC tryptic maps of the /sup 32/P-labeled ..beta..-subunit were identical to those for insulin-induced ...

Energy Technology Data Exchange (ETDEWEB)

Methylxanthines and their derivatives are antagonists at cell surface adenosine receptors. They report here a systematic study of xanthine structure-activity relationships which compares potency at two adenosine receptor subtypes, R/sub a/ and R/sub i/. Adenylate cyclase stimulation (R/sub a/ in platelet membranes) and inhibition (R/sub i/ in adipocyte membranes) were used as models of receptor activation. K/sub i/ values were obtained by Schild analysis. The orders of potency of the xanthines to attenuate the effects of adenosine analogues were similar to those previously reported. Earlier work utilizing radioligand binding (R/sub i/ and (/sup 3/H) cAMP formation (R/sub a/) claimed that IIX and PACPX are at least 10 and 400 fold, respectively, more potent at R/sub i/ than at R/sub a/. However, in their assays which utilize modulation of receptor-coupled adenylate cyclase, the xanthines show little ...

UK PubMed Central (United Kingdom)

MicroRNAs (miRs) can regulate many cellular functions, but their roles in regulating responses of vascular endothelial cells (ECs) to mechanical stimuli remain unexplored. We hypothesize that the physiological...Full Text Available