The parathyroid hormone receptor (PTHR) is a class B G protein-coupled receptor that plays critical roles in bone and mineral ion metabolism. Ligand binding to the PTHR involves interactions to both...Full Text Available
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
The aspartate receptorinvolved in chemotaxis is modified by methyl esterification at four distinct glutamate residues during the adaptive response of this receptor. To explain the high degree of specificity...Full Text Available
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
BackgroundTo evaluate whether P2X receptors are involved in responses to noxious pulp stimulation, the P2X3 and P2X2/3 receptor agonist α,β-methyleneATP...Full Text Available
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
TSH receptor (TSHR) plays a central role in regulating thyroid function and is targeted by IgGs in Graves’ disease (GD-IgG). Whether TSHR is involved in the pathogenesis of thyroid associated...Full Text Available
There is considerable evidence that purines are vasoactive molecules involved in the regulation of blood flow. Adenosine is a well known vasodilator that also acts as a modulator of the response to...Full Text Available
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
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
Klebsiella pneumoniae is able to grow anaerobically with citrate as a sole carbon and energy source by a fermentative pathway involving the Na+-dependent citrate...Full Text Available
A clone encoding a human D{sub 2} dopamine receptor was isolated from a pituitary cDNA library and sequenced. The deduced protein sequence is 96% identical with that of the cloned rat receptor with one major difference: the human receptor contains an additional 29 amino acids in its putative third cytoplasmic loop. Southern blotting demonstrated the presence of only one human D{sub 2} receptor gene. Two overlapping phage containing the gene were isolated and characterized. DNA sequence analysis of these clones showed that the coding sequence is interrupted by six introns and that the additional amino acids present in the human pituitary receptor are encoded by a single exon of 87 base pairs. The involvement of this sequence in alternative splicing and its biological significance are discussed.
Spinal cord injury (SCI) is a debilitating disorder, which produces profound deficits in volitional motor control. Following medical stabilization, recovery from SCI typically involves long term rehabilitation....Full Text Available
AimsIt is unclear as to which mediators are involved in mediating the response to nasal mannitol challenge, a novel osmotic stimulus.MethodsA...Full Text Available
Background:Endothelin-1 may be involved in the development of diabetic microangiopathy. We studied the effect of endothelin-1 blockade on myocardial microcirculation during coronary...Full Text Available
In this study we compared the molecular signalling elicited by rexinoids, selective retinoid X receptor (RXR)-activators, in several organs (i.e. liver, kidney,...Full Text Available
Cleavage of membrane-associated proteins with the release of biologically active macromolecules is an emerging theme in biology. However, little is known about the nature and regulation of the involved...Full Text Available
Disruption of circadian rhythms may be involved in the pathophysiology of psychiatric disorders, including drug addiction. Recently, we detected the significant association between prokineticin 2 receptor...Full Text Available
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
BackgroundMost rapidly evolving gene families are involved in immune responses and reproduction, two biological functions which have been assigned to the carcinoembryonic antigen...Full Text Available
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
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
The authors have been involved for the last few years in developing high affinity sigma-receptor-specific radiopharmaceuticals for use in nuclear medicine. They recently demonstrated that sigma-1 receptors are expressed in human melanoma cells and that sigma receptors could be used as external markers for non-invasive imaging. In order to determine the presence of sigma receptors in other human tumors they have screened numerous non-small cell lung carcinoma, melanoma and breast cancer cell lines. All of these cell lines expressed high sigma receptor densities using commercially available ["3H]-(+)-pentazocine or ["3H]DTG tritiated sigma ligands. Therefore, a sigma ligand with high affinity in both sigma-1 and sigma-2 subtype pharmacological assays could be potentially useful for imaging a variety of primary and metastatic sites of various origins. The authors ...
The aim of the safety calculation is to quantify through numerical modelling the radiological impact (molar flow, human dose) of a potential repository for radioactive waste on the Meuse/Haute Marne site at Bure. A selection process is underway for safety scenarios and their phenomenological and numerical conceptual models upstream from the safety calculation. This involves defining and quantifying the geometric and dimensional representations of the repository for each scenario plus the physical, mathematical and numerical models that reflect its behaviour and the uncertainties associated with all the parameters required to quantify the impact. A summary will be given of these various aspects. The numerical simulations are then performed on the Alliances platform which integrates the various computer codes required for the physical representation of the system. (authors)
(3H)Cyclofoxy (CF: 17-cyclopropylmethyl-3,14-dihydroxy-4,5-alpha-epoxy-6-beta-fluoromorp hinan) is an opioid antagonist with affinity to both mu and kappa subtypes that was synthesized for quantitative evaluation of opioid receptor binding in vivo. Two sets of experiments in rats were analyzed. The first involved determining the metabolite-corrected blood concentration and tissue distribution of CF in brain 1 to 60 min after i.v. bolus injection. The second involved measuring brain washout for 15 to 120 s following intracarotid artery injection of CF. A physiologically based model and a classical compartmental pharmacokinetic model were compared. The models included different assumptions for transport across the blood-brain barrier (BBB); estimates of nonspecific tissue binding and specific binding to a single opiate receptor site were found to be essentially the same with both models. The nonspecific ...
The aims of this study were to quantify the severity and extent of subclinical interstitial lung disease as depicted on HRCT and to study the relationship between the patterns of lung disease quantified by HRCT and the functional parameters and bronchoalveolar lavage findings in patients with rheumatic diseases. The results confirm that HRCT is a sensitive tool in detecting interstitial lung disease in patients with rheumatic diseases with no signs and symptoms of pulmonary involvement. The relationship between the different HRCT patterns and bronchoalveolar lavage cell profiles can identify patients at higher risk of developing irreversible lung fibrosis. A long-term, prospective follow-up study is needed to determine whether these patients will develop over pulmonary disease.
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...
The authors used radioligand binding and studies of cell contraction to characterize muscarinic receptors on dispersed smooth muscle cells from rabbit proximal and distal colon. Cells obtained after serial incubations in collagenase were used to measure binding of tritiated quinuclidinyl benzilate (["3H]QNB). At 37 degree C, specific ["3H]QNB binding was saturable and linearly related to cell number. Nonlinear regression analysis was used to determine the affinity of ["3H]QNB for its receptor. The IC_5_0 for the muscarinic agonists bethanechol and oxotremorine were 80 and 0.57 #mu#M, respectively. Hill coefficients were 0.67 for both, suggesting more complex interaction involvingreceptors of different affinities. In studies of cell contraction, bethanechol stimulated a dose-dependent decrease in cell length with half the maximal contraction occurring at 100 pM. These results suggest that (1) ...
Fgf receptor 2c (Fgfr2c) was expressed in mature adipocytes of mouse white adipose tissue (WAT). To examine the role of Fgfr2c in mature adipocytes, we generated adipocyte-specific Fgfr2 knockout (Fgfr2 CKO) mice. The hypertrophy impairment of adipocytes in the mesenteric WAT but not in the subcutaneous WAT and decreased plasma free fatty acid (FFA) levels were observed in Fgfr2 CKO mice. Although the expression of genes involved in adipocyte differentiation and lipid metabolism in the mesenteric WAT was essentially unchanged, the expression of uncoupling protein 2 potentially involved in energy dissipation was significantly increased. Among potential Fgf ligands for Fgfr2c, Fgf9 was preferentially expressed in the mesenteric WAT. The present findings indicate that Fgfr2c potentially activ...
The effect of the non-selective, 1-aminoindan-1,5-dicarboxylic acid (AIDA), and selective (3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-(cis-4- methoxycyclohexyl) methanone (JNJ16259685),...Full Text Available
G protein-coupled receptors (GPCRs) are known to modulate intracellular effectors involved in cardiac function. We recently reported homocysteine (Hcy)-induced ERK-phosphorylation was suppressed...Full Text Available
The metabotropic glutamate receptor 7 (mGluR7) has been reported to be involved in cocaine and alcohol self-administration. However, the role of mGluR7 in relapse to drug seeking is unknown....Full Text Available
Several examples of agonist-directed trafficking of receptor signalling at 5-HT2A and 5-HT2C receptors have been reported that involve independent downstream transduction pathways. We now report the functional selectivity of a series of chemically diverse agonists at human (h)5-HT2A, h5-HT2B and h5-HT2C-VSV by examining two related responses, the upstream activation of Gq/11 proteins in comparison with its associated cascade of calcium mobilisation. At the h5-HT2A receptor, d-lysergic acid diethylamide (LSD) and the antiparkinsonian agents lisuride, bromocriptine and pergolide exhibit a higher potency for Gq/11 activation than calcium release in contrast with all the other tested ligands such as 5-HT, mCPP and BW723C86, that show an opposite preference of signalling pathway. Comparable observations are made at h5-HT2B and h5-HT2C-VSV receptors, suggesting a similar mechanism of ...
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...
The T cell receptor is a fundamental mediator of the adaptive immune responses, since TR ab on T cells recognize foreign structures (peptides derived from processed antigens) bound to the major histocompatibility complex (MHC) on APC cells. In the present study, we report the cloning of six TRB chains cDNA sequences from gilthead sea bream (Sparus aurata), a fish of high economical impact in South Mediterranean aquaculture. The V-BETA domains have the canonical features of known teleost and mammalian TR V-BETA domains and have been divided in four different subgroups. A multiple alignment of the six sea bream TRB chains with other known TRB sequences was assembled and showed the conservation of the four cysteine residues involved in disulphide bonds and of some amino acids with an importan...
The anticonvulsant drugs carbamazepine, phenobarbital, trimethadione, valproic acid and ethosuximide at pharmacologically relevant concentrations inhibit (/sup 3/H)diazepam binding to astrocytes in primary cultures but have much less effect on a corresponding preparation of neurons. Phenytoin as well as pentobarbital (which is not used chronically as an anticonvulsant) are equipotent in the two cell types. The convulsants picrotoxinin and pentylenetetrazol, the convulsant benzodiazepine RO 5-3663 and the two convulsant barbiturates DMBB and CHEB similarly inhibit diazepam binding to astrocytes but have little effect on neurons. On the basis of these findings it is suggested that these convulsants and anticonvulsants owe at least part of their effect to an interaction with the astrocytic benzodiazepine receptor, perhaps by interference with a calcium channel.
Proton pump inhibitors are highly successful in treating gastroesophageal reflux disease, but a significant proportion of patients have persistent symptoms from weakly or nonacidic reflux. Transient lower esophageal sphincter relaxation (TLESR) represents the dominant mechanism of gastroesophageal reflux and has therefore become the most intensely investigated therapeutic target. The triggering of TLESR involve the vagal pathways and the ?-aminobutyric type B (GABA(B)) and metabotropic glutamate type 5 (mGluR5) receptors. Baclofen is a GABA(B) receptor agonist that is effective in inhibiting TLESR and reducing the number of reflux episodes, but is associated with significant central nervous system (CNS) side effects. The newer GABA(B) agonists, such as AZD9343 and AZD3355, and mGluR5 antag...
Serotonin is one of the neurotransmitters found in the brain and mediates brain functions. It is very well known that serotonin related brain abnormalities are exerted mainly via serotonin receptors in a similar manner to other neurotransmitters found in the brain. Recently, it has also been found that serotonin is involved in Alzheimer's disease either directly or indirectly by its actions on serotonergic neurons. To understand and treat the diseases caused by abnormalities in the serotonergic system in the brain, it is certain that its mechanism of function has to be well investigated. So far several 5-HT receptors and receptor subtypes have been well characterized. Moreover, serotonin agonists and antagonists acting on specific receptors are chemically synthesized and are now available for the prevention or treatment of serotonergic related diseases. In recent years, a great ...
Two mesoscopic SQUID rings which are far from each other are considered. A source of two-mode nonclassical microwaves irradiates the two rings with correlated photons. The Josephson currents are in this case quantum mechanical operators, and their expectation values with respect to the density matrix of the microwaves yield the experimentally observed currents. Classically correlated (separable) and quantum mechanically correlated (entangled) microwaves are considered, and their effect on the Josephson currents is quantified. Results for two different examples that involve microwaves in number states and coherent states are derived. It is shown that the quantum statistics of the tunnelling electron pairs through the Josephson junctions in the two rings are correlated.
Aims: Serotonin (5-hydroxytryptamine 3; 5-HT3) receptors are involved in chemotherapy-induced nausea and vomiting (CINV), and 5-HT3 antagonists are part of the `gold standard' antiemetic treatment during chemotherapy. We investigated the correlation of common variants in 5-HT3 receptor subunit genes with the occurrence of CINV. Materials & methods: A total of 110 previously characterized chemotherapy-naive women with primary breast cancer treated with anthracycline-containing chemotherapy served as a study group for mutational analysis by direct sequencing. Eight common SNPs in the 5-HT3 receptor genes, HTR3A, HTR3B, HTR3D and HTR3E, were selected for association analysis. Results: A nonsynonymous variant in HTR3D, p.G36A (rs6443930), was found to be over-represented in nonresponders, assu...
The two-compartment radioassay for microbial kinetics based on continuous measurement of the {sup 14}CO{sub 2} released by bacterial metabolism of 14C-labeled substrate offers a valuable approach to testing the potency of antimicrobial drugs. By using a previously validated radioassay with gram-positive and gram-negative bacteria, a group of protein synthesis inhibitors was evaluated for their effect on microbial growth kinetics. All tested drugs induced changes in both the slopes and intercepts of the growth curves. An exponential growth model was applied to quantify the drug effect on the processes of bacterial {sup 14}CO{sub 2} liberation and cell generation. The response was measured in terms of a generation rate constant. A linear dependence of the generation rate constant on the dose of spectinomycin was observed with Escherichia coli. Sigmoidal-shaped curves were found in the assays of chloramphenicol and tetracycline. The implications of dose-response ...
The contribution of platelets and clotting factors in thrombosis on cardiovascular prostheses had been quantified with several tracers. Thrombus formation in vivo could be measured semiquantitatively in animal models and patients with indium-111, Technetium-99m labeled platelets, iodine-123, iodine-131 labeled fibrinogen, and In-111 and Tc-99m labeled antibody to the fibrinogen-receptor on the platelet- membrane, or fibrin. The early studies demonstrated that certain platelet-inhibitors, e.g. sulfinpyrazone, aspirin or aspirin- persantine increased platelet survival time with mechanical valves implanted in the baboon model and patients. Thrombus localization by imaging is possible for large thrombus on thrombogenic surface of prosthesis in the acute phase. The majority of thrombus was found in the sewing ring (Dacron) in the acute phase in both the mechanical and tissue valves. The amount of retained thrombus in both mechanical and tissue ...
Background. In multiple myeloma 5 different infiltration patterns can be differentiated: 1. Normal appearance of bone marrow, 2. focal involvement, 3. homogeneous diffuse infiltration, 4. combined diffuse and focal infiltration, 5. 'salt-and pepper' pattern with inhomogeneous bone marrow with interposition of fat islands. Methods. For the fast and total acquisition of all patterns a combination of a T1-weighted spin echo sequence and a fat suppression technique is superior. The focal involvement is clearly demonstrated as areas of high signal intensity on e.g. STIR images. Diffuse involvement can be quantified objectively by calculation of the percentage of signal intensity increase after contrast material injection. MRI is superior to X-ray in focal and diffuse involvement. With ultrafast sequences a 'screening' of the whole red bone marrow as for myeloma infiltration is possible. ...
The receptor-associated protein (RAP) is a molecular chaperone that binds tightly to certain newly synthesized LDL receptor family members in the endoplasmic reticulum (ER) and facilitates their delivery...Full Text Available
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
Orphan G protein-coupled receptors (GPCRs) are receptors lacking endogenous ligands. Found by molecular biological analyses, they became the roots of reverse pharmacology, in which receptors are attempted...Full Text Available
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
AMPA receptors (AMPARs) are critical for synaptic plasticity, and are subject to alterations based on subunit composition and receptor trafficking to and from the plasma membrane. One of the...Full Text Available
Aldosterone has been suggested to elicit vessel contraction via a nongenomic mechanism. We tested this proposal in microdissected, perfused rabbit renal afferent arterioles. Aldosterone had no effect on internal diameter in concentrations from 10(-10) to 10(-5) mol/L, but aldosterone abolished the ability of 100 mmol/L KCl to induce vascular contraction. The inhibitory effect of aldosterone was observed from 1 pmol/L. The inhibitory effect was significant after 5 minutes and maximal after 20 minutes and was fully reversible. Actinomycin D (10(-6) mol/L) prolonged the effect of aldosterone. The effect was abolished by the mineralocorticoid receptor antagonist spironolactone (10(-7) mol/L) but not by the glucocorticoid receptor antagonist mifepristone (10(-6) mol/L). The K+-mediated increase of intracellular calcium concentration in afferent arterioles was not affected by aldosterone. Mineralocorticoid receptor was detected ...
In a given species, injected opioid peptides usually cause changes in temperature similar to those caused by nonpeptide opioids. The main effect in those species most studied, the cat, rat, and mouse, is an increase in the level about which body temperature is regulated; there is a coordinated change in the activity of thermoregulatory effectors such that hyperthermia is produced in both hot and cold environments. Larger doses may depress thermoregulation, thereby causing body temperature to decrease in the cold. Elicitation of different patterns of response over a range of environmental temperatures and studies with naloxone and naltrexone indicate that stimulation of a number of different receptors by both peptide and nonpeptide opioids can evoke thermoregulatory responses. ..beta..-Endorphin is readily antagonized by naloxone whereas methionine-enkephalin can act on naloxone-insensitive receptors. Moreover, synthetic peptide analogs do not ...
The widespread use of tobacco and alcohol among adolescents might be related to the ability of nicotine and ethanol to facilitate social interactions. To investigate the neurobehavioral mechanisms underlying the prosocial effects of nicotine and ethanol, we focused on social play behavior, the most characteristic social activity in adolescent rats. Social play behavior is rewarding, and it is modulated through opioid, cannabinoid and dopaminergic neurotransmission, which are also involved in the reinforcing properties of nicotine and ethanol. We found that nicotine and ethanol increased social play, without affecting locomotion or social exploration. Their effects depended on the level of social activity of the partner, and were comparable in familiar and unfamiliar environments. At doses that increased social play, nicotine and ethanol had no anxiolytic effects in the elevated plus-maze. By contrast, the prototypical anxiolytic drug diazepam reduced social play at ...
Most heat shock proteins (Hsps) function as molecular chaperones that help organisms to cope with stress. Although the best empirical evidence is related to heat shock, there is evidence that Hsps and their encoding genes are involved in resistance to other ecologically relevant types of stresses such as those imposed by high population density. We quantified density-dependent gene expression of large (i.e. Hsp40, Hsc70 and Hsp90) and small (Hsp20.5, Hsp20.6 and Hsp20.7) heat shock genes in neural tissue of fifth-instar nymphs of the Australian plague locust, Chortoicetes terminifera, using reverse transcription-quantitative PCR. Locusts are of particular interest when studying the influence of stress induced by high population density since they show an extreme form of phenotypic plastici...
The Surry low power and shutdown probabilistic risk analysis (PRA) is an ongoing project at Brookhaven National Laboratory (BNL) to identify and quantify potential accident scenarios that may occur in a pressurized water reactor (PWR) during low power and shutdown. It was initiated as a result of various incidents and accidents that have occurred within the United States and overseas. The project involves review and evaluation of PWR experience at shutdown, identification of accident scenarios, determination of methods to mitigate the accidents, and performance a level 1 PRA. An evaluation of accident progression, source terms and consequences has also been initiated. The results will be used to address issues related to shutdown conditions. The objective of this paper is to provide a progress report on the project, and to present the approach used as well as the preliminary results of the ongoing and completed tasks.
We quantified the resistance levels of transgenic rice plants, expressing Myxococcus xanthus protoporphyrinogen oxidase (PROTOX) in chloroplasts and mitochondria, to PROTOX inhibitors, acifluorfen, oxyfluorfen, carfentrazone-ethyl, and oxadiazon. We also determined whether active oxygen species-scavenging enzymes are involved in the resistance mechanism of transgenic rice. The transgenic rice line M4 was about >200-fold more resistant to oxyfluorfen than the wild-type (WT). M4 was also resistant to acifluorfen, carfentrazone-ethyl, and oxadiazon, but did not show multiple resistance to imazapyr and paraquat, which have different target sites. Acifluorfen, oxyfluorfen, carfentrazone-ethyl, and oxadiazon reduced the chlorophyll content in leaves of WT, but had minimal or no effect on M4. The...
Grating cloaks are a variation of dielectric carpet (or ground- plane) cloaks. The latter were introduced by Li and Pendry. In contrast to the numerical work involved in the quasi-conformal carpet cloak, the refractive-index profile of a conformal grating cloak follows a closed and exact analytical form. We have previously mentioned that finite-size conformal grating cloaks may exhibit better cloaking than usual finite-size carpet cloaks. In this letter, we directly visualize their performance using photorealistic ray-tracing simulations. We employ a Newtonian approach that is advantageous compared to conventional ray tracing based on Snell's law. Furthermore, we quantify the achieved cloaking quality by computing the cross-correlations of rendered images. The cross-correlations for the grating cloak are much closer to 100% (i.e., ideal) than those for the Gaussian carpet cloak.
This document is the report of a task group of the Radiation Therapy Committee of the AAPM and has been prepared primarily to advise hospital physicists involved in external beam treatment of patients with pelvic malignancies who have high atomic number (Z) hip prostheses. The purpose of the report is to make the radiation oncology community aware of the problems arising from the presence of these devices in the radiation beam, to quantify the dose perturbations they cause, and, finally, to provide recommendations for treatment planning and delivery. Some of the data and recommendations are also applicable to patients having implanted high-Z prosthetic devices such as pins, humeral head replacements. The scientific understanding and methodology of clinical dosimetry for these situations is still incomplete. This report is intended to reflect the current state of scientific understanding and technical methodology in clinical dosimetry for ...
Digital audio sampling is explained, and some of its implications in digital sound applications are discussed. Digital sound equipment is rapidly replacing analog recording devices as the state-of-the-art in audio technology. The philosophy of digital recording involves doing away with the continuously variable analog waveforms and turning the patterns into numbers. A digital recording device rapidly samples the incoming sounds, quantifying the signal into a series of numerical values (binary codes). Although digital sound eliminates many of the traditional analog problems, digital signal processing presents key problems in sampling rates and synchronization. Careful control is necessary to check signals through each step in the audio chain. The advantages of digital audio processing include increased signal-to-noise ratio, no flutter, transparent generation of copies, and sound manipulation. These benefits come with increased quality control ...
Biotin is an essential water-soluble vitamin crucial for maintaining normal body functions. The importance of biotin for human health has been under-appreciated but there is plenty of opportunity for future research with great importance for human health. Currently, carrying out predictions of biotin metabolism involves tedious manual manipulations. In this paper, we report the development of BiotinNet, an internet based program that uses Bayesian networks to integrate published data on various aspects of biotin metabolism. Users can provide a combination of values on the levels of biotin related metabolites to obtain the predictions on other metabolites that are not specified. As an inherent feature of Bayesian networks, the uncertainty of the prediction is also quantified and reported to...
Annual wormwood interference on soybean crop growth and yield may result from competition and allelopathy, which are modulated by crop management. Allelochemicals released by annual wormwood (e.g. artemisinin) may affect the crop directly or indirectly through the effect on the nitrogen fixing symbiont, Bradyrhizobium japonicum. The objectives were (i) to quantify the crop response (i.e. biomass production, nodulation and yield) to weed interference and (ii) to determinate the relative change of competition and allelopathy interferences, when a sublethal dose of herbicide is applied. Two split plot field experiments with three replications were used. The experiment involved a factorial combination of five weed-crop density (soybean/annual wormwood, plantsm^-^2) levels: D1, pure soybean, 40...
Leptospirillum ferriphilum and Acidithiobacillus caldus are two important acidophilic microorganisms involved in iron and sulfur oxidation during bioleaching. Cell adsorption to mineral surfaces is important for the direct leaching or contact leaching of minerals. In this study, we report the competitive adsorption of binary mixtures of L. ferriphilum LF-104 and A. caldus MTH-04 onto pyrite surfaces. The Langmuir adsorption parameter (CAm) indicated that these two bacteria underwent competitive adsorption to pyrite. Real-time quantitive PCR was used to quantify the relative amounts of L. ferriphilum and A. caldus adsorbed onto the surfaces of pyrite following exposure to a mixture of these two organisms. The adsorption of L. ferriphilum was not affected by A. caldus. However, adsorption of...
Managing service quality is vital to retain customer satisfaction and augment revenues for any business organization. Often it is difficult to assess service quality due to lack of quantifiable measures and limited data. In this paper, we present a hybrid approach based on SERVQUAL and fuzzy TOPSIS for evaluating service quality of urban transportation systems. The proposed approach consists of three steps. The first step involves development of a SERVQUAL based questionnaire to collect data for measuring transportation service quality. The participants provide linguistic assessments to rate the service quality criteria and the alternatives. In step 2, the linguistic ratings are combined through fuzzy TOPSIS to generate an overall performance score for each alternative. The alternative wit...
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
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
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
Analysts working at the International Data Centre in support of treaty monitoring through the Comprehensive Nuclear-Test-Ban Treaty Organization spend a significant amount of time reviewing hypothesized seismic events produced by an automatic processing system. When reviewing these events to determine their legitimacy, analysts take a variety of approaches that rely heavily on training and past experience. One method used by analysts to gauge the validity of an event involves examining the set of stations involved in the detection of an event. In particular, leveraging past experience, an analyst can say that an event located in a certain part of the world is expected to be detected by Stations A, B, and C. Implicit in this statement is that such an event would usually not be detected by Stations X, Y, or Z. For some well understood parts of the world, the absence of one or more 'expected' stations - or the presence of one or ...
The diffusion coefficients (De) in bentonite were measured to understand and quantify the influence of groundwater chemistry such as ionic strength and to quantify the alteration of smectite mineralogical transformations. (author)
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...
Gamma-aminobutyric acid type A receptor-associated protein (GABARAP) belongs to a family of small ubiquitin-like adaptor proteins implicated in intracellular vesicle trafficking and autophagy. We have used diffusion-ordered nuclear magnetic resonance spectroscopy to study the temperature and concentration dependence of the diffusion properties of GABARAP. Our data suggest the presence of distinct conformational states and provide support for self-association of GABARAP molecules. Assuming a monomer-dimer equilibrium, a temperature-dependent dissociation constant could be derived. Based on a temperature series of {sup 1}H{sup 15}N heteronuclear single quantum coherence nuclear magnetic resonance spectra, we propose residues potentially involved in GABARAP self-interaction. The possible biological significance of these observations is discussed with respect to alternative scenarios of oligomerization.
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...
The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the type of adrenergic receptor (AR) involved in the production of the major metabolite of this fatty acid. ({sup 14}C)AA was incubated with GPT-rings and the radiolabelled products were extracted and separated by TLC method. The medium was also assayed for radiolabelled immunoreactive PG's (iPG's) and leukotrienes (LT) B4 and C4 by RIA or Enzyme immunoassay (EIA) after exposure to various AR agonists. ({sup 14}C)AA was incorporated into GPT-rings and metabolized mainly into iPGE2 and smaller amounts into PGF2{alpha}. Trace amounts of PGD2 and 6-keto-PGF1{alpha} but not LTB4 or LTC4 were detected by RIA and/or EIA. Incubation of GPT rings for 15 minutes with isoproterenol and salbutamol resulted in a significant increase of PGE2 synthesis (optimum conc: 10{sup {minus}7}, 10{sup {minus}7}M respectively). In contrast, dobutamine, ...
The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the type of adrenergic receptor (AR) involved in the production of the major metabolite of this fatty acid. ["1"4C]AA was incubated with GPT-rings and the radiolabelled products were extracted and separated by TLC method. The medium was also assayed for radiolabelled immunoreactive PG's (iPG's) and leukotrienes (LT) B4 and C4 by RIA or Enzyme immunoassay (EIA) after exposure to various AR agonists. ["1"4C]AA was incorporated into GPT-rings and metabolized mainly into iPGE2 and smaller amounts into PGF2#alpha#. Trace amounts of PGD2 and 6-keto-PGF1#alpha# but not LTB4 or LTC4 were detected by RIA and/or EIA. Incubation of GPT rings for 15 minutes with isoproterenol and salbutamol resulted in a significant increase of PGE2 synthesis (optimum conc: 10"-"7, 10"-"7M respectively). In contrast, dobutamine, norepinephrine, phenylnephrine and xylazine (up to ...
We studied the effect of extracellular Ca"2"+ concentration ([Ca"2"+]_e) on adipocyte differentiation. Preadipocytes exposed to continuous [Ca"2"+]_e higher than 2.5 mmol/l accumulated little or no cytoplasmic lipid compared to controls in 1.8 mmol/l [Ca"2"+]_e. Differentiation was monitored by Oil Red O staining of cytoplasmic lipid and triglyceride assay of accumulated lipid, by RT-PCR analysis of adipogenic markers, and by the activity of glycerol-3-phosphate dehydrogenase (GPDH). Elevated [Ca"2"+]_e inhibited expression of peroxisome proliferator-activated receptor #gamma#, CCAAT/enhancer binding protein #alpha#, and steroid regulatory binding element protein. High [Ca"2"+]_e significantly inhibited differentiation marker expression including adipocyte fatty acid binding protein, and GPDH. The decrease in Pref-1 expression that accompanied differentiation also was prevented by high [Ca"2"+]_e. Treatment of 3T3-L1 cells with high [Ca"2"+]_e did not significantly ...
Acetylcholine and other neurotransmitters play unique trophic roles in brain development. Accordingly, drugs and environmental toxicants that promote or interfere with neurotransmitter function evoke neurodevelopmental abnormalities by disrupting the timing or intensity of neurotrophic actions. The current review discusses three exposure scenarios involving acetylcholine systems: nicotine from maternal smoking during pregnancy, exposure to environmental tobacco smoke (ETS), and exposure to the organophosphate insecticide, chlorpyrifos (CPF). All three have long-term, adverse effects on specific processes involved in brain cell replication and differentiation, synaptic development and function, and ultimately behavioral performance. Many of these effects can be traced to the sequence of cellular events surrounding the trophic role of acetylcholine acting on its specific cellular receptors and associated signaling cascades. ...
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
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.
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
The adenovirus fiber knob causes the first step in the interaction of adenovirus with cell membrane receptors. To obtain information on the receptor binding site(s), the interaction of labeled cell...Full Text Available
BackgroundThe epidermal growth factor receptor (Egfr) with its numerous ligands has fundamental roles in development, cell differentiation and physiology. Dysfunction of the receptor-ligand...Full Text Available
1. The effects of stimulation of atrial receptors on hypothalamic neurosecretory cells were investigated in anaesthetized dogs and cats. Atrial receptors were activated by stretching the left and the...Full Text Available
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
A specific immunoglobulin, the receptor antibody, can be found in most patients with myasthenia gravis. In order to study the kinetic properties of this antibody, serial determinations of receptor antibody,...Full Text Available
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
Activation of beta-adrenergic or muscarinic acetylcholine receptors expressed in transfected cells or epidermal growth factor receptors in human keratinocytes produces 15% to 200% changes in cellular...Full Text Available
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
Reproductive aging in males is characterized by a diminution in sexual behavior beginning in middle age. We investigated the relationships among testosterone, androgen receptor (AR) and estrogen...Full Text Available
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
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
Histamine and the histamine receptors are important regulators of a plethora of biological processes, including immediate hypersensitivity reactions and acid secretion in the stomach. In these...Full Text Available
Halothane, chloroform, and carbon tetrachloride, in the vapor and liquid phases, stimulate the water receptor of the blowfly Phormia regina. There are three successive phases of response to long-lasting...Full Text Available
The processes controlling total carbon (C) storage and release from the terrestrial biosphere are still poorly quantified. We conclude from analysis of paleodata and climatebiome model output that terrestrial C exchanges since the last glacial maximum (LGM) were dominated by slow processes of C sequestration in soils, possibly modified by C starvation and reduced water use efficiency of trees during the LGM. In contrast, future C cycling will be dominated by human activities, not only from increasing C release with burning of fossil fuels, and but also from indirect effects which increase C storage in the terrestrial biosphere and decrease C storage in the biosphere. Comparison of the positive and negative C flux processes involved suggests that if the C sequestration processes are important, they likely will be so during the next few decades, gradually being counteracted by the C release processes. (Copyright (c) l993 Kluwer Academic ...
A new method is being developed to quickly screen for the human exposure potential to polycyclic aromatic hydrocarbons (PAHs) and organochlorines (OCs). The development involves two key elements: identifying suitable signals that represent intracellular changes that are specific to PAH and OC exposure, and constructing a device to guide the biological cell growth so that signals from individual cells are consistent and reproducible. We are completing the identification of suitable signals by using synchrotron radiation-based (SR) Fourier-transform infrared (FTIR) spectromicroscopy in the mid-infrared region (4000-400 cm-1). Distinct changes have been observed in the IR spectra after treatment of human cells in culture medium with PAHs and OCs. The potential use of this method for detecting exposure to PAHs and OCs has been tested and compared to a reverse transcription polymerase chain reaction (RT-PCR) assay that quantifies increased ...
Recently, many experiments designed to quantify the parameters involved in microgravity two-phase flow have been performed. These experiments give significant insight to the differences between the flow regimes in 1-g and microgravity. However, the new correlations for pressure drop, heat transfer, and the flow regime maps are yet to be implemented into analytical methods. The purpose of this study is to model a KC-135 microgravity experiment, using the thermal-hydraulic does RELAP5/MOD2 and ATHENA. A comparison of these experimental results to code calculations from RELAP5/MOD2 and ATHENA is shown. Results show little difference between the ATHENA and the RELAP5 calculations. Also, modifications are made to the two-phase flow regime map in RELAP5 to model microgravity predictions. There is a substantial difference between the code's calculation before and after the changes were implemented. The heat transfer correlations of the code ...
Recently, many experiments designed to quantify the parameters involved in microgravity two-phase flow have been performed. These experiments give significant insight to the differences between the flow regimes in 1-g and microgravity. However, the new correlations for pressure drop, heat transfer, and the flow regime maps are yet to be implemented into analytical methods. The purpose of this study is to model a KC-135 microgravity experiment, using the thermal-hydraulic does RELAP5/MOD2 and ATHENA. A comparison of these experimental results to code calculations from RELAP5/MOD2 and ATHENA is shown. Results show little difference between the ATHENA and the RELAP5 calculations. Also, modifications are made to the two-phase flow regime map in RELAP5 to model microgravity predictions. There is a substantial difference between the code's calculation before and after the changes were implemented. The heat transfer correlations of the code should be ...
In Oslo, traffic has been one of the dominating sources of air pollution in the last decade. In one part of the city where most traffic collects, two tunnels were built. A series of before and after studies was carried out in connection with the tunnels in use. Dispersion models were used as a basis for estimating exposure to nitrogen dioxide and particulate matter in two fractions. Exposure estimates were based on the results of the dispersion model providing estimates of outdoor pollutant concentrations on an hourly basis. The estimates represent concentrations in receptor points and in a square kilometre grid. The estimates were used to assess development of air pollution load in the areas, compliance with air quality guidelines, and to provide a basis for quantifying exposure-effect relationships in epidemiological studies. After both tunnels were taken in use, the pollution levels in the study areas were lower than when the traffic was on ...
BackgroundThe effects of single or combined histamine H1-receptor and leukotriene CysLT1-receptor antagonism on nasal adenosine monophosphate (AMP) challenge...Full Text Available
BackgroundThe orphan nuclear receptor estrogen-related receptor α (ERRα) is a member of the nuclear receptor superfamily. It was identified through a search for genes...Full Text Available
The mechanism of action of Clostridium difficile enterotoxin A (CA), of Escherichia coli enterotoxin (STa) and of cholera toxin (CT), which are known to cause severe diarrhea, were studied in a preparation of ligated jejunal loops of anesthetized rats in vivo. The toxins were administered intraluminally. Pharmacological agents, which were tested for their potency to influence toxin-related effects, were administered subcutaneously. Net fluid transport was determined gravimetrically, prostaglandin (PG) E_2-output into the lumen, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) contents in the mucosa were measured by radioimmunoassay, serotonin-(5-HT)-output into the lumen was determined by high performance liquid chromatography. The histopathological effects of CA and CT were examined by light- and scanning electron microscopy. All three toxins caused net fluid secretion (FS). 5-HT_2-(ketanserin) and 5-HT_3-receptor antagonists ...
The sequence segment 181-200 of the Torpedo nicotinic acetylcholine receptor (nAChR) #alpha#subunit forms a binding site for #alpha#-bungarotoxin (#alpha#-BTX). Synthetic peptides corresponding to the homologous sequences of human, calf, mouse, chicken, frog, and cobra muscle nAChR #alpha#1 subunits were tested for their ability to bind "1"2"5I-#alpha#-BTX, and differences in #alpha#-BTX affinity were determined by using solution (IC_5_0s) and solid-phase (K_ds) assays. Panels of overlapping peptides corresponding to the complete #alpha#1 subunit of mouse and human were also tested for #alpha#-BTX binding, but other sequence segments forming the #alpha#-BTX site were not consistently detectable. The role of a putative vicinal disulfide bound between Cys-192 and -193, relative to the Torpedo sequence, was determined by modifying the peptides with sulfhydryl reagents. Reduction and alkylation of the peptides decreased #alpha#-BTX binding, whereas oxidation of the ...
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 ...
Neurotensin (NT) and its high affinity receptor (NTR1) are involved in several neoplastic processes. Thus, NT-based radiopharmaceuticals are potential tracers for targeted diagnosis and therapy of NTR-positive tumours. A new analogue based on NT(8-13), NT-XIX, with the three enzymatic cleavage sites stabilised, was synthesised and tested. The synthesis was performed by Boc strategy. Labelling with "9"9"mTc/"1"8"8Re was performed using the tricarbonyl technique. Metabolic stability was tested in vitro and in vivo. NT-XIX was further characterised in vitro in HT-29 cells and in vivo in nude mice with HT-29 xenografts. NT-XIX showed much longer half-lives than non-stabilised analogues. Binding to NTR1 was highly specific, although the affinity was lower than that of natural NT. Bound activity rapidly internalised into HT-29 cells and 50% remained trapped after 24 h. In the time-course biodistribution, the highest uptake was found in the tumour at ...
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 ...
Background. In multiple myeloma 5 different infiltration patterns can be differentiated: 1. Normal appearance of bone marrow, 2. focal involvement, 3. homogeneous diffuse infiltration, 4. combined diffuse and focal infiltration, 5. 'salt-and pepper' pattern with inhomogeneous bone marrow with interposition of fat islands. Methods. For the fast and total acquisition of all patterns a combination of a T1-weighted spin echo sequence and a fat suppression technique is superior. The focal involvement is clearly demonstrated as areas of high signal intensity on e.g. STIR images. Diffuse involvement can be quantified objectively by calculation of the percentage of signal intensity increase after contrast material injection. MRI is superior to X-ray in focal and diffuse involvement. With ultrafast sequences a 'screening' of the whole red bone marrow as ...
An /alpha//sub 2/-adrenergic receptor subtype has been cloned from a human kidney cDNA library using the gene for the human platelet /alpha//sub 2/-adrenergic receptor as a probe. The deduced amino acid sequence resembles the human platelet /alpha//sub 2/-adrenergic receptor and is consistent with the structure of other members of he family of guanine nucleotide-binding protein-coupled receptors. The cDNA was expressed in a mammalian cell line (COS-7), and the /alpha//sub 2/-adrenergic ligand (/sup 3/H)rauwolscine was bound. Competition curve analysis with a variety of adrenergic ligands suggests that this cDNA clone represents the /alpha//sub 2/B-adrenergic receptor. The gene for this receptor is on human chromosome 4, whereas the gene for the human platelet /alpha//sub 2/-adrenergic receptor (/alpha//sub 2/A) lies on chromosome 10. This ...
CD44, a transmembrane receptor for hyaluronic acid, is implicated in various adhesion-dependent cellular processes, including cell migration, tumor cell metastasis and invasion. Recent studies demonstrated that CD44 expressed in cancer cells can be proteolytically cleaved at the ectodomain by membrane type 1-matrix metalloproteinase (MT1-MMP) to form soluble CD44 and that CD44 cleavage plays a critical role in cancer cell migration. Here, we show that transforming growth factor-b (TGF-b), a multifunctional cytokine involved in cell proliferation, differentiation, migration and pathological processes, induces MT1-MMP expression in MDA-MB-435s cells. TGF-b-induced MT1-MMP expression was blocked by the specific extracellular regulated kinase-1/2 (ERK1/2) inhibitor PD98059 and the specific pho...
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, indicating a major role for TRPC1 in NFAT ...
Calcium (Ca) plays an important role in regulating various cellular processes. In a variety of cell types, Ca signaling occurs within microdomains where channels deliver localized pulses of Ca which activate a nearby collection of Ca-sensitive receptors. The small number of channels involved ensures that the signaling process is stochastic. The aggregate response of several thousand of these microdomains yields a whole-cell response which dictates the cell behavior. Here, we study analytically the statistical properties of a population of these microdomains in response to a trigger signal. We apply these results to understand the relationship between Ca influx and Ca release in cardiac cells. In this context, we use a first passage time approach to show analytically how Ca release in the whole cell depends on the single channel kinetics of Ca channels and the properties of microdomains. Using these results, we explain the underlying mechanism ...
The role of intracellular Ca2+ (Ca2+i) on hematopoiesis was investigated in long term bone marrow cultures using cytokines and agonists of P2 receptors. Cytokines interleukin 3 and granulocyte/macrophage colony stimulator factor promoted a modest increase in Ca2+i concentration ([Ca2+]i) with activation of phospholipase Cgamma, MEK1/2, and Ca2+/calmodulin kinase II. Involvement of protein kinase C was restricted to stimulation with interleukin 3. In addition, these cytokines promoted proliferation (20 times) and an increase in the Gr-1(-)Mac-1+ population with participation of gap junctions (GJ). Nevertheless ATP, ADP, and UTP promoted a large increase in [Ca2+]i, moderate proliferation (6 times), a reduction in the primitive Gr-1(-)Mac-1(-)c-Kit+ population, and differentiation into macrophages without participation of GJ. It is likely that Ca2+i participates as a regulator of hematopoietic signaling: moderate increases in [Ca2+]i would be ...
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 ...
It is well known that contact with metals can be responsible for allergic contact dermatitis; also, there is experimental evidence that nickel ions are readily available on the surface of used coins containing nickel and copper. The aim of this study was to prove that metal powders of nickel (Ni), cobalt (Co) and chromium (Cr) dispersed in synthetic sweat are oxidised into respective ions that can permeate the skin. Suspensions of 5 g of metal powder (Ni, Co and Cr) in 100 mL of synthetic sweat at pH 6.5 were prepared and shaken with a stirring plate at room temperature for 30 min. Human skin membranes were set up in Franz-diffusion cells and 2 mL of the freshly made suspension were applied to the outer surface of the skin for 24h. The appearance of metal ions in the aqueous receptor phase (NaCl 0.9%) was quantified by Electro Thermal Atomic Absorption Spectroscopy (ETAAS). Also, metals ions were analysed using Differential Pulse Polarography ...
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...
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 promoters to drive the luciferase reporter gene expression revealed ...
The hypothesis that intracellular Ca/sup 2 +/ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca/sup 2 +/ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin-stimulated glucose transport without affecting basal activity. The ability of insulin to stimulate glucose uptake in quin-2-loaded cells could be partially restored by preincubating cells with buffer supplemented with 1.2 mM CaCl/sub 2/ and the Ca/sup 2 +/ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl/sub 2/ from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation and the ability of insulin to inhibit cAMP-stimulated lipolysis without affecting their basal activities. Incubation of cells with 100 ..mu..M quin-2 or quin-2 AM had ...
The hypothesis that intracellular Ca"2"+ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca"2"+ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin-stimulated glucose transport without affecting basal activity. The ability of insulin to stimulate glucose uptake in quin-2-loaded cells could be partially restored by preincubating cells with buffer supplemented with 1.2 mM CaCl_2 and the Ca"2"+ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl_2 from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation and the ability of insulin to inhibit cAMP-stimulated lipolysis without affecting their basal activities. Incubation of cells with 100 #mu#M quin-2 or quin-2 AM had no effect on intracellular ...
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
The GABA-modulating and GABA-mimetic activities of the monoterpenoid thymol were explored on human GABAA and Drosophila melanogaster...Full Text Available
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
The plant hormone cytokinin is perceived by membrane-located sensor histidine kinases. Arabidopsis (Arabidopsis thaliana) possesses three cytokinin receptors: ARABIDOPSIS HISTIDINE...Full Text Available
BackgroundThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The...Full Text Available
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
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
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
Taste cells use multiple signaling mechanisms to generate appropriate cellular responses to discrete taste stimuli. Some taste stimuli activate G protein coupled receptors (GPCRs) that cause calcium...Full Text Available
The normal physiological contraction of the urinary bladder, which is required for voiding, is predominantly mediated by muscarinic receptors, primarily the M3 subtype, with the M2...Full Text Available
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
Nuclear hormone receptors comprise a characteristic family of transcription factors found in vertebrates, insects and nematodes. Here we show by cDNA and gene cloning that a Cnidarian, Tripedalia...Full Text Available
We previously reported that global deletion of insulin receptor substrate protein 1 (Irs1) extends lifespan and increases resistance to several age-related pathologies in female mice....Full Text Available
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
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
The neonatal Fc receptor FcRn provides IgG molecules with their characteristically long half-lives in vivo by protecting them from intracellular catabolism and then returning them to...Full Text Available
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
The presence of albumin structures with the capacity to bind to a surface receptor in group C and G streptococci was studied in serum samples from 45 mammalian species representing 15 different orders,...Full Text Available
Epidermal growth factor receptor (EGFR) kinase domain mutations hyperactivate the kinase and confer kinase addiction of the non-small-cell lung cancer (NSCLC) tumor...Full Text Available
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
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
Epidermal growth factor receptor (EGFR) related therapies – mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example,...Full Text Available
BackgroundPolymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung...Full Text Available
Antagonists for kainate receptors (KARs), a family of glutamate-gated ion channels, are efficacious in a number of animal models of neuropathologies, including epilepsy, migraine pain, and anxiety....Full Text Available
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
Gastrointestinal stromal tumors (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the KIT or PDGFRA receptor tyrosine kinases are present...Full Text Available
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
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
We have characterized the kinetic response of gene targets throughout the murine genome to transcriptional modulation by the glucocorticoid receptor (GR). In contrast to a model in which multiple genes...Full Text Available
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
The receptors for IGF-I (IGF-IR) and insulin (IR) have been implicated in physiological cardiac growth, but it is unknown whether IGF-IR or IR signaling are critically required. We generated mice with...Full Text Available
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
Osteoblasts are the primary cells responsible for bone formation. They also support osteoclast formation from bone marrow precursors in response to osteotropic factors by inducing receptor activator...Full Text Available
The murine cytomegalovirus (MCMV) M33 gene is conserved among all betaherpesviruses and encodes a homologue of seven-transmembrane receptors (7TMR) with the capacity for constitutive signaling. Previous...Full Text Available
Dysregulation of glutamate neurotransmission may play a role in cognitive deficits in schizophrenia. Manipulation of glutamate signaling using drugs acting at metabotropic glutamate receptors...Full Text Available
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
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
The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated...Full Text Available
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
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
Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine's abuse-related effects. Here, we sought to confirm and ...Full Text Available
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
Polyclonal antibodies were raised in rabbits by immunization with free peptides corresponding to positions 197-222 of the human beta 1-adrenergic receptor (beta 1 peptide) and the corresponding sequence...Full Text Available
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
The acetylcholine receptor from the electric tissue of Torpedo californica is a large, integral membrane protein containing four different types of polypeptide chains. The structure of the purified...Full Text Available
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights...Full Text Available
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
IntroductionVarious multigene predictors of breast cancer clinical outcome have been commercialized, but proved to be prognostic only for hormone receptor (HR) subsets overexpressing...Full Text Available
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
Gamma interferon (IFN-γ) and the cellular responses induced by it are essential for controlling mycobacterial infections. Most patients bearing an IFN-γ receptor ligand-binding chain...Full Text Available
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
SummaryThe transcriptional co-repressor SMRT utilizes two major receptor interacting domains (RID1 and RID2) to mediate nuclear receptor (NR) signaling through epigenetic modification....Full Text Available
BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...Full Text Available
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
The 37/67 kDa laminin receptor (LAMR) is a multifunctional protein, acting as an extracellular receptor, localizing to the nucleus, and playing roles in rRNA processing and ribosome assembly....Full Text Available
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
We have cloned and characterized a 77-kDa oestrogen receptor (ER) from an oestrogen-independent subclone of the MCF-7 human breast cancer cell line. This receptor contains an in-frame, tandem duplication...Full Text Available
The mechanisms involved in the glacial inception are still poorly constrained due to a lack of high resolution and cross-dated climate records at various locations. Using air isotopic measurements in the recently drilled NorthGRIP ice core, we show that no evidence exists for stratigraphic disturbance of the climate record of the last glacial inception ({proportional_to}123-100 kyears BP) encompassing Dansgaard-Oeschger events (DO) 25, 24 and 23, even if we lack sufficient resolution to completely rule out disturbance over DO 25. We quantify the rapid surface temperature variability over DO 23 and 24 with associated warmings of 10{+-}2.5 and 16{+-}2.5 C, amplitudes which mimic those observed in full glacial conditions. We use records of {delta}{sup 18}O of O{sub 2} to propose a common timescale for the NorthGRIP and the Antarctic Vostok ice cores, with a maximum uncertainty of 2,500 years, and to examine the interhemispheric sequence of events ...
A three-dimensional, three-phase, multiple-component numerical simulator was developed to investigate transport and growth of microorganisms in porous media and the impacts of microbial activities on oil recovery. The microbial activities modeled in this study included: (1) growth, retention, chemotaxis, and end product inhibition of growth, (2) the formation of metabolic products, and (3) the consumption of nutrients. Major mechanisms for microbial enhanced oil recovery (MEOR) processes were modeled as follows: (1) improvement in sweep efficiency of a displacement process due to in situ plugging of highly-permeable production zones by cell mass or due to improved mobility control achieved by increasing the viscosity of the displacing fluid with a biopolymer, and (2) solubilization and mobilization of residual oil in porous media due to the reduction of the interfacial tension between oleic and aqueous phases by the production of a biosurfactant. The numerical solutions for ...
The objective of this paper is to reveal to what degree bio-based jet fuels (bio-jet) can reduce greenhouse gas (GHG) emissions from the US aviation sector. A model of the supply and demand chain of bio-jet involving farmers, bio-refineries, airlines, and policymakers is developed by considering factors that drive the decisions of actors (i.e. decision-makers and stakeholders) in the life cycle stages. Two kinds of feedstock are considered: oil-producing feedstock (i.e. camelina and algae) and lignocellulosic biomass (i.e. corn stover, switchgrass, and short rotation woody crops). By factoring in farmer/ feedstock producer and bio-refinery profitability requirements, land availability and suitability, as well as a time delay factor, a more realistic estimate of the level of bio-jet supply and emissions reduction can be developed under different oil price assumptions. Factors that drive bio-jet GHG emissions and unit production costs from each feedstock are ...
The sulfur-iodine (SI) thermochemical cycle is one of the main candidate methods to produce hydrogen from non-fossil sources like nuclear (GEN IV reactor) or solar thermal power. A major issue for the successful implementation of the SI cycle is the selection of technically viable and economic materials for construction of process components, particularly heat exchangers. Challenging conditions are encountered in each of the three sections of the SI cycle due to the corrosive chemicals present, including sulfuric acid, iodine, hydroiodic acid, sulfur dioxide, hydrogen, oxygen, and others. In Section I, aqueous, non-aqueous (liquid iodine), and gaseous multi-component phases are present at about 120 {sup o}C and 0.7 MPa. Section II involves gaseous and aqueous phases of sulfuric acid, sulfur dioxide, and oxygen at up to about 830 {sup o}C and 3.6 MPa. In Section III , aqueous, non-aqueous, and gaseous phases, at up to 310 {sup o}C and 2.2 MPa, containing iodine, ...
Apoptosis is a pattern of cell death involving nuclear pycnosis, cytoplasmic condensation, and karyorrhexis. Apoptosis induced by continuous irradiation with gamma rays (externally given by a 137Cs source) or with beta rays (from tritiated water injected ip) was quantified in the crypts of two portions of mouse bowel, the small intestine and descending colon. The time-course change in the incidence of apoptosis after each type of radiation could be explained on the basis of the innate circadian rhythm of the cells susceptible to apoptotic death and of the excretion of tritiated water (HTO) from the body. For 6-h continuous gamma irradiation at various dose rates (0.6-480 mGy/h) and for 6 h after injection of HTO of various radioactivities (0.15-150 GBq per kg body wt), the relationships between dose and incidence of apoptosis were obtained. Survival curves were then constructed from the curves for dose vs incidence of apoptosis. For the ...
'The objective of this project is to provide a means to optimize ligand architecture for f-block metal recognition. The authors strategy builds on an innovative and successful molecular modeling approach in developing polyether ligand design criteria for the alkali and alkaline earth cations. The hypothesis underlying this proposal is that differences in metal ion binding with multidentate ligands bearing the same number and type of donor groups are primarily attributable to intramolecular steric factors. They propose quantifying these steric factors through the application of molecular mechanics models. The research involves close integration of theoretical and experimental chemistry. The experimental work entails synthesizing novel ligands and experimentally determining structures and binding constants for metal ion complexation by series of ligands in which architecture is systematically varied. The theoretical work entails using ...
BackgroundBrucellosis is a zoonosis of veterinary, public health and economic significance in most developing countries. Human brucellosis is a severely debilitating disease that...Full Text Available
the revealed stage of T Tauri star evolution, is only a mere shadow of its former self. Once primary accretion starts, one has the (poorly quantified) ...
The study design included an in vivo laboratory study. The objective of the study is to quantify the kinematics of the lumbar spinous processes in asymptomatic patients during un-restricted functional...Full Text Available
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 ...
The work presented here demonstrates the ability of proton-transfer-reaction mass spectrometry (PTR-MS) to perform fast-response measurements of volatile organic compounds (VOCs) (including methanol, acetonitrile, acetaldehyde, acetone, PAN-type compounds, alpha- and beta-pinene, nopinone and pinonaldehyde) at the pptv level and its versatile applicability in the field of environmental trace gas analysis. Laboratory and field experiments including various calibration techniques and intercomparisons with other measurement techniques such as gas chromatography, atmospheric pressure chemical ionization and Fourier transformation infrared spectroscopy were performed providing a first characterization of the PTR-MS instrument performance (sensitivity, detection limit, precision, accuracy). Typically a detection limit (S/N=2) of 50 pptv for a 10 s signal integration time, a precision of 5 % and an accuracy in the range between 10 and 25 % were observed. Due to its compactness and ruggedness ...
Incorporation of /sup 32/P from (gamma-32P)ATP into tyrosine residues of the insulin-like growth factor (IGF)-II receptor was observed in a Triton X-100-insoluble fraction of rat adipocyte plasma membranes. IGF-II receptor phosphorylation proceeded to a stoichiometry of approximately 0.5 mol of phosphate/IGF-II binding site after 10 min of incubation at 4 degrees C. A Km for ATP of 6 microM was calculated for this phosphorylation reaction. Addition of IGF-II caused an approximately 2-fold increase in tyrosine phosphorylation of the IGF-II receptor in this preparation. In contrast, phosphorylation of angiotensin II by the Triton X-100 washed membranes was not stimulated by IGF-II. Incubation of purified receptor immobilized on IGF-II agarose or of receptor-enriched low density microsomal membranes with (gamma-32P)ATP did not result in appreciable incorporation of (/sup 32/P)phosphate ...
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 ...
The murine 3T3-L1 fibroblast under appropriate incubation conditions differentiates into an adipocyte phenotype. This 3T3-L1 adipocyte exhibits many of the morphologic, biochemical, and insulin-responsive features of the normal rodent adipocyte. Using quantitative electron microscopic (EM) autoradiography we find that, when /sup 125/I-insulin is incubated with 3T3-L1 adipocytes, the ligand at early times of incubation localizes to the plasma membrane of the cell preferentially to microvilli and coated pits. When the incubation is continued at 37 degrees C, /sup 125/I-insulin is internalized by the cells and preferential binding to the villous surface is lost. With the internalization of the ligand, two intracellular structures become labeled, as determined by the method of hypothetical grain analysis. These include large clear, presumably endocytotic, vesicles and multivesicular bodies. Over the first hour of incubation the labeling of these structures increases in parallel, but in the ...
3-Quinuclidinyl benzilate (QNB) is a potent muscarinic antagonist that binds to muscarinic acetylcholine receptors. Iodination of QNB is difficult because it contains rings that are deactivated, while phenol rings are activated. The purpose of this research is to develop an appropriate method for the iodination of QNB at no-carrier-added concentrations of /sup 125/I/NaI. Phenol was chose as the test compound for direct iodination by adding chloramine T and nonradioactive sodium iodide to the phenol in a phosphate buffer and methanol system. A simple method to radioiodinate QNB at several concentrations was developed in situ in the presence of QNB, thallic trifluoroacetate /sup 125/I/NaI, /sup 127/I/NaI, and aluminium chloride. Using milligram amounts of QNB (7.12 x 10/sup -6/ moles), three reaction steps were involved: QNB was reacted with thallic trifluoroacetate at 60/sup 0/C for 24 hours, then radioactive /sup 125/I/NaI and aluminium ...
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 ...
The epileptogenic and neurodegenerative effects of gamma-dendrotoxin, from Dendroaspis angusticeps, a specific blocker of a non-inactivating, voltage-sensitive K+ channel, were studied after focal injection into one dorsal hippocampus in rats pretreated with CGP040116, a N-methyl-D-aspartate (NMDA) receptor antagonist, and in rats bearing a monolateral surgical lesion of the Schaffer collaterals whose terminals originate from CA3 pyramids and release glutamate in the CA1 hippocampal area. Administration of 35 pmol gamma-dendrotoxin elicited in all of the treated animals (n=8) bilateral EEG discharges and damage to the hippocampal formation. Quantitation of the damage revealed significant bilateral neuronal cell loss in the CA1, CA3 and CA4 pyramidal cell layers. The lowest dose (0.35 pmol; n=4) of the toxin used did not affect EEG activity and failed to cause significant hippocampal cell loss whereas the 3.5 pmol (n=6) dose caused EEG seizures and hippocampal cell ...
Twenty autopsy cases with 2009 pandemic influenza A (2009 H1N1) virus infection, performed between August 2009 and February 2010, were histopathologically analyzed. Hematoxylin-eosin staining, immunohistochemistry for type A influenza nucleoprotein antigen, and real-time reverse transcription-PCR assay for viral RNA were performed on formalin-fixed and paraffin-embedded specimens. In addition, the D222G amino acid substitution in influenza virus hemagglutinin, which binds to specific cell receptors, was analyzed in formalin-fixed and paraffin-embedded trachea and lung sections by direct sequencing of PCR-amplified products. There were several histopathological patterns in the lung according to the most remarkable findings in each case: acute diffuse alveolar damage (DAD) with a hyaline membrane (four cases), organized DAD (one case), acute massive intra-alveolar edema with variable degrees of hemorrhage (three cases), neutrophilic bronchopneumonia (five cases) and ...
Candoxin (PDB #1JGK), a three-finger neurotoxin from Bungarus candidus venom, inhibits post-synaptic neuromuscular and neuronal alpha7nACh-receptors, and induces delayed cell-death throughout the glial population. When applied to cultured human glial cell lines, candoxin (CDX) induced cell death in a concentration (EC(50) approximately 1muM) and time dependent manner. Results of TUNEL-histochemistry further confirm CDX-induced brain (hippocampus, frontal cortex, and temporal regions) damage when administered intracerebroventricularly (i.c.v) in adult mice. In this study, we explored differential gene expression profiles following exposure of human glial (Hs 683) cell lines to CDX at various time intervals using Affymetrix-GeneChips. By means of MAS and GeneSpring analyses, 105 genes whose expression was significantly (P<0.01) altered by at least 3-fold were selected. Results of the genome analysis reveal that the potential role of CDX at molecular level ...
Human chorionic gonadotropin (hCG) is a glycoprotein hormone, secreted by the syncytiotrophoblast cells of the fertilized ovum, that enters the maternal circulation at the time of endometrial implantation. It is composed of two nonidentical subunits; ..cap alpha.. and ..beta.., with molecular weights of 14 kD and 23 kD, respectively. Human chorionic gonadotropin binds to the same receptor as hLH and displays the same biological response, namely, to stimulate the declining function of the corpus luteum to produce progestins and estrogen late in the menstrual cycle. The differences in the structures of hCG and hLH have been exploited to develop antibodies that can measure hCG specifically in the presence of hLH. Two-site antibody binding assays have been developed, based on a surface immunological concept of hCG epitopes, that involve four distinct regions to which antibodies against hCG can bind simultaneously. Antibody cooperative effects, in ...
Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17beta-estradiol (E(2)), although glycyrrhizin did not show such an activity. Moreover, the estrogen receptor alpha-dependent neurite outgrowth induced by the extract was similar to that by E(2), whereas glycyrrhizin had no ...
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 receptor concentration. Scatchard analysis of ...
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 ...
The muscarinic receptor binding of trazodone, a new nontricyclic antidepressant, was compared with established tricyclic antidepressants. The ability to inhibit the binding of [3H]-quinuclidinyl benzilate...Full Text Available
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
SUMMARYTestosterone and estrogen are essential for male behaviors in vertebrates. How these two signaling pathways interact to control masculinization of the brain and behavior...Full Text Available
The rejection thresholds of Phormia regina Meigen for twenty-four glycols have been determined. A definite relationship between the concentration of the test material and the distribution...Full Text Available
Cellular actions of thyroid hormone may be initiated within the cell nucleus, at the plasma membrane, in cytoplasm, and at the mitochondrion. Thyroid hormone nuclear receptors (TRs) mediate the biological...Full Text Available
Laron syndrome (LS) is an autosomal recessively inherited condition characterized by insensitivity to endogenous and exogenous GH. Affected individuals have severe episodes and other characteristic features. GH receptor gene mutations are present in all affected individuals in whom molecular studies have been reported. The GH receptor is a plasma membrane-spanning protein in which the extracellular domain binds circulating GH and the intracellular domain interacts with the JAK-2 kinase and possibly other intracellular signaling molecules. GH receptor dimerization occurs on GH binding and is thought to be required for normal signal transduction. We have studied the GH receptor genes of four unrelated individuals affected with LS from the United States, Italy, Saudi Arabia, and India. We have identified four different missense mutations that alter consecutive amino acids 152 to 155 in or near the ...
A study was made of the kinetics of L-(/sup 3/H)quinuclidinyl benzilate binding with membrane-bound muscarine cholinoreceptors from the rat brain. Determination was made of the rate constants of this process, and constants as a function of ligand concentration was investigated, indicating that there is a complex mechanism of interaction of antagonists with muscarine receptor. With up to 3.5 nM concentrations of L-(/sup 3/H)quinuclidinyl benzilate, the binding reaction occurs in two stages: rapid equilibrated binding is followed by a slow process of conformational isomerization of the receptor-ligand complex. At higher ligand concentrations, there is additional drastic increase in constant of rate of ligand binding a new plateau is reached. Such dependence of rate constant on ligand concentration is indicative of the cooperative nature of interaction between antagonists and muscarine receptors. This is possible if there are ...
The tetrapeptide KDEL is commonly found at the C terminus of soluble proteins of the endoplasmic reticulum (ER), and it contributes to their localization by interacting with a receptor that recycles...Full Text Available
BackgroundWhereas there is increasing evidence that loss of expression and/or function of the thyroid hormone receptors (TRs) could result in a selective advantage for tumor development,...Full Text Available
The receptor occupancy-biological effect relationship for muscarinic receptors in guinea pig ileal smooth muscle has been studied by comparison of radioligand binding and contractile response. Muscarinic receptors in homogenates of ileal smooth muscle were labeled with (/sub 3/H)-1-Quinuclidinyl benzilate. Treatment with propylbenzilylcholine mustard (PrBCM), to inactivate irreversibly muscarinic receptors, caused a large dose dependent rightward shift of the dose-response curve to three agonistic furtrethonium derivatives with a concomitant decrease in maximal response. Using those data, the fraction of receptors remaining unoccupied (q-values) and true affinity constants (-log K/sub A/-values) were calculated. Exposure to 20 or 60 nM PrBCM for 15 minutes resulted in a 39% and a 61% reduction in specific (/sup 3/H)-1-Quinuclidinyl benzilate binding sites respectively to be compared ...
This paper describes attempts to isolate and characterize glycosaminoglycan (GAG)-binding molecules on the surface of lymphocytes and lymphoma cell lines and relate their expression to splenic and lymph...Full Text Available
OBJECTIVES:To investigate the effect of opioid receptor blockade on the myocardial protection conferred by chronic exercise and to compare exercise training with different strategies...Full Text Available
Carbohydrate-directed endocytosis is mediated by a receptor, the hepatic binding protein; it is responsible for the clearance of galactose-terminated glycoproteins from the circulation. This process...Full Text Available
Measurements of the taste thresholds of blowflies for a wide variety of carbohydrates, presented individually and in combination, showed that the stimulating effects of the compounds are not always...Full Text Available
Full text: An adaptive response is a decreased biological effect induced by a priming radiation dose given prior to a challenge dose. Adaptive responses contradict the linear-nothreshold model of risk estimation. The pKZ1 mouse chromosomal inversion assay is an extremely sensitive assay for studying the mutagenic effect of low dose radiation. A non-linear dose response for chromosomal inversion has been observed in pKZ1 spleen and prostate after a single whole body irradiation with doses between 1?Gy and 10mGy. Doses between 5-10?Gy resulted in an induction in inversions and doses between 1-10mGy resulted in a reduction below endogenous inversion frequency. These results suggest that doses in the 1-10 mGy range cause host responses which overcompensate by not only preventing inversions that would normally occur as a result of the low doses of radiation but also by preventing some of the endogenous inversions that would have occurred in the absence of radiation. It was hypothesised that ...
Background: Quantifying HIV levels in mucosal secretions is essential to study compartmentalized expression of HIV and facilitate development of intervention strategies to prevent disease progression and transmission. Objectives: To develop a sensitive, reliable, and cost-effective technique to quantify HIV from blood and vaginal secretions that is compatible with efficient implementation in clinical research environments. Study design: A sensitive, reliable, internally-controlled real-time reverse transcriptase (RT) PCR assay, which uses the HIV-1 pol gene as a target (Hpol assay) was developed to quantify HIV levels in plasma and genital secretions, and compared to the widely used Roche Amplicor(TM) HIV-1 Monitor assay. In addition, a simplified method of sample collection and processing...
Air toxics from the industrial wastewater treatment plants (IWTPs) impose serious health concerns on its surrounding residential neighborhoods. To address such health concerns, one of the key challenges is to quantify the air emissions from the IWTPs. The objective here is to characterize the air emissions from the IWTPs and quantify its associated uncertainty. An IWTP receiving the wastewaters from an airplane maintenance facility is used for illustration with focus on the quantification of air emissions for benzyl alcohol, phenol, methylene chloride, 2-butanone, and acetone. Two general fate models, i.e., WATER9 and TOXCHEM+V3.0 were used to model the IWTP and quantify the air emissions. Monte Carlo and Bootstrap simulation were used for uncertainty analysis. On average, air emissions fr...
The objective of this research project is to demonstrate sensing, communication, information and control technologies to achieve a seamless integration of multivendor distributed energy resource (DER) units at aggregation levels that meet individual user requirements for facility operations (residential, commercial, industrial, manufacturing, etc.) and further serve as resource options for electric and natural gas utilities. The fully demonstrated DER aggregation system with embodiment of communication and control technologies will lead to real-time, interactive, customer-managed service networks to achieve greater customer value. Work on this Advanced Communication and Control Project (ACCP) consists of a two-phase approach for an integrated demonstration of communication and control technologies to achieve a seamless integration of DER units to reach progressive levels of aggregated power output. Phase I involved design and proof-of-design, and Phase II ...
SummaryThe receptors for the second messenger InsP3 comprise a family of closely related ion channels that release Ca2+ from intracellular stores, most prominently...Full Text Available
BackgroundCannabinoids represent unique compounds for treating tumors, including astrocytomas. Whether CB1 and CB2receptors mediate this therapeutic effect...Full Text Available
To investigate mechanisms responsible for positive and negative transcriptional control, the authors have utilized two types of promoters that are diffferentially regulated by thyroid hormone (T{sub 3}) receptors. Promoters containing the palindromic T{sub 3} response element TCAGGTCA TGACCTGA are positively regulated by the T{sub 3} receptor after the administration of T{sub 3}, whereas otherwise identical promoters containing the estrogen response element TCAGGTCA CTG TGACCTGA can be regulated negatively; converse effects are observed with the estrogen receptor. They describe evidence that the transcriptional inhibitory effects of the T{sub 3} or estrogen receptors on the estrogen or T{sub 3} response elements, respectively, are imposed by amino acid sequences in the C'-terminal region that colocalize with dimerization and hormone-binding domains and that these sequences can transfer ...
BackgroundThe status of estrogen receptor-α (ERα) is critical to the clinical prognosis and therapeutic approach in breast cancer. ERα-negative breast cancer...Full Text Available
Background2-Methylthioadenosine 5'-triphosphate (2-MeSATP), formerly regarded as a specific P2Y (metabotropic) purinergic receptor agonist, stimulates Ca2+ influx and...Full Text Available
1. The induction of long-term potentiation (LTP) was investigated in the rat dentate gyrus in the presence of ryanodine, an agent which is known to selectively bind to the ryanodine receptor (RyR) Ca2+...Full Text Available
The Epstein-Barr virus protein, LMP1, is a functional mimic of the cellular receptor CD40, but signals to B lymphocytes in an amplified and sustained manner compared to CD40. LMP1 contributes...Full Text Available
1. The effects on micturition of RP 67,580, a selective NK1 receptor antagonist, and SR 48,968, a highly, potent antagonist at NK2 receptor sites, given intrathecally (i.t.) or intra-arterially (i.a.)...Full Text Available
σ-Receptor (σR) antagonists have been reported to block certain effects of psychostimulant drugs. The present study examined the effects of σR ligands in rats trained to self-administer...Full Text Available
We have previously described an allelic polymorphism in the V beta 6.1 T-cell receptor gene. The V beta 6.1B allele is associated with disease in a subgroup of patients with juvenile rheumatoid arthritis....Full Text Available
Here, we provide the first study of prolactin (PRL) and prolactin receptor (PRLR) expression during the nonseasonal murine hair cycle, which is, in contrast to sheep, comparable with the human scalp...Full Text Available
Airway ciliated cells express an ATP-gated P2X receptor channel of unknown subunit composition (P2Xcilia) which is modulated by Na+ and by long exposures to ATP. P2Xcilia...Full Text Available
AimsTo characterize the pharmacokinetics of terbogrel, a new combined thromboxane A2 (TxA2) receptor and synthase inhibitor, in healthy human subjects after...Full Text Available
The effects of neuroactive steroids on the function of GABAAreceptors were studied using cell-attached records of single channel activity recorded from HEK293 cells transfected with α1...Full Text Available
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
Peroxisome proliferator activated receptor-{gamma} (PPAR{gamma}) regulates metabolic homeostasis and adipocyte differentiation, and it is activated by oxidized and nitrated fatty acids. Here we report the crystal structure of the PPAR{gamma} ligand binding domain bound to nitrated linoleic acid, a potent endogenous ligand of PPAR{gamma}. Structural and functional studies of receptor-ligand interactions reveal the molecular basis of PPAR{gamma} discrimination of various naturally occurring fatty acid derivatives.
Asialoorosomucoid (ASOR) is internalized and degraded by HepG2 cells after binding to the asialoglycoprotein (ASGP) receptor, internalization through the coated pit/coated vesicle pathway, and trafficking to lysosomes. Primaquine, an 8-aminoquinoline antimalarial compound, inhibits ASOR degradation at concentrations greater than 0.2 mM by neutralizing intracellular acid compartments. This leads to alterations in surface receptor number, receptor-ligand dissociation, and receptor recycling. We have investigated the effects of primaquine on 125I-ASOR uptake and degradation as a function of primaquine concentration and duration of exposure. Concentrations below those required for neutralization of acidic compartments block 125I-ASOR degradation in HepG2 cells and lead to intracellular ligand accumulation. This effect is maximal at 80 microM primaquine. The intracellular 125I-ASOR is undegraded, dissociated ...
Asialoorosomucoid (ASOR) is internalized and degraded by HepG2 cells after binding to the asialoglycoprotein (ASGP) receptor, internalization through the coated pit/coated vesicle pathway, and trafficking to lysosomes. Primaquine, an 8-aminoquinoline antimalarial compound, inhibits ASOR degradation at concentrations greater than 0.2 mM by neutralizing intracellular acid compartments. This leads to alterations in surface receptor number, receptor-ligand dissociation, and receptor recycling. We have investigated the effects of primaquine on 125I-ASOR uptake and degradation as a function of primaquine concentration and duration of exposure. Concentrations below those required for neutralization of acidic compartments block 125I-ASOR degradation in HepG2 cells and lead to intracellular ligand accumulation. This effect is maximal at 80 microM primaquine. The intracellular 125I-ASOR is undegraded, dissociated ...
The immunolocalization of the low density lipoprotein receptor-related protein 1 (LRP1) and its ligand alpha 2-Macroglobulin (α2M) was examined in tissues from human donor...Full Text Available
Growth differentiation factor-9 (GDF-9), an oocyte-secreted member of the transforming growth factor β superfamily, progesterone receptor, cyclooxygenase 2 (Cox2; Ptgs2), and the EP2 prostaglandin...Full Text Available
Backgroundβ2-Adrenergic receptors (β2AR) play important regulatory roles in a variety of cells and organ systems and are important therapeutic...Full Text Available
An unusual S1-nuclease sensitive microsatellite (STMS) has been found in the single copy, rat polymeric immunoglobulin receptor gene (PIGR) terminal exon. In Fisher rats, elements within or beyond the...Full Text Available
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
The aim of this study was to investigate cumulus expansion, nuclear maturation and expression of connexin 43, cyclooxygenase-2 and FSH receptor transcripts in equine cumuli oophori during in vivo and...Full Text Available
Bovine leukemia virus (BLV), a retrovirus related to human T-cell leukemia virus types 1 and 2, can induce persistent nonneoplastic expansion of the CD5+ B-cell population, termed...Full Text Available
The substantia nigra pars reticulata (SNR) controls seizures in a sex-specific manner. At postnatal day 15 (P15), SNR infusion of GABAAreceptor agonist muscimol have proconvulsant...Full Text Available
T-cell activation requires the influx of extracellular calcium, although mechanistic details regarding such activation are not fully defined. Here, we show that P2X7receptors play a key...Full Text Available
This study focuses on the effects of long-term renin-angiotensin system suppression and/or incretin mimetic therapies on the regulation and binding affinity of GLP-1 to its receptor in the coronary...Full Text Available
It has been postulated that fetal vascular abnormalities in aryl hydrocarbon receptor null (ahr−/−) mice may alter cardiovascular homeostasis in adulthood....Full Text Available
Adenosine regulates a wide variety of physiological processes via interaction with one or more G-protein-coupled receptors (A1R, A2AR, A2BR, and A3R)....Full Text Available
This report investigates acute changes in the sensitivity of 5-HT1Areceptors in dorsal raphe (dr) neurons in response to elevated serotonin. DR neurons were isolated from adult rats...Full Text Available
α1-Fetoprotein transcription factor (FTF), also known as liver receptor homolog 1 (LRH-1) is highly expressed in liver and intestine, where it is implicated in the regulation...Full Text Available
1-Naphthylphthalamic acid (NPA) is a specific inhibitor of polar auxin transport that blocks carrier-mediated auxin efflux from plant cells. To allow identification of the NPA receptor thought to be...Full Text Available
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
The temporal development of the effect of THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) on the ultrastructure composition and GABA receptor expression in cerebellar granule cells was investigated by quantitative electron microscopy (morphometric analysis) and GABA binding assays. It was found that the cytoplasmic density of smooth endoplasmic reticulum was decreased, while the cytoplasmic density of rough endoplasmic reticulum, Golgi apparatus, vesicles and coated vesicles was greatly enhanced after exposure of the cells to THIP (150 microM) for only 1 hr. In cerebellar granule cells exposed to THIP (150 microM) for 3 hr low affinity GABA receptors were induced. These findings show that the effect of THIP on the ultrastructure composition and GABA receptor expression in cultured cerebellar granule cells may be interrelated and moreover it is likely that the turn-over of GABA receptors is ...
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 ...
By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reaction time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final {sup 125}I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding was 12-16%, nonspecific binding was as low as 2-4% in the ...
The recently described retinoid X receptors (RXRs) respond to the novel retinoid 9-cis-retinoic acid and also serve as heterodimeric partners for the vitamin D, thyroid hormone, and retinoic acid receptors (VDR, TR, and RAR, respectively). In this work, the authors report high-resolution localization of the human RXR genes within cytogenetic bands and also within a standard reference map of cosmid DNA markers on human chromosomes. They have determined the location of the human RXR genes by pairwise hybridization of the RXR cosmids and reference markers, using fluorescence in situ hybridization. They localized (i) RXR[alpha] (RXRA) to chromosome 9 band q34.3; (ii) RXR[beta] (RXRB) to chromosome 6 band 21.3; and (iii) RXR[gamma] (RXRG) to chromosome 1 band q22-q23. Six retinoid-responsive transcription factors have been identified so far, including three retinoic acid receptors in addition to the three RXRs. Interestingly, ...
Vulnerability to xylem embolism by freeze-thaw cycles and water stress was quantified in ring-porous (Quercus gambelii Nutt.), diffuse-porous (Populus tremuloides Michx.,...Full Text Available
Variability in motor performance decreases with practice but is never entirely eliminated, due in part to inherent motor noise. The present study develops a method that quantifies how performers...Full Text Available
A regional analysis of nucleotide substitution rates along human genes and their flanking regions allows us to quantify the effect of mutational mechanisms associated with transcription in germ line...Full Text Available
The interactions between biochemical processes and mechanical signaling play important roles during various cellular processes such as wound healing, embryogenesis, metastasis, and cell migration. While...Full Text Available
BackgroundIn Africa low birth weight (LBW) (<2500 g), is the strongest determinant of infant morbidity and mortality. The aim of this study was to quantify the effect of...Full Text Available
ObjectiveTo investigate and to quantify the relationship between hospital costs and health outcomes for patients with acute myocardial infarction (AMI) in Veterans Health Administration...Full Text Available
Four-dimensional (4D) radiotherapy is the explicit inclusion of the temporal changes in anatomy during the imaging, planning, and delivery of radiotherapy. One key component of 4D radiotherapy planning...Full Text Available
BackgroundSmall laboratory fish share many anatomical and histological characteristics with other vertebrates, yet can be maintained in large numbers at low cost for lifetime studies....Full Text Available
We quantified antibody responses to the HCV proteome that are associated with sustained virologic response (SVR) in HIV/HCV co-infected patients treated with pegylated interferon and ribavirin....Full Text Available
BackgroundConducted as part of the Urologic Diseases in America project whose aim was to quantify the burden of urologic diseases on the American public, this study focuses on Veterans...Full Text Available
Acoustic pharyngometry is a relatively new noninvasive method that quantifies geometrically complexed pharyngeal dimensions. Our study aimed to investigate the predictability and usefulness of acoustic...Full Text Available
School buses contribute substantially to childhood air pollution exposures yet they are rarely quantified in epidemiology studies. This paper characterizes fine particulate matter (PM2.5)...Full Text Available
The objectives of this study were to evaluate the current fitness of an area ambulance service based in Belfast and to quantify the physiological demands of accident and emergency work. From a total...Full Text Available
This study investigated weathering effects on polyvinyl chloride (PVC) based wood plastic composites (WPC), with a focus on the color and structure that is attributed to the material composition. It is directed towards quantifying the main chemical modifi...
The concentration of some organic acids in the atmosphere was determined using a wet effluent diffusion denuder-aerosol collector coupled with Ion Chromatography. Three organic acids and four inorganic anions were identified and quantified in the air sample, taken from the backyard of PSI. (author)
This dissertation presents the development of the novel mechanical testing technique of in situ nanoindentation in a transmission electron microscope (TEM). This technique makes it possible to simultaneously observe and quantify the mechanical behavior of nano-scale volumes of solids.
Genetic effects on mechanical properties have been demonstrated in rodents, but not confirmed in primates. Our aim was to quantify the proportion of variation in vertebral trabecular bone mechanical...Full Text Available
The method of linear analogue self-assessment (LASA) was used to quantify the views concerning day care which were held by patients attending a geriatric day hospital. The results suggest that day hospitals...Full Text Available
Many patients are currently suffering from nickel (Ni)-induced allergic contact dermatitis (ACD). There have been few Korean studies dealing with the threshold of Ni-induced ACD and quantifying the...Full Text Available
BackgroundEpidemiologic studies associate lung cancer in non-smoking Chinese women with Chinese-style wok cooking. Our goal was to quantify carcinogen and toxicant...Full Text Available
Pseudomonas mandelii liquid cultures were studied to determine the effect of pH and temperature on denitrification gene expression, which was quantified by quantitative reverse transcription-PCR....Full Text Available
Nursing infants may be exposed to lead from breast milk, but relatively few data exist with which to evaluate and quantify this relationship. This route of exposure constitutes a potential infant hazard...Full Text Available
The utility of a two-photon optical fiber fluorescence probe (TPOFF) for sensing and quantifying tumor fluorescent signals was tested in vivo. Xenograft tumors were developed in athymic mice using MCA207...Full Text Available
As part of an investigation of the mechanisms of coastal change in the Carolinas (http://woodshole.er.usgs.gov/project-pages/cccp/index.html), instrumented tripods were deployed on Diamond Shoals near Cape Hatteras, NC. These tripods recorded data quantifying the currents, waves, turbidity, temperat...
Quantitative metallography is often used to confirm the proper processing of aerospace metallic materials. A microstructural feature of great importance for titanium alloys processed in the alpha-beta phase field is the volume fraction of primary alpha. S...
There is limited information about the true incidence of acute renal failure (ARF). Most studies could not quantify disease frequency in the general population as they are hospital-based and...Full Text Available
BackgroundKinematic and kinetic measurements used in laboratory settings can quantify upper extremity movement impairment following stroke, but their relationship...Full Text Available
BackgroundThe aim of this cohort study was to quantify the effect of alcohol in the risk of oral cancer in different strata of folate intake, controlling for known...Full Text Available
The objectives of this study were to quantify the effect of 16 ppm of dietary monensin on milk production and composition of dairy cows, and to investigate factors having a potential impact on this...Full Text Available
We have continued to finish up our work on analyzing relationships between elastic properties and rock microstructure. We have worked on theoretical models for the effects of sorting and packing on elastic moduli and seismic velocities. After analyzing the scanning acoustic images of shales to quantify textures at different scales, we are now using theoretical inclusion models to quantify the elastic property variation with texture. In the closing phases of this project most of our efforts are now focused on writing up the results and preparing the final reports.
Werner states are paradigmatic examples of quantum states and play an innovative role in quantum information theory. In investigating the correlating capability of Werner states, we find the curious phenomenon that quantum correlations, as quantified by the entanglement of formation, may exceed the total correlations, as measured by the quantum mutual information. Consequently, though the entanglement of formation is so widely used in quantifying entanglement, it cannot be interpreted as a consistent measure of quantum correlations per se if we accept the folklore that total correlations are measured (or rather upper bounded) by the quantum mutual information.
A generalised procedure for quantifying the benefits of household biogas plants is presented. The sensitivity of the procedure to the uncertainty in input prices is reduced through the assumption of incremental benefits from the biogas plant. These benefits are quantified in terms of the quantity of fuelwood for which the biogas substitutes in cooking, the quantity of kerosene replaced through the use of biogas for lighting and the diesel fuel displaced through the use of a biogas fuelled dual-fuel engine for motive power. Sensitivity of the monetary benefits for these parameters is examined in order to identify variables which influence the viability of the technology to the end user. (author).
The plerocercoid stage of the tapeworm Spirometra mansonoides produces a functional analog of human growth hormone (hGH). Among the similarities between plerocercoid growth factor (PGF) and hGH is competition for the same receptors on rabbit liver membranes. To take advantage of this characteristic in a purification scheme for PGF, rabbit liver microsomes were solubilized in Triton X-100 and the hGH receptors were purified over an hGH affinity column. The purified receptors from six rabbit livers were coupled to Affi-Gel-10 to create a receptor affinity column which was used to purify PGF. Chromatography of crude PGF over the receptor column resulted in a 1044 fold increase in specific activity. SDS-PAGE in the presence of 2-mercaptoethanol showed that the affinity-purified PGF contained three protein bands with apparent Mrs of 27.5 K, 22 K, and 16.7 K. Injections of the ...
(3H)Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without ...
[3H]Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without ...
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 regulation of ...
Four major natriuretic peptides have been isolated: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Dendroaspis-type natriuretic peptide (DNP). Natriuretic peptides play an important role in the regulation of cardiovascular homeostasis maintaining blood pressure and extracellular fluid volume. The classical endocrine effects of natriuretic peptides to modulate fluid and electrolyte balance and vascular smooth muscle tone are complemented by autocrine and paracrine actions that include regulation of coronary blood flow and, therefore, myocardial perfusion; modulation of proliferative responses during myocardial and vascular remodeling; and cytoprotective anti-ischemic effects. The actions of natriuretic peptides are mediated by the specific binding of these peptides to three cell surface receptors: type A natriuretic peptide receptor (NPR-A), type B natriuretic peptide ...
Introduction: Development of agonist positron emission tomography (PET) radioligands for the 5-HT neurotransmitter system is an important target to enable the understanding of human 5-HT function in vivo. ["1"1C]CUMI-101, proposed as the first 5-HT_1_A receptor agonist PET ligand, has been reported to behave as a potent 5-HT_1_A agonist in a cellular system stably expressing human recombinant 5-HT_1_A receptors. In this study, we investigate the agonist properties of CUMI-101 in rat brain tissue. Methods: ["3"5S]-GTP#gamma#S binding studies were used to determine receptor function in HEK (human embryonic kidney) 293 cells transfected with human recombinant 5-HT_1_A receptors and in rat cortex and rat hippocampal tissue, following administration of CUMI-101 and standard 5-HT1A antagonists (5-HT, 5-CT and 8-OH-DPAT). Results: CUMI-101 behaved as an agonist at human recombinant 5-HT_1_A ...
Aminophenpyramine, a derivative of mepyramine (pyrilamine), a typical antagonists of histamine at its H_1 receptor was synthesized and converted into ["1"2"5I]iodoazidophenpyramine, a potential photoaffinity probe for the H_1 receptor. In the dark, reversible binding of this probe to cerebellar membranes occurred with a K/sub d/ of 1.2 x 10"-"1"1 M and a B/sub max/ of 240 fmol/mg of protein and was inhibited by various H_1-receptor antagonists with the expected potencies. These features establish the compound as one of the most potent H_1-receptor antagonists known so far. Upon IV irradiation, 5% of the bound radioactivity was covalently incorporated into cerebellar membrane polypeptides as shown by standard NaDodSO_4/PAGE. Two bands of 47 and 56 kDa were consistently labeled, labeling being prevented by various H_1-receptor antagonists with the expected potencies and ...
Background: Thyroid-stimulating autoantibodies (TSAb) bind to the thyrotropin receptor (TSHR) extracellular domain, or ectodomain (ECD), comprising a leucine-rich repeat domain (LRD) linked by a hinge region to the transmembrane domain (TMD). The LRD (residues 22???260; signal peptide 1???21) contains two disulfide-bonded loops at its N-terminus. In the crystal structure of the isolated LRD complexed with human TSAb monoclonal antibody (mAb) M22, N-terminal disulfide loop 1 (residues 22???30) could not be determined because of crystal disorder. Nevertheless, present crystal structure data are interpreted to exclude a role for the LRD N-terminal disulfide loops in the TSAb epitope(s), contradicting prior functional evidence of a role for these loops in TSAb function. Materials and Methods: ...
Somatostatin receptor scintigraphy (SRS) is a valuable method for the detection of somatostatin receptor-positive lesions. Most gastrinomas (over-)express the somatostatin receptor subtype 2 which can be targeted by In-111 labeled Octreotide. Different studies show a high sensitivity of SRS for the localization and staging of gastrinomas. SRS seems to be superior to other non-invasive imaging modalities and has been proven to significantly contribute to patient management. However, the sensitivity depends on the size and exact localization of the tumors. Smaller lesions and lesions located in the duodenum show a significantly lower sensitivity. In any case, SRS belongs to the routine imaging procedure for gastrinomas for localization and staging and can also be used for evaluation of the tumor progression. (author)
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 ...
Geologic sequestration is currently being practiced and scientifically evaluated as a critical component in a broad strategy, comprising new practices and technologies, for mitigating global climate change due to anthropogenic emissions of CO2. Demonstrating that geologic sequestration of CO2 is safe and effective, and gaining public acceptance of sequestration technologies are critically important in meeting these global climate change challenges. Monitored field-scale demonstrations of geologic sequestration of carbon dioxide will contribute greatly toward growing trust and confidence in the technology; however, pilot demonstrations ultimately will not be the norm for new geological sequestration deployments. Instead, scientists, engineers, regulators, and ultimately the public will rely on numerical simulations to predict the performance of geologic repositories for carbon dioxide sequestration. The U.S. Department of Energy (DOE), through the National Environmental Technology ...
{sup 14}C is a is a long-lived beta-emitting nuclide (T{sub 1/2} = 5730 years) produced naturally in the upper atmosphere as a result of reactions between neutrons and stable {sup 14}N({sup 14}N(n,p){sup 14}C). Although in a lesser extent, nuclear power plants produce {sup 14}C as well during their routine operation. Since it is converted in {sup 14}CO{sub 2} and mixed throughout the atmosphere, it is incorporated into plant tissues, via photosynthesis process, and hence in food chain. Because of the biological importance of {sup 14}C and long half-life, it is of interest to quantify the amounts released by nuclear industry. The Brazilian nuclear central named Nuclear Central Admiral Alvaro Alberto (CNAAA) has two nuclear reactors of PWR type in operation, Angra I (657 MWe) and Angra II (1350 MWe), and one under construction, Angra III (1309 MWe PWR). The aim of this study was to determine the strength of the sources and the {sup 14}C content in the environment ...
The mechanisms that contribute to the extinction of previously acquired memories are not well understood. These processes, often referred to as inhibitory learning, are thought to be parallel...Full Text Available
Transient receptor potential (TRP) ion channels have been implicated in detecting chemical, thermal and mechanical stimuli in organisms ranging from mammals to Caenorhabditis elegans....Full Text Available
BackgroundGreen tea consumption has been shown to have cancer preventive qualities. Among the constituents of green tea, (-)-Epigallocatechin-3-O-gallate (EGCG)...Full Text Available
Receptor protein tyrosine phosphatase T (PTPRT/PTPρ) is frequently mutated in human cancers including colon, lung, gastric and skin cancers. More than half of the identified tumor-derived...Full Text Available
BackgroundThe dynorphin-kappa opioid receptor (KOR) system regulates glial proliferation after sciatic nerve injury. Here, we investigated its role in cell proliferation following...Full Text Available
Experience-dependent plastic changes in the central sensory systems are due to activation of both the sensory and neuromodulatory systems. Nonspecific changes of cortical auditory neurons elicited by...Full Text Available
Recent research has implicated the nucleus accumbens (NAc) in consolidating recently acquired goal-directed appetitive memories, including spatial learning and other instrumental processes. However,...Full Text Available
1. The stereospecificity of the enantiomers of LY253352, a potent and selective alpha 1-adrenoceptor antagonist, were studied in the human prostate and canine brain using radioligand receptor binding...Full Text Available
Cervical spinal cord hemisection rostral to the phrenic nucleus leads to paralysis of the ipsilateral hemidiaphragm in adult rats. Respiratory function can be restored to the paralyzed hemidiaphragm...Full Text Available
[3,5-"3H] 4-Azidoclonidine 6 was prepared from [3,5-"3H] 4-aminoclonidine 4 and has emerged as a valuable tool to study the alpha-2-adrenergic receptor. (author)
Studies in rodents have shown that male sexual function can be disrupted by fetal or neonatal administration of compounds that alter endocrine homeostasis, such as the synthetic nonsteroidal estrogen...Full Text Available
BackgroundNFκB signaling is of paramount importance in the regulation of apoptosis, proliferation, and inflammatory responses during human development and homeostasis, as...Full Text Available
The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Δ32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested...Full Text Available
SummaryTRPV1 is the founding and best-studied member of the family of temperature-activated transient receptor potential ion channels (thermoTRPs). Voltage, chemicals, and heat...Full Text Available
Peptide toxins with high affinity, divergent pharmacological functions, and isoform-specific selectivity are powerful tools for investigating the structure-function relationships of voltage-gated...Full Text Available
The synthesis and structure-activity relationship analysis of a novel class of amide-based biaryl NR2B-selective NMDA receptor antagonists are presented. Some of the studied compounds are potent, selective, non-competitive, and voltage-independent antagonists of NR2B-containing NMDA receptors. Like the founding member of this class of antagonists (ifenprodil), several interesting compounds of the series bind to the amino terminal domain of the NR2B subunit to inhibit function. Analogue potency is modulated by linker length, flexibility, and hydrogen bonding opportunities. However, unlike previously described classes of NR2B-selective NMDA antagonists that exhibit off-target activity at a variety of monoamine receptors, the compounds described herein show much diminished effects against the...
Understanding the mechanisms whereby information encoded within patterns of action potentials is deciphered by neurons is central to cognitive psychology. The multiprotein complexes formed by...Full Text Available
Gonadal, adrenal, and thyroid hormones affect the brain directly, and the sensitivity to hormones begins in embryonic life with the appearance of hormone receptor sites in discrete populations of neurons....Full Text Available
Somatostatin receptor expression has been demonstrated on a number of plasma cell lines. Therefore, we questioned whether somatostatin receptor scintigraphy (SRS) can be used to demonstrate in vivo multiple myeloma (MM) activity. SRS was performed in newly diagnosed (n = 9) or relapsing (n = 18) MM patients or in patients with localized plasmacytoma (n = 2). The results were compared with radiographic findings. A positive SRS was demonstrated in 44% of the newly diagnosed patients, in 83% of the relapsed patients and in both patients with plasmacytoma. The SRS findings corresponded with radiographic abnormalities in 40% of the patients. However, in relapsed patients 60% demonstrated increased SRS uptake in areas without new radiographic abnormalities. The positive SRS corresponded with histologically proven disease activity and responded upon treatment. Moreover, immunohistochemical staining of MM material demonstrated concordant somatostatin ...
BackgroundPostoperative delirium is a topic of great importance in the geriatric surgical specialty. Although antipsychotic drugs are the medications most frequently used to treat...Full Text Available
Receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) play key roles in the pathogenesis of glucocorticoid-induced osteoporosis (GIO). The aim of our study was to determine whether the...Full Text Available
Human epidermal growth factor receptor 2 (HER2) is one of the most important prognostic and predictive factors for breast cancer patients. Recently, serum HER2...Full Text Available
The goal of ultrasonic molecular imaging is the detection of targeted contrast agents bound to receptors on endothelial cells. We propose imaging methods that can distinguish adherent microbubbles...Full Text Available
Rejection of eight aldehydes, eight ketones, five secondary alcohols, and 3-pentanol has been studied in the blowfly Phormia regina Meigen. The data agree with results previously reported...Full Text Available
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
PurposeIn our previous studies we showed that upregulating claudin-6 (CLDN6) expression may contribute to preventing breast cancer, and that 17β-estradiol induces a concentration-...Full Text Available
A statistical method is developed to determine the locations of major pollutant sources affecting a distant downwind receptor, provided that air trajectories can be estimated. Probability density functions are estimated which indicate the overall residence time of air parcels over a given geographic region as they travel toward a receptor and residence time for the case of high pollutant concentrations at the receptor. These functions are used to estimate a conditional probability function which indicates the potential for a source region to contribute to high air pollution concentrations. Finally, a source contribution function is formulated to indicate the relative contribution of different source regions to high concentrations at the receptor. The method is tested using data collected at Grand Canyon National Park in 1980. The dominant pathway for air masses arriving at Grand Canyon during this ...
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 receptor ...
Targeted studies completed include the evaluation of tritiated N-0437, evaluation of /sup 35/S-cysteamine, evaluation of /sup 18/F-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 ...
BackgroundGlucocorticoids down-regulate cytokine synthesis and suppress inflammatory responses. The glucocorticoid receptor (GR) antagonist RU486 may exacerbate the inflammatory...Full Text Available
Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation....Full Text Available
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
Cervical cancer is known to metastasize primarily by the lymphatic system. Dissemination through lymphatic vessels represents an early step in regional tumor progression, and the presence of lymphatic...Full Text Available
Hypoxia, or reduced oxygen, occurs in a variety of clinical and environmental situations. Hypoxic exposure is associated with decreased muscle mass and a concomitant reduction in exercise capacity,...Full Text Available
Prenatal cocaine exposure produces sustained neurobehavioral and brain synaptic changes closely resembling those of animals with defective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic...Full Text Available
Although the mechanism is unknown, Calculus Bovis and its active components, cholic acid analogs (CAAs), have been used in China to treat a wide range of diseases. Based on the previous finding that the potency of CAA is strongly dependent on the intrinsic surface activity, this paper aimed to investigate the role of the plasma membrane in the pharmacological activity of CAAs. First, CAAs (0.1 mM) caused a surface activity-dependent depression on ATPase activity in the cell membrane extract, but it had no effects on other cellular extracts, suggesting an indispensable role of the membrane environment for pharmacological activity. Second, CAAs lowered the membrane fluidity of cultured Caco-2 cells with the same rank-order of potency sequence. Third, the hypothesis that any functional protein located on the membrane is influenced by changes in cellular membrane fluidity was supported by: ileal contraction that was induced by acetylcholine and mediated by the muscarinic ...
BackgroundZibotentan (ZD4054) is a specific endothelin A (ETA) receptor antagonist being investigated for the treatment of prostate cancer. As zibotentan is eliminated...Full Text Available
A parallel bundle of transmembrane (TM) alpha-helices surrounding a central pore is present in several classes of ion channel, including the nicotinic acetylcholine receptor (nAChR). We have modeled...Full Text Available
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor survival. The identification of therapeutic targets is essential to improving outcomes. Previous studies found that expression...Full Text Available
Acute inflammation is important for tissue repair; however, chronic inflammation contributes to neurodegeneration in Alzheimer’s disease (AD) and occurs when glial cells undergo prolonged...Full Text Available
IntroductionIn the last few years, various studies have underlined a correlation between thyroid function and male sexual function, hypothesizing a direct action of thyroid hormones...Full Text Available
Macrophage activation by the proinflammatory cytokine interferon-γ (IFN-γ) is a critical component of the host innate response to bacterial pathogenesis. However, the precise nature...Full Text Available
The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated...Full Text Available
Nicotine is the main psychoactive ingredient in tobacco and its rewarding effects are considered primarily responsible for persistent tobacco smoking and relapse. Although dopamine has been extensively...Full Text Available
Women experience a decline in estrogen and androgen levels after natural or surgically induced menopause, effects that are associated with a loss of sexual desire and bone mineral density. Studies in...Full Text Available
The effects of paeoniflorin (PF), a compound isolated from Paeony radix, on neurological impairment and histologically measured infarction volume...Full Text Available
The CNS can exhibit features of inflammation in response to injury, infection or disease, whereby resident cells generate inflammatory mediators, including cytokines, prostaglandins, free radicals and...Full Text Available
Hypoxia–ischemia (H/I) in the premature infant leads to white matter injury termed periventricular leukomalacia (PVL), the leading cause of subsequent neurological deficits. Glutamatergic...Full Text Available
Myelin-associated glycoprotein (MAG) has been implicated in inhibition of nerve regeneration in the CNS. This results from interactions between MAG and the Nogo receptor and gangliosides on...Full Text Available
The X-ray crystallographic structural determinations of synthetic estrogens and antiestrogens provide reliable information on the global minimum energy conformation of these molecules or a local minimum...Full Text Available
Cytoadherence or sequestration is essential for the pathogenesis of the most virulent human malaria species, Plasmodium falciparum (P. falciparum). Similar to leukocyte-endothelium...Full Text Available
Human skin is a local source of corticotropin-releasing hormone (CRH) and expresses CRH and CRH receptors (CRH-R) at mRNA and protein levels. Epidermal melanocytes respond to CRH by induction...Full Text Available
Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been implicated in Multiple Sclerosis demyelination through activation of complement and/or macrophage-effector processes. We presented...Full Text Available
We had previously identified a macrophage surface protein whose expression is highly induced, transient, and specific, as it is restricted to actively fusing macrophages in vitro and in vivo. This protein...Full Text Available
A growing number of studies suggest that the development of compulsive drug seeking and taking depends on dorsostriatal mechanisms. We previously observed that ex vivo acute...Full Text Available
In addition to its role in megakaryocyte production, signaling initiated by thrombopoietin (TPO) activation of its receptor, myeloproliferative leukemia virus protooncogene (c-Mpl, or Mpl), controls...Full Text Available
Host cells use metabolic signaling through the LXRα nuclear receptor to defend against Listeria monocytogenes infection. 25-Hydroxycholesterol is a natural ligand of LXRs that...Full Text Available
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
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
BackgroundThe VP2 outer capsid protein Bluetongue Virus (BTV) is responsible for receptor binding, haemagglutination and eliciting host-specific immunity. However, the assembly of...Full Text Available
Sensory experience plays a crucial role in regulating neuronal shape and in developing synaptic contacts during brain formation. These features are required for a neuron to receive, integrate, and transmit...Full Text Available
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
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 ...
Neuropilin-1 (NRP1) acts as a co-receptor for class 3 semaphorins and vascular endothelial growth factor and is an attractive angiogenesis target for cancer therapy. In addition to the transmembrane...Full Text Available
Bacillus thuringiensis subsp. israelensis, which is used worldwide to control Aedes aegypti larvae, produces Cry11Aa and other toxins during...Full Text Available
This study addresses the mechanism of transport of the H2-receptor antagonist, cimetidine, by the human placenta. A 4-h recycling perfusion of a single placental cotyledon of normal, term, human placenta...Full Text Available
Histamine has been proposed to be an important regulator of energy intake and expenditure. The aim of this study was to evaluate histamine regulation of glucose and lipid metabolism and development...Full Text Available
Place fields of hippocampal pyramidal cells expand asymmetrically when adult rats repeatedly follow the same route. This behaviorally-induced expression of neuronal plasticity utilizes an NMDAR-dependent,...Full Text Available
The genetic basis of odorant-specific variations in human olfactory thresholds, and in particular of enhanced odorant sensitivity (hyperosmia), remains largely unknown. Olfactory receptor (OR) segregating...Full Text Available
The role of pheromone biosynthesis activating neuropeptide (PBAN) in the regulation of pheromone biosynthesis of several female moth species is well elucidated, but its role in the males has been a...Full Text Available
Exteriorized phosphatidylserine (PS) residues in apoptotic cells trigger rapid phagocytosis by macrophage scavenger receptor pathways. Mimicking apoptosis with liposomes containing PS may represent...Full Text Available
Dectin-1, the major β-glucan receptor in leukocytes, triggers an effective immune response upon fungal recognition. Here we use sortase-mediated transpeptidation, a technique that allows placement...Full Text Available
Tamoxifen (TAM) is a selective estrogen receptor modulator widely used in the prevention and treatment of breast cancer. A major mode of metabolism of the major active metabolites of TAM, 4-OH-TAM...Full Text Available
BackgroundLeukotrienes (LTs) belong to the large family of lipid mediators implicated in various inflammatory conditions such as asthma and rheumatoid arthritis. Four distinct types...Full Text Available
SUMMARYMotile dendritic filopodial processes are thought to be precursors of spine synapses, but how motility relates to cell-surface cues required for axon-dendrite recognition...Full Text Available
Protective innate immunity to the nematode Strongyloides stercoralis requires eosinophils in the parasite killing process. Experiments were performed to determine if an extract of S....Full Text Available
BackgroundThiazolidinediones (TZDs) activate peroxisome proliferator-activated receptor gamma (PPARγ) and are used clinically to help restore peripheral insulin sensitivity...Full Text Available
Porphyromonas gingivalis has been implicated as a causative pathogen in periodontitis. Immunotherapeutic approaches have recently been suggested to aid in the clearance of P....Full Text Available
The specific receptor sites and the endocytosis of transferrin (Tf) are evidenced in a cell line (HT-29) derived from a human colic adenocarcinoma by means of "1"2"5I radiolabeled Tf. The receptor density is studied in undifferentiated (UD) or differentiated (D) cells with respective doubling times of about 24 hours and 46 hours. The number of binding sites for Tf is 162,000 (K_d = 7.8 nmol/l in ND cells and 68,000 (K_d = 7.40 nmol/l) in D cells. The distribution between the Tf bound to the cell surface and the internalized Tf is investigated by elimination of Tf bound to the surface by an acid wash method. The intracellular cycle of Tf seems to be characterized by a slower kinetics in UD cells. The high density of Tf receptor sites in HT-29 UD cells should allow the detection or the treatment of highly evolutive colic adenocarcinoma by means of Tf.
Objective:To investigate the combined effect of both pioglitazone and methotrexate on disease activity of rheumatoid arthritis in a biphasic study; experimental and clinical.Methods:Experimentally:...Full Text Available
B lymphocytes can function independently as efficient APCs. However, our previous studies demonstrate that both dendritic cells and macrophages are necessary to propagate immune responses initiated...Full Text Available
Glioblastoma, the most common malignant brain tumor, is among the most lethal and difficult cancers to treat. Although epidermal growth factor receptor (EGFR) mutations are frequent in glioblastoma,...Full Text Available
BackgroundThe N-methyl-D-aspartate (NMDA)-type glutamate receptor expressed at excitatory glutamatergic synapses is required for learning and memory and is critical for normal brain...Full Text Available
Retinoic acid inducible gene I (RIG-I) is a pattern recognition receptor (PRR) responsible for detection of nucleic acids from pathogens in the cytoplasm of infected cells and induction of type I interferon...Full Text Available
SummaryHuman skin expresses elements of the hypothalamo-pituitary-adrenal (HPA) axis including pro-opiomelanocortin (POMC), corticotropin releasing hormone (CRH), the CRH receptor-1...Full Text Available
We investigated the effects of PSARK∷IPT (for Senescence-Associated Receptor Kinase∷Isopentenyltransferase) expression and cytokinin production...Full Text Available
Cyclophilins (Cyps), the intracellular receptors for Cyclosporine A (CsA), are responsible for peptidyl-prolyl cis-trans isomerisation and for chaperoning several membrane proteins. Those functions...Full Text Available
We presented data showing that the CART-19 cells expressing the 4-1BB signaling domain can have unprecedented and massive in-vivo expansion, traffic to tumor sites, persist long term in vivo, and induce...Full Text Available
Cytokinins are distributed through the vascular system and trigger responses of target cells via receptor-mediated signal transduction. Perception and transduction of the signal can occur at the plasma...Full Text Available
Cd36 is a small-molecular-weight integral membrane protein expressed in a diverse, but select, range of cell types. It has an equally diverse range of ligands and physiological functions, which has...Full Text Available
Benzodiazepine withdrawal anxiety is associated with potentiation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) currents in hippocampal CA1 pyramidal...Full Text Available
Calcium, vitamin D, exposure to sunshine, and vitamin D receptor (VDR) genotypes have been associated rectal cancer. We used data from 750 rectal tumors and 1,205 population-based...Full Text Available
Recent evidence suggests a role for corticotropin-releasing factor (CRF) in the regulation of pair bonding in prairie voles. We have previously shown that monogamous and non-monogamous vole...Full Text Available
The pharynx is the primary reservoir for strains of group A Streptococcus (GAS) associated both with pharyngitis (streptococcal sore throat) and with invasive or “flesh-eating”...Full Text Available
BackgroundCancer stem cells (CSCs) have increased resistance to cancer chemotherapy. They can be enriched as drug-surviving CSCs (D-CSCs) by growth with chemotherapeutic drugs, and/or...Full Text Available
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
AIM: To investigate atrial natriuretic peptide (ANP) secretion from gastric mucosa and the relationship between the ANP/natriuretic peptide receptor type A (NPR-A) pathway and diabetic gastroparesis.METHODS:...Full Text Available
Experimental studies have demonstrated that not only dopaminergic signaling but also glutamatergic/NMDA receptor signaling play indispensable roles in the development of methamphetamine psychosis. Our...Full Text Available
Pharmacologic or genetic deletion of components of the renin-angiotensin system leads to postnatal kidney injury, but the roles of these components in kidney development are unknown. To test the hypothesis...Full Text Available
Numerous xenobiotics, including therapeutics agents, are substrates for bioactivation to electrophilic reactive intermediates that may covalently modify biomolecules. Selective estrogen receptor...Full Text Available
BackgroundMale infertility is a common cause of reproductive failure in humans. In mice, targeted deletions of the genes coding for FKBP6 or FKBP52, members of the FK506 binding...Full Text Available
We sought to determine the effects of activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) on multilocularization of adipocytes in adult white adipose tissue (WAT). Male...Full Text Available
Endogenous immune complexes present in sera from 10 different patients with systemic lupus erythematosus (SLE) in an active phase were allowed to bind to Raji cells; the ability of intact complement...Full Text Available
BackgroundCentrosome aberrations can cause genomic instability and correlate with malignant progression in common human malignancies such as breast and prostate cancer. Deregulation...Full Text Available
ObjectiveThe goal of the study was to investigate the genetic and molecular basis of a novel syndrome of marked hyperglucagonemia and pancreatic α cell hyperplasia...Full Text Available
BackgroundThis in vitro study was conducted to compare the accuracy of two digital image receptors in identifying the location of tip of a fine endodontic file and radiographic apex...Full Text Available
ABSTRACT: Metabolomic analysis will provide the next large set of clues to further our understanding of human health and disease. A recent study has elucidated the significant differences in the metabolomes of adipocytes, serum and an adipocyte cell line after activation of two nuclear receptors, peroxisome proliferator activated receptor ?/? (PPAR?/?) and PPAR?. These findings hold great promise for explaining fundamental differences in the mechanisms of PPAR agonists and for identifying targets for the treatment of diabetes.See related research article: http://genomebiology.com/2011/12/8/R75. PMID:21861850
Resistance and tolerance are two types of host defense mechanisms that increase fitness in response to fungi. Several genetic polymorphisms in pattern recognition receptors, most remarkably Toll-like receptors (TLRs), have been described to influence resistance and tolerance to aspergillosis in distinct clinical settings. TLRs on dendritic cells pivotally contribute in determining the balance between immunopathology and protective immunity to the fungus. Epithelial cells also contribute to this balance via selected TLRs converging on indoleamine-2,3-dioxygenase (IDO). Studies in experimental hematopoietic transplantation confirmed the dichotomy of pathways leading to resistance and tolerance to the fungus providing new insights on the relative contribution of the hematopoietic/nonhematopoi...
Trastuzumab increases survival amongst women with human epidermal growth factor receptor (HER)-2 receptor positive metastatic breast cancer, but maternal and fetal risks are associated with advanced disease and its treatment in pregnancy. We present a case of a primigravid with HER-2 positive metastatic breast cancer who received trastuzumab throughout pregnancy. She presented with cerebral metastases, requiring surgical decompression and resection. Reversible oligohydramnios developed during pregnancy. Fetal safety data on trastuzumab in pregnancy is limited, but case reports suggest a recurring pattern of (mostly reversible) oligohydramnios.
The possibilities for therapy in the field of severe cardiac insufficiency have been extended in recent years by the introduction of novel agents endowed with a positive inotropic action. These substances may be arranged in two large classes: sympathomimetic agents and "non sympathomimetic--non digitalis-like" inotropic agents. The stimulant action of noradrenaline, adrenaline and isoproterenol on beta-adrenergic myocardial receptors has been clearly demonstrated but the usefulness of these medicines is limited by their positive chronotropic and arrhythmogenic actions. Dopamine and dobutamine have proved to be very useful in the treatment of patients in intensive care units. However, the exclusively intravenous route of administration limits their importance to the medium or long term. Several compounds, which are active by the oral route, have been the subject of therapeutic trials for the short or medium term. The problems posed by their use result, in the first ...
PACAP (pituitary adenylate cyclase activating polypeptide) is widely distributed neuropeptide acting via three subtypes of receptors, PAC(1), VPAC(1) and VPAC(2). Here we examined the localisation and nature of PACAP-immunoreactive nerves in the rat thyroid and parathyroid glands and defined the distribution of PAC(1), VPAC(1) and VPAC(2) receptor mRNA's. In the parathyroid gland a large number of nerve fibres displaying PACAP-immunoreactivity were distributed beneath the capsule, around blood vessels and close to glandular cells. Most of the PACAP-nerves were sensory, since they co-stored CGRP (calcitonin-gene-related peptide) and were sensitive to capsaicin-treatment. mRNA's for PAC(1) and VPAC(2) receptors occurred in the parathyroid gland, mainly located in the glandular cells. In the thyroid gland PACAP-immunoreactive nerve fibres were associated with blood vessels, thyroid follicles and parafollicular C-cells. A high ...
Screening of a human placenta lambdagt11 library has led to the isolation of the cDNA for the human ..beta../sub 1/-adrenergic receptor (..beta../sub 1/AR). Used as the probe was the human genomic clone termed G-21. This clone, which contains an intronless gene for a putative receptor, was previously isolated by virtue of its cross hybridization with the human ..beta../sub 2/-adrenergic receptor (..beta../sub 2/AR). The 2.4-kilobase cDNA for the human ..beta../sub 1/AR encodes a protein of 477 amino acid residues that is 69% homologous with the avian ..beta..AR but only 54% homologous with the human ..beta../sub 2/AR. This suggests that the avian gene encoding ..beta..AR and the human gene encoding ..beta../sub 1/AR evolved from a common ancestral gene. RNA blot analysis indicates a message of 2.5 kilobases in rat tissues, with a pattern of tissue distribution consistent with ..beta../sub 1/AR binding. This pattern is quite ...
The effect of mean daily air temperature (MDT) on flowering rate (the reciprocal of days to flower) was quantified for 18 species of annual bedding plants. Plants were grown in environmental growth chambers at constant air temperature set points of 5, 7.5, 10, 15, 25, or 30^oC and under an irradiance of 160-180mmolm^-^2s^-^1, with a 16-h photoperiod. Nonlinear mathematical equations were developed to predict the effect of MDT on flowering rate and to estimate the base, optimum, and maximum temperatures (Tmin, Topt, and Tmax), which are the temperatures at which flowering rates are zero (low temperature), maximal, and zero once again (high temperature), respectively. The estimated Tmin varied among species and ranged from 1.1^oC in French marigold (Tagetes patula L.) to 9.9^oC in angelonia ...
One of the challenges facing engineers is developing newer, safer detonators that are equivalent to devices currently in use. There is no clear consensus on an exact method for drawing equivalence of detonators. This paper summarizes our current efforts to develop diagnostics addressing various aspects of detonator design to better quantify and prove equivalency. We consider various optical techniques to quantify the output pressure and output wave shape. The development of a unique interpretation of streak camera breakouts, known as the apparent center of initiation, will be discussed as a metric for detonation wave shape. Specific examples apply these techniques to the comparison of a new laser-driven detonator with an existing exploding bridgewire (EBW) detonator. Successes and short-comings of the techniques will be discussed.
Remote sensing is the most practical method available to managers of fire-prone forests for quantifying and mapping fire impacts. Differenced Normalised Burn Ratio (?NBR) is among the most widely used spectral indices for the mapping of burn severity but is difficult to interpret in terms of fire-related changes in key biophysical attributes and processes. We propose to quantify burn severity as a change in the leaf area index (?LAI) of a stand. LAI is a key biophysical attribute of forests, and is central to understanding their water and carbon cycles. Previous studies have suggested that changes in canopy LAI may be a major contributor to ?NBR and to the composite burn index (CBI) that is frequently used in combination with the NBR to assess burn severity on the ground. We applied remote...
We investigate how, and to what extent, morphological complexity of the language influences text classification using support vector machines (SVM). The Croatian-English parallel corpus provides the basis for direct comparison of two languages of radically different morphological complexity. We quantified, compared, and statistically tested the effects of morphological normalisation on SVM classifier performance based on a series of parallel experiments on both languages, carried over a large scale of different feature subset sizes obtained by different feature selection methods, and applying different levels of morphological normalisation. We also quantified the trade-off between feature space size and performance for different levels of morphological normalisation, and compared the resul...
Properly quantified performance of a solar-thermal cavity receiver must not only account for the energy gains and losses as dictated by the First Law of thermodynamics, but it must also account for the quality of that energy. Energy quality can only be determined from the Second Law. In this paper, an equation developed for the Second-Law efficiency of a cavity receiver is presented as an evolution from the definition of available energy or ''availability'' (occasionally called exergy). The variables required are all either known or readily determined. The importance of considering the Second-Law is emphasized by a comparison of the First- and Second-Law efficiencies around an example of data collected from two receivers that were designed for different purposes, where the attempt was made to demonstrate that a Second-Law approach to quantifying the performance of a solarthermal cavity receiver lends more ...
This case study is an application, to a nuclear power plant, of the methodology for quantifying environmental costs and benefits, contained in the regional energy plan, adopted in April, 1983, by the Northwest Power Planning Council, pursuant to Public Law 96-501.The study is based on plant number 2 of the Washington Public Power Supply System (WNP-2), currently nearing completion on the Hanford Nuclear Reservation in eastern Washington State. This report describes and documents efforts to quantify and estimate monetary values for the following seven areas of environmental effects: radiation/health effects, socioeconomic/infrastructure effects, consumptive use of water, psychological/health effects (fear/stress), waste management, nuclear power plant accidents, and decommissioning costs. 103 references.
Laser-induced phase-separation polymerization of a porous acrylate polymer is used for in-situ fabrication of dialysis membranes inside glass microchannels. A shaped 355 nm laser beam is used to produce a porous polymer membrane with a thickness of about 15 .mu.m, which bonds to the glass microchannel and forms a semi-permeable membrane. Differential permeation through a membrane formed with pentaerythritol triacrylate was observed and quantified by comparing the response of the membrane to fluorescein and fluorescently tagging 200 nm latex microspheres. Differential permeation was observed and quantified by comparing the response to rhodamine 560 and lactalbumin protein in a membrane formed with SPE-methylene bisacrylamide. The porous membranes illustrate the capability for the present technique to integrate sample cleanup into chip-based analysis systems.
MRT is able to demonstrate arteries while MR angiography can quantify blood flow by a non-invasive method. In the present paper blood flow measurements were carried out in four selected cases on the basis of phase mapping. In 3 patients with lesions in the pelvis or thigh, angiography was performed in order to localise the stenosis or occlusion and this was followed by qantitative blood flow measurements. The results showed that angiography may not always provide all necessary information concerning a haemodynamically significant stenosis. The method may also be used for quantifying blood flow in the renal arteries and that it has significant advantages over the colour Doppler method. (orig.).
Abstract A method was developed to quantify the effect of scanner instability on functional MRI data by comparing the instability noise to endogenous noise present when scanning a human. The instability noise was computed from agar phantom data collected with two flip angles, allowing for a separation of the instability from the background noise. This method was used on human data collected at four 3 T scanners, allowing the physiological noise level to be extracted from the data. In a -well-operating- scanner, the instability noise is generally less than 10% of physiological noise in white matter and only about 2% of physiological noise in cortex. This indicates that instability in a well-operating scanner adds very little noise to functional MRI results. This new method allows researcher...
An exposure chamber is described for the quantifiable addition of fine and ultrafine aerosol particulate matter directly to cells and used to demonstrate the in vitro cytotoxicity of fine 1,4-naphthoquinone particles to murine lung epithelial cells. The electrostatic particulate dosage and exposure system (EPDExS) operates on the principle of electrostatic precipitation and is shown to deposit fine and ultrafine aerosol particles directly to cells with 100% efficiency for particle diameters in the range of 40-530nm. This range is not limited by the EPDExS, but rather by the aerosolization method used for this study. Numbers of particles deposited onto the cells are counted with a condensation particle counter, negating any need to calculate or estimate particle exposure. The process of par...
Aim: There has been a great demand for developments of the radioligands to visualize the N-methyl-D-aspartate (NMDA) receptors by PET/SPECT. We have recently synthesized two C-11 labeled antagonists for the glycine-binding site on NMDA receptors. The aim of this work is to examine for their in vitro and in vivo binding characteristics, and to evaluate their potentials as PET radioligands for the NMDA receptors. Materials and methods: Two C-11 labeled 4-hydroxy-2-quinolones (1 and 2) were synthesized by conventional methylation of the corresponding phenols with ["1"1C]methyl iodide. In vitro and ex vivo quantitative autoradiographs with imaging plate, as well as animal PET, were employed in order to evaluate their in vitro and in vivo binding to the NMDA receptors. Results: The compound 1 showed the specific binding to rat brain slices with higher localization in the hippocampus and cerebral cortex than ...
Nodular hepatic involvement of multiple myeloma is very rare. We report here on a case of nodular hepatic involvement of multiple myeloma that mimicked intrahepatic cholangiocarcinoma. In patients with multiple myeloma, hepatic involvement of the multiple myeloma might be included in the differential diagnosis of hepatic mass.
..cap alpha..-2 adrenergic agents have been shown to influence blood pressure, heart rate and other physiological and behavioral functions through interactions with adrenergic pathways within the central nervous system. Pharmacologically relevant ..cap alpha..-1 adrenergic receptors were biochemically characterized and radiohistochemically analyzed in intact tissue sections of the rat and human central nervous system. The anatomical distribution of the ..cap alpha..-2 receptors, labeled with the agonist (/sup 3/H)para-aminoclonidine, verified the concept that ..cap alpha..-2 receptors are closely associated with adrenergic nerve terminals and that ..cap alpha..-2 agents can influence autonomic and endocrine function through an action in the central nervous system. Since ..cap alpha..-2 agonists can influence sympathetic outflow, ..cap alpha..-2 binding sites were closely analyzed in the intermediolateral cell column of the ...
The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has two major functions: interacting with the receptor to mediate virus entry and inducing protective immunity. Coincidently, the receptor-binding domain (RBD, residues 318-510) of SAR-CoV S protein is a major antigenic site to induce neutralizing antibodies. Here, we used RBD-Fc, a fusion protein containing the RBD and human IgG1 Fc, as a model in the studies and found that a single amino acid substitution in the RBD (R441A) could abolish the immunogenicity of RBD to induce neutralizing antibodies in immunized mice and rabbits. With a panel of anti-RBD mAbs as probes, we observed that R441A substitution was able to disrupt the majority of neutralizing epitopes in the RBD, suggesting that this residue is critical for the antigenic structure responsible for inducing protective immune responses. We also demonstrated that the RBD-Fc bearing R441A mutation could not ...
This paper reports on a Level 1 PRA performed on the Omega West Reactor at Los Alamos National Laboratory. A Master Logic Diagram was used to identify possible initiating events. A chi-square distribution was used to quantify initiating event frequencies given that no initiating events have occurred in 30 years of OWR operation. The PRA results are presented as both probability density function and cumulative distribution function curves.
This paper describes a research and development project to quantify the effects of cleaning the coal feed on the yield patterns and processing rates for the Liquid Solvent Extraction (LSE) direct coal liquefaction process and to obtain information on the effect of the co-refining of coal-derived and petroleum distillates to premium transport fuels. 6 refs., 25 figs., 40 tabs.
We have measured the oxygen positions in LaNiO{sub 3} films to elucidate the coupling between epitaxial strain and oxygen octahedral rotations. The oxygen positions are determined by comparing the measured and calculated intensities of half-order Bragg peaks, arising from the octahedral rotations. Combining ab initio density-functional calculations with these experimental results, we show how strain systematically modifies both bond angles and lengths in this functional perovskite oxide.
Wax appearance temperature (WAT) of three petroleum waxes in different solvent systems under varying thermal conditions has been determined. It is observed that this temperature mainly is a function of the concentration of the wax and the solubility parameter ([delta]) of the solvent taken. This dependence of WAT has been quantified in terms of these variables in the form of mathematical equation and nomographs. (orig.)
Plantago ovata Forsk - an economically important medicinal plant - was analyzed for trace elements and chlorophyll in a study of the effects of gamma radiation on physiological responses of the seedlings. Proton-induced X-ray emission (PIXE) technique was used to quantify trace elements in unirradiated and gamma-irradiated plants at the seedling stage. The experiments revealed radiation-induced changes in the trace element and chlorophyll concentrations.
This research has two main goals; (1) to quantify mechanisms for radon entry into homes of different types and to determine the fraction of indoor radon attributable to each source and (2) to model and calculate the dose (and therefore alpha particle fluence) to cells in the human and animal tracheobronchial tree that is pertinent to induction of bronchogenic carcinoma from inhaled radon daughters.
The alkylation products formed by in vitro treatment of DNA with tritium-labeled 1,3-bis(2-chloroethyl)-1-nitrosourea (3H-BCNU) were identified and quantified. Twelve adducts were resolved...Full Text Available
Due to the intensity and vast number of subjects, this Bremen experts' discussion, too, could discuss only part of the problem of the possibilitiy to quantify the radiation hazard. One preliminary result is that there is no scientific proof of the harmlessness of radiation exposure during normal operation of a nuclear power plant, either within the plant or in its vicinity. Other results are that some important questions can not be answered yet, and that there are important hints on the dangers even of low radiation doses. (GL).
Veterinarians and farmers employing multivalent killed vaccines in lactating dairy cows have reported transient losses in milk production. Few studies have quantified this loss. In this report, effects...Full Text Available
DescriptionAs part of a wider effort to develop new approaches to evaluating and quantifying the benefits of chemicals regulation, this project will review the effectiveness of existing information provision tools (such as classification and labelling for hazardous properties) in terms of affecting user behaviour. As some EC legislation relating to regulation of chemicals has been in place for some time, an assumption is made that the information provided by it is leading to an improvement in the way chem [continued...
We analyze large diffusion-limited aggregates and uncover a {ital discrete} scaling invariance in their inner structure, which can be quantified by the introduction of a set of {ital complex} fractal dimensions. We provide a theoretical framework and prediction of their values based on renormalization group theory and a previous wavelet analysis. {copyright} {ital 1996 The American Physical Society.}
Helical tomotherapy presented many unique dosimetric challenges and solutions during the initial commissioning process, and some of them are presented. The dose calculation algorithm is convolution/superposition based. This requires that the energy fluence spectrum and magnitude be quantified. The methodology for doing so is described. Aspects of the energy fluence characterization that are unique to tomotherapy are highlighted. Many beam characteristics can be measured automatically by an included megavoltage computed tomography imaging system. This greatly improves data collection efficiency.
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 function.
The synthesis of (1',3'-{sup 3}H)4-(4'-azido-5',6',7',8'-tetrahydro-5'5'8',8'-tetramethyl-2'-anthracenyl)benzoic acid is described. This retinoid was designed as a photoaffinity probe of the receptor sites of cellular retinoic acid-binding protein and the nuclear retinoic acid receptor protein. The ({sup 3}H)azidoretinoid was prepared from 1,2,3,4-tetrahydro-1,1,4,4-tetra-methyl-7-(4-methylphenyl)-5-nitroanthracene in five steps in 15% yield (89% radiochemical purity by HPLC). {sup 1}H and {sup 3}H NMR was used to confirm the sites of {sup 3}H substitution on the ring. (author).
The measurement of physiological parameters in man is possible with the help of positron emission tomography (PET) and radiopharmaceuticals labeled with short lived positron emitters as C 11, N 13, O 15 and F 18. With the use of this substances it is possible to make a tomographic map defining regional metabolic parameters in normal and diseased brain. This technique has therefore also be named 'in vivo autoradiography'. The possibility of applying C 11 or F 18 labeled deoxyglucose with PET for detecting regional and local changes in cerebral metabolic rate of glucose in brain development in children of 5 days to 1 year of age is discussed. Beyond this a relationship between cerebral metabolic rate of glucose, cerebral blood flow and cerebral metabolic rate of oxygen by use of this technique after inhalation of O 15 and C 11-labeled CO_2 is shown. Attention is drawn to the application of C 11-methyl-spiperone and PET to visualize dopamine receptor density in the ...
A hallmark of congestive heart failure (CHF) is the activation of the cardiac endocrine system, in particular atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). The natriuretic peptides are a group of structurally similar but genetically distinct peptides that have diverse actions in cardiovascular, renal, and endocrine homeostasis. ANP and BNP are of myocardial cell origin and C-type natriuretic peptide (CNP) is of endothelial origin. ANP and BNP bind to the natriuretic peptide-A receptor (NPR-A), which, via 3',5'-cyclic guanosine monophosphate (cGMP), mediates natriuresis, vasodilatation, renin inhibition, antimitogenesis, and lusitropic properties. CNP lacks natriuretic actions but possesses vasodilating and growth inhibiting actions via the guanylyl cyclase-linked natriuretic peptide-B receptor. All three peptides are cleared by the natriuretic peptide-C receptor and degraded by the ectoenzyme neutral ...
This progress report covers period from Nov. 1, 1989 to Aug. 31, 1990. The long term objective was to develop receptor-binding radiotracers for SPECT or PET imaging of CNS or peripheral nervous system. The specific chemistry aims, as understood on the basis of past findings, were: to synthesize and develop a more polar analogs of 4IQNB, possessing similar binding characteristics but eliminated more rapidly from the surrounding tissues and the target organ, to design a method of introducing a technetium chelating group onto a molecule or cholinergic agent without drastic lowering of its apparent affinity, to synthesize and develop radiotracers based on m-AChR antagonists selective for one of the subtypes of the receptor. The chemistry service aims were to prepare and characterize (R,R)- and (R,S)-4IQNB and derivatives, to provide the triazene intermediate to other investigators, and to provide ({sup 123}I)4IQNB for in vivo imaging. The ...
Crystallography and computer modeling have been used to exploit a previously unexplored channel in the glucocorticoid receptor (GR). Highly potent, nonsteroidal indazole amides showing excellent complementarity to the channel were designed with the assistance of the computational technique AlleGrow. The accuracy of the design process was demonstrated through crystallographic structural determination of the GR ligand-binding domain-agonist complex of the D-prolinamide derivative 11. The utility of the channel was further exemplified through the design of a potent phenylindazole in which structural motifs, seen to interact with the traditional GR ligand pocket, were abandoned and replaced by interactions within the new channel. Occupation of the channel was confirmed with a second GR crystal structure of this truncated D-alaninamide derivative 13. Compound 11 displays properties compatible with development as an intranasal solution formulation, whereas oral ...
We report the isolation of cDNA clones for the mouse {alpha}7 neuronal nicotinic acetylcholine receptor subunit (gene symbol Acra7), the only nicotinic receptor subunit known to bind a-bungarotoxin in mammalian brain. This gene may have relevance to nicotine sensitivity and to some electrophysiologic findings in schizophrenia. The mouse {alpha}7 subunit gene encodes a protein of 502 amino acids with substantial identity to the rat (99.6%), human (92.8%), and chicken (87.5%) amino acid sequences. The {alpha}7 gene was mapped to mouse chromosome 7 near the p locus with the following gene order from proximal to distal: Myod1-3.5 {+-}1.7 cM-Gas2-0.9 cM {+-} 0.9 cM-D7Mit70-1.8 {+-} 1.2 cM- Acra7-4.4 {+-}1.0 cM-Hras1-ps11/Igf1r/Snrp2a. The human gene was confirmed to map to the homologous region of human chromosome 15q13-q14. 26 refs., 3 figs.
The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a ...
Structural instability of wild-type fibroblast growth factor (FGF)-1 and its dependence on exogenous heparin for optimal activity diminishes its potential utility as a therapeutic agent. Here we evaluated FGFC, an FGF1:FGF2 chimeric protein, for its receptor affinity, absolute heparin-dependence, stability and potential clinical applicability. Using BaF3 transfectants overexpressing each FGF receptor (FGFR) subtype, we found that, like FGF1, FGFC activates all of the FGFR subtypes (i.e., FGFR1c, FGFR1b, FGFR2c, FGFR2b, FGFR3c, FGFR3b and FGFR4) in the presence of heparin. Moreover, FGFC activates FGFRs even in the absence of heparin. FGFC stimulated keratinocytes proliferation much more strongly than FGF2, as would be expected from its ability to activate FGFR2b. FGFC showed greater struct...
Abstract Toll-like receptor 2 (TLR2) is an immune sensor for gram-positive bacterial cell wall components. Single-nucleotide polymorphisms (SNPs) in the TLR2 gene that impair its function may, therefore, influence the risk and outcomes of gram-positive bacterial infections. In a cohort of 694 liver transplant recipients, we assessed the TLR2 SNP that is translated into an amino acid substitution of arginine for glutamine at position 753 (R753Q), and we found that its presence was associated with the clinical characteristics and outcomes of gram-positive bacterial infections. The proportions of patients with the TLR2 R753Q SNP did not significantly differ between those with gram-positive bacterial infections and those without gram-positive bacterial infections (9.6% versus 9.6%, P = 0.999)....
Rationale Receptor occupancy study has been performed to evaluate pharmacokinetic profiles in new antipsychotic drug development. While these findings highlight the value of positron emission tomography (PET) for dose-finding study, what is unclear is if it is necessary to conduct these studies in patients with schizophrenia or whether studies in healthy volunteers are adequate. Objectives To determine if it is necessary to conduct dopamine receptor occupancy studies in patients with schizophrenia or whether studies in healthy volunteers are adequate for dose-finding study, we compared the concentration?occupancy relationship in terms of EC50 between patients and healthy volunteers. Methods Ten healthy volunteers and eight patients with schizophrenia participated in the study. We measured ...
Endogenous opioid peptides (EOP) are molecules affecting many biological functions influencing productive and reproductive performance. They increase in stress conditions and interact with specific opioidergic receptors (OR): delta, kappa and mu. Several studies in other animal species suggest that they can also affect sperm cell motility. In fish the ionic external environment modulates the increase of intracellular calcium ion that is required to activate sperm motility after spawning. In mammals OR are functionally associated to calcium channels and in fishes calcium is highly required for fish sperm activation. In this study the presence of OR on spermatozoa of two Perciform fish, the sharpsnout seabream (Diplodus puntazzo, family Sparidae) and the European sea bass (Dicentrarchus labr...
Intervertebral disc (IVD) cell apoptosis has been suggested to play an important role in promoting the degeneration process. It has been demonstrated that IVD cell apoptosis occurs through either death receptor, mitochondrial or endoplasmic reticulum (ER) pathway. Our study aimed to explore the relationship among these three pathways and grade of IVD degeneration (IVDD). IVDs were collected from patients with lumbar fracture, vertebral tumor, disc herniation or spondylolisthesis. IVDs were distinguished by MRI and histomorphological examination, cell apoptosis was detected by TUNEL staining. Biomarkers of these three apoptosis pathways were detected by RT-PCR and Western blot. Furthermore, the correlation between apoptosis pathways biomarkers and disc pathology were analyzed. Nucleus pulpo...
Aberrant amyloid-b peptide (Ab) accumulation along with altered expression and function of nicotinic acetylcholine receptors (nAChRs) stand prominently in the etiology of Alzheimer's disease (AD). Since the discovery that Ab is bound to a7 nAChRs under many experimental settings, including post-mortem AD brain, much effort has been expended to understand the implications of this interaction in the disease milieu. This research update will review the current literature on the a7 nAChR-Ab interaction in vitro and in vivo, the functional consequences of this interaction from sub-cellular to cognitive levels, and discuss the implications these relationships might have for AD therapies.
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...
Previous studies from this laboratory have shown that certain N-substituted phthalimides (NSPs) exhibit GA-like activity in a range of specific bioassays and that bioactive NSPs compete with ({sup 3}H)-GA{sub 4} for soluble binding sites in cucumber homogenates. As such, these compounds may prove useful in the purification and characterization of GA receptor proteins. To this end, five azido-NSPs have been synthesized and are currently being screened for biological activity and photochemical stability. Three azido-NSPs elicit {alpha}-amylase production in barley half-seeds and stimulate tissue elongation in d{sub 5} maize, lettuce, sunflower, and soybean. Further evaluations are in progress and these data as well as the utility of these compounds as photo-affinity ligands will be discussed.
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)
DNA methylation is considered as a potential cause of aberrations in regulation of gene expression during carcinogenesis. Therefore, changes in DNA methylation patterns may be targets for chemoprevention. In the present study, we investigated effects of all-trans retinoic acid (ATRA), vitamin D3, and resveratrol alone and in combination with adenosine analogues: 2-chloro-2'-deoxyadenosine (2CdA) and 9-beta-d-arabinosyl-2-fluoroadenine (F-ara-A), on methylation and expression of retinoic acid receptor beta 2 (RARbeta2) in MCF-7 and MDA-MB-231 breast cancer cell lines. Alterations in methylation and expression levels after treatment of cells with the tested compounds were evaluated by methylation-sensitive restriction analysis (MSRA) and real-time PCR, respectively. RARbeta2 promoter in the ...
The gene encoding the human type I pituitary adenylate cyclase activating polypeptide receptor (ADCYAP1R1) was mapped to chromosome 7 by PCR analysis of genomic DNA from a human/rodent somatic cell hybrid mapping panel. This assignment was confirmed and the gene localized to chromosome band 7p14 by fluorescence in situ hybridization. A yeast artificial chromosome containing ADCYAP1R1 was identified in the CEPH {open_quotes}B{close_quotes} Mega-YAC library. This YAC includes two highly polymorphic dinucleotide repeat sequences that will facilitate genetic studies of the contribution of ADCYAP1R1 in disease states of the central nervous and neuroendocrine systems. 13 refs., 1 fig.
The authors have cloned and determined the entire nucleotide sequence of cDNAs corresponding to the putative {alpha} subunits of the human and rat mast cell high-affinity IgE receptors. Both human and rat cDNAs encode an NH{sub 2}-terminal signal peptide, two immunoglobulin-like extracellular domains (encoded by discrete exons), a hydrophobic transmembrane region, and a positively charged cytoplasmic tail. The human and rat {alpha} subunits share an overall homology with one another and the immunoglobulin gene family, suggesting that they arose from a common ancestral gene and continue to share structural homology with their ligands. In addition, the rat gene is transcribed into at least three distinct forms, each of which yields a somewhat different coding sequence.
Cell surface glycosaminoglycans play important roles in cell adhesion and viral entry. Laboratory strains of two alphaviruses, Sindbis and Semliki Forest virus, have been shown to utilize heparan sulfate as an attachment receptor, whereas Ross River virus (RRV) does not significantly interact with it. However, a single amino acid substitution at residue 218 in the RRV E2 glycoprotein adapts the virus to heparan sulfate binding and expands the host range of the virus into chicken embryo fibroblasts. Structures of the RRV mutant, E2 N218R, and its complex with heparin were determined through the use of electron cryo-microscopy and image reconstruction methods. Heparin was found to bind at the distal end of the RRV spikes, in a region of the E2 glycoprotein that has been previously implicated in cell-receptor recognition and antibody binding.
Gonadal hormones modulate neurogenesis in the dentate gyrus differentially in male and female adult rodents. Neurogenesis is comprised of at least two components: cell proliferation (the production of new cells) and cell survival (the number of new neurons that survive to maturity). Previous studies have found sex differences in the level of cell proliferation in the dentate gyrus only when comparing females in a high estrogen state to males. This review focuses on the effects of acute and chronic levels of estrogens or androgens on hippocampal neurogenesis in the adult male and female rodent. Evidence is also reviewed for the co-localization of androgen receptors and estrogen receptors (ER) with markers for cell proliferation or immature new cell survival. Briefly, evidence suggests that ...
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...
Results in this study are consistent with those of Murdock and his colleagues who clearly demonstrated that clonidine, an agonist of octopaminergic receptors in some insects, significantly increases sucrose feeding. Their studies, however, did not examine the effect of clonidine on protein feeding. Injection of a 20mg/ml/fly dose of clonidine significantly reduces protein feeding in both sexes of Phormia regina, instead of stimulating feeding as is observed with carbohydrate feeding. The manner in which the flies are fed prior to starvation and the method of testing influences the amounts of diet consumed. It is proposed that the biogenic amines influence the state of hunger (i.e., protein versus carbohydrates) while other chemicals and neural mechanisms (i.e., such as sulfakinins and stre...
In many species social behaviors are dependent on integration of chemosensory and hormonal cues. Many chemosensory stimuli are detected by the vomeronasal organ, which projects to many regions that contain steroid receptors, including the medial amygdala. In male hamsters, testosterone is known to acutely increase in response to chemosensory stimulation, and can facilitate sexual behavior by direct action within the medial amygdala. Conspecific stimuli activate the anterior (MeA) and posterior (MeP) medial amygdala, while heterospecific stimuli activate only MeA. Chemosensory stimuli with different social significance differentially activate the dorsal and ventral subdivisions of MeA and MeP. Therefore, it is likely that steroids differentially facilitate stimulation of the medial amygdala...
Six genes involved in the heparan sulfate and heparin metabolism pathway, DSEL (dermatan sulfate epimerase-like), EXTL1 (exostoses (multiple)-like 1), HS6ST1...Full Text Available
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
The RNA packaging process for retroviruses involves a recognition event of the genome-length viral RNA by the viral Gag polyprotein precursor (PrGag), an important step in particle morphogenesis. The...Full Text Available
The cell types involved in the cellular immune response were studied with the GVH in vitro as a test system. Comparison of the activities of cells of different lymphoid organs in the...Full Text Available
The aim of this study was to investigate whether astroglia in the medullary dorsal horn (trigeminal spinal subnucleus caudalis; Vc) may be involved in orofacial neuropathic pain following trigeminal...Full Text Available
The incidence of arrhythmias after acute myocardial infarction of the inferior wall varies with the affected segment and increases when there is right ventricular involvement. This paper provides a...Full Text Available
Ataxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein...Full Text Available
BackgroundThe MYC transcription factors are known to be involved in the biology of many human cancer types. But little is known about the Myc/microRNAs cooperation in the regulation...Full Text Available
The effect of UV radiation in the wavelength region 230 nm to 302 nm on the ability of an irradiated mammalian cell to reactivate UV-irradiated mammalian virus was tested. An action spectrum for radiation enhanced reactivation (RER) is presented. The shape of the action spectrum points to a combined nucleic acid-protein target for UV radiation effects on this cellular parameter. An analysis of the results of others involving the biochemical and photobiological events involved in RER does not allow us to distinguish which macromolecule is the major contributor to this effect. Studies involving an analogous phenomenon in bacteris (Weigle reactivation) imply that RER and WR amy involve similar mechanisms. (author).
Photodiode Scintillation Detector for Anticoincidence Shielding An important goal of space research is to understand the physics involved in the activity of ...
Information Technology Glossary of Terms. Applets: Programs that run inside net browsers, usually in Java and typically involving modestly interactive ...
... Considering these observations, it is most likely that Brucela proteins involved in protective immunity will preferentially stimulate INF-g producing T ...
We reported previously that Fas-induced hepatic failure in normal mice was attenuated or prevented by exogenous transferrin (Tf), particularly apoTf. Here we show in C57BL6J/129 mice with genetic...Full Text Available
An analogue of hGH isolated from plerocercoids of the tapeworm Spirometra mansonoides displaces ["1"2"5I]hGH from its receptors in rabbit, rat, and hamster liver membranes. Biologically, plerocercoid growth factor (PGF) is more similar to hGH than to other mammalian GH's but has not been shown to bond human cells. Receptors specific for hGH have been described on cultured human lymphocytes (IM-9). In this study, the authors compared the binding of PGF and hGH in IM-9 cells and in rabbit hepatic membranes. IM-9 lymphocytes (12 x 10"6 cells/tube) were incubated with ["1"2"5I]hGH and increasing concentrations of hGH (ng/ml) or PGF (serial dilutions) for 90 min at 30"0 C. Specific binding (B_0 - NSB) was determined for each dose of hGH or PGF and the binding curves were analyzed by logit-log regression. The results show that PGF displaced ["1"2"5I]hGH from human cells in a dose dependent manner (r = 0.98). Based on the IM-9 assay, 1 ml of the PGF ...
Type II diabetes mellitus (T2DM) is often accompanied by non-alcoholic steatohepatitis (NASH) and associated with hypercholesterolemia, i.e. increased levels of plasma low-density...Full Text Available
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