Genetic studies of nicotine addiction in mice have utilized the oral self-administration model. However, it is unclear if strain differences in nicotine consumption are influenced by variation in bitter...Full Text Available
The actions of nicotine, hexamethonium, and ethanol on the hypothalamo-hypophysial system have been investigated in the rat. The antidiuretic action of nicotine was not inhibited by ethanol, nor by...Full Text Available
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...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
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
IntroductionThe objective of this study was to examine age-, hormone-, and sex-dependent differences to the behavioral effects of nicotine using place-conditioning...Full Text Available
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 ...
Environmental tobacco smoke (ETS), containing the developmental neurotoxicant, nicotine, is a prevalent component of indoor air pollution. Despite a strong association with active maternal smoking and sudden infant death syndrome (SIDS), information on the risk of SIDS due to prenatal and postnatal ETS exposure is relatively inconsistent. This literature review begins with a discussion and critique of existing epidemiologic data pertaining to ETS and SIDS. It then explores the biologic plausibility of this association, with comparison of the known association between active maternal smoking and SIDS, by examining metabolic and placental transfer issues associated with nicotine, and the biologic responses and mechanisms that may follow exposure to nicotine. Evidence indicates that prenatal ...
Tobacco use has been recognized to be a significant risk factor for the development and progression of periodontal disease. Its use is associated with increased pocket depths, loss of periodontal attachment,...Full Text Available
α7 neuronal nicotinic acetylcholine receptors (α7-nAChR) form Ca2+-permeable homopentameric channels modulating cortical network activity and cognitive processing....Full Text Available
Skeletal muscle uses calcium as a second messenger to respond and adapt to environmental stimuli. Elevations in intracellular calcium levels activate calcineurin, a serine/threonine phosphatase, resulting...Full Text Available
The second messenger signaling molecule bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) regulates many processes in bacteria, including motility, pathogenesis,...Full Text Available
BackgroundSynonymous sites are freer to vary because of redundancy in genetic code. Messenger RNA secondary structure restricts this freedom, as revealed by previous findings in...Full Text Available
BackgroundMicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the messenger RNA (mRNA) of protein coding genes. They control gene expression by either...Full Text Available
In heat-shocked tomato cell cultures, cytoplasmic heat shock granules (HSGs) are tightly associated with a specific subset of mRNAs coding mainly for the untranslated control proteins. This messenger...Full Text Available
Proteins that metabolize or bind the nucleotide second messenger cyclic diguanylate regulate a wide variety of important processes in bacteria. These processes include motility, biofilm formation, cell...Full Text Available
Calcium ions represent universal second messengers within neuronal cells integrating multiple cellular functions, such as release of neurotransmitters, gene expression, proliferation, excitability,...Full Text Available
Electrically triggered action potentials in the giant alga Chara corallina are associated with a transient rise in the concentration of free Ca(2)+ in the cytoplasm (Ca(2)+(cyt)). The present measurements of Ca(2)+(cyt) during membrane excitation show that stimulating pulses of low magnitude (subthreshold pulse) had no perceivable effect on Ca(2)+(cyt). When the strength of a pulse exceeded a narrow threshold (suprathreshold pulse) it evoked the full extent of the Ca(2)+(cyt) elevation. This suggests an all-or-none mechanism for Ca(2)+ mobilization. A transient calcium rise could also be induced by one subthreshold pulse if it was after another subthreshold pulse of the same kind after a suitable interval, i.e., not closer than a few 100 ms and not longer than a few seconds. This dependency of Ca(2)+ mobilization on single and double pulses can be simulated by a model in which a second messenger is produced in a voltage-dependent manner. This second ...
Electrically triggered action potentials in the giant alga Chara corallina are associated with a transient rise in the concentration of free Ca2+ in the cytoplasm (Ca2+cyt). The present measurements of Ca2+cyt during membrane excitation show that stimulating pulses of low magnitude (subthreshold pulse) had no perceivable effect on Ca2+cyt. When the strength of a pulse exceeded a narrow threshold (suprathreshold pulse) it evoked the full extent of the Ca2+cyt elevation. This suggests an all-or-none mechanism for Ca2+ mobilization. A transient calcium rise could also be induced by one subthreshold pulse if it was after another subthreshold pulse of the same kind after a suitable interval, i.e., not closer than a few 100 ms and not longer than a few seconds. This dependency of Ca2+ mobilization on single and double pulses can be simulated by a model in which a second messenger is produced in a voltage-dependent manner. This second messenger ...
This study focuses on comparing reports of nicotine withdrawal, craving, and depressive symptoms obtained using an Interactive Voice Response (IVR) system and several questionnaires. As part of a smoking cessation trial, daily reports of withdrawal, craving, and negative mood were collected using an IVR system for 7 days after participants attempted to quit smoking, and several pencil and paper questionnaires (i.e., the Minnesota Nicotine Withdrawal Scale, the Questionnaire on Smoking Urges, and the Center for Epidemiological Studies-Depression) were completed a week after the target quit date. The sample was composed of 378 daily smokers. Moderate to high correlations were found between the research questionnaires obtained at the end of the week and the corresponding daily IVR reports of ...
Intraindividual variability of measurements of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), nicotine, cotinine, and r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene...Full Text Available
A fast and sensitive LC-ESI-MS method is described for the comparative quantification of 16 estrogen metabolites based on the derivatization of estrogens with a novel derivatizing reagent, N-methyl-nicotinic...Full Text Available
Objective:This article examines relationships between reproductive onset and lifetime history of smoking, regular smoking, and nicotine dependence, and cannabis and other illicit...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
Background:Nicotine alters auditory event-related potentials (ERPs) in rodents and humans and is an effective treatment for smoking cessation. Less is known about the effects of...Full Text Available
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 present paper further characterizes the cholinergic properties of acetylselenonium choline (ASeCh, (CH3)2Se+CH2CH2OCOCH3). The data demonstrate that ASeCh possesses muscarinic receptor agonist properties as evidenced by vasodepressor and smooth muscle contractile activities which are enhanced by physostigmine and antagonized by atropine. ASeCh also possessed nicotinic agonist activity on frog rectus abdominis tissue which was potentiated by physostigmine, and blocked by d-tubocurarine. The relative potencies of ASeCh ranged from approximately 1% to approximately 6% of the potency of acetylcholine in the three types of preparations examined. PMID:1435078
A gamma-ray spectrometer (GRS) has been built and delivered to the Mercury MESSENGER spacecraft which launched on August 3, 2004, from Cape Canaveral, Florida. The GRS, a part of seven scientific instruments on board MESSENGER, is based on a coaxial high-purity germanium detector. Gamma-ray detectors based on germanium have the advantage of providing excellent energy resolution, which is critical to achieving the science goals of the mission. However, germanium has the disadvantage that it must operate at cryogenic temperatures (typically {approx}80 K). This requirement is easy to satisfy in the laboratory but difficult near Mercury, which has an extremely hot thermal radiation environment. To cool the detector, a Stirling cycle mechanical cooler is employed. In addition, radiation and conduction techniques a are used to reduce the GRS heat load. Before delivering the flight sensor, a complete thermal prototype was built and tested. The results ...
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
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
Positioning of release factor eRF1 toward adenines and the ribose-phosphate backbone of the UAAA stop signal in the ribosomal decoding site was studied using messenger RNA (mRNA) analogs containing...Full Text Available
Previous research utilizing the AcB/BcA recombinant congenic strains (RCS) of mice mapped provisional quantitative trait loci (QTLs) for the psychostimulant effects of nicotine to multiple regions on chromosomes 7, 11, 12, 14, 16, and 17. The current study was designed to confirm these QTLs in an A/J (A)??C57Bl/6J (B6) F2 cross and a panel of B6.A chromosome substitution strains (CSS). The panel of B6.A CSS consists of 21 strains, each carrying a different A/J chromosome on a B6 background. The A??B6 F2, CSS, A, and B6 mice were tested for sensitivity to the effects of nicotine on locomotor activity using a computerized open-field apparatus. In A??B6 F2 mice two QTLs were identified which confirm those previously observed in the AcB/BcA RCS. Significant differences in the expression of ...
Genome-wide association studies have linked lung cancer risk with a region of chromosome 15q25.1 containing CHRNA3, CHRNA5 and CHRNB4 encoding a3, a5 and b4 subunits of nicotinic acetylcholine receptors (nAChR), respectively. One of the strongest associations was observed for a non-silent single-nucleotide polymorphism at codon 398 in CHRNA5. Here, we have used pharmacological (antagonists) or genetic (RNA interference) interventions to modulate the activity of CHRNA5 in non-transformed bronchial cells and in lung cancer cell lines. In both cell types, silencing CHRNA5 or inhibiting receptors containing nAChR a5 with a-conotoxin MII exerted a nicotine-like effect, with increased motility and invasiveness in vitro and increasing calcium influx. The effects on motility were enhanced by addit...
A combination of sustained release (SR) naltrexone (32mg/day) and bupropion SR (360mg/day) plus behavioral counseling was evaluated for the treatment of smoking cessation and mitigation of nicotine withdrawal and weight gain. Thirty overweight or obese nicotine-dependent subjects were enrolled in a 24-week, open-label study; 85% and 63% completed 12 and 24weeks, respectively. The target quit date was Week 4. Week 4-12 continuous abstinence rate was 48%, 78% of subjects achieved CO 10ppm, serum cotinine decreased from 185 to 48mg/L, and tobacco use decreased from 129 to 14 cigarettes/week. Similar results were seen at Week 24. Body weight was essentially unchanged (Week 12: -0.1%; Week 24: +0.4%). Except for a transient significant increase 1week after the target quit date (p<0.05), nicotin...
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...
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.
This work aimed to develop a fast-dissolving film made of low dextrose equivalent maltodextrins (MDX) containing nicotine hydrogen tartrate salt (NHT). Particular attention was given to the selection of the suitable taste-masking agent (TMA) and the characterisation of the ductility and flexibility under different mechanical stresses. MDX with two different dextrose equivalents (DEs), namely DE 6 and DE 12, were selected in order to evaluate the effect of polymer molecular weight on film tensile properties. The bitterness and astringency intensity of NHT and the suppression effect of several TMA were evaluated by a Taste-Sensing System. The films were characterised in term of NHT content, tensile properties, disintegration time and drug dissolution test. As expected, placebo films made of ...
The relationship between cigarette smoking and cell damage is complicated, particularly considering the role of oxidative stress. The aim of this study was to identify the relationships among plasma nicotine metabolites, lipophilic antioxidants, and metabolic parameters in smokers and non-smokers. This cross-sectional study recruited 100 subjects who visited the Department of Family Medicine at Kaohsiung Medical University Hospital. Excluding 14 ineligible cases, 46 smokers and 40 non-smokers were enrolled. Plasma nicotine metabolites, lipophilic antioxidants (including retinol, lycopene, a-carotene, b-carotene, d-tocopherol, g-tocopherol and a-tocopherol), related metabolic parameters, and body composition (including height, weight, body mass index, body fat, and waist circumference) were...
Exogenous adenosine 5{prime}-triphosphate (ATP) mobilized intracellular calcium in human carcinoma A43l cells and in Swiss 3T3 and 3T6 mouse fibroblasts by increasing inositol trisphosphate similar to well down growth factors (platelet-derived growth factor (PDGF), epidermal growth factor (EGF), bradykinin (BK), serum). Calciummobilization was examined by video imaging of fura-2 fluorescence is single cells, following the radioactive isotope {sup 45}Ca, and monitoring the decrease in fluorescence of cells loaded with chlortetracycline. Uridine 5{prime}-triphosphate, but not other nucleotides, mimicked ATP. Single-cell analysis revealed synchronous responses in 10 sec to ATP, BK or serum, while PDGF (3T3) and EGF (A431) produced slower signals with significant cell-to-cell variation. PDGF desensitized 3T3 cells to ATP and BK added 100 sec later but ATP or BK did not desensitized to PDGF. Homologous desensitization was seen with all agonists. ...
Pharmacological activation of group II metabotropic glutamate (mGlu2 and mGlu3) receptors inhibits reward-seeking behavior and/or rewarding efficacy induced by drugs (cocaine, nicotine) or natural...Full Text Available
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. However, for chlorpyrifos, additional ...
Radioiodinated ..cap alpha..-bungarotoxin, the venom of Bungarus multicinctus, is commonly used for the detection and quantification of nicotinic acetylcholine receptors (nAChR) and anti-nAChR antibodies. A radioiodination method is described which is simple and yields a fully active product which, after fractionation, has a specific activity tenfold higher (900 Ci/mmol) than those routinely used, resulting in enhanced sensitivity of assays and conservation of material, especially muscle extracts.
The neuronal nicotinic acetylcholine receptor {alpha}7 subunit is a member of a family of ligand-gated ion channels, and is the only subunit know to bind {alpha}-bungarotoxin in mammalian brain. {alpha}-Bungarotoxin binding sites are known to be more abundant in the hippocampus of mouse strains that are particularly sensitive to nicotine-induced seizures. The {alpha}7 receptor is highly permeable to calcium, which could suggest a role in synaptic plasticity in the nervous system. Auditory gating deficiency, an abnormal response to a second auditory stimulus, is characteristic of schizophrenia. Mouse strains that exhibit a similar gating deficit have reduced hippocampal expression of the {alpha}7 subunit. We have cloned and sequenced the full length cDNA for the mouse {alpha}7 gene (Acra-7) and characterized its gene structure. The murine {alpha}7 shares amino acid identity of 99% and 93% with the rat and human {alpha}7 subunits, respectively. ...
Tungsten, in the form of tungstate, polymerizes with phosphate, and as extensive polymerization occurs, cellular phosphorylation and dephosphorylation reactions may be disrupted, resulting in negative effects on cellular functions. A series of studies were conducted to evaluate the effect of tungsten on several phosphate-dependent intracellular functions, including energy cycling (ATP), regulation of enzyme activity (cytosolic protein tyrosine kinase [cytPTK] and tyrosine phosphatase), and intracellular secondary messengers (cyclic adenosine monophosphate [cAMP]). Rat noncancerous hepatocyte (Clone-9), rat cancerous hepatocyte (H4IIE), and human cancerous hepatocyte (HepG2) cells were exposed to 1-1000 mg/l tungsten (in the form of sodium tungstate) for 24 h, lysed, and analyzed for the ab...
In virtually all forms of life on earth, proteins in each cell are made according to a genetic blueprint, in the form of DNA. The translation of copies of this genetic blueprint (in the form of messenger RNA) into polypeptides is performed on the ribosome, a highly complex molecular machine composed of RNAs and proteins. To this end, special adaptor molecules called transfer RNAs are lined up by the ribosome in the sequence dictated by the genetic code, such that the amino acids carried by these molecules can be linked into a polypeptide. Several cofactors are involved in these processes, some of which require energy freed up by GTP hydrolysis. Although the ribosome was discovered more than 50 years ago, its structure has only been solved recently by X-ray crystallography. Another technique, cryo-electron microscopy, is starting to contribute toward our understanding of the ribosome's function, by portraying its conformational changes and binding ...
Synthesis of protein molecules in a cell are carried out by ribosomes. A ribosome can be regarded as a molecular motor which utilizes the input chemical energy to move on a messenger RNA (mRNA) track that also serves as a template for the polymerization of the corresponding protein. The forward movement, however, is characterized by an alternating sequence of translocation and pause. Using a quantitative model, which captures the mechanochemical cycle of an individual ribosome, we derive an {\\it exact} analytical expression for the distribution of its dwell times at the successive positions on the mRNA track. Inverse of the average dwell time satisfies a ``Michaelis-Menten-like'' equation and is consistent with the general formula for the average velocity of a molecular motor with an unbranched mechano-chemical cycle. Extending this formula appropriately, we also derive the exact force-velocity relation for a ribosome. Often many ribosomes simultaneously move on ...
Proteins are polymers of amino acids. These macromolecules are synthesized by intracellular machines called {\\it ribosome}. Although, traditionally, the experimental investigation of protein synthesis has been an active area of research in molecular cell biology, important quantitative models of this phenomenon have been reported mostly in the research journals devoted to statistical physics and related interdisciplinary topics. From the perspective of a physicist, protein synthesis is a phenomenon of {\\it classical transport of interacting ribosomes on a messenger RNA (mRNA) template} that dictates the sequence of the amino acids on the protein. Here we bring this frontier area of contemporary research into the classroom by appropriate simplification of the models and methods. In particular, we develope a simple toy model and analyze it by some elementary techniques of non-equilibrium statistical mechanics to predict the average rate of protein synthesis and ...
This paper presents a review of the history, motivation and current status of high energy neutrino telescopes. Many years after these detectors were first conceived, the operation of kilometer-cubed scale detectors is finally on the horizon at both the South Pole and in the Mediterranean Sea. These new detectors will perhaps provide us the first view of high energy astrophysical objects with a new messenger particle and provide us with our first real glimpse of the distant universe at energies above those accessible by gamma-ray instruments. Some of the topics that can be addressed by these new instruments include the origin of cosmic rays, the nature of dark matter, and the mechanisms at work in high energy astrophysical objects such as gamma-ray bursts, active galactic nuclei, pulsar wind nebula and supernova remnants.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly accounting for the vast majority of dementia. Recently, many studies have implicated the role of inflammatory response, especially neuroinflammatory response in the development and progression of AD. However, the underlying mechanism of how inflammatory response induces AD is unknown. Kynurenine pathway is a major route of the amino acid tryptophan catabolism, resulting in the production of nicotine adenine dinucleotide and other neuroactive intermediates: quinolinic acid (QA) and kynurenic acid (KA). QA exerts different toxic effects, including over-activation of N-methyl-d-aspartate (NMDA) receptor and excitotoxicity, synaptic dysfunction and neuronal death. On the other hand, KA is identified as the only...
Summary There is a current popular recognition that cigarette smoking is deleterious to health. Although this is very clearly the case for physical health, the situation regarding mental health is, however, rather more complicated. This piece concentrates on the role of smoking in schizophrenia: it is important to consider why schizophrenia, exceptionally amongst the severe and enduring mental illnesses, is associated with increased cigarette consumption. People who suffer from schizophrenia consequently have a greater risk of the complications to physical health caused by this addiction and clearly, it is important to understand why this occurs. Numerous investigators have found that both neuroleptic-naive, first-onset schizophrenics, together with chronic sufferers of the illness, consum...
Alcohol dependence (AD) is clinically and etiologically heterogeneous. The goal of this study was to explore AD subtypes among a sample of 1221 participants in the Irish Affected Sib Pair Study of Alcohol Dependence, all of whom met DSM-IV criteria for AD. Variables used to identify the subtypes included major depressive disorder, antisocial personality disorder, illicit drug dependence (cannabis, sedatives, stimulants, cocaine, opioids, and hallucinogens), nicotine dependence, the personality traits of neuroticism and novelty seeking, and early alcohol use. Using latent class analysis, a 3-class solution was identified as the most parsimonious description of the data. Individuals in a Mild class were least likely to have comorbid psychopathology, whereas a severe class had highest probabi...
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 ...
1. Choline, and the choline analogues monoethylcholine (MEC) and N-aminodeanol (NAD) were examined for prophylactic activity in acute acetylcholinesterase inhibitor toxicity in mice. The rank order of potency of the compounds was MEC greater than NAD greater than choline. 2. Simultaneous administration of MEC (60 mg kg-1) or NAD (200 mg kg-1) with physostigmine reduced lethality to 17 and 13% respectively. MEC (60 mg kg-1) completely protected against disopropylfluorophosphate (DFP) and diazinon toxicity, and NAD reduced lethality to 17% for both agents. Choline (200 mg kg-1) exhibited only negligible antidotal activity against the inhibitors. 3. In vitro concentrations of choline, MEC, and NAD, similar to the estimated concentration obtained in vivo in the acute toxicity study, produced mixed inhibition of mouse brain acetylcholinesterase. The inhibition was dose-related and was additive to the inhibition produced by the cholinesterase inhibitors. 4. All three analogues reduced ligand ...
Regulatory genes called small RNAs (sRNAs) are known to play critical roles in cellular responses to changing environments. For several sRNAs, regulation is effected by coupled stoichiometric degradation with messenger RNAs (mRNAs). The nonlinearity inherent in this regulatory scheme indicates that exact analytical solutions for the corresponding stochastic models are intractable. Here, we present a variational approach to analyze a well-studied stochastic model for regulation by sRNAs via coupled degradation. The proposed approach is efficient and provides accurate estimates of mean mRNA levels as well as higher order terms. Results from the variational ansatz are in excellent agreement with data from stochastic simulations for a wide range of parameters, including regions of parameter space where mean-field approaches break down. The proposed approach can be applied to quantitatively model stochastic gene expression in complex regulatory networks.
The expression of three c-onc genes (c-erb, c-myc, c-myb) was investigated in five cell lines established from fibrosarcomas induced with 20-methylcholanthrene (MCA) of Japanese quails. These cell lines showed low levels of the three c-onc genes, with the exception of two cell lines that accumulated moderate (MCAQ 1-4) and large amounts (MCAQ 3-5) of c-myc RNA. Molecular cloning and restriction endonuclease analyses indicated that expression of c-myc in these two cell lines were not associated with detectable rearrangements in the c-myc locus, that the size of the c-myc transcript (2.7 kb) in MCAQ 3-5 was similar to that of the normal c-myc messenger RNAs (mRNA) and that the transcriptional activatin observed in MCAQ 3-5 was not mediated by the LTR (long terminal repeat) of a proximate ALV (avian leukosis virus) provirus. Finally, when analyzed with the restriction enzymes Msp I and Hpa II, the c-myc locus of MCAQ 3-5 and MCAQ 1-4 was found hypomethylated as ...
Gamma-ray burst (GRB) is one of the candidates of high-energy cosmic-ray acceleration sites. They may be also ultra-high-energy (above 3 EeV) cosmic-ray (UHECR) sources. In this paper, we discuss possibilities and implications of high-energy cosmic-ray acceleration in GRBs. (1) First, we show that not only protons but also heavier nuclei can be accelerated up to ultra-high energies in both usual high-luminosity (HL) and low-luminosity (LL) GRBs by using the Geant4. LL GRBs may also make a significant contribution to the observed UHECR flux if they form a distinct population, and we investigate cosmic-ray acceleration in LL GRBs in detail. (2) Second, we discuss implications of the GRB-UHECR hypothesis (and Hypernova-UHECR hypothesis) to cosmic-ray astronomy. HL GRBs and LL GRBs will lead to different source number densities as UHECR sources, so that the determination of the number density of UHECR sources and strength of the mean extragalactic magnetic field (EGMF) will give us useful ...
The fabrication and complete evaluation are described of a dihydropyridine in equilibrium pyridinium salt type redox system for the delivery of radioiodinated agents to the brain. The pivotal intermediate, N-succinimidyl (1-methylpyridinium iodide)-3-carboxylate was prepared by condensation of nicotinic acid and N-hydroxysuccinimide in the presence of dicyclohexylcarbodimide, followed by quaternization of III with methyl iodide. Tissue distribution studies of "1"2"5I-labeled 4-iodoaniline and the redox agents were performed in rats. ["1"2"5I]Iodoaniline initially showed moderate (0.58% dose/gm) brain uptake with subsequent release of the radioactivity from the brain. ["1"2"5I]Iodoaniline, when coupled to a dihydropyridine carrier showed higher uptake and retention in the brain. The ["1"2"5I]iodophenylethyl analogue showed uptake and retention in the brain to be very similar. Apparently the lipophilic agents cross the blood-brain barrier and are oxidized ...
1. The benzyl carbamyl analogue of lignocaine [2-(diethylaminoacetamido)-3-carbamyl-4-methyl-5-benzylpyrrole] at an intravenous dose of 4 mg/kg caused a blood pressure decrease of 54 mmHg. 2. A greater hypotensive effect was observed in hypertensive compared to normotensive animals. Anaesthesia magnified the vasodepressor effect in both groups. 3. The analogue did not possess centrally-mediated effects on blood pressure but exerted its hypotensive effect via a peripheral mechanism. 4. The analogue produced a relaxant effect on intestinal and vascular smooth muscle while exerting minimal effects on muscarinic, sympathetic, or ganglionic nicotinic receptors. 5. The analogue exhibited less cardiac depressant action on left ventricular rate (dp/dt) and force of contraction than lignocaine. 6. Lethal effects for the analogue were first observed at 16 mg/kg following intravenous administration and at 500 mg/kg following intraperitoneal administration. 7. In conclusion, ...
Six uranyl coordination compounds, UO_2(OH)(PYCA) (1), UO_2(PYCA)_2(H_2O).2H_2O (2), UO_2(PIC)_2 (3), UO_2(H_2O)_2(NIC)_2 (4), UO_2(OH)(HINIC)(INIC) (5), and UO_2(PYTAC)_2(H_2O)_2 (6) were grown as single crystals via hydrothermal synthesis (PYCA - pyrazine-2-carboxylate, PIC - picolinate, NIC - nicotinate, INIC - iso-nicotinate, and PYTAC - 2-(pyridin-4-yl)thiazole-5-carboxylate) to study their optical properties. All six compounds have been identified via single crystal X-ray diffraction and fully characterized via powder X-ray diffraction, infrared spectroscopy, UV-Vis spectroscopy, and fluorescence spectroscopy. Three of the complexes, 1, 3, and 6, represent new structures, and their synthesis and structural characterization is detailed within. The structures of 2, 4, and 5 have previously been reported in the literature. Coordination polymer 1 crystallizes in the orthorhombic space group Pca21 (a = 13.5476(5) Angstroms, b = 6.6047(2) ...
Purpose : To detect differentially expressed genes in the patients with uterine cervical cancer during the radiation therapy. Materials and Methods : In patients with biopsy proven uterine cervical cancer, we took a tumor tissue just before radiation therapy and at 40 minutes after external irradiation of 1.8 Gy. Total RNAs isolated from non-irradiated and irradiated tumor tissue samples were analyzed using the differential-display reverse transcription-polymerase chain reaction (DDRT-PCR). Complementary DNA (cDNA) fragments corresponding to differentially expressed messenger RNAs(mRNAs) were eluted, and cloned. The differential expression of the corresponding mRNAs was confirmed by reverse northern blot. Differentially expressed cDNA bands were sequenced. Nucleotide sequence data were analyzed in the Gene Bank and EMBL databases via the BLAST network server to identify homologies to known genes or cDNA fragments. Expression pattern of down-regulated clone was ...
Many hormones elicit effects on target cells by stimulating the enzyme phospholipase-C, which catalyzes the hydrolysis of phosphoinositides to the intracellular second messengers diacylglycerol and inositol phosphates. The present study examined the roles of FSH and guanine nucleotide-binding proteins (G-proteins) in regulating the hydrolysis of phosphoinositides in Sertoli cells. Sertoli cell cultures prepared from 16- to 18-day-old rats were incubated for 24 h with myo-[2-3H] inositol to label endogenous phospholipids. Treatment of cells from 0.5-20 min with preparations of ovine FSH ranging in potency from 1-60 times that of NIH FSH S1 did not affect accumulation of inositol phosphates. Levels of total [3H]inositol phosphates [[3H]inositol mono-, di-, and triphosphates (IP, IP2, and IP3)] in FSH-treated cultures was 75-120% the levels in control cultures over the various time intervals studied. Addition of testosterone and the combination of testosterone plus ...
The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 is normally expressed in a limited number of tissues, including the prostate, but its biological functions in prostate are largely unknown. In this study, we found that OLFM4 messenger RNA was reduced or undetectable in prostate cancer tissues and prostate cancer cell lines. To study the effects of OLFM4 on prostate cancer progression, we transfected PC-3 prostate cancer cells with OLFM4 to establish OLFM4-expressing PC-3 cell clones. The OLFM4-expressing PC-3 cell clones were found to have decreased proliferation and invasiveness compared with vector-transfected control PC-3 cells in vitro. In addition, nude mice injected with OLFM4-expressing PC-3 cells demonstrated reduced tumor growth and bone invasion and metastasis compared with mice injected with vector-transfected control cells. Mechanistic studies revealed that OLFM4 may exhibit its anticancer effects through ...
The natriuretic peptides are considered to be cardioprotective; however, their receptors have not been identified in human myocardium using radiolabeled analogs. Dendroaspis natriuretic peptide (DNP) has been recently identified as a new member of this peptide family and is thought to be less susceptible to enzymatic degradation. Therefore, we have developed the novel radiolabeled analog [125I]-DNP and used this to localize high-affinity (K(D)=0.2 nmol/L), saturable, specific binding sites in adult human heart (n=6) and coronary artery (n=8). In competition binding experiments, atrial natriuretic peptide and brain type natriuretic peptide had greater affinity for [125I]-DNP binding sites than C-type natriuretic peptide and the natriuretic peptide receptor (NPR)-C ligand, cANF. This rank order of potency suggested binding of [125I]-DNP was specific to NPR-A. Messenger RNA encoding NPR-A was identified in left ventricle and coronary artery smooth muscle, and ...
Approximately 700m of deep water clastic deposits of Mt. Messenger Formation are superbly exposed along the Taranaki coast of North Island, New Zealand. Biostratigraphy indicates the interval was deposited during the time span 10.5-9.2m.y. in water depths grading upward from lower bathyal to middle-upper bathyal. This interval is considered part of a 3rd order depositional sequence deposited under conditions of fluctuating relative sea-level, concomitant with high sedimentation rates. Several 4th order depositional sequences, reflecting successive sea-level falls, are recognized within the interval. Sequence boundaries display a range of erosive morphologies from metre-wide canyons to scours several hundred metres across. All components of a generic lowstand systems tract--basin floor fan, channel-levee complex and progading complex--are present in logical and temporal order. They are repetitive through the interval, with the relatively shallower-water components ...
1 Candoxin (MW 7334.6), a novel toxin isolated from the venom of the Malayan krait Bungarus candidus, belongs to the poorly characterized subfamily of nonconventional three-finger toxins present in Elapid venoms. The current study details the pharmacological effects of candoxin at the neuromuscular junction. 2 Candoxin produces a novel pattern of neuromuscular blockade in isolated nerve-muscle preparations and the tibialis anterior muscle of anaesthetized rats. In contrast to the virtually irreversible postsynaptic neuromuscular blockade produced by curaremimetic alpha-neurotoxins, the neuromuscular blockade produced by candoxin was rapidly and completely reversed by washing or by the addition of the anticholinesterase neostigmine. 3 Candoxin also produced significant train-of-four fade during the onset of and recovery from neuromuscular blockade, both, in vitro and in vivo. The fade phenomenon has been attributed to a blockade of putative presynaptic nicotinic ...
Solid fuels such as coal, wood, and crop straw supply some fraction of household cooking and heating fuel for more than one billion people in China. As these fuels do not generally combust cleanly in household stoves, their use levies large health and environmental burdens, particularly in rural regions. Production of clean-burning fuels from agricultural residue offers one prospect for mitigating health and social burdens imposed by household use of solid fuels. This dissertation explores the question: how might production of clean-burning household fuels from agricultural residues affect human health and social conditions in rural China? I approach this question from three perspectives. First, a technically plausible but currently unproven village-scale energy technology is explored in a scenario bounded by natural resources and substantiated by engineering specifications, estimates of indoor exposures to air pollution, and epidemiological analyses. This analysis asks at the national ...