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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...

UK PubMed Central (United Kingdom)

The pleiotropic actions of neuromodulators on pre- and postsynaptic targets present challenges to disentangling the mechanisms underlying regulation of synaptic transmission. Within the striatum,...Full Text Available

UK PubMed Central (United Kingdom)

Evidence is presented for a distinctive type of hippocampal synaptic modification [previously described for a molluscan gamma-aminobutyric acid (GABA) synapse after paired pre- and postsynaptic excitation]:...Full Text Available

UK PubMed Central (United Kingdom)

The acute acetoclastic methanogenic inhibition of several inorganic and organic arsenicals was assayed. Trivalent species, i.e., methylarsonous acid and arsenite, were highly inhibitory, with 50% inhibitory...Full Text Available

KoreaScience (Korea)

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KoreaScience (Korea)

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J-STORE (Japan)

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Environmental Research Database

ObjectivesObjectives Not AvailableDescriptionA collaborative study of the anaerobic treatment of wastes containing recalcitrant and inhibitory compounds using the SERC Anaerobic facility, in particular biomass structure, monitoring and control, catabolism and toxicity, pre-acidification and microbial growth and mesophilic and thermophilic lignocellulose degradation.~%~

UK PubMed Central (United Kingdom)

The inhibitory effects of indole-3-acetic acid (IAA) and 1-aminocyclopropane-1-carboxylic acid (ACC) on elongation growth of pea (Pisum sativum L.) seedling roots were investigated...Full Text Available

KoreaScience (Korea)

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UK PubMed Central (United Kingdom)

mRNP granules at adult central synapses are postulated to regulate local mRNA translation and synapse plasticity. However, they are very poorly characterized in vivo. Here, in Drosophila...Full Text Available

UK PubMed Central (United Kingdom)

Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Although cognitive performance in humans and experimental animals can be improved by administering omega-3 fatty acid docosahexaenoic acid (DHA), the neurochemical mechanisms underlying this effect remain uncertain. In general, nutrients or drugs that modify brain function or behavior do so by affecting synaptic transmission, usually by changing the quantities of particular neurotransmitters present within synaptic clefts or by acting directly on neurotransmitter receptors or signal-transduction molecules. We find that DHA also affects synaptic transmission in mammalian brain. Brain cells of gerbils or rats receiving this fatty acid manifest increased levels of phosphatides and of specific presynaptic or postsynaptic proteins. They also exhibit increased numbers of dendritic spines on post...

British Library Electronic Table of Contents (United Kingdom)

The power?time curves of mice splenic lymphocytes growth at 37??C affected by ginsenoside Rh2 were determined by microcalorimetry using a 3114/3236 TAM air bioactivity monitor with ampoule mode. Then, the minimal inhibitory concentration (MIC) of Rh2 on splenic lymphocytes growth was determined by serial dilution method. From factor analysis (FA) on six quantitative thermokinetic parameters from the power?time curves, the activity of Rh2 on splenic lymphocytes could be quickly evaluated by analyzing the changes in the two main parameters: growth rate constant k, and maximum heat-output power, P m. The results showed that Rh2 had strong inhibitory activity on splenic lymphocytes growth, and this inhibitory activity was strengthened with increasing concentration of Rh2 in the concentration r...

UK PubMed Central (United Kingdom)

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

UK PubMed Central (United Kingdom)

The receptive field of a neuron reflects its function. For example, for parallel fiber (PF) inputs in C3 zone the cerebellar cortex, the excitatory and inhibitory receptive fields of a Purkinje cell...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundAlzheimer's disease, known to be associated with the gradual loss of memory, is characterized by low concentration of acetylcholine in the hippocampus and cortex part of...Full Text Available

UK PubMed Central (United Kingdom)

The hypothesis that the antiarrhythmic drug amiodarone slows down the heart rate by its inhibitory action on the intracellular conversion of thyroxine (T4) to 3,5,3' triiodothyronine (T3) was investigated....Full Text Available

UK PubMed Central (United Kingdom)

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

UK PubMed Central (United Kingdom)

The mechanism by which enzyme IIIglc of the bacterial phosphotransferase system regulates the activity of crystalline glycerol kinase from Escherichia coli has been studied, and the inhibitory effects...Full Text Available

International Nuclear Information System (INIS)

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

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A series of 2-alkylthiopyrine-4-carbothioamides were synthesized, and their anti-fungal potency was tested. The chemical structures were proved by infrared spectroscopy (IR) and {sup 1}H nuclear magnetic resonance ({sup 1}H-NMR) data and by elemental analysis. The minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) assessment were used for the estimation of potential activity in vitro. The study comprising 21 clinical isolates of fungi showed that two compounds exhibited fair inhibitory activity against some yeasts and dermatophytes. Selective fungistatic activity against non-dermatophytes (MIC = 3.12-25.0 {mu}g/mL) was found also in another compound. None of the above compounds showed inhibitory activity against non-dermatophyte filamentous fungi. Microbiological activity of 2-alkylthiopyridine-4-carbothioamides appears to be mainly related to hydrophobicity of alkyl in position 2. (authors). ...

International Nuclear Information System (INIS)

By using the continuation theorem of coincidence degree theory and constructing suitable Lyapunov functions, we study the existence and stability of periodic solution for shunting inhibitory cellular neural networks (SICNNs) with delays x-bar _i_j(t)=-a_i_j(t)x_i_j(t)--bar B"k"l-bar Nr(i,j)B_i_j"k"l(t)f_i_j(x_k_l(t))x_i_j(t)--bar C"k"l-bar Nr(i,j)C_i_j"k"l(t)g_i_j(x_k_l(t-#tau#_k_l))x_i_j(t)+L_i_j(t).

UK PubMed Central (United Kingdom)

To analyze the proposed growth-inhibitory function of wild-type p53, we compared simian virus 40 (SV40) DNA replication in primary rhesus monkey kidney (PRK) cells, which express wild-type p53, and...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

The authors have shown previously that the domain recognizing receptors on activated human platelets is located on the human fibrinogen {gamma} chain between residues 400 and 411. To study the correlation between the structure of this segment of the {gamma} chain and its reactivity toward receptors on ADP-activated human platelets, they designed a series of analogues containing replacements at 9 out of 12 positions. A double substitution of the normal His{sup 400}-His{sup 401} sequence by Ala-Ala reduced the inhibitory potency of the dodecapeptide 3-fold. When Lys{sup 406} was replaced by Arg, the inhibitory potency of the dodecapeptide decreased 15 times. On the other hand, substitution of Ala{sup 408} with Arg increased the inhibitory potency of the dodecapeptide 6-fold. A drastic decrease in the reactivity of the dodecapeptide toward platelet receptors was observed when Val{sup 411} was replaced by leucine or cysteine or ...

CERN Document Server

We study the growth of colonies of the yeast Pichia membranaefaciens on agarose film. The growth conditions are controlled in a setup where nutrients are supplied through an agarose film suspended over a solution of nutrients. As the thickness of the agarose film is varied, the morphology of the front of the colony changes. The growth of the front is modeled by coupling it to a diffusive field of inhibitory metabolites. Qualitative agreement with experiments suggests that such a coupling is responsible for the observed instability of the front.

UK PubMed Central (United Kingdom)

Epidermal growth factor (EGF) stimulates adenylyl cyclase in the heart via activation of the stimulatory GTP-binding protein Gs. Therefore, employing peptides corresponding to regions in the cytosolic...Full Text Available

Science.gov (United States)

Functional activation of {beta}-catenin/Tcf signaling plays an important role in early events in carcinogenesis. We examined the effect of naringenin against {beta}-catenin/Tcf signaling in gastric cancer cells. Reporter gene assay showed that naringenin inhibited {beta}-catenin/Tcf signaling efficiently. In addition, the inhibition of {beta}-catenin/Tcf signaling by naringenin in HEK293 cells transiently transfected with constitutively mutant {beta}-catenin gene, whose product is not phosphorylated by GSK3{beta}, indicates that its inhibitory mechanism was related to {beta}-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed immunofluorescence, Western blot, and EMSA. As a result, our data revealed that the {beta}-catenin distribution and the levels of nuclear {beta}-catenin and Tcf-4 proteins were unchanged after naringenin treatment. Moreover, the binding activities of Tcf complexes to ...

International Nuclear Information System (INIS)

The thiazolidinedione (TZD) or glitazone class of peroxisome proliferator-activated-#gamma# (PPAR-#gamma#) ligands not only induce adipocyte differentiation and increase insulin sensitivity, but also exert growth inhibitory effects on several carcinoma cell lines in vitro as well as in vivo. In the current study the in vitro effect of four PPAR-#gamma# agonists (ciglitazone, pioglitazone, troglitazone, rosiglitazone) on the cell growth of seven human neuroblastoma cell lines (Kelly, LAN-1, LAN-5, LS, IMR-32, SK-N-SH, SH-SY5Y) was investigated. Growth rates were assessed by a colorimetric XTT-based assay kit. Expression of PPAR-#gamma# protein was examined by immunohistochemistry and Western blot analysis. All glitazones inhibited in vitro growth and viability of the human neuroblastoma cell lines in a dose-dependent manner showing considerable effects only at high concentrations (10 #mu#M and 100 #mu#M). Effectiveness of the glitazones on neuroblastoma cell growth ...

International Nuclear Information System (INIS)

Those materials that can be extracted from pine or oak by ether, ethanol, methyl methacrylate (MMA), or benzene--alcohol all act as inhibitors in the #gamma# polymerization of MMA--wood composites. It was found that preirradiation of either the wood or of the wood--monomer combination reduces or eliminates the inhibitory effect. The most practical industrial solution to this problem is to increase the dose, thereby achieving high molecular polymer in the composite. However, the presence of a maximum in the molecular weight--dose curves means that each wood--monomer pair may have a different optimum dose.

Science.gov (United States)

This study compares the effectiveness of potassium chloride with guanidine chlorhydrate in the prevention of clay swelling. The results given on various swelling tests on calcic montmorillonite led to the conclusions that (1) guanidine chlorhydrate is more effective than potassium chloride, especially in low concentrations, and (2) water immersion of samples treated by both solutions shows the permanent feature of the inhibitive action of guanidine chlorhydrate in swelling on one hand and the important increase in swelling of immersed samples treated by potassium chloride on the other. The viscosity measure of montmorillonite suspensions, before and after solution ion elimination by dialysis, confirms these observations.

Science.gov (United States)

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 ...

International Nuclear Information System (INIS)

Full text: Chemical-technology approaches allowing to intensification the prevention processes of gas hydrates formation at motion of gas-liquid stream of natural gas in system natural gas well - gas wire have been worked up. Technological regimes of treatment of gas stream have been determined. Linear correlation dependences inhibitor electrolytes contained hydrated ions with different ion radii and charges of subgroups of alkali elements with one - type electron configuration were obtained. Important physico-chemical parameters of electrolytes have been determined: activity; coefficients of activity, viscosity, diffusion; density; heat capacity; heat conductivity; surface tension and freezing-point. The features of continuous influence of inhibitory factors on process of gas flow at low temperatures and relatively high pressure differences ?P have been studied by using of technological installation modulating the system natural gas well - gas wire. The ...

British Library Electronic Table of Contents (United Kingdom)

This work reports the development of an automatic methodology based on the use of 1-anilinonaphthalene-8-sulfonate (ANS) as an interfacial fluorescent probe for detecting the hydrophobic environment shift around the probe, caused by the hydrolytic action of PLA2 on the liposomes. The implementation of this reaction in a sequential injection analysis (SIA) system along with the use of the mixing chambers permitted the evaluation of PLA2 activity and assessment of the inhibitory effect of the non-steroidal anti-inflammatory drugs (NSAIDs) on PLA2 activity. Several studies were performed with the aim of establishing the appropriate flow system configuration: the liposome substrate; PLA2 and ANS optimum concentrations and incubation times before and after the enzyme addition. Based on these st...

DEFF Research Database (Denmark)

We study the spike statistics of neurons in a network with dynamically balanced excitation and inhibition. Our model, intended to represent a generic cortical column, comprises randomly connected excitatory and inhibitory leaky integrate-and-fire neurons, driven by excitatory input from an external population. The high connectivity permits a mean field description in which synaptic currents can be treated as gaussian noise, the mean and autocorrelation function of which are calculated self-consistently from the firing statistics of single model neurons. Within this description, a wide range of Fano factors is possible. We find that the irregularity of spike trains is controlled mainly by the strength of the synapses relative to the difference between the firing threshold and the postfiring reset level of the membrane potential. For moderately strong synapses, we find spike statistics very similar to those observed in primary visual cortex.

British Library Electronic Table of Contents (United Kingdom)

The cephalosporin class antibacterial agent, cefazolin, was intercalated into layered double hydroxides (LDHs) in order to improve the drug efficiency as well as to achieve the controlled release property. Cefazolin molecules were incorporated into LDH through conventional ion exchange reaction. X-ray diffraction pattern analyses confirmed that cefazolin molecules were intercalated between the interlayer spaces of LDH. Fourier-transform infrared spectra and high performance liquid chromatographs clearly showed that the drug molecules were stabilized in LDH lattice through electrostatic interaction and released without any changes in their chemical integrity. Antibacterial activity of the cefazolin-LDH nanohybrid was also examined by an in vitro test, such as the minimal inhibitory concentr...

British Library Electronic Table of Contents (United Kingdom)

Abstract A Pseudomonas sp. isolate MSB1 efficiently inhibited the growth of Flavobacterium psychrophilum of different serotypes on agar medium. A significant difference in the inhibition was observed between isolates of the less virulent FpT serotype compared to the Fd and Th serotypes. In broth coculture experiments, a low number of cells of MSB1 inhibited and outcompeted the F.psychrophilum cells. Also cell-free culture supernatant of MSB1 clearly repressed the growth of F.psychrophilum. A chromoazurol S assay suggested that MSB1 produced efficient siderophores, which most probably were responsible for the iron deficiency in the supernatant. The limited growth of F.psychrophilum in the supernatant was found to be partly because of the lack of available iron, but the results also indicate...

British Library Electronic Table of Contents (United Kingdom)

Prepulse inhibition (PPI) is a measure of sensorimotor gating, a pre-attentional inhibitory brain mechanism that filters extraneous stimuli. Prepulse inhibition is correlated with measures of cognition and executive functioning, and is considered an endophenotype of schizophrenia and other psychiatric illnesses in which patients show PPI impairments. As a first step toward identifying genes that regulate PPI, we performed a quantitative trait locus (QTL) screen of PPI phenotypes in a panel of mouse chromosome substitution strains (CSSs). We identified five CSSs with altered PPI compared with the host C57BL/6J strain: CSS-4 exhibited decreased PPI, whereas CSS-10, -11, -16 and -Y exhibited higher PPI compared with C57BL/6J. These data indicate that A/J chromosomes 4, 10, 11, 16 and Y harbor...

British Library Electronic Table of Contents (United Kingdom)

Background, aim and scope Treatment performance of constructed wetlands (CWs) is largely dependent on the characteristics of the wastewater. Although livestock wastewater is readily biodegradable in general, its variety in biodegradability can still be significant in practice. In addition, it is a common practice to periodically use disinfectants in livestock activities for health concerns. Obviously, the residual of the disinfectants in livestock wastewater may have serious inhibitory effect on the microbial activities during wastewater treatment. Thus, the main objective of this study was to examine the variety of livestock wastewater in biodegradability and its effect on the performance of a pilot scale tidal flow CWs (TFCWs) in organic matter and nitrogen removal. Furthermore, investig...

British Library Electronic Table of Contents (United Kingdom)

Abstract This study aimed at developing a suitable cryopreservation protocol for embryonic stem (ES)-like cells of a tiny freshwater fish Leopard danio (Brachydanio frankei). Embryonic stem (ES)-like cells derived from blastomeres of the early blastulae stage of the developing embryo were cultured in vitro in a medium containing Leibowitz-15 supplemented with 10% foetal bovine serum, leopard danio embryo extract, sodium bicarbonate, sodium selenite, basic fibroblast growth factor, epidermal growth factor and leukaemia inhibitory factor. The ES-like cells showed properties similar to ES cells in other species. They were morphologically small, round to polygonal and present in patches and extensively expressed alkaline phosphatase and stage-specific embryonic antigen. The toxicity and chilli...

British Library Electronic Table of Contents (United Kingdom)

Abstract Background: This study involves a multicentre surveillance of tigecycline and tetracycline activity against Gram-negative and Gram-positive bacteria from primary care centres (PCCs), general hospital wards (GHWs) and intensive care units (ICUs) in Denmark (n == 9), Finland (n == 10), Norway (n == 7) and Sweden (n == 19). Methods: The hospitals were each asked to test 30 consecutive Gram-positive and 30 Gram-negative clinical isolates. Supportive information accompanying each isolate included the study centre, ward level (PCC, GHW, or ICU), patient identification and source of the isolate. Minimum inhibitory concentrations (MICs) for tetracycline and tigecycline were determined with the Etest. Results: The isolates collected comprised 1610 Gram-negative and 1767 Gram-positive clini...

British Library Electronic Table of Contents (United Kingdom)

Abstract The inhibitory effect of the extract from Magnolia officinalis (MOE) against L. monocytogenes, S. faecalis, E. coli, S. typhimurium, S. aureus and B. anthracis by paper-diffusion methods and the characterization of the mutton immersed in different concentrations of the MOE during storage were evaluated in this paper. The results showed that MOE could significantly inhibit the growth of S. aureus, S. faecalis, B. anthracis and E. coli, and their MIC was 0.02-mg/mL, 0.03-mg/mL, 0.05-mg/mL and 0.10-mg/mL, respectively. MOE showed weak inhibition for the S. typhimurium. The mutton treated with 2%, 4% and 6% MOE resulted in suppression in the increase of total volatile base nitrogen, thiobarbituric acid reactive substance, and the growth of Enterobacteriaceae, Pseudomonas. The cooled m...

Energy Technology Data Exchange (ETDEWEB)

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 inhibitory functions to other classes of ...

Science.gov (United States)

Four trypsin inhibitor homologs, the first known from Dendroaspis angusticeps venom, were characterized using a combination of gel filtration, cation exchange, reverse-phase liquid chromatography, Edman degradation and mass spectrometry. The four toxins comprise two 57 residue and two 59 residue isoforms. The long toxins possess a Lys-Gln N-terminal extension lacked by the short toxins. The only other structural difference is an Arg/His replacement at position 55. The long Arg55 variant is identical to trypsin inhibitor E from the venom of Dendroaspis polylepis. The name epsilon-dendrotoxin is suggested so as to follow the nomenclature of Benishin, C.G., Sorensen, R.G., Brown, W.E., Krueger, B.K., Blaustein, M.P., 1988. Four polypeptide components of green mamba venom selectively block certain potassium channels in rat brain synaptosomes. Mol. Pharmacol. 34, 152-159. Among snake venom protease inhibitors, the epsilon-dendrotoxins are structurally most like the delta-dendrotoxins, with ...

International Nuclear Information System (INIS)

To investigate the growth inhibitory effects, and the underlying mechanism of human colon cancer cell (HT-29) death, induced by a new synthetic bile derivative (HS-1200). Human colon cancer cells (HT-29), in exponential growth phase, were treated with various concentrations of a new synthetic bile acid derivative (HS-1200). The growth inhibitory effects on HT-19 cells were examined using a trypan blue exclusion assay. The extent of apoptosis was determined using agarose gel electrophoresis, TUNEL assays and Hoechst staining. The apoptotic cell death was also confirmed by Western blotting of PARP, caspase-3 and DNA fragmentation factor (DFF) analysis. To investigate the involvement of mitochondria, we employed immunofluorescent staining of cytochrome c and mitochondrial membrane potential analyses. The dose required for the half maximal inhibition (IC_5_0) of the HT-29 cell growth was 100 #approx# 150 #mu# M of HS-1200. Several changes, ...

International Nuclear Information System (INIS)

Several series of pyrimidine nucleosides were evaluated as part of a larger program to develop non-invasive brain imaging agents. The interaction of these antitumor/antiviral nucleosides with an NBMPR-sensitive murine erythroctye nucleoside transporter was evaluated by determining their inhibitory effect (K_i) on zero-trans influx of thymidine. Within each series of compounds, which had F, Cl, Br or I as halogen substituents, an increase in size of the halogen atom or a decrease in electronegativity decreased affinity for the transporter. Partition coefficients (P) of these pyrimidine nucleosides were measured to determine their potential to diffuse across the blood-brain-barrier (BBB). Most of the pyrimidine nucleosides had lower P values (log P < 0.9), and were considered to be poor candidates for simple diffusion across the BBB, although an active BBB transport mechanism for some nucleosides could be operative. For a given series, it was found that log P ...

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Conditioned medium from Sertoli cells, prepared from testes of 20-day-old rats, contains component(s) that inhibit the incorporation of (3H)-thymidine into DNA of peritubular myoid cells (PMC) and inhibit the proliferation of PMC. These components are trypsin-resistant, heat-stable compounds having a molecular weight less than 30,000. The active inhibitory components in Sertoli cell conditioned medium are inactivated by treatment with heparinase, but not by treatment with hyaluronidase or chondroitin sulfate lyases. Addition of heparin or heparan sulfate results in inhibition of DNA synthesis by PMC in a dose-dependent manner, whereas other glycosaminoglycans (GAGs) examined (hyaluronic acid, keratan sulfate, and chondroitin sulfate) have no detectable effects. Heparin and heparan sulfate are unique among GAGs tested in inhibiting the characteristic multilayer growth pattern of PMC following the attainment of confluence in serum-rich medium. On the basis of these ...

Science.gov (United States)

NFAT involvement in adipocyte physiological processes was examined by treatment with CsA and/or GSK3{beta} inhibitors (Li{sup +} or TZDZ-8), which prevent or increase NFAT nuclear translocation, respectively. CsA treatment reduced basal and TNF{alpha}-induced rates of lipolysis by 50%. Adipocytes preincubated with Li{sup +} or TZDZ-8 prior to CsA and/or TNF{alpha}, exhibited enhanced basal rates of lipolysis and complete inhibition of CsA-mediated decreased rates of lipolysis. CsA treatment dramatically reduced the mRNA levels of adipocyte-specific genes (aP2, HSL, PPAR{gamma}, ACS and Adn), compared with control or TNF{alpha}-treatment, whereas Li{sup +} pretreatment blocked the inhibitory effects of CsA, and mRNA levels of aP2, HSL, PPAR{gamma}, and ACS were found at or above control levels. NFAT nuclear localization, assessed by EMSA, confirmed that CsA or Li{sup +} treatments inhibited or increased NFAT nuclear translocation, respectively. These results show ...

British Library Electronic Table of Contents (United Kingdom)

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

Energy Technology Data Exchange (ETDEWEB)

The objective of this work was to investigate the efficiency of imidazole and its derivatives 4-methylimidazone, 4-methyl-5-hydroxymethylimidazone, 1-phenyl-4-methylimidazone, and 1-(p-tolyl)-4-methylimidazole for corrosion inhibition of copper in 0.5 M hydrochloric acid. Corrosion inhibition was studied using potentiodynamic methods. These studies have shown that 1-(p-tolyl)-4-methylimidazole has the best inhibitory efficiency. Activation energies were obtained by measuring the temperature dependence of the corrosion current. The activation energies in the presence of the various inhibitors are low (3--5 kJ/mol), with the best inhibitor showing the highest value. The adsorptive behavior of the imidazole derivatives on the copper electrode surface follows a Freundlich-type isotherm. The standard free energies of adsorption are also low (14--16 kJ/mol), indicating that imidazole and its derivatives physisorb on the copper surface. Possible mechanisms of corrosion ...

British Library Electronic Table of Contents (United Kingdom)

This study describes the role of "inflammatory" oxidized (Ox) phospholipids in regulation of rahU (PA0122) expression and biofilm formation in Pseudomonas aeruginosa (383) wild type (rahU+) and rahU mutant (rahU-) strains. Functional analysis of RahU protein from P. aeruginosa in presence of Ox-phospholipids show: (a) LysoPC modulates RahU gene/and protein expression in rahU+ cells; (b) rahU promoter activity is increased by lysoPC and inhibited by PAPC, Ox-PAPC and arachidonic acid; the latter inhibitory effect can be reversed by lysoPC, which was enzymatically derived from PAPC; (c) biofilm formation increased in rahU- cells as compared to rahU+; and (d) inhibition of rahU promoter activity by PAPC and AA (but not lysoPC) showed significantly augmented biofilm formation in rahU+ but not ...

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Effects of cell concentrations on the survival and repopulation of haemopoietic stem cells after irradiation were studied in the long-term culture of mouse bone marrow cells in vitro. No difference was observed in the survival of the stem cells among cultures in which 0 - 10/sup 7/ cells were re-inoculated on the adherent cell colonies in the culture flask. Stem cells showed a significant proliferation within 1 week and the number of the stem cells exceeded the control in 3 weeks after irradiation in the cultures with less than 10/sup 6/ re-inoculated cells per flask. In contrast, there was a considerable delay in the onset of stem cell proliferation after irradiation in the culture with 10/sup 7/ cells per flask. Based on these results, a possibility that a stimulator of stem cell proliferation, released from irradiated stromal cells, is cancelled by an inhibitory factor produced by irradiated or unirradiated haemopoietic cells is postulated.

International Nuclear Information System (INIS)

The accumulation of osmolytes in leaf tissues and the abscisic acid-induced stomatal closure are well-recognized mechanisms associated with drought tolerance in crop plants. We determine the response in terms of osmotic potential and the contents of leaf proline, glycine betaine and soluble sugar at booting and grain filling stages of four wheat (Triticum aestivum L.) cultivars to drought and exogenously applied abscisic acid (ABA) in a pot study. Leaf sample were collected 3, 6 and 9 days after drought induction and at 48 and 72 h of re-watering (recovery). Marked decreases in osmotic potential associated with the accumulation of proline, glycine betaine and soluble sugars occurred under conditions of drought stress Accession 011320 was most sensitive to drought and showed the largest decrease in osmotic potential and least accumulation of proline, sugar and glycine betaine The inhibitory effects of drought stress were ameliorated by exogenous application of ABA. ...

British Library Electronic Table of Contents (United Kingdom)

Abstract Four new dimeric naphtho--pyrones, named rubasperone D (1), rubasperone E (2), rubasperone F (3), and its atropisomer rubasperone G (4), together with four known monomeric naphtho--pyrones, TMC 256 A1 (5), rubrofusarin B (6), fonsecin (7), and flavasperone (8), were isolated from the mangrove endophytic fungus Aspergillus tubingensis (GX1-5E) cultivated in solid rice medium. Their structures were elucidated by spectroscopic methods, including IR, 1D- and 2D-NMR, and MS. In the in vitro cytotoxicity assays, 5 displayed inhibitory activities against tumor cell lines of MCF-7, MDA-MB-435, Hep3B, Huh7, SNB19, and U87-MG with IC50 values between 19.92 and 47.98-M. Compounds 1, 6, and 8 also showed mild cytotoxic activity.

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The human CDC25 tyrosine phosphatases trigger activation of CDC2 by removing inhibitory phosphates; thus the genes encoding these phosphatases may be suspected as potential oncogenes due to their role in promoting cell division. To date, three human CDC25 genes have been identified: CDC25A, B, and C. This communication describes the mapping of CDC25A to chromosome 3p21 and CDC25B to chromosome 20p13 by fluorescence in situ hybridization with confirmation by the polymerase chain reaction of hamster-human somatic cell hybrid DNA. 3p21 is near an area frequently involved in karyotypic abnormalities in renal carcinomas, small cell carcinomas of the lung, and benign tumors of the salivary gland. 20p13 does not seem to be a common area for karyotypic alteration in tumors. Mapping of these genes to their chromosomal loci may help identify tumors with abnormal regulation of CDC25 genes due to genomic alterations. 15 refs., 3 figs.

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Purified protein kinase C (C-kinase) from guinea pig pancreas and rat brain stimulated adenylate cyclase activity in purified rat adipocyte membranes. Cyclase stimulation occurred over 100 to 1000 mU/ml of C-kinase activity, required greater than 10 ..mu..M calcium, proceeded without a lag, was not readily reversible, and required no exogenous phospholipid. Moreover, C-kinase inhibitors, such as chlorpromazine and palmitoyl carnitine, inhibited selectively adenylate cyclase which was activated by C-kinase and calcium. Depending on assay conditions, 10 nM 12-0-tetradecanoylphorbol-13-acetate (TPA) either enhanced or was required for kinase action on cyclase. Also, TPA plus calcium promoted the quantitative association of C-kinase with membranes. Adenylate cyclase activation by C-kinase was seen both in the presence and absence of exogenous GTP, indicating that the kinase effect does not result from an action on the GTP-binding, inhibitory regulatory component (N/sub ...

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The grafted human glioblastoma cell CB109 was used as a model for intralesional therapy with 131I-labelled hyaluronectin glycoprotein (131I-HN). 131I-HN bound specifically to in situ hyaluronic acid (HA), a main component of the extracellular matrix which is involved in tumour invasion. Labelling experimental conditions were determined and, finally, 25 {mu}Ci/{mu}gHN, 1 {mu}g chloramine-T/{mu}gHN and a 60-s stirring period provided a 131I-HN preparation with an optimal affinity for HA (64% compared to unlabelled HN). Following intratumoral injection, 131I-HN was retained with a limited diffusion outside the tumour. On day 4 the radioactivity concentrated in the tumour was still 25 times greater than that in the liver, spleen and kidneys combined. For therapeutic assays, 65 {mu}Ci 131I-HN was injected into the tumour, resulting in a delivery of 6.8 Gy over a 7-day period. Controls received unlabelled HN, heat-inactivated HN, a mixture of inactivated HN plus free 131I or no treatment ...

Science.gov (United States)

In view of the findings that several Kunitz-type protein inhibitors suppress tumor invasion and metastasis, the aim of the present study is to explore whether Bungarus multicinctus protease inhibitor-like protein-2 (PILP-2) and PILP-3 exhibit anti-tumor activity. Although approximately 28% of amino acid substitutions occurred between PILP-2 and PILP-3, molecular modeling suggested that PILP-2 and PILP-3 shared similar folded structures. Unlike PILP-2, PILP-3 showed a notable activity in abolishing migration and invasion of human neuroblastoma SK-N-SH cells. The ability of PILP-3 to inhibit matrix metalloprotease-2 (MMP-2) activity was higher than that of PILP-2. Pull-down assay revealed protein-protein interaction between PILP-3 and MMP-2. In contrast to mutation on N-terminal region, replacement of amino acids at C-terminus attenuated notably the ability of PILP-3 to inhibit cell invasion, cell migration and MMP-2 activity as well as the binding capability of PILP-3 with MMP-2. ...

Science.gov (United States)

The steroidogenic factor 1 (SF-1, also known as NR5A1) is a transcription factor belonging to the nuclear receptor superfamily. Whereas most of the members of this family have been extensively characterized, the therapeutic potential and pharmacology of SF-1 still remains elusive. Described here is the identification and characterization of selective inhibitory chemical probes of SF-1 by a rational ultra-high-throughput screening (uHTS) strategy. A set of 64,908 compounds from the National Institute of Health's Molecular Libraries Small Molecule Repository was screened in a transactivation cell-based assay employing a chimeric SF-1 construct. Two analogous isoquinolinones, ethyl 2-[2-[2-(2,3-dihydro-1,4-benzodioxin-7-ylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate (SID7969543) and ethyl 2-[2-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate and (SID7970631), were identified as potent submicromolar inhibitors, yielding ...

International Nuclear Information System (INIS)

The influence of serum, IGF-1 and TGF-#beta# on the differentiation of preadipocytes was examined in primary cultures of porcine adipose tissue cells. In serum-supplemented or serum-free, IGF-1 (1 and 10 nM) had no effect on total cell number. However, IGF-1 (10nM) increased adipocyte number only in serum-supplemented (1% pig serum) cultures, whereas TGF-#beta# (15 pm) reduced the adipocyte number in the presence and absence of IGF-1. Replication of preadipocytes was analyzed with a ["3H] thymidine assay. Preadipocyte proliferation (cpm in adipocyte fraction) was increased by IGF-1 (10nM) only in cultures containing pig serum. TGF-#beta# had no effect on preadipocyte proliferation specifically, but slightly increased total ["3H] thymidine incorporation in cultures with serum. Glycerol phosphate dehydrogenase (GPDH) specific activity was decreased by adding TGF-#beta# to serum-free cultures but TGF-#beta# had little effect in serum-supplemented cultures. Cellular secretion of IGF-1 was ...

Science.gov (United States)

Inhibition of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is an appealing method for decreasing the immunoresistance and augmenting T cell-mediated immunotherapy. A major impediment to this strategy is the impact of conventional PI3K/mTOR pathway inhibitors on T cell function. In particular, rapamycin, is a well-known immunosuppressant that can decrease the activity of the PI3K/mTOR pathway in tumor cells, but also has a profound inhibitory effect on T cells. Here we show that Honokiol, a natural dietary product isolated from an extract of seed cones from Magnolia grandiflora, can decrease PI3K/mTOR pathway-mediated immunoresistance of glioma, breast and prostate cancer cell lines, without affecting critical proinflammatory T cell functions. Specifically, we show that at doses sufficient to down-regulate levels of phospho-S6 and the negative immune regulator B7-H1 in tumor cells, Honokiol does not significantly impair T cell ...

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Ethanol has excellent fuel properties, such as high octane, high heat of vaporization and low photochemical reactivity in the atmosphere. It is less volatile than gasoline and there is lower smog formation from evaporative emissions of pure ethanol compared to gasoline. As such, ethanol has emerged as an important alternative energy source that is sustainable, efficient, cost effective, convenient and safe. In 2006, global production of ethanol reached 13.5 billion gallons, up from 12.1 billion gallons in 2005. However, in light of the current debate of food versus fuel, the industry must shift to non-food feedstocks. This paper described an emerging technology to cost-effectively produce ethanol from sweet sorghum stalks, the most promising alternative feedstock to corn, via solid state fermentation (SSF). Experiments of advanced solid state fermentation (ASSF) for ethanol production from sweet sorghum by Saccharomyces cerevisiae were conducted in laboratory and pilot scales studies. ...

International Nuclear Information System (INIS)

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

Science.gov (United States)

From January 2008 to December 2009, 433 Streptococcus pneumoniae strains were examined to determine the serotype distribution and susceptibility to selected antibiotics. About 50% of them were invasive isolates. The strains were isolated from patients of all age groups and 33.55% were isolated from children below 5 years. The majority was isolated from blood (48.53%) and other sterile specimens (6.30%). Community acquired pneumonia (41.70%) is the most common diagnosis followed by sepsis (9.54%). Serotyping was done using Pneumotest Plus-Kit and antibiotic susceptibility pattern was determined by modified Kirby-Bauer disk diffusion method and measurement of minimum inhibitory concentration (MIC) using E-test strip. Ten most common serotypes were 19F (15.02%), 6B (10.62%), 19A (6.93%), 14 (6.70%), 1 (5.08%), 6A (5.08%), 23F (4.85%), 18C (3.93%), 3 (2.08%) and 5 (1.85%). Penicillin MIC ranged between ? 0.012-4 ?g/ml with MIC?? of 1 ?g/ml. Penicillin resistant rate is ...

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Biosorption is presented as an alternative choice to traditional physicochemical means for removing toxic metals from groundwater and wastewaters. Removal of lead (Pb) from solutions was studied using Escherichia coli (parental) and Vitreoscilla hemoglobin (VHb)-expressing E. coli (transformed) cells. Pb biosorption was increased in bacterial hemoglobin-expressing E. coli cells grown in Luria broth B containing different concentrations of Pb{sup 2+}. The maximum Pb{sup 2+} biosorption of transformed and parental cells was determined to be 612 and 370 {mu}g Pb/g biomass, respectively. The inhibitory effect of Pb{sup 2+} on the parental strain was determined at 10 ppm. However, in transformed cells, Pb{sup 2+} was lethal at 100 ppm. The optimum aeration required for the transformed cells was lower than that for the parental strain on a growth yield basis. A linear correlation was established between the biosorption and uptake amounts. The biosorption process was ...

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In the present study Balb/c mice were exposed to 3,4-benzopyrene, painted on the skin every 2nd day for a total of 6 months, and simultaneously irradiated with athermal (5 mW/cm/sup 2/) or subthermal (15 mW/cm/sup 2/) doses of 2,450 MHz microwaves. The other group of animals was preirradiated with microwaves at 10 mW/cm/sup 2/ power level for 1, 2, or 3 months and then treated with benzopyrene, as above. Control mice were exposed for 6 months to benzopyrene, resulting in the development of baso- or spinocellular skin carcinoma within approximately 9 months, and sham-irradiated with microwaves. The growth of the tumour was assessed according to a self-designed 7-range macroscopic scale, supported by microscopical examinations of skin sections. All protocols of microwave irradiations resulted in a significant acceleration of the development of benzopyrene-induced skin cancer and in shortening of life span of the tumour-bearing hosts. This effect seemed to be dose-dependent since ...

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Attention Deficit Hyperactivity Disorder (ADHD) is a neurobiological disorder of early childhood onset. Defining symptoms are chronic impairments of attention, impulse control and motor hyperactivity that frequently persist until adulthood. Miscellaneous causes of the disorder have been discussed. Accumulating evidence from imaging- and molecular genetic studies strengthened the theory of ADHS being a predominantly inherited disorder of neurobiological origin. In the last 15 years, non-invasive brain imaging methods were successfully implemented in pediatric research. Functional magnetic resonance imaging studies gave major insight into the neurobiological correlates of executive malfunction, inhibitory deficits and psychomotoric soft signs. These findings are in good accordance with brain morphometric data indicating a significant volumetric decrease of major components of striato-thalamo-cortical feedback loops, primarily influencing prefrontal executive ...