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M3
Terms modified by M3 Selected AbstractsThe importance of independent risk-factors for long-term mortality prediction after cardiac surgeryEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2006I. K. Toumpoulis Abstract Background, The purpose of the present study was to determine independent predictors for long-term mortality after cardiac surgery. The European System for Cardiac Operative Risk Evaluation (EuroSCORE) was developed to score in-hospital mortality and recent studies have shown its ability to predict long-term mortality as well. We compared forecasts based on EuroSCORE with other models based on independent predictors. Methods, Medical records of patients with cardiac surgery who were discharged alive (n = 4852) were retrospectively reviewed. Their operative surgical risks were calculated according to EuroSCORE. Patients were randomly divided into two groups: training dataset (n = 3233) and validation dataset (n = 1619). Long-term survival data (mean follow-up 5·1 years) were obtained from the National Death Index. We compared four models: standard EuroSCORE (M1); logistic EuroSCORE (M2); M2 and other preoperative, intra-operative and post-operative selected variables (M3); and selected variables only (M4). M3 and M4 were determined with multivariable Cox regression analysis using the training dataset. Results, The estimated five-year survival rates of the quartiles in compared models in the validation dataset were: 94·5%, 87·8%, 77·1%, 64·9% for M1; 95·1%, 88·0%, 80·5%, 64·4% for M2; 93·4%, 89·4%, 80·8%, 64·1% for M3; and 95·8%, 90·9%, 81·0%, 59·9% for M4. In the four models, the odds of death in the highest-risk quartile was 8·4-, 8·5-, 9·4- and 15·6-fold higher, respectively, than the odds of death in the lowest-risk quartile (P < 0·0001 for all). Conclusions, EuroSCORE is a good predictor of long-term mortality after cardiac surgery. We developed and validated a model using selected preoperative, intra-operative and post-operative variables that has better discriminatory ability. [source] Pregnancy-induced sympathetic overactivity: a precursor of preeclampsia,EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2004T. Fischer Abstract Background, Preeclampsia has been shown to constitute a state of sympathetic overactivity. However, it remains unclear if the sympathetic activity precedes preeclampsia or represents only a secondary phenomenon. To further investigate this issue, we performed a prospective study in pregnant women considered to be at increased risk for preeclampsia owing to preeclampsia during a preceding pregnancy. Materials and methods, Twenty-two women with a history of preeclampsia were longitudinally studied on three occasions: twice during pregnancy (M1: 22 ± 4, M2: 33 ± 5 weeks) and once postpartum (M3: 26 ± 6 weeks postpartum). We measured muscle sympathetic nerve activity (MSNA), forearm blood flow, and blood pressure at rest and during reactive hyperaemia after forearm occlusion. Results, At M1 and M2, none of the subjects was hypertensive, however, muscle sympathetic nerve activity levels were significantly augmented, compared with their postpartum values (M1: 21 ± 9, M2: 29 ± 14, M3: 9 ± 5 bursts min,1; P < 0·05). Forearm vascular resistance did not significantly change from M1 through M3 (M1: 16 ± 9, M2: 15 ± 7, M3: 16 ± 7 U; P = NS). Gestational muscle sympathetic nerve activity values did not differ significantly among the subjects with subsequent preeclampsia compared with those who remained normotensive [with preeclampsia (n = 6): M1: 21 ± 5, M2: 27 ± 6, M3: 7 ± 4 bursts min,1; without preeclampsia (n = 16): M1: 21 ± 11, M2: 30 ± 16, M3: 9 ± 6 bursts min,1; P = NS]. Conclusion, Invariably, all women at risk for preeclampisa showed a pregnancy-induced increase in MSNA (pregnancy-induced sympathetic overactivity, PISO), which normalized after delivery. Most importantly, PISO is not necessarily associated with peripheral vasoconstriction and hypertension. Furthermore, only a subset of patients developed preeclampsia later on. Therefore, we hypothesize that PISO constitutes a precursor of preeclampsia which is physiologically compensated for by vasodilating mechanisms, leading to preeclampsia only when they fail. [source] Pillared Layered Metal Phosphonates Showing Field-Induced Magnetic TransitionsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 6 2010Peng-Fei Wang Abstract The first examples of metal phosphonates based on 6-phosphononicotinic acid (pnaH3), namely, M3(pna)2(H2O)2 {1: M = CuII, 2: M = CoII} are reported. Both possess pillared layered structures. Within the inorganic layer, chains made up of dimers of edge-sharing {M2O6} octahedra and {M1O6} octahedra through O(1W), O,P,O, and O,C,O units are interconnected by {PO3C} tetrahedra. The pyridyl groups of pna3, serve as the pillars. An antiferromagnetic ground state is found for each compound. When the external field reaches critical points at low temperature, compound 1 features a spin flop transition, whereas 2 shows metamagnetic behavior. [source] Chain-Like Tetra-, Penta- and Heptanuclear Cyanide-Bridged Complexes by Attachment of Organometallic Cyanides to M2, M3 and M5 UnitsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 20 2003Tianlu Sheng Abstract Attachment of the "ligands" [Cp(dppe)Fe-CN], [Cp(PPh3)2Ru-CN], [Cp(CO)2Fe-CN] and [(CO)5M-CN],, (where M = Cr, Mo, W) to the polymetallic centres [Ru2(OAc)4]+, [Co3(dpa)4]2+ and [Ni5(tdpa)4]2+ yielded two tetra-, three penta- and five heptanuclear complexes with chain-like linear arrangements of the metal ions and the bridging cyanide ligands, as proved by the structure determination of [Ni5(tdpa)4{Cp(dppe)2Fe-CN}2](PF6)2. IR and CV data show that the Ru2, Co3 and Ni5 centres of these complexes withdraw electron density from the external organometallic units. This prevents electronic interactions between the two terminal metal ions, yet allows multistep one- and two-electron redox processes. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Muscarine activates the sodium,calcium exchanger via M3 receptors in basal forebrain neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2006Changqing Xu Abstract Neurons of the medial septum/diagonal band of Broca (MSDB) project to the hippocampus. Muscarinic cholinergic mechanisms within the MSDB are potent modulators of hippocampal functions; intraseptal scopolamine disrupts and intraseptal carbachol facilitates hippocampus-dependent learning and memory tasks, and the associated hippocampal theta rhythm. In earlier work, we demonstrated that, within the MSDB, the septohippocampal GABAergic but not cholinergic neurons are the primary target of muscarinic manipulations and that muscarinic activation of septohippocampal GABAergic neurons is mediated directly via M3 receptors. In the present study, we examined the ionic mechanism(s) underlying the excitatory actions of muscarine in these neurons. Using whole-cell patch-clamp recording techniques in rat brain slices, we demonstrated that M3 receptor-mediated muscarinic activation of MSDB neurons is dependent on external Na+ and is also reduced by bath-applied Ni2+ and KB-R7943 as well as by replacing external Na+ with Li+, suggesting a primary involvement of the Na+,Ca2+ exchanger. We conclude that the M3 receptor-mediated muscarinic activation of MSDB septohippocampal GABA-type neurons, that is important for cognitive functioning, is mediated via activation of the Na+,Ca2+ exchanger. [source] Postsynaptic M1 and M3 receptors are responsible for the muscarinic enhancement of retrograde endocannabinoid signalling in the hippocampusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2003Takako Ohno-Shosaku Abstract The cholinergic system is crucial for higher brain functions including learning and memory. These functions are mediated primarily by muscarinic acetylcholine receptors (mAChRs) that consist of five subtypes (M1,M5). A recent study suggested a novel role of acetylcholine as a potent enhancer of endocannabinoid signalling that acts retrogradely from postsynaptic to presynaptic neurons. In the present study, we further investigated the mechanisms of this cholinergic effect on endocannabinoid signalling. We made paired whole-cell recordings from cultured hippocampal neurons, and monitored inhibitory postsynaptic currents (IPSCs). The postsynaptic depolarization induced a transient suppression of IPSCs (DSI), a phenomenon known to involve retrograde signalling by endocannabinoids. The cholinergic agonist carbachol (CCh) markedly enhanced DSI at 0.01,0.3 µm without changing the presynaptic cannabinoid sensitivity. The facilitating effect of CCh on DSI was mimicked by the muscarinic agonist oxotremorine-M, whereas it was eliminated by the muscarinic antagonist atropine. It was also blocked by a non-hydrolizable analogue of GDP (GDP-,-S) that was applied intracellularly to postsynaptic neurons. The muscarinic enhancement of DSI persisted to a substantial degree in the neurons prepared from M1 -knockout and M3 -knockout mice, but was virtually eliminated in the neurons from M1/M3 -compound-knockout mice. CCh still enhanced DSI significantly under the blockade of postsynatpic K+ conductance, and did not significantly influence the depolarization-induced Ca2+ transients. These results indicate that the activation of postsynaptic M1 and M3 receptors facilitates the depolarization-induced release of endocannabinoids. [source] Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2003Manel M. Santafé Abstract We studied the presynaptic muscarinic autoreceptor subtypes controlling ACh release and their relationship with voltage-dependent calcium channels in the neuromuscular synapses of the Levator auris longus muscle from adult (30,40 days) and newborn (3,6 and 15 days postnatal) rats. Using intracellular recording, we studied how several muscarinic antagonists affected the evoked endplate potentials. In some experiments we previously incubated the muscle with calcium channel blockers (nitrendipine, ,-conotoxin-GVIA and ,-Agatoxin-IVA) before determining the muscarinic response. In the adult, the M1 receptor-selective antagonist pirenzepine (10 µm) reduced evoked neurotransmission (, 47%). The M2 receptor-selective antagonist methoctramine (1 µm) increased the evoked release (, 67%). Both M1- and M2-mediated mechanisms depend on calcium influx via P/Q-type synaptic channels. We found nothing to indicate the presence of M3 (4-DAMP-sensitive) or M4 (tropicamide-sensitive) receptors in the muscles of adult or newborn rats. In the 3,6-day newborn rats, pirenzepine reduced the evoked release (, 30%) by a mechanism independent of L-, N- and P/Q-type calcium channels, and the M2 antagonist methoctramine (1 µm) unexpectedly decreased the evoked release (, 40%). This methoctramine effect was a P/Q-type calcium-channel-dependent mechanism. However, upon maturation in the first two postnatal weeks, the M2 pathway shifted to perform the calcium-dependent release-inhibitory activity found in the adult. We show that the way in which M1 and M2 muscarinic receptors modulate neurotransmission can differ between the developing and adult rat neuromuscular synapse. [source] The role of the cutaneous cholinergic system in guttate psoriasisEXPERIMENTAL DERMATOLOGY, Issue 7 2008W. Dyck In previous studies, high levels of acetylcholine (ACh) have been reported in psoriasis lesions. In addition, patients with guttate psoriasis respond to oral treatment with atropine. We wanted to know how the cutaneous cholinergic system could be involved in this process. Since mast cells (MC) are characteristic components of the inflammatory infiltrate of guttate psoriasis, we compared ACh receptor (AChR) composition and ACh production in both epidermis and mast cells of 10 patients with guttate psoriasis in involved and uninvolved skin on protein level using immunofluorescence and in a MC line (HMC-1) using PCR. We could confirm the presence of numerous MC in guttate psoriasis lesion. Both in vivo and in vitro, MC lacked expression of cholinacetyltransferase (ChAT), vesicular acetylcholintransorter (VAChT) and cholintransporter-1 (ChT-1) but contained high levels of acetylcholinesterase (AChE). In mast cells of both involved and uninvolved skin we found both nicotinic (,3, ,5, ,7, ,9, ,10, ,2 and ,4 subunits) and muscarinic (M1, M3, M4, M5) AChR. In HMC-1 cells all AChR subunits found in skin where present on mRNA level, except ,7 and ,2. In lesional epidermis both ACh production and AChR expression was shifted from the basal to the suprabasal layers especially the nicotinic ,3, ,5, ,9, ,2 and ,4 and the muscarinic M3 and M5 AChR subunits. Our results exclude a role of the cholinergic system in the initiation of keratinocyte proliferation in the basal epidermal layer but point towards a role of epidermal AChR in suprabasal processes, most likely terminal differentiation and barrier formation as has been shown in other systems. Most importantly, mast cells are targets of paracrine and endocrine effects mediated by ACh and choline thus modulating inflammatory processes like guttate psoriasis and explaining the clinical efficacity of anticholinergic drugs like atropine. [source] Inhibition of SERCA Ca2+ pumps by 2-aminoethoxydiphenyl borate (2-APB)FEBS JOURNAL, Issue 15 20022-APB reduces both Ca2+ binding, by interfering with the pathway leading to the Ca2+ -binding sites, phosphoryl transfer from ATP 2-Aminoethoxydiphenyl Borate (2-APB) has been extensively used recently as a membrane permeable modulator of inositol-1,4,5-trisphosphate-sensitive Ca2+ channels and store-operated Ca2+ entry. Here, we report that 2-APB is also an inhibitor of sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) Ca2+ pumps, and additionally increases ion leakage across the phospholipid bilayer. Therefore, we advise caution in the interpretation of results when used in Ca2+ signalling experiments. The inhibition of 2-APB onthe SERCA Ca2+ pumps is isoform-dependent, with SERCA 2B being more sensitive than SERCA 1A (IC50 values for inhibition being 325 and 725 µm, respectively, measured at pH 7.2). The Ca2+ -ATPase is also more potently inhibited at lower pH (IC50 = 70 µm for SERCA1A at pH 6). 2-APB decreases the affinity for Ca2+ binding to the ATPase by more than 20-fold, and also inhibits phosphoryl transfer from ATP (by 35%), without inhibiting nucleotide binding. Activity studies performed using mutant Ca2+ -ATPases show that Tyr837 is critical for the inhibition of activity by 2-APB. Molecular modeling studies of 2-APB binding to the Ca2+ ATPase identified two potential binding sites close to this residue, near or between transmembrane helices M3, M4, M5 and M7. The binding of 2-APB to these sites could influence the movement of the loop between M6 and M7 (L6-7), and reduce access of Ca2+ to their binding sites. [source] Multifunctional Microporous MOFs Exhibiting Gas/Hydrocarbon Adsorption Selectivity, Separation Capability and Three-Dimensional Magnetic Ordering,ADVANCED FUNCTIONAL MATERIALS, Issue 15 2008Kunhao Li Abstract Microporous materials [M3(HCOO)6],·,DMF (M,=,Mn, Co, Ni) were synthesized solvothermally and structurally characterized by single crystal and powder X-ray diffraction methods. The metal network exhibits diamondoid connectivity and the overall framework gives rise to zigzag channels along the b axis where guest dimethylformamide molecules reside. The effective pore size of these channels is ,5,6,Å. The materials feature high thermal stability and permanent porosity with relatively small pore diameters which are attributed to the extensive strong dative bonding between the metal centers and formate molecules. The title compounds exhibit interesting multi-fold gas adsorption and magnetic properties. The adsorption study of a series of alcohols, aromatics, and linear hydrocarbons revealed strong control of the adsorbent channel structures on their adsorption capacity and selectivity. The study also indicated possibility of using these materials for separation of close boiling chemicals (e.g., ethylbenzene and p-xylene) via pressure swing adsorption (PSA) process and molecules with different diffusion parameters via kinetic-based process. Three-dimensional spontaneous magnetic ordering was found in all three network structures investigated and at ground states they behave somewhat like soft magnets. [source] SWICA,2 M3: Second Conference on Salt Water Intrusion in Coastal Aquifers: Monitoring, Modeling, and ManagementGROUND WATER, Issue 3 2004Luis E. Marin No abstract is available for this article. [source] Receptor architecture of human cingulate cortex: Evaluation of the four-region neurobiological modelHUMAN BRAIN MAPPING, Issue 8 2009Nicola Palomero-Gallagher Abstract The structural and functional organization of the human cingulate cortex is an ongoing focus; however, human imaging studies continue to use the century-old Brodmann concept of a two region cingulate cortex. Recently, a four-region neurobiological model was proposed based on structural, circuitry, and functional imaging observations. It encompasses the anterior cingulate, midcingulate, posterior cingulate, and retrosplenial cortices (ACC, MCC, PCC, and RSC, respectively). For the first time, this study performs multireceptor autoradiography of 15 neurotransmitter receptor ligands and multivariate statistics on human whole brain postmortem samples covering the entire cingulate cortex. We evaluated the validity of Brodmann's duality concept and of the four-region model using a hierarchical clustering analysis of receptor binding according to the degree of similarity of each area's receptor architecture. We could not find support for Brodmann's dual cingulate concept, because the anterior part of his area 24 has significantly higher AMPA, kainate, GABAB, benzodiazepine, and M3 but lower NMDA and GABAA binding site densities than the posterior part. The hierarchical clustering analysis distinguished ACC, MCC, PCC, and RSC as independent regions. The ACC has highest AMPA, kainate, ,2, 5-HT1A, and D1 but lowest GABAA densities. The MCC has lowest AMPA, kainate, ,2, and D1 densities. Area 25 in ACC is similar in receptor-architecture to MCC, particularly the NMDA, GABAA, GABAB, and M2 receptors. The PCC and RSC differ in the higher M1 and ,1 but lower M3 densities of PCC. Thus, multireceptor autoradiography supports the four-region neurobiological model of the cingulate cortex. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [source] Glutathione S -transferase M3 (A/A) genotype as a risk factor for oral cancer and leukoplakia among Indian tobacco smokersINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Nilabja Sikdar Abstract Polymorphism in glutathione S -transferase (GST) genes, causing variations in enzyme activities, may influence susceptibility to oral cancer and leukoplakia in smokers and/or smokeless tobacco users. In this case-control study consisting of 109 leukoplakia and 256 oral cancer patients and 259 controls, genotype frequencies at GSTM1, GSTT1, GSTM3 and GSTP1 loci were determined by polymerase chain reaction-restriction fragment length polymorphism methods and analyzed by multiple logistic regression to determine the risks of the diseases. There were no significant differences in the distributions of GSTM1, GSTM3 and GSTT1 genotypes in patients and controls when all individuals were compared. In contrast, frequencies of ile/ile genotype at codon 105 and variant val-ala haplotype of GSTP1 was significantly higher (OR = 1.5; 95% CI = 1.0,2.0) and lower (OR = 1.4; 95% CI = 1.0,1.9) in oral cancer patients compare to controls, respectively. The impacts of all genotypes on risks of oral cancer and leukoplakia were also analyzed in patients with different tobacco habits and doses. Increased risks of cancer and leukoplakia were observed in tobacco smokers with GSTM3 (A/A) genotype (OR = 2.0, 95% CI = 1.0,4.0; OR = 2.0, 95% CI = 1.0,4.4, respectively). So, GSTM3 (A/A) genotype could become one of the markers to know which of the leukoplakia would be transformed into cancer. Heavy tobacco chewing (> 124 chewing-year) increased the risk of cancer in individuals with GSTT1 homozygous null genotype (OR = 3.0; 95% CI = 1.0,9.8). Furthermore, increased lifetime exposure to tobacco smoking (> 11.5 pack-year) increased the risk of leukoplakia in individuals with GSTM1 homozygous null genotype (OR = 2.4; 95% CI = 1.0,5.7). It may be suggested that polymorphisms in GSTP1, GSTM1, GSTM3 and GSTT1 genes regulate risk of cancer and leukoplakia differentially among different tobacco habituals. © 2003 Wiley-Liss, Inc. [source] Peroxidase activity, chlorophylls and antioxidant profile of two leaf vegetables (Solanum nigrum L. and Amaranthus cruentus L.) under six pretreatment methods before cookingINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 1 2008Odunayo Clement Adebooye Summary The study evaluated the effects of six pretreatment methods before cooking on the peroxidase activity, chlorophyll and antioxidant profile of Amaranthus cruentus L. and Solanum nigrum L. The six pretreatments methods used were chopped only (raw sample) (coded M1); chopped and dried at 50 °C for 5 h (coded M2); chopped and squeezed in water (at room temperature) (coded M3); chopped and soaked in warm water (approximately 60 °C), then cooled and squeezed (coded M4); chopped and soaked in salt-treated water (approximately 20 g NaCl per litre of water) for 15 min, then squeezed (coded M5) and chopped and soaked in boiling water (100 °C), then cooled and squeezed (coded M6). The main effect of vegetable type and the main effect of pretreatment methods have significant effects (P 0.05) on the parameters measured, while the interaction of vegetable type and pretreatment methods have no significant effect on the parameters measured. Statistical analyses (P 0.05) showed that chlorophyll a and b occur in ratio 3:1 in the two vegetables, irrespective of the pretreatment imposed. Peroxidase activity test showed that A. cruentus, irrespective of the pretreatment imposed showed, no peroxidase activity, while S. nigrum showed high peroxidase activity for all the pretreatments except for M6. Results showed that there was a significantly (P 0.05) higher content of carotenoids in A. cruentus when compared with S. nigrum, while the total phenolics, total flavonoids and total tannins contents were higher in S. nigrum when compared with A. cruentus, irrespective of the pretreatment method used. For the two vegetables, the percentage losses in total carotenoids, phenolics, flavonoids and total tannins at M6 when compared with M1 were 53.3,60.5%, 55.6,57.1%, 62.4,63.6% and 66.1,73.5%, respectively. There was a sharp drop in the carotenoids, phenolics, flavonoids and tannins contents of the two vegetables at M4 and M6, with both treatments having closely similar values for each parameter. [source] Telomerase activity and telomere length in acute leukemia: correlations with disease progression, subtypes and overall survivalINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2010Y. WANG Summary The progressive shortening of telomeres and the activation of telomerase are considered to be one of the important mechanisms in cellular immortalization and disease progression. Bone marrow samples were collected from 148 patients with acute leukemia (AL). Based on the stage of the disease, patients were divided into the newly diagnosed group, the relapsed group and the complete remission (CR) group. telomerase activity (TA) was examined by PCR-ELISA, and telomere length (TL) was examined by Southern blot analyses. TA and TL were analyzed in relation to AL stage and subtype. Five-year survival was analyzed using Kaplan,Meier survival curve. TA in AL patients was higher than healthy individuals. TA level was the highest in the relapsed group, followed by the newly diagnosed group, and then the CR group. TA had no difference between acute nonlymphocytic leukemia (ANLL) group and acute lymphocytic leukemia (ALL) group. But TA in group of subtype M3 was lower than other subtypes of ANLL. TL in AL group was shorter than the control group. TL was the shortest in the relapsed group, followed by the newly diagnosed group, and finally the CR group. TL exhibited an inverse correlation with TA. The group of patients with high TA had a significantly poorer five-year-survival than that of low TA group. TA is elevated and TL is shortened in AL patients. There is a significant inverse correlation between TL and TA. Patients in late-stage disease had shorter TL and higher TA than those in early stages. The shortened TL and elevated TA correlated with disease progression and relapse, and they may serve as prognostic factors for AL patients with poor outcome. M3 subtype is special with relative lower TA and long-lasting survival than other subtypes. [source] Multipole moments and polarizability of molecular systems with D3h symmetry in orbitally degenerate statesINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 6 2006I. Ya. Abstract It was proved, by ab initio studies, that the electronic ground states of the molecules MF3 (MV, Cr, Mn), M3 (MLi, Na, K), and C3H3, with D3h symmetry, have orbital degeneracy. It was shown that in the base functions of these degenerate states, the reduced matrix elements of the in-plane E,-type components of the dipole moment, of the quadrupole moments and of the nontotal symmetric components of the (hyper)polarizability are nonzero. The computed values of the dipole and quadrupole moments of the polarizability and hyperpolarizabilities are comparable to those of the molecular systems of the lower than D3h symmetry. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006 [source] Electroporation-mediated muscarinic M3 receptor gene transfer into rat urinary bladderINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2004MASAYUKI OTANI Abstract Background: Muscarinic M3 (M3) receptor has been recognized as a major muscarinic receptor for smooth muscle contractions of the urinary bladder. Under the hypothesis that overexpression of M3 receptor in the urinary bladder would enhance urinary bladder contractions, we have transferred the M3 receptor gene into rat bladders using electroporation (EP) and evaluated the functional expression of the transferred gene. Methods: Plasmids expressing luciferase, a green fluorescence protein and M3 receptor were injected into the rat bladder and square-wave electric pulses were immediately applied. Two days after gene transfer, we analyzed gene expression. Immunohistochemical staining was performed and the contractile responses from isolated bladder strips, which were induced KCl, carbachol and electrical field stimulation (EFS), were evaluated. Results: The optimal conditions of electroporation were 8 pulses, 45 voltages, 50 milliseconds/pulses and 1 Hz. Under these conditions, luciferase gene expression was enhanced approximately 300-fold, compared to an injection of DNA only. Regarding immunohistochemistry with an anti-M3 receptor, an increase in immunoactivity was observed in the M3 receptor gene transferred rat bladder, compared to the bladder of the control rat. In rats with the transferred M3 receptor gene, carbachol- and EFS-induced maximum contractile responses of bladder smooth muscle strips significantly increased. Conclusions: These findings suggest that an in vivo EP procedure is an useful method for gene transfer into the bladder and that an overexpression of M3 receptor in the rat bladder enhances bladder contractility. This technique may become a new treatment modality for detrusor underactivity. [source] Structure and properties of phase change materials based on HDPE, soft Fischer-Tropsch paraffin wax, and wood flourJOURNAL OF APPLIED POLYMER SCIENCE, Issue 3 2010M. E. Mngomezulu Abstract Phase-change materials based on high density polyethylene (HDPE), soft Fischer-Tropsch paraffin wax (M3), and alkali-treated wood flour (WF) were investigated. The blend and composite samples were prepared by melt mixing using a Brabender Plastograph, followed by melt pressing. They were characterized in terms of their morphology, as well as thermal, mechanical, thermo-mechanical, and water absorption properties. Although SEM micrographs showed some evidence of intimate contact between the WF particles and the HDPE matrix as a result of alkali treatment, poor filler dispersion, and interfacial adhesion were also observed. Partial immiscibility of the HDPE and the M3 wax was noticed, with the WF particles covered by wax. There was plasticization of the HDPE matrix by the wax, as well as partial cocrystallization, inhomogeneity and uneven wax dispersion in the polymer matrix. The HDPE/WF/M3 wax composites were more homogeneous than the blends. The presence of wax reduced the thermal stability of the blends and composites. Both the presence of M3 wax and WF influenced the viscoelastic behavior of HDPE. The HDPE/M3 wax blends showed an increase in the interfacial amorphous content as the wax content increases, which resulted in the appearance of a ,-relaxation peak. The presence of M3 wax in HDPE reduced the mechanical properties of the blends. For the composites these properties varied with WF content. An increase in wax content resulted to a decrease in water uptake by the composites, probably because the wax covered the WF particles and penetrated the pores in these particles. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [source] FIAT represses bone matrix mineralization by interacting with ATF4 through its second leucine zipperJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2008Vionnie W.C. Yu Abstract We have characterized FIAT, a 66 kDa leucine zipper (LZ) protein that dimerizes with activating transcription factor 4 (ATF4) to form inactive dimers that cannot bind DNA. Computer analysis identifies three putative LZ motifs within the FIAT amino acid sequence. We have used deletion- and/or site-specific mutagenesis to individually inactivate these motifs in order to identify the functional LZ that mediates the FIAT,ATF4 interaction. Amino acids 194,222 that encode the FIAT LZ2 were deleted (mutant FIAT ZIP2 DEL). We inactivated each zipper individually by replacing two or three leucine residues within each zipper by alanine residues. The engineered mutations were L142A/L149A (mutant M1, first zipper), L208A/L215A/L222A (mutant M2, second zipper), and L441A/L448A (mutant M3, third zipper). MC3T3-E1 osteoblastic cells with an integrated 1.3 kb mouse osteocalcin gene promoter fragment driving expression of luciferase were transfected with expression vectors for ATF4 and the various FIAT deletion- or site-specific mutants. Inhibition of ATF4-mediated transcription was compared between wild-type (WT) and LZ FIAT mutants. The deletion mutant FIAT ZIP2 DEL and the sequence-specific M2 mutant did not interact with ATF4 and were unable to inhibit ATF4-mediated transcription. The M1 or M3 mutations did not affect the ability of FIAT to contact ATF4 or to inhibit its transcriptional activity. Stable expression of WT FIAT in osteoblastic cells inhibited mineralization, but not expression of the FIAT ZIP2 DEL and M2 mutants. This structure,function analysis reveals that FIAT interacts with ATF4 and modulates its activity through its second leucine zipper motif. J. Cell. Biochem. 105: 859,865, 2008. © 2008 Wiley-Liss, Inc. [source] Distribution of muscarinic receptor subtype M3 in melanomas and their metastasesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2008Matthias Oppitz Background:, Muscarinic acetylcholine receptors (mR) are involved in the regulation of cancer cell motility and cancer progression. mR have been shown in melanoma cell lines and cryostat sections of melanomas. To substantiate the experimental data, here the correlation of mR-expression with invasive growth was studied on the cellular level by comparison with HMB-45 immunoreactivity. Methods:, mR were detected by a M3 subtype-specific polyclonal antibody in normal skin, benign compound nevi, primary melanomas [nodular type, nodular malignant melanoma (NMM)] and metastases, and were compared with HMB-45 staining in parallel paraffin sections. Results:, The general staining pattern of anti-M3 and HMB-45 was similar with accentuation of zones with infiltrative growth. On the cellular level, only a subpopulation of the HMB-45 positive melanoma cells expressed mR. Immunoreactivity was encountered in 3 of 15 nevi, in 9 of 14 NMM and in 10 of 14 melanoma metastases. Polymorphonuclear granulocytes also exhibited strong reactivity for anti-M3. Conclusion:, mR-expression is associated with invasive migration of melanomas. [source] A monetary real-time conditional forecast of euro area inflation,JOURNAL OF FORECASTING, Issue 4 2010Sylvia Kaufmann Abstract Based on a vector error correction model we produce conditional euro area inflation forecasts. We use real-time data on M3 and HICP, and include real GPD, the 3-month EURIBOR and the 10-year government bond yield as control variables. Real money growth and the term spread enter the system as stationary linear combinations. Missing and outlying values are substituted by model-based estimates using all available data information. In general, the conditional inflation forecasts are consistent with the European Central Bank's assessment of liquidity conditions for future inflation prospects. The evaluation of inflation forecasts under different monetary scenarios reveals the importance of keeping track of money growth rate in particular at the end of 2005. Copyright © 2009 John Wiley & Sons, Ltd. [source] On the roles of deformation and fluid during rejuvenation of a polymetamorphic terrane: inferences on the geodynamic evolution of the Ruker Province, East AntarcticaJOURNAL OF METAMORPHIC GEOLOGY, Issue 8 2007G. PHILLIPS Abstract Evaluating pressure,temperature (P,T) conditions through mineral equilibria modelling within an amphibolite facies polymetamorphic terrane requires knowledge of the fluid content of the rocks. The Archean-Palaeoproterozoic basement rocks of the Ruker Province, East Antarctica, preserve evidence of three metamorphic events (M1,M3). Of particular interest is the M3 event, which is constrained to the early Palaeozoic (c. 550,480 Ma). Evaluation of the tectonic setting during this time is important because the Ruker Province is located within a critical region with respect to models of Gondwana assembly. Structural evidence of the early Palaeozoic event is preserved as large (up to ,500 m wide) high strain zones that cut the orthogneiss-metasedimentary basement (Tingey Complex) of the Ruker Province. Rocks within these zones have been thoroughly recrystallized and preserve a dominant shear fabric and M3 mineral assemblages that formed at P,T conditions of 4.0,5.2 kbar and 565,640 °C. Distal to these zones, rocks preserve more complex petrographic relationships with S1 and S2 foliations, being incompletely overgrown by M3 retrograde assemblages. We show that the mineral assemblages preserved during the M3 event are highly dependent on the availability of fluid H2O, which is strongly influenced by the structural setting (i.e. proximity to the high-strain zones). P,T structural and fluid flow constraints support a model of basin inversion during early Palaeozoic crustal rejuvenation in the Ruker Province. [source] Metamorphic evolution of kyanite,staurolite-bearing epidote,amphibolite from the Early Palaeozoic Oeyama belt, SW JapanJOURNAL OF METAMORPHIC GEOLOGY, Issue 4 2004T. Tsujimori Abstract Early Palaeozoic kyanite,staurolite-bearing epidote,amphibolites including foliated epidote,amphibolite (FEA), and nonfoliated leucocratic or melanocratic metagabbros (LMG, MMG), occur in the Fuko Pass metacumulate unit (FPM) of the Oeyama belt, SW Japan. Microtextural relationships and mineral chemistry define three metamorphic stages: relict granulite facies metamorphism (M1), high- P (HP) epidote,amphibolite facies metamorphism (M2), and retrogression (M3). M1 is preserved as relict Al-rich diopside (up to 8.5 wt.% Al2O3) and pseudomorphs after spinel and plagioclase in the MMG, suggesting a medium- P granulite facies condition (0.8,1.3 GPa at >,850 °C). An unusually low-variance M2 assemblage, Hbl + Czo + Ky ± St + Pg + Rt ± Ab ± Crn, occurs in the matrix of all rock types. The presence of relict plagioclase inclusions in M2 kyanite associated with clinozoisite indicates a hydration reaction to form the kyanite-bearing M2 assemblage during cooling. The corundum-bearing phase equilibria constrain a qualitative metamorphic P,T condition of 1.1,1.9 GPa at 550,800 °C for M2. The M2 minerals were locally replaced by M3 margarite, paragonite, plagioclase and/or chlorite. The breakdown of M2 kyanite to produce the M3 assemblage at <,0.5 GPa and 450,500 °C suggests a greenschist facies overprint during decompression. The P,T evolution of the FPM may represent subduction of an oceanic plateau with a granulite facies lower crust and subsequent exhumation in a Pacific-type orogen. [source] High-pressure granulites in the Sanggan area, North China craton: metamorphic evolution, P,T paths and geotectonic significanceJOURNAL OF METAMORPHIC GEOLOGY, Issue 8 2002J. H. Guo Abstract High-pressure basic granulites are widely distributed as enclaves and sheet-like blocks in the Huaian TTG gneiss terrane in the Sanggan area of the Central Zone of the North China craton. Four stages of the metamorphic history have been recognised in mineral assemblages based on inclusion, exsolution and reaction textures integrated with garnet zonation patterns as revealed by compositional maps and compositional profiles. The P,T conditions for each metamorphic stage were obtained using thermodynamically and experimentally calibrated geothermobarometers. The low-Ca core of growth-zoned garnet, along with inclusion minerals, defines a prograde assemblage (M1) of garnet + clinopyroxene + plagioclase + quartz, yielding 700 °C and 10 kbar. The peak of metamorphism at about 750,870 °C and 11,14.5 kbar (M2) is defined by high-Ca domains in garnet interiors and inclusion minerals of clinopyroxene, plagioclase and quartz. Kelyphites or coronas of orthopyroxene + plagioclase ± magnetite around garnet porphyroblasts indicate garnet breakdown reactions (M3) at conditions around 770,830 °C and 8.5,10.5 kbar. Garnet exsolution lamellae in clinopyroxene and kelyphites of amphibole + plagioclase around garnet formed during the cooling process at about 500,650 °C and 5.5,8 kbar (M4). These results help define a sequential P,T path containing prograde, near-isothermal decompression (ITD) and near-isobaric cooling (IBC) stages. The clockwise hybrid ITD and IBC P,T paths of the HP granulites in the Sanggan area imply a model of thickening followed by extension in a collisional environment. Furthermore, the relatively high-pressures (6,14.5 kbar) of the four metamorphic stages and the geometry of the P,T paths suggest that the HP granulites, together with their host Huaian TTG gneisses, represent the lower plate in a crust thickened during collision. The corresponding upper-plate might be the tectonically overlying Khondalite series, which was subjected to medium- to low-pressure (MP/LP: 7,4 kbar) granulite facies metamorphism with a clockwise P,T path including an ITD segment. Both the HP and the MP/LP granulite facies events occurred contemporaneously at c. 1.90,1.85 Ga in a collisional environment created by the assembly process of the North China craton. [source] Petrology and P,T path of the Fuping mafic granulites: implications for tectonic evolution of the central zone of the North China cratonJOURNAL OF METAMORPHIC GEOLOGY, Issue 4 2000G. C. Zhao The Fuping Complex and the adjoining Wutai and Hengshan Complexes are located in the central zone of the North China craton. The dominant rock types in the Fuping Complex are high-grade tonalitic,trondhjemitic,granodioritic (TTG) gneisses, with minor amounts of mafic granulites, syntectonic granitic rocks and supracrustal rocks. The petrological evidence from the mafic granulites indicates three stages of metamorphic evolution. The M1 stage is represented by garnet porphyroblasts and matrix plagioclase, quartz, orthopyroxene, clinopyroxene and hornblende. Orthopyroxene+plagioclase symplectites and clinopyroxene+plagioclase±orthopyroxene coronas formed in response to decompression during M2 following the peak metamorphism at M1. Hornblende+plagioclase symplectites formed as a result of further isobaric cooling and retrograde metamorphism during M3. The P,T estimates using TWQ thermobarometry are: 900,950 °C and 8.0,8.5 kbar for the peak assemblage (M1), based on the core compositions of garnet, matrix pyroxene and plagioclase; 700,800 °C and 6.0,7.0 kbar for the pyroxene+plagioclase symplectites or coronas (M2); and 550,650 °C and 5.3,6.3 kbar for the hornblende+plagioclase symplectites (M3), based on garnet rim and corresponding symplectic mineral compositions. These P,T estimates define a clockwise P,T path involving near-isothermal decompression for the Fuping Complex, similar to the P,T path estimated for the metapelitic gneisses. The inferred P,T path suggests that the Fuping Complex underwent initial crustal thickening, subsequent exhumation, and finally cooling and retrogression. This tectonothermal path is similar to P,T paths inferred for the Wutai and Hengshan Complexes and other tectonic units in the central zone of the North China craton, but different from anti-clockwise P,T paths estimated for the basement rocks in the eastern and western zones of the craton. Based on lithological, structural, metamorphic and geochronological data, the eastern and western zones of the craton are considered to represent two different Archean to Paleoproterozoic continental blocks that amalgamated along the central zone at the end of Paleoproterozoic. The P,T paths of the Fuping Complex and other tectonic units in the central zone record the collision between the eastern and western zones that led to the final assembly of the North China craton at c. 1800 Ma. [source] Role of M2, M3, and M4 muscarinic receptor subtypes in the spinal cholinergic control of nociception revealed using siRNA in ratsJOURNAL OF NEUROCHEMISTRY, Issue 4 2009You-Qing Cai Abstract Muscarinic acetylcholine receptors (mAChRs) are involved in the control of nociception in the spinal cord. The M2, M3, and M4 mAChR subtypes are present in the spinal dorsal horn. However, the role of the individual subtypes in the anti-nociceptive effect produced by mAChR agonists is uncertain. Here, we determined the contribution of M2, M3, and M4 subtypes to spinal muscarinic analgesia by using small-interference RNA (siRNA) targeting specific mAChR subtypes in rats. The neuronal uptake and distribution of a chitosan-siRNA conjugated fluorescent dye in the spinal cord and dorsal root ganglion were confirmed after intrathecal injection. The control and gene-specific siRNA-chitosan complexes were injected intrathecally for three consecutive days. Quantitative reverse-transcription polymerase chain reaction analysis showed that treatment with siRNA targeting M2, M3, or M4 subtype produced a large reduction in the corresponding mRNA levels in the dorsal root ganglion and dorsal spinal cord. Also, the protein levels of the mAChR subtypes in the spinal cord were significantly down-regulated by siRNA treatment, as determined by the immunoprecipitation and receptor-binding assay. Treatment with the M2 -siRNA caused a large reduction in the inhibitory effect of muscarine on the nociceptive withdrawal threshold. Furthermore, M4 knockdown at the spinal level significantly reduced the anti-nociceptive effect of muscarine. However, the anti-nociceptive effect of muscarine was not significantly changed by the M3 -specific siRNA. Our study suggests that chitosan nanoparticles can be used for efficient delivery of siRNA into the neuronal tissues in vivo. Our findings also provide important functional evidence that M2 and M4, but not M3, contribute to nociceptive regulation by mAChRs at the spinal level. [source] Restricted, but abundant, expression of the novel rat gene-3 (R3) relaxin in the dorsal tegmental region of brainJOURNAL OF NEUROCHEMISTRY, Issue 6 2002Tanya C. D. Burazin Abstract Relaxin is a peptide hormone with known actions associated with female reproductive physiology, but it has also been identified in the brain. Only one relaxin gene had been characterized in rodents until recently when a novel human relaxin gene, human gene-3 (H3) and its mouse equivalent (M3) were identified. The current study reports the identification of a rat homologue, rat gene-3 (R3) relaxin that is highly expressed in a discrete region of the adult brain. The full R3 relaxin cDNA was generated using RT-PCR and 3, and 5, RACE protocols. The derived amino acid sequence of R3 relaxin retains all the characteristic features of a relaxin peptide and has a high degree of homology with H3 and M3 relaxin. The distribution of R3 relaxin mRNA in adult rat brain was determined and highly abundant expression was only detected in neurons of the ventromedial dorsal tegmental nucleus (vmDTg) in the pons, whereas all other brain areas were unlabelled or contained much lower mRNA levels. Relaxin binding sites and relaxin immunoreactivity were also detected in the vmDTg. These together with earlier findings provide strong evidence for a role(s) for multiple relaxin peptides as neurotransmitters and/or modulators in the rat CNS. [source] Transmembrane signaling through phospholipase C-, in the developing human prefrontal cortexJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2006Iñigo Ruiz de Azúa Abstract To investigate changes in muscarinic receptor-stimulated phospholipase C-, (PLC-,) activity during brain development, we examined the functional coupling of each of the three major protein components of the phosphoinositide system (M1, M3, and M5 muscarinic receptor subtypes; Gq/11 proteins; PLC-,1,4 isoforms) in membrane preparations from post-mortem human prefrontal cerebral cortex collected at several stages of prenatal and postnatal development. In human prenatal brain membranes, PLC was found to be present and could be activated by calcium, but the ability of guanosine-5,-o-3 thiotriphosphate (GTP,S) or carbachol (in the presence of GTP,S) to modulate prenatal PLC-, was significantly weaker than that associated with postnatal PLC-,. Western blot analysis revealed that the levels of G,q/11 did not change significantly during development. In contrast, dramatically higher levels of expression of PLC-,1,4 isoforms and of M1, M3, and M5 muscarinic receptors were detected in the child vs. the fetal brain, a finding that might underlie the observed increased activity of PLC. Thus, inositol phosphate production may be more efficiently regulated by altering the amount of effectors (PLC-,1,4) and receptors (M1,3,5 subtypes) than by altering the level of G,q/11 subunits. These results demonstrate that different PLC isoforms are expressed in the prefrontal cortex of the developing human brain in an age-specific manner, suggesting specific roles not only in synaptic transmission but also in the differentiation and maturation of neurons in the developing brain. © 2006 Wiley-Liss, Inc. [source] Metabolism and disposition of resveratrol in the isolated perfused rat liver: Role of Mrp2 in the biliary excretion of glucuronidesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2008Alexandra Maier-Salamon Abstract In this study, the hepatic metabolism and transport system for resveratrol was examined in isolated perfused livers from Wistar and Mrp2-deficient TR, rats. Based on extensive metabolism to six glucuronides and sulfates (M1,M6), the hepatic extraction ratio and clearance of resveratrol was very high in Wistar and TR, rats (E: 0.998 vs. 0.999; Cl: 34.9 mL/min vs. 36.0 mL/min). However, biliary excretion and efflux of conjugates differs greatly in TR, rats. While cumulative biliary excretion of the glucuronides M1, M2, M3, and M5 dropped dramatically to 0,6%, their efflux into perfusate increased by 3.6-, 1.8-, 2.5-, and 1.5-fold. In contrast, biliary secretion of the sulfates M4 and M6 was partially maintained in the Mrp2-deficient rats (61% and 39%) with a concomitant decline of their efflux into perfusate by 33.2% and 78.1%. This indicates that Mrp2 exclusively mediates the biliary excretion of resveratrol glucuronides but only partly that of sulfates. Cumulative secretion of unconjugated resveratrol into bile of TR, rats was only reduced by 40%, and into perfusate by 19%, suggesting only a minor role of Mrp2 in resveratrol elimination. In summary, resveratrol was dose-dependently metabolized to several conjugates whereby the canalicular transporter Mrp2 selectively mediated the biliary excretion of glucuronides. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1615,1628, 2008 [source] Genetic and Pathogenic Variation Among Tobacco Black Shank Strains of Phytophthora parasitica var. nicotianae from the Main Tobacco Growing in ChinaJOURNAL OF PHYTOPATHOLOGY, Issue 5 2003X. G. Zhang Abstract Pathogenic and genetic variability among seven populations of Phytophthora parasitica var. nicotianae from individual tobacco fields (Yunnan, Shandong, Henan, Heilongjiang, Shanxi, Fujian and Sichuan provinces) were investigated using pathogenicity and randomly amplified polymorphic DNA (RAPD) analyses; 63 strains were isolated from different fields of seven tobacco growing regions, using tobacco cv. Hongda as a baiting host. Pathogenic variability was evaluated in greenhouse studies using five tobacco cultivars that have different levels of resistance to tobacco black shank; 75 and 73% of the strains were pathogenic on M3 and M4, 29 and 33% on M1 and M2, and 94% were pathogenic on M5, respectively. Disease severity incited by different strains varied significantly on individual tobacco cultivars. The percentage of strains pathogenic on different cultivars varied among locations. Genotypic variation among 63 strains was evaluated by RAPD analysis. Ten primers detected 89 polymorphic bands. Cluster and principal coordinates analysed cluster groups. the minor group contained 26 strains, and major group contained 37 strains. Estimates of genetic diversity based on RAPD analysis ranged from 0.24 to 0.34 within populations to 0.36 among all strains from all populations. Phytophthora parasitica var. nicotianae populations were genotypically and phenotypically variable, but no distinct genotypic differences were identified among populations from the seven locations. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||