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Functional Role (functional + role)
Kinds of Functional Role Selected AbstractsFunctional Role of ,3-Adrenoreceptors in the BladderLUTS, Issue 2009Masahide HIGAKI The detrusor muscle contains ,-adrenoceptors (,-AR) and three subtypes, such as ,1-AR, ,2-AR, and ,3-AR, which have been identified in most species. There is a predominant expression of ,3-AR messenger RNA in human bladder tissue when compared with the ,1-AR and ,2-AR subtypes. Moreover, the presence of ,1, ,2, and ,3-AR in the human urothelium has been identified. It has also been demonstrated in animals that relaxation mediated through ,s-AR is achieved solely by cAMP-dependent mechanisms in non-contracted detrusor muscles, whereas in KCl precontracted detrusor muscles, cAMP-dependent and -independent mechanisms by way of calcium-activated K +(BK Ca) channels may be involved in ,-adrenergic relaxation. In addition, a recent phase II proof-of-concept study using a novel selective ,3-adrenoceptor agonist (YM178) has shown clinical efficacy in the treatment of overactive bladder (OAB) symptoms, suggesting that ,3-AR should be used as a therapeutic target for the treatment of OAB disorders. [source] Action Mechanisms of the Secondary Metabolite Euplotin C: Signaling and Functional Role in EuplotesTHE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 5 2008FRANCESCA TRIELLI ABSTRACT. Among secondary metabolites, the acetylated hemiacetal sesquiterpene euplotin C has been isolated from the marine, ciliated protist Euplotes crassus, and provides an effective mechanism for reducing populations of potential competitors through its cytotoxic properties. However, intracellular signaling mechanisms and their functional correlates mediating the ecological role of euplotin C are largely unknown. We report here that, in E. vannus (an Euplotes morphospecies that does not produce euplotin C and shares with E. crasssus the same interstitial habitat), euplotin C rapidly increases the intracellular concentration of both Ca2+ and Na+, suggesting a generalized effect of this metabolite on cation transport systems. In addition, euplotin C does not induce oxidative stress, but modulates the electrical properties of E. vannus through an increase of the amplitude of graded action potentials. These events parallel the disassembling of the ciliary structures, the inhibition of cell motility, the occurrence of aberrant cytoplasmic vacuoles, and the rapid inhibition of phagocytic activity. Euplotin C also increases lysosomal pH and decreases lysosomal membrane stability of E. vannus. These results suggest that euplotin C exerts a marked disruption of those homeostatic mechanisms whose efficiency represents the essential prerequisite to face the challenges of the interstitial environment. [source] Functional role of human NK cell receptor 2B4 (CD244) isoformsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2009Stephen O. Mathew Abstract 2B4 (CD244), a member of the signaling lymphocyte-activation molecule (SLAM/CD150), is expressed on all NK cells, a subpopulation of T cells, monocytes and basophils. Human NK cells express two isoforms of 2B4, h2B4-A and h2B4-B that differ in a small portion of the extracellular domain. In the present investigation, we have studied the functions of h2B4-A and h2B4-B. Our study demonstrated that these two isoforms differ in their binding affinity for CD48, which results in differential cytotoxic activity as well as intracellular calcium release by NK cells upon target cell recognition. Analysis of the predicted 3-D structure of the two isoforms showed conformational differences that could account for their differences in binding affinity to CD48. h2B4-A was able to mediate natural cytotoxicity against CD48-expressing K562 target cells and induce intracellular calcium release, whereas h2B4-B showed no effects. NK-92MI, U937, THP-1, KU812, primary monocytes, basophils and NK cells showed expression of both h2B4-A and h2B4-B whereas YT and IL-2-activated NK cells did not show any h2B4-B expression. Stimulation of NK cells through 2B4 resulted in decreased mRNA levels of both h2B4-A and h2B4-B indicating that down-regulation of 2B4 isoforms may be an important factor in controlling NK cell activation during immune responses. [source] Functional role of the linker region in purified human P-glycoproteinFEBS JOURNAL, Issue 13 2009Tomomi Sato Human P-glycoprotein (P-gp), which conveys multidrug resistance, is an ATP-dependent drug efflux pump that transports a wide variety of structurally unrelated compounds out of cells. P-gp possesses a ,linker region' of , 75 amino acids that connects two homologous halves, each of which contain a transmembrane domain followed by a nucleotide-binding domain. To investigate the role of the linker region, purified human P-gp was cleaved by proteases at the linker region and then compared with native P-gp. Based on a verapamil-stimulated ATP hydrolase assay, size-exclusion chromatography analysis and a thermo-stability assay, cleavage of the P-gp linker did not directly affect the preservation of the overall structure or the catalytic process in ATP hydrolysis. However, linker cleavage increased the kcat values both with substrate (ksub) and without substrate (kbasal), but decreased the ksub/kbasal values of all 10 tested substrates. The former result indicates that cleaving the linker activates P-gp, while the latter result suggests that the linker region maintains the tightness of coupling between the ATP hydrolase reaction and substrate recognition. Inspection of structures of the P-gp homolog, MsbA, suggests that linker-cleaved P-gp has increased ATP hydrolase activity because the linker interferes with a conformational change that accompanies the ATP hydrolase reaction. Moreover, linker cleavage affected the specificity constants [ksub/Km(D)] for some substrates (i.e. linker cleavage probably shifts the substrate specificity profile of P-gp). Thus, this result also suggests that the linker region regulates the inherent substrate specificity of P-gp. [source] Functional role of fumarate site Glu59 involved in allosteric regulation and subunit,subunit interaction of human mitochondrial NAD(P)+ -dependent malic enzymeFEBS JOURNAL, Issue 4 2009Ju-Yi Hsieh Here we report on the role of Glu59 in the fumarate-mediated allosteric regulation of the human mitochondrial NAD(P)+ -dependent malic enzyme (m-NAD-ME). In the present study, Glu59 was substituted by Asp, Gln or Leu. Our kinetic data strongly indicated that the charge properties of this residue significantly affect the allosteric activation of the enzyme. The E59L enzyme shows nonallosteric kinetics and the E59Q enzyme displays a much higher threshold in enzyme activation with elevated activation constants, KA,Fum and ,KA,Fum. The E59D enzyme, although retaining the allosteric property, is quite different from the wild-type in enzyme activation. The KA,Fum and ,KA,Fum of E59D are also much greater than those of the wild-type, indicating that not only the negative charge of this residue but also the group specificity and side chain interactions are important for fumarate binding. Analytical ultracentrifugation analysis shows that both the wild-type and E59Q enzymes exist as a dimer,tetramer equilibrium. In contrast to the E59Q mutant, the E59D mutant displays predominantly a dimer form, indicating that the quaternary stability in the dimer interface is changed by shortening one carbon side chain of Glu59 to Asp59. The E59L enzyme also shows a dimer,tetramer model similar to that of the wild-type, but it displays more dimers as well as monomers and polymers. Malate cooperativity is not significantly notable in the E59 mutant enzymes, suggesting that the cooperativity might be related to the molecular geometry of the fumarate-binding site. Glu59 can precisely maintain the geometric specificity for the substrate cooperativity. According to the sequence alignment analysis and our experimental data, we suggest that charge effect and geometric specificity are both critical factors in enzyme regulation. Glu59 discriminates human m-NAD-ME from mitochondrial NADP+ -dependent malic enzyme and cytosolic NADP+ -dependent malic enzyme in fumarate activation and malate cooperativity. [source] Functional role of B,-chain N-terminal fragment in the fibrin polymerization processFEBS JOURNAL, Issue 17 2007E. V. Lugovskoy Four mAbs of the IgG1 class to the thrombin-treated N-terminal disulfide knot of fibrin, secreted by various hybridomas, have been selected. Epitopes for two mAbs, I-3C and III-10d, were situated in human fibrin fragment B,15,26, and those for two other mAbs, I-5G and I-3B, were in fragment B,26,36. Three of these mAbs, I-5G, I-3B and III-10D, as well as their Fab-fragments, decreased the maximum rate of fibrin desAA and desAABB polymerization up to 90,95% at a molar ratio of mAb (or Fab-fragment) to fibrin of 1 or 2. The fourth mAb, I-3C, did not influence the fibrin desAABB polymerization and inhibited by 50% the maximum rate of fibrin desAA polymerization. These results suggest that these mAb inhibitors block a longitudinal fibrin polymerization site. As the mAbs retard both fibrin desAABB and fibrin desAA polymerization, one can conclude that the polymerization site does not coincide with polymerization site ,B' (B,15,17). To verify this suggestion, the polymerization inhibitory activity of synthetic peptides B,SARGHRPLDKKREEA(12,26), B,LDKKREEA(19,26), B,APSLRPAPPPI(26,36), B,APSLRPAPPPISGGGYRARPA(26,46) and B,GYRARPA(40,46), which imitate the various sequences in the N-terminal region of the fibrin B,-chain, have been investigated. Peptides B,12,26 and B,26,46, but not B,40,46, B,19,26, and B,26,36, proved to be specific inhibitors of fibrin polymerization. The IC50 values for B,12,26 and B,26,46 were 2.03 × 10,4 and 2.19 × 10,4 m, respectively. Turbidity and electron microscopy data showed that peptides B,12,26 and B,26,46 inhibited the fibrin protofibril formation stage of fibrin polymerization. The conclusion was drawn that fibrin fragment B,12,46 took part in fibrin protofibril formation simultaneously with site ,A' (A,17,19) prior to removal of fibrinopeptide B. A model of the intermolecular connection between fragment B,12,46 of one fibrin desAA molecule and the D-domain of another has been constructed. [source] Functional role of cyclic nucleotide-gated channels in rat medial vestibular nucleus neuronsTHE JOURNAL OF PHYSIOLOGY, Issue 3 2008Maria Vittoria Podda Although cyclic nucleotide-gated (CNG) channels are expressed in numerous brain areas, little information is available on their functions in CNS neurons. The aim of the present study was to define the distribution of CNG channels in the rat medial vestibular nucleus (MVN) and their possible involvement in regulating MVN neuron (MVNn) excitability. The majority of MVNn expressed both CNG1 and CNG2 A subunits. In whole-cell current-clamp experiments carried out on brainstem slices containing the MVNn, the membrane-permeant analogues of cyclic nucleotides, 8-Br-cGMP and 8-Br-cAMP (1 mm), induced membrane depolarizations (8.9 ± 0.8 and 9.2 ± 1.0 mV, respectively) that were protein kinase independent. The cGMP-induced depolarization was associated with a significant decrease in the membrane input resistance. The effects of cGMP on membrane potential were almost completely abolished by the CNG channel blockers, Cd2+ and l - cis -diltiazem, but they were unaffected by blockade of hyperpolarization-activated cyclic nucleotide-gated channels. In voltage-clamp experiments, 8-Br-cGMP induced non-inactivating inward currents (,22.2 ± 3.9 pA) with an estimated reversal potential near 0 mV, which were markedly inhibited by reduction of extracellular Na+ and Ca2+ concentrations. Membrane depolarization induced by CNG channel activation increased the firing rate of MVNn without changing the action potential shape. Collectively, these findings provide novel evidence that CNG channels affect membrane potential and excitability of MVNn. Such action should have a significant impact on the function of these neurons in sensory,motor integration processes. More generally, it might represent a broad mechanism for regulating the excitability of different CNS neurons. [source] Functional role of KLF10 in multiple disease processesBIOFACTORS, Issue 1 2010Malayannan Subramaniam Abstract Since the discovery by this laboratory of the zinc finger transcription factor, KLF10, a member of the Krüppel-like family of transcription factors, there have been multiple publications regarding its functions and its immediate family members, in numerous cell types. KLF10 has been shown to be rapidly induced by TGF,1, 2, 3, E2, epidermal growth factor, and bone morphogenetic protein-2. TGF, inducible early gene-1 activates the TGF,-Smad signaling pathway via repression of Smad 7 expression and activation of Smad 2 expression and activity. Overall, KLF10 has been implicated in cell differentiation, as a target gene for a variety of signaling pathways, and in serving as a potential marker for human diseases such as breast cancer, cardiac hypertrophy, and osteoporosis. Like other KLF members, KLF10 is expressed in specific cell types in numerous tissues and is known to be involved in repressing cell proliferation and inflammation as well as inducing apoptosis similar to that of TGF,. KLF10 binds to Sp-1-GC rich DNA sequences and can activate or repress the transcription of a number of genes. Overall, KLF10 has been shown to play a major role in the TGF, inhibition of cell proliferation and inflammation and induction of apoptosis, and its overexpression in human osteoblasts and pancreatic carcinoma cells mimics the actions of TGF,. [source] Functional role of Coenzyme Q in the energy coupling of NADH-CoQ oxidoreductase (Complex I): Stabilization of the semiquinone state with the application of inside-positive membrane potential to proteoliposomesBIOFACTORS, Issue 1-4 2008Tomoko Ohnishi Ph.D. Abstract Coenzyme Q10 (which is also designated as CoQ10, ubiquinone-10, UQ10, CoQ, UQ or simply as Q) plays an important role in energy metabolism. For NADH-Q oxidoreductase (complex I), Ohnishi and Salerno proposed a hypothesis that the proton pump is operated by the redox-driven conformational change of a Q-binding protein, and that the bound form of semiquinone (SQ) serves as its gate [FEBS Letters 579 (2005) 45,55]. This was based on the following experimental results: (i) EPR signals of the fast-relaxing SQ anion (designated as Q) are observable only in the presence of the proton electrochemical potential (,,); (ii) iron-sulfur cluster N2 and Q are directly spin-coupled; and (iii) their center-to-center distance was calculated as 12Å, but Q is only 5Å deeper than N2 perpendicularly to the membrane. After the priming reduction of Q to Nf, the proton pump operates only in the steps between the semiquinone anion (Q) and fully reduced quinone (QH2). Thus, by cycling twice for one NADH molecule, the pump transports 4H+ per 2e,. This hypothesis predicts the following phenomena: (a) Coupled with the piericidin A sensitive NADH-DBQ or Q1 reductase reaction, ,, would be established; (b) ,, would enhance the SQ EPR signals; and (c) the dissipation of ,, with the addition of an uncoupler would increase the rate of NADH oxidation and decrease the SQ signals. We reconstituted bovine heart complex I, which was prepared at Yoshikawa's laboratory, into proteoliposomes. Using this system, we succeeded in demonstrating that all of these phenomena actually took place. We believe that these results strongly support our hypothesis. [source] Functional roles of remnant plant populations in communities and ecosystemsGLOBAL ECOLOGY, Issue 6 2000Ove Eriksson Abstract A hypothesis is suggested for functional roles of remnant plant populations in communities and ecosystems. A remnant population is capable of persistence during extended time periods, despite a negative population growth rate, due to long-lived life stages and life-cycles, including loops that allow population persistence without completion of the whole life cycle. A list of critera is suggested to help identification of remnant plant populations. Several community and ecosystem features may result from the presence of remnant plant populations. Apart from increasing community and ecosystem resilience just by being present, remnant populations may contribute to resilience through enhancing colonization by other plant species, by providing a persistent habitat for assemblages of animals and microorganisms, and by reducing variation in nutrient cycling. It is suggested that the common ability of plants to develop remnant populations is a contributing factor to ecosystem stability. Remnant populations are important for the capacity of ecosystems to cope with the present-day impact caused by human society, and their occurrence should be recognized in surveys of threatened plant species and communities. [source] Functional roles of the factor VIII B domainHAEMOPHILIA, Issue 6 2009S. W. PIPE Summary., Unravelling the structure, function and molecular interactions of factor VIII (FVIII) throughout its life cycle from biosynthesis to clearance has advanced our understanding of the molecular mechanisms of haemophilia and the development of effective treatment strategies including recombinant replacement therapy. These insights are now influencing bioengineering strategies toward novel therapeutics. Whereas available molecular models and crystal structures have helped elucidate the structure and function of the A and C domains of FVIII, these models have not included detailed structural information of the B domain. Therefore, insights into the role of the FVIII B domain have come primarily from expression studies in heterologous systems, biochemical studies on bioengineered FVIII variants and clinical studies with B domain-deleted FVIII. This manuscript reviews the available data on the potential functional roles of the FVIII B domain. A detailed literature search was performed, and the data extracted were qualitatively summarized. Intriguing emerging evidence suggests that the FVIII B domain is involved in intracellular interactions that regulate quality control and secretion, as well as potential regulatory roles within plasma during activation, platelet binding, inactivation and clearance. [source] Functional roles of N -glycans in cell signaling and cell adhesion in cancerCANCER SCIENCE, Issue 7 2008Yan-Yang Zhao Glycosylation is one of the most common post-translational modification reactions and nearly half of all known proteins in eukaryotes are glycosylated. In fact, changes in oligosaccharide structures are associated with many physiological and pathological events, including cell growth, migration, differentiation, tumor invasion, host,pathogen interactions, cell trafficking, and transmembrane signaling. Emerging roles of glycan functions have been highly attractive to scientists in various fields of life science as they open a field, "Functional Glycomics", that is a comprehensive study of the glycan structures in relation to functions. In particular, the N-glycans of signaling molecules including receptors or adhesion molecules are considered to be involved in cellular functions. This review will focus on the roles of glycosyltransferases involved in the biosynthesis of N-glycan branching and identification of cell surface receptors as their target proteins. We also suggest that the modulation of N-glycans of those receptors alters their important functions such as cell signaling and cell adhesion which are implicated in cancer invasion and metastasis. (Cancer Sci 2008; 99: 1304,1310) [source] Functional roles of immature dendritic cells in impaired immunity of solid tumour and their targeted strategies for provoking tumour immunityCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2006R. Kim Summary Dendritic cells play a crucial role in initiating tumour immunity as well as in the immune response for invading foreign pathogens such as bacteria and viruses. For bacterial and viral infections, the immature dendritic cells (iDCs) residing in peripheral tissues are efficiently activated and matured by pathogen signals for performing the immune response. In contrast, for self-antigens, the naive T cells are not activated by iDCs but proceed to anergy/deletion, and the generation of regulatory T cells for immune tolerance. The induction of immune response and tolerance is regulated strictly by iDCs as the sensor for homeostasis of immune response in the host. Despite the identification of some tumour antigens, tumour immunity is not provoked successfully. Even though there are some critical obstacles to inhibit effective tumour immunity, tumour cells are able to exploit the functional roles of iDCs for tumour progression, which are induced by tumour-derived soluble factors such as vascular endothelial growth factor (VEGF) and functionally modulated in the microenvironment. The iDCs still remain as the critical target for provoking tumour immunity. In this review, the functional roles of tumour-associated iDCs and the strategy for targeting iDCs in effective tumour immunity for the cancer patient are discussed. [source] Lactate kinetics in human tissues at rest and during exerciseACTA PHYSIOLOGICA, Issue 4 2010Gerrit Van Hall Abstract Lactate production in skeletal muscle has now been studied for nearly two centuries and still its production and functional role at rest and during exercise is much debated. In the early days skeletal muscle was mainly seen as the site of lactate production during contraction and lactate production associated with a lack of muscle oxygenation and fatigue. Later it was recognized that skeletal muscle not only played an important role in lactate production but also in lactate clearance and this led to a renewed interest, not the least from the Copenhagen School in the 1930s, in the metabolic role of lactate in skeletal muscle. With the introduction of lactate isotopes muscle lactate kinetics and oxidation could be studied and a simultaneous lactate uptake and release was observed, not only in muscle but also in other tissues. Therefore, this review will discuss in vivo human: (1) skeletal muscle lactate metabolism at rest and during exercise and suggestions are put forward to explain the simultaneous lactate uptake and release; and (2) lactate metabolism in the heart, liver, kidneys, brain, adipose tissue and lungs will be discussed and its potential importance in these tissues. [source] Angiotensin II regulates endothelial cell migration through calcium influx via T-type calcium channel in human umbilical vein endothelial cellsACTA PHYSIOLOGICA, Issue 4 2010A. Martini Abstract Aim:, The T-type calcium channel is expressed in vascular endothelial cells, but its role in endothelial cell function is yet to be elucidated. We analysed the endothelial functional role of T-type calcium channel-dependent calcium under angiotensin II (Ang II) stimulation. Methods:, Human umbilical vein endothelial cells were co-incubated with hormone at 10,7 m and either Efonidipine 10,5 m or Verapamil 10,5 m or Mibefradil 10,5 m or Wortmannin 10,6 m. The contribution of Ang II receptors was evaluated using PD123319 10,7 m and ZD 7155 10,7 m. The calcium ion concentration was observed using Fluo-3 acetossimetil ester. The cells were observed after 3, 6, 9 and 12 h. Results:, The microfluorescence method points out that Ang II induces intracellular calcium modulation in time by distinct mechanisms. AT2 receptor blockade is necessary to observe significant increase in [Ca2+]i levels. Pre-treatment with Mibefradil abolishes Ang II -induced cell migration. Conclusions:, Our data show that Ang II, via AT1 receptor, modulates calcium concentration involving T-type calcium channel and L-type calcium channel but only the calcium influx via T-type calcium channels regulates endothelial cell migration which is essential for angiogenesis. [source] Role of orexin in the regulation of glucose homeostasisACTA PHYSIOLOGICA, Issue 3 2010H. Tsuneki Abstract Orexin-A (hypocretin-1) and orexin-B (hypocretin-2) are hypothalamic neuropeptides that play key roles in the regulation of wakefulness, feeding, reward, autonomic functions and energy homeostasis. To control these functions indispensable for survival, orexin-expressing neurones integrate peripheral metabolic signals, interact with many types of neurones in the brain and modulate their activities via the activation of orexin-1 receptor or orexin-2 receptor. In addition, a new functional role of orexin is emerging in the regulation of insulin and leptin sensitivities responsible for whole-body glucose metabolism. Recent evidence indicates that orexin efficiently protects against the development of peripheral insulin resistance induced by ageing or high-fat feeding in mice. In particular, the orexin receptor-2 signalling appears to confer resistance to diet-induced obesity and insulin insensitivity by improving leptin sensitivity. In fact, the expression of orexin gene is known to be down-regulated by hyperglycaemia in the rodent model of diabetes, such as ob/ob and db/db mice. Moreover, the levels of orexin receptor-2 mRNA have been shown to decline in the brain of mice along with ageing. These suggest that hyperglycaemia due to insulin insensitivity during ageing or by habitual consumption of a high-fat diet leads to the reduction in orexin expression in the hypothalamus, thereby further exacerbating peripheral insulin resistance. Therefore, orexin receptor controlling hypothalamic insulin/leptin actions may be a new target for possible future treatment of hyperglycaemia in patients with type 2 diabetes. [source] The calcium-conducting ion channel transient receptor potential canonical 6 is involved in macrophage inflammatory protein-2-induced migration of mouse neutrophils,ACTA PHYSIOLOGICA, Issue 1 2009N. Damann Abstract Aim:, The role of the calcium-conducting ion channel transient receptor potential canonical 6 (TRPC6) in macrophage inflammatory protein-2 (MIP-2) induced migration of mouse neutrophils was investigated. Methods:, Neutrophil granulocytes isolated from murine bone marrow of wild-type (TRPC6+/+) and TRPC6 knockout (TRPC6,/,) mice were tested for the presence of TRPC6 channel expression using quantitative real-time polymerase chain reactions and immunocytochemistry. The effect of different stimuli (e.g. MIP-2, 1-oleoyl-2-acetyl-sn-glycerol, formyl-methionyl-leucyl-phenylalanin) on migration of isolated neutrophils was tested by two-dimensional (2D) migration assays, phalloidin staining and intracellular calcium imaging. Results:, We found that neutrophil granulocytes express TRPC6 channels. MIP-2 induced fast cell migration of isolated neutrophils in a 2D cell-tracking system. Strikingly, MIP-2 was less potent in neutrophils derived from TRPC6,/, mice. These cells showed less phalloidin-coupled fluorescence and the pattern of cytosolic calcium transients was altered. Conclusions:, We describe in this paper for the first time a role for transient receptor potential (TRP) channels in migration of native lymphocytes as a new paradigm for the universal functional role of TRPs. Our data give strong evidence that TRPC6 operates downstream to CXC-type Gq -protein-coupled chemokine receptors upon stimulation with MIP-2 and is crucial for the arrangement of filamentous actin in migrating neutrophils. This is a novel cell function of TRP channel beyond their well-recognized role as universal cell sensors. [source] Relaxant effects of , -adrenergic agonists on porcine and human detrusor muscleACTA PHYSIOLOGICA, Issue 2 2005J. K. Badawi Abstract Aim:, Relaxant effects of different , -adrenoceptor agonists on porcine and human detrusor were examined. Thus, the , -adrenoceptor subtype mainly responsible for relaxation in the detrusor muscle of pigs was characterized. Additionally, different effects of several , -agonists in both species were shown. Methods:, Experiments were performed on muscle strips of porcine and human detrusor suspended in a tissue bath. The relaxant effects of the non-selective , -agonist isoprenaline, the selective ,2-agonists procaterol, salbutamol and the selective ,3-agonists BRL 37344, CL 316 243 and CGP 12177 on potassium-induced contraction were investigated. The inhibitory effect of different substances on the maximum contraction and the rank order of potency for endogenous catecholamines was determined in pigs. Furthermore, concentration-relaxation curves were performed for pigs and humans. Results:,Pigs: In the pre-treatment experiments isoprenaline and procaterol showed similar effects. The concentration,response experiments showed that the maximum relaxation induced by procaterol and salbutamol was more than 90%, not significantly different from isoprenaline, whereas the maximum relaxations of CL 316 243, BRL 37344 and CGP 12177 amounted to 68, 70 or 30%, respectively. Rank order of potencies was isoprenaline , adrenaline > noradrenaline. Humans: Isoprenaline, procaterol, salbutamol and CL 316 243 showed a maximum relaxation of 80, 41, 24 and 35% and pD2 values of 6.24, 5.65, 5.48 and 5.55, respectively. Conclusion:,,2-receptors play a main functional role in mediating relaxation of porcine detrusor. Selective ,2- and ,3-agonists similarly relax the human detrusor. Effects were smaller compared with the pig. [source] Cell type,specific expression of adenomatous polyposis coli in lung development, injury, and repairDEVELOPMENTAL DYNAMICS, Issue 8 2010Aimin Li Abstract Adenomatous polyposis coli (Apc) is critical for Wnt signaling and cell migration. The current study examined Apc expression during lung development, injury, and repair. Apc was first detectable in smooth muscle layers in early lung morphogenesis, and was highly expressed in ciliated and neuroendocrine cells in the advanced stages. No Apc immunoreactivity was detected in Clara or basal cells, which function as stem/progenitor cell in adult lung. In ciliated cells, Apc is associated mainly with apical cytoplasmic domain. In response to naphthalene-induced injury, Apcpositive cells underwent squamous metaplasia, accompanied by changes in Apc subcellular distribution. In conclusion, both spatial and temporal expression of Apc is dynamically regulated during lung development and injury repair. Differential expression of Apc in progenitor vs. nonprogenitor cells suggests a functional role in cell-type specification. Subcellular localization changes of Apc in response to naphthalene injury suggest a role in cell shape and cell migration. Developmental Dynamics 239:2288,2297, 2010. © 2010 Wiley-Liss, Inc. [source] Platelet-derived growth factor is involved in the differentiation of second heart field-derived cardiac structures in chicken embryosDEVELOPMENTAL DYNAMICS, Issue 10 2009Noortje A.M. Bax Abstract For the establishment of a fully functional septated heart, addition of myocardium from second heart field-derived structures is important. Platelet-derived growth factors (PDGFs) are known for their role in cardiovascular development. In this study, we aim to elucidate this role of PDGF-A, PDGF-C, and their receptor PDGFR-,. We analyzed the expression patterns of PDGF-A, -C, and their receptor PDGFR-, during avian heart development. A spatiotemporal pattern of ligands was seen with colocalization of the PDGFR-,. This was found in second heart field-derived myocardium as well as the proepicardial organ (PEO) and epicardium. Mechanical inhibition of epicardial outgrowth as well as chemical disturbance of PDGFR-, support a functional role of the ligands and the receptor in cardiac development. Developmental Dynamics 238:2658,2669, 2009. © 2009 Wiley-Liss, Inc. [source] Beyond early development: Xenopus as an emerging model for the study of regenerative mechanismsDEVELOPMENTAL DYNAMICS, Issue 6 2009Caroline W. Beck Abstract While Xenopus is a well-known model system for early vertebrate development, in recent years, it has also emerged as a leading model for regeneration research. As an anuran amphibian, Xenopus laevis can regenerate the larval tail and limb by means of the formation of a proliferating blastema, the lens of the eye by transdifferentiation of nearby tissues, and also exhibits a partial regeneration of the postmetamorphic froglet forelimb. With the availability of inducible transgenic techniques for Xenopus, recent experiments are beginning to address the functional role of genes in the process of regeneration. The use of soluble inhibitors has also been very successful in this model. Using the more traditional advantages of Xenopus, others are providing important lineage data on the origin of the cells that make up the tissues of the regenerate. Finally, transcriptome analyses of regenerating tissues seek to identify the genes and cellular processes that enable successful regeneration. Developmental Dynamics 238:1226,1248, 2009. © 2009 Wiley-Liss, Inc. [source] Characterization of dendritic spines in the Drosophila central nervous systemDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2009Florian Leiss Abstract Dendritic spines are a characteristic feature of a number of neurons in the vertebrate nervous system and have been implicated in processes that include learning and memory. In spite of this, there has been no comprehensive analysis of the presence of spines in a classical genetic system, such as Drosophila, so far. Here, we demonstrate that a subset of processes along the dendrites of visual system interneurons in the adult fly central nervous system, called LPTCs, closely resemble vertebrate spines, based on a number of criteria. First, the morphology, size, and density of these processes are very similar to those of vertebrate spines. Second, they are enriched in actin and devoid of tubulin. Third, they are sites of synaptic connections based on confocal and electron microscopy. Importantly, they represent a preferential site of localization of an acetylcholine receptor subunit, suggesting that they are sites of excitatory synaptic input. Finally, their number is modulated by the level of the small GTPase dRac1. Our results provide a basis to dissect the genetics of dendritic spine formation and maintenance and the functional role of spines. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] Neuronal calcium sensor-1 gene ncs-1a is essential for semicircular canal formation in zebrafish inner earDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2005Brian Blasiole Abstract We have analyzed the functional role of neuronal calcium sensor-1 (Ncs-1) in zebrafish development. We identified two orthologs of the mammalian NCS-1 gene. Full-length cDNAs encoding zebrafish Ncs-1a and Ncs-1b polypeptides were cloned and characterized. Whole-mount in situ hybridization revealed that ncs-1a mRNA was expressed beginning at early somitogenesis. As development progressed, ncs-1a mRNA was present throughout the embryo with expression detected in ventral hematopoietic mesoderm, pronephric tubules, CNS nuclei, and otic vesicle. By 4.5 days post fertilization (dpf), ncs-1a expression was detected primarily in the brain. Expression of ncs-1b mRNA was first detected at 36 hours post fertilization (hpf) and was restricted to the olfactory bulb. By 4.5 dpf, ncs-1b was expressed at low levels throughout the brain. Knockdown of ncs-1a mRNA translation with antisense morpholinos blocked formation of semicircular canals. These studies identify a novel function for ncs-1a in inner ear development and suggest that this calcium sensor plays an important role in vestibular function. © 2005 Wiley Periodicals, Inc. J Neurobiol, 2005 [source] Biodiversity in tropical agroforests and the ecological role of ants and ant diversity in predatory functionECOLOGICAL ENTOMOLOGY, Issue 4 2006STACY M. PHILPOTT Abstract 1.,Intensive agricultural practices drive biodiversity loss with potentially drastic consequences for ecosystem services. To advance conservation and production goals, agricultural practices should be compatible with biodiversity. Traditional or less intensive systems (i.e. with fewer agrochemicals, less mechanisation, more crop species) such as shaded coffee and cacao agroforests are highlighted for their ability to provide a refuge for biodiversity and may also enhance certain ecosystem functions (i.e. predation). 2.,Ants are an important predator group in tropical agroforestry systems. Generally, ant biodiversity declines with coffee and cacao intensification yet the literature lacks a summary of the known mechanisms for ant declines and how this diversity loss may affect the role of ants as predators. 3.,Here, how shaded coffee and cacao agroforestry systems protect biodiversity and may preserve related ecosystem functions is discussed in the context of ants as predators. Specifically, the relationships between biodiversity and predation, links between agriculture and conservation, patterns and mechanisms for ant diversity loss with agricultural intensification, importance of ants as control agents of pests and fungal diseases, and whether ant diversity may influence the functional role of ants as predators are addressed. Furthermore, because of the importance of homopteran-tending by ants in the ecological and agricultural literature, as well as to the success of ants as predators, the costs and benefits of promoting ants in agroforests are discussed. 4.,Especially where the diversity of ants and other predators is high, as in traditional agroforestry systems, both agroecosystem function and conservation goals will be advanced by biodiversity protection. [source] Inverse nickel-responsive regulation of two urease enzymes in the gastric pathogen Helicobacter mustelaeENVIRONMENTAL MICROBIOLOGY, Issue 10 2008Jeroen Stoof Summary The acidic gastric environment of mammals can be chronically colonized by pathogenic Helicobacter species, which use the nickel-dependent urea-degrading enzyme urease to confer acid resistance. Nickel availability in the mammal host is low, being mostly restricted to vegetarian dietary sources, and thus Helicobacter species colonizing carnivores may be subjected to episodes of nickel deficiency and associated acid sensitivity. The aim of this study was to investigate how these Helicobacter species have adapted to the nickel-restricted diet of their carnivorous host. Three carnivore-colonizing Helicobacter species express a second functional urea-degrading urease enzyme (UreA2B2), which functions as adaptation to nickel deficiency. UreA2B2 was not detected in seven other Helicobacter species, and is in Helicobacter mustelae only expressed in nickel-restricted conditions, and its expression was higher in iron-rich conditions. In contrast to the standard urease UreAB, UreA2B2 does not require activation by urease or hydrogenase accessory proteins, which mediate nickel incorporation into these enzymes. Activity of either UreAB or UreA2B2 urease allowed survival of a severe acid shock in the presence of urea, demonstrating a functional role for UreA2B2 in acid resistance. Pathogens often express colonization factors which are adapted to their host. The UreA2B2 urease could represent an example of pathogen adaptation to the specifics of the diet of their carnivorous host, rather than to the host itself. [source] Bacterial community structure and function in a metal-working fluidENVIRONMENTAL MICROBIOLOGY, Issue 6 2003Christopher J. Van Der Gast Summary The diversity of bacterial populations colonizing spatially and temporally separated samples of the same metal-working fluid (MWF) formulation was investigated. Analyses were performed with a view to improve strategies for bioaugmentation of waste MWF in bioreactor systems and prevention of in-use MWF biodeterioration in engineering workshops. Significantly, complementary phenotypic, genotypic and in situ methods revealed that the bacterial communities in operationally exhausted MWFs had low diversity and were similar in species composition from different locations and uses. Of the 179 bacterial isolates studied, only 11 genera and 15 species were identified using fatty acid methyl ester (FAME) analysis, with culture independent analyses by 16S rDNA denaturing gradient gel electrophoresis (DGGE) and fluorescent in situ hybridization being congruent with these FAME data. In order to gain some insight into functional role of detected populations, we correlated the MWF chemical composition and potential pollution load with bacterial abundance and community composition detected within samples. [source] The Mechanics of Duetting in a New Zealand Endemic, the Kokako (Callaeas cinerea wilsoni): Song at a Snail's PaceETHOLOGY, Issue 5 2006Laura E. Molles New Zealand's endemic, duetting kokako (Callaeas cinerea wilsoni) produce one of the longest known bird songs (ca 30 s) and duets that differ strikingly from those of most duetters in their unusual length and non-repetitive structure, long pauses between component phrases, and the great flexibility in sex roles. Here we present a structural analysis of the vocalizations of 17 kokako pairs collected during natural song bouts and in response to conspecific playback, to gain insight into the functional role of this extraordinary vocal behavior. Males tend to sing a greater proportion of the duet than females. Like many duetting species, kokako have a moderately sized repertoire of phrases (mean repertoire size =18) and pair members tend to sing antiphonally rather than in unison. Sharing of phrase types is high among neighboring kokako ( = 86%) and repertoires are not sex specific, as is typical of some but not all duetting species. Timing characteristics, broad sharing of phrase types, and countersinging behavior strongly suggest that kokako duets play an important role in territory defense. Additionally, differences in pairs' sex role and phrase sequence flexibility suggest that these aspects of duet performance may reflect pair-bond length or commitment, and require a time investment by pair members. [source] Trophic Egg Production in a Subsocial Shield Bug, Parastrachia japonensis Scott (Heteroptera: Parastrachiidae), and its Functional ValueETHOLOGY, Issue 12 2005Mantaro Hironaka Females of the gregarious shield bug, Parastrachia japonensis Scott (Heteroptera: Parastrachiidae) engage in extensive parental care behaviors that include egg and nymph guarding and progressive provisioning of drupes of the solitary host tree, Schoepfia jasminodora (Olacaceae: Rosidae: Santales). We noted that some eggs in every egg mass failed to turn pink and develop eye-spots indicative of developing embryos, suggesting that they are infertile, and therefore non-viable. We also observed newly hatched nymphs probing, and presumably feeding, on the egg mass remains. In the present report, through field observations and experiments involving removal of these non-viable eggs in the laboratory, we demonstrate that their presence is correlated with significant increases in nymphal weight, developmental rate and survival in the absence of other food. Thus, we conclude that an additional manifestation of the parental care behaviors that P. japonensis females use to increase their reproductive success is the production of trophic eggs. Some physical traits of the trophic eggs and their functional role in this system are discussed in the context of our current theoretical understanding of extended parental care. [source] The role of MAPK in governing lymphocyte adhesion to and migration across the microvasculature in inflammatory bowel diseaseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2009Franco Scaldaferri Abstract Lymphocyte recruitment is a key pathogenic event in inflammatory bowel disease (IBD). Adhesion of T cells to human intestinal microvascular endothelial cells (HIMEC) is mediated by ICAM-1, VCAM-1 and fractalkine (FKN), but the signaling molecules that orchestrate this process have yet to be identified. Because MAPK play an important role in the response of many cell types to pro-inflammatory stimuli, we assessed the functional role of p38 MAPK, p42/44 MAPK and JNK in the regulation of lymphocyte adhesion to and chemotaxis across the microvasculature in IBD. We found that the MAPK were phosphorylated in the bowel microvasculature and human intestinal fibroblasts of patients with IBD but not of healthy individuals. Stimulation of HIMEC with TNF- , triggered phosphorylation of the MAPK, and up-regulation of VCAM-1, FKN and ICAM-1. Blockade of p38 decreased the expression of all MAPK by 50% (p<0.01), whereas inhibition of p42/44 decreased the expression of ICAM-1 and FKN by 50% (p<0.01). Treatment of human intestinal fibroblasts with TNF- , elicited production of IL-8 and MCP-1, which was reduced (p<0.05) by blockade of p38 and p42/44. Finally, blockade of p38 and p42/44 reduced lymphocyte adhesion to (p<0.05) and transmigration across (p<0.05) HIMEC monolayers. These findings suggest a critical role for MAPK in governing lymphocyte influx into the gut in IBD patients, and their blockade may offer a molecular target for blockade of leukocyte recruitment to the intestine. [source] Genomic variants of TLR1 , It takes (TLR-)two to tangoEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2007Abstract Toll-like receptors (TLR) are innate immune sensors of microbial cell wall products that initiate early host responses. The TLR2 receptor complex has been shown to contain heterodimers of TLR2 with either TLR1 or TLR6 enabling the host to detect different microbial molecules, such as lipopeptides of different chemical composition. In this issue of the European Journal of Immunology, an important role in the sensing of microbial products for I602S, a single nucleotide polymorphism (SNP) in human TLR1 has been identified. This result, in combination with another recently published report on this polymorphism elucidating a functional role in cell trafficking (surface expression of the receptor complex in individuals carrying the SNP was altered), provide genetic evidence affirming the important function of TLR1 as an essential co-receptor for TLR2. See accompanying article: http://dx.doi.org/10.1002/eji200737034 [source] | ||||||||||||||||||||||||||||||||||||||||