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Physiological Significance (physiological + significance)
Selected AbstractsVascular effects of adenosine and its analoguesDRUG DEVELOPMENT RESEARCH, Issue 1-2 2001Debbie Prentice Abstract The main action of adenosine on vascular beds is vasodilation via A2 receptors. In addition, A1 receptors are found in some blood vessels, where they cause contraction. Traditionally, adenosine-induced vasodilation in vitro has been attributed to A2A receptor activation; however, it is now clear that A2B receptors are also involved in the regulation of vascular tone. Endothelium dependence of A2 receptor-mediated responses is variable; in some tissues they are blocked by removal of endothelium and/or inhibition of NO-synthase and in some they are not. In addition to A2 receptor-mediated relaxation, there is much evidence that relaxations to adenosine and some of its analogues can also be mediated by a mechanism which cannot be blocked by adenosine receptor antagonists. There is evidence that these responses are endothelium- and NO-independent and that, under conditions where adenosine is taken up into cells, relaxations to the endogenous ligand are entirely mediated by this mechanism, suggesting it is of physiological significance. Drug Dev. Res. 52:346,349, 2001. © 2001 Wiley-Liss, Inc. [source] GABA selectively controls the secretory activity of oxytocin neurons in the rat supraoptic nucleusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2004Mario Engelmann Abstract Recently we reported that a single social defeat experience triggers the release of oxytocin (OXT) from somata and dendrites, but not axon terminals, of neurons of the hypothalamic,neurohypophysial system. To further investigate the regulatory mechanisms underlying this dissociated release, we exposed male Wistar rats to a 30-min social defeat and monitored release of the inhibitory amino acids gamma amino butyric acid (GABA) and taurine within the hypothalamic supraoptic nucleus (SON) using microdialysis. Social defeat caused a significant increase in the release of both GABA and taurine within the SON (up to 480%; P < 0.01 vs. prestress release). To reveal the physiological significance of centrally released GABA, the specific GABAA -receptor antagonist bicuculline (0.02 mm) was administered into the SON via retrodialysis. This approach caused a significant increase in the release of OXT both within the SON and into the blood under basal conditions and during stress (up to 300 and 200%, respectively; P < 0.05 vs. basal values), without affecting plasma vasopressin. Electrophysiological studies confirmed the selective action of bicuculline on the firing activity of OXT neurons in the SON. Taken together, our data demonstrate that GABA is released within the SON during emotional stress to act as a selective inhibitor of both central and peripheral OXT secretion. [source] Taurine selectively modulates the secretory activity of vasopressin neurons in conscious ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2001Mario Engelmann Abstract Previous experiments have shown that a 10-min forced swimming session triggers the release of vasopressin from somata and dendrites, but not axon terminals, of neurons of the hypothalamic,neurohypophysial system. To further investigate regulatory mechanisms underlying this dissociated release, we forced male Wistar rats to swim in warm (20 °C) water and monitored release of the potentially inhibitory amino acids gamma amino butyric acid (GABA) and taurine into the hypothalamic supraoptic nucleus using microdialysis. Forced swimming caused a significant increase in the release of taurine (up to 350%; P < 0.05 vs. prestress release), but not GABA. To reveal the physiological significance of centrally released taurine, the specific taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide was administered into the supraoptic nucleus via retrodialysis. Administration of this antagonist caused a significant increase in the release of vasopressin within the supraoptic nucleus and into the blood both under basal conditions and during stress (up to 800%; P < 0.05 vs. basal values), without affecting hypothalamic or plasma oxytocin. Local administration of the GABAA receptor antagonist bicuculline, in contrast, failed to influence vasopressin secretion at either time point. In a separate series of in vivo electrophysiological experiments, administration of the same dosage of the taurine antagonist into the supraoptic nucleus via microdialysis resulted in an increased electrical activity of identified vasopressinergic, but not oxytocinergic, neurons. Taken together our data demonstrate that taurine is released within the supraoptic nucleus during physical/emotional stress. Furthermore, at the level of the supraoptic nucleus, taurine inhibits not only the electrical activity of vasopressin neurons but also acts as an inhibitor of both central and peripheral vasopressin secretion during different physiological states. [source] Maintenance of the alcohol dehydrogenase polymorphism in Tiger Salamanders, II.FUNCTIONAL ECOLOGY, Issue 1 2000Differences in biochemical function among allozymes Abstract 1.,Previous studies of Tiger Salamanders demonstrated that variation in alcohol dehydrogenase (Adh) contributed significantly to associations between multilocus heterozygosity and oxygen consumption traits, and that Adh variation was associated with levels of pond-oxygen and metamorphic ability in extreme oxygen environments. Here Adh allozymes are characterized kinetically, and relationships between Adh and oxygen-related physiological traits (ATP/Hb, 2,3-DPG/Hb) are measured. 2.,Kinetic differences were measured among Adh allozymes in the acetaldehyde-to-ethanol direction: kcat/Km ratios (the catalytic constant divided by the Michaelis,Menton constant) were significantly higher in Adh-SF than the other two genotypes, and in Adh-SS compared with Adh-FF. No significant differences were measured in the ethanol to acetaldehyde direction. 3.,Adh-SS had a significantly higher ATP/Hb than Adh-FF, with the Adh-SF intermediate. In addition, a significant interaction between Hb and body mass was measured, such that Adh-FF showed a negative relationship between Hb concentration and body mass while the other two genotypes showed a positive relationship. 4.,These results are consistent with the hypothesis that variation at the Adh locus has adaptive and physiological significance, and that functional differences among Adh allozymes partly explain significant associations between multilocus genotype and organismal traits. [source] Calcium Channel TRPV6 Is Involved in Murine Maternal,Fetal Calcium Transport,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2008Yoshiro Suzuki Abstract Maternal,fetal calcium (Ca2+) transport is crucial for fetal Ca2+ homeostasis and bone mineralization. In this study, the physiological significance of the transient receptor potential, vanilloid 6 (TRPV6) Ca2+ channel in maternal,fetal Ca2+ transport was investigated using Trpv6 knockout mice. The Ca2+ concentration in fetal blood and amniotic fluid was significantly lower in Trpv6 knockout fetuses than in wildtypes. The transport activity of radioactive Ca2+ (45Ca) from mother to fetuses was 40% lower in Trpv6 knockout fetuses than in wildtypes. The ash weight was also lower in Trpv6 knockout fetuses compared with wildtype fetuses. TRPV6 mRNA and protein were mainly localized in intraplacental yolk sac and the visceral layer of extraplacental yolk sac, which are thought to be the places for maternal,fetal Ca2+ transport in mice. These expression sites were co-localized with calbindin D9K in the yolk sac. In wildtype mice, placental TRPV6 mRNA increased 14-fold during the last 4 days of gestation, which coincides with fetal bone mineralization. These results provide the first in vivo evidence that TRPV6 is involved in maternal,fetal Ca2+ transport. We propose that TRPV6 functions as a Ca2+ entry pathway, which is critical for fetal Ca2+ homeostasis. [source] The polybasic sequence in the C2B domain of rabphilin is required for the vesicle docking step in PC12 cellsJOURNAL OF NEUROCHEMISTRY, Issue 3 2007Takashi Tsuboi Abstract Rabphilin is generally thought to be involved in the regulation of secretory vesicle exocytosis in neurons and neuroendocrine cells, and it has recently been hypothesized that the C2B domain of rabphilin promotes the docking of dense-core vesicles to the plasma membrane through simultaneous interaction with a vesicle protein, Rab3A/27A, and a plasma membrane protein, SNAP-25 (synaptosome-associated protein of 25 kDa). However, the physiological significance of the rabphilin,SNAP-25 interaction in the vesicle-docking step has never been elucidated. In this study we demonstrated by a mutation analysis that the polybasic sequence (587 KKAKHKTQIKKK 598) in the C2B domain of rabphilin is required for SNAP-25 binding, and that the Asp residues in the Ca2+ -binding loop 3 (D628 and D630) of the C2B domain are not required. We also investigated the effect of Lys,Gln (KQ) mutations in the polybasic sequence of the C2B domain on vesicle dynamics by total internal reflection fluorescence microscopy in individual PC12 cells. A rabphilin(KQ) mutant that completely lacks SNAP-25-binding activity significantly decreased the number of plasma-membrane-docked vesicles and strongly inhibited high-KCl-induced dense-core vesicle exocytosis. These results indicate that the polybasic sequence in the C2B domain functions as an effector domain for SNAP-25 and controls the number of ,releasable' vesicles docked to the plasma membrane. [source] Reproduction Phase-Related Expression of ,-Endorphin-Like Immunoreactivity in the Nucleus Lateralis Tuberis of the Female Indian Major Carp Cirrhinus mrigala: Correlation with the Luteinising Hormone Cells-Ovary AxisJOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2006A. J. Sakharkar Abstract The present study aimed to determine whether ,-endorphin immunoreactivity (bEP-ir) in the neurones of the nucleus lateralis tuberis (NLT) is linked to the seasonal cycle and shows correlation with the number of luteinising hormone (LH) cells in the pituitary gland and ovaries in the teleost, Cirrhinus mrigala. Although LH cells were moderately immunostained during the resting phase (December to January), the morphological profile suggested increased synthetic and secretory activity during the preparatory (February to April) and prespawning (May to June) phases. However, LH immunoreactivity was greatly reduced (P < 0.001) in the spawning (July to August) phase, suggesting massive discharge of the hormone; this pool was partly replenished in the postspawning (September to November) phase. The ovaries grew rapidly in the preparatory and prespawning phases; maximal size was attained during spawning, when ovulation occurred. Thereafter, the ovaries regressed. The NLT of C. mrigala is divisible into the pars lateralis (NLTl) and medialis (NLTm). During the postspawning and resting phases, bEP-ir was readily detectable in the NLTm as well as NLTl neurones. However, a steady reduction in the immunoreactivity was observed in the NLTm neurones during the preparatory through spawning phases (P < 0.001), suggesting a negative correlation with the LH cells-ovary axis. Thus, the inhibitory influence of ,-endorphin on the gonadotrophin-releasing hormone (GnRH)-LH axis appears to be attenuated during the preparatory through spawning phases. This may be necessary for the rapid stimulation of the axis culminating in spawning. Neurones of the NLTl also showed a gradual reduction in bEP-ir during the preparatory and prespawning phases (P < 0.01) and may therefore play a similar role. However, significant augmentation of the immunoreactivity was noticed in these neurones during the spawning phase (P < 0.001), the physiological significance of which is unknown. Although the present study demonstrated a temporal correlation between the ,-endorphin in the NLT, LH cells and the ovary, we suggest that the peptide in the NLTl and NLTm may show functional duality during the spawning phase. [source] Comparison between analytical methods and biological assays for the assessment of tannin-related antinutritive effects in some Spanish browse speciesJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 11 2004Hajer Ammar Abstract Twenty-two samples of leaves and flowers of six Mediterranean browse species (Erica australis, Quercus pyrenaica, Cistus laurifolius, Cytisus scoparius, Genista florida and Rosa canina) were analysed for total extractable phenols (TP), extractable tannins (ET) and condensed tannins (CTb (butanol/HCl assay) and CTv (vanillin assay)). The biological activity of the phenolic compounds was assessed as the increases in in vitro dry matter digestibility and gas production after in vitro incubation in rumen fluid following the addition of polyethylene glycol 6000 (PEG). The concentrations of phenolics and tannins varied with species, sampling time and part of the plant (leaves or flowers). There were also large differences in the values determined by different analytical methods. The highest correlation coefficients (P < 0.001) were found between TP and ET (r = 0.973) and between CTb and CTv (r = 0.758). However, only low correlations were observed between TP and CTb or CTv. Positive and significant (P < 0.01) correlations were observed between tannins and their biological activity determined as the effect of PEG on gas production. It is concluded that, although further research is required to develop methods for the accurate quantification of biologically active tannins, the effect of PEG on in vitro gas production seems to have promising potential for the assessment of phenolic-related antinutritive effects in browse plants. This technique, coupled with other tannin assays, could provide a better understanding of the nutritional and physiological significance of tannins. Copyright © 2004 Society of Chemical Industry [source] Salt glands in a Tithonian metriorhynchid crocodyliform and their physiological significanceLETHAIA, Issue 4 2000Marta Fernández Our knowledge of Mesozoic tetrapods is based mainly on osteological evidence. The discussion of the evolution of any homeostatic system is highly speculative because direct non-osteological evidence is uncommon. Here we report an extraordinarily well-preserved cast of a pair of lobulated protuberances in the skull of the marine metriorhynchid crocodiliform Geosaurus from the Tithonian (Jurassic) of Patagonia (Argentina). These protuberances are interpreted as representing salt glands. Based on their topology, these glands are identified as the nasals. Optimization of this character on a phylogenetic tree permits us to infer the ancestral condition for archosaurs. The relationship between salt gland and diet is also analysed. The presence of hypertrophied salt glands in the skull of Geosaurus suggests that as early as 140 million years ago, some Mesozoic marine reptiles had evolved an extra-renal osmoregulatory system. This achievement was an important clue in the successful colonization of marine environments. Salt glands preclude the risk of lethal dehydration and allow marine reptiles to include an important amount of invertebrates in their diet. [source] Increased proline loading to phloem and its effects on nitrogen uptake and assimilation in water-stressed white clover (Trifolium repens)NEW PHYTOLOGIST, Issue 3 2009Bok-Rye Lee Summary ,,The aim of this study was to investigate the physiological significance of increased proline loading to phloem caused by water-deficit stress in relation to nitrogen (N) uptake and assimilation. ,,N uptake and N assimilation were quantified by 15N tracing in well-watered (control) and water deficit-stressed white clover (Trifolium repens). De novo proline synthesis and proline loading to the phloem were also compared between treatments. The relationships among proline concentrations in phloem exudates, N uptake, and assimilation of newly absorbed N were assessed. ,,The newly synthesized proline in the phloem exudates increased rapidly after 3 d of water deficit. The water-deficit treatment significantly reduced the maximum nitrate reductase activity (NRA), and also attenuated de novo synthesis of amino acids and proteins in the roots. The increase in proline concentrations in phloem exudates was closely related to reductions in NRA in the roots, N uptake, and the assimilation of newly absorbed N. The accumulation of proline induced in roots by exogenous proline and NH4Cl treatments was closely associated with the decrease in NRA. ,,These results indicate that increased proline transport to roots via phloem caused by water deficit has a significant influence on the down-regulation of N uptake and the assimilation of newly absorbed N. [source] Deregulation of miR-92a expression is implicated in hepatocellular carcinoma developmentPATHOLOGY INTERNATIONAL, Issue 5 2010Masatoshi Shigoka MicroRNAs (miRNAs) belong to a class of the endogenously expressed non-coding small RNAs which primarily function as gene regulators. Growing evidence suggests that miRNAs have a significant role in tumor development and may constitute robust biomarkers for cancer diagnosis and prognosis. The miR-17-92 cluster especially is markedly overexpressed in several cancers, and is associated with the cancer development and progression. In this study, we have demonstrated that miR-92a is highly expressed in hepatocellular carcinoma (HCC). In addition, the proliferation of HCC-derived cell lines was enhanced by miR-92a and inhibited by the anti-miR-92a antagomir. On the other hand, we have found that the relative amount of miR-92a in the plasmas from HCC patients is decreased compared with that from the healthy donors. Interestingly, the amount of miR-92a was elevated after surgical treatment. Thus, although the physiological significance of the decrease of miR-92a in plasma is still unknown, deregulation of miR-92 expression in cells and plasma should be implicated in the development of HCC. [source] Electrical signals and their physiological significance in plantsPLANT CELL & ENVIRONMENT, Issue 3 2007JÖRG FROMM ABSTRACT Electrical excitability and signalling, frequently associated with rapid responses to environmental stimuli, are well known in some algae and higher plants. The presence of electrical signals, such as action potentials (AP), in both animal and plant cells suggested that plant cells, too, make use of ion channels to transmit information over long distances. In the light of rapid progress in plant biology during the past decade, the assumption that electrical signals do not only trigger rapid leaf movements in ,sensitive' plants such as Mimosa pudica or Dionaea muscipula, but also physiological processes in ordinary plants proved to be correct. Summarizing recent progress in the field of electrical signalling in plants, the present review will focus on the generation and propagation of various electrical signals, their ways of transmission within the plant body and various physiological effects. [source] Composition of alveolar surfactant changes with training in humansRESPIROLOGY, Issue 3 2000Ian R. Doyle Objective: We test the hypothesis that the changes we observed previously in the relative amounts of disaturated phospholipids (DSP), cholesterol (CHOL), and surfactant protein-A (SP-A) in human alveolar surfactant in response to acute exercise, and which were related to fitness, can be induced by training. Methodology: We examine the effect of 7 weeks' training on these major surfactant components, together with surfactant protein-B (SP-B), in bronchoalveolar lavage fluid harvested from 17 males, both at rest and after acute exercise. Fitness was assessed as workload/heart rate achieved during cycling for 30 min at 90% of theoretical maximal heart rate, and was increased in all subjects following training (mean increase 22.2 ± 3.91%; P = 0.001). Results: Training significantly increased the SP-A/DSP, SP-B/DSP, SP-A/CHOL and SP-A/SP-B ratios in whole surfactant harvested from subjects both at rest and immediately following exercise. Training also increased the SP-B/CHOL ratio at rest. Changes were particularly marked at rest in the SP-A/DSP, SP-A/CHOL, and SP-B/CHOL ratios in the tubular myelin-rich fraction, and after exercise in the SP-A/DSP, SP-A/CHOL, and SP-A/SP-B ratios in the tubular myelin-poor fraction. Conclusion: We conclude that training markedly alters the composition of alveolar surfactant both at rest and with exercise; the physiological significance of these changes remains to be determined. [source] The role of activins during decidualisation of human endometriumAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 3 2006Rebecca L. JONES Decidualisation of the endometrial stroma is critical to create a specialised environment for embryo implantation and trophoblast invasion; however, the mechanisms involved are poorly understood. We have established that activin A is an important regulator of decidualisation of endometrial stromal cells in vitro. Here we describe studies that verify the physiological significance of these findings. We demonstrate that high concentrations of activin A are produced by decidualising cells in excess of the antagonists, inhibin and follistatin, thus confirming its bioavailability within the decidual environment. Furthermore, we demonstrate that all components of the activin signalling pathway (activin receptors and Smads) are expressed in decidualised cells, and identify a downstream mechanism for activin in the endometrium, through the regulation of matrix metalloproteinases (MMPs). This new knowledge is important for understanding the roles for activins and inhibins in regulating fertility. [source] Pit membrane remnants in perforation plates of Hydrangeales with comments on pit membrane remnant occurrence, physiological significance and phylogenetic distribution in dicotyledonsBOTANICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 1 2004SHERWIN CARLQUIST FLS Perforation plates from ten species of seven genera of Hydrangeales sensu Thorne were studied using scanning electron microscopy (SEM). The presence of pit membranes in perforations ranges from abundant, as in Carpenteria and Hydrangea, to minimal, as in Deutzia, Escallonia and Philadelphus. Abnormally great pit membrane presence may result from the presence of secondary compounds that inhibit lysis, as in Quintinia serrata; such interference with the natural lysis process may or may not be evident from coarseness and irregularity of pit membrane surface and of threads composing the pit membrane remnants. The presence of pit membrane remnants in perforation plates is hypothesized to be a symplesiomorphy, found in a fraction of dicotyledons with scalariform perforation plates (but still in an appreciable number of species). Pit membrane remnant presence may represent incomplete lysis of primary wall material (cellulose microfibrils) in species that occupy highly mesic habitats, where such impedance in the conductive stream does not have an appreciable negative selective value. This physiological interpretation of pit membrane remnants in perforations is enhanced by the phylogenetic distribution as well as the strongly mesic ecological preferences of species that exemplify this phenomenon in dicotyledons at large. Families with pit membrane presence in perforations are scattered throughout phylogenetic trees, but they occur most often in basal branches of major clades (superorders) or as basal branches of orders within the major clades. Further study will doubtless reveal other families and genera in which this phenomenon occurs, although it is readily detected only with SEM. Phylogenetic stages in the disappearance of pit membrane remnants from perforation plates are described, ranging from intact pit membranes except for presence of pores of various sizes, to presence of membrane remnants only at lateral ends of perforations and in one or two perforations (arguably pits) at the transition between a perforation plate and subadjacent lateral wall pitting. Developmental study of the mechanism and timing of lysis of pit membranes in perforations, and assessment of the role of the conductive stream in their removal, are needed to enhance present understanding of vessel evolution. © 2004 The Linnean Society of London, Botanical Journal of the Linnean Society, 2004, 146, 41,51. [source] The effect of drug eluting stents on cardiovascular events in patients with intermediate lesions and borderline fractional flow reserve,CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 4 2007Shahar Lavi MD Abstract Objective: To assess the role of fractional flow reserve (FFR) in guiding therapy in the drug eluting stent (DES) era. Background: FFR is a useful index for evaluation of the physiological significance of angiographically indeterminate coronary artery lesions. However, its role in the DES era is unknown. Methods: Long term outcome of 281 patients with angiographically indeterminate coronary lesions and borderline FFR (0.75 , FFR < 0.9) was obtained. The outcome of patients who had a DES placed (n = 58), was compared with that of consecutive patients with borderline FFR that were treated by PCI with bare metal stents (BMS, n = 58), or were deferred from revascularization (n = 165). Results: FFR was significantly higher in the deferred group (median and IQR); 0.85 (0.82 to 0.88) compared with the BMS (0.78; 0.76 to 0.82) and the DES (0.79; 0.77 to 0.82), P < 0.001. Pretreatment FFR was a significant determinant of long term event rates in the deferred patients (P = 0.002) but had no effect in patients treated by PCI. In the deferred group, there were fewer events (death, myocardial infarction, target vessel revascularization) compared with the BMS group; but no significant difference was observed between the DES and the deferred groups. Conclusions: In borderline FFR, long term outcome after PCI with BMS is inferior to conservative therapy or PCI with DES. While conservative management is preferable in these patients, PCI with DES may be considered in specific circumstances. © 2007 Wiley-Liss, Inc. [source] Blockade of superoxide generation prevents high-affinity immunoglobulin E receptor-mediated release of allergic mediators by rat mast cell line and human basophilsCLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2002T. Yoshimaru Summary Background Previous studies have shown that rat peritoneal mast cells and mast cell model rat basophilic leukaemia (RBL-2H3) cells generate intracellular reactive oxygen species (ROS) in response to antigen challenge. However, the physiological significance of the burst of ROS is poorly understood. Objective The present study was undertaken to investigate the role of superoxide anion in mediator release in rat and human cell systems. Methods RBL-2H3 cells were directly stimulated with anti-rat Fc,RI ,-subunit monoclonal antibody (mAb). For the analysis of human cell system, leucocytes were isolated by dextran sedimentation from healthy volunteers or from patients, and challenged either with anti-human Fc,RI mAb or with the relevant antigens. Superoxide generation was determined by chemiluminescence-based methods. The releases of histamine and leukotrienes (LT)s were determined by enzyme-linked immunosorben assay (ELISA). Results Cross-linking of Fc,RI on RBL-2H3 cells or on human leucocytes from healthy donors by the anti-Fc,RI mAb resulted in a rapid generation of superoxide anion, as determined by chemiluminescence using superoxide-specific probes. Similarly, leucocytes from patients generated superoxide anion in response to the challenge with the relevant allergen but not with the irrelevant allergen. Furthermore, diphenyleneiodonium (DPI), a well-known inhibitor of flavoenzymes suppressed the superoxide generation and the release of histamine and LTC4 induced by the anti-Fc,RI mAb or by allergen in parallel. Conclusion These results indicate that both RBL-2H3 cells and human basophils generate superoxide anion upon Fc,RI cross-linking either by antibody or by allergen challenge and that blockade of the generation prevents the release of allergic mediators. The findings strongly support the role of superoxide generation in the activation of mast cells and basophils under both physiological and pathological conditions. The findings suggest that drugs regulating the superoxide generation have potential therapeutic use for allergic disorders. [source] | |||||||||||||