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Selected AbstractsGenetics of type 2 diabetes mellitus: status and perspectivesDIABETES OBESITY & METABOLISM, Issue 2 2005Lars Hansen Throughout the last decade, molecular genetic studies of non-autoimmune diabetes mellitus have contributed significantly to our present understanding of this disease's complex aetiopathogenesis. Monogenic forms of diabetes (maturity-onset diabetes of the young, MODY) have been identified and classified into MODY1,6 according to the mutated genes that by being expressed in the pancreatic ,-cells confirm at the molecular level the clinical presentation of MODY as a predominantly insulin secretory deficient form of diabetes mellitus. Genomewide linkage studies of presumed polygenic type 2 diabetic populations indicate that loci on chromosomes 1q, 5q, 8p, 10q, 12q and 20q contain susceptibility genes. Yet, so far, the only susceptibility gene, calpain-10 (CAPN10), which has been identified using genomewide linkage studies, is located on chromosome 2q37. Mutation analyses of selected ,candidate' susceptibility genes in various populations have also identified the widespread Pro12Ala variant of the peroxisome proliferator-activated receptor-, and the common Glu23Lys variant of the ATP-sensitive potassium channel, Kir6.2 (KCNJ11). These variants may contribute significantly to the risk type 2 diabetes conferring insulin resistance of liver, muscle and fat (Pro12Ala) and a relative insulin secretory deficiency (Glu23Lys). It is likely that, in the near future, the recent more detailed knowledge of the human genome and insights into its haploblocks together with the developments of high-throughput and cheap genotyping will facilitate the discovery of many more type 2 diabetes gene variants in study materials, which are statistically powered and phenotypically well characterized. The results of these efforts are likely to be the platform for major progress in the development of personalized antidiabetic drugs with higher efficacy and few side effects. [source] Boundary characteristics in Heavily Deformed Metals,ADVANCED ENGINEERING MATERIALS, Issue 5 2003G. Winther Abstract The potential of creating nanostructured metals by plastic deformation to very high strains is currently the subject of intensive research. An important part of this research concerns evolution of the characteristics of deformation induced boundaries, in particular boundary spacing and boundary misorientation. The aim of this paper is to give an overview of the present understanding of the relations between these characteristics, the microscopic deformation mechanisms and the macroscopic deformation mode. [source] Microbial life in glacial ice and implications for a cold origin of lifeFEMS MICROBIOLOGY ECOLOGY, Issue 2 2007P. Buford Price Abstract Application of physical and chemical concepts, complemented by studies of prokaryotes in ice cores and permafrost, has led to the present understanding of how microorganisms can metabolize at subfreezing temperatures on Earth and possibly on Mars and other cold planetary bodies. The habitats for life at subfreezing temperatures benefit from two unusual properties of ice. First, almost all ionic impurities are insoluble in the crystal structure of ice, which leads to a network of micron-diameter veins in which microorganisms may utilize ions for metabolism. Second, ice in contact with mineral surfaces develops a nanometre-thick film of unfrozen water that provides a second habitat that may allow microorganisms to extract energy from redox reactions with ions in the water film or ions in the mineral structure. On the early Earth and on icy planets, prebiotic molecules in veins in ice may have polymerized to RNA and polypeptides by virtue of the low water activity and high rate of encounter with each other in nearly one-dimensional trajectories in the veins. Prebiotic molecules may also have utilized grain surfaces to increase the rate of encounter and to exploit other physicochemical features of the surfaces. [source] Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4IMMUNOLOGY, Issue 2 2004Eva M. Pålsson-McDermott Summary An understanding of lipopolysaccharide (LPS) signal transduction is a key goal in the effort to provide a molecular basis for the lethal effect of LPS during septic shock and point the way to novel therapies. Rapid progress in this field during the last 6 years has resulted in the discovery of not only the receptor for LPS , Toll-like receptor 4 (TLR4) , but also in a better appreciation of the complexity of the signalling pathways activated by LPS. Soon after the discovery of TLR4, the formation of a receptor complex in response to LPS, consisting of dimerized TLR4 and MD-2, was described. Intracellular events following the formation of this receptor complex depend on different sets of adapters. An early response, which is dependent on MyD88 and MyD88-like adapter (Mal), leads to the activation of nuclear factor-,B (NF-,B). A later response to LPS makes use of TIR-domain-containing adapter-inducing interferon-, (TRIF) and TRIF-related adapter molecule (TRAM), and leads to the late activation of NF-,B and IRF3, and to the induction of cytokines, chemokines, and other transcription factors. As LPS signal transduction is an area of intense research and rapid progress, this review is intended to sum up our present understanding of the events following LPS binding to TLR4, and we also attempt to create a model of the signalling pathways activated by LPS. [source] Computational approach to the blood,aluminum problem?,INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 2 2007Christopher Exley Abstract Aluminum has no known function in biota and, when biologically available, is inimical to life. A key to understanding its potential toxicity in humans is its transport in blood. A consensus of opinion has identified the binding of aluminum by the iron-transport protein transferrin as the preeminent factor in the transport of aluminum in blood, although this idea has emanated from in vitro analysis of isolated blood and has never been tested in vivo. We have highlighted what we believe to be inadequacies of our present understanding of aluminum transport in blood, and we have proposed the application of computational methods to test rigorously what we have coined "the blood-aluminum problem." © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007 [source] The Adaptive Brain: Glenn Hatton and the Supraoptic NucleusJOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2010G. Leng In December 2009, Glenn Hatton died, and neuroendocrinology lost a pioneer who had done much to forge our present understanding of the hypothalamus and whose productivity had not faded with the passing years. Glenn, an expert in both functional morphology and electrophysiology, was driven by a will to understand the significance of his observations in the context of the living, behaving organism. He also had the wit to generate bold and challenging hypotheses, the wherewithal to expose them to critical and elegant experimental testing, and a way with words that gave his papers and lectures clarity and eloquence. The hypothalamo-neurohypophysial system offered a host of opportunities for understanding how physiological functions are fulfilled by the electrical activity of neurones, how neuronal behaviour changes with changing physiological states, and how morphological changes contribute to the physiological response. In the vision that Glenn developed over 35 years, the neuroendocrine brain is as dynamic in structure as it is adaptable in function. Its adaptability is reflected not only by mere synaptic plasticity, but also by changes in neuronal morphology and in the morphology of the glial cells. Astrocytes, in Glenn's view, were intimate partners of the neurones, partners with an essential role in adaptation to changing physiological demands. [source] A HYPOTHESIS FOR PLASTID EVOLUTION IN CHROMALVEOLATES,JOURNAL OF PHYCOLOGY, Issue 5 2008M. Virginia Sanchez-Puerta Four eukaryotic lineages, namely, haptophytes, alveolates, cryptophytes, and heterokonts, contain in most cases photosynthetic and nonphotosynthetic members,the photosynthetic ones with secondary plastids with chl c as the main photosynthetic pigment. These four photosynthetic lineages were grouped together on the basis of their pigmentation and called chromalveolates, which is usually understood to imply loss of plastids in the nonphotosynthetic members. Despite the ecological and economic importance of this group of organisms, the phylogenetic relationships among these algae are only partially understood, and the so-called chromalveolate hypothesis is very controversial. This review evaluates the evidence for and against this grouping and summarizes the present understanding of chromalveolate evolution. We also describe a testable hypothesis that is intended to accommodate current knowledge based on plastid and nuclear genomic data, discuss the implications of this model, and comment on areas that require further examination. [source] Genetic diversity assessment of anoxygenic photosynthetic bacteria by distance-based grouping analysis of pufM sequencesLETTERS IN APPLIED MICROBIOLOGY, Issue 6 2007Y.H. Zeng Abstract Aim:, To assess how completely the diversity of anoxygenic phototrophic bacteria (APB) was sampled in natural environments. Methods and Results:, All nucleotide sequences of the APB marker gene pufM from cultures and environmental clones were retrieved from the GenBank database. A set of cutoff values (sequence distances 0·06, 0·15 and 0·48 for species, genus, and (sub)phylum levels, respectively) was established using a distance-based grouping program. Analysis of the environmental clones revealed that current efforts on APB isolation and sampling in natural environments are largely inadequate. Analysis of the average distance between each identified genus and an uncultured environmental pufM sequence indicated that the majority of cultured APB genera lack environmental representatives. Conclusions:, The distance-based grouping method is fast and efficient for bulk functional gene sequences analysis. The results clearly show that we are at a relatively early stage in sampling the global richness of APB species. Periodical assessment will undoubtedly facilitate in-depth analysis of potential biogeographical distribution pattern of APB. Significance and Impact of the Study:, This is the first attempt to assess the present understanding of APB diversity in natural environments. The method used is also useful for assessing the diversity of other functional genes. [source] Pathophysiological concepts of restless legs syndromeMOVEMENT DISORDERS, Issue 10 2007Walter Paulus MD Abstract Pathophysiological concepts of restless legs syndrome (RLS) are based mainly on neuroimaging and on neurophysiological data. Furthermore treatment effects contribute essentially to the present understanding of the disease, unless the genetic progress expected in the near future will clarify substantially open issues. The concept agreed on assumes a dysfunction of the dopaminergic system, possibly on the level of striatal and/or spinal dopamine receptors, and the A11 neuron group localized in the hypothalamus as an integrated part of the system. These neurons modulate spinal excitability, alterations of which in turn affect sensory processing predominantly of leg afferents in brain stem structures. Neurophysiologically excitability alterations can be measured by a variety of methods such as determination of pain thresholds, H-reflex testing, and quantitative sensory testing. © 2007 Movement Disorder Society [source] Number III Mucous membrane pemphigoidORAL DISEASES, Issue 4 2005J Bagan Mucous membrane pemphigoid (MMP) is a sub-epithelial vesiculobullous disorder. It is now quite evident that a number of sub-epithelial vesiculobullous disorders may produce similar clinical pictures, and also that a range of variants of MMP exist, with antibodies directed against various hemidesmosomal components or components of the epithelial basement membrane. The term immune-mediated sub-epithelial blistering diseases (IMSEBD) has therefore been used. Immunological differences may account for the significant differences in their clinical presentation and responses to therapy, but unfortunately data on this are few. The diagnosis and management of IMSEBD on clinical grounds alone is impossible and a full history, general, and oral examination, and biopsy with immunostaining are now invariably required, sometimes supplemented with other investigations. No single treatment regimen reliably controls all these disorders, and it is not known if the specific subsets of MMP will respond to different drugs. Currently, apart from improving oral hygiene, immunomodulatory,especially immunosuppressive,therapy is typically used to control oral lesions. The present paper reviews pemphigoid, describing the present understanding of this fascinating clinical phenotype, summarising the increasing number of subsets with sometimes-different natural histories and immunological features, and outlining current clinical practice. [source] Nitrogen balance in forest soils: nutritional limitation of plants under climate change stressesPLANT BIOLOGY, Issue 2009H. Rennenberg Abstract Forest ecosystems with low soil nitrogen (N) availability are characterized by direct competition for this growth-limiting resource between several players, i.e. various components of vegetation, such as old-growth trees, natural regeneration and understorey species, mycorrhizal fungi, free-living fungi and bacteria. With the increase in frequency and intensity of extreme climate events predicted in current climate change scenarios, also competition for N between plants and/or soil microorganisms will be affected. In this review, we summarize the present understanding of ecosystem N cycling in N-limited forests and its interaction with extreme climate events, such as heat, drought and flooding. More specifically, the impacts of environmental stresses on microbial release and consumption of bioavailable N, N uptake and competition between plants, as well as plant and microbial uptake are presented. Furthermore, the consequences of drying,wetting cycles on N cycling are discussed. Additionally, we highlight the current methodological difficulties that limit present understanding of N cycling in forest ecosystems and the need for interdisciplinary studies. [source] Nitric oxide synthesis and signalling in plantsPLANT CELL & ENVIRONMENT, Issue 5 2008IAN D. WILSON ABSTRACT As with all organisms, plants must respond to a plethora of external environmental cues. Individual plant cells must also perceive and respond to a wide range of internal signals. It is now well-accepted that nitric oxide (NO) is a component of the repertoire of signals that a plant uses to both thrive and survive. Recent experimental data have shown, or at least implicated, the involvement of NO in reproductive processes, control of development and in the regulation of physiological responses such as stomatal closure. However, although studies concerning NO synthesis and signalling in animals are well-advanced, in plants there are still fundamental questions concerning how NO is produced and used that need to be answered. For example, there is a range of potential NO-generating enzymes in plants, but no obvious plant nitric oxide synthase (NOS) homolog has yet been identified. Some studies have shown the importance of NOS-like enzymes in mediating NO responses in plants, while other studies suggest that the enzyme nitrate reductase (NR) is more important. Still, more published work suggests the involvement of completely different enzymes in plant NO synthesis. Similarly, it is not always clear how NO mediates its responses. Although it appears that in plants, as in animals, NO can lead to an increase in the signal cGMP which leads to altered ion channel activity and gene expression, it is not understood how this actually occurs. NO is a relatively reactive compound, and it is not always easy to study. Furthermore, its biological activity needs to be considered in conjunction with that of other compounds such as reactive oxygen species (ROS) which can have a profound effect on both its accumulation and function. In this paper, we will review the present understanding of how NO is produced in plants, how it is removed when its signal is no longer required and how it may be both perceived and acted upon. [source] The Evolution of Surgery on the Maxillary Sinus for Chronic Rhinosinusitis,THE LARYNGOSCOPE, Issue 3 2002FRCS(Ed), Valerie Lund FRCS Objective To examine the management of the maxillary sinus in chronic rhinosinusitis over the last 500 years. Method A literature review was conducted. Result The maxillary sinus was first recognized in the 16th century and its role as a source of infection became the focus of attention, beginning with Nathaniel Highmore in 1651 and continuing up until the 21st century. The surgical drainage of the sinus was achieved by a variety of routes, including the alveolar margin, anterior wall, and middle and inferior meati. The rationale for these procedures, developed in a pre-antibiotic era, may be re-examined in the context of our present understanding of the pathophysiology of chronic rhinosinusitis. Conclusion The maxillary sinus has been the focus of surgical attention from the 17th century onward largely as a result of its size and accessibility, initially reinforced by plain x-ray. However, in the 20th century, the advent of computed tomography and nasal endoscopy has reaffirmed the relationship of the maxillary sinus to the ostiomeatal complex in chronic rhinosinusitis, as originally demonstrated by pioneers such as Zuckerkandl, and redirected the focus of our therapeutic approaches. [source] Calmodulin activity and cAMP signalling modulate growth and apical secretion in pollen tubesTHE PLANT JOURNAL, Issue 6 2004Cláudia Rato Summary Our present understanding implicates both calmodulin (CaM) and 3,,5,-cyclicAMP (cAMP) in the regulation of pollen tube growth. However, downstream molecules of these signalling pathways and the cellular processes they modulate remain largely unknown. In order to elucidate the role of CaM, we mapped its activity in growing pollen tubes. 2-chloro-(,-amino-Lys75)-[6-4-(N,N, -diethylaminophenyl)-1,3,5-triazin-4-yl]-calmodulin (TA-CaM) and fluorescein-calmodulin (FL-CaM), fluorescent analogues of CaM, were loaded into pollen tubes and CaM activity was mapped by fluorescence ratio imaging. It was found that CaM activity exhibits a tip-focused gradient, similar to the distribution of cytosolic-free calcium ([Ca2+]c). In long pollen tubes, apical CaM activity was also found to oscillate with a period similar to [Ca2+]c (40,80 sec). This oscillatory behaviour was not observed in small pollen tubes or in tubes that had stopped growing. Changes in CaM activity within the dome of the pollen tube apex resulting from the photolysis of caged photolysis of RS-20 (a peptide antagonist of CaM) induced re-orientation of the growth axis, suggesting that CaM is also involved in the guidance mechanism. CaM activity was strongly modulated by intracellular changes in cAMP (induced by activators and antagonists of adenylyl cyclase). These results indicate that the action of this protein is dependent not solely on [Ca2+]c but also on a cross-talk with other signalling pathways. A putative target of this cross-talk is the secretory machinery as observed in pollen tubes loaded with the FM (N -(3-triethylammoniumpropyl)-4-(4-dibutylamino)styryl)pyridinium dibromide 1-43 dye and exposed to different antagonists and activators of these molecules. Our data thus suggest that pollen tube growth and orientation depend on an intricate cross-talk between multiple signalling pathways in which CaM is a key element. [source] Tumour virology , history, status and future challengesAPMIS, Issue 5-6 2009KARL-HENNING KALLAND Viruses enter host cells in order to complete their life cycles and have evolved to exploit host cell structures, regulatory factors and mechanisms. The virus and host cell interactions have consequences at multiple levels, spanning from evolution through disease to models and tools for scientific discovery and treatment. Virus-induced human cancers arise after a long duration of time and are monoclonal or oligoclonal in origin. Cancer is therefore a side effect rather than an essential part of viral infections in humans. Still, 15,20% of all human cancers are caused by viruses. A review of tumour virology shows its close integration in cancer research. Viral tools and experimental models have been indispensible for the progress of molecular biology. In particular, retroviruses and DNA tumour viruses have played major roles in our present understanding of the molecular biology of both viruses and the host. Recently, additional complex relationships due to virus and host co-evolution have appeared and may lead to a further understanding of the overall regulation of gene expression programmes in cancer. [source] A glossary of DNA structures from A to ZACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2003Anirban Ghosh The right-handed double-helical Watson,Crick model for B-form DNA is the most commonly known DNA structure. In addition to this classic structure, several other forms of DNA have been observed and it is clear that the DNA molecule can assume different structures depending on the base sequence and environment. The various forms of DNA have been identified as A, B, C etc. In fact, a detailed inspection of the literature reveals that only the letters F, Q, U, V and Y are now available to describe any new DNA structure that may appear in the future. It is also apparent that it may be more relevant to talk about the A, B or C type dinucleotide steps, since several recent structures show mixtures of various different geometries and a careful analysis is essential before identifying it as a `new structure'. This review provides a glossary of currently identified DNA structures and is quite timely as it outlines the present understanding of DNA structure exactly 50,years after the original discovery of DNA structure by Watson and Crick. [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] Implications of an interpretive understanding of LCA practiceBUSINESS STRATEGY AND THE ENVIRONMENT, Issue 7 2008Emma Rex Abstract Despite the desirability of a life cycle perspective and many attempts to facilitate life cycle assessment (LCA), industry has been relatively slow to adopt LCA. In this research, we thus set out to investigate the underpinnings of LCA practice in industry. A literature review shows that the present understanding is that ,structural' conditions such as location and sector determine the use of LCA in industry. However, a field study of two companies in the Swedish forest product industry (thus in the same sector and country) indicates that LCA practice is shaped more by individual preferences and chance events. Our results imply a more interpretive understanding of LCA practice than has been put forward by previous research. The two types of understanding are discussed and their implications for practitioners in industry, organizations promoting the use of LCA and further research are presented. Copyright © 2008 John Wiley & Sons, Ltd and ERP Environment. [source] Role of haem oxygenase-1 in microbial host defenceCELLULAR MICROBIOLOGY, Issue 2 2009Su Wol Chung Summary Haem oxygenase (HO)-1 is a cytoprotective enzyme that plays a critical role in defending the body against oxidant-induced injury during inflammatory processes. HO catalydes the degradation of haem to carbon monoxide (CO), biliverdin and ferrous iron. Biliverdin is converted to bilirubin, a potent endogenous antioxidant. CO has a number of biological functions, including anti-inflammatory properties. In various models of disease, HO-1 is known to play a critical role by ameliorating the pathological consequences of injury. In many of these models, the beneficial effects of HO-1 and its products of haem catabolism are by suppressing an inflammatory response. However, when investigating diseases due to microbial infections, inhibition of the inflammatory response could disrupt the ability of the immune system to eradicate an invading pathogen. Thus, questions remain regarding the role of HO-1 in microbial host defence. This microreview will address our present understanding of HO-1 and its functional significance in a variety of microbial infections. [source] Intraneural ganglion cyst: A 200-year-old mystery solvedCLINICAL ANATOMY, Issue 7 2008Robert J. Spinner Abstract We describe the first reported case of an intraneural ganglion cyst, an ulnar ("cubital") intraneural cyst, which, on literature review, dated to 1810. For over 80 years, its original brief description by Beauchêne was wrongly attributed to Duchenne, effectively making the reference and specimen inaccessible to scrutiny. Fortunately, the intact cyst had been safely housed in the Musée Dupuytren, Paris, France, thus permitting its examination. Although originally described as a "serous" cyst, our present understanding of the anatomy of the ulnar nerve and of peripheral nerve pathology allowed us to reinterpret it as a mucin-filled, elbow-level, ulnar intraneural ganglion cyst. In addition to its description as a fusiform cystic enlargement of the nerve, we documented similar enlargement of a lumen-bearing branch, the articular branch at the level of the elbow. Based on our assessment of the specimen and with a modern perspective, we concluded that the origin of the cyst was from the postero-medial aspect of the elbow joint and that its fluid content, having dissected through a capsular defect, followed the path of the articular branch into the parent ulnar nerve. The purpose of this report is to clarify historical misconceptions regarding the pathogenesis of this controversial entity. Clin. Anat. 21:611,618, 2008. © 2008 Wiley-Liss, Inc. [source] Bison breeding characteristics and interpretation of archaeological seasonality revisitedINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 6 2006D. WaldeArticle first published online: 17 JUL 200 Abstract Bison breeding behaviour has been used for the last three decades as the basis for developing methods for assigning season-of-occupation estimates to archaeological sites on the North American Plains. These methods are based upon the supposition that the North American bison breeding season is extremely short and that genetically controlled ontological characteristics such as foetal growth and tooth eruption sequences can therefore be used to infer site seasonality in a reasonably straightforward and precise manner. This paper reviews bison population studies conducted during the past 30 years to reassess present understandings of the length of North American bison breeding seasons. It is concluded that the bison breeding season regularly extends over a period of three to four months, and that initiation of ontological development will therefore also vary over the same period of time. Bison development characteristics cannot provide a reliable or precise means of assigning seasonality to archaeological sites on the North American Plains. It is suggested that methods using physical characteristics such as dental cementum incrementation which are directly affected by seasonal changes could be more productive. Copyright © 2006 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||