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Useful Models (useful + models)
Selected AbstractsAtaxic mutant mice with defects in Ca2+ channel ,1A subunit gene: morphological and functional abnormalities in cerebellar cortical neuronsCONGENITAL ANOMALIES, Issue 2 2000Kazuhiko Sawada ABSTRACT This review summarizes recent studies in the morphological and functional abnormalities of cerebella in three ataxic mutant mice, i.e. tottering mouse, leaner mouse, and rolling mouse Nagoya (RMN). These mutants carry mutations in the Ca2+ channel ,1A subunit gene, and become useful models for human neurological diseases such as episodic ataxia type-2, familial hemiplegic migraine, and spinocerebellar ataxia type-6. All three mutants exhibited altered morphology of the Purkinje cells, ectopic synaptic contacts between granule cell axons (parallel fibers) and Purkinje cell dendritic spines and abnormal expression of tyrosine hydroxylase in Purkinje cells. In leaner mice, Purkinje cell loss was observed in alternating sagittal compartments of the cerebellar cortex corresponding to the Zebrin II-negative zones. The mutated Ca2+ channel ,1A subunit was highly expressed in granule and Purkinje cells, and the P-type Ca2+ currents in Purkinje cells were selectively reduced in the mutant mice. Therefore, we concluded that altered Ca2+ currents through the mutated Ca2+ channel ,1A subunit might be involved in the functional and morphological abnormalities in granule and Purkinje cells, and might result in expressions of behavioral phenotypes including ataxia. Increased levels of corticotropin-releasing factor and cholecystokinin in some climbing and mossy fibers were observed in RMN. These neuropeptides modulated the excitability of granule and Purkinje cells, indicating the possible expression of ataxic symptoms. [source] Vascular regeneration and angiogenic-like sprouting mechanism in a compound ascidian is similar to vertebratesEVOLUTION AND DEVELOPMENT, Issue 5 2008Fabio Gasparini SUMMARY Tunicates are useful models for comparing differing developmental processes such as embryogenesis, asexual reproduction, and regeneration, because they are the closest relatives to vertebrates and are the only chordates to reproduce both sexually and asexually. Among them, the ascidian Botryllus schlosseri displays high regenerative potential of the colonial circulatory system (CCS). The CCS runs in the common tunic, forming an anastomized network of vessels defined by simple epithelia and connected to the open circulatory system of the zooids. During asexual propagation, new vessels form by means of a tubular-sprouting mechanism, resembling that occurring in other metazoans, particularly during vertebrate angiogenesis. We studied the regeneration of experimentally ablated CCS by analyzing the general dynamics of reorganization of vessels and tunic, their ultrastructure, cell proliferation, and the immunohistology of regenerating structures using antibodies against vertebrate angiogenic factors-vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), epidermal growth factor (EGF), and receptors: VEGFR-1, VEGFR-2, and EGFR. Results show that the regenerative process of CCS occurs by a sprouting mechanism, with participation of angiogenic factors. They also show correspondence between the CCS sprouting of B. schlosseri and angiogenic sprouting in vertebrates, during both normal development and regeneration, and support the idea that this morphogenetic mechanism was co-opted during the evolution of various developmental processes in different taxa. [source] Protein engineering of Bacillus megaterium CYP102FEBS JOURNAL, Issue 10 2001The oxidation of polycyclic aromatic hydrocarbons Cytochrome P450 (CYP) enzymes are involved in activating the carcinogenicity of polycyclic aromatic hydrocarbons (PAHs) in mammals, but they are also utilized by microorganisms for the degradation of these hazardous environmental contaminants. Wild-type CYP102 (P450BM-3) from Bacillus megaterium has low activity for the oxidation of the PAHs phenanthrene, fluoranthene and pyrene. The double hydrophobic substitution R47L/Y51F at the entrance of the substrate access channel increased the PAH oxidation activity by up to 40-fold. Combining these mutations with the active site mutations F87A and A264G lead to order of magnitude increases in activity. Both these mutations increased the NADPH turnover rate, but the A264G mutation increased the coupling efficiency while the F87A mutation had dominant effects in product selectivity. Fast NADPH oxidation rates were observed (2250 min,1 for the R47L/Y51F/F87A mutant with phenanthrene) but the coupling efficiencies were relatively low (< 13%), resulting in a highest substrate oxidation rate of 110 min,1 for fluoranthene oxidation by the R47L/Y51F/A264G mutant. Mutation of M354 and L437 inside the substrate access channel reduced PAH oxidation activity. The PAHs were oxidized to a mixture of phenols and quinones. Notably mutants containing the A264G mutation showed some similarity to mammalian CYP enzymes in that some 9,10-phenanthrenequinone, the K -region oxidation product from phenanthrene, was formed. The results suggest that CYP102 mutants could be useful models for PAH oxidation by mammalian CYP enzymes, and also potentially for the preparation of novel PAH bioremediation systems. [source] Production of fermentation aroma compounds by Saccharomyces cerevisiae wine yeasts: effects of yeast assimilable nitrogen on two model strainsFEMS YEAST RESEARCH, Issue 7 2008Francisco M. Carrau Abstract The contribution of yeast fermentation metabolites to the aromatic profile of wine is well documented; however, the biotechnological application of this knowledge, apart from strain selection, is still rather limited and often contradictory. Understanding and modeling the relationship between nutrient availability and the production of desirable aroma compounds by different strains must be one of the main objectives in the selection of industrial yeasts for the beverage and food industry. In order to overcome the variability in the composition of grape juices, we have used a chemically defined model medium for studying yeast physiological behavior and metabolite production in response to nitrogen supplementation so as to identify an appropriate yeast assimilable nitrogen level for strain differentiation. At low initial nitrogen concentrations, strain KU1 produced higher quantities of esters and fatty acids whereas M522 produced higher concentrations of isoacids, ,-butyrolactone, higher alcohols and 3-methylthio-1-propanol. We propose that although strains KU1 and M522 have a similar nitrogen consumption profile, they represent useful models for the chemical characterization of wine strains in relation to wine quality. The differential production of aroma compounds by the two strains is discussed in relation to their capacity for nitrogen usage and their impact on winemaking. The results obtained here will help to develop targeted metabolic footprinting methods for the discrimination of industrial yeasts. [source] Micro-magnetic resonance imaging of avian embryosJOURNAL OF ANATOMY, Issue 6 2007Xiaojing Li Abstract Chick embryos are useful models for probing developmental mechanisms including those involved in organogenesis. In addition to classic embryological manipulations, it is possible to test the function of molecules and genes while the embryo remains within the egg. Here we define conditions for imaging chick embryo anatomy and for visualising living quail embryos. We focus on the developing limb and describe how different tissues can be imaged using micro-magnetic resonance imaging and this information then synthesised, using a three-dimensional visualisation package, into detailed anatomy. We illustrate the potential for micro-magnetic resonance imaging to analyse phenotypic changes following chick limb manipulation. The work with the living quail embryos lays the foundations for using micro-magnetic resonance imaging as an experimental tool to follow the consequences of such manipulations over time. [source] Development of inland lakes as hubs in an invasion networkJOURNAL OF APPLIED ECOLOGY, Issue 1 2005JIM R. MUIRHEAD Summary 1The ability to predict spatially explicit dispersal by non-indigenous species is a difficult but increasingly important undertaking as it allows management efforts to be focused around areas identified as susceptible to invasion. Lakes may serve as useful models for these studies because the habitats are well defined, and vectors of spread may be readily identified and quantified. In this study, we examined patterns of spread of the non-indigenous spiny waterflea Bythotrephes longimanus to inland lakes in Ontario, Canada, to identify lakes for which management efforts to reduce traffic would be most effective. 2We surveyed people using lakes for recreational purposes to quantify movements of trailered boats and other risky activities, to model relative vector traffic from invaded lakes to non-invaded and other invaded lakes. Non-linear functions were developed to describe the cumulative number of invaded and non-invaded destination lakes visited by people leaving five important lakes already invaded by the spiny waterflea (Huron, Simcoe, Muskoka, Panache and Kashagawigamog). The relative difference in these functions was used to identify which lakes will develop into future invasion hubs and will therefore be most important to future dispersal of the species. 3In the recent past, Lake Muskoka has been an important hub from which the spiny waterflea has invaded other lakes. It is unlikely to continue to be a source for waterflea invasion as most outbound traffic is to previously invaded lakes. Conversely, most outbound traffic from Lakes Kashagawigamog and Simcoe is to non-invaded lakes and, therefore, these lakes are likely to develop into hubs in the future. 4Synthesis and applications. These data on zooplankton in lake systems and associated mechanisms of transport indicate patterns not only of intrinsic value to lake management, but also of potential importance in understanding invasions more generally. Frequency distributions of the number of outbound connections to both invaded and non-invaded destinations from invaded sources follow a power function, consistent with scale-free networks. These networks indicate that small proportions of sources function as hubs. Management efforts targeted to remove developing hubs from the invasion network, rather than equal effort applied to outbound vector traffic from all sources, may reduce the predicted rate of new invasions. [source] Use of software to facilitate pharmaceutical formulation,experiences from a tablet formulationJOURNAL OF CHEMOMETRICS, Issue 3-4 2004Nils-Olof Lindberg Abstract This paper exemplifies the benefits of using experimental design together with software to facilitate the formulation of a tablet for specific purposes, from screening to robustness testing. By applying a multivariate design for the screening experiments, many excipients were evaluated in comparatively few experiments. The formulation work was generally based on designed experiments. Most of the experiments were fractional or full factorial designs, generated and evaluated in Modde with the centre point replicated. The robustness of the formulation was evaluated with experimental designs on two different occasions. Tested flavours were found to have limited influence on the important responses, which was key information in order to proceed with that particular composition. The formulation was also robust towards normal batch-to-batch variation of the excipients and the active pharmaceutical ingredient. A process step was investigated and, by applying experimental design and keeping in mind previous findings, important information could be gained from the study. The different studies yielded good and very useful models. Established relationships between design factors and responses provided information that was vital for the project. In cases of poor models, essential information regarding robustness was obtained. Copyright © 2004 John Wiley & Sons, Ltd. [source] Induction of early murine cytomegalovirus infection by different reporter gene-associated recombinant virusesJOURNAL OF VIRAL HEPATITIS, Issue 6 2006U. Drebber Summary., Murine cytomegalovirus (MCMV) has provided useful models for acute, chronic and latent CMV infection because of its similarities in structure and biology with human CMV. We report the induction of acute MCMV hepatitis with different bacterial artificial chromosome (BAC)-cloned virus constructs [MCMV-SEAP which includes the gene for secreted alkaline phosphatase (SEAP) under Rous sarcoma virus (RSV)-promoter control, MCMV-GFP which includes the gene for enhanced green fluorescent protein (eGFP) under HCMV-ie promoter control, MCMV-HBs includes the gene for hepatitis B surface antigen (HBsAg) under simian virus (SV)40-promoter control and the DeltaMC95.21 virus in which the m152 gene was deleted and substituted by the reporter gene lacZ] in order to elucidate the histopathological changes together with different reporter-gene products in the liver tissue and the effect of the deletion of a certain gene. All the virus constructs induced a similar mild acute hepatitis which had its climax from days 3 to 5 post-infection in immunocompetent mice. In situ, the reporter-gene products beta-galactosidase and secreted alkaline phosphatase could be visualized in relation to the inflammatory changes. The composition of the invading cell populations did not change even in the absence of the m152 gene. Additionally discrete inflammatory changes were seen in kidney and serosa while the other organs were not involved. This model helps us understand the immunological and histopathological mechanisms of the CMV-induced hepatitis, which plays an important role especially in the immunocompromised patient. The morphological changes can be analysed while the respective reporter gene product is expressed by the virus construct. [source] Comparison of chronic renal failure rats and modification of the preparation protocol as a hyperphosphataemia modelNEPHROLOGY, Issue 2 2008KAZUHIRO TERAI SUMMARY: Background: Several animal models with chronic renal failure have been established and used for demonstrating complications including hyperphosphataemia. Although long-time feeding is required to cause hyperphosphataemia in animals, a few modifications have been reported to provide more useful models for research. Methods: Three separate experiments were carried out in the present study. First, characteristics of commonly used subnephrectomized (5/6Nx) rats and rats fed an adenine diet (0.75% adenine in normal diet) were compared as hyperphosphataemia models. Next, using adenine-diet rats, the inhibitory effect of sevelamer hydrochloride (Sev) on serum phosphorus elevation was examined. Third, oral adenine dosing for induction of hyperphosphataemia and validation as a model using Sev were examined. Results: Serum phosphorus in 5/6Nx rats became elevated in 8,17 weeks, but the levels and time points of elevation differed among animals. In adenine-fed rats, the elevation was more clearly demonstrated with less diversity at 4 weeks. The data revealed a potential shorter model preparation period and the importance of controlling feeding amounts. Oral adenine dosing induced hyperphosphataemia by 12 days, and Sev treatment was inhibitory. After a maintenance period of over a month (no treatments), Sev-treated rats showed hyperphosphataemia as did oral adenine-dosed control rats. The serum phosphorus levels significantly decreased on further Sev treatment. Conclusion: Oral dosing with adenine made the model preparation period definitely shorter, and its usefulness as a hyperphosphataemia model was revealed using Sev. [source] Market Perceptions and Opportunities for Native Plant Production on the Southern Colorado PlateauRESTORATION ECOLOGY, Issue 2010Donna L. Peppin Increases in revegetation activities have created a large demand for locally adapted native plant materials (NPM) in the southwestern United States. Currently, there is a minimal supply of local genotypes to meet this demand. We investigated the potential for the initiation of a native plant market in the southern Colorado Plateau. Through a literature search, interviews, and site visits, we identified existing native plant markets outside of the region as useful models to help initiate a regional market. We used web-based surveys to identify and analyze current and future NPM needs and concerns. Survey results indicate that management policy strongly drives decisions regarding the use and purchase of NPM. From a demand perspective , lack of availability and cost of NPM has kept purchasing minimal, despite policy changes favoring the use of natives. For suppliers, further development of NPM is limited by inconsistent and unreliable demand and lack of production knowledge. The knowledge and tools necessary to initiate an NPM market are available, but inadequate funding sources and insufficient information sharing hinder its development. Communication among producers, land managers, buyers, and researchers, as well as partnerships with local growers, appear to be vital to initiating a functional market. [source] The unique value of primate models in translational researchAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009Carol A. Shively Abstract This special issue of AJP is focused on research using nonhuman primates as models to further the understanding of women's health. Nonhuman primates play a unique role in translational science by bridging the gap between basic and clinical investigations. The use of nonhuman primates in biomedical research challenges our resolve to treat all life as sacred. The scientific community has responded by developing ethical guidelines for the care and the use of primates and clarifying the responsibility of investigators to insure the physical and psychological well-being of nonhuman primates used in research. Preclinical investigations often involve the use of animal models. Rodent models have been the mainstay of biomedical science and have provided enormous insight into the workings of many mammalian systems that h ave proved applicable to human biological systems. Rodent models are dissimilar to primates in numerous ways, which may limit the generalizability to human biological systems. These limitations are much less likely in nonhuman primates and in Old World primates, in particular, Macaques are useful models for investigations involving the reproductive system, bioenergetics, obesity and diabetes, cardiovascular health, central nervous system function, cognitive and social behavior, the musculoskeletal system, and diseases of aging. This issue considers primate models of polycystic ovary syndrome; diet effects on glycemic control, breast and endometrium; estrogen, reproductive life stage and atherosclerosis; estrogen and diet effects on inflammation in atherogenesis; the neuroprotective effects of estrogen therapy; social stress and visceral obesity; and sex differences in the role of social status in atherogenesis. Unmet research needs in women's health include the use of diets in nonhuman primate studies that are similar to those consumed by human beings, primate models of natural menopause, dementia, hypertension, colon cancer, and frailty in old age, and dedicated colonies for the study of breast cancer. Am. J. Primatol. 71:715,721, 2009. © 2009 Wiley-Liss, Inc. [source] Pharmacological and Functional Characterization of Novel EP and DP Receptor Agonists: DP1 Receptor Mediates Penile Erection in Multiple SpeciesTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2008Nadia Brugger PhD ABSTRACT Introduction., Despite the widespread use of prostaglandin E1 as an efficacious treatment for male erectile dysfunction for more than two decades, research on prostanoid function in penile physiology has been limited. Aim., To characterize the pharmacological and physiological activity of novel subtype-selective EP and DP receptor agonists. Methods., Radioligand binding and second messenger assays were used to define receptor subtype specificity of the EP and DP agonists. Functional activity was further characterized using isolated human and rabbit penile cavernosal tissue in organ baths. In vivo activity was assessed in rabbits and rats by measuring changes in cavernous pressure after intracavernosal injection of receptor agonists. Main Outcome Measures., Receptor binding and signal transduction, smooth muscle contractile activity, erectile function. Results., In organ bath preparations of human cavernosal tissue contracted with phenylephrine, EP2- and EP4-selective agonists exhibited variable potency in causing relaxation. One of the compounds caused mild contraction, and none of the compounds was as effective as PGE1 (EC50 = 0.23 µM). There was no consistent correlation between the pharmacological profile (receptor binding and second messenger assays) of the EP agonists and their effect on cavernosal tissue tone. In contrast, the DP1-selective agonist AS702224 (EC50 =29 nM) was more effective in relaxing human cavernosal tissue than either PGE1, PGD2 (EC50 = 58 nM), or the DP agonist BW245C (EC50 =59 nM). In rabbit cavernosal tissue, PGE1 and PGD2 caused only contraction, while AS702224 and BW245C caused relaxation. Intracavernosal administration of AS702224 and BW245C also caused penile tumescence in rabbits and rats. For each compound, the erectile response improved with increasing dose and was significantly higher than vehicle alone. Conclusions., These data suggest that AS702224 is a potent DP1-selective agonist that causes penile erection. The DP1 receptor mediates relaxation in human cavernosal tissue, and stimulates pro-erectile responses in rat and rabbit. Thus, rabbits and rats can be useful models for investigating the physiological function of DP1 receptors. Brugger N, Kim NN, Araldi GL, Traish AM, and Palmer SS. Pharmacological and functional characterization of novel EP and DP receptor agonists: DP1 receptor mediates penile erection in multiple species. J Sex Med 2008;5:344,356. [source] Life-cycle phenology of some aquatic insects: implications for pond conservationAQUATIC CONSERVATION: MARINE AND FRESHWATER ECOSYSTEMS, Issue 6 2005Jérôme Cayrou Abstract 1.Life-cycles and growth patterns were determined for 21 dominant aquatic insect species in small permanent ponds in an arid, karstic region (SW France, site fr7300909 of the Natura 2000 conservation network). The species studied are widely distributed throughout Europe, but some life-cycle patterns are reported here for the first time. 2.The life-history patterns of the 21 species can be divided into five main types: (i) a semivoltine cycle spreading over 2 years; (ii) slow univoltine cycles; (iii) fast univoltine cycles; (iv) multivoltine life-cycles with a long winter generation and two or three summer generations per year; and (v) bivoltine life-cycles with two fast generations per year. Growth was either exponential over the whole developmental period for a given cohort, or divided into two or three successive periods during each of which the growth rate was fairly constant. 3.Biodiversity estimates strongly depend on the temporal and spatial scale over which observations are made. Ponds thus provide useful models to show how life-history patterns enable many temporally segregated populations to utilize small ecosystems. Conservation frameworks should therefore carefully consider the time-frame needed to survey ponds, as many species with fast cycles could be overlooked. The spatial scale needed to manage threatened habitats and thus preserve pond networks must be broadened, rather than attempting to target individual water bodies for particular management actions. Copyright © 2005 John Wiley & Sons, Ltd. [source] A unifying explanation for diverse metabolic scaling in animals and plantsBIOLOGICAL REVIEWS, Issue 1 2010Douglas S. Glazier The scaling of metabolic rate with body mass has long been a controversial topic. Some workers have claimed that the slope of log-log metabolic scaling relationships typically obeys a universal 3/4-power law resulting from the geometry of resource-transport networks. Others have attempted to explain the broad diversity of metabolic scaling relationships. Although several potentially useful models have been proposed, at present none successfully predicts the entire range of scaling relationships seen among both physiological states and taxonomic groups of animals and plants. Here I argue that our understanding may be aided by three shifts in focus: from explaining average tendencies to explaining variation between extreme boundary limits, from explaining the slope and elevation (metabolic level) of scaling relationships separately to showing how and why they are interrelated, and from focusing primarily on internal factors (e.g. body design) to a more balanced consideration of both internal and external (ecological) factors. By incorporating all of these shifts in focus, the recently proposed metabolic-level boundaries hypothesis appears to provide a useful way of explaining both taxonomic and physiological variation in metabolic scaling relationships. This hypothesis correctly predicts that the scaling slope should vary mostly between 2/3 and 1 and that it should be related to metabolic (activity) level according to an approximately U-shaped function. It also implies that the scaling of other energy-dependent biological processes should be related to the metabolic level of the organisms being examined. Some data are presented that support this implication, but further research is needed. [source] Evidence-based Reviews and Databases: Are They Worth the Effort?ACADEMIC EMERGENCY MEDICINE, Issue 11 2007Developing Evidence Summaries for Emergency Medicine A broad range of relevant evidence-based resources within and outside of emergency medicine (EM) collates and summarizes research evidence pertaining to many questions relevant to clinical emergency care. Such resources may or may not constitute the equivalent of health care recommendations, and their relationship to clinical decision-making may be complex. Many efforts in evidence-based medicine resource development, and their products, are marginally relevant to EM practice but may serve as useful models for parallel EM relevant efforts. A trade-off exists between synthesis quality and ease of practitioner access and use. Keeping all such resources up to date is a major challenge. Although observational evidence suggests that dynamic interactivity and information retrieval technology may enhance practitioner utilization, little evidence exists supporting the absolute or comparative effectiveness of different kinds of resources and databases in enhancing evidence uptake or changing clinician behavior. [source] Association of HLA-DRB1*07 and DRB1*04 to citrus red mite (Panonychus citri) and house dust mite sensitive asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2000S.-H. Cho Background Specific IgE responses to allergens provide useful models for evaluating the genetic factors that control human immune responses. A recent survey demonstrated that the citrus red mite (Panonychus citri, CRM) is the most important allergen in the development of asthma in citrus farmers. Objective The aim of this study was to evaluate whether susceptibility or resistance to CRM-induced asthma was associated with HLA-DRB1 gene. Methods DNAs were extracted from two groups of unrelated Korean adults living around citrus farms: (1) Ninety-one adults with CRM-sensitive asthma; and (2) 98 exposed, healthy nonatopic controls. Genotypes of HLA-DRB1 alleles were carried out using PCR-based methods. Results Allelic frequency of HLA-DRB1*07 was higher in the CRM-sensitive asthmatics compared to the controls (17.6% vs 4.1%, Pc = 0.01). Conversely, the frequency of DRB1*04 was lower in the CRM-sensitive asthmatics compared to the controls (19.8% vs 40.8%, Pc = 0.01). No significant difference was found in the distributions of the other HLA-DRB1 gene-encoded antigens between the two groups. Conclusion HLA-DRB1 genes may be involved in the development of CRM-induced asthma. In addition, HLA-DR7 may increase, and DR4 decrease, the risk of developing the asthma in CRM-exposed adults. 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