Trichomes as models for studying plant cell differentiation

Trichomes, originating from epidermal cells, are present on nearly all terrestrial plants. They exist in diverse forms, are readily accessible, and serve as an excellent model system for analyzing the molecular mechanisms in plant cell differentiation, including cell fate choices, cell cycle control, and cell morphogenesis. In Arabidopsis, two regulatory models have been identified that function in parallel in trichome formation; the activator–inhibitor model and the activator–depletion model. Cotton fiber, a similar unicellular structure, is controlled by some functional homologues of Arabidopsis trichome-patterning genes. Multicellular trichomes, as in tobacco and tomato, may form through a distinct pathway from unicellular trichomes. Recent research has shown that cell cycle control participates in trichome formation. In this review, we summarize the molecular mechanisms involved in the formation of unicellular and multicellular trichomes, and discuss the integration of the cell cycle in its initiation and morphogenesis.     

Spermatozoa: models for studying regulatory aspects of energy metabolism

Spermatozoa are highly specialized cells, and they offer advantages for studying several basic aspects of metabolic control such as the role of adenosine triphosphate-(ATP)-homeostasis for cell function, the mechanisms of fatigue and metabolic depression, the metabolic channelling through the cytoplasm and the organization and regulation of glycolytic enzymes. Spermatozoa of four species with different reproductive modes are, introduced and the first results are presented: Spermatozoa of the marine wormArenicola marina are well adapted to external fertilization in sea water with fluctuating oxygen tension: they are motile for several hours in oxygen-free sea water, even when the ATP level is dramatically reduced. Anaerobic ATP production occurs by alanine, acetate and propionate fermentation probably by the same pathways known from somatic cells of this species. Under aerobic conditions the phosphagen system might function like a shuttle for energy-rich phosphate from mitochondria to the dynein-ATPases. Storage of turkey and carp spermatozoa for several hours without exogenous substrates and oxygen results in the degradation of phosphocreatine and ATP to inorganic phosphate and adenosine monophosphate (AMP), respectively. Despite low energy charges, stored spermatozoa of both species are capable of progressive movements. In carp spermatozoa fatigue of motility is not accompanied by the dramatic acidosis one discusses as an important effect in muscle fatigue. Energy metabolism of boar spermatozoa is typically based on glycolysis consuming extracellular carbohydrates and producing lactate and protons. The sperm seem to tolerate low intracellular pH (<6.5). The lack of a phosphagen system (no energy shuttle from mitochondria to the distal dynein-ATPases) is probably compensated by a high glycolytic ATP-production in the mitochondria-free piece of the flagellum.     

Transgenic animal models of sickle cell disease

An animal model which allows study of chronic processes occurring in sickle cell disease has finally been realized with the development of several lines of transgenic mice which express high levels of ^s or ^s-variants in their red cells. The red cells of all mouse lines exhibit characteristic sickle shapes on deoxygenation and most lines have enlarged spleens and mildly elevated reticulocytes in adult mice; both of these properties are suggestive of enhanced red cell destruction and erythropoiesis. However, all lines examined to date have normal hemoglobin levels in adult mice. In one mouse line under ambient conditions, retinopathy and abnormal renal function have been observed and in the same line under hypoxic conditions, anemia, irreversibly sickled cell formation, and urine concentrating defect have been observed. The current mouse lines will allow some aspects of sickle cell disease to be studied, but sigificant improvements can still be made in the transgenic mouse model.     

Murine models of colorectal cancer: studying the role of oncogenic K-<Emphasis Type="Italic">ras</Emphasis>

Cancers of the intestine are amongst the most frequent tumors in the Western countries. They arise through the stepwise, progressive disruption of cellular signalling cascades which control cell proliferation, survival and differentiation. The proto-oncogene K-ras functions as an important molecular switch linking several of these signalling pathways. Activating mutations of K-ras are found in about 50% of colorectal cancers, but their contribution to tumor initiation and progression is still poorly understood. Murine models provide excellent opportunities to identify and define the roles of genes involved in cancer formation and growth in the digestive tract. In this review, I will discuss the biological properties of oncogenic K-ras, its influence on cell signalling and its role in colorectal tumorigenesis based on recently established murine models.     

Computational models: a modest role for content

The computational theory of mind construes the mind as an information-processor and cognitive capacities as essentially representational capacities. Proponents of the view (hereafter, ‘computationalists’) claim a central role for representational content in computational models of these capacities. In this paper I argue that the standard view of the role of representational content in computational models is mistaken; I argue that representational content is to be understood as a gloss on the computational characterization of a cognitive process.     

Physiological roles of glycerol-transporting aquaporins: the aquaglyceroporins

A subclass of aquaporin (AQP) water channels, termed aquaglyceroporins, are also able to transport glycerol and perhaps urea and other small solutes. Although extensive data exist on the physiological roles of aquaporin-facilitated water transport, until recently the biological significance of glycerol transport by the mammalian aquaglyceroporins has been unknown. There is now compelling evidence for involvement of aquaglyceroporin- facilitated glycerol transport in skin hydration and fat cell metabolism. Mice deficient in AQP3 have dry skin, reduced skin elasticity and impaired epidermal biosynthesis. Mice lacking AQP7 manifest progressive adipocyte fat accumulation and hypertrophy. These skin and fat phenotypes are attributable to impaired glycerol transport. A potential implication of these findings is the possibility of modulation of aquaglyceroporin expression or function in the therapy of skin diseases and obesity. Received 20 January 2006; received after revision 21 February 2006; accepted 20 March 2006     

Evidence for mimicry by viral antigens in animal models of autoimmune disease including myocarditis

Molecular mimicry of viral antigens with self determinants has been proposed as one of the pathogenic mechanisms in autoimmune disease. Evidence of viral mimicry in animal models of autoimmunity is accumulating. Murine adenovirus, Semliki forest virus, lactate dehydrogenase-elevating virus, herpes simplex virus type-1, hepatitis B virus, encephalomyocarditis virus, Theiler's murine encephalomyelitis virus, Coxsackievirus and cytomegalovirus have been found to mimic physiologically important host proteins. However, epitope homology of a viral and self determinant is not in itself strong evidence for mimicry as a pathogenic mechanism. The mimicking determinant must also be capable of inducing disease in the absence of replicative virus. Animal models provide evaluation of the viral trigger, and development and therapy for autoimmune diseases. Identification of host proteins that can induce disease together with the knowledge of immune system dysregulation, genetic association and environmental factors may lead to improved immunotherapeutic strategies for human autoimmune diseases.     

The possible role of glutamine in some cells of the immune system and the possible consequence for the whole animal

Glutamine is important for the function of lymphocytes and macrophages. A role for the high rate of glutamine utilisation by these cells is presented. Since muscle syntheses, stores and releases glutamine, this tissue may play a role in the immune response. Since the number of immune cells utilising glutamine may be large, the demand for glutamine from muscle, especially during trauma sepsis or burns, may be very high. A speculative suggestion is put forward that this requirement for glutamine from muscle may play a role in cachexia under some of these conditions.     

Model-as-replica,model-as-instrument: Representational power and contextual versatility in animal models

Existing scholarship on animal models tends to foreground either of the two major roles research organisms play in different epistemic contexts, treating their representational and instrumental roles separately. Based on an empirical case study, this article explores the changing relationship between the two epistemic roles of a research organism over the span of a decade, while the organism was used to achieve various knowledge ends. This rat model was originally intended as a replica of human susceptibility to cardiac arrest. In a fortunate stroke of serendipity, however, the experimenters detected the way mother-infant interactions regulated the pups’ resting cardiac rate. This intriguing outcome thus became the model’s new representational target and began driving the development of an experimental system. Henceforth, the model acquired an instrumental function, serving to detect and measure system-specific differences. Its subsequent development involved creating stimulus-response measures to explain and theorize those differences. It was this instrumental use of the model that pushed the experimenters into unchartered territory and conferred to the model an ability to adapt to varied epistemic contexts. Despite the prominence of this instrumental role, however, the model’s representational power continued to guide research. The model’s representational target was widened beyond heart rate to reflect other functional phenomena, such as behavioral activity and sleep/wake rhythm. The rat model was thus transformed from an experimental organism designed to instantiate cardiac regulation to a model organism taken to represent the development of a whole, intact animal under the regulatory influence of maternal care. This article examines this multifaceted transformation within the context of the salient shifts in modeling practice and variations in the model’s representational power. It thus explores how the relationship between the representational and instrumental uses of the model changed with respect to the varying exigencies of the investigative context, foregrounding its contextual versatility.     

Intergenerational programming of metabolic disease: evidence from human populations and experimental animal models

We are in the midst of unparalleled epidemics of obesity and type 2 diabetes—complex phenotypes originating at the intersection of genetic and environmental risk. As detailed in other chapters, evidence indicates that non-genetic, or environmental, risk may initiate during prenatal and early postnatal life [1]. Striking examples in humans include the association of low birth weight (LBW) and/or accelerated early growth with increased risk of insulin resistance, obesity, type 2 diabetes (T2DM), and cardiovascular disease (CVD), and the close relationship between maternal obesity or diabetes with childhood obesity. In this chapter, we will focus on the intriguing emerging data from both human and animal models that indicate that intrauterine and childhood exposures can also influence risk for diabetes and cardiovascular disease in subsequent generations. Understanding the mechanisms responsible for these effects is critical in order to develop effective metabolic and nutritional interventions to interrupt such vicious intergenerational cycles potentiating risk for metabolic disorders.     

Cell number and cell doubling times during the development of carrot embryoids in suspension culture

Summary A time course for the appearance of different stages in embryogenesis in carrot cell cultures is presented, together with the data on cell doubling times. Removal of auxin appears to dramatically increase the rate of cell division, particularly in early embryogenesis.Acknowledgment. GSW thanks the Science Research Council U. K. for a post graduate research studentship.     

The role of time series analysis in the evaluation of econometric models

This paper compares the properties of a structural model—the London Business School model of the U.K. economy—with a time series model. Information provided by this type of comparison is a useful diagnostic tool for detecting types of model misspecification. This is a more meaningful way of proceeding rather than attempting to establish the superiority of one type of model over another. In lieu of a better structural model, the effects of inappropriate dynamic specification can be reduced by combining the forecasts of both the structural and time series models. For many variables considered here these provide more accurate forecasts than each of the model types alone.     

The adequacy of thiamine in liquid diets used in animal models of alcoholism

Summary The effects of chronic administration of 2 types of liquid diets on brain thiamine pyrophosphate (TPP) levels have been investigated. With the Lieber-DeCarli diet, rats in the control group had significantly lower TPP levels compared with those of the ethanol group. The Nutrament diet used in mice was apparently adequate in the thiamine supply.Acknowledgment. The authors are thankful to Dr Hebe Greizerstein for her review and comments on this mansucript.     

The role of macroeconometric models in forecasting and policy analysis in the united states

This article stresses how little is known about the quality, particularly the relative quality, of macroeconometric models. Most economists make a strict distinction between the quality of a model per se and the accuracy of solutions based on that model. While this distinction is valid, it leaves unanswered how to compare the‘validity’of conditional models. The standard test, the accuracy of ex post simulations, is not definitive when models with differing degrees of exogeneity are compared. In addition, it is extremely difficult to estimate the relative quantitative importance of conceptual problems of models, such as parameter instability across‘policy regimes’ In light of the difficulty in comparisons of conditional macroeconometric models, many model-builders and users assume that the best models are those that have been used to make the most accurate forecasts are those made with the best models. Forecasting experience indicates that forecasters using macroeconometric models have produced more accurate macroeconomic forecasts than either naive or sophisticated unconditional statistical models. It also suggests that judgementally adjusted forecasts have been more accurate than model-based forecasts generated mechanically. The influence of econometrically-based forecasts is now so pervasive that it is difficult to find examples of‘purely judgemental’forecasts.     

The role of prices in models of innovation diffusion

When evaluating the launch of a new product or service, forecasts of the diffusion path and the effects of the marketing mix are critically important. Currently no unified framework exists to provide guidelines on the inclusion and specification of marketing mix variables into models of innovation diffusion. The objective of this research is to examine empirically the role of prices in diffusion models, in order to establish whether price can be incorporated effectively into the simpler time-series models. Unlike existing empirical research which examines the models' fit to historical data, we examine the predictive validity of alternative models. Only if the incorporation of prices improves the predictive performance of diffusion models can it be argued that these models have validity. A series of diffusion models which include prices are compared against a number of well-accepted diffusion models, including the Bass (1969) model, and more recently developed ‘flexible’ diffusion models. For short data series and long-lead time forecasting, the situation typical of practical situations, price rarely added to the forecasting capability of simpler time-series models. Copyright © 1998 John Wiley & Sons, Ltd.