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Biomedical subjects

S J Simpson

Publications and source records attributed to S J Simpson.

At least 19 recordsLinked to original sources

From disorder to order in marching locusts.

Recent models from theoretical physics have predicted that mass-migrating animal groups may share group-level properties, irrespective of the type of animals in the group. One key prediction is that as the density of animals in the group increases, a rapid transition occurs from disordered movement of individuals within the group to highly aligned collective motion. Understanding such a transition is crucial to the control of mobile swarming insect pests such as the desert locust. We confirmed the prediction of a rapid transition from disordered to ordered movement and identified a critical density for the onset of coordinated marching in locust nymphs. We also demonstrated a dynamic instability in motion at densities typical of locusts in the field, in which groups can switch direction without external perturbation, potentially facilitating the rapid transfer of directional information.

Animals↗

Flexible diet choice offsets protein costs of pathogen resistance in a caterpillar.

Mounting effective resistance against pathogens is costly in terms of energy and nutrients. However, it remains unexplored whether hosts can offset such costs by adjusting their dietary intake so as to recoup the specific resources involved. We test this possibility by experimentally challenging caterpillars (Spodoptera littoralis) with a highly virulent entomopathogen (nucleopolyhedrovirus), under dietary regimes varying in the content of protein and digestible carbohydrate. We found that dietary protein influenced both resistance to pathogen attack and constitutive immune function to a greater extent than did dietary carbohydrate, indicating higher protein costs of resistance than energy costs. Moreover, when allowed to self-compose their diet, insects surviving viral challenge increased their relative intake of protein compared with controls and those larvae dying of infection, thus demonstrating compensation for protein costs associated with resistance. These results suggest that the change in the host's nutritional demands to fight infection induces a compensatory shift in feeding behaviour.

Animal Feed↗

Does Bertrand's rule apply to macronutrients?

It has been known for over a century that the dose-response curve for many micronutrients is non-monotonic, having an initial stage of increasing benefits with increased intake, followed by increasing costs as excesses become toxic. This phenomenon, termed Bertrand's rule, is widely assumed not to apply to caloric macronutrients. To date this assumption has been safe, owing to the considerable methodological challenges involved in coaxing animals to over-ingest macronutrients in a way that enables the effects of specific food components to be isolated. Here we report an experiment which overcomes these difficulties, to test whether the second phase (incurring costs with excessive intake) applies to carbohydrate intake by the generalist-feeding caterpillar Spodoptera littoralis. The results showed that excess carbohydrate intake caused increased mortality, thus extending Bertrand's rule to macronutrients.

Animal Feed↗

Obesity: the protein leverage hypothesis.

The obesity epidemic is among the greatest public health challenges facing the modern world. Regarding dietary causes, most emphasis has been on changing patterns of fat and carbohydrate consumption. In contrast, the role of protein has largely been ignored, because (i) it typically comprises only approximately 15% of dietary energy, and (ii) protein intake has remained near constant within and across populations throughout the development of the obesity epidemic. We show that, paradoxically, these are precisely the two conditions that potentially provide protein with the leverage both to drive the obesity epidemic through its effects on food intake, and perhaps to assuage it. We formalize this hypothesis in a mathematical model. Some supporting epidemiological, experimental and animal data are presented, and predictions are made for future testing.

Animals↗

Dietary influences over proliferating cell nuclear antigen expression in the locust midgut.

We have studied the influence of variations in dietary protein (P) and digestible carbohydrate (C), the quantity of food eaten, and insect age during the fifth instar on the expression of the proliferating cell nuclear antigen (PCNA) in the epithelial cells of the midgut (with special reference to the midgut caeca) in the African migratory locust, Locusta migratoria. Densitometric analysis of PCNA-immunostained cells was used as an indirect measure of the levels of expression of PCNA, and a PCNA cellular index (PCNA-I) was obtained. Measurements of the DNA content of the cells have also been carried out by means of microdensitometry of Feulgen-stained, thick sections of midgut. A comparison between the PCNA nuclear level and the DNA content was performed. The PCNA levels were significantly different among the cells of the five regions studied: caeca, anterior ventricle, medial ventricle, posterior ventricle and ampullae of the Malpighian tubules. We have studied in more detail the region with highest PCNA-I, i.e. the caeca. The quality and the quantity of food eaten under ad libitum conditions were highly correlated with both the PCNA and DNA levels in the caeca cells. Locusts fed a diet with a close to optimal P:C content (P 21%, C 21%) showed the highest PCNA and DNA content. In locusts fed a food that also contained a 1:1 ratio of P to C but was diluted three-fold by addition of indigestible cellulose (P 7%, C 7%), a compensatory increase in consumption was critical to maintaining PCNA levels. Our measurements also showed that the nuclear DNA content of the mature and differentiated epithelial cells was several-fold higher than the levels in the undifferentiated stem cells of the regenerative nests. These results, combined with the low number of mitotic figures found in the regenerative nests of the caeca and the marked variation in PCNA levels among groups, suggest that some type of DNA endoreduplication process may be taking place. Our data also indicate that the DNA synthetic activity in the midgut is related to feeding in locusts. The possible dietary and nutritional regulatory mechanisms and the significance of the differences found are discussed.

Age Factors↗

Nutrient balancing in grasshoppers: behavioural and physiological correlates of dietary breadth.

We examined correlates of nutrient balancing with dietary range by comparing diet selection and ingestive, post-ingestive and performance-related responses to macronutrient imbalance in two species of grasshopper. One of the two species, Locusta migratoria (the African migratory locust), is a specialist grass-feeder, while the other, Schistocerca gregaria (the desert locust), is a generalist herbivore that includes both grasses and forbs in its diet. In ad libitum conditions, both species composed a balanced intake of the two macronutrients protein and carbohydrate from nutritionally complementary synthetic foods, but the composition of the selected diet differed, with the generalist selecting more protein, but not carbohydrate, than the grass-specialist. The grass-specialist, by contrast, retained ingested nitrogen more efficiently on the ad libitum diets. When confined to nutritionally imbalanced foods, both species regulated ingestion in such a way as to mitigate excesses as well as deficits of the two nutrients. The responses were, however, distinct in the two species, with the generalist feeder ingesting greater excesses of protein than the specialist. The species also differed in their post-ingestive responses to ingested excesses of nutrient, with the generalist but not the specialist using protein-derived carbon as an energy source when fed carbohydrate-deficient foods. The generalist also retained a higher level of body protein when confined to protein-deficient diets. The data suggested one functional reason why the generalist species selected a diet with higher protein content in the ad libitum treatment because, when confined to the nutritionally imbalanced foods, development rate peaked on higher protein foods for the generalist compared with the specialist. Many aspects of these data agree with the prediction that generalist-feeding animals should show greater behavioural and physiological flexibility in their responses to nutrient imbalance than do specialists.

Animal Nutritional Physiological Phenomena↗

A comparison of nutritional regulation in solitarious- and gregarious-phase nymphs of the desert locust Schistocerca gregaria.

Nutritional regulatory responses were compared for the cryptic 'solitarious' and the conspicuously coloured, aggregating 'gregarious' phases of the desert locust Schistocerca gregaria. The desert locust has the genetic potential to exist in either phase, changing between them within a lifetime and epigenetically across generations. Our aim was to compare final-instar nymphs of the two phases with respect to key nutritional variables, including (i) points of regulated intake (the 'intake target') for protein and carbohydrate, (ii) the nature of trade-offs between over-eating nutrients in excess and under-eating those in deficit when fed nutritionally unbalanced foods, (iii) diet-related patterns of nutrient utilisation, and (iv) the performance consequences of eating nutritionally unbalanced diets. When provided with pairs of nutritionally unbalanced but complementary foods, both phases regulated their intake of protein and carbohydrate to a similar point. However, when confined to foods that were of unbalanced protein to carbohydrate ratio, gregarious nymphs ate more than solitarious insects. Both phases regulated protein growth, but gregarious insects did so to a lower adult body protein content and converted ingested protein to growth less efficiently. When fed a food high in carbohydrate and low in protein, gregarious nymphs deposited more body lipid and survived less well than did solitarious insects. Solitarious nymphs developed more quickly than gregarious nymphs except on the two most extremely unbalanced diets, on which development time was similar. The results are discussed with respect to the different nutritional ecologies of the two phases and used to develop the hypothesis that animals have evolved to trade-off the cost of eating excess of a nutritionally unbalanced diet against the probability of encountering foods of complementary composition in the future.

Animal Nutritional Physiological Phenomena↗

Gregarious behavior in desert locusts is evoked by touching their back legs.

Desert locusts in the solitarious phase were repeatedly touched on various body regions to identify the site of mechanosensory input that elicits the transition to gregarious phase behavior. The phase state of individual insects was measured after a 4-h period of localized mechanical stimulation, by using a behavioral assay based on multiple logistic regression analysis. A significant switch from solitarious to gregarious behavior occurred when the outer face of a hind femur had been stimulated, but mechanical stimulation of 10 other body regions did not result in significant behavioral change. We conclude that a primary cause of the switch in behavior that seeds the formation of locust swarms is individuals regularly touching others on the hind legs within populations that have become concentrated by the environment.

Analysis of Variance↗

High resolution 1H NMR spectroscopic studies of the composition of the haemolymph of crowd- and solitary-reared nymphs of the desert locust, Schistocerca gregaria.

High resolution 1H NMR spectroscopy provided a rapid and non-invasive means of establishing a multicomponent profile of the low molecular weight organic metabolites present in the haemolymph of crowd-reared and solitary-reared desert locusts. Assignments of the 1H NMR resonances detected in the one-dimensional (1D) spectra were supported by the comparison of chemical shifts with those of commonly found metabolites, the application of 2D NMR spectroscopy, and spiking of authentic standards into the sample. The haemolymph metabolite profile was found to comprise trehalose, a series of amino acids, organic acids, lipids, ethanol and the polyamine putrescine. In total, it was possible to detect simultaneously and potentially quantify over 20 endogenous compounds. An interesting difference between the phases was the higher putrescine concentrations present in solitary-reared nymphs, which may indicate a role of this compound in phase determination. In addition, differences in the concentrations of trehalose, lipids, acetate and ethanol were also observed between solitary-reared and gregarious-reared nymphs enabling the ready differentiation of the two phases based on the NMR spectra of the haemolymph.

Amino Acids↗

Density-dependent aposematism in the desert locust.

The ecological processes underlying locust swarm formation are poorly understood. Locust species exhibit phenotypic plasticity in numerous morphological, physiological and behavioural traits as their population density increases. These density-dependent changes are commonly assumed to be adaptations for migration under heterogeneous environmental conditions. Here we demonstrate that density-dependent nymphal colour change in the desert locust Schistocerca gregaria (Orthoptera: Acrididae) results in warning coloration (aposematism) when the population density increases and locusts consume native, toxic host plants. Fringe-toed lizards (Acanthodactylus dumerili (Lacertidae)) developed aversions to high-density-reared (gregarious-phase) locusts fed Hyoscyamus muticus (Solanaceae). Lizards associated both olfactory and visual cues with locust unpalatability, but only gregarious-phase coloration was an effective visual warning signal. The lizards did not associate low rearing density coloration (solitarious phase) with locust toxicity. Predator learning of density-dependent warning coloration results in a marked decrease in predation on locusts and may directly contribute to outbreaks of this notorious pest.

Animals↗

The role of female accessory glands in maternal inheritance of phase in the desert locust Schistocerca gregaria.

Accessory glands of crowd-reared females of Schistocerca gregaria were ligatured from the lateral oviducts. Hatchlings resulting from egg pods laid after the treatment showed a significant shift towards solitarious behaviour as compared to hatchlings from control-treated females. Morphometric measurement of hatchlings revealed no consistent difference between ligatured and control females, however, one ratio (hind femur length/vertex width) was approaching significance. Hatchlings from eggs of crowd-reared females behaved solitariously when freshly laid eggs were washed with a saline solution. Gregarious behaviour could be restored when washed eggs were treated with a saline extract of the accessory glands. The colouration of hatchlings was not affected by any treatment. Our findings implicate the accessory glands in the production, release or activation of the recently reported gregarizing factor found in the egg pod foam [McCaffery, A.R., Simpson, S.J., Islam, M.S., Roessingh, P., 1998. A gregarizing factor present in the egg pod foam of the desert locust Schistocerca gregaria. Journal of Experimental Biology 201, 347-363].

Journal Article↗

High- and low-affinity single-peptide/MHC ligands have distinct effects on the development of mucosal CD8alphaalpha and CD8alphabeta T lymphocytes.

In this study, we compared the influence of two peptides on the selection of CD8alphaalpha and CD8alphabeta intraepithelial lymphocytes (IELs) of the intestine, which develop by a unique and partially thymus-independent process. Mice were used in which all T cells carried one transgenic T cell antigen receptor (TCR) (F5), and in which only well defined transgenic peptides were presented by H-2Db. The first peptide, for which the F5 TCR has a high affinity, derives from the influenza virus nucleoprotein (NP68). The second peptide, NP34, is an antagonistic variant of NP68 and is recognized by the F5 TCR with low affinity. To avoid presentation of endogenous peptides or production of T cells carrying alternative TCRs, F5 TCR transgenic mice were generated that were deficient for Tap-1 and Rag-1. In these mice, no CD3(+)CD8(+) cells were found in lymph nodes, spleen, or intestine. Introduction of transgenes encoding either NP34 or NP68 along with an endoplasmic reticulum signal sequence enabled Tap-1-independent expression of each peptide in these mice. Positive selection of F5TCR+CD8(+) thymocytes was not rescued by these transgenic peptides. However, the high-affinity NP68 peptide induced maturation of CD8alphaalpha IEL, whereas the low-affinity NP34 peptide stimulated development of both CD8alphabeta and CD8alphaalpha IEL, but in smaller numbers. When both peptides were present, CD8alphabeta T cells failed to develop and the number of CD8alphaalpha IELs was lower than in mice carrying the NP68 transgene alone. These data demonstrate that single ligands with a high or low affinity for TCR are capable of inducing or inhibiting the maturation of alternative subsets of IELs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Assuaging nutritional complexity: a geometrical approach.

We have introduced a framework that enables the identification of the important elements in complex nutritional systems, and the quantification of the interactions among them. These interactions include those among the multiple constituents of the ingesta, as well as between behavioural (ingestive) and physiological (post-ingestive) components of nutritional homeostasis. The resulting descriptions provide a powerful means to generate and test hypotheses concerning the mechanisms, ecology and evolution of nutritional systems. We provide an overview of the key concepts involved in our scheme, and then introduce four examples in which the framework is used to develop and test hypotheses. In the first example we use comparative methods based on a data set of 117 insect species to test a prediction about the relationship between evolving an association with bacterial endosymbionts and the composition of the optimal diet. Second, using two species of locusts (a grass specialist and a generalist), we consider the relationship between an animal's diet breadth and the decision rules employed when feeding on foods containing suboptimal protein: carbohydrate values. Third, we introduce a mathematical model that predicts the dose-response properties of gustatory systems in the context of nutritional homeostasis. Finally, we consider the interaction between tannic acid and macronutrient balance in the diet of locusts.

Animal Nutritional Physiological Phenomena↗

Spatial scales of desert locust gregarization.

Central to swarm formation in migratory locusts is a crowding-induced change from a "solitarious" to a "gregarious" phenotype. This change can occur within the lifetime of a single locust and accrues across generations. It represents an extreme example of phenotypic plasticity. We present computer simulations and a laboratory experiment that show how differences in resource distributions, conspicuous only at small spatial scales, can have significant effects on phase change at the population level; local spatial concentration of resource induces gregarization. Simulations also show that populations inhabiting a locally concentrated resource tend to change phase rapidly and synchronously in response to altered population densities. Our results show why information about the structure of resource at small spatial scales should become key components in monitoring and control strategies.

Journal Article↗

T cell-mediated pathology in two models of experimental colitis depends predominantly on the interleukin 12/Signal transducer and activator of transcription (Stat)-4 pathway, but is not conditional on interferon gamma expression by T cells.

The requirements for interleukin (IL)-12/signal transducer and activator of transcription (Stat)-4 signaling and induction of T cell-specific interferon (IFN)-gamma expression in the development of T helper cell (Th)1-type pathology were examined in two different models of experimental colitis. In each model, abnormal reconstitution of the T cell compartment in immunodeficient mice by adoptive cell transfer leads to a wasting syndrome and inflammation of the colon, induced by IFN-gamma and tumor necrosis factor (TNF)-alpha-producing T cells. We show here that treatment with anti-IL-12 antibodies in one of the models, or reconstitution with T cells from Stat-4-deficient (Stat-4(null)) mice in both models resulted in a milder disease in the majority of recipient animals, compared with those that were left untreated or that had been reconstituted with wt cells. Protected mice in each group also harbored lower frequencies of IFN-gamma-producing T cells than did diseased mice, suggesting that effects on wasting and colitis resulted from the attenuation of IFN-gamma expression by T cells. To test whether the development of pathogenic T cells in the two colitis models was directly dependent on T cell-specific IFN-gamma expression, IFN-gammanull donors were used for T cell reconstitution in each system. Surprisingly, large numbers of IFN-gammanull-reconstituted mice developed wasting and colitis, which in many cases was of comparable severity to that seen in animals reconstituted with wt cells. Furthermore, T cells from these animals expressed TNF-alpha, demonstrating that they had retained the ability to produce another proinflammatory cytokine. Taken together, these results demonstrate that in some forms of chronic experimental colitis the development of pathogenic T cells is influenced predominantly, though not exclusively, by IL-12 via the actions of Stat-4 proteins. Furthermore, our data suggest that in the models of colitis studied here the effects of IL-12/Stat-4 or other Th1 promoting pathways are not limited to the induction of IFN-gamma gene expression in T lymphocytes.

Animals↗

Both the lymphotoxin and tumor necrosis factor pathways are involved in experimental murine models of colitis.

BACKGROUND & AIMS: Membrane lymphotoxin (LT) alpha/beta, a member of the tumor necrosis factor (TNF) family of immune regulatory molecules, is involved both in the development of secondary lymphoid tissues and the maintenance of organized lymphoid tissues in the adult. Defects observed in the mucosal immune system in animals with a genetically disrupted LTalpha/beta pathway coupled with the expression of LTalpha/beta in activated T cells motivated an examination of the importance of this pathway in experimental colitis. METHODS: Soluble LTbeta receptor (LTbetaR) immunoglobulin fusion protein was used to inhibit the LTalpha/beta/light axis in two independent rodent models of colitis: CD45RBhi CD4(+)-reconstituted SCID mice and bone marrow-transplanted tg26 mice (BM --> tg26). RESULTS: Treatment with LTbetaR immunoglobulin attenuated the development of both the clinical and histological manifestations of the disease in these two murine models of colitis. Given the success of TNF inhibitors in the treatment of human Crohn's disease, the effects of LTbetaR immunoglobulin have been compared with antibody to TNF in the BM --> tg26 model, and both treatments were equally efficacious. CONCLUSIONS: The LT pathway plays a role in the development of colitis as important as that of the TNF system and, therefore, represents a potential novel intervention point for the treatment of inflammatory bowel disease.

Animals↗

Consequences of Fas-ligand and perforin expression by colon T cells in a mouse model of inflammatory bowel disease.

BACKGROUND & AIMS: We describe a type of colitis that develops after transplantation of nonallogeneic wt bone marrow cells into T cell- and natural killer cell-deficient Tg26 mice (BM-->Tg26). In these animals, severe wasting and inflammation of the colon correlates with the expansion of mucosal T lymphocytes that displays cytotoxic activity. The aims of this study were to determine the relative contribution of perforin and Fas ligand (Fas-L) expression to the cytotoxic action of these T cells and to examine the influence of each pathway in this model of colitis. METHODS: Colonic T cells were tested for their ability to mediate Fas- and perforin-dependent killing in redirected cytotoxicity assays. Bone marrow cells from donor mice lacking either Fas-L (gld mice) or perforin (PFPnull mice) or both molecules were used to reconstitute Tg26 mice. RESULTS: Colon cytotoxic T lymphocyte displayed both Fas- and perforin-dependent killing. Deficiency in perforin, but not Fas-L, resulted in reduced incidence of wasting and, to a lesser extent, severe colitis in BM-->Tg26 animals. CONCLUSIONS: Colon T cells from BM-->Tg26 mice express both perforin and Fas-L. Although neither pathway is critical in the development of colitis, perforin does have a measurable influence on disease in the BM-->Tg26 colitis model.

Animals↗