Changes in food neophobia and dietary habits of international students.

BACKGROUND: International study is becoming more prevalent, yet aspects such as food neophobia often militate against visiting students consuming a nutritionally balanced diet. The present study aimed to evaluate the extent to which international post-graduate students experience food neophobia, how this might vary by nationality and other demographic characteristics, and how acculturation might manifest itself in students' dietary behaviour. METHODS: International students (n = 228) attending a Masters course were invited to complete a validated food neophobia and dietary habits questionnaire during their first week at university. The questionnaire was subsequently re-administered to the same students approximately 4 and 8 months later. RESULTS: In total, 226 usable responses were analysed (124, 58 and 44, respectively) for the first, second and final data collection. Perhaps surprisingly, the overall food neophobia scores increased from an mean (SD) initial value of 27.95 (16.95) to 33.67 (33.67) after 3 months, although, when comparing European and Asian students, only the former were significantly different (P < 0.05). Both Asian and European students reported small but not significant changes in their eating habits, although, after 3 months, significantly (P = <0.05) fewer changes were reported. No significant changes were reported in students' perceived healthiness of their diets either by nationality or over time. CONCLUSIONS: Understanding the complexities of food neophobia, other aspects of dietary change and at what point these changes might take place in the acculturation process when students arrive in the UK needs to be fully understood if a climate for positive learning is to be established.

Neural regeneration: delayed formation of central contacts by insect sensory cells.

Correlated anatomical and electrophysiological results demonstrate that sensory neurons, which differentiate de novo within the epidermis of regenerate abdominal cerci of crickets, enter the terminal ganglion and form functional central connections even when regeneration of the cerci is delayed through the greater part of postembryonic development. Stimulation of regenerate cerci evokes activity in giant interneurons which is normal by several physiological criteria.

Fetal movement: development and time course.

Prenatal behavior develops in three phases: early rates, acceleration and maintenance, and deceleration to birth. Fetal activity occurs as discrete movements, bursts of activity, and prolonged activity. Four-hour samples were most representative of the daily rates of movement.

Metabolic modeling of microbial strains in silico.

The large volume of genome-scale data that is being produced and made available in databases on the World Wide Web is demanding the development of integrated mathematical models of cellular processes. The analysis of reconstructed metabolic networks as systems leads to the development of an in silico or computer representation of collections of cellular metabolic constituents, their interactions and their integrated function as a whole. The use of quantitative analysis methods to generate testable hypotheses and drive experimentation at a whole-genome level signals the advent of a systemic modeling approach to cellular and molecular biology.

In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data.

A significant goal in the post-genome era is to relate the annotated genome sequence to the physiological functions of a cell. Working from the annotated genome sequence, as well as biochemical and physiological information, it is possible to reconstruct complete metabolic networks. Furthermore, computational methods have been developed to interpret and predict the optimal performance of a metabolic network under a range of growth conditions. We have tested the hypothesis that Escherichia coli uses its metabolism to grow at a maximal rate using the E. coli MG1655 metabolic reconstruction. Based on this hypothesis, we formulated experiments that describe the quantitative relationship between a primary carbon source (acetate or succinate) uptake rate, oxygen uptake rate, and maximal cellular growth rate. We found that the experimental data were consistent with the stated hypothesis, namely that the E. coli metabolic network is optimized to maximize growth under the experimental conditions considered. This study thus demonstrates how the combination of in silico and experimental biology can be used to obtain a quantitative genotype-phenotype relationship for metabolism in bacterial cells.

Sea-level performance in runners using altitude tents: a field study.

In this study of effects of simulated altitude exposure on sea-level performance, 10 competitive runners slept in a hypoxic environment achieved with tents for 9.8+/-1.3 h.d(-1) (mean+/-standard deviation) for 24 days-30 days at 2500-3500 m (PIO2=117-103 mmHg) above sea level. The altitude group and a control group of 10 runners performed usual training (PIO2=149 mmHg). At approximately 4-wk intervals before and after exposure both groups performed an incremental test for lactate threshold. The altitude group performed an additional test, a treadmill run to exhaustion lasting approximately 5 min. One week following exposure lactate threshold speed of the altitude group relative to the control group increased by 1.2% (90% likely limits +/-3.1%), but the effect became slightly negative after controlling for baseline differences in running speed between the groups. A 16% increase in time to exhaustion was observed in the altitude group, equivalent to a 1.9% (+/-1.4%) increase in speed in a time trial. Change in performance had an unclear relationship to total altitude exposure, genotype for angiotensin converting enzyme, and change in haemoglobin concentration. Our findings are consistent with little or no effect of use of altitude tents on sea-level performance.

Sir Vincent Wigglesworth and the coming of age of insect development.

Sir Vincent Wigglesworth (1899-1994), a founder of the discipline of Insect Physiology, was a central figure in the emergence of the concept of postembryonic insect development as sequential polymorphism regulated by endocrine signals. At a time in mid-century when genetics and developmental physiology were severely compartmentalized, he made the conceptual linkage with the recognition that sequential polymorphism must have a genetic basis with gene activation regulated by internal signals.

Metabolic flux balance analysis and the in silico analysis of Escherichia coli K-12 gene deletions.

BACKGROUND: Genome sequencing and bioinformatics are producing detailed lists of the molecular components contained in many prokaryotic organisms. From this 'parts catalogue' of a microbial cell, in silico representations of integrated metabolic functions can be constructed and analyzed using flux balance analysis (FBA). FBA is particularly well-suited to study metabolic networks based on genomic, biochemical, and strain specific information. RESULTS: Herein, we have utilized FBA to interpret and analyze the metabolic capabilities of Escherichia coli. We have computationally mapped the metabolic capabilities of E. coli using FBA and examined the optimal utilization of the E. coli metabolic pathways as a function of environmental variables. We have used an in silico analysis to identify seven gene products of central metabolism (glycolysis, pentose phosphate pathway, TCA cycle, electron transport system) essential for aerobic growth of E. coli on glucose minimal media, and 15 gene products essential for anaerobic growth on glucose minimal media. The in silico tpi-, zwf, and pta- mutant strains were examined in more detail by mapping the capabilities of these in silico isogenic strains. CONCLUSIONS: We found that computational models of E. coli metabolism based on physicochemical constraints can be used to interpret mutant behavior. These in silica results lead to a further understanding of the complex genotype-phenotype relation.

Thromboxane A2 receptor antagonism and synthase inhibition in essential hypertension.

Short-term effects of ridogrel, a combined thromboxane synthase inhibitor and receptor antagonist, were investigated in 16 patients with uncomplicated essential hypertension. After a 2-week placebo period without antihypertensive medication, patients were admitted to the hospital overnight on two occasions 3 weeks apart. On each occasion, they received two doses of either placebo or ridogrel (300 mg) 12 hours apart according to a double-blind crossover protocol. Renal and systemic thromboxane A2 and prostacyclin biosynthesis were investigated by measuring urinary excretion of thromboxane B2, 6-oxo-prostaglandin F1 alpha, and their respective 2,3-dinor metabolites using gas chromatography/mass spectrometry. Responses of platelets to a thromboxane A2 mimetic and to adenosine diphosphate were studied turbidometrically. Blood pressure was measured automatically at 20-minute intervals. Ridogrel reduced excretion of 2,3-dinor-thromboxane B2 and thromboxane B2 compared with placebo (21 +/- 6 versus 279 +/- 28 and 14 +/- 4 versus 39 +/- 9 ng/g creatinine, respectively; P < .0001 and P < .05). Excretion of 2,3-dinor-6-oxoprostaglandin F1 alpha and 6-oxoprostaglandin F1 alpha was increased by ridogrel compared with placebo (184 +/- 20 versus 146 +/- 11 and 86 +/- 9 versus 58 +/- 6 ng/g creatinine, respectively; P < .05). Ridogrel selectively antagonized platelet aggregation to the thromboxane mimetic (P < .0001). Blood pressure did not differ significantly between ridogrel and placebo treatment periods. Thus, in patients with essential hypertension, acute administration of ridogrel reduces renal and extrarenal thromboxane A2 biosynthesis, increases renal and extrarenal prostacyclin biosynthesis, inhibits thromboxane receptor-activated platelet aggregation, but has no effect on systemic arterial pressure.

Mechanosensory appendages and giant interneurons in the firebrat (Thermobia domestica, Thysanura): a prototype system for terrestrial predator evasion.

Aspects of the structure and function of the abdominal cerci and caudal filament sensory systems, and associated giant interneurons of the thysanuran insect Thermobia domestica, the firebrat, extend comparative studies of a widespread predator evasion system. All elements of the cercal system, which is well known from diverse orthopteroid insects, are present in the primitively wingless thysanuran. In addition, a median terminal sensory appendage, the caudal filament, projects to the same general regions of the terminal ganglion but shows limited overlap of synaptic regions with cercal input. A segmental series of giant interneurons appears to be homologous with those of the orthopteroid insects. The cercal system, which may have evolved with the first terrestrial hexapods, reaches its zenith in the orthopteroid insects, but was replaced in holometabolan insects by visual startle mechanisms with descending giant interneurons.

The differentiation between neuroglia and connective tissue sheath in insect ganglia revisited: the neural lamella and perineurial sheath cells are absent in a mesodermless mutant of Drosophila.

Two morphogenetic mutations, twist and Delta, that affect the embryonic development of Drosophila in known ways were used to examine the derivation and function of the outer layers of the central nervous system (CNS). Both the extracellular neural lamella, which ensheaths the CNS, and its source, the underlying perineurial sheath cell layer, fail to develop in Drosophila embryos that are homozygous for a loss of function mutation in the twist gene, and which thus lack mesodermal derivatives. The cell layer immediately below the perineurial sheath cells, here termed barrier glial cells, constitute the ion permeability barrier in wild-type embryos. They are present in twist mutant embryos, appear to be normal at the ultrastructural level, and function as a blood-brain ion barrier. The apparent derivation of perineurial sheath cells from mesodermal precursors distinguishes them from neurons, glia and other nonneural components of the CNS, such as tracheae, all of which are of ectodermal origin. We confirm Scharrer's interpretation of the relationship between the perineurium and underlying neuroglia. In embryos homozygous for the neurogenic mutant Delta, an embryonic lethal in which excess ventral blastoderm gives rise to neuroblasts, the CNS forms as an amorphous cell mass, with discontinuous perineurial sheath and barrier glial cell layers. We propose that the cell mass is permeable to lanthanum ions and fails to form a blood-brain barrier because volume growth prevents the formation of continuous surface cell layers.

Deafferentation slows the growth of specific dendrites of identified giant interneurons.

The effect deafferentation has on the morphology of giant interneurons was studied in the abdominal nervous system of crickets (Acheta domesticus). The morphology of four uniquely identified giant interneurons was exxamined by iontophoresing cobalt chloride into the neurons of interest. A major source of afferents for these interneurons consists of mechanoreceptors located on paired abdominal sensory appendages -- the cerci. Partial deafferentation of the giant interneurons was obtained by pinching off the cercus at hatching and maintaing the specimen in this deprived condition until adulthood. The interneurons of three groups of animals were examined; control specimens which were not treated surgically, unilaterally treated specimens which had a single cercus removed and bilaterally treated specimens which had both cerci removed. Two types of morphological changes were detected. (1) Chronic removal of a cercus was correlated with a reduction in length of dendrites ipsilateral to the ablated cercus; however, the general form of the dendritic branching pattern remained constant and recognizable. Two dendrites of a single neuron could be influenced independently if they were innervated by separate cerci. Thus deprivation did not have a generalized effect on growth of a neuron, rather it specifically influenced the dendrites deprived of afferents. (2) It was also observed that the projection of cercal sensory fibers in specimens reared with a single cercus differed from normal in that scattered fibers cross the midline in regions of the ganglion where none usually exist. It is suggested that modifications in the response properties of these deprived neurons are based on these two changes in morphology.

Neurogenesis in adult insect mushroom bodies.

The occurrence of neurogenesis in mushroom bodies of adult insects belonging to several orthopteroid and coleopteran families is described. Using injections of 5-bromo, T2'-deoxyuridine, we showed that neuroblasts, which are progenitors of Kenyon cells during preimaginal instars, continue to divide in adult Acheta domesticus. Their progeny constitute a central column in mushroom body cortices of 3-week-old females. Other Gryllidae, Gryllus bimaculatus and Gryllomorpha dalmatina, show the same pattern of neuroblast activity and migration of their progeny. Immunocytochemical staining of glial cells failed to reveal any immunoreactivity, either in proliferating regions or in the resulting cells. In another orthopteran, Locusta migratoria, discrete clusters of cells, located dorsolateral to the Kenyon cells, incorporated 5-bromo, 2'-deoxyuridine, but we could not detect any neuronal progeny migrating to the mushroom body cortices. These cells were strongly labeled with an antiglial antibody, indicating that the replicating cells are glioblasts rather than neuroblasts. In Periplaneta americana (Dictyoptera), cells replicating their DNA were similarly shown to immunoreact with glial antibodies. In contrast, three coleopterans (Tenebrio molitor, Zophobas species, Harmonia axyridis) have two large neuroblasts located in the middle of the mushroom body cortices. These produce cells which migrate within the group of Kenyon cells, their nuclei having the same shape and size as those of surrounding Kenyon cells. In adult insects, neurogenesis in mushroom bodies occurs in Gryllidae and several coleopteran families, but could not be demonstrated in Dictyoptera and Acrididae. Its occurrence and distribution raise the issue of unexpected plasticity in the adult insect brain.

Inhibition by nitroprusside of platelet calcium mobilization: evidence for reduced sensitivity to nitric oxide in essential hypertension.

OBJECTIVE: Although platelets from patients with moderate hypertension are abnormally sensitive to agonist-induced aggregation, their sensitivity to antagonists is not known. Nitric oxide (NO) is an endogenous antagonist of platelet function. The objective of this study was to determine whether platelet sensitivity to the inhibitory activity of sodium nitroprusside, a donor of NO, is abnormal in hypertension. DESIGN AND METHODS: Untreated patients with uncomplicated essential hypertension (mean arterial pressure > 120 mmHg) were studied. The rise in cytosolic calcium in response to 9,11-deoxy-11 alpha, 9 alpha-epoxymethanoprostaglandin F2 alpha (U46619, a thromboxane mimetic) was measured in fura-2-loaded platelets from 20 patients and 15 normotensive healthy subjects. Inhibition by sodium nitroprusside was measured in a further group of 14 patients and 20 normotensive subjects. RESULTS: Basal cytosolic calcium concentration and the rise in this parameter induced by U46619 were significantly greater in platelets from hypertensive patients than in those from normotensive controls. The mean half-maximal inhibitory concentration of nitroprusside to calcium mobilization induced by 3 mumol/l U46619 was 3.1-fold greater in platelets from hypertensive patients than in those from controls (95% confidence interval 1.6-6.0). CONCLUSION: The sensitivity of platelets to nitroprusside is reduced in essential hypertension. This reduced sensitivity to NO might influence the risk of arterial thrombosis in hypertensives.

Effect of cytoplasmic pH on Ca(2+)-stimulated eicosanoid biosynthesis in human platelets.

1. We have investigated the effect of cytoplasmic pH (pHi) on the relationship between platelet cytoplasmic Ca2+ concentration ([Ca2+]i) and eicosanoid biosynthesis. Stirred gel-filtered human platelets loaded with fluorescent indicators of Ca2+ and H+ were suspended in balanced salt solutions at 37 degrees C. [Ca2+]i was controlled by calcium ionophore (ionomycin). Increased [Ca2+]i was associated with increased production of thromboxane A2 (TXA2) as determined by radioimmunoassay of its stable hydrolysis product TXB2, and of 12-hydroxy eicosatetraenoic acid (12-HETE) measured by high performance liquid chromatography. 2. Varying pHi with a K+/H+ ionophore (nigericin) in platelets suspended in K+ rich solutions of pH 6.8, 7.4 or 7.8 with subsequent resuspension in solution of pH 7.4 containing albumin (1 g l-1) and Ca2+ (1 mM) resulted in pHi of 6.72 +/- 0.05, 7.31 +/- 0.02 and 7.71 +/- 0.04 (mean +/- s.e. mean, n = 5). Ionomycin (1.2 microM) increased [Ca2+]i by 97.1 +/- 17.6, 191.9 +/- 48.7 and 322.8 +/- 55.7 nM at the different values of pHi respectively; TXB2 production was 0.7 +/- 0.2, 2.1 +/- 0.4 and 10.7 +/- 3.3 ng micrograms-1 protein, and 12-HETE production was 150.9 +/- 68.2, 184.4 +/- 77.9 and 302.3 +/- 62.8 ng micrograms-1 protein. 3. Ammonium chloride (50 mM) caused a small reduction in pHo while increasing pHi from 7.32 +/- 0.04 to 7.89 +/- 0.05 and increasing ionomycin (1.2 microM)-induced [Ca2+]i responses from 94.1 +/- 67.3 to 721.6 +/- 288.3 nM. TXB2 production increased from 3.1 +/- 2.1 to 17.3 +/- 8.2 and 12-HETE production increased from 100.5 +/- 26.7 to 203.2 +/- 36.4 ng microg-1 protein. Responses of [Ca2+]i and TXB2 production to epoxymethano prostaglandin H2 (U46619, an endoperoxide-thromboxane receptor agonist) increased significantly in the presence of NH4C1.4. Alterations of pHi (such as may occur under pathological conditions) influence [Ca2+]i responses and eicosanoid synthesis in human platelets.

Intestinal carbohydrate absorption and permeability at high altitude (5,730 m).

To investigate the effects of high altitude on intestinal function, the absorption and permeation of nonmetabolizable carbohydrates were measured in 14 volunteers (median age 21 yr, range 19-37 yr) at sea level in Oxford, UK; at 1,050 m in Nepal; at 5,570 m after 5 days at > 5,500 m; and at 5,730 m after 11 days at > 5,500 m. Body weight decreased 5.7 +/- 1.19 kg from sea level to 5,570 m (P < 0.001 by paired t test) despite 72-h dietary records showing no change in energy intake. Absorption of carbohydrates by mediated transport was measured by urinary xylose and 3-O-methyl-D-glucose excretion. Xylose excretion (%oral dose) decreased from 31.4 +/- 4.5% to 20.7 +/- 4.5% (P < 0.001) and 3-O-methyl-D-glucose excretion decreased from 39.7 +/- 6.1 to 33.7 +/- 7.0% (P = 0.003) from sea level to 5,730 m. Monosaccharide permeation measured by L-rhamnose excretion decreased from 11.3 +/- 2.5 to 6.2 +/- 2.0% (P = 0.001). Intestinal permeability, a measure of barrier function (ratio of lactulose to L-rhamnose), increased from 0.036 +/- 0.014 at sea level to 0.084 +/- 0.042 at 1,050 m (P = 0.006), possibly due to infective enteropathy after arrival in Nepal, but reverted to normal (0.045 +/- 0.013; P = 0.062) at 5,730 m. Absorption of all carbohydrates returned to normal after return to the UK. This study showed that a decrease in mediated (D-xylose or 3-O-methyl-D-glucose) and diffusional (L-rhamnose) monosaccharide absorption occurs at high altitude but that intestinal permeability at 5,730 m is unchanged.

The effect of age and liver disease on the pharmacokinetics of the calcium antagonist, nisoldipine.

Two studies were performed-one in elderly, hypertensive patients and one in patients with chronic liver disease-to investigate the effect of age and liver disease upon the pharmacokinetics of nisoldipine, a dihydropyridine-type calcium antagonist. The effect of acute and chronic administration of nisoldipine (once and twice daily) was investigated in 17 elderly hypertensive patients. Compared with previously published data from young healthy volunteers, the values for Cmax and AUC appear to be higher in elderly hypertensive patients while Tmax and half-life were unchanged. Nisoldipine significantly reduced both systolic and diastolic blood pressure when given acutely to elderly hypertensive patients. Major alterations in the pharmacokinetics of nisoldipine were found in 7 patients with chronic liver disease when compared with the elderly hypertensives and healthy volunteers. The values for AUC, Cmax, half-life and volume of distribution were all higher than expected from the volunteer data while clearance was lower. One patient receiving primidone had very low nisoldipine levels, suggesting that the concomitant administration of agents that may induce the metabolism of nisoldipine should be discouraged. Nevertheless, comparisons of nisoldipine plasma levels after acute and chronic administration showed no evidence of any accumulation in either patient population in the doses used. The drug was generally well tolerated although 1 patient with chronic liver disease was withdrawn due to fluid retention.

Robustness analysis of the Escherichia coli metabolic network.

Genomic, biochemical, and strain-specific data can be assembled to define an in silico representation of the metabolic network for a select group of single cellular organisms. Flux-balance analysis and phenotypic phase planes derived therefrom have been developed and applied to analyze the metabolic capabilities and characteristics of Escherichia coli K-12. These analyses have shown the existence of seven essential reactions in the central metabolic pathways (glycolysis, pentose phosphate pathway, tricarboxylic acid cycle) for the growth in glucose minimal media. The corresponding seven gene products can be grouped into three categories: (1) pentose phosphate pathway genes, (2) three-carbon glycolytic genes, and (3) tricarboxylic acid cycle genes. Here we develop a procedure that calculates the sensitivity of optimal cellular growth to altered flux levels of these essential gene products. The results indicate that the E. coli metabolic network is robust with respect to the flux levels of these enzymes. The metabolic flux in the transketolase and the tricarboxylic acid cycle reactions can be reduced to 15% and 19%, respectively, of the optimal value without significantly influencing the optimal growth flux. The metabolic network also exhibited robustness with respect to the ribose-5-phosphate isomerase, and the ribose-5-phosephate isomerase flux was reduced to 28% of the optimal value without significantly effecting the optimal growth flux. The metabolic network exhibited limited robustness to the three-carbon glycolytic fluxes both increased and decreased. The development presented another dimension to the use of FBA to study the capabilities of metabolic networks.