Transient changes in the pattern of food intake following a simulated time-zone transition to the east across eight time zones

Twelve healthy adults were studied, singly or in groups of up to four, in an Isolation Unit before (control days) and for 3 days after a simulated time-zone transition to the east across 8 time zones (the clock being changed from 15:00 to 23:00 h). Subjects were free to choose how to pass their waking hours (though naps were forbidden), and to eat what and when they wanted. A wide selection of food was provided, though the subjects had to prepare it. Subjects completed food intake questionnaire on waking and at 3 h intervals during the waking day. This questionnaire assessed the reasons for choosing not to eat a meal or, if a meal was eaten, the reasons for doing so, the type of meal chosen and the reasons for this choice, and subjective responses to the meal (hunger before, enjoyment during, and satiety afterwards). Subjects also recorded the incidence and degree of indigestion and jet lag at 3 h intervals after the time-zone transition. Following the time-zone transition, the subjects experienced significant amounts of jet lag and recorded a significant increase in the incidence of indigestion. They also showed significant changes in their pattern of food intake, but, whereas the patterns of food intake were no longer significantly different from control days by the third post-shift day, the symptoms of jet lag and indigestion were still present then. The distribution of daytime meals was significantly affected on the first post-shift day, with a redistribution of the times that the main, hot meals were eaten; these times indicated some influence of an unadjusted body clock. On this day also, the reasons for determining food intake continued to be dominated by hunger and appetite (hunger even increasing in the frequency with which it was cited), and the reason for not eating a meal, by a lack of hunger. On both control and post-shift days, there was a marked effect of meal type upon the responses to food intake, with cold food being rated least and large hot meals most when appetite before the meal, enjoyment during it, and satiety afterward were considered. However, evidence suggested that the degree to which larger hot meals were preferred to cold meals was significantly less marked after the time-zone transition. On control days, sleep was unbroken; whereas, after the time-zone transition, all subjects woke on at least one of the 3 nights studied. During the first post-shift night, about half of the subjects ate a meal, the reason given being that they were “hungry.” On those occasions when subjects woke but did not eat a meal, the reason cited was because they “could not be bothered” as frequently as because they were “not hungry.”. A simulated time-zone transition is associated with significant changes to the incidence of indigestion, pattern of food intake, and subjective responses to food. However, these changes are generally transient and are only weakly linked to the sensation of jet lag.     

Regime shifts between free-floating plants and phytoplankton: a review

Field studies evidence shifts between phytoplankton and free-floating plant regimes; yet, it is unclear what drives these shifts and if they are critical transitions (alternative stable states). In this review, we synthesized field and experimental data on free-floating plants (of varying size and phylogenies) and phytoplankton regimes, to assess the effects of these producers on the environment. Nutrient-rich environments promote free-floating plants dominance—regardless of life form—which causes dark and anoxic environments, and nutrient release from sediments. This reinforces free-floating plants dominance, but controls phytoplankton biomass by strong shading (despite high nutrients and low grazing). Phytoplankton dominance renders turbid and oxygen-rich (when producing) environments. We also searched for case studies of regime shifts for free-floating plants and phytoplankton dominance. Most studies showed that when free-floating plants dominance was interrupted, phytoplankton biomass (usually Cyanobacteria) rose steeply. Likewise, when phytoplankton-dominated, the development of dense mats of free-floating plants covers usually controlled phytoplankton. Field evidence that suggests critical transitions include abrupt regime transitions in time and space; yet, evidence including indoor controlled experiments and mathematical models is needed for conclusive evidence of alternative stable states to be drawn.     

Fluxes of greenhouse gases between soils and the atmosphere in a temperate forest following a simulated hurricane blowdown

Fluxes of nitrous oxide (N₂O), carbon dioxide (CO₂), and methane (CH₄) between soils and the atmosphere were measured monthly for one year in a 77-year-old temperate hardwood forest following a simulated hurricane blowdown. Emissions of CO₂ and uptake of CH₄ for the control plot were 4.92 MT C ha⁻¹ y⁻¹ and 3.87 kg C ha⁻¹ y⁻¹, respectively, and were not significantly different from the blowdown plot. Annual N₂O emissions in the control plot (0.23 kg N ha⁻¹ y⁻¹) were low and were reduced 78% by the blowdown. Net N mineralization was not affected by the blowdown. Net nitrification was greater in the blowdown than in the control, however, the absolute rate of net nitrification, as well as the proportion of mineralized N that was nitrified, remained low. Fluxes of CO₂ and CH₄ were correlated positively to soil temperature, and CH, uptake showed a negative relationship to soil moisture. Substantial resprouting and leafing out of downed or damaged trees, and increased growth of understory vegetation following the blowdown, were probably responsible for the relatively small differences in soil temperature, moisture, N availability, and net N mineralization and net nitrification between the control and blowdown plots, thus resulting in no change in CO₂ or CH₄ fluxes, and no increase in N₂O emissions.     

Amplitude reduction and phase shifts of melatonin, cortisol and other circadian rhythms after a gradual advance of sleep and light exposure in humans

Background

The phase and amplitude of rhythms in physiology and behavior are generated by circadian oscillators and entrained to the 24-h day by exposure to the light-dark cycle and feedback from the sleep-wake cycle. The extent to which the phase and amplitude of multiple rhythms are similarly affected during altered timing of light exposure and the sleep-wake cycle has not been fully characterized.

Methodology/Principal Findings

We assessed the phase and amplitude of the rhythms of melatonin, core body temperature, cortisol, alertness, performance and sleep after a perturbation of entrainment by a gradual advance of the sleep-wake schedule (10 h in 5 days) and associated light-dark cycle in 14 healthy men. The light-dark cycle consisted either of moderate intensity ‘room’ light (∼90–150 lux) or moderate light supplemented with bright light (∼10,000 lux) for 5 to 8 hours following sleep. After the advance of the sleep-wake schedule in moderate light, no significant advance of the melatonin rhythm was observed whereas, after bright light supplementation the phase advance was 8.1 h (SEM 0.7 h). Individual differences in phase shifts correlated across variables. The amplitude of the melatonin rhythm assessed under constant conditions was reduced after moderate light by 54% (17–94%) and after bright light by 52% (range 12–84%), as compared to the amplitude at baseline in the presence of a sleep-wake cycle. Individual differences in amplitude reduction of the melatonin rhythm correlated with the amplitude of body temperature, cortisol and alertness.

Conclusions/Significance

Alterations in the timing of the sleep-wake cycle and associated bright or moderate light exposure can lead to changes in phase and reduction of circadian amplitude which are consistent across multiple variables but differ between individuals. These data have implications for our understanding of circadian organization and the negative health outcomes associated with shift-work, jet-lag and exposure to artificial light.     

Biodiversity collapse and early warning indicators in a spatial phase transition between neutral and niche communities

The dynamics of ecological communities have been described by neutral and niche theories that are now increasingly integrated into unified models. It is known that a critical transition exists between these two states, but the spatial aspect of this transition has not been studied. Our aim is to study the spatial aspect of the transition and propose early warning signals to detect it. We used a stochastic, spatially explicit model that spans a continuum from neutral to niche communities, and is driven by the intensity of hierarchical competition. The transition is indicated by the emergence of a large patch formed by one species that connects the whole area. The properties of this patch can be used as early warning indicators of a critical transition. If competition intensity increases beyond the critical point, our model shows a sudden decrease of the Shannon diversity index and a gentle decline in species richness. The critical point occurs at a very low value of competitive intensity, with the rate of migration from the metacommunity greatly influencing the position of this critical point. As an example, we apply our new method of early warning indicators to the Barro Colorado Tropical forest, which, as expected, appears to be far from a critical transition. Low values of competitive intensity were also reported by previous studies for different high‐diversity real communities, suggesting that these communities are located before the critical point. A small increase of competitive interactions could push them across the transition, however, to a state in which diversity is much lower. Thus this new early warnings indicator could be used to monitor high diversity ecosystems that are still undisturbed.     

The interplay between shifts in biomass allocation and costs of reproduction in four grassland perennials under simulated successional change

When perennial herbs face the risk of being outcompeted in the course of succession, they are hypothesized to either increase their biomass allocation to flowers and seeds or to invest more in vegetative growth. We tested these hypotheses in a 3-year garden experiment with four perennials (Hypochaeris radicata, Cirsium dissectum, Succisa pratensis and Centaurea jacea) by growing them in the midst of a tall tussock-forming grass (Molinia caerulea) that may successionally replace them in their natural habitat. In all species except for the short-lived H. radicata, costs of sexual reproduction were significant over the 3 years, since continuous bud removal enhanced total biomass or rosette number. To mimic succession we added nutrients, which resulted in a tripled grass biomass and higher death rates in the shorter-lived species. The simulated succession resulted also in a number of coupled growth responses in the survivors: enhanced plant size as well as elevated seed production. The latter was partly due to larger plant sizes, but mostly due to higher reproductive allocation, which in turn could be partly explained by lower relative somatic costs and by lower root–shoot ratios in the high-nutrient plots. Our results suggest that perennial plants can increase both their persistence and their colonization ability by simultaneously increasing their vegetative size and reproductive allocation in response to enhanced competition and nutrient influxes. These responses can be very important for the survival of a species in a metapopulation context. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Measuring the successes and deficiencies of constant pH molecular dynamics: a blind prediction study

A constant pH molecular dynamics method has been used in the blind prediction of pK(a) values of titratable residues in wild type and mutated structures of the Staphylococcal nuclease (SNase) protein. The predicted values have been subsequently compared to experimental values provided by the laboratory of García-Moreno. CpHMD performs well in predicting the pK(a) of solvent-exposed residues. For residues in the protein interior, the CpHMD method encounters some difficulties in reaching convergence and predicting the pK(a) values for residues having strong interactions with neighboring residues. These results show the need to accurately and sufficiently sample conformational space in order to obtain pK(a) values consistent with experimental results.     

Ontogenetic phase shifts in metabolism: links to development and anti-predator adaptation

The allometric relationships between resting metabolism (VO₂) and body mass (M), VO₂ = a_iM^b, are considered a fundamental law of nature. A distinction though needs to be made between the ontogeny (within a species) and phylogeny (among species) of metabolism. However, the nature and significance of the intraspecific allometry (ontogeny of metabolism) have not been established in fishes. In this study, we present experimental evidence that a puffer fish ranging 0.0008–3 g in wet body mass has four distinct allometric phases in which three stepwise increases in scaling constants (a_i, i = 1–4), i.e. ontogenetic phase shifts in metabolism, occur with growth during its early life stages at around 0.002, 0.01 and 0.1 g, keeping each scaling exponent constant in each phase (b = 0.795). Three stepwise increases in a_i accompanied behavioural and morphological changes and three peaks of severe cannibalism, in which the majority of predation occurred on smaller fish that had a lower value of a_i. Though fishes are generally highly fecund, producing a large number of small eggs, their survivability is very low. These results suggest that individuals with the ability to rapidly grow and step up ‘a_i’ develop more anti-predator adaptation as a result of the decreased predatory risk.     

Olfactory cues accelerate reentrainment following phase shifts and entrain free-running rhythms in female Octodon degus (Rodentia).

Social interactions between conspecifics is a type of nonphotic zeitgeber common to several species. In the diurnal rodent Octodon degus, social interactions enhance reentrainment after phase shifts and can act as a weak zeitgeber. Olfactory stimuli appear necessary for these effects since bulbectomy eliminates socially enhanced reentrainment. In Experiment 1, the authors examined whether stimulation of the main olfactory system was sufficient to enhance reentrainment after 6-h phase advances and delays in the adult female O. degus. When test animals received conspecific odor cues during reentrainment, they entrained 39% faster after phase advances (p < 0.05) and 33% faster after phase delays (p < 0.001) than when they did not receive odor cues. Thus, olfactory cues from distant female donors were sufficient to enhance rates of entrainment in female O. degus and provided results equivalent to earlier studies with donors and shifters housed in the cages together. In Experiment 2, the authors examined whether discrete 3-h and 1-h daily pulses of airborne odors from a group of 5 entrained female degus would be sufficient to produce entrainment of wheel-running activity in adult female conspecifics. During the period of exposure to 3-h pulses, 50% (4/8) of the subjects temporarily entrained to a 24-h cycle, while 12.5% (1/8) of the subjects fully entrained. Exposure to 1-h pulses allowed 37.5% (3/8) of the subjects to temporarily entrain and 12.5% (1/8) of the subjects to fully entrain. Duration of entrained episodes was positively correlated with psi, daily onset of activity with respect to the timing of odor exposure (Pearson r = 0.731; p < 0.05), such that animals with the entraining odor pulse beginning during subjective day (psi = 7.8 h, CT 7.8 +/- 1.4) had longer periods of entrainment (22.2 +/- 5.6 days) than animals with the entraining pulse occurring during subjective night (psi = -4.6 h; CT 19.4 +/- 0.9; 5.6 +/- 0.9 days; p < 0.001). In addition, for each animal, the combined duration of all episodes of 24-h entrainment correlated with increased period length (tau) of free-running rhythms (Pearson r = 0.733; p < 0.05). Thus, daily discrete pulses of odors with durations of either 1 or 3 h from female conspecifics were sufficient to produce both temporary and full entrainment to a 24-h cycle in the majority of female O. degus, and the likelihood of long periods of entrainment correlated with long taus and coordination of the odor pulse with mid subjective day.     

Peptide differential display: a novel approach for phase transition in locusts

Today, the question of the physiological cause of phase transition, the transition from the solitary to the gregarious phase, in locusts remains unanswered. We hereby present a novel approach by which we have attempted to determine whether different phases express or release different peptides in similar physiological conditions. For this purpose, a peptidomic analysis of the corpora cardiaca and hemolymph of crowded and isolated locusts of Schistocerca gregaria was performed using high performance liquid chromatography and matrix-assisted laser desorption ionisation time of flight mass spectrometry. A comparison between the two conditions reveals differences in the number and amount of peptides present in the corpora cardiaca and the hemolymph. Further research will have to identify these phase specific differences and their role in locust phase polymorphism.     

Genomics: shifts in metaphorical landscape between 2000 and 2003

This article examines the shifts and changes in the metaphors used to describe the human genome and the human genome project (HGP) between 2000 and 2003, with the year 2001 as a trigger for genomic and metaphorical reflection. We want to answer questions, such as: Did the findings announced in 2001 shake the metaphorical foundations on which the HGP had been built or not? Did novel metaphors capture the imagination of scientists and the public or did old metaphors survive throughout this period? What influence does the continuity or discontinuity in metaphorical framing of the HGP have on the public perception of the HGP as well as on its scientific understanding? To answer these questions we have systematically compared the metaphors used in one major scientific journal, Nature, and in one major UK newspaper, the online edition of the Guardian/The Observer during a period of two months around June 2000, February 2001 and April 2003.     

Genomics: shifts in metaphorical landscape between 2000 and 2003

Modern biotechnology has been characterized by being surrounded by scientific and public debate and by interest conflicts. An early Danish debate and regulation has been criticized for inhibiting or retarding development and thus growth. Though much regulation and debate have been transferred to the European arena, their role and extension are still an issue. In this paper, the often anticipated innovation-inhibiting effects of regulation are questioned by giving an account of regulations and debates in Denmark. An account which includes the shifting positions of industry, the research community, environmental groups, regulators and other interest groups. The paper indicates that the regulatory measures, introduced as a response to public and interest group critique, have generally reduced industrial uncertainty and promoted industrial Danish biotechnology development. It is further found that regulation and debate changed the rate and direction of new biotechnology development, contributing to technology acceptance, without however ensuring it. The paper thus questions the caricatured assumptions in economics and industrial policy that regulation restrict techno-economic growth. The paper further states regulation and controversies to have contributed actively to the specific technology development, but also states the difficulties in setting radically different technology development agendas.     

Intrinsic period and light intensity determine the phase relationship between melatonin and sleep in humans

The internal circadian clock and sleep-wake homeostasis regulate the timing of human brain function, physiology, and behavior so that wakefulness and its associated functions are optimal during the solar day and that sleep and its related functions are optimal at night. The maintenance of a normal phase relationship between the internal circadian clock, sleep-wake homeostasis, and the light-dark cycle is crucial for optimal neurobehavioral and physiological function. Here, the authors show that the phase relationship between these factors-the phase angle of entrainment (psi)-is strongly determined by the intrinsic period (tau) of the master circadian clock and the strength of the circadian synchronizer. Melatonin was used as a marker of internal biological time, and circadian period was estimated during a forced desynchrony protocol. The authors observed relationships between the phase angle of entrainment and intrinsic period after exposure to scheduled habitual wakefulness-sleep light-dark cycle conditions inside and outside of the laboratory. Individuals with shorter circadian periods initiated sleep and awakened at a later biological time than did individuals with longer circadian periods. The authors also observed that light exposure history influenced the phase angle of entrainment such that phase angle was shorter following exposure to a moderate bright light (approximately 450 lux)-dark/wakefulness-sleep schedule for 5 days than exposure to the equivalent of an indoor daytime light (approximately 150 lux)-dark/wakefulness-sleep schedule for 2 days. These findings demonstrate that neurobiological and environmental factors interact to regulate the phase angle of entrainment in humans. This finding has important implications for understanding physiological organization by the brain's master circadian clock and may have implications for understanding mechanisms underlying circadian sleep disorders.     

Measuring distances between TRPV1 and the plasma membrane using a noncanonical amino acid and transition metal ion FRET

Despite recent advances, the structure and dynamics of membrane proteins in cell membranes remain elusive. We implemented transition metal ion fluorescence resonance energy transfer (tmFRET) to measure distances between sites on the N-terminal ankyrin repeat domains (ARDs) of the pain-transducing ion channel TRPV1 and the intracellular surface of the plasma membrane. To preserve the native context, we used unroofed cells, and to specifically label sites in TRPV1, we incorporated a fluorescent, noncanonical amino acid, L-ANAP. A metal chelating lipid was used to decorate the plasma membrane with high-density/high-affinity metal-binding sites. The fluorescence resonance energy transfer (FRET) efficiencies between L-ANAP in TRPV1 and Co²⁺ bound to the plasma membrane were consistent with the arrangement of the ARDs in recent cryoelectron microscopy structures of TRPV1. No change in tmFRET was observed with the TRPV1 agonist capsaicin. These results demonstrate the power of tmFRET for measuring structure and rearrangements of membrane proteins relative to the cell membrane.     

Interplay between humans and infective agents: a population genetic study

The genetic composition of present day human populations is determined largely by the interaction between the human host and infective agents. Therefore, theoretical analysis of the host-infective-agent system is required in order for us to be able to understand human evolution. Classical population genetics has been confined largely to analysing the interplay of various mechanisms, such as selection, mutation and drift, in one species at a time. Unfortunately, there have been few studies of such interactive systems. In the present investigation, these studies have been enlarged, with problems of human genetics in mind, by mathematical examination of a model in which a diploid host with three alleles interacts with a haploid infective agent with two alleles. The results are compared with those obtained from simpler models analysed in the past. The assumptions inherent in such “gene for gene” models and our results are discussed. An increase in the number of alleles appears to enhance the chances for the establishment of permanent genetic polymorphisms, improving genetic “elasticity” of a population for coping with changing challenges by various infective agents. Interaction between two haploid species leads to a loss of polymorphism in both of them and, hence, to a severe loss of evolutionary elasticity. The hypothesis that the evolution of diploidy might have been favoured by a selective advantage of diploid organisms interacting with environmental challenges, such as infective agents, is supported. Received: 6 October 1997 / Accepted: 26 November 1997     

Presynaptic inhibition in humans: a comparison between normal and spastic patients.

During the last 40 years, several studies in man have been devoted to the pathophysiological mechanisms underlying spasticity. Spasticity is characterised by a velocity dependent increase in muscle tone. Many spinal pathways control stretch reflex excitability and a malfunction in any one of them could theoretically produce the exaggeration of the stretch reflex. Delwaide showed that the vibration-induced inhibition of Ia fibres is reduced in spastic patients. However, the relation between a decrease in presynaptic Ia inhibition and the pathophysiology of spasticity has been recently questioned since it was argued that homosynaptic depression (or post-activation depression) also contributes to the vibratory-induced depression of monosynaptic reflexes. This paper is thus devoted to a review of the methods recently developed to study selectively presynaptic Ia inhibition in man and to a reevaluation of the relations between modifications in presynaptic Ia inhibition and spasticity in hemiplegic and spinal spastic patients.     

Acute and subacute toxicity of chemotactic conjugates between monoclonal antibody and fMet-Leu-Phe in humans: A phase I clinical trial

Summary Conjugates of the chemotactic peptide fMet-Leu-Phe (fMLP) to IgG retain chemotactic and antigen recognition function in vitro and enhance intra-tumour macrophage numbers in a guinea pig model. We report a study approved by the ethics committee on the acute toxicity of fMLP conjugates in ten consenting cancer patients with metastasizing melanoma and colon cancer. They were given increasing single doses (1–2500 µg) IgG-fMLP made with the anti-melanoma monoclonal antibody (mAb) 9.2.27. Clinical examinations and blood cell counts, urinalysis, electrolytes, and liver and kidney function tests before and after the infusion and weekly thereafter revealed no relevant toxicities. One patient had a herpes zooster exacerbation on day 1, which was judged to be coincidental. Peak post-infusion conjugate serum concentrations fell to unmeasurable levels within a few days. In no case was a human humoral anti-(mouse Ig) immune response detected.This work was supported by grant FOR.254.AK.83 of the Swiss Cancer League.     

An ionotropic phase transition in phosphatidylcholine: cation and anion cooperativity

Evidence is presented for cooperative interaction between cations and anions specifically bound to dimyristoylphosphatidylcholine (DMPC). The cooperativity is with regard to an ion-induced (ionotropic) phase transition for the lipid and is signalled by a change in the luminescence from bound Tb3+. The intrinsic binding of Tb3+ to DMPC was determined from equilibrium dialysis experiments, using conventional methods to correct for electrostatic contributions. Preliminary results demonstrate great potential for infrared spectroscopy as a means to relate these Tb3+ luminescence studies to experiments involving less tractable cations. This work provides insight into the role of bound ions in modifying lateral phase behavior in phospholipid membranes.     

Measuring endothelial glycocalyx dimensions in humans: a potential novel tool to monitor vascular vulnerability.

The endothelial glycocalyx is increasingly considered as an intravascular compartment that protects the vessel wall against pathogenic insults. The purpose of this study was to translate an established experimental method of estimating capillary glycocalyx dimension into a clinically useful tool and to assess its reproducibility in humans. We first evaluated by intravital microscopy the relation between the distance between the endothelium and erythrocytes, as a measure of glycocalyx thickness, and the transient widening of the erythrocyte column on glycocalyx compression by passing leukocytes in hamster cremaster muscle capillaries. We subsequently assessed sublingual microvascular glycocalyx thickness in 24 healthy men using orthogonal polarization spectral imaging. In parallel, systemic glycocalyx volume (using a previously published tracer dilution technique) as well as cardiovascular risk profiles were assessed. Estimates of microvascular glycocalyx dimension from the transient erythrocyte widening correlated well with the size of the erythrocyte-endothelium gap (r = 0.63). Measurements in humans were reproducible (0.58 +/- 0.16 and 0.53 +/- 0.15 microm, coefficient of variance 15 +/- 5%). In univariate analysis, microvascular glycocalyx thickness significantly correlated with systemic glycocalyx volume (r = 0.45), fasting plasma glucose (r = 0.43), and high-density lipoprotein-cholesterol (r = 0.40) and correlated negatively with low-density lipoprotein-cholesterol (r = -0.41) as well as body mass index (r = -0.45) (all P < 0.05). In conclusion, the dimension of the endothelial glycocalyx can be measured reproducibly in humans and is related to cardiovascular risk factors. It remains to be tested whether glycocalyx dimension can be used as an early marker of vascular damage and whether therapies aimed at glycocalyx repair can protect the vasculature against pathogenic challenges.