Breathing with your belly: Abdominal exhalation,loco-ventilatory integration and size constraints on locomotion in small mammals

In mammals, diaphragmatic contractions control inhalation while contraction of some thoracic hypaxial muscles and the transversus abdominis muscle contribute to exhalation. Additional thoracic hypaxial muscles are recruited as accessory ventilatory muscles to improve inhalation and exhalation during locomotion. However, the contribution of abdominal hypaxial muscles to resting and locomotor ventilation is little understood in mammals and loco-ventilatory integration has not been studied in small basal mammals. We show for the first time that all of the abdominal hypaxial muscles actively contribute to both resting and locomotory ventilation in mammals but in a size-dependent manner. In large opossums (Didelphis), hypaxial muscles exhibit uniform mild tonus during resting ventilation (pressurizing the gut to aid in exhalation) and shift to phasic bursts of activity during each exhalation during locomotion. Smaller opossums (Monodelphis) actively exhale by firing the abdominal hypaxial muscles at ～10 Hz at both rest and at preferred locomotor speeds. Furthermore, the large opossums entrained ventilation to limb cycling as speed increased while the small opossums entrained limb cycling to the resting ventilation rate during locomotion. Differences in these species are related to size effects on the natural frequency of the ventilatory system and increasing resting ventilation rates at small size. Large mammals, with lower resting ventilation rates, can increase ventilatory rates during locomotion, while the high resting ventilation rates of small mammals limits their ability to increase ventilation rates during locomotion. We propose that increase in mammalian body size during the Cenozoic may have been an adaptation or exaptation to overcome size effects on ventilation frequency.     

HEART RATE AND ELECTROCARDIOGRAM CHARACTERISTICS OF A YOUNG CALIFORNIA GRAY WHALE (ESCHRICHTIUS ROBUSTUS)1

Electrocardiogram (ECG) analyses of Holter monitor recordings from a young California gray whale were performed to determine ECG waveform characteristics, evaluate the heart rate pattern for sinus arrhythmia, obtain resting heart rates at known body masses as the whale increased in size, and compare those heart rates with predicted heart rates from allometric equations. The PR and QRS intervals (475 ± 35 msec, 208 ± 24 msec, respectively, n= 20) support the concept (Meijler et al. 1992) that atrioventricular transmission and ventricular excitation times do not increase linearly in very large mammals. A sinus arrhythmia pattern at rest (apneic heart rates of 15–25 beats per min [bpm] and eupneic heart rates of 34–40 bpm) is consistent with a relative eupneic tachycardia and apneic bradycardia during diving activity of whales. The heart rate-body mass measurements (35–24 bpm at body masses of 3,591-8,200 kg) in this study (1) extend the range of allometric heart rate and body mass data in mammals a full order of magnitude, to almost 10,000 kg, (2) support the use of allometric equations (based primarily on mammals <1,000 kg in body mass) in estimating resting heart rates in whales, and (3) demonstrate that previously reported heart rates in large whales are not representative of resting heart rate, probably secondary to circumstances during measurement.     

Temperature effects on metabolic rate and cardiorespiratory physiology of the spiny rock lobster (Jasus edwardsii) during rest,emersion and recovery

Although spiny rock lobster (Jasus edwardsii) is a wholly sub-littoral species, they show a considerable ability to survive prolonged emersion, a fact exploited during the commercial export of this species. Yet, despite this remarkable hardiness, basic information on how this species responds physiologically to emersion is somewhat lacking. Using flow-through respirometry and electrophysiological techniques, we identified that J. edwardsii undergoes marked physiological changes during rest, emersion and recovery over a broad range of temperatures (3.7–17.8 °C). Under resting conditions, routine metabolic rates (RMR) were 22.57 ± 2.39, 9.69 ± 0.55 and 8.09 ± 0.27 mL O₂ h^?1, average heart rates (Hr) were 54.72 ± 4.46, 37.68 ± 2.86 and 29.67 ± 0.59 BPM, and ventilation frequencies were 83.71 ± 5.86, 45.34 ± 2.91 and 41.62 ± 0.65 BPM at 15.0, 7.5 and 3.7 °C, respectively. Notably, the surgical implantation of electrodes elevated RMR compared with non-surgical treatments. In surgery and non-surgery groups, Q ₁₀ was calculated to be ca. 3.0. Upon emersion, rate of oxygen consumption and Hr decreased below resting rates in a temperature-dependent manner, but, along with rate of CO₂ production, increased steadily during 24-h emersion. Ventilation frequencies upon emersion showed a contrasting response and increased significantly above resting rates. When returned to flow-through sea water for recovery, elevated respiration rates provided clear evidence of an O₂ debt, and near-complete recovery was observed after 17 h at both 15.0 and 7.5 °C, but close to no debt was recovered at 3.7 °C. In addition, J. edwardsii was observed to undergo marked diurnal and periodic ventilation cycles, characterised by synchronous changes in RMR, Hr and ventilation frequency.     

Agrobacterium-mediated high-frequency transformation of an elite commercial maize (Zea mays L.) inbred line

Key message

An improved Agrobacterium -mediated transformation protocol is described for a recalcitrant commercial maize elite inbred with optimized media modifications and AGL1. These improvements can be applied to other commercial inbreds.

Abstract

This study describes a significantly improved Agrobacterium-mediated transformation protocol in a recalcitrant commercial maize elite inbred, PHR03, using optimal co-cultivation, resting and selection media. The use of green regenerative tissue medium components, high copper and 6-benzylaminopurine, in resting and selection media dramatically increased the transformation frequency. The use of glucose in resting medium further increased transformation frequency by improving the tissue induction rate, tissue survival and tissue proliferation from immature embryos. Consequently, an optimal combination of glucose, copper and cytokinin in the co-cultivation, resting and selection media resulted in significant improvement from 2.6 % up to tenfold at the T₀ plant level using Agrobacterium strain LBA4404 in transformation of PHR03. Furthermore, we evaluated four different Agrobacterium strains, LBA4404, AGL1, EHA105, and GV3101 for transformation frequency and event quality. AGL1 had the highest transformation frequency with up to 57.1 % at the T₀ plant level. However, AGL1 resulted in lower quality events (defined as single copy for transgenes without Agrobacterium T-DNA backbone) when compared to LBA4404 (30.1 vs 25.6 %). We propose that these improvements can be applied to other recalcitrant commercial maize inbreds.     

The distribution of fitness effects of spontaneous mutations in Chlamydomonas reinhardtii inferred using frequency changes under experimental evolution

The distribution of fitness effects (DFE) for new mutations is fundamental for many aspects of population and quantitative genetics. In this study, we have inferred the DFE in the single-celled alga Chlamydomonas reinhardtii by estimating changes in the frequencies of 254 spontaneous mutations under experimental evolution and equating the frequency changes of linked mutations with their selection coefficients. We generated seven populations of recombinant haplotypes by crossing seven independently derived mutation accumulation lines carrying an average of 36 mutations in the haploid state to a mutation-free strain of the same genotype. We then allowed the populations to evolve under natural selection in the laboratory by serial transfer in liquid culture. We observed substantial and repeatable changes in the frequencies of many groups of linked mutations, and, surprisingly, as many mutations were observed to increase as decrease in frequency. Mutation frequencies were highly repeatable among replicates, suggesting that selection was the cause of the observed allele frequency changes. We developed a Bayesian Monte Carlo Markov Chain method to infer the DFE. This computes the likelihood of the observed distribution of changes of frequency, and obtains the posterior distribution of the selective effects of individual mutations, while assuming a two-sided gamma distribution of effects. We infer that the DFE is a highly leptokurtic distribution, and that approximately equal proportions of mutations have positive and negative effects on fitness. This result is consistent with what we have observed in previous work on a different C. reinhardtii strain, and suggests that a high fraction of new spontaneously arisen mutations are advantageous in a simple laboratory environment.     

Finding the optimal lengths for three branches at a junction

This paper presents an exact analytical solution to the problem of locating the junction point between three branches so that the sum of the total costs of the branches is minimized. When the cost per unit length of each branch is known the angles between each pair of branches can be deduced following reasoning first introduced to biology by Murray. Assuming the outer ends of each branch are fixed, the location of the junction and the length of each branch are then deduced using plane geometry and trigonometry. The model has applications in determining the optimal cost of a branch or branches at a junction. Comparing the optimal to the actual cost of a junction is a new way to compare cost models for goodness of fit to actual junction geometry. It is an unambiguous measure and is superior to comparing observed and optimal angles between each daughter and the parent branch. We present data for 199 junctions in the pulmonary arteries of two human lungs. For the branches at each junction we calculated the best fitting value of x from the relationship that flow ∞ (radius)^x. We found that the value of x determined whether a junction was best fitted by a surface, volume, drag or power minimization model. While economy of explanation casts doubt that four models operate simultaneously, we found that optimality may still operate, since the angle to the major daughter is less than the angle to the minor daughter. Perhaps optimality combined with a space filling branching pattern governs the branching geometry of the pulmonary artery.     

Ventilatory and cardiovascular modulation associated with burying behaviour in two sympatric crab species, Cancer magister and Cancer productus

Physiological parameters associated with burying were investigated in the Dungeness crab, Cancer magister, and the red rock crab, Cancer productus. Ventilation frequency of the branchial chambers increased while the crabs were burying, this was associated with the greater oxygen demand of the tissues. The number of ventilatory reversals in C. magister increased in number as well as in duration and magnitude when the crabs were buried, which functioned to clear the branchial chambers of sediment. In contrast, the number of ventilatory reversals in C. productus decreased. On the surface of the sand, cardiac parameters (heart rate, stroke volume, cardiac output) of both species remained stable. During the burial process, there was a large increase in cardiac output which was afforded primarily by an increased stroke volume of the heart. Once buried, cardiac output declined in both species; this was due to a decrease in stroke volume in C. productus, but a decreased heart rate in C. magister. There were also differences in haemolymph flows through each arterial system. During the burying process, both species increased haemolymph flow to the muscles of the limbs via the sternal artery. Once buried haemolymph flows to the limbs decreased, and increased flow to eyestalks and antennae via the anterior aorta occurred. Perfusion of the digestive organs via the anterolateral and hepatic arteries did not change when the crabs were buried. There was an increase in flow through the posterior aorta, of C. magister, but flow through this artery did not change in C. productus. Periods of spontaneous cardiac arrest were observed in both species while resting on the surface. These increased in duration in C. productus when buried, but there was no change in C. magister. Changes in ventilatory and cardiac variables were closely linked on the surface, but tended to uncouple when the animals were buried. The physiological responses of C. magister resembled those of true sand-dwelling crabs, whereas the responses of C. productus paralleled those of crabs that only bury occasionally in the substrate. Although these two species often occur sympatrically, they employ different physiological mechanisms when buried in the sediment.     

The blood supply to the abdominal and pelvic regions in talpids: character analysis and implications for specific relationships among Insectivora

The morphology of the abdominal and pelvic arterial system was analysed in two talpid species, the common mole (Talpa europaea) and the Pyrenean desman (Galemys pyrenaicus). Animals were studied by injection of coloured latex solution into the aorta by cannulation through the left ventricle of the heart, and subsequent dissection under a surgical microscope. In spite of the intra- and interspecific variation observed in the main abdominal and pelvic vessels examined, the general arrangements observed in talpids are consistent with the patterns described in other Insectivora, such as Soricinae and Crocidurinae. Interspecific morphological comparisons within the Insectivora and with representatives of other mammal orders revealed that the origin and arrangement of certain arteries, such as the renal, gonadal, caudal mesenteric, and median sacral arteries are clearly uncorrelated with function and phylogeny. Similar conclusions can be extended to the common or separate origin of the cœliac and the cranial mesenteric arteries. In contrast, other specific arterial traits can be interpreted from a functional and/or evolutionary standpoint. We discuss these implications for the following characteristics: the absence of gastroepiploic arteries; the presence of double lienal arteries and right gastric artery; the course of the cranial mesenteric artery; the presence of the ductus deferentis artery; and the origin of the cranial gluteal, deep iliac circumflex, and medial and lateral femoral circumflex arteries. Phenetic relationships among Soricomorpha were evaluated by cluster analysis. Congruence between the phenogram obtained and an accepted evolutionary hypothesis corroborates the phylogenetic significance of some arterial arrangements.     

The influence of carotid arterial sounds on hearing sensitivity in mammals

Pulsations of the internal carotid and stapedial arteries produce unwanted sounds (noise) in the middle ear cavity which influence hearing in some mammals. 'Noise' pressure levels calculated from pulse rates, volume pulsations of the arteries, and Fourier analysis of arterial waveforms, correlate well with low frequency thresholds of hearing in the Long-eared hedgehog, Tree shrew and Kangaroo rat. In mammals adapted to hear low frequency sounds, such as the Kangaroo rat and fossorial insectivores, the arteries are enclosed in noise attenuating bony tubes. However, most small mammals possess extended high frequency hearing with little sensitivity at the low frequencies of the arterial sounds. In lower tetrapods such as anurans and most lizards, the broad connection between the middle ear cavity and the pharynx creates a leakage pathway which greatly reduces the noise from the stapedial artery. It is probably for these reasons that the large intratympanic arteries did not disturb hearing in early mammals or submammalian forms.     

Long-term adaptation capacity of ponies: effect of season and feed restriction on blood and physiological parameters

Domesticated horses are increasingly kept under semi-natural housing conditions, whereas their adaptation capacity is not fully investigated. In all, 10 Shetland pony mares were held under semi-extensive conditions for 1 year. In winter animals were allocated into two feeding groups (60% and 100% of maintenance energy requirement, respectively). Triiodothyronine, thyroxine, non-esterified fatty acids (NEFA), total bilirubin, total protein, triglyceride, glucose, insulin and hair length were measured at monthly intervals, whereas BW, body condition score, cresty neck score and resting heart rate were recorded every 2 weeks. From summer to winter all Ponies showed a reduction in resting heart rate (P<0.001) and triiodothyronine (P<0.001) but an increase in NEFA (P<0.001), thyroxine (P<0.001) and triglyceride (P<0.001) concentrations. Feed restriction led to a reduced resting heart rate (P=0.009), increased NEFA (P<0.001) and total bilirubin (P=0.008) concentrations. Thyroid hormones did not differ between feeding groups (P>0.05). Refeeding of restrictively fed ponies resulted in a rapid increase in resting heart rate and BW and a return of blood parameters to reference values. Adequately supplied animals adapted without difficulty to varying environmental conditions, whereas feed restriction in ponies during winter resulted in reduced resting heart rates suggesting a reduced basal metabolic rate. The energy restriction was compensated by mobilizing body fat reserves which led to changes in blood parameters. Refeeding in feed restricted animals revealed a remarkably quick recovery of physiological and blood parameters to reference values. We therefore suggest that year round-outdoor housing can be a suitable housing system for robust horse breeds provided that an adequate food supply is available.     

Symbiont infection affects whitefly dynamics in the field

Inherited intracellular insect endosymbionts may manipulate host reproduction or provide fitness benefits to their hosts in ways that result in their rapid spread throughout a host population. Fitness benefits in particular can result in the increased pest potential of agriculturally important insects. While benefits due to endosymbiont infection have been well studied in laboratory assays, very little is known about how these benefits translate to insect performance in the field. Laboratory experiments have shown that the maternally inherited bacterial endosymbiont, Rickettsia, increases the fitness of its whitefly host, Bemisia tabaci, through improved fecundity, faster development times and female-biased sex ratios. We conducted field population cage studies to determine whether the benefits conferred by Rickettsia to whiteflies in the laboratory were evident on one of its major hosts, cotton, under field conditions in Arizona, USA. In cages with either Rickettsia-infected or uninfected whiteflies, we observed up to ten-fold higher whitefly egg and nymph densities when whiteflies were Rickettsia-infected compared with uninfected whiteflies throughout the season. We also observed a steep initial increase in Rickettsia frequency in population cages started with either 25% or 50% Rickettsia-infected whiteflies, with the 50% cages approaching fixation within three generations. Using growth rates obtained in the density cages, we calculated and compared an expected trajectory of the frequencies of Rickettsia infection with the observed frequencies. Results showed similar observed and expected frequencies of Rickettsia in the first two generations, followed by a significantly lower than expected frequency in three of four treatment/sample combinations at the end of the season. Taken together, these results confirm the patterns of fecundity and population growth observed in laboratory assays, under field conditions, as well as provides preliminary empirical support for a Rickettsia equilibrium frequency of less than 100%.     

Basal EDRF activity helps to keep the geometrical configuration of arterial bifurcations close to the Murray optimum

We have used X-ray microangiography to investigate the hypothesis that the potent endogenous vasodilator endothelium-derived relaxing factor (EDRF) contributes to the maintenance of "optimality" in vascular branching by modulating the diameters of the parent (D0) and daughter (D1 and D2) arteries at bifurcations. Five anatomically different types of bifurcation were studied in buffer-perfused rabbit ear preparations both under resting conditions and after pharmacological constriction by 5-hydroxytryptamine (5HT). A range of flow rates (1-5 ml min-1) was employed as release of EDRF from endothelial cells is stimulated by shear stress. Experimental data obtained in the presence and absence of EDRF activity were compared with theoretical predictions in three ways. (1) Junction exponents (x) were determined at each bifurcation from the equation Dx1 + Dx2 = Dx0, and their frequency distributions constructed. Murray (1926a, Proc. natn. Acad. Sci., U.S.A. 12, 207-214; 1926b, J. gen. Physiol. 9, 835-841.) proposed that x will be exactly 3 if power losses and intravascular volume are minimized simultaneously. In unconstricted preparations, either in the presence or absence of EDRF activity, and in preparations constricted by 0.1 microM 5HT in the presence of EDRF activity, the modes and medians of the frequency distributions of x were found to be close to 3 at all flow rates. In contrast, in 0.1 microM 5HT-constricted preparations in the absence of EDRF activity, no single mode common to all flow rates was apparent and medians were significantly larger at all flow rates. (2) Theoretically "optimal" branching angles were derived from experimental diameter measurements using four mathematical models which minimize respectively the total surface area, total volume, total drag (shear stress) and total power losses at bifurcations (Murray, 1926b). These calculated branching angles were then compared with actual branching angles. EDRF activity was found to be necessary for accurate prediction of branching angles by the minimum volume and power loss models in 5HT-constricted but not in resting preparations. (3) For each model or "minimization principle", there is an optimal mathematical relationship between the junction exponent, x, and the angle between daughter arteries, psi 12, at a bifurcation (Roy & Woldenberg, 1982, Bull. math. Biol. 44, 349-360.) Experimentally determined values of x and psi 12 agreed closely with those predicted both by the minimum volume and the minimum power loss principles, except again in 5HT-constricted preparations in the absence of EDRF activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms of acetylcholine-mediated vasodilation in systemic arteries from mourning doves (Zenaida macroura)

For mammals, acetylcholine (ACh) promotes endothelium-dependent vasodilation primarily through nitric oxide (NO) and prostaglandin-mediated pathways, with varying reliance on endothelial-derived hyperpolarizing factors. Currently, no studies have been conducted on small systemic arteries from wild birds. We hypothesized that ACh-mediated vasodilation of isolated small arteries from mourning doves (Zenaida macroura) would likewise depend on endothelial-derived factors. Small resistance mesenteric and cranial tibial (c. tibial) arteries (80–150 μm, inner diameter) were cannulated and pre-constricted to 50 % of resting inner diameter with phenylephrine then exposed to increasing concentrations of ACh (10^?9–10^?5 M) or the NO donor, sodium nitroprusside (SNP; 10^?12–10^?3 M). For mesenteric arteries, ACh-mediated vasodilation was significantly blunted with the potassium channel antagonist tetraethylammonium chloride (TEA, 10 mM); whereas responses were only moderately impaired with endothelial disruption or inhibition of prostaglandins (indomethacin, 10 μM). In contrast, endothelial disruption as well as exposure to TEA largely abolished vasodilatory responses to ACh in c. tibial arteries while no effect of prostaglandin inhibition was observed. For both vascular beds, responses to ACh were moderately dependent on the NO signaling pathway. Inhibition of NO synthase had no impact, despite complete reversal of phenylephrine-mediated tone with SNP, whereas inhibition of soluble guanylate cyclase (sGC) caused minor impairments. Endothelium-independent vasodilation also relied on potassium channels. In summary, ACh-mediated vasodilation of mesenteric and c. tibial arteries occurs through the activation of potassium channels to induce hyperpolarization with moderate reliance on sGC. Prostaglandins likewise play a small role in the vasodilatory response to ACh in mesenteric arteries.     

Tree visitation and seed dispersal of wild cherries by terrestrial mammals along a human land-use gradient

The role of terrestrial mammals as seed dispersers of fleshy-fruited plants has only rarely been investigated in temperate regions although recent studies underline the importance of these animals for long-distance seed dispersal. Here we examine the potential role of mammals as seed dispersers of wild cherry (Prunus avium L.) along a gradient of human land-use intensity. We placed camera traps at 21 wild cherry trees to identify the mammal species that visited the trees. We conducted feeding trials to test if the recorded species were legitimate seed dispersers or seed predators and to assess gut passage times. We tested the influence of human land-use intensity by quantifying habitat and landscape structure around the study trees at different spatial scales and analyzing its influence on visitation rates of tree visitors. Red fox (Vulpes vulpes), roe deer (Capreolus capreolus), wild boar (Sus scrofa), marten (Martes spp.) and badger (Meles meles) were identified as seed dispersers of wild cherry, of which wild boar was largely a seed predator. Habitat and landscape structure at local spatial scales (70 m, 500 m radius) had no effect on the total visitation rates of mammals. At larger spatial scales (1.0–10.0 km radius) total visitation rates increased with increasing proportion of extensively used farmland and seminatural habitat in the area. The proportion of forest had no influence on visitation rates. The results suggest that high proportions of extensively used farmland and seminatural habitat increase the visitation and seed dispersal rates of large mammals. Comparing gut passage times with home range sizes and daily travel distances suggests that these mammals have the potential to disperse seeds over long distances and can provide gene flow in fragmented agricultural landscapes.     

The contribution of differential hatching success to the fitness of species and interspecific hybrids

Resting egg banks of microcrustaceans have been used to reconstruct the evolutionary and ecological history of species. However, recent studies provided evidence for a discrepancy between dormant propagules in the sediment and the planktonic population. This pattern raises two questions: First, what is the value of data on resting egg banks for population dynamics over time and second, which component of the reproductive cycle causes the observed inconsistency? In our study we focussed on the second question by comparing the taxon composition of a resting egg bank with the reproductive success of ex-ephippial hatchlings. Species and interspecific hybrid identification of dormant and hatched stages was achieved through the application of restriction fragment length polymorphism analysis of an internal transcribed spacer region. We found no significant deviation between the proportion of hatched Daphnia galeata, D. galeata × hyalina and D. hyalina individuals and the observed taxon composition of the resting egg bank. However, species and hybrids differed in their mode and relative success of reproduction. We conclude that the components of reproductive success in Daphnia contribute differentially to the fitness of species and interspecific hybrids. The discrepancy between resting egg banks and “active” planktonic populations results not from differential hatching of species but from the reproductive success of ex-ephippial females and the timing and frequency of sexual reproduction of the different taxa.     

Identifying the Evolutionary Building Blocks of the Cardiac Conduction System

The endothermic state of mammals and birds requires high heart rates to accommodate the high rates of oxygen consumption. These high heart rates are driven by very similar conduction systems consisting of an atrioventricular node that slows the electrical impulse and a His-Purkinje system that efficiently activates the ventricular chambers. While ectothermic vertebrates have similar contraction patterns, they do not possess anatomical evidence for a conduction system. This lack amongst extant ectotherms is surprising because mammals and birds evolved independently from reptile-like ancestors. Using conserved genetic markers, we found that the conduction system design of lizard (Anolis carolinensis and A. sagrei), frog (Xenopus laevis) and zebrafish (Danio rerio) adults is strikingly similar to that of embryos of mammals (mouse Mus musculus, and man) and chicken (Gallus gallus). Thus, in ectothermic adults, the slow conducting atrioventricular canal muscle is present, no fibrous insulating plane is formed, and the spongy ventricle serves the dual purpose of conduction and contraction. Optical mapping showed base-to-apex activation of the ventricles of the ectothermic animals, similar to the activation pattern of mammalian and avian embryonic ventricles and to the His-Purkinje systems of the formed hearts. Mammalian and avian ventricles uniquely develop thick compact walls and septum and, hence, form a discrete ventricular conduction system from the embryonic spongy ventricle. Our study uncovers the evolutionary building plan of heart and indicates that the building blocks of the conduction system of adult ectothermic vertebrates and embryos of endotherms are similar.     

Variation in relapse frequency and the transmission potential of Plasmodium vivax malaria

There is substantial variation in the relapse frequency of Plasmodium vivax malaria, with fast-relapsing strains in tropical areas, and slow-relapsing strains in temperate areas with seasonal transmission. We hypothesize that much of the phenotypic diversity in P. vivax relapses arises from selection of relapse frequency to optimize transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of P. vivax transmission and calculate the basic reproduction number R₀ to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year-round transmission, transmission potential is optimized at intermediate relapse frequencies of two to three months: slower-relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster-relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be six to nine months, coinciding with the duration between seasonal transmission peaks. We predict that there is a threshold degree of seasonality, below which fast-relapsing tropical strains are selected for, and above which slow-relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes.     

"Body-In-The-Loop": Optimizing Device Parameters Using Measures of Instantaneous Energetic Cost

This paper demonstrates methods for the online optimization of assistive robotic devices such as powered prostheses, orthoses and exoskeletons. Our algorithms estimate the value of a physiological objective in real-time (with a body “in-the-loop”) and use this information to identify optimal device parameters. To handle sensor data that are noisy and dynamically delayed, we rely on a combination of dynamic estimation and response surface identification. We evaluated three algorithms (Steady-State Cost Mapping, Instantaneous Cost Mapping, and Instantaneous Cost Gradient Search) with eight healthy human subjects. Steady-State Cost Mapping is an established technique that fits a cubic polynomial to averages of steady-state measures at different parameter settings. The optimal parameter value is determined from the polynomial fit. Using a continuous sweep over a range of parameters and taking into account measurement dynamics, Instantaneous Cost Mapping identifies a cubic polynomial more quickly. Instantaneous Cost Gradient Search uses a similar technique to iteratively approach the optimal parameter value using estimates of the local gradient. To evaluate these methods in a simple and repeatable way, we prescribed step frequency via a metronome and optimized this frequency to minimize metabolic energetic cost. This use of step frequency allows a comparison of our results to established techniques and enables others to replicate our methods. Our results show that all three methods achieve similar accuracy in estimating optimal step frequency. For all methods, the average error between the predicted minima and the subjects’ preferred step frequencies was less than 1% with a standard deviation between 4% and 5%. Using Instantaneous Cost Mapping, we were able to reduce subject walking-time from over an hour to less than 10 minutes. While, for a single parameter, the Instantaneous Cost Gradient Search is not much faster than Steady-State Cost Mapping, the Instantaneous Cost Gradient Search extends favorably to multi-dimensional parameter spaces.     

Post-Surgical Analgesia in Rainbow Trout: Is Reduced Cardioventilatory Activity a Sign of Improved Animal Welfare or the Adverse Effects of an Opioid Drug?

The use of fish models in biomedical research is increasing. Since behavioural and physiological consequences of surgical procedures may affect experimental results, these effects should be defined and, if possible, ameliorated. Thus, the use of post-surgical analgesia should be considered after invasive procedures also in fish, but presently, little information exists on the effects of analgesics in fish. This study assessed the effects of an opioid drug, buprenorphine (0.05 mg/kg IM), on resting ventilation and heart rates during 7 days of postsurgical recovery in rainbow trout (Oncorhynchus mykiss) at 10°C by non-invasively recording bioelectric potentials from the fish via electrodes in the water. Baseline ventilation and heart rates were considerably lower compared to previously reported values for rainbow trout at 10°C, possibly due to the non-invasive recording technique. Buprenorphine significantly decreased both ventilation and heart rates further, and the effects were most pronounced at 4–7 days after anaesthesia, surgical procedures and administration of the drug. Somewhat surprisingly, the same effects of buprenorphine were seen in the two control groups that had not been subject to surgery. These results indicate that the reductions in ventilation and heart rates are not caused by an analgesic effect of the drug, but may instead reflect a general sedative effect acting on both behaviour as well as e.g. central control of ventilation in fishes. This resembles what has previously been demonstrated in mammals, although the duration of the drug effect is considerably longer in this ectothermic animal. Thus, before using buprenorphine for postoperative analgesic treatment in fish, these potentially adverse effects need further characterisation.     

Blood flow response to a postural challenge in older men and women

BACKGROUND: The purpose of this study was to measure blood flow in the carotid and femoral arteries, heart rate and blood pressure in response to postural challenge in older adults. A second purpose was to determine if older men and women have different cardiovascular responses to a postural challenge such as tilt. METHODS: Thirty-seven healthy elderly men and women participated in this study (69-82 years old). All subjects had similar physical activity levels. Postural challenge was induced by a 60 degrees tilt at the level of the waist. Continuous carotid blood flow and femoral blood flow was measured with Doppler ultrasound. RESULTS: Carotid blood flow was significantly reduced 17% in both men and women immediately after tilt (p < 0.001), and by 3.2% two minutes after tilt (p < 0.001). Femoral blood flow decreased 59.4% in men and 61% in women immediately after tilt (p < 0.001), and remained significantly decreased two minutes after tilt by 21% (p <0.001). Heart rate increased by 15% in men (p < 0.001), and 26% in women immediately after the tilt (p < 0.001). Heart rate returned to resting values within two minutes in both men and women. Response to tilt was not significantly related to self-report physical activity levels or to six-minute walk time. CONCLUSION: A postural challenge induced larger changes in the femoral artery compared to the carotid artery. There were no differences between men and women to a tilt table test except for differences in heart rate response. There was no difference in the blood flow responses to postural challenge with physical activity level or between healthy older men and women.