Heterogeneity in stable isotope profiles predicts coexistence of populations of barn swallows Hirundo rustica differing in morphology and reproductive performance

Population studies assume that individuals belonging to a study population are homogeneous for natal and breeding origin, although this assumption is rarely tested. We tested for heterogeneity in stable-isotope profiles (delta15N, delta13C, deltaD) of feathers grown in the African winter quarters from a Danish breeding population of adult barn swallows, Hirundo rustica. Deuterium isotope values did not provide useful information on population segregation of wintering swallows in Africa. However, both delta15N and delta13C values showed a clearly bimodal distribution with 6% belonging to one category and the remaining birds belonging to another category, resulting in this population comprising three categories of birds. Adults belonging to the two categories of delta13C isotope profiles differed weakly in morphology for several different characters. The frequency and the size of second broods differed between categories of delta13C isotope profiles. Phenotypes of nestlings from the first brood in terms of tarsus length, body mass and T-cell response differed significantly between the two delta15N isotope categories, suggesting that conditions during winter carried over to the breeding season at least as late as the first brood. Polymorphism can be maintained only if fitness is similar for birds from categories of isotope profiles. We suggest that fluctuating selection or migration-selection balance may maintain the observed polymorphism.     

The pathogenesis of autism: insights from congenital blindness

There is substantial heterogeneity in the aetiology and clinical presentation of autism. So how do we account for homogeneity in the syndrome? The answer to this question will be critical for any attempt to trace the links between brain pathology and the psychological disabilities that characterize autism. One possibility is that the source of homogeneity in autism is not to be found ''in the child'', but rather in dysfunction of the system constituted by child-in-relation-to-other. We have been exploring this hypothesis through the study of congenitally blind children, among whom features of autism, and the syndrome of autism itself, are strikingly common. To justify such an approach, one needs to establish that the clinical features in blind children have qualities that are indeed ''autistic-like''. We conducted systematic observations of the social interactions of two matched groups of congenitally blind children who do not have autism, rating their social engagement, emotional tone, play and language during three sessions of free play in the school playground. The qualities of social impairment in the more disabled children were similar to those in sighted children with autism. Additional evidence came from independent ratings of the children in a different play setting: on the childhood autism rating scale (CARS), the socially impaired children had ''autistic-like'' abnormalities in both social and non-social domains. If we can determine the way in which congenital blindness predisposes to features of autism, we shall be in a better position to trace the developmental pathways that lead to the syndrome in sighted children.     

Stable isotopes as indicators of altitudinal distributions and movements in an Ecuadorean hummingbird community

Altitudinal migration and dispersal is an important component of the life history of several temperate and tropical birds but remains poorly understood due to the limited success of mark and recapture techniques. Stable isotopes of hydrogen (deltaD) in rainfall, and to a lesser extent, carbon (delta13C) in plants are known to change with altitude and hence may provide the basis of a technique for tracking the altitudinal movements in birds and other wildlife. We investigated the potential for this technique by measuring delta13C, deltaD, and delta15N values in tail feathers of eight species of hummingbirds ( Phaethornis malaris, P. syrmatophorus, P. guy, Adelomyia melanogenys, Coeligena torquata, C. lutetiae, Metallura baroni, M. williami) along an altitudinal gradient (300-3,290 m asl) in the Andes Mountains of Ecuador. Feather delta13C and deltaD values were correlated and each changed significantly with elevation above 400 m. In general, we found good agreement between feather deltaD values and those predicted from a generalized relationship of precipitation and surface water deltaD with altitude. Similarly, feather delta13C values showed an enrichment of approximately 1.5 per thousand per 1,000 m over the linear portion of the elevational response. Stable-nitrogen isotope values were variable, and so did not provide useful information on elevation in birds, apart from trophic effects. Overall there appears to be good potential for using the (deltaD, delta13C) stable isotope approach to track altitudinal movements and to elucidate previously unrecognized patterns of life history variation in both temperate and tropical species that migrate across elevational isotopic gradients.     

Functional characterization of alternatively spliced 5-HT2 receptor isoforms from the pharynx and muscle of the parasitic nematode,Ascaris suum

Serotonin (5-HT) receptors play key regulatory roles in nematodes and alternatively spliced 5-HT2 receptor isoforms have been identified in the parasitic nematode, Ascaris suum. 5-HT2As1 and 5-HT2As2 contain different C-termini, and 5-HT2As1Delta4 lacks 42 amino acids at the C-terminus of the third intracellular loop. 5-HT2As1 and 5-HT2As2 exhibited identical pharmacological profiles when stably expressed in human embryonic kidney (HEK) 293 cells. Both 5-HT2As isoforms had higher affinity for 5-HT than their closely related Caenorhabditis elegans homolog (5-HT2Ce). This increased 5-HT affinity was not related to the substitution in 5-HT2As1 of F120 for Y in the highly conserved DRY motif found in the second intracellular loop of other 5-HT receptors, since a 5-HT2As1F120Y mutant actually exhibited increased 5-HT affinity compared with that of 5-HT2As1. As predicted, cells expressing either 5-HT2As1 or 5-HT2As2 exhibited a 5-HT-dependent increase in phosphatidylinositol (PI) turnover. In contrast, although 5-HT2As1Delta4 displayed a 10-fold higher affinity for 5-HT and 5-HT agonists than either 5-HT2As1 or 5-HT2As2, 5-HT2As1Delta4 did not couple to either PI turnover or adenyl cyclase activity. Based on RT-PCR, 5-HT2As1 and 5-HT2As2 were more highly expressed in pharynx and body wall muscle and 5-HT2As1Delta4 in nerve cord/hypodermis. This is the first report of different alternatively spliced 5-HT2 receptor isoforms from any system.     

Driving plasticity in human adult motor cortex is associated with improved motor function after brain injury

Changes in somatosensory input can remodel human cortical motor organization, yet the input characteristics that promote reorganization and their functional significance have not been explored. Here we show with transcranial magnetic stimulation that sensory-driven reorganization of human motor cortex is highly dependent upon the frequency, intensity, and duration of stimulus applied. Those patterns of input associated with enhanced excitability (5 Hz, 75% maximal tolerated intensity for 10 min) induce stronger cortical activation to fMRI. When applied to acutely dysphagic stroke patients, swallowing corticobulbar excitability is increased mainly in the undamaged hemisphere, being strongly correlated with an improvement in swallowing function. Thus, input to the human adult brain can be programmed to promote beneficial changes in neuroplasticity and function after cerebral injury.     

Mucosal immunization with DNA vaccines

DNA vaccines represent a new approach to the control of infectious disease. Both cellular and humoral immune responses are induced without the attendant concerns associated with live, attenuated vaccines. The vast majority of DNA vaccines are delivered by parental routes, which rarely elicit immune responses at the mucosal epithelia, the primary sites of pathogen transmission. In view of the importance of mucosal and regional lymph node immunity in the control of pathogens transmitted across the mucosal epithelia, a number of groups, including our own, have developed immunization strategies that target plasmid DNA to mucosal inductive sites associated with the lymphoid tissues of the respiratory, gastrointestinal, and genital tracts. Here, we describe the procedures for the formulation and delivery of plasmid DNA to mucosal inductive tissues and address the theoretical basis to selection of particular mucosal locations for the induction of effective immune responses.     

<Emphasis Type="Italic">In situ</Emphasis>transduction of target cells on solid surfaces by immobilized viral vectors

Background

For both in vitro and in vivo gene transfer applications, recombinant viral vectors have almost always been used free in solution. Some site-specificity of the delivery of viral vectors can be achieved by applying a solution containing viral particles specifically to the site of interest. However, such site-specificity is seriously limited since viral vectors can diffuse freely in solution after application.

Results

We have developed a novel strategy for in situ transduction of target cells on solid surfaces by viral vectors. In this strategy, adenoviral vectors are attached stably to solid surfaces by using the extremely tight interaction between (strept)avidin and biotin, while maintaining the infectivity of the viral vectors. Target cells are cultured directly on such virus-coated solid surfaces, resulting in the transduction of the cells, in situ, on the solid surface. When compared using an equal number of viral particles present in each well (either immobilized or free), the efficiencies of such in situ transduction on solid surfaces were equivalent to those seen with the adenoviral vectors used free in solution. Since viral particles can be attached at desired locations on solid surfaces in any sizes, shapes, and patterns, the ultimate spatial arrangements of transduced cells on solid surfaces can be predetermined at the time of the preparation of the virus-coated solid surfaces.

Conclusions

We have devised a method of immobilizing adenoviral vectors, tightly and stably, on solid surfaces, while maintaining their ability to infect cells. Such immobilized viral vectors can infect target cells, in situ, on solid surfaces. This strategy should be very useful for the development of a variety of both in vitro and in vivo applications, including the creation of cell-based expression arrays for proteomics and drug discovery and highly site-specific delivery of transgenes for gene therapy and tissue engineering.

     

Central neural mechanisms mediating human visceral hypersensitivity

Although visceral hypersensitivity is thought to be important in generating symptoms in functional gastrointestinal disorders, the neural mechanisms involved are poorly understood. We recently showed that central sensitization (hyperexcitability of spinal cord sensory neurones) may play an important role. In this study, we demonstrate that after a 30-min infusion of 0.15 M HCl acid into the healthy human distal esophagus, we see a reduction in the pain threshold to electrical stimulation of the non-acid-exposed proximal esophagus (9.6 +/- 2.4 mA) and a concurrent reduction in the latency of the N1 and P2 components of the esophageal evoked potentials (EEP) from this region (10.4 +/- 2.3 and 15.8 +/- 5.3 ms, respectively). This reduced EEP latency indicates a central increase in afferent pathway velocity and therefore suggests that hyperexcitability within the central visceral pain pathway contributes to the hypersensitivity within the proximal, non-acid-exposed esophagus (secondary hyperalgesia/allodynia). These findings provide the first electrophysiological evidence that central sensitization contributes to human visceral hypersensitivity.     

A cortical evoked potential study of afferents mediating human esophageal sensation

The aim of this study was to compare the characteristics of esophageal cortical evoked potentials (CEP) following electrical and mechanical stimulation in healthy subjects to evaluate the afferents involved in mediating esophageal sensation. Similarities in morphology and interpeak latencies of the CEP to electrical and mechanical stimulation suggest that they are mediated via similar pathways. Conduction velocity of CEP to either electrical or mechanical stimulation was 7.9-8.6 m/s, suggesting mediation via thinly myelinated Adelta-fibers. Amplitudes of CEP components to mechanical stimulation were significantly smaller than to electrical stimulation at the same levels of perception, implying that electrical stimulation activates a larger number of afferents. The latency delay of approximately 50 ms for each mechanical CEP component compared with the corresponding electrical CEP component is consistent with the time delay for the mechanical stimulus to distend the esophageal wall sufficiently to trigger the afferent volley. In conclusion, because the mechanical and electrical stimulation intensities needed to obtain esophageal CEP are similar and clearly perceived, it is likely that both spinal and vagal pathways mediate esophageal CEP. Esophageal CEP to both modalities of stimulation are mediated by myelinated Adelta-fibers and produce equally robust CEP responses. Both techniques may have important roles in the assessment of esophageal sensory processing in health and disease.     

Effects of Beta-Alanine Supplementation on Brain Homocarnosine/Carnosine Signal and Cognitive Function: An Exploratory Study

Objectives

Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d^-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2).

Methods

In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion.

Results

In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P<0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise.

Conclusion

28 d of beta-alanine supplementation at 6.4g d^-1 appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists.