bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic algorithm for shift-uncertainty correction in 1-D NMR-based metabolite identifications and quantifications
Authors: Schleif F.-M. , Riemer T. , Börner U. , Schnapka-Hille L. , Cross M.
Published: December 2010

Motivation: The analysis of metabolic processes is becoming increasingly important to our understanding of complex biological systems and disease states. Nuclear magnetic resonance spectroscopy (NMR) is a particularly relevant technology in this respect, since the NMR signals provide a quantitative measure of the metabolite concentrations. However, due to the complexity of the spectra typical of biological samples, the demands of clinical and high-throughput analysis will only be fully met by a system capable of reliable, automatic processing of the spectra. An initial step in this direction has been taken by Targeted Profiling (TP), employing a set of known and predicted metabolite signatures fitted against the signal. However, an accurate fitting procedure for 1H NMR data is complicated by shift uncertainties in the peak systems caused by measurement imperfections. These uncertainties have a large impact on the accuracy of identification and quantification and currently require compensation by very time consuming manual interactions. Here, we present an approach, termed Extended Targeted Profiling (ETP), that estimates shift uncertainties based on a genetic algorithm (GA) combined with a least squares optimization (LSQO). The estimated shifts are used to correct the known metabolite signatures leading to significantly improved identification and quantification. In this way, use of the automated system significantly reduces the effort normally associated with manual processing and paves the way for reliable, high-throughput analysis of complex NMR spectra.

Results: The results indicate that using simultaneous shift uncertainty correction and least squares fitting significantly improves the identification and quantification results for 1H NMR data in comparison to the standard targeted profiling approach and compares favorably with the results obtained by manual expert analysis. Preservation of the functional structure of the NMR spectra makes this approach more realistic than simple binning strategies.

Availability: The simulation descriptions and scripts employed are available under: http://139.18.218.40/metastemwww/bioinf/bioinf_suppl_nmr_ga_opt_schleif_et_al.tgz

Contact:  schleif@informatik.uni-leipzig.de
Songs differing in consistency elicit differential aggressive response in territorial birds
Authors: Rivera-Gutierrez Hector Fabio , Pinxten Rianne , Eens Marcel
Published: December 2010

Acoustic signals during intrasexual interactions may help receivers to establish the cost and benefits of engaging in a confrontation versus avoiding the cost of escalation. Although birdsong repertoires have been previously suggested as providing information during agonistic encounters, the cost (time/neural resources) of assessing large repertoires may decrease the efficiency of the signal for mutual assessment. Acoustic-structural features may, therefore, be used to enable a fast and accurate assessment during this kind of encounters. Recently, it has been suggested that the consistency of songs may play a key role during intrasexual interactions in bird species. Using a playback experiment in a colour-ringed great tit population, we tested the hypothesis that songs differing in consistency may elicit a differential response, indicating that the signal is salient for the receivers. Great tit males clearly responded more aggressively towards highly consistent songs. Our findings, together with previous evidence of increased song consistency with age in the great tit, suggest that song consistency provides information on experience or dominance in this species, and this phenomenon may be more widespread than currently acknowledged.
Offspring viability benefits but no apparent costs of mating with high quality males
Authors: Simmons Leigh W. , Holley Rebecca
Published: December 2010

Traditional models of sexual selection posit that male courtship signals evolve as indicators of underlying male genetic quality. An alternative hypothesis is that sexual conflict over mating generates antagonistic coevolution between male courtship persistence and female resistance. In the scarabaeine dung beetle
Onthophagus taurus
, females are more likely to mate with males that have high courtship rates. Here, we examine the effects of exposing females to males with either high or low courtship rates on female lifetime productivity and offspring viability. Females exposed to males with high courtship rates mated more often and produced offspring with greater egg–adult viability. Female productivity and lifespan were unaffected by exposure to males with high courtship rates. The data are consistent with models of sexual selection based on indirect genetic benefits, and provide little evidence for sexual conflict in this system.
The role of female dominance hierarchies in the mating behaviour of mosquitofish
Authors: Chen Therese , Beekman Madeleine , Ward Ashley J. W.
Published: December 2010

While studies of sexual selection focus primarily on female choice and male–male competition, males should also exert mate choice in order to maximize their reproductive success. We examined male mate choice in mosquitofish,
Gambusia holbrooki
, with respect to female size and female dominance. We found that the number of mating attempts made by a male was predicted by the dominance rank of females in a group, with dominant females attracting more mating attempts than subordinates. The number of mating attempts made by males was independent of the female size. The observed bias in the number of mating attempts towards dominant females may be driven either by straightforward male mate choice, since dominance and female fecundity are often closely related, or via the dominant females mediating male mating behaviour by restricting their access to subordinate females.
Stability in flux: community structure in dynamic networks
Authors: Bryden John , Funk Sebastian , Geard Nicholas , Bullock Seth , Jansen Vincent A. A.
Published: December 2010

The structure of many biological, social and technological systems can usefully be described in terms of complex networks. Although often portrayed as fixed in time, such networks are inherently dynamic, as the edges that join nodes are cut and rewired, and nodes themselves update their states. Understanding the structure of these networks requires us to understand the dynamic processes that create, maintain and modify them. Here, we build upon existing models of coevolving networks to characterize how dynamic behaviour at the level of individual nodes generates stable aggregate behaviours. We focus particularly on the dynamics of groups of nodes formed endogenously by nodes that share similar properties (represented as node state) and demonstrate that, under certain conditions, network modularity based on state compares well with network modularity based on topology. We show that if nodes rewire their edges based on fixed node states, the network modularity reaches a stable equilibrium which we quantify analytically. Furthermore, if node state is not fixed, but can be adopted from neighbouring nodes, the distribution of group sizes reaches a dynamic equilibrium, which remains stable even as the composition and identity of the groups change. These results show that dynamic networks can maintain the stable community structure that has been observed in many social and biological systems.
A probabilistic approach to identify putative drug targets in biochemical networks
Authors: Murabito Ettore , Smallbone Kieran , Swinton Jonathan , Westerhoff Hans V. , Steuer Ralf
Published: December 2010

Network-based drug design holds great promise in clinical research as a way to overcome the limitations of traditional approaches in the development of drugs with high efficacy and low toxicity. This novel strategy aims to study how a biochemical network as a whole, rather than its individual components, responds to specific perturbations in different physiological conditions. Proteins exerting little control over normal cells and larger control over altered cells may be considered as good candidates for drug targets. The application of network-based drug design would greatly benefit from using an explicit computational model describing the dynamics of the system under investigation. However, creating a fully characterized kinetic model is not an easy task, even for relatively small networks, as it is still significantly hampered by the lack of data about kinetic mechanisms and parameters values. Here, we propose a Monte Carlo approach to identify the differences between flux control profiles of a metabolic network in different physiological states, when information about the kinetics of the system is partially or totally missing. Based on experimentally accessible information on metabolic phenotypes, we develop a novel method to determine probabilistic differences in the flux control coefficients between the two observable phenotypes. Knowledge of how differences in flux control are distributed among the different enzymatic steps is exploited to identify points of fragility in one of the phenotypes. Using a prototypical cancerous phenotype as an example, we demonstrate how our approach can assist researchers in developing compounds with high efficacy and low toxicity.
A polymer–solvent model of biofilm growth
Authors: Winstanley H. F. , Chapwanya M. , McGuinness M. J. , Fowler A. C.
Published: December 2010

We provide and analyse a model for the growth of bacterial biofilms based on the concept of an extracellular polymeric substance as a polymer solution, whose viscoelastic rheology is described by the classical Flory–Huggins theory. We show that one-dimensional solutions exist, which take the form at large times of travelling waves, and we characterize their form and speed in terms of the describing parameters of the problem. Numerical solutions of the time-dependent problem converge to the travelling wave solutions.
Sequential games and optimal strategies
Authors: Escardó Martín , Oliva Paulo
Published: December 2010

This article gives an overview of recent work on the theory of selection functions. We explain the intuition behind these higher type objects, and define a general notion of sequential game whose optimal strategies can be computed via a certain product of selection functions. Several instances of this game are considered in a variety of areas such as fixed point theory, topology, game theory, higher type computability and proof theory. These examples are intended to illustrate how the fundamental construction of optimal strategies based on products of selection functions permeates several research areas.
What makes a feather shine? A nanostructural basis for glossy black colours in feathers
Authors: Maia Rafael , D'Alba Liliana , Shawkey Matthew D.
Published: December 2010

Colours in feathers are produced by pigments or by nanostructurally organized tissues that interact with light. One of the simplest nanostructures is a single layer of keratin overlying a linearly organized layer of melanosomes that create iridescent colours of feather barbules through thin-film interference. Recently, it has been hypothesized that glossy (i.e. high specular reflectance) black feathers may be evolutionarily intermediate between matte black and iridescent feathers, and thus have a smooth keratin layer that produces gloss, but not the layered organization of melanosomes needed for iridescence. However, the morphological bases of glossiness remain unknown. Here, we use a theoretical approach to generate predictions about morphological differences between matte and glossy feathers that we then empirically test. Thin-film models predicted that glossy spectra would result from a keratin layer 110–180 nm thick and a melanin layer greater than 115 nm thick. Transmission electron microscopy data show that nanostructure of glossy barbules falls well within that range, but that of matte barbules does not. Further, glossy barbules had a thinner and more regular keratin cortex, as well as a more continuous underlying melanin layer, than matte barbules. Thus, their quasi-ordered nanostructures are morphologically intermediate between matte black and iridescent feathers, and perceived gloss may be a form of weakly chromatic iridescence.
Vocal frequency change reflects different responses to anthropogenic noise in two suboscine tyrant flycatchers
Authors: Francis Clinton D. , Ortega Catherine P. , Cruz Alexander
Published: December 2010

Anthropogenic noise is prevalent across the globe and can exclude birds from otherwise suitable habitat and negatively influence fitness; however, the mechanisms responsible for species' responses to noise are not always clear. One effect of noise is a reduction in effective acoustic communication through acoustic masking, yet some urban songbirds may compensate for masking by noise through altering their songs. Whether this vocal flexibility accounts for species persistence in noisy areas is unknown. Here, we investigated the influence of noise on habitat use and vocal frequency in two suboscine flycatchers using a natural experiment that isolated effects of noise from confounding stimuli common to urban habitats. With increased noise exposure, grey flycatcher (
Empidonax wrightii
) occupancy declined, but vocal frequency did not change. By contrast, ash-throated flycatcher (
Myiarchus cinerascens
) occupancy was uninfluenced by noise, but individuals in areas with greater noise amplitudes vocalized at a higher frequency, although the increase (≈200 kHz) may only marginally improve communication and may represent a secondary effect from increased vocal amplitude. Even so, the different flycatcher behavioural responses suggest that signal change may help some species persist in noisy areas and prompt important questions regarding which species will cope with an increasingly noisy world.
Bacillus Calmette-Guérin vaccination reduces the severity and progression of tuberculosis in badgers
Authors: Chambers Mark A. , Rogers Fiona , Delahay Richard J. , Lesellier Sandrine , Ashford Roland , Dalley Deanna , Gowtage Sonya , Davé Dipesh , Palmer Si , Brewer Jacky , Crawshaw Timothy , Clifton-Hadley Richard , Carter Steve , Cheeseman Chris , Hanks Chris , Murray Alistair , Palphramand Kate , Pietravalle Stéphane , Smith Graham C. , Tomlinson Alexandra , Walker Neil J. , Wilson Gavin J. , Corner Leigh A. L. , Rushton Stephen P. , Shirley Mark D. F. , Gettinby George , McDonald Robbie A. , Hewinson R. Glyn
Published: December 2010

Control of bovine tuberculosis (TB) in cattle has proven particularly challenging where reservoirs of infection exist in wildlife populations. In Britain and Ireland, control is hampered by a reservoir of infection in Eurasian badgers (
Meles meles
). Badger culling has positive and negative effects on bovine TB in cattle and is difficult, costly and controversial. Here we show that Bacillus Calmette-Guérin (BCG) vaccination of captive badgers reduced the progression, severity and excretion of
Mycobacterium bovis
infection after experimental challenge. In a clinical field study, BCG vaccination of free-living badgers reduced the incidence of positive serological test results by 73.8 per cent. In common with other species, BCG did not appear to prevent infection of badgers subjected to experimental challenge, but did significantly reduce the overall disease burden. BCG vaccination of badgers could comprise an important component of a comprehensive programme of measures to control bovine TB in cattle.
Gait-specific energetics contributes to economical walking and running in emus and ostriches
Authors: Watson Rebecca R. , Rubenson Jonas , Coder Lisa , Hoyt Donald F. , Propert Matthew W. G. , Marsh Richard L.
Published: December 2010

A widely held assumption is that metabolic rate (Ėmet) during legged locomotion is linked to the mechanics of different gaits and this linkage helps explain the preferred speeds of animals in nature. However, despite several prominent exceptions,Ėmetof walking and running vertebrates has been nearly uniformly characterized as increasing linearly with speed across all gaits. This description of locomotor energetics does not predict energetically optimal speeds for minimal cost of transport (Ecot). We tested whether large bipedal ratite birds (emus and ostriches) have gait-specific energetics during walking and running similar to those found in humans. We found that during locomotion, emus showed a curvilinear relationship betweenĖmetand speed during walking, and both emus and ostriches demonstrated an abrupt change in the slope ofĖmetversus speed at the gait transition with a linear increase during running. Similar to human locomotion, the minimum netEcotcalculated after subtracting resting metabolism was lower in walking than in running in both species. However, the difference in netEcotbetween walking and running was less than is found in humans because of a greater change in the slope ofĖmetversus speed at the gait transition, which lowers the cost of running for the avian bipeds. For emus, we also show that animals moving freely overground avoid a range of speeds surrounding the gait-transition speed within which theEcotis large. These data suggest that deviations from a linear relation of metabolic rate and speed and variations in transport costs with speed are more widespread than is often assumed, and provide new evidence that locomotor energetics influences the choice of speed in bipedal animals. The low cost of transport for walking is probably ecologically important for emus and ostriches because they spend the majority of their active day walking, and thus the energy used for locomotion is a large part of their daily energy budget.
Could controlling mammalian carnivores lead to mesopredator release of carnivorous reptiles?
Authors: Sutherland Duncan R. , Glen Alistair S. , de Tores Paul J.
Published: December 2010

Emerging evidence increasingly illustrates the importance of a holistic, rather than taxon-specific, approach to the study of ecological communities. Considerable resources are expended to manage both introduced and native mammalian carnivores to improve conservation outcomes; however, management can result in unforeseen and sometimes catastrophic outcomes. Varanid lizards are likely to be apex- or mesopredators, but being reptiles are rarely considered by managers and researchers when investigating the impacts of mammalian carnivore management. Instances of mesopredator release have been described for
Varanus gouldii
as a result of fox and cat management in Australia, with cascading effects on faunal community structure. A meta-analysis showing extensive dietary niche overlap between varanids, foxes and cats plus a review of experimental and circumstantial evidence suggests mesopredator release of
V. gouldii
and about five other medium to large species of varanid lizard is likely in other regions. This highlights the need for managers to adopt a whole-of-community approach when attempting to manage predators for sustained fauna conservation, and that additional research is required to elucidate whether mesopredator release of varanids is a widespread consequence of carnivore management, altering the intended faunal responses.
Evolution of tolerance by magpies to brood parasitism by great spotted cuckoos
Authors: Soler J. J. , Martín-Gálvez D. , Martínez J. G. , Soler M. , Canestrari D. , Abad-Gómez J. M. , Møller A. P.
Published: December 2010

Hosts may use two different strategies to ameliorate negative effects of a given parasite burden: resistance or tolerance. Although both resistance and tolerance of parasitism should evolve as a consequence of selection pressures owing to parasitism, the study of evolutionary patterns of tolerance has traditionally been neglected by animal biologists. Here, we explore geographical covariation between tolerance of magpies (Pica pica) and brood parasitism by the great spotted cuckoo (Clamator glandarius) in nine different sympatric populations. We estimated tolerance as the slope of the regression of number of magpie fledglings (i.e. host fitness) on number of cuckoo eggs laid in non-depredated nests (which broadly equals parasite burden). We also estimated prevalence of parasitism and level of host resistance (i.e. rejection rates of mimetic model eggs) in these nine populations. In accordance with the hypothetical role of tolerance in the coevolutionary process between magpies and cuckoos we found geographical variation in tolerance estimates that positively covaried with prevalence of parasitism. Levels of resistance and tolerance were not associated, possibly suggesting the lack of a trade-off between the two kinds of defences against great spotted cuckoo parasitism for magpies. We discuss the results in the framework of a mosaic of coevolutionary interactions along the geographical distribution of magpies and great spotted cuckoos for which we found evidence that tolerance plays a major role.
On the origins of sexual dimorphism in butterflies
Authors: Oliver Jeffrey C. , Monteiro Antónia
Published: December 2010

The processes governing the evolution of sexual dimorphism provided a foundation for sexual selection theory. Two alternative processes, originally proposed by Darwin and Wallace, differ primarily in the timing of events creating the dimorphism. In the process advocated by Darwin, a novel ornament arises in a single sex, with no temporal separation in the origin and sex-limitation of the novel trait. By contrast, Wallace proposed a process where novel ornaments appear simultaneously in both sexes, but are then converted into sex-limited expression by natural selection acting against showy coloration in one sex. Here, we investigate these alternative modes of sexual dimorphism evolution in a phylogenetic framework and demonstrate that both processes contribute to dimorphic wing patterns in the butterfly generaBicyclusandJunonia. In some lineages, eyespots and bands arise in a single sex, whereas in other lineages they appear in both sexes but are then lost in one of the sexes. In addition, lineages displaying sexual dimorphism were more likely to become sexually monomorphic than they were to remain dimorphic. This derived monomorphism was either owing to a loss of the ornament (‘drab monomorphism’) or owing to a gain of the same ornament by the opposite sex (‘mutual ornamentation’). Our results demonstrate the necessity of a plurality in theories explaining the evolution of sexual dimorphism within and across taxa. The origins and evolutionary fate of sexual dimorphism are probably influenced by underlying genetic architecture responsible for sex-limited expression and the degree of intralocus sexual conflict. Future comparative and developmental work on sexual dimorphism within and among taxa will provide a better understanding of the biases and constraints governing the evolution of animal sexual dimorphism.
The importance of surface-based cues for face discrimination in non-human primates
Authors: Parr Lisa A. , Taubert Jessica
Published: December 2010

Understanding how individual identity is processed from faces remains a complex problem. Contrast reversal, showing faces in photographic negative, impairs face recognition in humans and demonstrates the importance of surface-based information (shading and pigmentation) in face recognition. We tested the importance of contrast information for face encoding in chimpanzees and rhesus monkeys using a computerized face-matching task. Results showed that contrast reversal (positive to negative) selectively impaired face processing in these two species, although the impairment was greater for chimpanzees. Unlike chimpanzees, however, monkeys performed just as well matching negative to positive faces, suggesting that they retained some ability to extract identity information from negative faces. A control task showed that chimpanzees, but not rhesus monkeys, performed significantly better matching face parts compared with whole faces after a contrast reversal, suggesting that contrast reversal acts selectively on face processing, rather than general visual-processing mechanisms. These results confirm the importance of surface-based cues for face processing in chimpanzees and humans, while the results were less salient for rhesus monkeys. These findings make a significant contribution to understanding the evolution of cognitive specializations for face processing among primates, and suggest potential differences between monkeys and apes.
The role of desire, duty and intention in predicting attempts to quit smoking
Authors: Smit Eline S. , Fidler Jennifer A. , West Robert
Published: December 2010

Aims  Motivation to quit smoking predicts quit attempts, although little is known about the role played by its different aspects. This study assessed the predictive value of desire, duty and intention to quit, three different aspects of motivation.

Design  A longitudinal study was conducted involving a nationally representative sample of smokers assessed at baseline and 3 and 6 months later. Baseline assessment took place by face‐to‐face computer‐assisted interviews; follow‐up assessments by postal questionnaires.

Setting  England.

Participants  From April 2008 to June 2009, a total of 5593 adult smokers were recruited; 1263 were followed‐up at 3 months and 1096 at 6 months.

Measurements  Three dichotomous measures of motivation to quit (wanting to quit, believing one ought to quit, intention to quit soon) were taken at baseline. Whether a subsequent quit attempt was made was recorded at 3‐ and 6‐month follow‐up.

Findings  More smokers believed they ought to quit smoking than wanted to or intended to soon (39.0, 29.3 and 23.5%, respectively). Desire and intention were independent predictors of quit attempts at both follow‐ups, whereas combining them did not add predictive value and duty was not a predictor. While the predictive value of desire or intention alone disappeared when accompanied by duty, their combination was robust against its negative effect.

Conclusions  Desire and intention independently positively predict quit attempts, while duty appears to mitigate their effect. It would be worth monitoring all three aspects of motivation when evaluating the impact of smoking cessation interventions on motivation to quit.
Developmental variations in metabolic capacity of flavin‐containing mono‐oxygenase 3 in childhood
Authors: Shimizu Makiko , Denton Travis , Kozono Marie , Cashman John R. , Leeder J. Steven , Yamazaki Hiroshi
Published: December 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The function of the human flavin‐containing mono‐oxygenase (FMO) has been shown to have large inter‐individual variation related to trimethylaminuria.

WHAT THIS STUDY ADDS

• The study suggests that a developmental variation in functional metabolic capacity of FMO3 is occurring in childhood on the basis of in vivo phenotyping tests and in vitro liver microsomal determinations.

AIM The aim of this study was to investigate intra‐ and inter‐individual variations of functional metabolic capacity of flavin‐containing mono‐oxygenase (FMO) during childhood using trimethylamine N‐oxygenation as a probe reaction.

METHODS Trimethylamine N‐oxygenation functional activity and presence of FMO1 (fetal form), FMO3 (adult form), and FMO5 (endogenous form) were immunochemically determined and compared in human liver microsomes obtained from children at various ages. As a control, the same parameters were studied with recombinant FMO1, FMO3 and FMO5 proteins as enzyme sources. Developmental variation in functional metabolic capacity of FMO was estimated by measuring urinary trimethylamine and its N‐oxide in several individuals at different ages and in a group of 77 subjects in childhood.

RESULTS There was a significant correlation between trimethylamine N‐oxygenation functional activity and FMO3 expression levels in human liver microsomes (r= 0.71, P < 0.05, n= 9). Trimethylamine N‐oxygenation was catalyzed largely by FMO3 and not by FMO1 or FMO5. On the basis of analysis of intra‐individual observations and collective urine samples under daily dietary conditions it was possible that neonates or infants harbouring at least one non‐inactive‐allele of the FMO3 gene could have developmental FMO3 metabolic capacity in childhood.

CONCLUSIONS Developmental variations in functional metabolic capacity of FMO3 in childhood were shown both on the basis of in vivo phenotyping tests and in in vitro liver microsomal determinations.
Strain‐specific immunomodulatory effects of Lactobacillus plantarum strains on birch‐pollen‐allergic subjects out of season
Authors: Snel J. , Vissers Y. M. , Smit B. A. , Jongen J. M. J. , van der Meulen E. T. , Zwijsen R. , Ruinemans‐Koerts J. , Jansen A. P. H. , Kleerebezem M. , Savelkoul H. F. J.
Published: December 2010

Cite this as: J. Snel, Y. M. Vissers,B. A. Smit, J. M. J. Jongen, E. T. van der Meulen, R. Zwijsen, J. Ruinemans‐Koerts, A. P. H. Jansen,M. Kleerebezem and H. F. J. Savelkoul,Clinical & Experimental Allergy, 2011 (41) 232–242.

Background
Allergic diseases are increasing world‐wide, and according to the hygiene hypothesis may be related to a decreased exposure to environmental bacteria. Probiotic bacteria are recognized for their immunomodulating properties, and may benefit allergy patients. In vitro studies reveal immunomodulatory effects that are strain dependent. Differential immunomodulatory in vitro capacities cannot be extrapolated directly to in vivo efficacy. Thus, in vitro screening should preferably be followed by a comparative analysis of the selected immunomodulatory strains in an in vivo setting.

Objective
We selected five Lactobacillus strains on their IL‐10‐inducing capacity, and evaluated the immunomodulatory properties in birch‐pollen‐allergic subjects outside the hayfever season, with a reduction of IL‐13 as the primary outcome.

Methods
A double‐blind, placebo‐controlled parallel study was performed in which 62 subjects with a proven birch‐pollen allergy consumed one of five different probiotic yoghurts containing four Lactobacillus plantarum strains and one Lactobacillus casei strain or a placebo yoghurt. Blood samples were collected at the start and after 4 weeks. Several immune parameters were determined in serum and peripheral blood mononuclear cell cultures (PBMC) derived from these subjects.

Results
A decrease in birch‐pollen‐specific IgE was found for four probiotic strains. L. casei Shirota reduced the number of CD16+/CD56+ cells in peripheral blood mononuclear cells. For strain L. plantarum CBS125632, the decrease in IgE coincided with significant decreases in IL‐5 and IL‐13 production by αCD3/αCD28‐stimulated PBMC cultures.

Conclusion and Clinical Relevance
Subjects with seasonal allergy can be used to determine immunomodulatory responses outside the pollen season within a 4‐week study period. L. plantarum CBS125632 decreased several immune markers related to allergy, and may have the potential to alleviate the severity of seasonal allergy symptoms.
Efficacy of fluticasone furoate nasal spray vs. placebo for the treatment of ocular and nasal symptoms of allergic rhinitis: a systematic review
Authors: Rodrigo G. J. , Neffen H.
Published: December 2010

Cite this as: G. J. Rodrigo and H. Neffen,Clinical & Experimental Allergy, 2011 (41) 160–170.

Background
Although previous data suggest that intranasal fluticasone furoate (FF) improves ocular symptoms of allergic rhinitis (AR), it presents serious limitations that question its results and conclusions. Therefore, an independent systematic review with meta‐analysis is required to confirm and clarify the magnitude of the effect of FF.

Methods
This review compared the efficacy of intranasal FF to placebo on ocular and nasal symptoms in patients with AR. Primary outcomes were reflective and instantaneous total ocular symptom scores (rTOSS and iTOSS), and reflective and instantaneous total nasal symptom scores (rTNSS and iTNSS). Secondary outcomes included the assessment of response to therapy, quality of life (QoL), and adverse effects.

Results
Sixteen trials (5.348 patients) were selected. Seven studies included seasonal AR patients and nine studies, perennial AR patients. Intranasal FF significantly improved rTOSS and iTOSS scores compared with placebo in patients with seasonal (weighted mean difference [WMD] −0.54, 95% CI, −0.70 to −0.37, and −0.59, 95% CI, −0.76 to −0.43) and perennial AR (−0.33, 95% CI, −0.31 to −0.05, and −0.38, 95% CI, −0.69 to –0.07). Intranasal FF was also significantly more effective in improving rTNSS and iTNSS scores in seasonal (WMD=−1.14, 95% CI, −1.57 to −0.72, and −1.32, 95% CI, −1.64 to −1.01) and perennial AR patients (−0.83, 95% CI, −1.08 to −0.59, and −0.90, 95% CI, −1.33 to −0.48). Finally, there were greater improvements in response to therapy and QoL with a favourable safety profile.

Conclusions and Clinical Relevance
Intranasal FF showed a consistent ocular and nasal efficacy along with improvement in QoL in AR patients. This review provides significant evidence that treatment with FF nasal spray at a dose of 110 mcg once daily is effective in relieving ocular and nasal symptoms in adolescents and adults with AR.
Mitogen‐activated protein kinase signalling and ERK1/2 bistability in asthma
Authors: Alam R. , Gorska M. M.
Published: December 2010

Cite this as: R. Alam and M. M. Gorska,Clinical & Experimental Allergy, 2011 (41) 149–159.

Mitogen‐activated protein kinases (MAPKs) integrate signals from numerous receptors and translate these signals into cell functions. MAPKs are critical for immune cell metabolism, migration, production of pro‐inflammatory mediators, survival and differentiation. We provide a concise review of the involvement of MAPK in important cells of the immune system. Certain cell functions, e.g. production of pro‐inflammatory mediators resolve quickly and may require a transient MAPK activation, other processes such as cell differentiation and long‐term survival may require persistent MAPK signal. The persistent MAPK signal is frequently a consequence of positive feedback loops or double negative feedback loops which perpetuate the signal after removal of an external cell stimulus. This self‐perpetuated activation of a signalling circuit is a manifestation of its bistability. Bistable systems can exist in ‘on’ and ‘off’ states and both states are stable. We have demonstrated the existence of self‐perpetuated activation mechanism for ERK1/2 in bronchial epithelial cells. This sustained activation of ERK1/2 supports long‐term survival of these cells and primes them for cytokine transcription. ERK1/2 bistability arises from repetitive stimulation of the cell. The repeated stimulation (e.g. repeated viral infection or repeated allergen exposure) seems to be a common theme in asthma and other chronic illnesses. We thus hypothesize that the self‐perpetuated ERK1/2 signal plays an important role in the pathogenesis of asthma.
Associations of social and behavioural factors with early childhood caries in Xiamen city in China
Authors: Li Yang , Zhang Ye , Yang Ran , Zhang Qiong , Zou Jing , Kang Deying
Published: December 2010

Background

Early childhood caries (ECC) is the presence of caries in primary teeth in children 71 months of age or younger. Despite a decreasing prevalence of caries in China, ECC and related risk factors in China have not been well studied.

Aims

This study aimed to investigate the status of ECC in children living in Xiamen city in China and to analyse the associated social and behaviour determinants.

Design

A stratified random sample consisted of 1523 children with normal birth records. Clinical examination was performed to record caries at the surface level. Parents filled in questionnaires regarding eating habits, family status, childcare provider, and oral intervention.

Results

Prevalence of ECC in studied child population was 56.8–78.31%, with an increasing tendency with age. The following factors were found to be significantly associated with ECC: age, candy, carbonated drink, bedtime eating, late start of brushing, low education of parents, private childcare, increased number of siblings, rural residence, and lack of oral health knowledge. Using a stepwise forward logistic regression analysis, a prediction model was established.

Conclusion

Early childhood caries in children living in Xiamen city was strongly associated with eating habits, family‐ and childcare‐related factors and tooth‐brushing. The ECC‐high‐risk group is children in rural private childcare facilities.
Comparison of the remineralizing potential of child formula dentifrices
Authors: Ekambaram Manikandan , Itthagarun Anut , King Nigel Martyn
Published: December 2010

Background

Although child formula fluoridated dentifrices can be used safely by young children their remineralizing capability remains questionable.

Aim

To evaluate the remineralizing potential of child formula dentifrices on primary teeth.

Design

In vitro single‐section technique utilizing a 7 days pH‐cycling model.

Methods

Primary teeth were placed in demineralizing solution for 96 h to produce artificial carious lesions 100 μm deep, and then cut longitudinally into 50 sections 100–150 μm thick and randomly assigned to five groups. Sections in Groups A to D were treated with dentifrices containing 500 ppm AmF, 500 ppm MFP, 500 ppm MFP and xylitol, or 500 ppm NaF, respectively. Group E sections were treated with a nonfluoridated dentifrice.

Outcome measurements

Lesions were evaluated using polarized light microscopy and microradiography.

Results

Group D (500 ppm NaF) sections exhibited a significant decrease in lesion depth, whereas those in Group E (nonF) showed a significant increase in depth (P < 0.05, paired t‐test). Decrease in lesion progression was observed in Groups A, B and C.

Conclusions

The 500 ppm NaF dentifrice demonstrated remineralization of carious lesions by virtue of a significant decrease in lesion depth; whereas dentifrices that contained AmF, MFP and MFP with xylitol decelerated the progression of demineralization.
Working memory subsystems and task complexity in young boys with Fragile X syndrome
Authors: Baker S. , Hooper S. , Skinner M. , Hatton D. , Schaaf J. , Ornstein P. , Bailey D.
Published: December 2010

Background  Working memory problems have been targeted as core deficits in individuals with Fragile X syndrome (FXS); however, there have been few studies that have examined working memory in young boys with FXS, and even fewer studies that have studied the working memory performance of young boys with FXS across different degrees of complexity. The purpose of this study was to investigate the phonological loop and visual–spatial working memory in young boys with FXS, in comparison to mental age‐matched typical boys, and to examine the impact of complexity of the working memory tasks on performance.

Methods  The performance of young boys (7 to 13‐years‐old) with FXS (n = 40) was compared with that of mental age and race matched typically developing boys (n = 40) on measures designed to test the phonological loop and the visuospatial sketchpad across low, moderate and high degrees of complexity. Multivariate analyses were used to examine group differences across the specific working memory systems and degrees of complexity.

Results  Results suggested that boys with FXS showed deficits in phonological loop and visual–spatial working memory tasks when compared with typically developing mental age‐matched boys. For the boys with FXS, the phonological loop was significantly lower than the visual–spatial sketchpad; however, there was no significant difference in performance across the low, moderate and high degrees of complexity in the working memory tasks. Reverse tasks from both the phonological loop and visual–spatial sketchpad appeared to be the most challenging for both groups, but particularly for the boys with FXS.

Conclusions  These findings implicate a generalised deficit in working memory in young boys with FXS, with a specific disproportionate impairment in the phonological loop. Given the lack of differentiation on the low versus high complexity tasks, simple span tasks may provide an adequate estimate of working memory until greater involvement of the central executive is achieved.
Neuropsychological differences between survivors of supratentorial and infratentorial brain tumours
Authors: Patel S. K. , Mullins W. A. , O'Neil S. H. , Wilson K.
Published: December 2010

Background  The purpose of this study is to evaluate the relationship between brain tumour location and core areas of cognitive and behavioural functioning for paediatric brain tumour survivors. The extant literature both supports and refutes an association between paediatric brain tumour location and neurocognitive outcomes. We examined neuropsychological test data to identify any differences in neurocognitive and behavioural profile associated with supratentorial versus infratentorial tumour location.

Methods  Following Institutional Review Board approval, the medical records and neuropsychological test data collected between 1997 and 2002 for 70 children treated for brain tumour at Children's Hospital Los Angeles were reviewed. Fifty‐one per cent of the participants had tumours located in the supratentorial regions of the brain, whereas 49% had infratentorial tumours. Primary medical treatments involved tumour resection (90%), cranial radiation therapy (76%), chemotherapy (71%), and 59% all three medical procedures. The two tumour location groups did not differ significantly in the cumulative treatment dose of irradiation to the tumour bed or in the dose delivered to the whole brain. Neuropsychological test data included measures of verbal and non‐verbal intellectual functioning, attention/working memory, processing speed, verbal and visual memory, fine motor skills, visual–motor integration, academic achievement, and social–emotional functioning. Differences between the two groups were evaluated using anova, t‐tests and chi‐squared statistical tests.

Results  The supratentorial and infratentorial tumour location groups did not differ on measures of intellectual functioning. However, survivors of infratentorial tumours performed more poorly on selected measures of more specific cognitive functions and on parent‐report of social–emotional functioning relative to survivors of supratentorial tumours, even when age at diagnosis was held as a covariate. Higher frequency of auditory deficits was noted in the infratentorial tumour group and was associated with lowered academic achievement scores.

Conclusions  The differences by location found in more specific neurocognitive and social–emotional variables, after controlling for age at diagnosis, may possibly reflect tumour location‐specific effects. However, this interpretation remains tentative given the limitations in our study and inability to control for the range of medical and treatment‐related factors that may have contributed towards the outcomes observed in our sample. At the same time, most of our findings appear consistent with reports from recent studies in this area.
The role of community nurses and residential staff in supporting women with intellectual disability to access breast screening services
Authors: Taggart L. , Truesdale‐Kennedy M. , McIlfatrick S.
Published: December 2010

Background  Women with intellectual disability (ID) are surviving to the age group at greatest risk of developing breast cancer (50–69 years). These women are more likely to experience a greater number of risk factors placing them at an advanced threat of developing breast cancer. However, as a result of cognitive deficits and communication difficulties these women are dependent upon staff to support them to attend the breast screening clinics.

Aim  The aim of this paper was to examine how community nurses and residential staff support women with ID to access breast screening services.

Methodology  Six focus groups were held with community nurses and residential staff who work in the field of ID in one region of the UK. The focus groups were tape recorded and the transcriptions were subjected to a thematic content analysis.

Findings  Although many of the participants recognised the risk factors and signs/symptoms of breast cancer, there was still a deficit of knowledge. Both positive and negative experiences of women with ID attending for breast screening were reported; however, greater discussion focused on the latter. The participants identified ‘a lack of health educational material’ and also negative ‘emotions, attitudes and physical barriers’ as inhibiting factors for attendance.

Discussion  This paper highlights the need for developing a health promotion programme for women with ID focusing on breast awareness and information on screening, and also healthier lifestyles. Breast awareness via visual checks was identified for women with ID who refused to attend the breast clinics; however, issues of informed ‘consent’ and ‘vulnerability’ were raised for staff and also family carers having to undertake these checks. Development of user‐friendly health educational literature using ‘pictures, symbols, signs’ and simplified words should be accessible to all ID staff, healthcare staff, and also women with ID.
In Sup35p filaments (the [PSI+] prion), the globular C‐terminal domains are widely offset from the amyloid fibril backbone
Authors: Baxa Ulrich , Keller Paul W. , Cheng Naiqian , Wall Joseph S. , Steven Alasdair C.
Published: December 2010

In yeast cells infected with the [PSI+] prion, Sup35p forms aggregates and its activity in translation termination is downregulated. Transfection experiments have shown that Sup35p filaments assembled in vitro are infectious, suggesting that they reproduce or closely resemble the prion. We have used several EM techniques to study the molecular architecture of filaments, seeking clues as to the mechanism of downregulation. Sup35p has an N‐terminal ‘prion’ domain; a highly charged middle (M‐)domain; and a C‐terminal domain with the translation termination activity. By negative staining, cryo‐EM and scanning transmission EM (STEM), filaments of full‐length Sup35p show a thin backbone fibril surrounded by a diffuse 65‐nm‐wide cloud of globular C‐domains. In diameter (∼8 nm) and appearance, the backbones resemble amyloid fibrils of N‐domains alone. STEM mass‐per‐unit‐length data yield ∼1 subunit per 0.47 nm for N‐fibrils, NM‐filaments and Sup35p filaments, further supporting the fibril backbone model. The 30 nm radial span of decorating C‐domains indicates that the M‐domains assume highly extended conformations, offering an explanation for the residual Sup35p activity in infected cells, whereby the C‐domains remain free enough to interact with ribosomes.