3,745 research outputs found

    Electrochemical fecal pellet sensor for simultaneous real-time ex vivo detection of colonic serotonin signalling and motility

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    Various investigations have focused on understanding the relationship between mucosal serotonin (5-HT) and colonic motility, however contradictory studies have questioned the importance of this intestinal transmitter. Here we described the fabrication and use of a fecal pellet electrochemical sensor that can be used to simultaneously detect the release of luminal 5-HT and colonic motility. Fecal pellet sensor devices were fabricated using carbon nanotube composite electrodes that were housed in 3D printed components in order to generate a device that had shape and size that mimicked a natural fecal pellet. Devices were fabricated where varying regions of the pellet contained the electrode. Devices showed that they were stable and sensitive for ex vivo detection of 5-HT, and no differences in the fecal pellet velocity was observed when compared to natural fecal pellets. The onset of mucosal 5-HT was observed prior to the movement of the fecal pellet. The release of mucosal 5-HT occurred oral to the fecal pellet and was linked to the contraction of the bowel wall that drove pellet propulsion. Taken, together these findings provide new insights into the role of mucosal 5-HT and suggest that the transmitter acts as a key initiator of fecal pellet propulsion

    Divergence and Remarkable Diversity of the Y Chromosome in Guppies

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    The guppy sex chromosomes show an extraordinary diversity in divergence across populations and closely related species. In order to understand the dynamics of the guppy Y chromosome, we used linked-read sequencing to assess Y chromosome evolution and diversity across upstream and downstream population pairs that vary in predator and food abundance in three replicate watersheds. Based on our population-specific genome assemblies, we first confirmed and extended earlier reports of two strata on the guppy sex chromosomes. Stratum I shows significant accumulation of male-specific sequence, consistent with Y divergence, and predates the colonization of Trinidad. In contrast, Stratum II shows divergence from the X, but no Y-specific sequence, and this divergence is greater in three replicate upstream populations compared to their downstream pair. Despite longstanding assumptions that sex chromosome recombination suppression is achieved through inversions, we find no evidence of inversions associated with either Stratum I or Stratum II. Instead, we observe a remarkable diversity in Y chromosome haplotypes within each population, even in the ancestral Stratum I. This diversity is likely due to gradual mechanisms of recombination suppression, which, unlike an inversion, allow for the maintenance of multiple haplotypes. In addition, we show that this Y diversity is dominated by low-frequency haplotypes segregating in the population, suggesting a link between haplotype diversity and female-preference for rare Y-linked colour variation. Our results reveal the complex interplay between recombination suppression and Y chromosome divergence at the earliest stages of sex chromosome divergence

    CANINES AND CHILDHOOD CANCER: THE EFFECTS OF ANIMAL-ASSISTED THERAPY FOR PATIENTS, FAMILIES AND THERAPY DOGS

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    PLEASE USE THE PDF (available from the download link) TO FOLLOW ALONG WITH THE VIDEO For many people, animals take center stage in their daily lives, offering companionship, comfort, joy and for some, even kinship. Increasingly, greater attention has been given to the roles that animals can play in supporting the health and emotional well-being of people in need, specifically through the use of animal-assisted therapy (AAT). However, while the field of human-animal interaction (HAI) research has expanded enormously in recent years, it is still unclear whether the incorporation of animals into clinical settings is effective from a scientific standpoint. Likewise, although many studies have examined the complex bio-psychosocial impacts of childhood cancer for patients and their families, few have identified complementary therapeutic interventions to help families with the coping process. Finally, there remains a lack of sound HAI research on how AAT may affect therapy dogs. The Canines and Childhood Cancer (CCC) study seeks to address these research gaps by examining the ability of AAT to impact the well-being and distress levels of pediatric oncology patients and their parents/caregivers, as well as the therapy dogs who visit them, throughout the child’s treatment process. Researchers will present the preliminary findings from a pilot trial conducted with three pediatric oncology sites, including data from patients, families and therapy dogs, as well as information on the feasibility of conducting rigorous and innovative AAT research across multiple pediatric healthcare settings. CCC is a collaborative project between American Humane Association and Pfizer Animal Health

    Population-genomic insights into emergence, crop-adaptation, and dissemination of Pseudomonas syringae pathogens

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    This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Many bacterial pathogens are well characterized but, in some cases, relatively little is known about the populations from which they emerged. This limits understanding of the molecular mechanisms underlying disease. The crop pathogen Pseudomonas syringae sensu lato has been widely isolated from the environment, including wild plants and components of the water cycle, and causes disease in several economically important crops. Here, we compared genome sequences of 45 P. syringae crop pathogen outbreak strains with 69 closely related environmental isolates. Phylogenetic reconstruction revealed that crop pathogens emerged many times independently from environmental populations. Unexpectedly, differences in gene content between environmental populations and outbreak strains were minimal with most virulence genes present in both. However, a genome-wide association study identified a small number of genes, including the type III effector genes hopQ1 and hopD1, to be associated with crop pathogens, but not with environmental populations, suggesting that this small group of genes may play an important role in crop disease emergence. Intriguingly, genome-wide analysis of homologous recombination revealed that the locus Psyr 0346, predicted to encode a protein that confers antibiotic resistance, has been frequently exchanged among lineages and thus may contribute to pathogen fitness. Finally, we found that isolates from diseased crops and from components of the water cycle, collected during the same crop disease epidemic, form a single population. This provides the strongest evidence yet that precipitation and irrigation water are an overlooked inoculum source for disease epidemics caused by P. syringae.Caroline L. Monteil received support from INRA and the European Union, in the framework of the Marie-Curie FP7 COFUND People Programme, through the award of an AgreenSkills’ fellowship (under grant agreement n° 267196). Research in Boris A. Vinatzer’s laboratory and genome sequencing was funded by the National Science Foundation of the USA (grants IOS-1354215 and DEB-1241068). Funding for work in the Vinatzer laboratory was also provided in part by the Virginia Agricultural Experiment Station and the Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture. Work carried out in the Sheppard laboratory was supported by the Medical Research Council (MRC) grant MR/L015080/1, and the Wellcome Trust grant 088786/C/09/Z. GM was supported by a NISCHR Health Research Fellowship (HF-14-13)

    Supporting the game construction process: development of artefacts in the context of a Toolkit to Game Design

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    The Gamers4Nature project aims to deliver a set of strategies to empower and en-courage youngsters (upper-secondary and undergraduate students) to actively participate in games creation while raising knowledge about environmental preservation and biodiversity conservation. To accomplish these goals, a Toolkit to Game Design is being created, containing a set of resources and tools aiming to help in the creation of mobile digital games, namely a Game Construction Cards Set. This paper presents the creation process of the project’s general identi-ty and its concept adaptation to the Game Construction Cards Set, which required a deep understanding of the target audience and the development of a strategy to engage the participants in its activities. A general identity was defined, where a specific “language” to reach this audience was designed and a brand to support it was created. This “language” was applied in all graphic materials developed since day one, namely to the Game Construction Cards Set – focus of this paper. The validation of the prototypes was made through focus groups, using an iterative design approach. The focus groups participants’ inputs were integrated in the de-sign and helped with the graphic elements’ evolution, allowing the project to maintain a coherent strategy in all its representations that exceeds its graphic lan-guage and a deeper identification with the developed artefacts.publishe

    Agricultural Recovery: Food Security and Beyond

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    Burundi is still experiencing a major food crisis. One important element that will help to avoid new episodes of violence is revised agricultural policies that support sustainable food security. Food crops and livestock supply 91 percent of agricultural GDP and the major livelihood for most households, thus it is essential to promote production and commercialization of subsistence crops and livestock. These subsectors currently perform poorly and foster a chronic food deficit, a condition that underlines the extreme vulnerability of the population to production-related risks. With food demand increasing at an annual rate of 3 to 6 percent, it is urgent to improve the contribution of the subsistence crops and livestock subsectors. The potential for improvement is great, and beyond the need for reforms that will benefit all sectors, improvements will require public investments to enhance productivity and better market access. Necessary changes in the short-run include fostering the use of high quality seed and fertilizer, and improving the management of small livestock. In the long run, research-extension links should be strengthened, producer organizations should be encouraged and supported, and sustainable land and water management practices should be promoted. Investments in infrastructure and market intelligence will need to meet demands generated by the development of urban centers and foster competitiveness of Burundian agricultural commodities relative to those from the region. This chapter explains the food security issue in Burundi and identifies priority actions that will help overcome the major obstacles that prevent growth and improvement of the subsistence crops and livestock subsectors.Burundi; agriculture; food security

    Design of Experiments for Screening

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    The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

    Bidirectional Transcription Directs Both Transcriptional Gene Activation and Suppression in Human Cells

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    Small RNAs targeted to gene promoters in human cells have been shown to modulate both transcriptional gene suppression and activation. However, the mechanism involved in transcriptional activation has remained poorly defined, and an endogenous RNA trigger for transcriptional gene silencing has yet to be identified. Described here is an explanation for siRNA-directed transcriptional gene activation, as well as a role for non-coding antisense RNAs as effector molecules driving transcriptional gene silencing. Transcriptional activation of p21 gene expression was determined to be the result of Argonaute 2–dependent, post-transcriptional silencing of a p21-specific antisense transcript, which functions in Argonaute 1–mediated transcriptional control of p21 mRNA expression. The data presented here suggest that in human cells, bidirectional transcription is an endogenous gene regulatory mechanism whereby an antisense RNA directs epigenetic regulatory complexes to a sense promoter, resulting in RNA-directed epigenetic gene regulation. The observations presented here support the notion that epigenetic silencing of tumor suppressor genes, such as p21, may be the result of an imbalance in bidirectional transcription levels. This imbalance allows the unchecked antisense RNA to direct silent state epigenetic marks to the sense promoter, resulting in stable transcriptional gene silencing

    Evaluating case studies of community-oriented integrated care.

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    This paper summarises a ten-year conversation within London Journal of Primary Care about the nature of community-oriented integrated care (COIC) and how to develop and evaluate it. COIC means integration of efforts for combined disease-treatment and health-enhancement at local, community level. COIC is similar to the World Health Organisation concept of a Community-Based Coordinating Hub - both require a local geographic area where different organisations align their activities for whole system integration and develop local communities for health. COIC is a necessary part of an integrated system for health and care because it enables multiple insights into 'wicked problems', and multiple services to integrate their activities for people with complex conditions, at the same time helping everyone to collaborate for the health of the local population. The conversation concludes seven aspects of COIC that warrant further attention
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