A Computational Clonal Analysis of the Developing Mouse Limb Bud

A comprehensive spatio-temporal description of the tissue movements underlying organogenesis would be an extremely useful resource to developmental biology. Clonal analysis and fate mappings are popular experiments to study tissue movement during morphogenesis. Such experiments allow cell populations to be labeled at an early stage of development and to follow their spatial evolution over time. However, disentangling the cumulative effects of the multiple events responsible for the expansion of the labeled cell population is not always straightforward. To overcome this problem, we develop a novel computational method that combines accurate quantification of 2D limb bud morphologies and growth modeling to analyze mouse clonal data of early limb development. Firstly, we explore various tissue movements that match experimental limb bud shape changes. Secondly, by comparing computational clones with newly generated mouse clonal data we are able to choose and characterize the tissue movement map that better matches experimental data. Our computational analysis produces for the first time a two dimensional model of limb growth based on experimental data that can be used to better characterize limb tissue movement in space and time. The model shows that the distribution and shapes of clones can be described as a combination of anisotropic growth with isotropic cell mixing, without the need for lineage compartmentalization along the AP and PD axis. Lastly, we show that this comprehensive description can be used to reassess spatio-temporal gene regulations taking tissue movement into account and to investigate PD patterning hypothesis

Relationship between craving and personality in treatment-seeking women with substance-related disorders

BACKGROUND: Individual differences may impact susceptibility to addiction. The impact of personality features on drug craving, however, has not been studied, particularly in women. METHODS: Ninety-five treatment-seeking women with substance dependence, abstinent for at least 5 and no more than 21 days, were investigated regarding the correlation between personality factors and craving. Personality was assessed using the Temperament and Character Inventory (TCI), the NEO Personality Inventory Revised (NEO-PI-R), and the Barratt Impulsiveness Scale version 11 (BIS-11). Cravings were assessed through the Pennsylvania Craving Scale (PCS), and the Craving Questionnaire (CQ). Anxiety and depressive symptomatology were also recorded. RESULTS: Craving scores were positively correlated with depression and negatively correlated with number of days abstinent from substance use. Also, craving scores were positively associated with the novelty-seeking factor from the TCI and the total score on the BIS-11, and negatively associated with the conscientiousness and agreeableness facets of the NEO-PI-R. CONCLUSION: Findings suggest that personality features, particularly impulsiveness, can be important predictors of craving in women, which has important implications for treatment planning

Electronic Cigarette Advertising Impacts Adversely on Smoking Behaviour Within a London Student Cohort: A Cross-Sectional Structured Survey.

INTRODUCTION: In contrast to tobacco smoking, electronic cigarette ("vaping") advertisement had been approved in the United Kingdom (UK) in January 2013. Currently, there are an estimated 3.2 million UK e-cigarette users. The impact of e-cigarette advertisement on tobacco use has not been studied in detail. We hypothesised that e-cigarette advertisement impacts on conventional smoking behaviour. METHODS: A cross-sectional structured survey assessed the impact of e-cigarette advertising on the perceived social acceptability of cigarette and e-cigarette smoking and on using either cigarettes or e-cigarettes (on a scale of 1 to 5/'not at all' to 'a lot'). The survey was administered between January to March 2015 to London university students, before and after viewing 5 UK adverts including a TV commercial. RESULTS: Data were collected from 106 participants (22 ± 2 years, 66% male), comprising cigarette smokers (32%), non-smokers (54%) and ex-smokers (14%). This included vapers (16%), non-vapers (77%) and ex-vapers (7%). After viewing the adverts, smokers (2.6 ± 1.0 vs. 3.8 ± 1.1, p = 0.001) and non-smokers (3.2 ± 0.7 vs. 3.7 ± 0.8, p = 0.007) felt smoking was more socially acceptable, compared to before viewing them. Participants were more likely to try both e-cigarettes (1.90 ± 1.03 to 3.09 ± 1.11, p < 0.001) and conventional cigarettes (1.73 ± 0.83 to 2.27 ± 1.13, p < 0.001) after viewing the adverts compared to before. Vapers were less likely to smoke both an e-cigarette, and a conventional cigarette after viewing the adverts. CONCLUSION: E-cigarette advertising encourages both e-cigarette and conventional cigarette use in young smokers and non-smokers. The adverts increase the social acceptability of smoking without regarding the importance of public health campaigns that champion smoking cessation

Geodemographics profiling of influenza A and B virus infections in community neighborhoods in Japan

<p>Abstract</p> <p>Background</p> <p>The spread of influenza viruses in a community are influenced by several factors, but no reports have focused on the relationship between the incidence of influenza and characteristics of small neighborhoods in a community. We aimed to clarify the relationship between the incidence of influenza and neighborhood characteristics using GIS and identified the type of small areas where influenza occurs frequently or infrequently.</p> <p>Methods</p> <p>Of the 19,077 registered influenza cases, we analyzed 11,437 influenza A and 5,193 influenza B cases that were diagnosed by the rapid antigen test in 66-86 medical facilities in Isahaya City, Japan, from 2004 to 2008. We used the commercial geodemographics dataset, Mosaic Japan to categorize and classify each neighborhood. Furthermore, we calculated the index value of influenza in crude and age adjusted rates to evaluate the incidence of influenza by Mosaic segmentation. Additional age structure analysis was performed to geodemographics segmentation to explore the relationship between influenza and family structure.</p> <p>Results</p> <p>The observed number of influenza A and B patients in the neighborhoods where young couples with small children lived was approximately 10-40% higher than the expected number (p < 0.01) during all seasons. On the contrary, the number of patients in the neighborhoods of the aging society in a rural area was 20-50% lower than the expected number (p < 0.01) during all seasons. This tendency was consistent after age adjustment except in the case of influenza B, which lost significance in higher incidence areas, but the overall results indicated high transmission of influenza in areas where young families with children lived.</p> <p>Conclusions</p> <p>Our analysis indicated that the incidence of influenza A and B in neighborhood groups is related to the family structure, especially the presence of children in households. Simple statistical analysis of geodemographics data is an effective method to understand the differences in the incidence of influenza among neighborhood groups, and it provides a valuable basis for community strategies to control influenza.</p

The Hall Technique; a randomized controlled clinical trial of a novel method of managing carious primary molars in general dental practice: acceptability of the technique and outcomes at 23 months

<p>Abstract</p> <p>Background</p> <p>Scotland has high levels of untreated dental caries in primary teeth. The Hall Technique is a simplified method of managing carious primary molars using preformed metal crowns (PMCs) cemented with no local anaesthesia, caries removal or tooth preparation. This study compared the acceptability of the Hall Technique for children, their carers, and dentists, and clinical outcomes for the technique, with conventional restorations.</p> <p>Methods</p> <p>General dental practice based, split mouth, randomized controlled trial (132 children, aged 3–10). General dental practitioners (GDPs, n = 17) in Tayside, Scotland (dmft 2.7) placed conventional (Control) restorations in carious primary molars, and Hall Technique PMCs on the contralateral molar (matched clinically and radiographically). Dentists ranked the degree of discomfort they felt the child experienced for each procedure; then children, their carers and dentists stated which technique they preferred. The teeth were followed up clinically and radiographically.</p> <p>Results</p> <p>128 conventional restorations were placed on 132 control teeth, and 128 PMCs on 132 intervention teeth. Using a 5 point scale, 118 Hall PMCs (89%) were rated as no apparent discomfort up to mild, not significant; for Control restorations the figure was 103 (78%). Significant, unacceptable discomfort was recorded for two Hall PMCs (1.5%) and six Control restorations (4.5%). 77% of children, 83% of carers and 81% of dentists who expressed a preference, preferred the Hall technique, and this was significant (Chi square, p < 0.0001). There were 124 children (94% of the initial sample) with a minimum follow-up of 23 months. The Hall PMCs outperformed the Control restorations:</p> <p>a) 'Major' failures (signs and symptoms of irreversible pulpal disease): 19 Control restorations (15%); three Hall PMCs (2%) (P < 0.000);</p> <p>b) 'Minor' failures (loss of restoration, caries progression): 57 Control restorations (46%); six Hall PMCs (5%) (P < 0.000)</p> <p>c) Pain: 13 Control restorations (11%); two Hall PMCs (2%) (P = 0.003).</p> <p>Conclusion</p> <p>The Hall Technique was preferred to conventional restorations by the majority of children, carers and GDPs. After two years, Hall PMCs showed more favourable outcomes for pulpal health and restoration longevity than conventional restorations. The Hall Technique appears to offer an effective treatment option for carious primary molar teeth.</p> <p>Trial registration number</p> <p>Current Controlled Trials ISRCTN47267892 – A randomized controlled trial in primary care of a novel method of using preformed metal crowns to manage decay in primary molar teeth: the Hall technique.</p

IQuaD dental trial; improving the quality of dentistry : a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care

Peer reviewedPublisher PD

Osteological and Soft-Tissue Evidence for Pneumatization in the Cervical Column of the Ostrich (Struthio camelus) and Observations on the Vertebral Columns of Non-Volant, Semi-Volant and Semi-Aquatic Birds

© 2015 Apostolaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License [4.0], which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Genetic and Structural Basis for Selection of a Ubiquitous T Cell Receptor Deployed in Epstein-Barr Virus Infection

Despite the ∼1018 αβ T cell receptor (TCR) structures that can be randomly manufactured by the human thymus, some surface more frequently than others. The pinnacles of this distortion are public TCRs, which exhibit amino acid-identical structures across different individuals. Public TCRs are thought to result from both recombinatorial bias and antigen-driven selection, but the mechanisms that underlie inter-individual TCR sharing are still largely theoretical. To examine this phenomenon at the atomic level, we solved the co-complex structure of one of the most widespread and numerically frequent public TCRs in the human population. The archetypal AS01 public TCR recognizes an immunodominant BMLF1 peptide, derived from the ubiquitous Epstein-Barr virus, bound to HLA-A*0201. The AS01 TCR was observed to dock in a diagonal fashion, grasping the solvent exposed peptide crest with two sets of complementarity-determining region (CDR) loops, and was fastened to the peptide and HLA-A*0201 platform with residue sets found only within TCR genes biased in the public response. Computer simulations of a random V(D)J recombination process demonstrated that both TCRα and TCRβ amino acid sequences could be manufactured easily, thereby explaining the prevalence of this receptor across different individuals. Interestingly, the AS01 TCR was encoded largely by germline DNA, indicating that the TCR loci already comprise gene segments that specifically recognize this ancient pathogen. Such pattern recognition receptor-like traits within the αβ TCR system further blur the boundaries between the adaptive and innate immune systems

Limb proportions show developmental plasticity in response to embryo movement

Animals have evolved limb proportions adapted to different environments, but it is not yet clear to what extent these proportions are directly influenced by the environment during prenatal development. The developing skeleton experiences mechanical loading resulting from embryo movement. We tested the hypothesis that environmentally-induced changes in prenatal movement influence embryonic limb growth to alter proportions. We show that incubation temperature influences motility and limb bone growth in West African Dwarf crocodiles, producing altered limb proportions which may, influence post-hatching performance. Pharmacological immobilisation of embryonic chickens revealed that altered motility, independent of temperature, may underpin this growth regulation. Use of the chick also allowed us to merge histological, immunochemical and cell proliferation labelling studies to evaluate changes in growth plate organisation, and unbiased array profiling to identify specific cellular and transcriptional targets of embryo movement. This disclosed that movement alters limb proportions and regulates chondrocyte proliferation in only specific growth plates. This selective targeting is related to intrinsic mTOR (mechanistic target of rapamycin) pathway activity in individual growth plates. Our findings provide new insights into how environmental factors can be integrated to influence cellular activity in growing bones and ultimately gross limb morphology, to generate phenotypic variation during prenatal development