The range of axial rotation of the glenohumeral joint.

Accepted versio

Sources of variability in cytosolic calcium transients triggered by stimulation of homogeneous uro-epithelial cell monolayers

Epithelial tissue structure is the emergent outcome of the interactions between large numbers of individual cells. Experimental cell biology offers an important tool to unravel these complex interactions, but current methods of analysis tend to be limited to mean field approaches or representation by selected subsets of cells. This may result in bias towards cells that respond in a particular way and/or neglect local, context-specific cell responses. Here, an automated algorithm was applied to examine in detail the individual calcium transients evoked in genetically homogeneous, but asynchronous populations of cultured non-immortalized normal human urothelial cells when subjected to either the global application of an external agonist or a localized scratch wound. The recorded calcium transients were classified automatically according to a set of defined metrics and distinct sub-populations of cells that responded in qualitatively different ways were observed. The nature of this variability in the homogeneous cell population was apportioned to two sources: intrinsic variation in individual cell responses and extrinsic variability due to context-specific factors of the environment, such as spatial heterogeneity. Statistically significant variation in the features of the calcium transients evoked by scratch wounding according to proximity to the wound edge was identified. The manifestation of distinct sub-populations of cells is considered central to the coordination of population-level response resulting in wound closure

Mindblind eyes: an absence of spontaneous theory of mind in Asperger syndrome

Adults with Asperger syndrome can understand mental states such as desires and beliefs (mentalizing) when explicitly prompted to do so, despite having impairments in social communication. We directly tested the hypothesis that such individuals nevertheless fail to mentalize spontaneously. To this end, we used an eye-tracking task that has revealed the spontaneous ability to mentalize in typically developing infants. We showed that, like infants, neurotypical adults’ (n = 17 participants) eye movements anticipated an actor’s behavior on the basis of her false belief. This was not the case for individuals with Asperger syndrome (n = 19). Thus, these individuals do not attribute mental states spontaneously, but they may be able to do so in explicit tasks through compensatory learning

The Epitheliome: agent-based modelling of the social behaviour of cells

We have developed a new computational modelling paradigm for predicting the emergent behaviour resulting from the interaction of cells in epithelial tissue. As proof-of-concept, an agent-based model, in which there is a one-to-one correspondence between biological cells and software agents, has been coupled to a simple physical model. Behaviour of the computational model is compared with the growth characteristics of epithelial cells in monolayer culture, using growth media with low and physiological calcium concentrations. Results show a qualitative fit between the growth characteristics produced by the simulation and the in vitro cell models

Understanding the self in relation to others: Infants spontaneously map another's face to their own at 16–26 months

The current study probed whether infants understand themselves in relation to others. Infants aged 16-26 months (n = 102) saw their parent wearing a sticker on their forehead or cheek, depending on experimental condition, placed unwitnessed by the child. Infants then received a sticker themselves, and their spontaneous behavior was coded. Regardless of age, from 16 months, all infants who placed the sticker on their cheek or forehead, placed it on the location on their own face matching their parent's placement. This shows that infants as young as 16 months of age have an internal map of their face in relation to others that they can use to guide their behavior. Whether infants placed the sticker on the matching location was related to other measures associated with self-concept development (the use of their own name and mirror self-recognition), indicating that it may reflect a social aspect of children's developing self-concept, namely their understanding of themselves in relation and comparison to others. About half of the infants placed the sticker on themselves, while others put it elsewhere in the surrounding, indicating an additional motivational component to bring about on themselves the state, which they observed on their parent. Together, infants' placement of the sticker in our task suggests an ability to compare, and motivation to align, self and others

Automated Motion Analysis of Adherent Cells in Monolayer Culture

This paper presents a novel method for tracking and characterizing adherent cells in monolayer culture. A system of cell tracking employing computer vision techniques was applied to time-lapse videos of replicate normal human uro-epithelial cell cultures exposed to different concentrations of adenosine triphosphate (ATP), acquired over a 20 h period. Subsequent analysis, comprising feature extraction, demonstrated the ability of the technique to successfully separate the modulated classes of cell

Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction.

Circulating cancer cells in the blood play a central role in the metastatic process. Their number can be very small and techniques for their detection need to be both sensitive and specific. Polymerase chain reaction (PCR) has been successfully used to detect small numbers of tumour cells in haematological cancer in which abnormalities in DNA are sufficiently consistent to make this possible. For most solid tumours this not yet feasible. However, we have found that reverse transcriptase (RT)-PRC for tissue-specific gene expression is a useful technique for identifying small numbers of circulating cells in melanoma and neuroblastoma patients. In this report we describe detection of colon carcinoma cells by RT-PCR using CK 20 mRNA as a marker. Unlike other cytokeratin genes examined (CK 8 and CK 19), CK 20 was not transcribed in normal haematopoietic cells. This suggests a role for RT-PCR in the detection of colon carcinoma metastasis in blood and bone marrow, using CK 20 as the target gene. Future analysis of clinical material will determine the clinical significance of this technique

A provisional database for the silicon content of foods in the United Kingdom

Si may play an important role in bone formation and connective tissue metabolism. Although biological interest in this element has recently increased, limited literature exists on the Si content of foods. To further our knowledge and understanding of the relationship between dietary Si and human health, a reliable food composition database, relevant for the UK population, is required. A total of 207 foods and beverages, commonly consumed in the UK, were analysed for Si content. Composite samples were analysed using inductively coupled plasma&ndash;optical emission spectrometry following microwave-assisted digestion with nitric acid and H2O2. The highest concentrations of Si were found in cereals and cereal products, especially less refined cereals and oat-based products. Fruit and vegetables were highly variable sources of Si with substantial amounts present in Kenyan beans, French beans, runner beans, spinach, dried fruit, bananas and red lentils, but undetectable amounts in tomatoes, oranges and onions. Of the beverages, beer, a macerated whole-grain cereal product, contained the greatest level of Si, whilst drinking water was a variable source with some mineral waters relatively high in Si. The present study provides a provisional database for the Si content of UK foods, which will allow the estimation of dietary intakes of Si in the UK population and investigation into the role of dietary Si in human health.<br /

Dynamic causal modelling on infant fNIRS data: A validation study on a simultaneously recorded fNIRS-fMRI dataset

Tracking the connectivity of the developing brain from infancy through childhood is an area of increasing research interest, and fNIRS provides an ideal method for studying the infant brain as it is compact, safe and robust to motion. However, data analysis methods for fNIRS are still underdeveloped compared to those available for fMRI. Dynamic causal modelling (DCM) is an advanced connectivity technique developed for fMRI data, that aims to estimate the coupling between brain regions and how this might be modulated by changes in experimental conditions. DCM has recently been applied to adult fNIRS, but not to infants. The present paper provides a proof-of-principle for the application of this method to infant fNIRS data and a demonstration of the robustness of this method using a simultaneously recorded fMRI-fNIRS single case study, thereby allowing the use of this technique in future infant studies. fMRI and fNIRS were simultaneously recorded from a 6-month-old sleeping infant, who was presented with auditory stimuli in a block design. Both fMRI and fNIRS data were preprocessed using SPM, and analysed using a general linear model approach. The main challenges that adapting DCM for fNIRS infant data posed included: (i) the import of the structural image of the participant for spatial pre-processing, (ii) the spatial registration of the optodes on the structural image of the infant, (iii) calculation of an accurate 3-layer segmentation of the structural image, (iv) creation of a high-density mesh as well as (v) the estimation of the NIRS optical sensitivity functions. To assess our results, we compared the values obtained for variational Free Energy (F), Bayesian Model Selection (BMS) and Bayesian Model Average (BMA) with the same set of possible models applied to both the fMRI and fNIRS datasets. We found high correspondence in F, BMS, and BMA between fMRI and fNIRS data, therefore showing for the first time high reliability of DCM applied to infant fNIRS data. This work opens new avenues for future research on effective connectivity in infancy by contributing a data analysis pipeline and guidance for applying DCM to infant fNIRS data. [Abstract copyright: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Influenza classification from short reads with VAPOR facilitates robust mapping pipelines and zoonotic strain detection for routine surveillance applications

Motivation: Influenza viruses represent a global public health burden due to annual epidemics and pandemic potential. Due to a rapidly evolving RNA genome, inter-species transmission, intra-host variation, and noise in short-read data, reads can be lost during mapping, and de novo assembly can be time consuming and result in misassembly. We assessed read loss during mapping, and designed a graph-based classifier, VAPOR, for selecting mapping references, assembly validation, and detection of strains of non-human origin. Results: Standard human reference viruses were insufficient for mapping diverse influenza samples in simulation. VAPOR retrieved references for 257 real whole genome sequencing (WGS) samples with a mean of >99.8% identity to assemblies, and increased the proportion of mapped reads by up to 13.3% compared to standard references. VAPOR has the potential to improve the robustness of bioinformatics pipelines for surveillance and could be adapted to other RNA viruses