Feasibility of Silicon Quantum Dots as a Biomarker for the Bioimaging of Tear Film

This study investigated the fluorescence and biocompatibility of hydrophilic silicon quantum dots (SiQDs) that are doped with scandium (Sc-SiQDs), copper (Cu-SiQDs), and zinc (Zn-SiQDs), indicating their feasibility for the bioimaging of tear film. SiQDs were investigated for fluorescence emission by the in vitro imaging of artificial tears (TheraTears®), using an optical imaging system. A trypan blue exclusion test and MTT assay were used to evaluate the cytotoxicity of SiQDs to cultured human corneal epithelial cells. No difference was observed between the fluorescence emission of Sc-SiQDs and Cu-SiQDs at any concentration. On average, SiQDs showed stable fluorescence, while Sc-SiQDs and Cu-SiQDs showed brighter fluorescence emissions than Zn-SiQDs. Cu-SiQDs and Sc-SiQDs showed a broader safe concentration range than Zn-SiQDs. Cu-SiQDs and Zn-SiQDs tend to aggregate more substantially in TheraTears® than Sc-SiQDs. This study elucidates the feasibility of hydrophilic Sc-SiQDs in studying the tear film’s aqueous layer

A genome-wide association study to identify genetic markers associated with endometrial cancer grade

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Understanding communication pathways to foster community engagement for health improvement in North West Pakistan

Background: This paper describes the community engagement process undertaken to ascertain the focus, development and implementation of an intervention to improve iodised salt consumption in rural communities in North West Pakistan. The Jirga is a traditional informal structure, which gathers men respected within their community and acts in a governing and decision making capacity in the Pukhtoon culture. The Jirga system had a dual purpose for the study; to access men from the community to discuss the importance of iodised salt, and as an engagement process for the intervention. Methods: A number of qualitative data collection activities were undertaken, with Jirga members and their wives, male and female outreach workers and two groups of women, under and over forty years old. The aim of these were to highlight the communication channels and levers of influence on health behaviour, which were multiple and complex and all needed to be taken into consideration in order to ensure successful and locally sensitive community engagement. Results: Communication channels are described within local families and the communities around them. The key influential role of the Jirga is highlighted as linked both to the standing of its members and the community cohesion ethos that it embodies. Engaging Jirga members in discussions about iodised salt was key in designing an intervention that would activate the most influential levers to decision making in the community. Gendered decision making-processes within the household have been highlighted as restricting women’s autonomy. Whilst in one respect our data confirm this, a more complex hierarchy of decisional power has been highlighted, whereby the concept of ‘wisdom’, an amalgamation of age, experience and education, presents important possibilities. Community members with the least autonomy are the youngest uneducated females, who rely on a web of socially and culturally determined ways to influence decision-making. Conclusions: The major lines of communication and influence in the local community described are placed within the wider literature on community engagement in health improvement. The process of maximisation of local cultural knowledge as part of a community engagement effort is one that has application well beyond the particular setting of this study

Systematic Reviews in Educational Research: Methodology, Perspectives and Application

This chapter explores the processes of reviewing literature as a research method. The logic of the family of research approaches called systematic review is analysed and the variation in techniques used in the different approaches explored using examples from existing reviews. The key distinctions between aggregative and configurative approaches are illustrated and the chapter signposts further reading on key issues in the systematic review process

Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia

Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells. We also show that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized BBB disruption and behavioural changes. Using an inducible ‘knockdown’ mouse model, we further link claudin-5 suppression with psychosis through a distinct behavioural phenotype showing impairments in learning and memory, anxiety-like behaviour and sensorimotor gating. In addition, these animals develop seizures and die after 3–4 weeks of claudin-5 suppression, reinforcing the crucial role of claudin-5 in normal neurological function. Finally, we show that anti-psychotic medications dose-dependently increase claudin-5 expression in vitro and in vivo while aberrant, discontinuous expression of claudin−5 in the brains of schizophrenic patients post mortem was observed compared to age-matched controls. Together, these data suggest that BBB disruption may be a modifying factor in the development of schizophrenia and that drugs directly targeting the BBB may offer new therapeutic opportunities for treating this disorder

The impact of ageing reveals distinct roles for human dentate gyrus and CA3 in pattern separation and object recognition memory

© 2017 The Author(s). Both recognition of familiar objects and pattern separation, a process that orthogonalises overlapping events, are critical for effective memory. Evidence is emerging that human pattern separation requires dentate gyrus. Dentate gyrus is intimately connected to CA3 where, in animals, an autoassociative network enables recall of complete memories to underpin object/event recognition. Despite huge motivation to treat age-related human memory disorders, interaction between human CA3 and dentate subfields is difficult to investigate due to small size and proximity. We tested the hypothesis that human dentate gyrus is critical for pattern separation, whereas, CA3 underpins identical object recognition. Using 3 T MR hippocampal subfield volumetry combined with a behavioural pattern separation task, we demonstrate that dentate gyrus volume predicts accuracy and response time during behavioural pattern separation whereas CA3 predicts performance in object recognition memory. Critically, human dentate gyrus volume decreases with age whereas CA3 volume is age-independent. Further, decreased dentate gyrus volume, and no other subfield volume, mediates adverse effects of aging on memory. Thus, we demonstrate distinct roles for CA3 and dentate gyrus in human memory and uncover the variegated effects of human ageing across hippocampal regions. Accurate pinpointing of focal memory-related deficits will allow future targeted treatment for memory loss

A potential new, stable state of the E-cadherin strand-swapped dimer in solution

E-cadherin is a transmembrane glycoprotein that facilitates inter-cellular adhesion in the epithelium. The ectodomain of the native structure is comprised of five repeated immunoglobulin-like domains. All E-cadherin crystal structures show the protein in one of three alternative conformations: a monomer, a strand-swapped trans homodimer and the so-called X-dimer, which is proposed to be a kinetic intermediate to forming the strand-swapped trans homodimer. However, previous studies have indicated that even once the trans strand-swapped dimer is formed, the complex is highly dynamic and the E-cadherin monomers may reorient relative to each other. Here, molecular dynamics simulations have been used to investigate the stability and conformational flexibility of the human E-cadherin trans strand-swapped dimer. In four independent, 100 ns simulations, the dimer moved away from the starting structure and converged to a previously unreported structure, which we call the Y-dimer. The Y-dimer was present for over 90% of the combined simulation time, suggesting that it represents a stable conformation of the E-cadherin dimer in solution. The Y-dimer conformation is stabilised by interactions present in both the trans strand-swapped dimer and X-dimer crystal structures, as well as additional interactions not found in any E-cadherin dimer crystal structures. The Y-dimer represents a previously unreported, stable conformation of the human E-cadherin trans strand-swapped dimer and suggests that the available crystal structures do not fully capture the conformations that the human E-cadherin trans homodimer adopts in solution

Biological Earth observation with animal sensors.

Space-based tracking technology using low-cost miniature tags is now delivering data on fine-scale animal movement at near-global scale. Linked with remotely sensed environmental data, this offers a biological lens on habitat integrity and connectivity for conservation and human health; a global network of animal sentinels of environmen-tal change

An analysis-ready and quality controlled resource for pediatric brain white-matter research

We created a set of resources to enable research based on openly-available diffusion MRI (dMRI) data from the Healthy Brain Network (HBN) study. First, we curated the HBN dMRI data (N = 2747) into the Brain Imaging Data Structure and preprocessed it according to best-practices, including denoising and correcting for motion effects, susceptibility-related distortions, and eddy currents. Preprocessed, analysis-ready data was made openly available. Data quality plays a key role in the analysis of dMRI. To optimize QC and scale it to this large dataset, we trained a neural network through the combination of a small data subset scored by experts and a larger set scored by community scientists. The network performs QC highly concordant with that of experts on a held out set (ROC-AUC = 0.947). A further analysis of the neural network demonstrates that it relies on image features with relevance to QC. Altogether, this work both delivers resources to advance transdiagnostic research in brain connectivity and pediatric mental health, and establishes a novel paradigm for automated QC of large datasets