Decellularised extracellular matrix-derived peptides from neural retina and retinal pigment epithelium enhance the expression of synaptic markers and light responsiveness of human pluripotent stem cell derived retinal organoids

Tissue specific extracellular matrices (ECM) provide structural support and enable access to molecular signals and metabolites, which are essential for directing stem cell renewal and differentiation. To mimic this phenomenon in vitro, tissue decellularisation approaches have been developed, resulting in the generation of natural ECM scaffolds that have comparable physical and biochemical properties of the natural tissues and are currently gaining traction in tissue engineering and regenerative therapies due to the ease of standardised production, and constant availability. In this manuscript we report the successful generation of decellularised ECM-derived peptides from neural retina (decel NR) and retinal pigment epithelium (decel RPE), and their impact on differentiation of human pluripotent stem cells (hPSCs) to retinal organoids. We show that culture media supplementation with decel RPE and RPE-conditioned media (CM RPE) significantly increases the generation of rod photoreceptors, whilst addition of decel NR and decel RPE significantly enhances ribbon synapse marker expression and the light responsiveness of retinal organoids. Photoreceptor maturation, formation of correct synapses between retinal cells and recording of robust light responses from hPSC-derived retinal organoids remain unresolved challenges for the field of regenerative medicine. Enhanced rod photoreceptor differentiation, synaptogenesis and light response in response to addition of decellularised matrices from RPE and neural retina as shown herein provide a novel and substantial advance in generation of retinal organoids for drug screening, tissue engineering and regenerative medicine

Victims in Restorative Justice at Post-sentencing level. A Manual

The content of this manual evolved from the research project ‘Restorative Justice at post-sentencing level; supporting and protecting victims’ carried out by an international European team from Belgium, Croatia, Germany, Portugal, Spain and the United Kingdom. This manual is one of several project publications. The target group of this manual consists of those who are, in the widest sense, related to the work with victims of crime but also those, who are interested in Restorative Justice. This manual describes how victims of crime and therewith offenders and the community can be supported in various different ways. Therefore, the awareness of their needs is central at the outset. Furthermore, it aims to provide understanding of the individual process of coping and may therefore also lead to more self-awareness. If the victim is interested and prepared, it is possible to carry out Restorative Justice procedures in all types of crime and at all levels of seriousness, as long as it fits the person’s needs. The different steps to gain understanding of the situation of a victim and to provide support, as well as to empower in order to deal with what has occurred, are described in this manual. The different phases, before, during and after a restorative process, will be outlined as well as various RJ-procedures, from indirect victim-offendermediation to conferencing and possible techniques to apply during these procedures. That an atmosphere of trust is essential during the whole process appears evident as it is a basic principle of all Restorative Justice procedures. In order to provide better orientation, each sub-section is initiated with a number of key issues, which are then elaborated in a short text and concluded with a precise recommendation for practitioners to apply in the work with victims. More experienced practitioners can use this manual as a book of reference and concentrate on the recommendation whereas those, who have had less contact with victims in their work, can use it as an additional guide. In the final section, some case studies from the project partners England, Schleswig-Holstein, Portugal and Croatia give an exemplary insight into the restorative work carried out, from the victim perspective only

Who determines the ideal body? A Summary of Research Findings on Body Image

The globalization of media have paved way for Print and television advertisements to use images of thin female bodies to sell products and these advertisements are viewed by women all over the world. Through the media we are constantly bombarded with the western images of beautiful women and perfect bodies. Many surveys have proved the fact that men and women feel negative about their body image not only in the west but also in other parts of the world and the feminist scholars have tended that one should try to view the portrayal of idealized body image critically . In this connection, this paper, through a survey of relevant literature on body image, attempts to understand the following: 1) The concept of body image 2) Various determinants that idealize a woman’s body and define beauty standards 3) Influence of media on the body image of women 4) How the various determinants are interwoven targeting women, making them vulnerable to the idealized images. Keywords: Body image, Determinants, Medi

Exploring the relative lack of impact of research on ‘ability grouping’ in England: a discourse analytic account

Grouping students by ‘ability’ is a topic of long-standing contention in English education policy, research and practice. While policy-makers have frequently advocated the practice as reflecting educational ‘standards’, research has consistently failed to find significant benefits of ‘ability’ grouping; and indeed has identified disadvantages for some (low-attaining) pupil groups. However, this research evidence has apparently failed to impact on practice in England. This article, contextualised by the authors’ interests in education and social inequality, seeks to do two things. First, it provides a brief analysis of the existing research evidence on the impact of ‘ability’ grouping, with particular reference to socio-economic inequality, identifying seven different explanations for the poorer progress of pupils in low sets that emerge from the literature. Second, it applies Foucaultian ‘analysis of discourse’ to propose potential explanations for the apparent lack of traction of existing research with policy and practice, arguing that practices of ‘ability grouping’ reflect cultural investments in discourses of ‘natural order’ and hierarchy, with particular resonance for the discursive and political habitus of middle-class parents. The authors postulate that investing in a powerful counter-discourse of enlightenment science, illustrated via their current randomised control trial of different approaches to pupil grouping, may offer a means to challenge hegemonic discourses that underpin current classroom practice

Hidden in the Middle : Culture, Value and Reward in Bioinformatics

Bioinformatics - the so-called shotgun marriage between biology and computer science - is an interdiscipline. Despite interdisciplinarity being seen as a virtue, for having the capacity to solve complex problems and foster innovation, it has the potential to place projects and people in anomalous categories. For example, valorised 'outputs' in academia are often defined and rewarded by discipline. Bioinformatics, as an interdisciplinary bricolage, incorporates experts from various disciplinary cultures with their own distinct ways of working. Perceived problems of interdisciplinarity include difficulties of making explicit knowledge that is practical, theoretical, or cognitive. But successful interdisciplinary research also depends on an understanding of disciplinary cultures and value systems, often only tacitly understood by members of the communities in question. In bioinformatics, the 'parent' disciplines have different value systems; for example, what is considered worthwhile research by computer scientists can be thought of as trivial by biologists, and vice versa. This paper concentrates on the problems of reward and recognition described by scientists working in academic bioinformatics in the United Kingdom. We highlight problems that are a consequence of its cross-cultural make-up, recognising that the mismatches in knowledge in this borderland take place not just at the level of the practical, theoretical, or epistemological, but also at the cultural level too. The trend in big, interdisciplinary science is towards multiple authors on a single paper; in bioinformatics this has created hybrid or fractional scientists who find they are being positioned not just in-between established disciplines but also in-between as middle authors or, worse still, left off papers altogether

Prevalent genome streamlining and latitudinal divergence of planktonic bacteria in the surface ocean

Planktonic bacteria dominate surface ocean biomass and influence global biogeochemical processes, but remain poorly characterized owing to difficulties in cultivation. Using large-scale single cell genomics, we obtained insight into the genome content and biogeography of many bacterial lineages inhabiting the surface ocean. We found that, compared with existing cultures, natural bacterioplankton have smaller genomes, fewer gene duplications, and are depleted in guanine and cytosine, noncoding nucleotides, and genes encoding transcription, signal transduction, and noncytoplasmic proteins. These findings provide strong evidence that genome streamlining and oligotrophy are prevalent features among diverse, freeliving bacterioplankton, whereas existing laboratory cultures consist primarily of copiotrophs. The apparent ubiquity of metabolic specialization and mixotrophy, as predicted from single cell genomes, also may contribute to the difficulty in bacterioplankton cultivation. Using metagenome fragment recruitment against single cell genomes, we show that the global distribution of surface ocean bacterioplankton correlates with temperature and latitude and is not limited by dispersal at the time scales required for nucleotide substitution to exceed the current operational definition of bacterial species. Single cell genomes with highly similar small subunit rRNA gene sequences exhibited significant genomic and biogeographic variability, highlighting challenges in the interpretation of individual gene surveys and metagenome assemblies in environmental microbiology. Our study demonstrates the utility of single cell genomics for gaining an improved understanding of the composition and dynamics of natural microbial assemblages. comparative genomics | marine microbiology | microbial ecology | microbial microevolution | operational taxonomic uni

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation