Addition to "Nanostars carrying multifunctional neurotrophic dendrimers protect neurons in preclinical in vitro models of neurodegenerative disorders".

In the original version of this article (p. 47457), some acknowledgments were not included. In the revised Acknowledgments section provided below, we additionally provide The REC reference for the ethical approval of the human astrocyte isolation, an acknowledgment to Dr. Alize Proust at the Francis Crick Institute for establishing the triple coculture BBB model used in this study, and the reference and the grant number for the source of the human fetal material. This does not affect the results or conclusions of our work

Automated Retinopathy of Prematurity Case Detection with Convolutional Neural Networks

Retinopathy of Prematurity (ROP) is an ocular disease observed in premature babies, considered one of the largest preventable causes of childhood blindness. Problematically, the visual indicators of ROP are not well understood and neonatal fundus images are usually of poor quality and resolution. We investigate two ways to aid clinicians in ROP detection using convolutional neural networks (CNN): (1) We fine-tune a pretrained GoogLeNet as a ROP detector and with small modifications also return an approximate Bayesian posterior over disease presence. To the best of our knowledge, this is the first completely automated ROP detection system. (2) To further aid grading, we train a second CNN to return novel feature map visualizations of pathologies, learned directly from the data. These feature maps highlight discriminative information, which we believe may be used by clinicians with our classifier to aid in screening

A Distance-Dependent Distribution of Presynaptic Boutons Tunes Frequency-Dependent Dendritic Integration

How presynaptic inputs and neurotransmitter release dynamics are distributed along a dendritic tree is not well established. Here, we show that presynaptic boutons that form onto basal dendrites of CA1 pyramidal neurons display a decrease in active zone (AZ) size with distance from the soma, resulting in a distance-dependent increase in short-term facilitation. Our findings suggest that the spatial distribution of short-term facilitation serves to compensate for the electrotonic attenuation of subthreshold distal inputs during repeated stimulation and fine-tunes the preferred input frequency of dendritic domains

Lentiviral Engineered Fibroblasts Expressing Codon Optimized COL7A1 Restore Anchoring Fibrils in RDEB

Cells therapies, engineered to secrete replacement proteins, are being developed to ameliorate otherwise debilitating diseases. Recessive dystrophic epidermolysis bullosa (RDEB) is caused by defects of type VII collagen (C7), a protein essential for anchoring fibril formation at the dermal-epidermal junction (DEJ). Whilst allogeneic fibroblasts injected directly into the dermis can mediate transient disease modulation, autologous gene-modified fibroblasts should evade immunological rejection and support sustained delivery of C7 at the DEJ. We demonstrate the feasibility of such an approach using a therapeutic grade, self-inactivating-lentiviral vector, encoding codon optimized COL7A1, to transduce RDEB fibroblasts under conditions suitable for clinical application. Expression and secretion of C7 was confirmed, with transduced cells exhibiting supra-normal levels of protein expression and ex vivo migration of fibroblasts was restored in functional assays. Gene modified RDEB fibroblasts also deposited C7 at the DEJ of human RDEB skin xenografts placed on NOD-scid IL2Rgamma(null) recipients, with reconstruction of human epidermal structure and regeneration of anchoring fibrils at the DEJ. Fibroblast mediated restoration of protein and structural defects in this RDEB model strongly supports proposed therapeutic applications in man

“Excellence R Us”: university research and the fetishisation of excellence

The rhetoric of “excellence” is pervasive across the academy. It is used to refer to research outputs as well as researchers, theory and education, individuals and organisations, from art history to zoology. But does “excellence” actually mean anything? Does this pervasive narrative of “excellence” do any good? Drawing on a range of sources we interrogate “excellence” as a concept and find that it has no intrinsic meaning in academia. Rather it functions as a linguistic interchange mechanism. To investigate whether this linguistic function is useful we examine how the rhetoric of excellence combines with narratives of scarcity and competition to show that the hypercompetition that arises from the performance of “excellence” is completely at odds with the qualities of good research. We trace the roots of issues in reproducibility, fraud, and homophily to this rhetoric. But we also show that this rhetoric is an internal, and not primarily an external, imposition. We conclude by proposing an alternative rhetoric based on soundness and capacity-building. In the final analysis, it turns out that that “excellence” is not excellent. Used in its current unqualified form it is a pernicious and dangerous rhetoric that undermines the very foundations of good research and scholarship