Mutations in the EYS gene are a common cause of autosomal recessive retinitis pigmentosa (arRP), yet the role of the EYS protein in humans is presently unclear. The aim of this study was to investigate the isoform structure, expression and potential function of EYS in the mammalian retina in order to better understand its involvement in the pathogenesis of arRP. To achieve the objective, we examined the expression of mRNA transcripts of EYS isoforms in human tissues and cell lines by RT-PCR. We also investigated the localisation of EYS in cultured cells and retinal cryo-sections by confocal fluorescence microscopy and Western blot analysis. RT-PCR analysis confirmed that EYS has at least four isoforms. In addition to the previously reported EYS isoforms 1 and 4, we present the experimental validation of two smaller variants referred to as EYS isoforms 2 and 3. All four isoforms are expressed in the human retina and Y79 cells and the short variants were additionally detected in the testis. Immunofluorescent confocal microscopy and Western blot analysis revealed that all EYS isoforms preferentially localise to the cytoplasm of Y79 and HeLa cells. Moreover, an enrichment of the endogenous protein was observed near the centrosomes in Y79 cells. Interestingly, EYS was observed at the ciliary axoneme in Y79 ciliated cells. In macaque retinal cryosections, EYS was found to localise in the region of the photoreceptor ciliary axoneme in both rods and cones as well as in the cytoplasm of the ganglion cells. The results obtained in this study lead us to speculate that, in photoreceptor cells, EYS could be a protein involved in maintaining the stability of the ciliary axoneme in both rods and cones. The variability of its isoform structure suggests that other roles are also possible and yet to be established.

MicroRNA regulation of key biological and developmental pathways is a rapidly expanding area of research, accompanied by vast amounts of experimental data. This data, however, is not widely available in bioinformatic resources, making it difficult for researchers to find and analyze microRNA-related experimental data and define further research projects. We are addressing this problem by providing two new bioinformatics data sets that contain experimentally verified functional information for mammalian microRNAs involved in cardiovascular-relevant, and other, processes. To date, our resource provides over 4400 Gene Ontology annotations associated with over 500 microRNAs from human, mouse, and rat and over 2400 experimentally validated microRNA:target interactions. We illustrate how this resource can be used to create microRNA-focused interaction networks with a biological context using the known biological role of microRNAs and the mRNAs they regulate, enabling discovery of associations between gene products, biological pathways and, ultimately, diseases. This data will be crucial in advancing the field of microRNA bioinformatics and will establish consistent data sets for reproducible functional analysis of microRNAs across all biological research areas.

Background: Gene Ontology (GO) is a major bioinformatic resource used for analysis of large biomedical datasets, for example from genome-wide association studies, applied universally across biological fields, including Alzheimer’s disease (AD) research. Objective: We aim to demonstrate the applicability of GO for interpretation of AD datasets to improve the understanding of the underlying molecular disease mechanisms, including the involvement of inflammatory pathways and dysregulated microRNAs (miRs). Methods: We have undertaken a systematic full article GO annotation approach focused on microglial proteins implicated in AD and the miRs regulating their expression. PANTHER was used for enrichment analysis of previously published AD data. Cytoscape was used for visualizing and analyzing miR-target interactions captured from published experimental evidence. Results: We contributed 3,084 new annotations for 494 entities, i.e., on average six new annotations per entity. This included a total of 1,352 annotations for 40 prioritized microglial proteins implicated in AD and 66 miRs regulating their expression, yielding an average of twelve annotations per prioritized entity. The updated GO resource was then used to re-analyze previously published data. The re-analysis showed novel processes associated with AD-related genes, not identified in the original study, such as ‘ gliogenesis’, ‘ regulation of neuron projection development’, or ‘ response to cytokine’, demonstrating enhanced applicability of GO for neuroscience research. Conclusions: This study highlights ongoing development of the neurobiological aspects of GO and demonstrates the value of biocuration activities in the area, thus helping to delineate the molecular bases of AD to aid the development of diagnostic tools and treatments.

The analysis and interpretation of high-throughput datasets relies on access to high-quality bioinformatics resources, as well as processing pipelines and analysis tools. Gene Ontology (GO, geneontology.org) is a major resource for gene enrichment analysis. The aim of this project, funded by the Alzheimer’s Research United Kingdom (ARUK) foundation and led by the University College London (UCL) biocuration team, was to enhance the GO resource by developing new neurological GO terms, and use GO terms to annotate gene products associated with dementia. Specifically, proteins and protein complexes relevant to processes involving amyloid-beta and tau have been annotated and the resulting annotations are denoted in GO databases as ‘ARUK-UCL’. Biological knowledge presented in the scientific literature was captured through the association of GO terms with dementia-relevant protein records; GO itself was revised, and new GO terms were added. This literature biocuration increased the number of Alzheimer’s-relevant gene products that were being associated with neurological GO terms, such as ‘amyloid-beta clearance’ or ‘learning or memory’, as well as neuronal structures and their compartments. Of the total 2055 annotations that we contributed for the prioritised gene products, 526 have associated proteins and complexes with neurological GO terms. To ensure that these descriptive annotations could be provided for Alzheimer’s-relevant gene products, over 70 new GO terms were created. Here, we describe how the improvements in ontology development and biocuration resulting from this initiative can benefit the scientific community and enhance the interpretation of dementia data.

Alzheimer’s disease (AD) is the most common cause of dementia. With the increasing average age of humans worldwide, the total number of people with dementia is projected to reach 82 million by 2030 and 152 million by 2050. No effective pharmaceutical agents exist to halt or slow down the disease progression. Hence, there is a tremendous imperative to gain a better understanding of the pathogenesis of AD and to develop effective treatments. This book brings together an international team of experts to provide a comprehensive and up-to-date overview of AD. The most current information on several critical aspects of AD are presented, providing the readers with a broad picture of the underlying neuropathology, genetics, proteomics, risk factors, novel biomarkers, and potential interventions. Chapters 1–5 discuss the underlying AD pathogenesis using genomic and proteomic approaches, linking diverse pathways that can lead to complex metabolic dysfunction. Chapter 6 reviews the potential role of trace metals in AD, while Chapter 7 examines the diversity of Aβ species involved in AD pathology. Chapter 8 discusses the contributions of white matter degeneration in AD. Chapter 9 examines the potential intriguing role of the brain-gut-microbiota axis in mediating AD. Chapters 10 and 11 discuss potential biomarkers for AD, such as deficits in ocular exploration and early language impairments, respectively. Chapters 12–15 examine possible novel preventative and/or therapeutic methodologies such as exercise, optimizing depression therapy, and diverse psychosocial interventions. The book will be of value to clinicians and health professionals caring for patients with AD and will provide a comprehensive and thought-provoking introduction to young investigators interested in translational aspects of the AD and related dementias.