Unilateral acute idiopathic maculopathy: angiography, optical coherence tomography and microperimetry findings

Unilateral acute idiopathic maculopathy (UAIM) is an uncommon inflammatory disease of the retinal pigment epithelium (RPE) that affects young adults. The variability of clinical features of UAIM makes the diagnosis cumbersome. We report on a 25-year-old man with sudden loss of visual acuity (VA) and a central scotoma in his right eye. Fluorescein angiography localised the lesion in the RPE. Microperimetry revealed a central scotoma extending beyond the lesion margins with complete recovery of retinal sensitivity over weeks. Optical coherence tomography at presentation showed a thickened RPE. We are unaware of previous reports of UAIM studied by microperimetry and could find no reference to it in a computerised search using MEDLINE

Down regulation of the high-affinity IgE receptor associated with successful treatment of chronic idiopathic urticaria with omalizumab

Chronic idiopathic urticaria is a condition that is often controllable with antihistamine therapy. However, some patients have disease burden that is difficult to manage, non-responsive to antihistamines and often requires immunosuppressive medications such as corticosteroids or cyclosporine. We present here a study that demonstrates the effectiveness of omalizumab in treating this condition and the temporal relationship between improvement and down regulation of the high affinity IgE receptor (FcεRI). For this, blood samples were obtained from a symptomatic patient before each treatment and processed for flow cytometric analysis of FcεRI levels on the surface of blood basophils. Down regulation of FcεRI was observed in association with significant clinical improvement and discontinuation of immunosuppressive medications

GenomeChronicler: The Personal Genome Project UK Genomic Report Generator Pipeline

In recent years, there has been a significant increase in whole genome sequencing data of individual genomes produced by research projects as well as direct to consumer service providers. While many of these sources provide their users with an interpretation of the data, there is a lack of free, open tools for generating reports exploring the data in an easy to understand manner. GenomeChronicler was developed as part of the Personal Genome Project UK (PGP-UK) to address this need. PGP-UK provides genomic, transcriptomic, epigenomic and self-reported phenotypic data under an open-access model with full ethical approval. As a result, the reports generated by GenomeChronicler are intended for research purposes only and include information relating to potentially beneficial and potentially harmful variants, but without clinical curation. GenomeChronicler can be used with data from whole genome or whole exome sequencing, producing a genome report containing information on variant statistics, ancestry and known associated phenotypic traits. Example reports are available from the PGP-UK data page (personalgenomes.org.uk/data). The objective of this method is to leverage existing resources to find known phenotypes associated with the genotypes detected in each sample. The provided trait data is based primarily upon information available in SNPedia, but also collates data from ClinVar, GETevidence, and gnomAD to provide additional details on potential health implications, presence of genotype in other PGP participants and population frequency of each genotype. The analysis can be run in a self-contained environment without requiring internet access, making it a good choice for cases where privacy is essential or desired: any third party project can embed GenomeChronicler within their off-line safe-haven environments. GenomeChronicler can be run for one sample at a time, or in parallel making use of the Nextflow workflow manager. The source code is available from GitHub (https://github.com/PGP-UK/GenomeChronicler), container recipes are available for Docker and Singularity, as well as a pre-built container from SingularityHub (https://singularity-hub.org/collections/3664) enabling easy deployment in a variety of settings. Users without access to computational resources to run GenomeChronicler can access the software from the Lifebit CloudOS platform (https://lifebit.ai/cloudos) enabling the production of reports and variant calls from raw sequencing data in a scalable fashion

Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology

Chronic kidney disease (CKD) related cardiovascular disease (CVD) is characterized by vascular remodelling with well-established structural and functional changes in the vascular wall such as arterial stiffness, matrix deposition, and calcification. These phenotypic changes resemble pathology seen in ageing, and are likely to be mediated by sustained alterations in gene expression, which may be caused by epigenetic changes such as tissue-specific DNA methylation. We aimed to investigate tissue specific changes in DNA methylation that occur in CKD-related CVD. Genome-wide DNA methylation changes were examined in bisulphite converted genomic DNA isolated from the vascular media of CKD and healthy arteries. Methylation-specific PCR was used to validate the array data, and the association between DNA methylation and gene and protein expression was examined. The DNA methylation age was compared to the chronological age in both cases and controls. Three hundred and nineteen differentially methylated regions (DMR) were identified spread across the genome. Pathway analysis revealed that DMRs associated with genes were involved in embryonic and vascular development, and signalling pathways such as TGFβ and FGF. Expression of top differentially methylated gene HOXA5 showed a significant negative correlation with DNA methylation. Interestingly, DNA methylation age and chronological age were highly correlated, but there was no evidence of accelerated age-related DNA methylation in the arteries of CKD patients. In conclusion, we demonstrated that differential DNA methylation in the arterial tissue of CKD patients represents a potential mediator of arterial pathology and may be used to uncover novel pathways in the genesis of CKD-associated complications

A novel cell-type deconvolution algorithm reveals substantial contamination by immune cells in saliva, buccal and cervix

AIM: An outstanding challenge in epigenome studies is the estimation of cell-type proportions in complex epithelial tissues. MATERIALS & METHODS: Here, we construct and validate a DNA methylation reference and algorithm for complex tissues that contain epithelial, immune and nonimmune stromal cells. RESULTS: Using this reference, we show that easily accessible tissues such as saliva, buccal and cervix exhibit substantial variation in immune cell (IC) contamination. We further validate our reference in the context of oral cancer, where it correctly predicts an increased IC infiltration in cancer but suppressed in patients with highest smoking exposure. Finally, our method can improve the specificity of differentially methylated CpG calls in epithelial cancer. CONCLUSION: The degree and variation of IC contamination in complex epithelial tissues is substantial. We provide a valuable resource and tool for assessing the epithelial purity and IC contamination of samples and for identifying differential methylation in such complex tissues

Exploring the adoption of precision agricultural technologies: a cross regional study of EU farmers

Precision agricultural technologies (PATs) allow more detailed management of in-field variability. Policy and advisory communities have championed PATs as a route to preserving natural capital whilst increasing productivity from agricultural land. A range of PATs are currently available for the agricultural producer but uptake varies by the type of technology and region. Whereas most studies on uptake have focused on US or Australia we empirically examine uptake of machine guidance (MG) and variable rate nitrogen technologies (VRNT) within European farming systems. Using primary information from 971 arable crop growers across five countries: Belgium, Germany, Greece, the Netherlands and the UK, a multilevel random intercept regression estimated a) the differences between adoption and non-adoption and b) the differences between VRNT and MG adoption. We find, aside from size and income differences, which reflect the economic cost barrier to adoption, an attitudinal difference, in terms of optimism towards the technology's economic return leading to more probability of uptake. Moreover innovative and information seeking behaviour also proved significant when upgrading from machine guidance to variable rate technologies. Subsidy and taxation were considered positive drivers of uptake within the community. However, results suggest that more indirect interventions, such as informational support to counteract industry bias, and demonstration to prove the viability of economic return may be effective at meeting land manager and policy expectations towards PATs

Productive restructuring and the reallocation of work and employment: a survey of the “new” forms of social inequality

O propósito do presente artigo consiste em questionar a inevitabilidade dos processos de segmentação e precarização das relações de trabalho e emprego, responsáveis pela inscrição de “novas” formas de desigualdade social que alicerçam o actual modelo de desenvolvimento das economias e sociedades. Visa-se criticar os limites da lógica econômica e financeira, de contornos globais, que configuram um “novo espírito do capitalismo”, ou seja, uma espécie de divinização da ordem natural das coisas. Impõe-se fazer, por isso, um périplo analítico pelas transformações em curso no mercado de trabalho, acompanhado pela vigilância epistemológica que permita enquadrar e relativizar as (di)visões neoliberais e teses tecnodeterministas dominantes. A perspectivação de cenários sobre o futuro do trabalho encerrará este périplo, permitindo-nos alertar para os condicionalismos histórico-temporais, para a urgência de se desocultar o que de ideológico e político existe nas actuais lógicas de racionalização e para os processos de ressimbolização do trabalho e emprego enquanto “experiência social central” na contemporaneidade.The scope of this paper is to question the inevitability of the processes of segmentation and increased precariousness of the relations of labor and employment, which are responsible for the introduction of “new” forms of social inequality that underpin the current model of development of economies and societies. It seeks to criticize the limits of global financial and economic logic, which constitute a “new spirit of capitalism,” namely a kind of reverence for the natural order of things. It is therefore necessary to conduct an analytical survey of the ongoing changes in the labor market, accompanied by epistemological vigilance which makes it possible to see neoliberal (di)visions and dominant technodeterministic theses in context. The enunciation of scenarios on the future of work will conclude this survey and will make it possible to draw attention to both the historical and temporal constraints and to the urgent need to unveil what is ideological and political in the prevailing logic of rationalization and processes to reinstate work and employment as a “central social experience” in contemporary times

Immunolocalization of dually phosphorylated MAPKs in dividing root meristem cells of Vicia faba, Pisum sativum, Lupinus luteus and Lycopersicon esculentum

Key message In plants, phosphorylated MAPKs display constitutive nuclear localization; however, not all studied plant species show co-localization of activated MAPKs to mitotic microtubules. Abstract The mitogen-activated protein kinase (MAPK) signaling pathway is involved not only in the cellular response to biotic and abiotic stress but also in the regulation of cell cycle and plant development. The role of MAPKs in the formation of a mitotic spindle has been widely studied and the MAPK signaling pathway was found to be indispensable for the unperturbed course of cell division. Here we show cellular localization of activated MAPKs (dually phosphorylated at their TXY motifs) in both interphase and mitotic root meristem cells of Lupinus luteus, Pisum sativum, Vicia faba (Fabaceae) and Lycopersicon esculentum (Solanaceae). Nuclear localization of activated MAPKs has been found in all species. Colocalization of these kinases to mitotic microtubules was most evident in L. esculentum, while only about 50 % of mitotic cells in the root meristems of P. sativum and V. faba displayed activated MAPKs localized to microtubules during mitosis. Unexpectedly, no evident immunofluorescence signals at spindle microtubules and phragmoplast were noted in L. luteus. Considering immunocytochemical analyses and studies on the impact of FR180204 (an inhibitor of animal ERK1/2) on mitotic cells, we hypothesize that MAPKs may not play prominent role in the regulation of microtubule dynamics in all plant species

Non-local effects in the mean-field disc dynamo. II. Numerical and asymptotic solutions

The thin-disc global asymptotics are discussed for axisymmetric mean-field dynamos with vacuum boundary conditions allowing for non-local terms arising from a finite radial component of the mean magnetic field at the disc surface. This leads to an integro-differential operator in the equation for the radial distribution of the mean magnetic field strength, $Q(r)$ in the disc plane at a distance $r$ from its centre; an asymptotic form of its solution at large distances from the dynamo active region is obtained. Numerical solutions of the integro-differential equation confirm that the non-local effects act similarly to an enhanced magnetic diffusion. This leads to a wider radial distribution of the eigensolution and faster propagation of magnetic fronts, compared to solutions with the radial surface field neglected. Another result of non-local effects is a slowly decaying algebraic tail of the eigenfunctions outside the dynamo active region, $Q(r)\sim r^{-4}$, which is shown to persist in nonlinear solutions where $\alpha$-quenching is included. The non-local nature of the solutions can affect the radial profile of the regular magnetic field in spiral galaxies and accretion discs at large distances from the centre.Comment: Revised version, as accepted; Geophys. Astrophys. Fluid Dyna

The Personal Genome Project-UK, an open access resource of human multi-omics data

Integrative analysis of multi-omics data is a powerful approach for gaining functional insights into biological and medical processes. Conducting these multifaceted analyses on human samples is often complicated by the fact that the raw sequencing output is rarely available under open access. The Personal Genome Project UK (PGP-UK) is one of few resources that recruits its participants under open consent and makes the resulting multi-omics data freely and openly available. As part of this resource, we describe the PGP-UK multi-omics reference panel consisting of ten genomic, methylomic and transcriptomic data. Specifically, we outline the data processing, quality control and validation procedures which were implemented to ensure data integrity and exclude sample mix-ups. In addition, we provide a REST API to facilitate the download of the entire PGP-UK dataset. The data are also available from two cloud-based environments, providing platforms for free integrated analysis. In conclusion, the genotype-validated PGP-UK multi-omics human reference panel described here provides a valuable new open access resource for integrated analyses in support of personal and medical genomics