Search bioRxivSearch

Biology subjects

Gilbert, C.

Publications and source records attributed to Gilbert, C..

4 recordsLinked to original sources

Systematic Review on Barriers and Facilitators for Access to Diabetic Retinopathy Screening Services

ObjectivesThe aim of this systematic review is to identify the barriers/enablers for the people with diabetes (PwDM) in accessing DRS services (DRSS) and challenges/facilitators for the providers.\n\nBackgroundDiabetic retinopathy (DR) can lead to visual impairment and blindness if not detected and treated in time. Achievement of an acceptable level of screening coverage is a challenge in any setting. Both patient-related and provider-related factors affect provision of DR screening (DRS) and uptake of services.\n\nMethodsWe searched MEDLINE, Embase, CENTRAL in the Cochrane Library from the databases start date to September 2016. We included the studies reported on barriers and enablers to access DRS by PwDM and studies which have assessed barriers or facilitators experienced by the providers in provision of DRSS. We identified and classified the studies that used quantitative or qualitative methods for data collection and analysis in reporting themes of barriers and enablers.\n\nMain ResultsWe included 63 studies primarily describing the barriers and enablers. The findings of these studies were based on PwDM from different socio-economic backgrounds and different levels of income settings. Most of the studies were from high income settings (48/63, 76.2%) and cross sectional in design (49/63, 77.8%). From the perspectives of users, lack of knowledge, attitude, awareness and motivation were identified as major barriers to access DRSS. The enablers to access DRSS were fear of blindness, proximity of screening facility, experiences of vision loss and being concerned of eye complications. Providers often mentioned that lack of awareness and knowledge among the PwDM was the main barrier to access. In their perspective lack of skilled human resources, training programs and infrastructure of retinal imaging and cost of services were the main obstacles in provision of screening services.\n\nConclusionKnowing the barriers to access DRS is a pre-requisite in development of a successful screening program. The awareness, knowledge and attitude of the consumers, availability of skilled human resources and infrastructure emerged as the major barriers to access to DRS in any income setting.

epidemiology

Pan-arthropod analysis reveals somatic piRNAs as an ancestral TE defence

In animals, small RNA molecules termed PIWI-interacting RNAs (piRNAs) silence transposable elements (TEs), protecting the germline from genomic instability and mutation. piRNAs have been detected in the soma in a few animals, but these are believed to be specific adaptations of individual species. Here, we report that somatic piRNAs were likely present in the ancestral arthropod more than 500 million years ago. Analysis of 20 species across the arthropod phylum suggests that somatic piRNAs targeting TEs and mRNAs are common among arthropods. The presence of an RNA-dependent RNA polymerase in chelicerates (horseshoe crabs, spiders, scorpions) suggests that arthropods originally used a plant-like RNA interference mechanism to silence TEs. Our results call into question the view that the ancestral role of the piRNA pathway was to protect the germline and demonstrate that small RNA silencing pathways have been repurposed for both somatic and germline functions throughout arthropod evolution.

evolutionary biology

Burden-driven feedback control of gene expression

Cells use feedback regulation to ensure robust growth despite fluctuating demands on resources and different environmental conditions. Yet the expression of foreign proteins from engineered constructs is an unnatural burden on resources that cells are not adapted for. Here we combined multiplex RNAseq with an in vivo assay to reveal the major transcriptional changes in two E. coli strains when a set of inducible synthetic constructs are expressed. We identified that native promoters related to the heat-shock response activate expression rapidly in response to synthetic expression, regardless of the construct. Using these promoters, we built a CRISPR/dCas9-based feedback regulation system that automatically adjusts synthetic construct expression in response to burden. Cells equipped with this general-use controller maintain capacity for native gene expression to ensure robust growth and as such outperform unregulated cells at protein yields in batch production. This engineered feedback is the first example of a universal, burden-based biomolecular control system and is modular, tuneable and portable.

synthetic biology

Tunable Extracellular Self-Assembly of Multi-Protein Conjugates from Bacillus subtilis

The ability to stably and specifically conjugate recombinant proteins to one another is a powerful in vitro technique for engineering multifunctional enzymes, protein therapeutics and novel biological materials. However, for many applications spontaneous in vivo protein conjugation would be preferable to in vitro methods. Exploiting the recently described SpyTag-SpyCatcher system, we describe here how enzymes and structural proteins can be genetically-encoded to covalently conjugate in culture media following programmable secretion by Bacillus subtilis. Using this novel approach, we demonstrate how self-conjugation of a secreted industrial enzyme, XynA, dramatically increases its resilience to boiling and we show that cellular consortia can be engineered to self-assemble functional multi-protein complexes with tunable composition. This genetically-encoded modular system provides a new, flexible strategy for protein conjugation harnessing the substantial advantages of extracellular self-assembly.

synthetic biology