Viscoelastic and poroelastic mechanical characterization of hydrated gels

Measurement of the mechanical behavior of hydrated gels is challenging due to a relatively small elastic modulus and dominant time-dependence compared with traditional engineering materials. Here polyacrylamide gel materials are examined using different techniques (indentation, unconfined compression, dynamic mechanical analysis) at different length-scales and considering both viscoelastic and poroelastic mechanical frameworks. Elastic modulus values were similar for nanoindentation and microindentation, but both indentation techniques overestimated elastic modulus values compared to homogeneous loading techniques. Hydraulic and intrinsic permeability values from microindentation tests, deconvoluted using a poroelastic finite element model, were consistent with literature values for gels of the same composition. Although elastic modulus values were comparable for viscoelastic and poroelastic analyses, time-dependent behavior was length-scale dependent, supporting the use of a poroelastic, instead of a viscoelastic, framework for future Studies of gel mechanical behavior under indentation

Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy

Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo

Functional Analysis of the Cathepsin-Like Cysteine Protease Genes in Adult Brugia malayi Using RNA Interference

Filarial nematodes are an important group of human pathogens, causing lymphatic filariasis and onchocerciasis, and infecting around 150 million people throughout the tropics with more than 1.5 billion at risk of infection. Control of filariasis currently relies on mass drug administration (MDA) programs using drugs which principally target the microfilarial life-cycle stage. These control programs are facing major challenges, including the absence of a drug with macrofilaricidal or permanent sterilizing activity, and the possibility of the development of drug-resistance against the drugs available. Cysteine proteases are essential enzymes which play important roles in a wide range of cellular processes, and the cathepsin-like cysteine proteases have been identified as potential targets for drug or vaccine development in many parasites. Here we have studied the function of several of the cathepsin-like enzymes in the filarial nematode, B. malayi, and demonstrate that these cysteine proteases are involved in the development of embryos, show similar functions to their counterparts in C. elegans, and therefore, provide an important target for future drug development targeted to eliminate filariasis

Scientific, sustainability and regulatory challenges of cultured meat

Producing meat without the drawbacks of conventional animal agriculture would greatly contribute to future food and nutrition security. This Review Article covers biological, technological, regulatory and consumer acceptance challenges in this developing field of biotechnology. Cellular agriculture is an emerging branch of biotechnology that aims to address issues associated with the environmental impact, animal welfare and sustainability challenges of conventional animal farming for meat production. Cultured meat can be produced by applying current cell culture practices and biomanufacturing methods and utilizing mammalian cell lines and cell and gene therapy products to generate tissue or nutritional proteins for human consumption. However, significant improvements and modifications are needed for the process to be cost efficient and robust enough to be brought to production at scale for food supply. Here, we review the scientific and social challenges in transforming cultured meat into a viable commercial option, covering aspects from cell selection and medium optimization to biomaterials, tissue engineering, regulation and consumer acceptance

Understanding the growth in outdoor recreation participation: an opportunity for sport development in the United Kingdom

© 2018, © 2019 Informa UK Limited, trading as Taylor & Francis Group. This paper examines the growth in importance and scale of the outdoor recreation sector in the United Kingdom. It establishes a five-component model to help understand the growth in this sub-sector of the wider sport and physical activity industry. The paper is based on a narrative literature review of the importance of outdoor recreation and also sets the position of the sector in terms of sport policy in the UK. From determining the factors that are underpinning the growing importance of the sector the article goes on to establish implications for policy and practice in sport policy and development in the UK and beyond. It seeks to establish lesson learning between industry and academia that has underpinned the evolution of outdoor recreation policy development in recent years. Furthermore, it establishes future research agendas and directions for those working in outdoor recreation and physical activity spaces and places

The need for an integrated approach to understanding and managing coastal change in river delta areas - the case of the Rewa river

The watershed area of the Rewa River, the largest river in Fiji, takes up about one-third of the total land area of Viti Levu. The Rewa watershed receives high rainfall, and the Rewa catchment has the highest run-off coefficient for the major rivers in Fiji. Flooding of the Rewa River and delta causes massive losses, to the local people and to the nation in damage to infrastructure, economic costs of rehabilitation and financial assistance to affected communities. Not only is flooding of the Rewa River a major stumbling block to the expansion of Nausori Town, it also affects land formations in the delta: over time, the Rewa delta has undergone physical change, as is characteristic of deltas around the world. The causes of flooding have been attributed to a combination of factors, both natural and anthropogenic . Mitigating the effects of flooding requires an integrated approach