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"Smith, John"
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Advances in understanding nociception and neuropathic pain
Pain results from the activation of a subset of sensory neurones termed nociceptors and has evolved as a “detect and protect” mechanism. However, lesion or disease in the sensory system can result in neuropathic pain, which serves no protective function. Understanding how the sensory nervous system works and what changes occur in neuropathic pain are vital in identifying new therapeutic targets and developing novel analgesics. In recent years, technologies such as optogenetics and RNA-sequencing have been developed, which alongside the more traditional use of animal neuropathic pain models and insights from genetic variations in humans have enabled significant advances to be made in the mechanistic understanding of neuropathic pain.
Journal Article
In vivo gene editing of CAMKIID: out with the bad and in with the good
The ability to change an organism's DNA through gene editing is of great importance for the prevention and treatment of genetic and acquired diseases. Rapid progress has been made during the last decade due to the discovery and refinement of CRISPR/Cas9 as an accurate, fast, and reliable genome editing technique. In this issue of the JCI, Lebek et al. present the culmination from a line of work in the Olson laboratory focused on in vivo gene editing of CAMK2D. The paper presents a combined state-of-the-art gene therapy approach that demonstrates how gene therapy can yield cardioprotection in a mouse model and takes notable steps toward potential applicability in patients.
Journal Article
Titin mutations and muscle disease
The introduction of next-generation sequencing technology has revealed that mutations in the gene that encodes titin (TTN) are linked to multiple skeletal and cardiac myopathies. The most prominent of these myopathies is dilated cardiomyopathy (DCM). Over 60 genes are linked to the etiology of DCM, but by far, the leading cause of DCM is mutations in TTN with truncating variants in TTN (TTNtvs) associated with familial DCM in ∼ 20% of the cases. Titin is a large (3–4 MDa) and abundant protein that forms the third myofilament type of striated muscle where it spans half the sarcomere, from the Z-disk to the M-line. The underlying mechanisms by which titin mutations induce disease are poorly understood and targeted therapies are not available. Here, we review what is known about TTN mutations in muscle disease, with a major focus on DCM. We highlight that exon skipping might provide a possible therapeutic avenue to address diseases that arise from TTNtvs.
Journal Article
Music in religious cults of the ancient Near East
This work presents the first extended discussion of the relationship between music and cultic worship in ancient western Asia. It covers ancient Israel and Judah, the Levant, Anatolia, Mesopotamia, Elam, and ancient Egypt, focusing on the period from approximately 3000 BCE to around 586 BCE.
Book
Evolutionary theory can advance and revitalise the biopsychosocial model
The biopsychosocial model remains a key paradigm for healthcare, despite widely recognised scientific and philosophical shortcomings. Here we report on recent updates integrating evolutionary theory with the biopsychosocial model to provide a more comprehensive and scientifically complete approach to understanding the multiple relevant levels of causation of medical and psychiatric problems.
Journal Article
Nanoparticles in Construction Materials and Other Applications, and Implications of Nanoparticle Use
Nanoparticles are defined as ultrafine particles sized between 1 and 100 nanometres in diameter. In recent decades, there has been wide scientific research on the various uses of nanoparticles in construction, electronics, manufacturing, cosmetics, and medicine. The advantages of using nanoparticles in construction are immense, promising extraordinary physical and chemical properties for modified construction materials. Among the many different types of nanoparticles, titanium dioxide, carbon nanotubes, silica, copper, clay, and aluminium oxide are the most widely used nanoparticles in the construction sector. The promise of nanoparticles as observed in construction is reflected in other adoptive industries, driving the growth in demand and production quantity at an exorbitant rate. The objective of this study was to analyse the use of nanoparticles within the construction industry to exemplify the benefits of nanoparticle applications and to address the short-term and long-term effects of nanoparticles on the environment and human health within the microcosm of industry so that the findings may be generalised. The benefits of nanoparticle utilisation are demonstrated through specific applications in common materials, particularly in normal concrete, asphalt concrete, bricks, timber, and steel. In addition, the paper addresses the potential benefits and safety barriers for using nanomaterials, with consideration given to key areas of knowledge associated with exposure to nanoparticles that may have implications for health and environmental safety. The field of nanotechnology is considered rather young compared to established industries, thus limiting the time for research and risk analysis. Nevertheless, it is pertinent that research and regulation precede the widespread adoption of potentially harmful particles to mitigate undue risk.
Journal Article