Publications by authors named "Karl J A McCullagh"

Angiogenesis is the formation of new blood vessels from pre-existing vessels. Adequate oxygen transport and waste removal are necessary for tissue homeostasis. Restrictions in blood supply can lead to ischaemia which can contribute to disease pathology.

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The chick chorioallantoic membrane (CAM) assay model of angiogenesis has been highlighted as a relatively quick, low cost and effective model for the study of pro-angiogenic and anti-angiogenic factors. The chick CAM is a highly vascularised extraembryonic membrane which functions for gas exchange, nutrient exchange and waste removal for the growing chick embryo. It is beneficial as it can function as a treatment screening tool, which bridges the gap between cell based in vitro studies and in vivo animal experimentation.

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Critical limb ischemia (CLI) is characterized by the impairment of microcirculation, necrosis and inflammation of the muscular tissue. Although the role of glycans in mediating inflammation has been reported, changes in the glycosylation following muscle ischemia remains poorly understood. Here, a murine CLI model was used to show the increase of high mannose, α-(2, 6)-sialic acid and the decrease of hybrid and bisected N-glycans as glycosylation associated with the ischemic environment.

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The dermal striated muscle panniculus carnosus (PC), prevalent in lower mammals with remnants in humans, is highly regenerative, and whose function is purported to be linked to defence and shivering thermogenesis. Given the heterogeneity of responses of different muscles to disease, we set out to characterize the PC in wild-type and muscular dystrophic mdx mice. The mouse PC contained mainly fast-twitch type IIB myofibers showing body wide distribution.

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The panniculus carnosus is a thin striated muscular layer intimately attached to the skin and fascia of most mammals, where it provides skin twitching and contraction functions. In humans, the panniculus carnosus is conserved at sparse anatomical locations with high interindividual variability, and it is considered of no functional significance (most possibly being a remnant of evolution). Diverse research fields (such as anatomy, dermatology, myology, neuroscience, surgery, veterinary science) use this unique muscle as a model, but several unknowns and misconceptions remain in the literature.

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Skeletal muscle has a tremendous ability to regenerate, attributed to a well-defined population of muscle stem cells called satellite cells. However, this ability to regenerate diminishes with age and can also be dramatically affected by multiple types of muscle diseases, or injury. Extrinsic and/or intrinsic defects in the regulation of satellite cells are considered to be major determinants for the diminished regenerative capacity.

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Ageing is a biological certainty for all living organisms, and is due to the loss of tissue homeostasis and regenerative capacity (except for newts) in which somatic stem cells are thought to play an important role. Many ageing-associated dysfunctions in stem cells have been described, but it remains ambiguous whether these are merely an outcome of ageing or are causal. Parabiotic animal studies suggest there are factors in the systemic environment that can influence the regenerative capacity of tissues.

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Syncoilin is an atypical type III intermediate filament (IF) protein, which is expressed in muscle and is associated with the dystrophin-associated protein complex. Here, we show that syncoilin is expressed in both the central and peripheral nervous systems. Isoform Sync1 is dominant in the brain, but isoform Sync2 is dominant in the spinal cord and sciatic nerve.

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Syncoilin is a 64-kDa intermediate filament protein expressed in skeletal muscle and enriched at the perinucleus, sarcolemma, and myotendinous and neuromuscular junctions. Due to its pattern of cellular localization and binding partners, syncoilin is an ideal candidate to be both an important structural component of myocytes and a potential mediator of inherited myopathies. Here we present a report of a knockout mouse model for syncoilin and the results of an investigation into the effect of a syncoilin null state on striated muscle function in 6-8-week-old mice.

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The intermediate filament-like protein syncoilin is a member of the dystrophin protein complex, and links the complex to the cytoskeleton through binding alpha-dystrobrevin and desmin in muscle. Here, we identify further sites of syncoilin location in normal muscle: at the perinuclear space, myotendinous junction, and enrichment in the sarcolemma and sarcoplasm of oxidative muscle fibers in mice. To understand the importance of the dystrophin protein complex-syncoilin-cytoskeletal link and its implication to disease, we analyzed syncoilin in mice null for alpha-dystrobrevin (adbn-/-) and desmin (des-/-).

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Calcineurin (Cn) signaling has been implicated in nerve activity-dependent fiber type specification in skeletal muscle, but the downstream effector pathway has not been established. We have investigated the role of the transcription factor nuclear factor of activated T cells (NFAT), a major target of Cn, by using an in vivo transfection approach in regenerating and adult rat muscles. NFAT transcriptional activity was monitored with two different NFAT-dependent reporters and was found to be higher in slow compared to fast muscles.

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