Browsing by Author "Parry DAD"

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    50 Years of the steric-blocking mechanism in vertebrate skeletal muscle: a retrospective
    (Springer Nature Switzerland AG, 2023-09) Parry DAD
    Fifty years have now passed since Parry and Squire proposed a detailed structural model that explained how tropomyosin, mediated by troponin, played a steric-blocking role in the regulation of vertebrate skeletal muscle. In this Special Issue dedicated to the memory of John Squire it is an opportune time to look back on this research and to appreciate John’s key contributions. A review is also presented of a selection of the developments and insights into muscle regulation that have occurred in the years since this proposal was formulated.
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    An experimental model of contusion injury in humans
    (Public Library of Science, 17/11/2022) Barnes M; Lomiwes D; Parry DAD; Stephen M
    Introduction Contusion injuries are common in sport, but our knowledge of the responses to injury primarily come from animal studies and research using eccentric exercise. Therefore, the aim of this study was to develop a model of contusion injury in human participants and, additionally, investigate and compare physiological responses to four impact loads. Methods Thirty-two males were exposed to a single impact of either 4.2, 5.2, 6.2 or 7.2kg, dropped from 67 cm, on to the vastus lateralis of one leg. Maximum voluntary and electrically induced quadriceps force, and pressure pain threshold were measured, and blood sampling carried out, prior to and 30min, 24, 48 and 72h post-impact. Magnetic resonance imaging was carried out 24h post-impact to quantify oedema. Results Despite impact force with 7.2kg (1681.4 ± 235.6 N) not being different to 6.2kg (1690.7 ± 117.6 N), 7.2kg resulted in greater volume of oedema, voluntary force loss, pain and elevations in creatine kinase than the other loads. Although electrically induced force changed over time, post-hoc analysis failed to identify any changes. Interleukin-6 and prostaglandin-E2 did not change over time for any of the loads. Significant correlations were found between oedema volume, pressure pain threshold and maximum voluntary contraction force. Conclusions This is the first experimental study to investigate traumatic loading of skeletal muscle and the subsequent physiological responses associated with contusion injuries in humans. The absence of immediate elevations in creatine kinase and changes in electrically induced force suggest impact, with forces similar to those experienced in contact sport, does not cause significant, direct damage to skeletal muscle. However, the relationship between oedema volume, changes in pressure pain threshold and maximum voluntary contraction force suggests central inhibition plays a role in contusion-related muscle dysfunction.
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    Cornified Epithelial Teeth of Jawless Vertebrates Contain Proteins Similar to Keratin-Associated Proteins of Mammalian Skin Appendages
    (MDPI (Basel, Switzerland), 2025-06-01) Sachslehner AP; Parry DAD; Eckhart L; Iwata J; Johnston CA
    Keratins and keratin-associated proteins (KRTAPs) are the main components of mammalian nails and hair. Comparative genomics and gene expression studies have revealed that keratins are conserved in all vertebrates, whereas KRTAPs exist only in mammals. Recently, we found hair keratin-like cysteine-rich keratins in jawless vertebrates with confirmed expression in the cornified epithelial teeth of the sea lamprey (Petromyzon marinus). Here, we report that KRTAP-like proteins are also present in the horny teeth of the lamprey. Mass spectrometry-based proteomics identified proteins that share features with KRTAPs, such as high contents of cysteine and tyrosine residues, which support intermolecular interactions, and abundant glycine residues, which endow the proteins with flexibility. Genes encoding KRTAP-like proteins are arranged in a cluster in P. marinus, and the presence of at least one KRTAP-like protein is conserved in phylogenetically diverse species of lamprey, including Lampetra fluviatilis, Lethenteron reissneri, Geotria australis, and Mordacia mordax. The KRTAP-like genes of lampreys contain two exons, whereas mammalian KRTAPs have only a single exon. Although KRTAPs and KRTAP-like proteins are products of independent evolution, their common expression in cornified skin appendages suggests that they fulfill similar functions.
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    Structures of the ß-Keratin Filaments and Keratin Intermediate Filaments in the Epidermal Appendages of Birds and Reptiles (Sauropsids)
    (MDPI (Basel, Switzerland), 2021-04) Parry DAD
    The epidermal appendages of birds and reptiles (the sauropsids) include claws, scales, and feathers. Each has specialized physical properties that facilitate movement, thermal insulation, defence mechanisms, and/or the catching of prey. The mechanical attributes of each of these appendages originate from its fibril-matrix texture, where the two filamentous structures present, i.e., the corneous ß-proteins (CBP or ß-keratins) that form 3.4 nm diameter filaments and the α-fibrous molecules that form the 7–10 nm diameter keratin intermediate filaments (KIF), provide much of the required tensile properties. The matrix, which is composed of the terminal domains of the KIF molecules and the proteins of the epidermal differentiation complex (EDC) (and which include the terminal domains of the CBP), provides the appendages, with their ability to resist compression and torsion. Only by knowing the detailed structures of the individual components and the manner in which they interact with one another will a full understanding be gained of the physical properties of the tissues as a whole. Towards that end, newly-derived aspects of the detailed conformations of the two filamentous structures will be discussed and then placed in the context of former knowledge.