Now showing items 21-40 of 1023

    • Quantifying the hip-ankle synergy in short-term maximal cycling

      Burnie, Louise; Barratt, Paul; Davids, Keith; Worsfold, Paul; Wheat, Jon; Northumbria University; Sheffield Hallam University; English Institute of Sport; BAE Systems Digital; University of Chester (Elsevier, 2022-08-24)
      Simulation studies have demonstrated that the hip and ankle joints form a task-specific synergy during the downstroke in maximal cycling to enable the power produced by the hip extensor muscles to be transferred to the crank. The existence of the hip-ankle synergy has not been investigated experimentally. Therefore, we sought to apply a modified vector coding technique to quantify the strength of the hip-ankle moment synergy in the downstroke during short-term maximal cycling at a pedalling rate of 135 rpm. Twelve track sprint cyclists performed 3 × 4 s seated sprints at 135 rpm, interspersed with 2 × 4 s seated sprints at 60 rpm on an isokinetic ergometer. Data from the 60 rpm sprints were not analysed in this study. Joint moments were calculated via inverse dynamics, using pedal forces and limb kinematics. The hip-ankle moment synergy was quantified using a modified vector coding method. Results showed, for 28.8% of the downstroke the hip and ankle moments were in-phase, demonstrating the hip and ankle joints tend to work in synergy in the downstroke, providing some support findings from simulation studies of cycling. At a pedalling rate of 135 rpm the hip-phase was most frequent (42.5%) significantly differing from the in- (P = 0.044), anti- (P < 0.001), and ankle-phases (P = 0.004), demonstrating hip-dominant action. We believe this method shows promise to answer research questions on the relative strength of the hip-ankle synergy between different cycling conditions (e.g., power output and pedalling rates).
    • Postnatal Protein Intake as a Determinant of Skeletal Muscle Structure and Function in Mice-A Pilot Study

      Giakoumaki, Ifigeneia; Pollock, Natalie; Aljuaid, Turki; Sannicandro, Anthony J.; Alameddine, Moussira; Owen, Euan; Myrtziou, Ioanna; Ozanne, Susan E.; Kanakis, Ioannis; Goljanek-Whysall, Katarzyna; et al. (MDPI, 2022-08-08)
      Sarcopenia is characterised by an age-related decrease in the number of muscle fibres and additional weakening of the remaining fibres, resulting in a reduction in muscle mass and function. Many studies associate poor maternal nutrition during gestation and/or lactation with altered skeletal muscle homeostasis in the offspring and the development of sarcopenia. The aim of this study was to determine whether the musculoskeletal physiology in offspring born to mouse dams fed a low-protein diet during pregnancy was altered and whether any physiological changes could be modulated by the nutritional protein content in early postnatal stages. Thy1-YFP female mice were fed ad libitum on either a normal (20%) or a low-protein (5%) diet. Newborn pups were cross-fostered to different lactating dams (maintained on a 20% or 5% diet) to generate three groups analysed at weaning (21 days): Normal-to-Normal (NN), Normal-to-Low (NL) and Low-to-Normal (LN). Further offspring were maintained ad libitum on the same diet as during lactation until 12 weeks of age, creating another three groups (NNN, NLL, LNN). Mice on a low protein diet postnatally (NL, NLL) exhibited a significant reduction in body and muscle weight persisting up to 12 weeks, unlike mice on a low protein diet only prenatally (LN, LNN). Muscle fibre size was reduced in mice from the NL but not LN group, showing recovery at 12 weeks of age. Muscle force was reduced in NLL mice, concomitant with changes in the NMJ site and changes in atrophy-related and myosin genes. In addition, μCT scans of mouse tibiae at 12 weeks of age revealed changes in bone mass and morphology, resulting in a higher bone mass in the NLL group than the control NNN group. Finally, changes in the expression of miR-133 in the muscle of NLL mice suggest a regulatory role for this microRNA in muscle development in response to postnatal diet changes. Overall, this data shows that a low maternal protein diet and early postnatal life low-protein intake in mice can impact skeletal muscle physiology and function in early life while postnatal low protein diet favours bone integrity in adulthood.
    • Small-RNA Sequencing Reveals Altered Skeletal Muscle microRNAs and snoRNAs Signatures in Weanling Male Offspring from Mouse Dams Fed a Low Protein Diet during Lactation

      Kanakis, Ioannis; Alameddine, Moussira; Folkes, Leighton; Moxon, Simon; Myrtziou, Ioanna; Ozanne, Susan E.; Peffers, Mandy J.; Goljanek-Whysall, Katarzyna; Vasilaki, Aphrodite; University of Liverpool; University of Chester; University of East Anglia; University of Cambridge; NUI Galway (MDPI, 2021-05-11)
      Maternal diet during gestation and lactation affects the development of skeletal muscles in offspring and determines muscle health in later life. In this paper, we describe the association between maternal low protein diet-induced changes in offspring skeletal muscle and the differential expression (DE) of small non-coding RNAs (sncRNAs). We used a mouse model of maternal protein restriction, where dams were fed either a normal (N, 20%) or a low protein (L, 8%) diet during gestation and newborns were cross-fostered to N or L lactating dams, resulting in the generation of NN, NL and LN offspring groups. Total body and tibialis anterior (TA) weights were decreased in weanling NL male offspring but were not different in the LN group, as compared to NN. However, histological evaluation of TA muscle revealed reduced muscle fibre size in both groups at weaning. Small RNA-sequencing demonstrated DE of multiple miRs, snoRNAs and snRNAs. Bioinformatic analyses of miRs-15a, -34a, -122 and -199a, in combination with known myomiRs, confirmed their implication in key muscle-specific biological processes. This is the first comprehensive report for the DE of sncRNAs in nutrition-associated programming of skeletal muscle development, highlighting the need for further research to unravel the detailed molecular mechanisms.
    • MicroRNAs as central regulators of adult myogenesis and proteostasis loss in skeletal muscle ageing

      Kanakis, Ioannis; Myrtziou, Ioanna; Goljanek-Whysall, Katarzyna; Vasilaki, Aphrodite; University of Liverpool; University of Chester; NUI Galway (CRC Press, 2021-11-23)
      Sarcopenia (from the Greek words sarca (σάρκα) = flesh and penia (πενία) = deficiency) is considered as an age-associated disease, characterized by dysregulation of the balance between muscle hypertrophy, atrophy and regeneration, which leads to advanced loss of skeletal muscle mass and function associated with a high risk of falls and fractures in the elderly. Numerous studies in humans and animals have explored the pathophysiology of musculoskeletal aging but the detailed mechanisms that contribute to skeletal muscle dysfunction have not been yet fully elucidated. Recently, several studies have focused on the role of microRNAs as a dynamic and promising epigenetic mechanism which may regulate post-transcriptional gene expression that modulate skeletal muscle homeostasis. In this chapter, we describe the crucial role of microRNAs in skeletal myogenesis during adulthood and their association with the pathogenesis of sarcopenia linked to proteostasis loss.
    • Age-related changes in microRNAs expression in cruciate ligaments of wild-stock house mice

      Nye, Gareth; Kharaz, Yalda; Goljanek‐Whysall, Katarzyna; Hurst, Jane; McArdle, Anne; Comerford, Eithne; University of Chester; University of Liverpool
      Cruciate ligaments (CL) of the knee joint are injured following trauma or aging. MicroRNAs (miRs) are potential therapeutic targets in musculoskeletal disorders, but there is little known about the role of miRs and their expression ligaments during aging. This study aimed to (1) identify if mice with normal physical activity, wild-stock house mice are an appropriate model to study age-related changes in the knee joint and (2) investigate the expression of miRs in aging murine cruciate ligaments. Knee joints were collected from 6 and 24 months old C57BL/6 and wild-stock house mice (Mus musculus domesticus) for ligament and cartilage (OARSI) histological analysis. Expression of miR targets in CLs was determined in 6-, 12-, 24-, and 30-month-old wild-stock house mice, followed by the analysis of predicted mRNA target genes and Ingenuity Pathway Analysis. Higher CL and knee OARSI histological scores were found in 24-month-old wild-stock house mice compared with 6- and 24-month-old C57BL/6 and 6-month-old wild-stock house mice (p < 0.05). miR-29a and miR-34a were upregulated in 30-month-old wild-stock house mice in comparison with 6-, 12-, and 24-month-old wild-stock house mice (p < 0.05). Ingenuity Pathway Analysis on miR-29a and 34a targets was associated with inflammation through interleukins, TGFβ and Notch genes, and p53 signaling. Collagen type I alpha 1 chain (COL1A1) correlated negatively with both miR-29a (r = −0.35) and miR-34a (r = −0.33). The findings of this study support wild-stock house mice as an appropriate aging model for the murine knee joint. This study also indicated that miR-29a and miR-34a may be potential regulators of COL1A1 gene expression in murine CLs.
    • Are you lookin’ at me? A mixed-methods case study to investigate the influence of coaches’ presence on performance testing outcomes in male academy rugby league players

      Richardson, Ben; Dobbin, Nick; White, Christopher; Bloyce, Daniel; Twist, Craig; University of Chester; York St John University; Manchester Metropolitan University; Wrexham Glyndwr University; University of Chester (Sage Publications, 2022-09-21)
      The study used a mixed-methods approach to examine how the presence of coaches influenced male academy rugby league players’ performance during physical performance testing. Fifteen male rugby players completed two trials of 20 m sprint, countermovement jump and prone Yo-Yo test; one with only the lead researcher present and a second where the lead researcher conducted the battery with both the club’s lead S&C coach, academy manager, and the first team assistant and head coach present. Players and coaches then completed one-to-one semi-structured interviews to explore their beliefs, attitudes and opinions towards physical performance testing. In all tests, the players’ performance was better when the coaches were present compared to when this was conducted by the sport scientist alone. Interviews revealed performance testing was used by coaches to exercise their power over players to socialise them into a desired culture. Players’ own power was evident through additional effort during testing when coaches were present. Practitioners should ensure consistency in the presence of significant observers during performance testing of male rugby players to minimise their influence on test outcome.
    • From dyads to collectives: a review of honeybee signalling

      Hasenjager, Matthew; Franks, Victoria; Leadbeater, Ellouise; University of Tennessee; University of Chester; Royal Holloway University of London (Springer, 2022-08-22)
      The societies of honeybees (Apis spp) are microcosms of divided labour where the fitness interests of individuals are so closely aligned that, in some contexts, the colony behaves as an entity in itself. Self-organization at this extraordinary level requires sophisticated communication networks, so it is not surprising that the celebrated “waggle dance”, by which bees share information about locations outside the hive, evolved here. Yet bees within the colony respond to several other lesser-known signalling systems, including the tremble dance, the stop signal and the shaking signal, whose roles in coordinating worker behaviour are not yet fully understood. Here, we firstly bring together the large but disparate historical body of work that has investigated the “meaning” of such signals for individual bees, before going on to discuss how network-based approaches can show how such signals function as a complex system to control the collective foraging effort of these remarkable social insect societies.
    • Chapter 5: Applying Proteomics to Investigate Extracellular Matrix in Health and Disease

      Randles, Michael; Lennon, Rachel; University of Manchester; Manchester Academic Health Science Centre (Academic Press, 2015-11-23)
      The molecular composition of basement membranes (BMs) has traditionally been investigated by candidate-based approaches leading to the identification of key structural components as described in previous chapters. Laminins, collagen IV, nidogens, perlecan, and type XV/XVIII collagen are integral to BMs with isoforms showing tissue specificity. More recently the application of mass spectrometry (MS)-based proteomics has led to the discovery of many more structural and regulatory components of BMs and more broadly, extracellular matrix (ECM). These investigations have revealed tissue-specific signatures of between 100 and 150 ECM components, demonstrating the complexity of the extracellular niche. In addition to providing a structural scaffold for cells, ECM is a dynamic extracellular environment capable of regulating the physical properties of tissues. Global investigations of ECM with proteomics in turn enable systems level analyses and when applied to health and disease states these investigations provide insights into pathways regulating matrix dysregulation. This chapter focuses on the methods used to extract ECM and on the analysis of its composition using MS-based proteomics, and it provides examples of how these approaches have been used to investigate health and disease states.
    • Peptide mass fingerprinting of preserved collagen in archaeological fish bones for the identification of flatfish in European waters

      Dierickx, Katrien; Presslee, Samantha; Hagan, Richard; Oueslati, Tarek; Harland, Jennifer; Hendy, Jessica; Orton, David; Alexander, Michelle; Harvey, Virginia L.; University of York; University of Lille (The Royal Society, 2022-07-27)
      Bones of Pleuronectiformes (flatfish) are often not identified to species due to the lack of diagnostic features on bones that allow adequate distinction between taxa. This hinders in-depth understanding of archaeological fish assemblages and particularly flatfish fisheries throughout history. This is especially true for the North Sea region, where several commercially significant species have been exploited for centuries, yet their archaeological remains continue to be understudied. In this research, 8 peptide biomarkers for 18 different species of Pleuronectiformes from European waters are described using MALDI-TOF MS and LC-MS/MS data obtained from modern reference specimens. Bone samples (n=202) from three archaeological sites in the UK and France dating to the medieval period (c. 7th–16th century CE) were analysed using ZooMS. Of the 201 that produced good quality spectra, 196 were identified as flatfish species, revealing a switch in targeted species through time and indicating that ZooMS offers a more reliable and informative approach for species identification than osteological methods alone. We recommend this approach for future studies of archaeological flatfish remains as the precise species uncovered from a site can tell much about the origin of the fish, where people fished and whether they traded between regions.
    • Collagen fingerprinting of Caribbean archaeological fish bones: Methodological implications for historical fisheries baselines and anthropogenic change

      Harvey, Virginia L.; LeFebvre, Michelle J.; Sharpe, Ashley E.; Toftgaard, Casper; DeFrance, Susan D.; Giovas, Christina M.; Fitzpatrick, Scott M.; Buckley, Michael; University of Manchester; University of Florida; Smithsonian Tropical Research Institute; National Museum of Denmark; Simon Fraser University; University of Oregon. (Elsevier, 2022-08-22)
      The Caribbean Sea is the most species-rich sea in the Atlantic, largely due to its vast coral reef systems. However, its high biodiversity and endemism face unprecedented anthropogenic threats, including synergistic modern pressures from overfishing, climate change and bioinvasion. Archaeological data indicate initial human settle- ment of the Caribbean ~7000 years before present (yr BP), with regionally variable human impacts on fisheries through time based on standard morphological identification of fish bone. Such studies, however, are challenged by the low taxonomic resolution of archaeological fish bone identifications due to high species diversity and morphological similarity between members of different families or genera. Here, we present collagen finger- printing (Zooarchaeology by Mass Spectrometry; ZooMS) as a method to overcome this challenge, applying it to 1000 archaeological bone specimens identified morphologically as ray-finned fish (superclass Actinopterygii) from 13 circum-Caribbean sites spanning ca. 3150–300 yr BP (years before present). The method successfully identified collagen-containing samples (n = 720) to family (21%), genus (57%), and species (13%) level. Of the 209 samples that were morphologically identified below superclass, collagen fingerprinting verified the taxo- nomic identity of 94% of these, but also refined the identifications to a lower [more precise] taxon in 45% of cases. The remaining 6% of morphological identifications were found to be incorrectly assigned. This study represents the largest application of ZooMS to archaeological fish bones to date and advances future research through the identification of up to 20 collagen biomarkers for 45 taxa in 10 families and 2 orders. The results indicate that refinement of ZooMS archaeological fish identifications in this study is limited not by the quality of the preserved collagen but by the extent of the available modern collagen reference collection. Thus, efforts should be directed towards expanding collagen fingerprint databases in the first instance. Significantly, the high- resolution taxonomic identifications of archaeological bone that ZooMS can offer make ancient fisheries data highly relevant to modern sustainability and conservation efforts in the Caribbean. Additionally, more precise identifications will allow archaeologists to address a variety of questions related to cultural fishing practices and changes in fish stocks through time. This study supports the use of ZooMS as an effective biochemical tool available for mass-taxonomic identification of archaeological fish bone samples spanning century to millennial time scales in the circum-Caribbean.
    • From dyads to collectives: a review of honeybee signalling

      Hasenjager, Matthew J.; Franks, Victoria R.; Leadbeater, Ellouise; orcid: 0000-0002-4029-7254; email: (Springer Berlin Heidelberg, 2022-08-22)
      Abstract: The societies of honeybees (Apis spp.) are microcosms of divided labour where the fitness interests of individuals are so closely aligned that, in some contexts, the colony behaves as an entity in itself. Self-organization at this extraordinary level requires sophisticated communication networks, so it is not surprising that the celebrated waggle dance, by which bees share information about locations outside the hive, evolved here. Yet bees within the colony respond to several other lesser-known signalling systems, including the tremble dance, the stop signal and the shaking signal, whose roles in coordinating worker behaviour are not yet fully understood. Here, we firstly bring together the large but disparate historical body of work that has investigated the “meaning” of such signals for individual bees, before going on to discuss how network-based approaches can show how such signals function as a complex system to control the collective foraging effort of these remarkable social insect societies.
    • Baseline Behavioral Data and Behavioral Correlates of Disturbance for the Lake Oku Clawed Frog (Xenopus longipes)

      Dias, Jemma E.; Ellis, Charlotte; Smith, Tessa E; Hosie, Charlotte A; Tapley, Benjamin; Michaels, Christopher J.; University of Chester; Zoological Sciety of London Outer Circle
      Animal behavior and welfare science can form the basis of zoo animal management. However, even basic behavioral data are lacking for the majority of amphibian species, and species-specific research is required to inform management. Our goal was to develop the first ethogram for the critically endangered frog Xenopus longipes through observation of a captive population of 24 frogs. The ethogram was applied to produce a diurnal activity budget and to measure the behavioral impact of a routine health check where frogs were restrained. In the activity budget, frogs spent the vast majority of time swimming, resting in small amounts of time devoted to feeding, foraging, breathing, and (in males) amplexus. Using linear mixed models, we found no effect of time of day or sex on baseline behavior, other than for breathing, which had a greater duration in females. Linear mixed models indicated significant effects of the health check on duration of swimming, resting, foraging, feeding, and breathing behaviors for all frogs. This indicates a welfare trade-off associated with veterinary monitoring and highlights the importance of non-invasive monitoring where possible, as well as providing candidates for behavioral monitoring of acute stress. This investigation has provided the first behavioral data for this species which can be applied to future research regarding husbandry and management practices.
    • Long term analysis of social structure: evidence of age-based consistent associations in male Alpine ibex

      Brambilla, Alice; von Hardenberg, Achaz; Canedoli, Claudia; Brivio, Francesca; Sueur, Cédric; Stanley, Christina R.; University of Zurich; University of Chester; University of Milano Bicocca; University of Sassari; University de Strasbourg; Institut Universitaire de France (Wiley, 2022-06-28)
      Despite its recognized importance for understanding the evolution of animal sociality as well as for conservation, long term analysis of social networks of animal populations is still relatively uncommon. We investigated social network dynamics in males of a gregarious mountain ungulate (Alpine ibex, Capra ibex) over ten years focusing on groups, sub-groups and individuals, exploring the dynamics of sociality over different scales. Despite the social structure changing between seasons, the Alpine ibex population was highly cohesive: fission–fusion dynamics lead almost every male in the population to associate with each other male at least once. Nevertheless, we found that male Alpine ibex showed preferential associations that were maintained across seasons and years. Age seemed to be the most important factor driving preferential associations while other characteristics, such as social status, appeared less crucial. We also found that centrality measures were influenced by age and were also related to individual physical condition. The multi-scale and long-term frame of our study helped us show that ecological constrains, such as resource availability, may play a role in shaping associations in a gregarious species, but they cannot solely explain sociality and preferential association that are likely also to be driven by life-history linked physiological and social needs. Our results highlight the importance of long-term studies based on individually recognizable subjects to help us build on our understanding of the evolution of animal sociality.
    • Lrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladder

      Roberts, Neil A.; Hilton, Emma N.; Lopes, Filipa M.; Singh, Subir; Randles, Michael J.; Gardiner, Natalie J.; Chopra, Karl; Coletta, Riccardo; Bajwa, Zunera; Hall, Robert J.; et al. (Elsevier, 2019-03-08)
      Mutations in leucine-rich-repeats and immunoglobulin-like-domains 2 (LRIG2) or in heparanase 2 (HPSE2) cause urofacial syndrome, a devastating autosomal recessive disease of functional bladder outlet obstruction. It has been speculated that urofacial syndrome has a neural basis, but it is unknown whether defects in urinary bladder innervation are present. We hypothesized that urofacial syndrome features a peripheral neuropathy of the bladder. Mice with homozygous targeted Lrig2 mutations had urinary defects resembling those found in urofacial syndrome. There was no anatomical blockage of the outflow tract, consistent with a functional bladder outlet obstruction. Transcriptome analysis revealed differential expression of 12 known transcripts in addition to Lrig2, including 8 with established roles in neurobiology. Mice with homozygous mutations in either Lrig2 or Hpse2 had increased nerve density within the body of the urinary bladder and decreased nerve density around the urinary outflow tract. In a sample of 155 children with chronic kidney disease and urinary symptoms, we discovered novel homozygous missense LRIG2 variants that were predicted to be pathogenic in 2 individuals with non-syndromic bladder outlet obstruction. These observations provide evidence that a peripheral neuropathy is central to the pathobiology of functional bladder outlet obstruction in urofacial syndrome, and emphasize the importance of LRIG2 and heparanase 2 for nerve patterning in the urinary tract.
    • Identification of an Altered Matrix Signature in Kidney Aging and Disease

      Randles, Michael; Lausecker, Franziska; Kong, Qingyang; Suleiman, Hani; Reid, Graeme; Kolatsi-Joannou, Maria; Davenport, Bernard; Tian, Pinyuan; Falcone, Sara; Potter, Paul; et al. (American Society of Nephrology, 2021-06-30)
      Background: Accumulation of extracellular matrix in organs and tissues is a feature of both aging and disease. In the kidney, glomerulosclerosis and tubulointerstitial fibrosis accompany the decline in function, which current therapies cannot address, leading to organ failure. Although histologic and ultrastructural patterns of excess matrix form the basis of human disease classifications, a comprehensive molecular resolution of abnormal matrix is lacking. Methods: Using mass spectrometry–based proteomics, we resolved matrix composition over age in mouse models of kidney disease. We compared the changes in mice with a global characterization of human kidney matrix during aging and to existing kidney disease datasets to identify common molecular features. Results: Ultrastructural changes in basement membranes are associated with altered cell adhesion and metabolic processes and with distinct matrix proteomes during aging and kidney disease progression in mice. Within the altered matrix, basement membrane components (laminins, type IV collagen, type XVIII collagen) were reduced and interstitial matrix proteins (collagens I, III, VI, and XV; fibrinogens; and nephronectin) were increased, a pattern also seen in human kidney aging. Indeed, this signature of matrix proteins was consistently modulated across all age and disease comparisons, and the increase in interstitial matrix was also observed in human kidney disease datasets. Conclusions: This study provides deep molecular resolution of matrix accumulation in kidney aging and disease, and identifies a common signature of proteins that provides insight into mechanisms of response to kidney injury and repair.
    • Basement membrane ligands initiate distinct signalling networks to direct cell shape

      Randles, Michael; Lausecker, Franziska; Humphries, Jonathan D.; Byron, Adam; Clark, Simon J.; Miner, Jeffrey H.; Zent, Roy; Humphries, Martin J.; Lennon, Rachel; The University of Manchester; University of Edinburgh; Eberhard Karls University of Tübingen; Washington University School of Medicine; Vanderbilt University Medical Center; Royal Manchester Children's Hospital; Manchester Academic Health Science Centre; University of Chester (Elsevier, 2020-03-06)
      Cells have evolved mechanisms to sense the composition of their adhesive microenvironment. Although much is known about general mechanisms employed by adhesion receptors to relay signals between the extracellular environment and the cytoskeleton, the nuances of ligand-specific signalling remain undefined. Here, we investigated how glomerular podocytes, and four other basement membrane-associated cell types, respond morphologically to different basement membrane ligands. We defined the composition of the respective adhesion complexes using mass spectrometry-based proteomics. On type IV collagen, all epithelial cell types adopted a round morphology, with a single lamellipodium and large adhesion complexes rich in actin-binding proteins. On laminin (511 or 521), all cell types attached to a similar degree but were polygonal in shape with small adhesion complexes enriched in endocytic and microtubule-binding proteins. Consistent with their distinctive morphologies, cells on type IV collagen exhibited high Rac1 activity, while those on laminin had elevated PKCa. Perturbation of PKCa was able to interchange morphology consistent with a key role for this pathway in matrix ligand-specific signalling. Therefore, this study defines the switchable basement membrane adhesome and highlights two key signalling pathways within the systems that determine distinct cell morphologies. Proteomic data are available via ProteomeXchange with identifier PXD017913.
    • A novel model of nephrotic syndrome results from a point mutation in Lama5 and is modified by genetic background

      Falcone, Sara; Nicol, Thomas; Blease, Andrew; Randles, Michael J.; Angus, Elizabeth; Page, Anton; Tam, Frederick W. K.; Pusey, Charles D.; Lennon, Rachel; Potter, Paul K.; et al. (Elsevier, 2021-11-10)
      Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminaemia, edema and hyperlipidaemia. Genetic studies of nephrotic syndrome have led to the identification of proteins playing a crucial role in slit diaphragm signaling, regulation of actin cytoskeleton dynamics and cell-matrix interactions. The laminin α5 chain is essential for embryonic development and, in association with laminin β2 and laminin γ1, is a major component of the glomerular basement membrane, a critical component of the glomerular filtration barrier. Mutations in LAMA5 were recently identified in children with nephrotic syndrome. Here, we have identified a novel missense mutation (E884G) in the uncharacterized L4a domain of LAMA5 where homozygous mice develop nephrotic syndrome with severe proteinuria with histological and ultrastructural changes in the glomerulus mimicking the progression seen in most patients. The levels of LAMA5 are reduced in vivo and the assembly of the laminin 521 heterotrimer significantly reduced in vitro. Proteomic analysis of the glomerular extracellular fraction revealed changes in the matrix composition. Importantly, the genetic background of the mice had a significant effect on aspects of disease progression from proteinuria to changes in podocyte morphology. Thus, our novel model will provide insights into pathologic mechanisms of nephrotic syndrome and pathways that influence the response to a dysfunctional glomerular basement membrane that may be important in a range of kidney diseases.
    • Cucumeropsis mannii seed oil (CMSO) attenuates alterations in testicular biochemistry and histology against Bisphenol a-induced toxicity in male Wister albino rats

      Agu, P. C.; Aja, P. M.; Ekpono Ugbala, Ezebuilo; Ogwoni, H. A.; Ezeh, E. M.; Oscar-Amobi, P. C.; Asuk Atamgba, Agbor; Ani, O. G.; Awoke, J. N.; Nwite, F. E.; et al. (2022-03-24)
      Male reproductive health has deteriorated in recent years as a result of industrialization, which has led to the use of desirable chemicals, like Bisphenol A (BPA), of underlying toxicity. seed is a common soup thickener that produces vegetable oil as well as essential nutrients making it a source of nutraceuticals enlisted with a wide range of therapeutic effects. A total of 48 adult male Wistar rats (120 ± 200g) were used in this study. They were completely randomized and divided into six groups: A (1ml olive oil) irrespective of the weight, B [BPA 100 mg/kg body weight (bw)], C (CMSO 7.5 ml/kg bw), D (CMSO 7.5 ml/kg bw + BPA 100 mg/kg bw), E (CMSO 5.0 ml/kg bw + BPA 100 mg/kg bw), and E (CMSO 2.5 ml/kg bw + BPA 100 mg/kg bw). At the end of the administration via oral routes, rats were sacrificed and testes were collected for biochemistry and histological analysis. BPA significantly (P < 0.05) decreased total testicular protein, epididymal sperm parameters (count, volume, and motility), Mitochondrial Membrane Potential (MMP), body weight, testicular volume; and significantly (P < 0.05) increased testicular enzymes (alkaline phosphatase and lactate dehydrogenase), testicular index; plus histological damages. Interestingly, co-administration of BPA and CMSO significantly (P < 0.05) reversed the biochemical and histological changes. CMSO prevented the biochemistry and histological alterations hence reducing the testicular toxicity. Therefore, CMSO has the potential to be a promising novel nutraceutical for the treatment and management of BPA-induced testicular toxicity. [Abstract copyright: © 2022 The Authors. Published by Elsevier Ltd.]
    • The kidney matrisome in health, aging and disease

      Lausecker, Franziska; Lennon, Rachel; Randles, Michael J.; The University of Manchester; University of Chester (Elsevier, 2022-07-20)
      Dysregulated extracellular matrix is the hallmark of fibrosis, and it has a profound impact on kidney function in disease. Furthermore, perturbation of matrix homeostasis is a feature of aging and is associated with declining kidney function. Understanding these dynamic processes, in the hope of developing therapies to combat matrix dysregulation, requires the integration of data acquired by both well-established and novel technologies. Owing to its complexity, the extracellular proteome, or matrisome, still holds many secrets and has great potential for the identification of clinical biomarkers and drug targets. The molecular resolution of matrix composition during aging and disease has been illuminated by cutting-edge mass spectrometry-based proteomics in recent years, but there remain key questions about the mechanisms that drive altered matrix composition. Basement membrane components are particularly important in the context of kidney function; and data from proteomic studies suggest that switches between basement membrane and interstitial matrix proteins are likely to contribute to organ dysfunction during aging and disease. Understanding the impact of such changes on physical properties of the matrix, and the subsequent cellular response to altered stiffness and viscoelasticity, is of critical importance. Likewise, the comparison of proteomic datasets from multiple organs is required to identify common matrix biomarkers and shared pathways for therapeutic intervention. Coupled with single cell transcriptomics there is the potential to identify the cellular origin of matrix changes, which could enable cell targeted therapy. This review provides a contemporary perspective of the complex kidney matrisome and draws comparison to altered matrix in heart and liver disease.
    • Individual and situational factors affecting the movement characteristics and internal responses to Touch match-play during an international tournament.

      Dobbin, Nick; Thorpe, Cari; Highton, Jamie; Twist, Craig; Manchester Metropolitan University; University of Chester (Taylor and Francis, 2022-08-03)
      The purpose of this study was to examine the influence of individual and situational factors on the movement characteristics and internal responses of players to an international Touch tournament. Using 47 International Touch players (25 men and 22 women), the associations between the movement characteristics and internal responses with individual (sprint, glycolytic test, Yo-Yo intermittent recovery test level 1 [Yo-Yo IR1], jump performance and wellbeing) and situational (sex, squad, position, competition day, points scored/conceded, result, and opposition rank) factors were examined using linear mixed modelling. Yo-Yo IR1 distance was associated with all movement characteristics and internal responses (r=-0.29 to 0.37), whilst sprint and glycolytic times only influenced mean heart rate (HRmean) (r=0.15) and high-speed distance (r=0.10), respectively. Sex influenced high-speed distance (r=-0.41), whilst squad was associated with playing time and HRmean (r=-0.10-0.33). Other associations included: playing position with all movement characteristics (r=-0.67-0.81); points conceded with relative distance (r=-0.14); winning with high metabolic power and session RPE (r=-0.07-0.09), and opposition rank with HRmean and RPE (r=0.11-0.35). Individual and situational factors can influence the movement characteristics and internal responses to Touch and should be considered when developing the characteristics of players and interpreting responses to match-play.